Nelson Teng
Professor of Obstetrics and Gynecology (Oncology), Emeritus
Obstetrics & Gynecology - Gynecologic Oncology
Academic Appointments
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Emeritus Faculty, Acad Council, Obstetrics & Gynecology - Gynecologic Oncology
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Member, Stanford Cancer Institute
Professional Education
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Medical Education: University of Miami Miller School of Medicine (1977) FL
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Board Certification: American Board of Obstetrics and Gynecology, Gynecologic Oncology (1987)
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Board Certification: American Board of Obstetrics and Gynecology, Obstetrics and Gynecology (1985)
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Fellowship: Stanford University School of Medicine (1984) CA
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Residency: UCLA Medical Center Radiology Fellowship (1981) CA
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Internship: UCLA Medical Center Radiology Fellowship (1978) CA
Current Research and Scholarly Interests
Gynecologic Malignancies
Immunotherapy
Biologic Response Modifiers
New Drug Development
Antigenic specificities of human antibodies encoded by the VH4-34 gene
Clinical Trials
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A Controlled Study of the Effectiveness of Oregovomab (Antibody) Plus Chemotherapy in Advanced Ovarian Cancer
Not Recruiting
This is a Phase 2 randomized study with two treatment arms to compare the effectiveness of oregovomab (a murine monoclonal antibody directed against cancer antigen 125 (CA125)) when combined with first-line chemotherapy (carboplatin and paclitaxel) to first-line chemotherapy (carboplatin and paclitaxel alone) in female patients with advanced ovarian cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Ashley Powell, 650-724-3308.
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A Study of Adavosertib (MK-1775) in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone for Participants With Platinum-Sensitive Ovarian Tumors With the P53 Gene Mutation (MK-1775-004)
Not Recruiting
This is a study of the safety and efficacy of adavosertib in combination with paclitaxel plus carboplatin in the treatment of ovarian, fallopian tube, and primary peritoneal tumors with the P53 mutation. In Part 1, a small group of participants will receive adavosertib along with paclitaxel plus carboplatin to establish the tolerability of adavosertib with this combination. In Part 2, participants will be randomly assigned to receive either adavosertib plus paclitaxel and carboplatin OR placebo plus paclitaxel and carboplatin to assess efficacy of adavosertib compared to placebo. The primary hypothesis of the study (Part 2) is that administration of adavosertib in combination with paclitaxel plus carboplatin in participants with platinum sensitive p53 mutant ovarian cancer will result in improvement in progression free survival (PFS) per enhanced Response Evaluation Criteria In Solid Tumors version 1.1 (enhanced RECIST 1.1) compared to participants treated with paclitaxel plus carboplatin alone.
Stanford is currently not accepting patients for this trial. For more information, please contact Kashif Naseem, 650724-3155.
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A Study of Carboplatin and Gemcitabine Plus Bevacizumab in Patients With Ovary, Peritoneal, or Fallopian Tube Carcinoma
Not Recruiting
This is a placebo-controlled, randomized, multicenter Phase III study that will evaluate the safety and efficacy of bevacizumab, administered in combination with carboplatin with gemcitabine, in women with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma.
Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Charlesworth, (650) 796 - 0344.
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A Study of GDC-0980 in the Treatment of Recurrent or Persistent Endometrial Carcinoma
Not Recruiting
This is a multicenter, single-arm, open-label Phase II study to evaluate the activity of GDC-0980 in patients with recurrent or persistent endometrial cancer. The safety, tolerability, and pharmacokinetics of GDC-0980 will also be evaluated.
Stanford is currently not accepting patients for this trial. For more information, please contact Anthea Buchin, (650) 724 - 3155.
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A Study of HGS1036 in Combination With Chemotherapy in Subjects With Advanced Solid Malignancies
Not Recruiting
The primary purpose of this study is to determine the maximally tolerated dose (MTD) of HGS1036 when used in combination with the standard chemotherapeutic regimens paclitaxel plus carboplatin, cisplatin plus etoposide, or docetaxel.
Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Vargas, 650-723-0371 .
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A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)
Not Recruiting
The purpose of this study is to determine which patients with ovarian, fallopian tube, and primary peritoneal cancer will best respond to treatment with rucaparib.
Stanford is currently not accepting patients for this trial. For more information, please contact Alma Gonzalez, 650-498-0624.
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Bevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II-III Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
Not Recruiting
This randomized phase III trial studies bevacizumab and intravenous (given into a vein) chemotherapy to see how well they work compared with bevacizumab and intraperitoneal (given into the abdominal cavity) chemotherapy in treating patients with stage II-III ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer. Monoclonal antibodies, such as bevacizumab, can block the ability of tumor cells to grow and spread by blocking the growth of new blood vessels necessary for tumor growth. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving bevacizumab together with intravenous chemotherapy is more effective than giving bevacizumab together with intraperitoneal chemotherapy in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer
Not Recruiting
This randomized phase III trial studies carboplatin, paclitaxel, and bevacizumab to see how well they work compared to carboplatin, paclitaxel, and placebo in treating patients with stage III or stage IV ovarian epithelial, primary peritoneal, or fallopian tube cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether carboplatin, paclitaxel, and bevacizumab are more effective than carboplatin, paclitaxel, and placebo in treating ovarian epithelial, primary peritoneal, or fallopian tube cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Tine Bjornlund, (650) 725 - 9167.
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Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer
Not Recruiting
This randomized phase III trial studies carboplatin and paclitaxel to see how well they work with or without cisplatin and radiation therapy in treating patients with stage I-IVA endometrial cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether carboplatin and paclitaxel are more effective with or without cisplatin and radiation therapy in treating patients with endometrial cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Carboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian, Epithelial, Primary Peritoneal, or Fallopian Tube Cancer
Not Recruiting
This randomized phase III trial studies carboplatin, paclitaxel and gemcitabine hydrochloride when given together with or without bevacizumab after surgery to see how well it works in treating patients with ovarian, epithelial, primary peritoneal, or fallopian tube cancer that has come back. Drugs used in chemotherapy, such as carboplatin, paclitaxel and gemcitabine hydrochloride work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as bevacizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether combination chemotherapy is more effective when given with or without bevacizumab after surgery in treating patients with ovarian, epithelial, primary peritoneal, or fallopian tube cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Sharanya Ramasubramanian, 650-723-0622.
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Cetuximab in Treating Patients With Persistent or Recurrent Cervical Cancer
Not Recruiting
This phase II trial is studying cetuximab to see how well it works in treating patients with persistent or recurrent cervical cancer. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer
Not Recruiting
This trial studies the chemotherapy toxicity on quality of life in older patients with stage I, stage II, stage III, or stage IV ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer. Learning about the side effects of chemotherapy in older patients may help doctors plan better ways to treat cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Sharanya Ramasubramanian, 650-723-0622.
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Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer
Not Recruiting
This randomized phase III trial is studying cisplatin, radiation therapy, and tirapazamine to see how well they work compared to cisplatin and radiation therapy in treating patients with cervical cancer. Drugs used in chemotherapy, such as cisplatin and tirapazamine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Cisplatin and tirapazamine may make tumor cells more sensitive to radiation therapy. It is not yet known whether giving cisplatin together with radiation therapy is more effective with or without tirapazamine in treating cervical cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Clinical Trial for Ovarian Cancer (OvaRex®)
Not Recruiting
This study will compare the time to disease relapse between OvaRex® MAb-B43.13-treated patients and placebo-treated patients. This study will also compare assessments of survival, quality of life, immune response and safety between active and placebo groups.
Stanford is currently not accepting patients for this trial. For more information, please contact Jim Batterson, (650) 725 - 5974.
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Clinical Trial of Lurbinectedin (PM01183) in Platinum Resistant Ovarian Cancer Patients
Not Recruiting
Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate the activity and safety of PM01183 versus PLD or topotecan as control arm in patients with platinum-resistant ovarian cancer. PM01183 will be explored as single agent in the experimental arm (Arm A) versus PLD or topotecan in the control arm (Arm B).
Stanford is currently not accepting patients for this trial. For more information, please contact Aarti Kale, 650-723-0622.
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Combination Study Of SB-485232 (Interleukin 18) And Doxil For Advanced Stage Epithelial Ovarian Cancer
Not Recruiting
The purpose of this study is to identify a dose of SB-485232 which is safe, tolerable and biologically active when used in combination with pegylated liposomal doxorubicin (Doxil) in patients with epithelial ovarian cancer. This study will use a standard treatment regimen of pegylated liposomal doxorubicin (Doxil) in combination with rising doses of SB-485232. The dose selected from this study will be used in a future studies to evaluate the efficacy of this combination.
Stanford is currently not accepting patients for this trial. For more information, please contact Anthea Buchin, (650) 724 - 3155.
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Cvac as Maintenance Treatment in Patients With Epithelial Ovarian Cancer in Complete Remission Following First-line Chemotherapy or Second-line Treatment
Not Recruiting
As \< 10% of the necessary patients required by the protocol were recruited and the data were not intended to support a labeling claim, it was determined that the abbreviated clinical study report (CSR) was the appropriate reporting format. No efficacy analyses were performed as the trial was terminated early with incomplete enrollment of \< 10%. The purpose of this study is to determine if an investigational cell therapy called Cvac can help epithelial ovarian cancer (EOC) from returning when administered to patients who are in complete remission after surgical removal of their tumor followed by standard first-line (Part A) or second-line (Part B) chemotherapy. Following remission, patients will undergo leukapheresis for the manufacture of the study agent. After completion of chemotherapy and confirmation of remission, patients will enter the treatment phase of the study.
Stanford is currently not accepting patients for this trial. For more information, please contact Kashif Naseem, 650-724-3155.
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Dose Escalation Study of OMP-54F28 in Combination With Paclitaxel and Carboplatin in Patients With Recurrent Platinum-Sensitive Ovarian Cancer
Not Recruiting
This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of OMP-54F28 when combined with paclitaxel and carboplatin. OMP-54F28 will be administered IV on Days 1 of each 21-day cycle. Paclitaxel (175 mg/m2) and carboplatin (AUC = 5 mg/mL • min) will be administered IV on Day 1 of each cycle. A total of 6 cycles of paclitaxel and carboplatin will be given. Additional cycles may be given as per institutional standard of care after discussion with the Medical Monitor. Treatment with OMP-54F28 will continue after completion of treatment with paclitaxel and carboplatin. The planned dose levels of OMP-54F28 are 5 and 10 mg/kg.
Stanford is currently not accepting patients for this trial. For more information, please contact Ashley Powell, 650-724-3308.
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Doxorubicin Hydrochloride, Cisplatin, and Paclitaxel or Carboplatin and Paclitaxel in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer
Not Recruiting
This randomized phase III trial compares how well two different combination chemotherapy regimens (doxorubicin hydrochloride, cisplatin, and paclitaxel versus carboplatin and paclitaxel) work in treating patients with endometrial cancer that is stage III-IV or has come back (recurrent). Drugs used in chemotherapy such as doxorubicin hydrochloride, cisplatin, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known which combination chemotherapy regimen is more effective in treating endometrial cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Efficacy and Safety of Farletuzumab (MORAb-003) in Combination With Carboplatin and Taxane in Participants With Platinum-sensitive Ovarian Cancer in First Relapse
Not Recruiting
This research is being done to find out if Carboplatin and Taxane works better alone or when given with an experimental drug called MORAb-003(farletuzumab) in subjects with first platinum sensitive relapsed ovarian cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Anthea Buchin, (650) 724 - 3155.
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Efficacy Multicentre Trial of ImmunoTherapy Vaccination With Abagovomab to Treat Ovarian Cancer Patients
Not Recruiting
The purpose of this study is to evaluate the benefit of vaccination with Abagovomab, an experimental immunotherapy in ovarian cancer patients. The benefit will be evaluated in terms of time the remission status is kept as well as prolongation of life expectancy.
Stanford is currently not accepting patients for this trial. For more information, please contact Fitzsimmons Colleen, (650) 724 - 3155.
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Efficacy of Panobinostat in Patients With Relapsed and Bortezomib-refractory Multiple Myeloma
Not Recruiting
This study is designed to assess the effectiveness of the combination of Panobinostat plus Bortezomib and Dexamethasone in patients with relapsed and bortezomib refractory Multiple Myeloma.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Health and Recovery Program in Increasing Physical Activity Level in Stage IA-IIIA Endometrial Cancer Survivors
Not Recruiting
This randomized phase II trial studies how well a health and recovery program works in increasing physical activity level in stage IA-IIIA endometrial cancer survivors. Health and recovery program which includes exercise counseling, Fitbit tracker, and phone or email/text communication may increase the level of physical activity in endometrial cancer survivors and promote and maintain behavior change at a lower cost.
Stanford is currently not accepting patients for this trial. For more information, please contact Melissa Usoz, 650-723-8843.
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Monoclonal Antibody (mAb) 216 With Chemotherapy in Adult Relapsed or Refractory B-Lineage Acute Lymphoblastic Leukemia
Not Recruiting
A phase I trial in patients with relapsed or refractory leukemia of a human monoclonal antibody that kills B cell acute lymphoblastic leukemia. Trial will study safety, pharmacokinetics, and anti tumor activity of the antibody given as a single agent and with vincristine.
Stanford is currently not accepting patients for this trial.
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Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy.
Not Recruiting
Olaparib Monotherapy in Patients with BRCA Mutated Ovarian Cancer following First Line Platinum Based Chemotherapy.
Stanford is currently not accepting patients for this trial. For more information, please contact Suzanne Friedrich, 650-725-0426.
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OPT-821 With or Without Vaccine Therapy in Treating Patients With Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer in Second or Third Complete Remission
Not Recruiting
This randomized phase II trial studies OPT-821 and vaccine therapy to see how well they work compared with OPT-821 alone in treating patients with ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer that has decreased or disappeared, but the cancer may still be in the body. Biological therapies, such as OPT-821, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines may help the body build an effective immune response to kill tumor cells. It is not yet known whether OPT-821 is more effective with or without vaccine therapy in treating patients with ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Ovarian Cancer Vaccine for Patients in Remission
Not Recruiting
The purpose of this study is to determine the safety and efficacy of an investigational therapeutic agent (Cvac) in ovarian cancer patients in first or second remission and to determine its ability to prevent cancer from returning. Study objectives Primary objectives: * To confirm the safety of administering Cvac in this population. * To determine the effects of Cvac on progression-free survival (PFS). Secondary objectives: * To determine overall survival (OS) for ovarian cancer patients who receive Cvac after achieving remission in the first or second-line setting. * Evaluation of host immunologic response to Cvac administration.
Stanford is currently not accepting patients for this trial. For more information, please contact Anthea Buchin, (650) 724 - 3155.
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Overcoming Obstacles to Clinical Trials Enrollment Through a Navigator Program
Not Recruiting
Pilot study for assessing the effectiveness of a Navigator program to aid in clinical trial participation amongst the Chinese demographic
Stanford is currently not accepting patients for this trial. For more information, please contact Mei-Chin Kuo, (650) 736 - 1977.
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Paclitaxel and Carboplatin or Ifosfamide in Treating Patients With Newly Diagnosed, Persistent or Recurrent Uterine, Ovarian, Fallopian Tube, or Peritoneal Cavity Cancer
Not Recruiting
This randomized phase III trial studies paclitaxel and carboplatin see how well they work compared with paclitaxel and ifosfamide in treating patients with fallopian tube, or peritoneal cavity cancer that is newly diagnosed, persistent, or has come back (recurrent). Drugs used in chemotherapy, such as paclitaxel, carboplatin, and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether paclitaxel is more effective when given with carboplatin or ifosfamide in treating patients with uterine, ovarian, fallopian tube, or peritoneal cavity cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Paclitaxel and Carboplatin With or Without Bevacizumab in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
Not Recruiting
This phase III clinical trial studies two different dose schedules of paclitaxel to see how well they work in combination with carboplatin with or without bevacizumab in treating patients with stage II, III or IV ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab is a type of drug called a monoclonal antibody and blocks tumor growth by stopping the growth of blood vessels that tumors need to grow. It is not yet known whether giving paclitaxel with combination chemotherapy once every three weeks is more effective than giving paclitaxel once a week in treating patients with ovarian, primary peritoneal, or fallopian tube cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Paclitaxel and Carboplatin With or Without Metformin Hydrochloride in Treating Patients With Stage III, IV, or Recurrent Endometrial Cancer
Not Recruiting
This randomized phase II/III trial studies how well paclitaxel, carboplatin, and metformin hydrochloride works and compares it to paclitaxel, carboplatin, and placebo in treating patients with endometrial cancer that is stage III, IV, or has come back. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Metformin hydrochloride may help paclitaxel and carboplatin work better by making cancer cells more sensitive to the drugs. It is not yet known whether paclitaxel and carboplatin is more effective with or without metformin hydrochloride in treating endometrial cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Suzanne Friedrich, 650-725-0436.
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Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab in Treating Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer
Not Recruiting
This randomized phase III trial studies the side effects of paclitaxel when given together with cisplatin or topotecan with or without bevacizumab and to compare how well they work in treating patients with stage IVB, cervical cancer that has come back or is persistent. Drugs used in chemotherapy, such as paclitaxel, cisplatin, and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether paclitaxel is more effective when given together with cisplatin or topotecan with or without bevacizumab in treating patients with cervical cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Pazopanib Plus Lapatinib Compared to Lapatinib Alone and Pazopanib Alone In Subjects With Metastatic Cervical Cancer
Not Recruiting
This study is being conducted to compare the efficacy and safety of pazopanib in combination with lapatinib with that of lapatinib alone or pazopanib alone in subjects with metastatic cervical cancer
Stanford is currently not accepting patients for this trial. For more information, please contact Tine Bjornlund, (650) 725 - 9167.
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Pelvic Radiation Therapy or Vaginal Implant Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With High-Risk Stage I or Stage II Endometrial Cancer
Not Recruiting
This randomized phase III trial studies pelvic radiation therapy to see how well it works compared with vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with high-risk stage I or stage II endometrial cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Implant radiation therapy uses radioactive material placed directly into or near a tumor to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether pelvic radiation therapy alone is more effective than vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with endometrial cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Phase I Stereotactic Body Radiation for Metastatic or Recurrent Platinum-Resistant Ovarian Cancer
Not Recruiting
This phase I trial studies the side effects and the best dose of stereotactic body radiation therapy (SBRT) in treating patients with metastatic or recurrent ovarian cancer or primary peritoneal cancer. SBRT may be able to send x-rays directly to the tumor and cause less damage to normal tissue.
Stanford is currently not accepting patients for this trial. For more information, please contact Elizabeth A. Kidd, 650-725-2174.
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Safety and Efficacy Clinical Study of SNS-595 in Patients With Platinum-Resistant Ovarian Cancer
Not Recruiting
The purpose of this study is to evaluate the objective response rate, safety and identify potential biomarkers in platinum-resistant ovarian cancer patients treated with voreloxin injection given on a 28-day cycle.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Safety and Efficacy Study of Catumaxomab to Treat Ovarian Cancer After a Complete Response to Chemotherapy
Not Recruiting
The purpose of this study is to determine whether the investigational drug catumaxomab delivered in the planned treatment schedule is a safe and effective treatment for women with advanced ovarian cancer who experience a complete response to chemotherapy.
Stanford is currently not accepting patients for this trial. For more information, please contact Colleen Fitzsimmons, (650) 724 - 3155.
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Second Curettage in Treating Patients With Persistent Non-metastatic Gestational Trophoblastic Tumors
Not Recruiting
This phase II trial studies how well a second curettage (removal of the abnormal cancer cells in the uterus using a method of surgically removing the lining of the uterus) works in treating patients with gestational trophoblastic tumors that did not go away after a first curettage (persistent) and has not yet spread to other places in the body (non-metastatic). A second curettage may be effective in treating persistent gestational trophoblastic tumors and may decrease the likelihood that patients will need chemotherapy in the near future.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Second-Line Therapy Study For Potentially Platinum-Sensitive Relapsed Ovarian Cancer
Not Recruiting
This study was designed to find the most effective and safest doses of both HYCAMTIN and CARBOPLATIN that can be given for the treatment of ovarian cancer. This study may allow researchers to determine the effectiveness of combining HYCAMTIN and CARBOPLATIN.
Stanford is currently not accepting patients for this trial. For more information, please contact Tine Bjornlund, (650) 725 - 9167.
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Selumetinib Sulfate in Treating Woman With Recurrent Low-Grade Ovarian Cancer or Peritoneum Cancer
Not Recruiting
This phase II trial studies the side effects and how well selumetinib sulfate works in treating patients with low-grade ovarian cancer that has come back (recurrent). Selumetinib sulfate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Study of FP-1039 in Subjects With Endometrial Cancers
Not Recruiting
An open-label, non-randomized, single arm study to assess the safety, tolerability, and pharmacokinetics of FP-1039 given by weekly intravenous (IV) administrations in advanced endometrial cancer patients with FGFR2-specific mutations. FP-1039 will be dosed weekly starting at a dose of up to 16 mg/kg.
Stanford is currently not accepting patients for this trial. For more information, please contact Dana Supan, (650) 736 - 1694.
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Study of the Trifunctional Antibody Catumaxomab to Treat Recurrent Symptomatic Malignant Ascites
Not Recruiting
The purpose of this study is to determine whether the investigational drug catumaxomab is a safe and effective treatment for recurrent symptomatic malignant ascites.
Stanford is currently not accepting patients for this trial. For more information, please contact Colleen Fitzsimmons, (650) 724 - 3155.
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Study to Compare the Efficacy and Safety of Olaparib When Given in Combination With Carboplatin and Paclitaxel, Compared With Carboplatin and Paclitaxel in Patients With Advanced Ovarian Cancer
Not Recruiting
To compare the efficacy of olaparib in combination with paclitaxel and carboplatin (AUC4) when compared with carboplatin (AUC6) and paclitaxel alone in patients with advanced ovarian cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Colleen Fitzsimmons, (650) 724 - 3155.
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Temsirolimus With or Without Megestrol Acetate and Tamoxifen Citrate in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer
Not Recruiting
This randomized phase II trial studies how well temsirolimus with or without megestrol acetate and tamoxifen citrate works in treating patients with endometrial cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment, has returned after a period of improvement, or is persistent. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of endometrial cancer cells. Hormone therapy using megestrol acetate and tamoxifen citrate may fight endometrial cancer by blocking the use of estrogen by the tumor cells. It is not yet known whether temsirolimus is more effective when given alone or together with megestrol acetate and tamoxifen citrate in treating endometrial cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Tissue and Plasma Biomarkers of Lymph Node Involvement in Cervical Cancer
Not Recruiting
The purpose of this study is to measure the levels of serum proteins and other biomarkers in cervical cancer patients. We believe that some of these markers may be useful in selecting patients for specific types of cancer therapies. These markers may also help to predict response to therapy, relapse after therapy, and survival after therapy.
Stanford is currently not accepting patients for this trial. For more information, please contact Dylann Fujimoto, 650-723-8843.
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Trabectedin in Treating Patients With Advanced, Persistent, or Recurrent Leiomyosarcoma of the Uterus
Not Recruiting
RATIONALE: Drugs used in chemotherapy, such as trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well trabectedin works in treating patients with advanced, persistent, or recurrent leiomyosarcoma of the uterus.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer
Not Recruiting
This phase II/III trial studies how well trametinib works and compares it to standard treatment with either letrozole, tamoxifen, paclitaxel, pegylated liposomal doxorubicin, or topotecan in treating patients with low-grade ovarian cancer or peritoneal cavity cancer that has come back (recurrent), become worse (progressive), or spread to other parts of the body. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether trametinib is more effective than standard therapy in treating patients with ovarian or peritoneal cavity cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Madelyn Gutierrez Gomez, 650-723-0298 .
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TRINOVA-1: A Study of AMG 386 or Placebo, in Combination With Weekly Paclitaxel Chemotherapy, as Treatment for Ovarian Cancer, Primary Peritoneal Cancer and Fallopian Tube Cancer
Not Recruiting
The purpose of this study is to determine if treatment with paclitaxel plus AMG 386 is superior to paclitaxel plus placebo in women with recurrent partially platinum sensitive or resistant epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer. AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Veliparib in Treating Patients With Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Not Recruiting
This phase II trial studies how well veliparib works in treating patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer that has come back or does not respond to treatment. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
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Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
Not Recruiting
This randomized phase II trial is studying zoledronate to see how well it works compared to observation in maintaining bone mineral density in patients who are undergoing surgery to remove both ovaries. Zoledronate may prevent bone loss in patients who are undergoing surgery to remove the ovaries.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
2024-25 Courses
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Independent Studies (5)
- Directed Reading in Obstetrics and Gynecology
OBGYN 299 (Aut, Win, Spr, Sum) - Early Clinical Experience in Obstetrics and Gynecology
OBGYN 280 (Aut, Win, Spr, Sum) - Graduate Research in Reproductive Biology
OBGYN 399 (Aut, Win, Spr, Sum) - Medical Scholars Research
OBGYN 370 (Aut, Win, Spr, Sum) - Undergraduate Research in Reproductive Biology
OBGYN 199 (Aut, Win, Spr, Sum)
- Directed Reading in Obstetrics and Gynecology
All Publications
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Phase II Trial Evaluating Efficacy of a Fitbit Program for Improving the Health of Endometrial Cancer Survivors
LIPPINCOTT WILLIAMS & WILKINS. 2021: S13
View details for Web of Science ID 000701779700022
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INFLAMMATORY PROTEINS AS PREDICTORS OF DIMINISHED OVARIAN RESERVE
ELSEVIER SCIENCE INC. 2021: E4
View details for Web of Science ID 000680508800003
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Phase II trial evaluating efficacy of a Fitbit program for improving the health of endometrial cancer survivors.
Gynecologic oncology
2021
Abstract
Despite the favorable prognosis of early stage endometrial cancer, mortality from cardiovascular disease is high. We aimed to evaluate the efficacy of a Fitbit program to improve physical activity in endometrial cancer survivors.Eligible patients were diagnosed with stage IA-IIIA endometrial adenocarcinoma, ≥3 months out from treatment. Participants received a Fitbit Alta and were randomized to receive communication via telephone or electronic methods (email/text). Communication was every two weeks for two months, then once during months four and five. Average daily steps were assessed weekly for nine months.The 46 analyzable patients demonstrated a baseline of 5641 median daily average steps. Average steps increased by 22% at 6 months but decreased to baseline by nine months. Baseline activity level (daily steps and walks per week) was the greatest predictor of activity level. Only the telephone intervention participants demonstrated increased activity level at several timepoints, although not maintained by nine months. BMI was unchanged. There was mild improvement in physical and social well-being in those with low baseline well-being (p = 0.009 and 0.014, respectively), regardless of intervention group. Emotional well-being correlated with step count (p = 0.005).Activity level was low and mildly improved on the Fitbit program with the telephone intervention, but effects did not persist by study completion. The program had the greatest impact on a select group of telephone intervention patients with high baseline walking frequency and low baseline step count. Others may require more intense intervention to promote more robust/persistent lifestyle changes.
View details for DOI 10.1016/j.ygyno.2021.01.033
View details for PubMedID 33551199
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Epigenetic clock measuring age acceleration via DNA methylation levels in blood is associated with decreased oocyte yield.
Journal of assisted reproduction and genetics
2020
Abstract
PURPOSE: To investigate how biologic age (phenotypic age at which your body functions) greater than chronologic age, (age acceleration (AgeAccel)), correlates with oocyte yield.METHODS: Thirty-nine women undergoing ovarian stimulation, inclusive of all infertility diagnoses, were included in this pilot study. Methylome analysis of peripheral blood was utilized to determine biologic age. AgeAccel was defined as biologic age >2years older than chronologic age. A negative binomial model was used to obtain the crude association of AgeAccel with number of oocytes. A parsimonious adjusted model for the number of oocytes was obtained using backwards selection (p<0.05).RESULTS: Measures of age were negatively correlated with number of oocytes (chronological age Pearson rho=-0.45, biologic age Pearson rho=-0.46) and AMH was positively correlated with number of oocytes (Pearson rho=0.91). Patients with AgeAccel were noted to have lower AMH values (1.29ng/mL vs. 2.29, respectively (p=0.049)) and lower oocyte yield (5.50 oocytes vs. 14.50 oocytes, respectively (p=0.0030)). A crude association of a 7-oocyte reduction in the age-accelerated group was found (-6.9 oocytes (CI -11.6, -2.4)). In a model with AMH and antral follicle count, AgeAccel was associated with a statistically significant 3.3 reduction in the number of oocytes (-3.1; 95% CI -6.5, -0.1; p=0.036).CONCLUSIONS: In this small pilot study, AgeAccel is associated with a lower AMH and lower oocyte yield providing preliminary evidence that biologic age, specifically AgeAccel, may serve as an epigenetic biomarker to improve the ability of predictive models to assess ovarian reserve.
View details for DOI 10.1007/s10815-020-01763-0
View details for PubMedID 32285295
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What drives E-Health usage? Integrated institutional forces and top management perspectives
COMPUTERS IN HUMAN BEHAVIOR
2019; 97: 260–70
View details for DOI 10.1016/j.chb.2019.01.010
View details for Web of Science ID 000469154400026
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EPIGENETIC CLOCK MEASURING AGE ACCELERATION VIA DNA METHYLATION LEVELS IN BLOOD IS ASSOCIATED WITH DECREASED OOCYTE YIELD.
ELSEVIER SCIENCE INC. 2019: E4–E5
View details for DOI 10.1016/j.fertnstert.2019.02.039
View details for Web of Science ID 000463487700003
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Ovarian carcinoma glyco-antigen targeted by human IgM antibody
PLOS ONE
2017; 12 (12): e0187222
Abstract
Epithelial Ovarian Cancer (EOC) cells expression of a novel carbohydrate antigen was defined using a human VH4-34 encoded IgM monoclonal antibody (mAb216). MAb216 binds to a poly N-acetyllactosamine epitope expressed on B cells and kills normal and malignant B cells in vitro and in vivo. EOC patient ascites and EOC cell lines were used to study the anti tumor effect of mAb216. Various assays were used to characterize the epitope and demonstrate antibody-mediated binding and cytotoxicity in EOC. Drug and antibody combination effects were determined by calculating the combination index values using the Chou and Talalay method. MAb216 displays direct antibody mediated cytotoxicity on a population of human EOC tumor and ascites samples and EOC cell lines, which express high amounts of poly N-acetyllactosamine epitope, carried by CD147/CD98. Eighty four percent of patient samples, including platin resistant, had a tumor population that bound the monoclonal antibody. The binding pattern of mAb216 and mechanism of cytotoxicity was similar to that seen on normal and malignant B cells with unique general membrane disruption and "pore" formation. In vitro incubation with mAb216 and cisplatin enhanced killing of OVCAR3 cell line. In EOC cell lines percent cytotoxicity correlated with percent expression of epitope. Although in vitro data shows specific EOC cytotoxicity, for possible treatment of EOC MAb216 would need to be evaluated in a clinical trial with or without chemotherapy.
View details for PubMedID 29267289
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Targeting FOXM1 Improves Cytotoxicity of Paclitaxel and Cisplatinum in Platinum-Resistant Ovarian Cancer
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
2017; 27 (8): 1602–9
Abstract
Aberrantly activated FOXM1 (forkhead box protein M1) leading to uncontrolled cell proliferation and dysregulation of FOXM1 transcription network occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if targeting the FOXM1 pathway with thiostrepton could improve the efficacy of paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo.Human ovarian cancer cell lines and patients' ascites cells were treated with paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and cytotoxicity was assessed. Drug combination effects were determined by calculating the combination index values using the Chou and Talalay method. Quantitative reverse transcriptase-polymerase chain reaction was performed to determine changes in FOXM1 expression and its downstream targets.Ovarian cancer cell lines and the patients' ascites cancer cells had an overexpression of FOXM1 expression levels. Targeting FOXM1 with thiostrepton decreased FOXM1 mRNA expression and its downstream targets such as CCNB1 and CDC25B, leading to cell death in both cell lines and patients' ascites cancer cells. Furthermore, addition of thiostrepton to paclitaxel and cisplatin showed synergistic effects in chemoresistant ovarian cancer patients' ascites cells ex vivo.Targeting FOXM1 may lead to novel therapeutics for chemoresistant epithelial ovarian cancer.
View details for PubMedID 28692634
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Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-grade Ovarian Carcinoma.
Cancer discovery
2017
Abstract
High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations.
View details for DOI 10.1158/2159-8290.CD-17-0419
View details for PubMedID 28588062
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Targeting Foxm1 Improves Cytotoxicity of Paclitaxel and Cisplatinum in Platinum-Resistant Ovarian Cancer
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
2017; 27 (5): 887–94
Abstract
Aberrantly activated FOXM1 (forkhead box protein M1) leading to uncontrolled cell proliferation and dysregulation of FOXM1 transcription network occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if targeting the FOXM1 pathway with thiostrepton could improve the efficacy of paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo.Human ovarian cancer cell lines and patients' ascites cells were treated with paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and cytotoxicity was assessed. Drug combination effects were determined by calculating the combination index values using the Chou and Talalay method. Quantitative real-time polymerase chain reaction was performed to determine changes in FOXM1 expression and its downstream targets.Ovarian cancer cell lines and the patients' ascites cancer cells had an overexpression of FOXM1 expression levels. Targeting FOXM1 with thiostrepton decreased FOXM1 mRNA expression and its downstream targets such as CCNB1, CDC25B, leading to cell death in both cell lines and patients' ascites cancer cells. Furthermore, addition of thiostrepton to paclitaxel and cisplatin showed synergistic effects in chemoresistant ovarian cancer patients' ascites cells ex vivo.Targeting FOXM1 may lead to novel therapeutics for chemoresistant epithelial ovarian cancer.
View details for PubMedID 28498253
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Radiation Therapy for Recurrent Clear-Cell Cancer of the Ovary.
International journal of gynecological cancer
2016; 26 (9): 1608-1614
Abstract
Given the relative chemo-resistant nature of clear-cell gynecologic cancers, we investigated the utility of radiation therapy (RT) to treat recurrent clear-cell carcinoma (CCC) of the ovary.A retrospective chart review of patients with recurrent CCC managed from 1994-2012 was conducted at 2 academic medical centers. Demographic and clinicopathologic factors were abstracted and evaluated using Pearson χ or t tests, Kaplan-Meier and Cox regression analyses.Fifty-three patients had recurrent CCC, and 24 (45.3%) of these patients received RT. There were no significant differences in age, stage, optimal cytoreduction, platinum response, or the percentage of patients that received more than 3 regimens of chemotherapy between the 2 groups. Patients who received RT for recurrent CCC were more likely to have had a focal recurrence (62.5% vs 10.3%, P ≤ 0.001) and to have undergone secondary cytoreduction (70.8% vs 10.3%, P ≤ 0.001). Of patients who received RT, 73.9% underwent surgery with or before their treatment. Five-year survival after recurrence was significantly higher in the group that received RT, 62.9% versus 18.8% (P = 0.002). In a multivariate analysis, platinum-sensitive disease and RT were associated with improved survival from recurrence, (hazard ratio, 0.26; 95% confidence interval, 0.08-0.81; P = 0.02 and hazard ratio, 0.28; 95% confidence interval, 0.09-0.90, P = 0.03, respectively).In this cohort of patients with recurrent CCC, platinum-sensitive disease and RT are associated with improved survival. However, it is important to note that the majority of these patients underwent surgery along with RT, and it may be that the benefit of RT is limited to those who undergo secondary cytoreduction.
View details for PubMedID 27575628
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Morphological and physiological differences between dehiscent and indehiscent anthers of Chrysanthemum morifolium
JOURNAL OF PLANT RESEARCH
2016; 129 (6): 1069-1082
Abstract
Spray cut chrysanthemums ornamental value and vase life are rapidly reduced with an increase in the pollen dispersal of the middle tubular bisexual flowers, and excessive pollen grains floating in the air are usually harmful to people. Thus, two cultivars were selected: the dehiscent 'Qx-097' and the indehiscent 'Qx-007', to investigate the morphological, structural and physiological differences in anthers. (1) Prior to the opening of the tubular flower, the anther was completely dehisced, and the pollen grains of 'Qx-097' were then released. 'Qx-007' inflorescences showed no pollen dispersal, and this cultivar was therefore not contaminated by its own pollen grains during flowering. (2) The anther cell structure of 'Qx-007' was abnormal, such that the entire anther wall exhibited hypertrophy due to the non-selective thickening of the endothecium cell size in different areas. Moreover, cracks did not form in the 'Qx-007' anther due to failure of septum degradation and stomium breakage, which resulted in the anther locules being inwardly crushed. Besides, the indehiscent anther accompanies partial pollen abortion due to the impairment of tapetum development, this is not conducive to pollen dispersal. (3) The 'Qx-007' anther contained higher water levels compared with 'Qx-097', and the dehydration of the 'Qx-007' anther was relatively moderate. Furthermore, the 'Qx-007' anther exhibited higher Ca(2+) and Mg(2+) levels compared with 'Qx-097' during dehiscing periods. (4) The 'Qx-007' anther showed significantly lower jasmonic acid levels and higher indole-3-acetic acid levels compare with the 'Qx-097' anther. These results suggest that the endothecium, septum and stomium constituent of the anther structure exhibit developmental abnormalities, which likely serve as the cellular basis of anther indehiscence. In addition, anther dehydration, the enhancement of anther cell toughness due to a high level of ions, and JA (IAA) dysregulation may be the determining physiological factors of anther indehiscence.
View details for DOI 10.1007/s10265-016-0854-8
View details for Web of Science ID 000386506000008
View details for PubMedID 27491415
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In Vitro and In Vivo Study of a Novel Porcine Collagen Membrane for Guided Bone Regeneration
MATERIALS
2016; 9 (11)
View details for DOI 10.3390/ma9110949
View details for Web of Science ID 000390114400035
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Chromosome doubling to overcome the chrysanthemum cross barrier based on insight from transcriptomic and proteomic analyses
BMC GENOMICS
2016; 17
Abstract
Cross breeding is the most commonly used method in chrysanthemum (Chrysanthemum morifolium) breeding; however, cross barriers always exist in these combinations. Many studies have shown that paternal chromosome doubling can often overcome hybridization barriers during cross breeding, although the underlying mechanism has seldom been investigated.In this study, we performed two crosses: C. morifolium (pollen receptor) × diploid C. nankingense (pollen donor) and C. morifolium × tetraploid C. nankingense. Seeds were obtained only from the latter cross. RNA-Seq and isobaric tags for relative and absolute quantitation (iTRAQ) were used to investigate differentially expressed genes and proteins during key embryo development stages in the latter cross. A previously performed cross, C. morifolium × diploid C. nankingense, was compared to our results and revealed that transcription factors (i.e., the agamous-like MADS-box protein AGL80 and the leucine-rich repeat receptor protein kinase EXS), hormone-responsive genes (auxin-binding protein 1), genes and proteins related to metabolism (ATP-citrate synthase, citrate synthase and malate dehydrogenase) and other genes reported to contribute to embryo development (i.e., LEA, elongation factor and tubulin) had higher expression levels in the C. morifolium × tetraploid C. nankingense cross. In contrast, genes related to senescence and cell death were down-regulated in the C. morifolium × tetraploid C. nankingense cross.The data resources helped elucidate the gene and protein expression profiles and identify functional genes during different development stages. When the chromosomes from the male parent are doubled, the genes contributing to normal embryo developmentare more abundant. However, genes with negative functions were suppressed, suggesting that chromosome doubling may epigenetically inhibit the expression of these genes and allow the embryo to develop normally.
View details for DOI 10.1186/s12864-016-2939-0
View details for Web of Science ID 000381226400010
View details for PubMedID 27506621
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A Novel HA/beta-TCP-Collagen Composite Enhanced New Bone Formation for Dental Extraction Socket Preservation in Beagle Dogs
MATERIALS
2016; 9 (3)
View details for DOI 10.3390/ma9030191
View details for Web of Science ID 000373805400038
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In Vitro Analysis of Fibronectin-Modified Titanium Surfaces
PLOS ONE
2016; 11 (1)
View details for DOI 10.1371/journal.pone.0146219
View details for Web of Science ID 000367801400119
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Fibronectin-Grafted Titanium Dental Implants: An In Vivo Study
BIOMED RESEARCH INTERNATIONAL
2016
Abstract
Modification of the physiochemical properties of titanium surfaces using glow discharge plasma (GDP) and fibronectin coating has been shown to enhance the surface hydrophilicity, surface roughness, cell adhesion, migration, and proliferation. This in vivo study aimed to evaluate the bone integration efficacy of a biologically modified implant surface. Two different surface-modified implants (Ar-GDP and GDP-fib) were placed in the mandibular premolar area of six beagle dogs for 2-8 weeks. Three techniques [histologic evaluation, resonance frequency analysis (RFA), and microcomputed tomography (micro-CT) evaluation] were used to detect the implant stability and bone-implant contact. The implant stability quotient values of GDP-fib implants were significantly greater than the Ar-GDP implants at 2 and 4 weeks (P < 0.01). The bone volume/total volume ratio of GDP-fib implants was greater than the Ar-GDP implants in micro-CT evaluation. A high positive correlation was observed between RFA and micro-CT measurements. At 2 weeks, osteoblasts were seen to line the implant surface, and multinuclear osteoclasts could be seen on the surface of old parent bone. After 8 weeks, a majority of the space in the wound chamber appeared to be replaced by bone. Enhancement of the stability of biologically modified implants was proved by the results of RFA, micro-CT, and histological analysis. This enhanced stability may help fasten treatment and be clinically beneficial.
View details for DOI 10.1155/2016/2414809
View details for Web of Science ID 000378283800001
View details for PubMedID 27366739
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Identification of Cell Surface Straight Chain Poly-N-Acetyl-Lactosamine Bearing Protein Ligands for VH4-34-Encoded Natural IgM Antibodies.
Journal of immunology
2015; 195 (11): 5178-5188
Abstract
B cell binding and cytotoxicity by human VH4-34-encoded Abs of the IgM isotype has been well documented. A VH4-34-IgM has recently shown a favorable early response in a phase 1 trial for treatment of B cell acute lymphoblastic leukemia. Although its B cell ligand has been identified as straight chain poly-N-acetyl-lactosamine (SC-PNAL), the carrier of the sugar moiety has not been identified. Using nanoelectrospray ionization mass spectrometry, we identify the metabolic activation related protein complex of CD147-CD98 as a major carrier of poly-N-acetyl-lactosamine (SC-PNAL) on human pre-B cell line Nalm-6. Previous studies have suggested CD45 as the SC-PNAL carrier for VH4-34-encoded IgG Abs. Because Nalm-6 is CD45 negative, human peripheral blood B lymphocytes and human B cell line, Reh, with high CD45 expression, were examined for SC-PNAL carrier proteins. Western blot analysis shows that the CD147-98 complex is indeed immunoprecipitated by VH4-34-encoded IgMs from human peripheral blood B lymphocytes and human B cell lines, Reh, OCI-Ly8, and Nalm-6. However, CD45 is immunoprecipitated only from peripheral B lymphocytes, but not from Reh despite the high expression of CD45. These results suggest that human B cells retain SC-PNAL on the CD147-98 complex, but modulate the sugar moiety on CD45. Because the carbohydrate moiety may act as a selecting Ag for VH4-34 autoantibody repertoire, its differential expression on proteins may provide a clue to the intricate atypical regulation of the VH4-34 gene.
View details for DOI 10.4049/jimmunol.1501697
View details for PubMedID 26503955
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Modal Damping Factor Detected with an Impulse-Forced Vibration Method Provides Additional Information on Osseointegration During Dental Implant Healing
INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS
2015; 30 (6): 1333-1340
View details for Web of Science ID 000367254100014
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Cytotoxic natural human MAb against ovarian carcinoma
AMER ASSOC CANCER RESEARCH. 2015
View details for DOI 10.1158/1557-3265.OVCASYMP14-POSTER-THER-1407
View details for Web of Science ID 000361386100112
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In silico investigation of FOXM1 binding and novel inhibitors in epithelial ovarian cancer.
Bioorganic & medicinal chemistry
2015; 23 (15): 4576-4582
Abstract
Using TCGA database, we had demonstrated that aberrantly activated Forkhead box M1 (FOXM1) correlates to worse overall survival in a subgroup of platinum resistant patients. Application of thiostrepton, a natural thiazole antibiotics that inhibits FOXM1 transcription activity in the clinic is hampered by difficulties in synthesis, degradation potential, and solubility. In this study, we aim to identify potential FOXM1 small molecule inhibitors to develop a new class of therapeutic agents to address the challenges in treating chemotherapy resistant EOC.We used in silico screening of compounds against a solved structure of FOXM1 and subsequently to derive a list of possible compounds that could inhibit FOXM1. Three compounds were tested for in vitro cytotoxicity and FOXM1 expression level was confirmed by RT-PCR and Western blot in EOC cell lines.The FOXM1 structure obtained from 3G73 represented the DNA binding region of FOXM1 and possessed the winged helix fold representative of the Forkhead family of enzymes with two wings in direct contact with DNA. For ease of representation, we described both wings as a dimer and a single wing as a monomer. From this structure, we hypothesized two main models of how thiostrepton binding to FOXM1 could possibly curtail its transcriptional activity. In the first model thiostrepton could bind either of the wings or both wings and prevent association to DNA. In the second model thiostrepton bind the FOXM1/DNA complex and weaken association of FOXM1 to DNA. Subsequently, small molecular inhibitors could also use either of the models to inhibit transcription. To account for both models, the NCI diversity set was screened against the FOXM1 dimer:DNA complex (39 hits), dimer (11 hits) and monomer (14 hits). Those hits were further classified by chemical structure, biological function and chemical similarities to known molecules that target FOXM1. In cellular cytotoxicity assays, N-phenylphenanthren-9-amine (related to hit #225) successfully showed cytotoxicity to all three cell lines with IC50 around 1μM, and downregulate FOXM1 and transcription of its downstream molecules such as CCNB1.By a combination of in silico screening coupled to cellular cytotoxicity studies, we have taken the first step towards identifying potential inhibitors of FOXM1 that can replace thiostrepton.
View details for DOI 10.1016/j.bmc.2015.06.002
View details for PubMedID 26164623
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Differentiating between borderline and invasive malignancies in ovarian tumors using a multivariate logistic regression model
TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY
2015; 54 (4): 398-402
Abstract
The objective of this study was to build a model to differentiate between borderline and invasive ovarian tumors.We performed a retrospective study involving 148 patients with borderline or invasive ovarian tumors in our institute between 1997 and 2012. Clinical and pathologic data were collected. Logistic regression was used to build the model.The model was created based on the following variables (p < 0.05): menopausal status; preoperative serum level of cancer antigen 125; the greatest diameter of the tumor; and the presence of solid parts on ultrasound imaging. The sensitivity and specificity of the model were 94.6% [95% confidence interval (CI), 0.887-1] and 78.3% (95% CI, 0.614-0.952) for patients aged ≥ 50 years, and 76.0% (95% CI, 0.622-0.903) and 60.0% (95% CI, 0.438-0.762) for those aged < 50 years, respectively. The performance of the model was tested using cross-validation.Differentiation between borderline and invasive ovarian tumors can be achieved using a model based on the following criteria: menopausal status; cancer antigen 125 level; and ultrasound parameters. The model is helpful to oncologists and patients in the initial evaluation phase of ovarian tumors.
View details for DOI 10.1016/j.tjog.2014.02.004
View details for PubMedID 26384058
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Impact of Navigation on Knowledge and Attitudes About Clinical Trials Among Chinese Patients Undergoing Treatment for Breast and Gynecologic Cancers
JOURNAL OF IMMIGRANT AND MINORITY HEALTH
2015; 17 (3): 976-979
Abstract
Racial, ethnic and economic disparities in cancer rates, outcomes, and clinical trials participation persist despite significant research. We examined barriers to clinical trials enrollment among Chinese patients, and developed a navigation program for Chinese gynecologic and breast cancer patients. Six bilingual navigators were trained and a navigator assigned to each patient for at least 2 months. All patients received a clinical trials booklet in Chinese and English. Data collection included pre-and post-navigation surveys, intake forms, and documentation of navigation encounters. Between July 2010 and May 31, 2011, we recruited 28 breast and gynecologic cancer patients. Patients averaged 317 min of navigation (range 63-1,852) during 8 sessions (range 3-28). They improved in 4 of 10 true-false knowledge statements about clinical trials. A patient navigation program for Chinese-speaking cancer patients is feasible. It results in high patient satisfaction rates and modest improvements in clinical trials knowledge and participation.
View details for DOI 10.1007/s10903-013-9901-x
View details for Web of Science ID 000355254500037
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Surface Analysis of Titanium Biological Modification with Glow Discharge
CLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH
2015; 17 (3): 469-475
Abstract
Glow discharge plasma (GDP) technology has been used to graft various proteins to the titanium surface, including albumin, type I collagen, but without fibronectin.The aim of this study was to evaluate and analyze the physical properties of fibronectin-grafted titanium surfaces after GDP treatment.Grade II titanium discs after cleaning and autoclaving were considered as original specimens, thus divided into four groups. The groups were different upon two treatments (GDP only and fibronectin grafting after GDP) and two storage temperature (4°C and 25°C). The implant surface morphology was characterized by scanning electron microscopy (SEM), roughness measurement, and wettability evaluation. The concentration relationship of fibronectin was by fluorescein isothiocyanate (FITC) labeling.SEM images showed that regular planar texture revealed on the surface of GDP-treated group, and irregular-folding protein was found on the fibronectin-grafted discs. Fibronectin-grafted groups had higher hydrophilicity and greater surface roughness than GDP-treated specimens. The storage temperature did not make obvious difference on the surface topography, wettability, and roughness. The number of fibronectin dots on the titanium surface labeling by FITC had positive relationship with the concentration of fibronectin solution used.Biologically modified titanium surface is more hydrophilic and rougher than GDP-treated ones. GDP treatment combined with fibronectin grafting increased the surface hydrophilicity and surface roughness of titanium discs, which may attribute to the affinity of cell adhesion, migration, proliferation, and differentiation.
View details for DOI 10.1111/cid.12141
View details for Web of Science ID 000355655500007
View details for PubMedID 23981288
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Impact of navigation on knowledge and attitudes about clinical trials among chinese patients undergoing treatment for breast and gynecologic cancers.
Journal of immigrant and minority health
2015; 17 (3): 976-979
Abstract
Racial, ethnic and economic disparities in cancer rates, outcomes, and clinical trials participation persist despite significant research. We examined barriers to clinical trials enrollment among Chinese patients, and developed a navigation program for Chinese gynecologic and breast cancer patients. Six bilingual navigators were trained and a navigator assigned to each patient for at least 2 months. All patients received a clinical trials booklet in Chinese and English. Data collection included pre-and post-navigation surveys, intake forms, and documentation of navigation encounters. Between July 2010 and May 31, 2011, we recruited 28 breast and gynecologic cancer patients. Patients averaged 317 min of navigation (range 63-1,852) during 8 sessions (range 3-28). They improved in 4 of 10 true-false knowledge statements about clinical trials. A patient navigation program for Chinese-speaking cancer patients is feasible. It results in high patient satisfaction rates and modest improvements in clinical trials knowledge and participation.
View details for DOI 10.1007/s10903-013-9901-x
View details for PubMedID 23963874
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Does Omentectomy in Epithelial Ovarian Cancer Affect Survival? An Analysis of the Surveillance, Epidemiology, and End Results Database
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
2015; 25 (4): 607-615
Abstract
Although omentectomy is part of the staging and treatment of epithelial ovarian cancer (EOC), its performance in a patient with a grossly normal omentum—acknowledging its role in debulking gross tumor deposits—has never been definitively shown to improve survival.Using Surveillance, Epidemiology, and End Results data from 1998 to 2010, we identified patients with EOC and assessed their age, race, year of diagnosis, tumor grade, histologic subtype, International Federation of Gynecology and Obstetrics stage, lymph node dissection, nodal findings, and performance of omentectomy. We compared disease-specific survival (DSS) based on the presence or absence of omentectomy using log-rank univariate analysis, Cox multivariate analysis, and Kaplan-Meier survival curves.A total of 20,975 patients with invasive EOC underwent surgical treatment. Initial univariate analysis indicated a lower mean DSS with performance of omentectomy. However, multivariate analysis demonstrated no significant association between DSS and performance of omentectomy (hazard ratio, 0.978; P = 0.506). The DSS was improved if lymphadenectomy was performed (hazard ratio, 0.60; P < 0.001). In recent years, there was a trend toward decreased performance of omentectomy.To look specifically at patients without bulky omental disease, a subset analysis was done looking at patients with stage I-IIIA disease who had had lymphadenectomy performed. There were 5454 patients in the group who underwent an omentectomy and 2404 patients in the group who did not. No difference in DSS was seen between the groups based on performance of omentectomy (P = 0.89). However, the analysis was limited by the lack of Surveillance, Epidemiology, and End Results data on the extent of omentectomy, amount of residual disease, and adjuvant chemotherapy.In this analysis, performance of omentectomy in patients with EOC without bulky disease (≤stage IIIA) did not seem to confer improvement in survival. A randomized control trial would be needed to fully address this question.
View details for DOI 10.1097/IGC.0000000000000412
View details for Web of Science ID 000354103000011
View details for PubMedID 25756404
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Identification of MicroRNAs and their Targets Associated with Embryo Abortion during Chrysanthemum Cross Breeding via High-Throughput Sequencing
PLOS ONE
2015; 10 (4)
Abstract
MicroRNAs (miRNAs) are important regulators in plant development. They post-transcriptionally regulate gene expression during various biological and metabolic processes by binding to the 3'-untranslated region of target mRNAs to facilitate mRNA degradation or inhibit translation. Chrysanthemum (Chrysanthemum morifolium) is one of the most important ornamental flowers with increasing demand each year. However, embryo abortion is the main reason for chrysanthemum cross breeding failure. To date, there have been no experiments examining the expression of miRNAs associated with chrysanthemum embryo development. Therefore, we sequenced three small RNA libraries to identify miRNAs and their functions. Our results will provide molecular insights into chrysanthemum embryo abortion.Three small RNA libraries were built from normal chrysanthemum ovules at 12 days after pollination (DAP), and normal and abnormal chrysanthemum ovules at 18 DAP. We validated 228 miRNAs with significant changes in expression frequency during embryonic development. Comparative profiling revealed that 69 miRNAs exhibited significant differential expression between normal and abnormal embryos at 18 DAP. In addition, a total of 1037 miRNA target genes were predicted, and their annotations were defined by transcriptome data. Target genes associated with metabolic pathways were most highly represented according to the annotation. Moreover, 52 predicted target genes were identified to be associated with embryonic development, including 31 transcription factors and 21 additional genes. Gene ontology (GO) annotation also revealed that high-ranking miRNA target genes related to cellular processes and metabolic processes were involved in transcription regulation and the embryo developmental process.The present study generated three miRNA libraries and gained information on miRNAs and their targets in the chrysanthemum embryo. These results enrich the growing database of new miRNAs and lay the foundation for the further understanding of miRNA biological function in the regulation of chrysanthemum embryo abortion.
View details for DOI 10.1371/journal.pone.0124371
View details for Web of Science ID 000353376800079
View details for PubMedID 25909659
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The Secular Trends in the Incidence Rate and Outcomes of Out-of-Hospital Cardiac Arrest in Taiwan-A Nationwide Population-Based Study
PLOS ONE
2015; 10 (4)
Abstract
This study investigated the trends in incidence and mortality of out-of-hospital cardiac arrest (OHCA), as well as factors associated with OHCA outcomes in Taiwan.Our study included OHCA patients requiring cardiopulmonary resuscitation (CPR) upon arrival at the hospital. We used national time-series data on annual OHCA incidence rates and mortality rates from 2000 to 2012, and individual demographic and clinical data for all OHCA patients requiring mechanical ventilation (MV) care from March of 2010 to September of 2011. Analytic techniques included the time-series regression and the logistic regression.There were 117,787 OHCAs in total. The overall incidence rate during the 13 years was 51.1 per 100,000 persons, and the secular trend indicates a sharp increase in the early 2000s and a decrease afterwards. The trend in mortality was also curvilinear, revealing a substantial increase in the early 2000s, a subsequent steep decline and finally a modest increase. Both the 30-day and 180-day mortality rates had a long-term decreasing trend over the period (p<0.01). For both incidence and mortality rates, a significant second-order autoregressive effect emerged. Among OHCA patients with MV, 1-day, 30-day and 180-day mortality rates were 31.3%, 75.8%, and 86.0%, respectively. In this cohort, older age, the female gender, and a Charlson comorbidity index score ≥ 2 were associated with higher 180-day mortality; patients delivered to regional hospitals and those residing in non-metropolitan areas had higher death risk.Overall, both the 30-day and the 180-day mortality rates after OHCA had a long-term decreasing trend, while the 1-day mortality had no long-term decline. Among OHCA patients requiring MV, those delivered to regional hospitals and those residing in non-metropolitan areas tended to have higher mortality, suggesting a need for effort to further standardize and improve in-hospital care across hospitals and to advance pre-hospital care in non-metropolitan areas.
View details for DOI 10.1371/journal.pone.0122675
View details for Web of Science ID 000353015800070
View details for PubMedID 25875921
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Cervical cancer, version 2.2015.
Journal of the National Comprehensive Cancer Network
2015; 13 (4): 395-404
Abstract
The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN Cervical Cancer Panel's discussion and major guideline updates from 2014 and 2015. The recommended systemic therapy options for recurrent and metastatic cervical cancer were amended upon panel review of new survival data and the FDA's approval of bevacizumab for treating late-stage cervical cancer. This article outlines relevant data and provides insight into panel decisions regarding various combination regimens. Additionally, a new section was added to provide additional guidance on key principles of evaluation and surgical staging in cervical cancer. This article highlights 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches.
View details for PubMedID 25870376
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Cervical Cancer, Version 2.2015 Featured Updates to the NCCN Guidelines
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
2015; 13 (4): 395-404
Abstract
The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN Cervical Cancer Panel's discussion and major guideline updates from 2014 and 2015. The recommended systemic therapy options for recurrent and metastatic cervical cancer were amended upon panel review of new survival data and the FDA's approval of bevacizumab for treating late-stage cervical cancer. This article outlines relevant data and provides insight into panel decisions regarding various combination regimens. Additionally, a new section was added to provide additional guidance on key principles of evaluation and surgical staging in cervical cancer. This article highlights 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches.
View details for Web of Science ID 000352962200005
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IgG Subclasses and Isotypes of VH4-34 Encoded Antibodies
IMMUNOLOGICAL INVESTIGATIONS
2015; 44 (4): 400-410
Abstract
VH4-34 gene encoded autoantibodies are elevated in systemic lupus erythematosus (SLE) and in other diseases associated with B-cell hyperproliferation/dysfunction. One of the autoantigens recognized by VH4-34-encoded antibodies are branched/linear poly N-acetyl lactosamine chains. Since the anti-carbohydrate response in humans is dominated by the IgG2 subclass, here we tested whether VH4-34 encoded IgG showed similar subclass segregation. Serum samples from SLE, infectious mononucleosis, nasopharyngeal carcinoma and hepatitis-C were analyzed. Levels of VH4-34-encoded IgM and IgA isotypes were also tested. VH4-34-IgM and IgA were elevated in all four clinical conditions. VH4-34-IgG was detected in the IgG1 and IgG3 subclass but not in the IgG2 and IgG4 subclass. Interestingly, VH4-34-IgG3 was also detected in serum samples of normal healthy adults. These observations are discussed in context of the VH4-34 gene regulation. VH4-34 repertoire development is of interest since it is the only human VH gene profoundly overrepresented in the naïve repertoire but counter-selected for antibody secretion. VH4-34 B-cell could thus become a unique tool to inspect germinal center independent/dependent pathways of subclass and isotype-specific antibody secretion.
View details for DOI 10.3109/08820139.2015.1015682
View details for Web of Science ID 000353918800007
View details for PubMedID 25942350
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In silico investigation of FOXM1 binding and novel inhibitors in epithelial ovarian cancer (EOC)
AMER ASSOC CANCER RESEARCH. 2014
View details for DOI 10.1158/1538-7445.AM2014-5373
View details for Web of Science ID 000349910204292
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Artemisinin derivatives synergize with paclitaxel by targeting FOXM1 through Raf/MEK/MAPK signaling pathway in ovarian cancer
AMER ASSOC CANCER RESEARCH. 2014
View details for DOI 10.1158/1538-7445.AM2014-470
View details for Web of Science ID 000349906904434
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IGM-55.5, a novel monoclonal human recombinant IgM antibody with potent activity against B cell leukemia and lymphoma
AMER ASSOC CANCER RESEARCH. 2014
View details for DOI 10.1158/1538-7445.AM2014-645
View details for Web of Science ID 000349906905107
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Cell-penetrating, guanidinium-rich molecular transporters for overcoming efflux-mediated multidrug resistance.
Molecular pharmaceutics
2014; 11 (8): 2553-2565
Abstract
Multidrug resistance (MDR) is a major cause of chemotherapy failure in the clinic. Drugs that were once effective against naïve disease subsequently prove ineffective against recurrent disease, which often exhibits an MDR phenotype. MDR can be attributed to many factors; often dominating among these is the ability of a cell to suppress or block drug entry through upregulation of membrane-bound drug efflux pumps. Efflux pumps exhibit polyspecificity, recognizing and exporting many different types of drugs, especially those whose lipophilic nature contributes to residence in the membrane. We have developed a general strategy to overcome efflux-based resistance. This strategy involves conjugating a known drug that succumbs to efflux-mediated resistance to a cell-penetrating molecular transporter, specifically, the cell-penetrating peptide (CPP), d-octaarginine. The resultant conjugates are discrete single entities (not particle mixtures) and highly water-soluble. They rapidly enter cells, are not substrates for efflux pumps, and release the free drug only after cellular entry at a rate controlled by linker design and favored by target cell chemistry. This general strategy can be applied to many classes of drugs and allows for an exceptionally rapid advance to clinical testing, especially of drugs that succumb to resistance. The efficacy of this strategy has been successfully demonstrated with Taxol in cellular and animal models of resistant cancer and with ex vivo samples from patients with ovarian cancer. Next generation efforts in this area will involve the extension of this strategy to other chemotherapeutics and other MDR-susceptible diseases.
View details for DOI 10.1021/mp500161z
View details for PubMedID 24798708
View details for PubMedCentralID PMC4123947
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Hedgehog Signaling Regulates Drug Sensitivity by Targeting ABC Transporters ABCB1 and ABCG2 in Epithelial Ovarian Cancer
MOLECULAR CARCINOGENESIS
2014; 53 (8): 625-634
Abstract
A major challenge of successful chemotherapy in ovarian cancer is overcoming intrinsic or acquired multi-drug resistance caused by active drug efflux mediated by ATP-binding cassette (ABC) transporters. Regulation of these transporters in ovarian cancer is poorly understood. We have found that abnormal expression of the hedgehog (Hh) signaling pathway transcription factor Gli1 is involved in the regulation of ABC transporters ABCB1 and ABCG2 in ovarian cancer. Hh is a known regulator of cancer cell proliferation and differentiation in several other types of invasive and metastatic malignancies. Our work has demonstrated that Gli1 is abnormally activated in a portion of ovarian cancers. Inhibition of Gli1 expression decreases ABCB1 and ABCG2 gene expression levels and enhances the response of ovarian cancer cells to certain chemotherapeutic drugs. The underlying mechanism is a direct association of Gli1 with a specific consensus sequence located in the promoter region of ABCB1 and ABCG2 genes. This study provides new understanding of ABC gene regulation by Hh signaling pathway, which may lead to the identification of new markers to detect and to anticipate ovarian cancer chemotherapy drug sensitivity. © 2013 Wiley Periodicals, Inc.
View details for DOI 10.1002/mc.22015
View details for Web of Science ID 000339562800004
View details for PubMedID 23423781
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Uterine neoplasms, version 1.2014.
Journal of the National Comprehensive Cancer Network
2014; 12 (2): 248-280
Abstract
Adenocarcinoma of the endometrium (also known as endometrial cancer or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. An estimated 49,560 new uterine cancer cases will occur in 2013, with 8190 deaths resulting from the disease. Uterine sarcomas (stromal/mesenchymal tumors) are uncommon malignancies, accounting for approximately 3% of all uterine cancers. The NCCN Guidelines for Uterine Neoplasms describe malignant epithelial carcinomas and uterine sarcomas; each of these major categories contains specific histologic groups that require different management. This excerpt of these guidelines focuses on early-stage disease.
View details for PubMedID 24586086
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The omentum and omentectomy in epithelial ovarian cancer: a reappraisal: part II--The role of omentectomy in the staging and treatment of apparent early stage epithelial ovarian cancer.
Gynecologic oncology
2013; 131 (3): 784-790
Abstract
This article reviews the literature concerning the role of omentectomy in the staging and treatment of clinically apparent early stage epithelial ovarian cancer.A review of the English language literature based on a MEDLINE (PubMed) database search using the keywords: ovary, cancer, carcinoma, omentum, and omentectomy. An additional collection of reports was found by systematically reviewing all references from retrieved papers.Historically, the realization that ovarian cancer cells have a predisposition to metastasize to the omentum has led to the inclusion of omentectomy, both for the purpose of accurate staging of ovarian cancer and for its possible therapeutic benefit. In apparently early stage epithelial ovarian cancer, microscopic disease in the omentum is found in 0-22% of the cases; however extra-ovarian disease isolated to the omentum is found in 2-7% of cases at most. There are no specific guidelines as to how much of the omentum should be removed, but pathology studies show that for the purpose of staging and detecting microscopic disease, omental biopsies are probably sufficient in a grossly normal appearing omentum. In cases where adjuvant chemotherapy is planned, the role of omentectomy appears to be primarily for staging, while its therapeutic role remains unclear in microscopic omental disease.In apparent early stage ovarian cancer, the presence of isolated omental metastases is relatively rare. For staging purposes in such cases, random omental biopsies rather than total omentectomy may suffice. Furthermore, chemotherapy appears to effectively treat microscopic disease and therefore if this is already planned the benefit of omentectomy is unclear.
View details for DOI 10.1016/j.ygyno.2013.09.013
View details for PubMedID 24056005
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The omentum and omentectomy in epithelial ovarian cancer: A reappraisal: Part II - The role of omentectomy in the staging and treatment of apparent early stage epithelial ovarian cancer.
Gynecologic oncology
2013; 131 (3): 784-790
View details for DOI 10.1016/j.ygyno.2013.09.013
View details for PubMedID 24056005
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The Omentum and omentectomy in epithelial ovarian cancer: A reappraisal Part I - Omental function and history of omentectomy.
Gynecologic oncology
2013; 131 (3): 780-783
Abstract
This article reviews the literature concerning the function of the omentum and how omentectomy came to be part of the staging and treatment of epithelial ovarian cancer.A review of the English language literature based on a MEDLINE (PubMed) database search using the key words: ovary, cancer, carcinoma, omentum, and omentectomy. An additional collection of reports was found by systematically reviewing all references from retrieved papers.Descriptions of the omentum can be found as far back as the time of the ancient Egyptians. An immunologic role of the omentum was confirmed in 1980s when "milky spots" were described. Omentectomy arrived as part of the ovarian cancer guidelines in the 1960s after observing that the omentum was a frequent site of metastasis and that patients with removal of all diseased tissue did better. The exact role of the omentum in immunology and cancer remains incompletely understood.Historically, occult omental metastases in otherwise early disease have led to the inclusion of omentectomy for the purpose of accurate staging and for a possible therapeutic benefit. Laboratory studies on the role in cancer of the omental fat and milky spots are controversial.
View details for DOI 10.1016/j.ygyno.2013.09.014
View details for PubMedID 24056004
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Ovarian cancer, version 2.2013.
Journal of the National Comprehensive Cancer Network
2013; 11 (10): 1199-1209
Abstract
These NCCN Guidelines Insights focus on the major updates to the 2013 NCCN Guidelines for Ovarian Cancer. Four updates were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials. The topics include 1) intraperitoneal chemotherapy, 2) CA-125 monitoring for ovarian cancer recurrence, 3) surveillance recommendations for less common ovarian histopathologies, and 4) recent changes in therapy for recurrent epithelial ovarian cancer. These NCCN Guidelines Insights also discuss why some recommendations were not made.
View details for PubMedID 24142821
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Ovarian Cancer, Version 2.2013 Featured Updates to the NCCN Guidelines
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
2013; 11 (10): 1199-1209
Abstract
These NCCN Guidelines Insights focus on the major updates to the 2013 NCCN Guidelines for Ovarian Cancer. Four updates were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials. The topics include 1) intraperitoneal chemotherapy, 2) CA-125 monitoring for ovarian cancer recurrence, 3) surveillance recommendations for less common ovarian histopathologies, and 4) recent changes in therapy for recurrent epithelial ovarian cancer. These NCCN Guidelines Insights also discuss why some recommendations were not made.
View details for Web of Science ID 000325929600004
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Cervical cancer.
Journal of the National Comprehensive Cancer Network
2013; 11 (3): 320-343
Abstract
These NCCN Clinical Practice Guidelines in Oncology for Cervical Cancer focus on early-stage disease, because it occurs more frequently in the United States. After careful clinical evaluation and staging, the primary treatment of early-stage cervical cancer is either surgery or radiotherapy. These guidelines include fertility-sparing and non-fertility-sparing treatment for those with early-stage disease, which is disease confined to the uterus. A new fertility-sparing algorithm was added for select patients with stage IA and IB1 disease..
View details for PubMedID 23486458
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Cervical Cancer Clinical Practice Guidelines in Oncology
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
2013; 11 (3): 320-343
Abstract
These NCCN Clinical Practice Guidelines in Oncology for Cervical Cancer focus on early-stage disease, because it occurs more frequently in the United States. After careful clinical evaluation and staging, the primary treatment of early-stage cervical cancer is either surgery or radiotherapy. These guidelines include fertility-sparing and non-fertility-sparing treatment for those with early-stage disease, which is disease confined to the uterus. A new fertility-sparing algorithm was added for select patients with stage IA and IB1 disease..
View details for Web of Science ID 000316037400011
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Ovarian Cancer, Version 3.2012 Featured Updates to the NCCN Guidelines
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
2012; 10 (11): 1339-1349
Abstract
These NCCN Guidelines Insights focus on the major updates for the 2012 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer by describing how and why the new recommendations were made. The 6 update topics were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials, and include: 1) screening, 2) diagnostic tests for assessing pelvic masses, 3) primary treatment using neoadjuvant chemotherapy, 4) primary adjuvant treatment using bevacizumab in combination with chemotherapy, 5) therapy for recurrent disease, and 6) management of drug/hypersensitivity reactions. These NCCN Guidelines Insights also discuss why some recommendations were not made (eg, panel members did not feel the new data warranted changing the guideline). See "Updates" in the NCCN Guidelines for Ovarian Cancer for a complete list of all the recent revisions.
View details for Web of Science ID 000310822900005
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Ovarian cancer, version 3.2012.
Journal of the National Comprehensive Cancer Network
2012; 10 (11): 1339-1349
Abstract
These NCCN Guidelines Insights focus on the major updates for the 2012 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer by describing how and why the new recommendations were made. The 6 update topics were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials, and include: 1) screening, 2) diagnostic tests for assessing pelvic masses, 3) primary treatment using neoadjuvant chemotherapy, 4) primary adjuvant treatment using bevacizumab in combination with chemotherapy, 5) therapy for recurrent disease, and 6) management of drug/hypersensitivity reactions. These NCCN Guidelines Insights also discuss why some recommendations were not made (eg, panel members did not feel the new data warranted changing the guideline). See "Updates" in the NCCN Guidelines for Ovarian Cancer for a complete list of all the recent revisions.
View details for PubMedID 23138163
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Phenotypic heterogeneity in serous ovarian cancer
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2012: S9–S9
View details for DOI 10.1016/j.ygyno.2012.07.025
View details for Web of Science ID 000308783800074
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Er:YAG Laser-Roughened Enamel Promotes Osteoblastic Differentiation
PHOTOMEDICINE AND LASER SURGERY
2012; 30 (9): 516-522
Abstract
The aim of this study was to test whether Er:YAG laser-etched enamel of human teeth could act as a biologically active scaffold for tissue regeneration.Hydroxylapatite (HA) with rough surface created by acid etching treatment has been used as a scaffold for tissue engineering. However, whether tooth HA can be a scaffold for osteoblastic cell seeding is still unclear.Enamel samples from human teeth were pretreated with an Er:YAG laser to create a rough surface. Then the surface of the laser-treated enamel was examined using a surface roughness profilometer and a scanning electron microscope. In addition, static water contact angles of the Er:YAG laser-treated enamel samples were measured using goniometry. To observe the effects of cell behavior on an Er:YAG laser-roughened enamel surface, we cultured MG63 osteoblast-like cells on the surface-modified enamel samples. Alkaline phosphatase activity, a marker of cell proliferation and differentiation, was monitored and compared with that in untreated control and acid-etched enamel samples.Er:YAG laser treatment significantly improved the surface roughness of the enamel samples. Furthermore, MG63 osteoblast-like cells cultured on the Er:YAG laser-roughened enamel surface expressed more alkaline phosphatase activity and exhibited greater degrees of cellular differentiation than did cells that had been cultured on untreated enamel samples.These results demonstrate that Er:YAG laser-roughened enamel promotes osteoblastic differentiation. This finding suggests that Er:YAG laser-roughened enamel surfaces can potentially serve as a scaffold for tissue engineering.
View details for DOI 10.1089/pho.2011.3214
View details for Web of Science ID 000308081600003
View details for PubMedID 22793262
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Taxol-oligoarginine conjugates overcome drug resistance in-vitro in human ovarian carcinoma
GYNECOLOGIC ONCOLOGY
2012; 126 (1): 118-123
Abstract
Multidrug resistance is the major cause of failure of many chemotherapeutic agents. While resistance can arise from several factors, it is often dominated by drug efflux mediated by P-glycoprotein (P-gp), a membrane-bound polysubstrate export pump expressed at high levels in resistant cells. While co-administration of pump inhibitors and a drug could suppress efflux, this two-drug strategy has not yet advanced to therapy. We recently demonstrated that the reversible attachment of a guanidinium-rich molecular transporter, polyarginine, to a drug provides a conjugate that overcomes efflux-based resistance in cells and animals. This study is to determine whether this strategy for overcoming resistance is effective against human disease.Tumor samples from ovarian cancer patients, both malignant ascites cells and dissociated solid tumor cells, were exposed to Taxol-oligoarginine conjugates designed to release free drug only after cell entry. Cell viability was determined via propidium-iodide uptake by flow cytometry. To analyze bystander effect, toxicity of the drug conjugates was also tested on peripheral blood leucocytes.Human ovarian carcinoma specimens resistant to Taxol in vitro demonstrated increased sensitivity to killing by all Taxol-transporter conjugates tested. These studies also show that the drug conjugates were not significantly more toxic to normal human peripheral blood leukocytes than Taxol.These studies with human tumor indicate that oligoarginine conjugates of known drugs can be used to overcome the efflux-based resistance to the drug, providing a strategy that could improve the treatment outcomes of patients with efflux-based drug-resistance.
View details for DOI 10.1016/j.ygyno.2012.03.049
View details for Web of Science ID 000305878400023
View details for PubMedID 22484398
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The AP2-like gene NsAP2 from water lily is involved in floral organogenesis and plant height
JOURNAL OF PLANT PHYSIOLOGY
2012; 169 (10): 992-998
Abstract
APETALA2 (AP2) genes are ancient and widely distributed among the seed plants, and play an important role during the plant life cycle, acting as key regulators of many developmental processes. In this study, an AP2 homologue, NsAP2, was characterized from water lily (Nymphaea sp. cv. 'Yellow Prince') and is believed to be rather primitive in the evolution of the angiosperms. In situ RNA hybridization showed that NsAP2 transcript was present in all regions of the floral primordium, but had the highest level in the emerging floral organ primordium. After the differentiation of floral organs, NsAP2 was strongly expressed in sepals and petals, while low levels were found in stamens and carpels. The NsAP2 protein was suggested to be localized in the cell nucleus by onion transient expression experiment. Overexpression of NsAP2 in Arabidopsis led to more petal numbers, and Arabidopsis plants expressing NsAP2 exhibited higher plant height, which may be a result of down-regulated expression of GA2ox2 and GA2ox7. Our results indicated that the NsAP2 protein may function in flower organogenesis in water lily, and it is a promising gene for plant height improvement.
View details for DOI 10.1016/j.jplph.2012.02.018
View details for Web of Science ID 000307413000009
View details for PubMedID 22591856
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Factors influencing fecundity in experimental crosses of water lotus (Nelumbo nucifera Gaertn.) cultivars
BMC PLANT BIOLOGY
2012; 12
Abstract
Breeding programs for the water lotus (Nelumbo nucifera) are hampered by an inability to account for variation in seed set associated with crosses between different cultivars. We studied seed set in two reciprocal crosses between lotus cultivars ('Guili' × 'Aijiangnan' and 'Molingqiuse' × 'Qinhuaiyanzhi') to obtain insights into factors that govern fecundity in these experimental hybrids. Pollen viability, stigma receptivity and embryo development were compared for each hybrid and reciprocal cross.Pollen viability of the individual cultivars ranged from 4.1% to 20.2%, with the highest level (>11.9%) for all cultivars observed from the earliest collected grains (05:00-06:00 a.m.). Stigmatic pollen germination peaked at 4 h after pollination and varied from 4.8 to 60.6 grains per stigma among the crosses. Production of normal embryos ranged from 7.6% to 58.8% at 1 d after pollination and from 0 to 25% by 11 d after pollination. Seed set in crosses (0.2-23.3%) was generally lower than in open-pollinated plants (8.4-26.5%). Similar to the germination results, seed set was substantially reduced in both reciprocal crosses.These results suggested that poor pollen fertility, low stigma receptivity, and embryo abortion were responsible for the failure of the crosses 'Molingqiuse' × 'Qinhuaiyanzhi', 'Qinhuaiyanzhi' × 'Molingqiuse', and 'Aijiangnan' × 'Guili'.
View details for DOI 10.1186/1471-2229-12-82
View details for Web of Science ID 000310379000001
View details for PubMedID 22676293
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The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2012; 109 (17): 6662-6667
Abstract
CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.
View details for DOI 10.1073/pnas.1121623109
View details for PubMedID 22451913
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Interplay between Cell Migration and Neurite Outgrowth Determines SH2B1 beta-Enhanced Neurite Regeneration of Differentiated PC12 Cells
PLOS ONE
2012; 7 (4)
Abstract
The regulation of neurite outgrowth is crucial in developing strategies to promote neurite regeneration after nerve injury and in degenerative diseases. In this study, we demonstrate that overexpression of an adaptor/scaffolding protein SH2B1β promotes neurite re-growth of differentiated PC12 cells, an established neuronal model, using wound healing (scraping) assays. Cell migration and the subsequent remodeling are crucial determinants during neurite regeneration. We provide evidence suggesting that overexpressing SH2B1β enhances protein kinase C (PKC)-dependent cell migration and phosphatidylinositol 3-kinase (PI3K)-AKT-, mitogen activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) kinase (MEK)-ERK-dependent neurite re-growth. Our results further reveal a cross-talk between pathways involving PKC and ERK1/2 in regulating neurite re-growth and cell migration. We conclude that temporal regulation of cell migration and neurite outgrowth by SH2B1β contributes to the enhanced regeneration of differentiated PC12 cells.
View details for DOI 10.1371/journal.pone.0034999
View details for Web of Science ID 000305341000017
View details for PubMedID 22539954
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Hedgehog signaling regulates drug sensitivity by targeting ABC transporters in epithelial ovarian cancer (EOC)
AMER ASSOC CANCER RESEARCH. 2012
View details for DOI 10.1158/1538-7445.AM2012-3068
View details for Web of Science ID 000209701605094
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The impact of chemotherapy and fertility-sparing surgery on recurrence of serous borderline ovarian tumors: A multi-institutional study of 491 patients
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2012: S5–S5
View details for DOI 10.1016/j.ygyno.2011.12.007
View details for Web of Science ID 000303227600008
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Phase I trial of a novel human monoclonal antibody mAb216 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
2012; 97 (1): 30-37
Abstract
This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy.Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts.Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6-65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients.Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.
View details for DOI 10.3324/haematol.2011.045997
View details for Web of Science ID 000299870500009
View details for PubMedID 21993685
View details for PubMedCentralID PMC3248928
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Effects of CO2 Enrichment on Growth and Development of Impatiens hawkeri
SCIENTIFIC WORLD JOURNAL
2012: 1-9
View details for DOI 10.1100/2012/601263
View details for Web of Science ID 000303021400001
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Prox-1, Podoplanin and HPV staining assists in identification of lymphangioma circumscriptum of the vulva and discrimination from vulvar warts
HISTOPATHOLOGY
2011; 59 (6): 1274-1277
View details for DOI 10.1111/j.1365-2559.2011.03994.x
View details for Web of Science ID 000298358000028
View details for PubMedID 22026919
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Real-time detection of beta 1 integrin expression on MG-63 cells using electrochemical impedance spectroscopy
BIOSENSORS & BIOELECTRONICS
2011; 28 (1): 221-226
Abstract
Beta 1 integrin is a membrane protein responsible for attachment and migration of osteosarcoma cells. In this study, expression of β1 integrin on MG-63 cells, a human osteogenic sarcoma cell line, was monitored using electrochemical impedance spectroscopy (EIS). ITO-based biochips were developed using a semiconductor technique. Differences in electric resistance (ΔR) were measured continuously when cells binding with anti-β1 integrin antibody coagulated with nano-scale gold particles. The results of the EIS system were compared with traditional immunofluorescence staining. We found that sample chambers with higher cell densities had larger ΔR values. When the cell densities increased from 5 × 10(4) cells/ml to 5 × 10(5) cells/ml, the ΔR value dose-dependently increased from 14 Ω to 37 Ω. In addition, a highly linear relationship (correlation coefficient, 0.921) was found between the ΔR values and the corresponding fluorescence intensities (p<0.05). These results suggest that electrochemical impedance spectroscopy can be a useful tool for evaluating β1 integrin expression on cell membranes.
View details for DOI 10.1016/j.bios.2011.07.022
View details for Web of Science ID 000295661700033
View details for PubMedID 21816605
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The expression of floral organ identity genes in contrasting water lily cultivars
PLANT CELL REPORTS
2011; 30 (10): 1909-1918
Abstract
The floral organs of typical eudicots such as Arabidopsis thaliana are arranged in four characteristic whorls, namely the sepal, petal, stamen and carpel, and the "ABC" floral organ identity model has been based on this arrangement. However, the floral organs in most basal angiosperms are spirally arranged with a gradual transition from the inside to outside, and an alternative model referred to as "fading borders" was developed to take account of this. The flower morphology of the water lily was tested against the "fading borders" model by determining the expression profile of the six primary floral organ identity genes AP2, AGL6, AP3, PI, AG and SEP1 in two cultivars showing contrasting floral morphology. In addition, to get accurate floatation of the genes expression level from outer to inner, we divided the floral organs into eight whorls according to morphological features. All these genes were expressed throughout all whorls of the flower, but their expression level changed gradually from the outside of the flower to its inside. This pattern was consistent with the "fading borders" model.
View details for DOI 10.1007/s00299-011-1098-7
View details for Web of Science ID 000297200600011
View details for PubMedID 21660548
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Wnt and Hedgehog Gene Pathway Expression in Serous Ovarian Cancer
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
2011; 21 (6): 975-980
Abstract
Ovarian cancer has very heterogeneous histological classification, and response to therapy of the same grade and type varies. We studied genes in the Wnt and hedgehog (Hh) pathways, which are essential for embryonic development and which play critical roles in proliferation in a variety of human cancers. Variations in these pathway genes causing proliferation could play a role in the variation in tumor progression and response to therapy.Using real-time polymerase chain reaction, we studied 16 primary grade 3 International Federation of Gynecology and Obstetrics stage III serous ovarian cancer samples for expression of the Wnt pathway gene AXIN2, fibroblast growth factor 9, and Hh pathway gene expressions of glioma-associated oncogene 1, glioma-associated oncogene 2, patched homolog 1, patched homolog 2, Indian Hedgehog (HH), sonic HH, and Smoothened, a G protein-coupled receptor protein. Normal ovary epithelial cell line was used as control.We found wide variation of up-regulation of pathway component and target genes in the primary tumor samples and apparent cross talk between the pathways. AXIN2, a Wnt target gene, showed increased expression in all serous ovarian cancer samples. Fibroblast growth factor 9 was also overexpressed in all tumors with greater than 1000-fold increase in gene expression in 4 tumors. Expression of Hh pathway genes varied greatly. More than half of the tumor samples showed involvement of Hh signaling or pathway activation either by expression of transcription factors and Hh ligands or by overexpression of Indian HH/sonic HH and the receptor-encoding patched homolog 1/patched homolog 2.We found a wide variation in fold expression of genes involved in the Wnt and Hh pathway between patient samples.
View details for DOI 10.1097/IGC.0b013e31821caa6f
View details for Web of Science ID 000293169500004
View details for PubMedID 21666490
View details for PubMedCentralID PMC3285558
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SH2B1 beta Regulates N-Cadherin Levels, Cell-Cell Adhesion and Nerve Growth Factor-Induced Neurite Initiation
JOURNAL OF CELLULAR PHYSIOLOGY
2011; 226 (8): 2063-2074
Abstract
Little is known regarding the role of inter-cellular interaction during neuronal differentiation. Homophilic N-cadherin engagement between cells contributes to neuronal migration. However, its function in neurite initiation is not clear. In this study, we provide the first evidence that the adaptor protein SH2B1β regulated N-cadherin levels and neurite initiation. Overexpression of SH2B1β reduces N-cadherin levels and increased phosphotyrosine 654 β-catenin, leading to increased nerve growth factor-induced neurite initiation in PC12 cells, an established model for neuronal differentiation. In contrast, overexpression of the dominant-negative mutant SH2B1β(R555E) increases N-cadherin expression, cell-cell aggregation, and reduces neurite initiation. Moreover, SH2B1β binds directly or indirectly to N-cadherin indicative of its involvement in regulating the levels of N-cadherin. Taken together, these findings provide significant new insights into how N-cadherin-mediated inter-cellular interactions may influence neurite initiation and how SH2B1β may regulate these processes.
View details for DOI 10.1002/jcp.22544
View details for Web of Science ID 000290520900012
View details for PubMedID 21520058
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Structural Analysis of Cyclic-loaded Nickel-Titanium Rotary Instruments by Using Resonance Frequency as a Parameter
JOURNAL OF ENDODONTICS
2011; 37 (7): 993-996
Abstract
The aim of this study was to investigate the relationship between fatigue life and resonance frequency (RF) of various types of nickel-titanium (NiTi) rotary instruments. In addition, the influence of NiTi instruments with different manufacturing methods on cyclic loading was evaluated by using RF as a parameter.Twenty-eight ProFile instruments and 10 Twisted File instruments were subjected to cyclic fatigue-loading until fracture by repeated preparation with simulated root canals made of clear resin. The RF of each sample was recorded immediately after the simulated canal block was prepared. For each sample, the microscopic images on the fracture surface, change in lengthening deformation, number of canal blocks prepared, and corresponding RF changes were recorded.For all the tested instruments, RF values decreased gradually before breakdown when the fatigue failure of the instruments was associated with plastic deformation. In addition, there was a linear relationship between the RF change and the corresponding deformation of the failed instruments.These results demonstrate that the RF analysis has potential as a tool for structural analysis in NiTi instruments.
View details for DOI 10.1016/j.joen.2011.03.022
View details for Web of Science ID 000292793800018
View details for PubMedID 21689558
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Gynecologic malignancies in female-to-male transgender patients: the need of original gender surveillance
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
2011; 204 (5): E9-E12
Abstract
We report a case of uterine cancer and invasive cervical cancer, detected incidentally during the female-to-male sex reassignment surgery. The management of these patients is presented. Such individuals may not be receiving regular gynecologic care appropriate to their remaining genital organs; symptoms of malignant disease may be missed.
View details for DOI 10.1016/j.ajog.2010.12.057
View details for Web of Science ID 000290206200003
View details for PubMedID 21354550
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The incidence of isolated para-aortic nodal metastasis in completely staged endometrial cancer patients
GYNECOLOGIC ONCOLOGY
2011; 121 (1): 122-125
Abstract
To describe and review the incidence of para-aortic (PA) nodal metastasis in completely staged endometrial cancer patients who are negative for pelvic nodal metastasis.Using an institutionally maintained database, we identified all patients with endometrial cancer from 2002 to 2006 who had both pelvic and aortic nodal dissections and determined the rate of isolated para-aortic nodal metastasis in non-malignant (i.e. negative) pelvic nodes.201 endometrial cancer patients were surgically treated at our institution from 2002 to 2006. 171 patients had both pelvic and PA nodes removed during surgery, and specimens examined by a pathologist. Only 2 (1.2%) had PA nodes that tested positive for malignance (i.e. positive PA nodes) with pelvic nodes that tested negative for malignance (i.e. negative pelvic nodes). The final International Federation of Gynecology and Obstetrics (FIGO) grade for the endometrial tumor cells in the two patients was "G1" with endometrioid adenocarcinoma and "G3" with endometrioid adenocarcinoma and mucinous differentiation, respectively.Based on the very low incidence of patients inflicted with endometrial cancer that have positive para-aortic lymph nodes (PALNs) with negative pelvic nodes found both in our literature review (1.5%) and in our own study (1.2%), the addition of PA lymphadenectomy in all patients was found to have minimal diagnostic and therapeutic value. At the present, the role of complete PA lymphadenectomy in all patients with endometrial cancer should be re-examined. Individualized algorithms should be developed based on risk factors and status of pelvic nodes.
View details for DOI 10.1016/j.ygyno.2010.11.026
View details for Web of Science ID 000288920700021
View details for PubMedID 21194737
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Squamous Cell Carcinoma Arising From Mature Cystic Teratoma of the Ovary
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
2011; 21 (3): 466-474
Abstract
Squamous cell carcinoma (SCC) is the most common type of malignant transformation in mature cystic teratoma (MCT) of the ovary. The SCC is difficult to preoperatively diagnose. We conducted a retrospective study to seek the possible risk/prognostic factors and treatments for SCC arising from MCT of the ovary.Using an institutional database, we identified 3 women treated for SCC arising from an MCT of the ovary at the Kaohsiung Veteran General Hospital. A retrospective chart review was conducted, with information obtained from radiographs, operative reports, pathology reports, and radiation oncology records.A total of 1551 cases of MCT were diagnosed at Kaohsiung Veteran General Hospital from 1990 to 2009, of which, malignant teratoma SCC type was noted in 3 cases (0.19%). The median age of the subjects was 39 years. Abdominal fullness was the most common symptom (3/3 cases). The mean diameter of the ovarian tumor was 17.3 cm, ranging from 16 to 18 cm. All 3 patients received simple right salpingo-oophorectomy or debulking surgery. Two of the patients reached stage IIIC and died.: With our review as basis, we recommend being cautious of the following risk factors: patient age, tumor size, ultrasound characteristics, sonar tumor vessel wave form, computed tomography, and levels of SCC and CA125 tumor markers. We suggest that patients have regular ovarian ultrasound examination. Based on our literature review, stage IA patients who undergo standardized operational procedures do well without adjuvant treatment, but such patients must be confirmed accurately with complete surgical staging to be in stage IA before undergoing conservative management. The optimal approach to the management of patients with advanced stage and recurrent disease is unclear. Surgical cytoreduction with proper staging, adjuvant therapy with platinum-based or paclitaxel-based chemotherapy, and concurrent whole pelvic radiation have been recommended as possible methods of treatment.
View details for DOI 10.1097/IGC.0b013e31820d3e5b
View details for Web of Science ID 000288743700008
View details for PubMedID 21430455
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Overcoming pre-fertilization barriers in the wide cross between Chrysanthemum grandiflorum (Ramat.) Kitamura and C. nankingense (Nakai) Tzvel. by using special pollination techniques
EUPHYTICA
2011; 178 (2): 195-202
View details for DOI 10.1007/s10681-010-0297-6
View details for Web of Science ID 000287457500005
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Epithelial Ovarian Cancer
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
2011; 9 (1): 82-113
View details for Web of Science ID 000287217200008
View details for PubMedID 21233246
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Leukemia inhibitory factor downregulates human papillomavirus-16 oncogene expression and inhibits the proliferation of cervical carcinoma cells.
Infectious diseases in obstetrics and gynecology
2011; 2011: 463081-?
Abstract
The constitutive proliferation and resistance to differentiation and apoptosis of neoplastic cervical cells depend on sustained expression of human papillomavirus oncogenes. Inhibition of these oncogenes is a goal for the prevention of progression of HPV-induced neoplasias to cervical cancer. SiHa cervical cancer cells were transfected with an HPV-16 promoter reporter construct and treated with leukemia inhibitory factor (LIF), a human cytokine of the interleukin 6 superfamily. SiHa and CaSki cervical cancer cells were also assessed for proliferation by MTT precipitation, programmed cell death by flow cytometry, and HPV E6 and E7 expression by real-time PCR. LIF-treated cervical cancer cells showed significantly reduced HPV LCR activation, reduced levels of E6 and E7 mRNA, and reduced proliferation. We report the novel use of LIF to inhibit viral oncogene expression in cervical cancer cells, with concomitant reduction in proliferation suggesting re-engagement of cell-cycle regulation.
View details for DOI 10.1155/2011/463081
View details for PubMedID 21747640
View details for PubMedCentralID PMC3124004
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Cervical Cancer Screening
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
2010; 8 (12): 1358-1386
View details for Web of Science ID 000285132200006
View details for PubMedID 21147902
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Cervical Cancer
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
2010; 8 (12): 1388-1416
View details for Web of Science ID 000285132200007
View details for PubMedID 21147903
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Anther wall development, microsporogenesis and microgametogenesis in male fertile and sterile chrysanthemum (Chrysanthemum morifolium Ramat., Asteraceae)
SCIENTIA HORTICULTURAE
2010; 126 (2): 261-267
View details for DOI 10.1016/j.scienta.2010.06.013
View details for Web of Science ID 000282201700028
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Interspecific hybrids between Chrysanthemum grandiflorum (Ramat.) Kitamura and C. indicum (L.) Des Moul. and their drought tolerance evaluation
EUPHYTICA
2010; 174 (1): 51-60
View details for DOI 10.1007/s10681-009-0117-z
View details for Web of Science ID 000278348200005
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Factors affecting seed set in the crosses between Dendranthema grandiflorum (Ramat.) Kitamura and its wild species
EUPHYTICA
2010; 171 (2): 181-192
View details for DOI 10.1007/s10681-009-0005-6
View details for Web of Science ID 000272572200003
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A Novel Accelerator for Improving the Handling Properties of Dental Filling Materials
JOURNAL OF ENDODONTICS
2009; 35 (9): 1292-1295
Abstract
Mineral trioxide aggregate (MTA) fulfills many of the ideal properties of a root end filling material and repair material for furcal perforation. However, its low cohesive property often makes it difficult to handle. To improve the handling properties of MTA root canal filling materials, MTA-like cement was made, and calcium lactate gluconate (CLG) aqueous solution was used to shorten the setting time and enhance the paste viscosity.CLG solution was prepared by mixing lactic acid, glucono delta lactone, and calcium oxide by wet process. The crystalline property of the CLG powder was characterized by x-ray diffraction. The MTA-like cements were prepared by mixing Portland cement/bismuth oxide/gypsum (75/20/5); ProRoot white MTA (Dentsply Tulsa Dental, Tulsa, OK) was used as a control group. The influence of various liquid phases on initial setting time, handling properties, and pH value were investigated by a Vicat needle, questionnaire of operational hand feel, and pH meter, respectively.By using 23.1 wt% CLG solutions as a liquid phase, the setting time of white MTA was significantly decreased from 155.5 +/- 5.0 to 12.3 +/- 2.5 minutes. The pH values for hydrated white MTA with deionized water and 23.1 wt% CLG solutions were 12.29 +/- 0.02 and 11.81 +/- 0.04 at 72 hours.The results suggest that the addition of amorphous CLG-based liquid phase provides improvement in sealing ability as well as clinical manageability of dental filling materials.
View details for DOI 10.1016/j.joen.2009.06.007
View details for Web of Science ID 000269760600024
View details for PubMedID 19720234
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Uterine Neoplasms Clinical Practice Guidelines in Oncology
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
2009; 7 (5): 496-531
View details for Web of Science ID 000270265000002
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Hedgehog pathway activation and inhibition in epithelial ovarian cancer
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2009: S106–S106
View details for Web of Science ID 000264230200210
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Molecular and Bioinformatic Identification of Epithelial Ovarian Cancer Stem Cells for Radiotherapeutic Targeting
51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO)
ELSEVIER SCIENCE INC. 2009: S543–S544
View details for Web of Science ID 000270573602116
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Imputed food insecurity as a predictor of disease and mental health in Taiwanese elementary school children
ASIA PACIFIC JOURNAL OF CLINICAL NUTRITION
2009; 18 (4): 605-619
Abstract
This study investigated the association between food insecurity and Taiwanese children's ambulatory medical care use for treating eighteen disease types linked to endocrine and metabolic disorders, nutrition, immunity, infections, asthma, mental health, injury, and poisoning. We used longitudinal data in the Taiwan National Health Insurance scheme (NHI) for 764,526 elementary children, and employed approximate NHI data to construct three indicators imputed to food insecurity: low birth weight status, economic status (poverty versus non-poverty), and time of year (summer break time versus semester time). We compared ambulatory care for these diseases between children with low birth weight and those not, and between children living in poverty and those not. A difference-in-differences method was adopted to examine the potential for a publicly- funded lunch program to reduce the harmful health effects of food insecurity on poor children. We found that children in poverty were significantly more likely to have ambulatory visits linked with diabetes, inherited disorders of metabolism, iron deficiency anemias, ill-defined symptoms concerning nutrition, metabolism and development, as well as mental disorders. Children with low birth weight also had a significantly higher likelihood of using care for other endocrine disorders and nutritional deficiencies, in addition to the above diseases. The study failed to find any significant effect of the semester school lunch program on alleviating the harmful health effects of food insecurity for poor children, suggesting that a more intensive food program or other program approaches might be required to help poor children overcome food insecurity and its related health outcomes.
View details for Web of Science ID 000273103500022
View details for PubMedID 19965355
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INTRAOPERATIVE RADIATION THERAPY FOR LOCALLY ADVANCED AND RECURRENT SOFT-TISSUE SARCOMAS IN ADULTS
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
2008; 72 (4): 1146-1153
Abstract
To analyze the outcomes of and identify prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for locally advanced and recurrent soft-tissue sarcoma in adults from a single institution.We retrospectively reviewed 50 consecutive patients treated with IORT to 62 sites of disease. Primary sites included retroperitoneum-pelvis (78%), extremity (8%), and other (14%). Seventy percent of patients had recurrent disease failing prior surgery (70%) and/or radiation (32%). Mean disease-free interval (DFI) before IORT was 1.9 years (range, 2 weeks-5.4 years). The IORT was delivered with orthovoltage X-rays using individually sized beveled cone applicators. Clinical characteristics were as follows: mean tumor size, 10 cm (range, 1-25 cm); high-grade histologic subtype (72%); and mean dose, 1,159 cGy (range, 600-1,600 cGy). Postoperative radiation or chemotherapy was administered to 37% of IORT Sites and 32% of patients, respectively. Outcomes measured were infield control (IFC), locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications. Mean and median follow-up of alive patients were 59 and 35 months, respectively.Kaplan-Meier 5-year IFC, LRC, DMFS, and DSS probabilities for the entire group were 55%, 26%, 51%, and 25%, respectively. Prognostic factors found to be significant (p < 0.05) on multivariate analysis were prior DFI and tumor size for LRC, extremity location and leiomyosarcoma histologic subtype for DMFS, and prior DFI for DSS. Our cohort had five Grade 3/4 complications associated with treatment or a 5-year Kaplan-Meier Grade 3/4 complication-free survival rate of 85%.IORT after tumor reductive surgery is well tolerated and seems to confer IFC in carefully selected patients.
View details for DOI 10.1016/j.ijrobp.2008.02.012
View details for Web of Science ID 000260592600026
View details for PubMedID 18394818
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Integrative proteomic and cytological analysis of the effects of extracellular Ca2+ influx on Pinus bungeana pollen tube development
JOURNAL OF PROTEOME RESEARCH
2008; 7 (10): 4299-4312
Abstract
Ca (2+) is an essential ion in the control of pollen germination and tube growth. However, the control of pollen tube development by Ca (2+) signaling and its interactions with cytoskeletal components, energy-providing pathways, and cell-expansion machinery remain elusive. Here, we used nifedipine (Nif) to study Ca (2+) functions in differential protein expression and other cellular processes in Pinus bungeana pollen tube growth. Proteomics analysis indicated that 50 proteins showed differential expression with varying doses of Nif. Thirty-four of these were homologous to previously reported proteins and were classified into different functional categories closely related to tip-growth machinery. Blocking the L-type Ca (2+) channel with Nif in the pollen tube membrane induced several early alterations within a short time, including a reduction of extracellular Ca (2+) influx and a subsequently dramatic decrease in cytosolic free Ca (2+) concentration ([Ca (2+)] c), concomitant with ultrastructural abnormalities and changes in the abundance of proteins involved in energy production and signaling. Secondary alterations included actin filament depolymerization, disrupted patterns of endocytosis/exocytosis, and cell wall remodeling, along with changes in the proteins involved in these processes. These results suggested that extracellular Ca (2+) influx was necessary for the maintenance of the typical tip-focused [Ca (2+)] c gradient in the P. bungeana pollen tube, and that reduced adenosine triphosphate production (ATP), depolymerization of the cytoskeleton, and abnormal endocytosis/exocytosis, together with enhanced rigidity of cell walls, were responsible for the growth arrest observed in pollen tubes treated with Nif.
View details for DOI 10.1021/pr800241u
View details for Web of Science ID 000259784300010
View details for PubMedID 18715029
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Ovarian cancer. Clinical practice guidelines in oncology.
Journal of the National Comprehensive Cancer Network
2008; 6 (8): 766-794
View details for PubMedID 18926089
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Natural frequency analysis of tooth stability under various simulated types and degrees of alveolar vertical bone loss.
Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine
2008; 222 (6): 983-989
Abstract
The aim of this study was to test natural teeth stability under various simulated types and degrees of alveolar vertical bone loss, as well as to assess the role that the surrounding bone played for maintaining tooth stability. A three-dimensional finite element model of the human maxillary central incisor with surrounding tissue, including periodontal ligament, enamel, dentin, pulp, and alveolar bone, was established. One side and multiple vertical bone loss were simulated by means of decreasing the surrounding bone level apically from the cemento-enamel junction in 1 mm steps incrementally downward for 10 mm. Natural frequency values of the incisor model with various types and degrees of bone loss were then calculated. The results showed that, with one-sided bone resorption, the model with labial bone loss had the lowest natural frequency decreasing rates (8.2 per cent). On the other hand, in cases of multiple bone loss, vertical bone resorption at the mesial and distal sides had more negative effects on tooth stability compared to vertical bone losses on facial and lingual sides. These findings suggest that the natural frequency method may be a useful, auxiliary clinical tool for diagnosis of vertical periodontal diseases.
View details for PubMedID 18935815
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Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
2008; 198 (2)
Abstract
The purpose of this study was to determine factors responsible for the increasing number of deaths from corpus cancer over three time periods.Data were collected from the Surveillance, Epidemiology and End Results database from 1988-2001. Kaplan-Meier and Cox proportional hazards regression analyses were performed.Of 48,510 women with corpus cancer, there was an increase in the proportion of patients dying from advanced cancers (52.1% to 56.0% to 68.8%; P < .001), grade 3 disease (47.5% to 53.3% to 60.6%; P < .001), serous tumors (14.3% to 18.4% to 16.6%; P < .001), and sarcomas (19.1% to 20.4% to 27.2%; P < .001) over time. On multivariate analysis, older age, African American race, lack of primary staging procedures, advanced-stage, high-grade, and non-endometrioid histology were independent prognostic factors for worse survival.Our data suggest that the increase in mortality in women with corpus cancer over the last 14 years may be related to an increased rate of advanced-stage cancers and high-risk histologies.
View details for DOI 10.1016/j.ajog.2007.08.075
View details for Web of Science ID 000253587300027
View details for PubMedID 18226630
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Ovarian clear cell carcinoma with papillary features: A potential mimic of serous tumor of low malignant potential
96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology
LIPPINCOTT WILLIAMS & WILKINS. 2008: 269–74
Abstract
The differential diagnostic problems usually associated with clear cell carcinoma (CCC) of the ovary have been well characterized and include primitive germ cell tumor, sex cord stromal tumor, and metastasis. Distinction from other types of surface epithelial carcinoma may also pose a diagnostic challenge, but the potential for misdiagnosis of serous tumor of low malignant potential (S-LMP) is not well recognized. We report 13 cases of ovarian CCC with prominent papillary architecture that were initially misdiagnosed as S-LMP or low-grade serous carcinoma either on frozen section or at final diagnosis. The ages of the patients ranged from 39 to 65 years (mean, 52.2 y). All patients presented with a pelvic mass; 1 was undergoing evaluation for infertility. Macroscopically, most were described as unilateral, multilocular cysts with internal papillary structures. On microscopic examination, each tumor had a papillary architecture that accounted for 30% to 95% of the tumor; in 6 cases, the cores of the papillae were hyalinized. The neoplastic cells covering the papillae had clear to granular and eosinophilic cytoplasm. Hobnail cells were focal and often subtle. Most had a low mitotic index (9/13) and/or deceptively bland cytology (8/13); only careful attention to the cytologic features and/or mitotic index allowed correct identification of the tumor type in 5 cases. Six were associated with pelvic/ovarian endometriosis. Ten were Federation of Gynecology and Obstetrics stage I (8 IA, 2 IC), 2 were stage II (1 IIB, 1 IIC), and 1 stage IIIC. CCC with prominent papillary architecture is uncommon, but may pose a challenging differential diagnosis with S-LMP, resulting in inadequate staging and delayed treatment. Features most helpful in distinguishing papillary CCC are unilaterality, nonhierarchical branching, monomorphous cell population, and the presence of more typical CCC patterns elsewhere in the tumor. The presence of endometriosis, although not specific, should also prompt consideration for papillary CCC. Increased numbers of mitotic figures may not be present and high-grade cytologic atypia may be focal, requiring careful examination of multiple tumor sections for detection. As CCC and S-LMP exhibit significantly different immunoreactivity for Wilms' Tumor 1 and estrogen receptor, these markers may also be useful adjunctive tests in problematic cases.
View details for Web of Science ID 000252759900012
View details for PubMedID 18223330
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Prognostic factors and risk of extrauterine metastases in 3867 women with grade 1 endometrioid corpus cancer
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
2008; 198 (2)
Abstract
The purpose of this study was to evaluate the role of surgical staging in patients with grade 1 endometrioid uterine cancer.Data were extracted from Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Kaplan-Meier and Cox proportional hazards analyses were used to determine predictors for disease-specific survival.Twelve thousand seven hundred and twelve women were reported with endometrioid carcinoma, including 3867 with grade 1 disease, of which 25.5% had stage IC or more advanced disease, 15.4% with disease extending beyond the uterine corpus, 7.3% with extrauterine metastases, and 3.3% with lymph node metastases. On multivariate analysis, younger age and earlier stage remained as significant prognostic factors for improved survival.Since grade 1 endometrioid uterine cancers have a 15.4% risk of extrauterine spread, a complete surgical staging procedure is recommended when clinically feasible. Younger age and earlier stage are significant prognostic factors for improved survival.
View details for DOI 10.1016/j.ajog.2007.08.028
View details for Web of Science ID 000253587300026
View details for PubMedID 18226629
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Cervical cancer screening.
Journal of the National Comprehensive Cancer Network
2008; 6 (1): 58-82
View details for PubMedID 18267060
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Cervical cancer.
Journal of the National Comprehensive Cancer Network
2008; 6 (1): 14-36
View details for PubMedID 18267056
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A phase I study of a novel human monoclonal antibody (mAb216) with chemotherapy for the treatment of patients with relapsed or refractory B-lineage acute lymphoblastic leukemia
AMER SOC HEMATOLOGY. 2007: 833A
View details for Web of Science ID 000251100803613
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A novel technique for the enrichment of primary ovarian cancer cells
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
2007; 197 (5)
Abstract
Primary cancer cells that are extracted from ovarian tumors can serve as an optimal substrate to study the biologic characteristics of ovarian cancer. We describe an efficient and effective method of enriching ovarian tumor cells from ascitic fluid using an immunomagnetic-based method.Mononuclear cells were isolated from ascites specimens by Ficoll gradient separation. Epithelial ovarian cancer cells were labeled magnetically with monoclonal human epithelial antigen-125 that is conjugated to microbeads. After immunomagnetic separation, the purity of tumor cells before and after purification was quantified by cytologic analysis and confirmed by fluorescence-activated cell sorter analysis.Peritoneal ascites specimens were obtained from 6 patients with ovarian cancer. The median age of our patients was 61.5 years (range, 46-79 years). Three patients had papillary serous carcinoma; 2 patients had clear cell carcinoma, and 1 patient had an undifferentiated adenocarcinoma. The mean tumor purity was only 22.8% +/- 10% (range, 1%-60%) before separation. After enrichment, the purity improved to 82.3% +/- 4.0% (range, 70%-90%). Our enrichment technique increased the tumor purity by 59.5% +/- 8.4%. The mean percent yield after positive enrichment was 30.1% +/- 14.5%.The immunomagnetic cell separation technique is an efficient and effective method for isolating and purifying ovarian tumor cells from ascites. Results from experiments with fresh tumor cells rather than cancer cell lines may be more relevant for clinical application.
View details for DOI 10.1016/j.ajog.2007.05.006
View details for Web of Science ID 000250915500021
View details for PubMedID 17980191
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A successful strategy for generating monoclonal antibodies for the identification of human ovarian cancer and stem cells
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2007: 375–76
View details for DOI 10.1016/j.ygyno.2007.08.044
View details for Web of Science ID 000250654900073
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A xenograft model of human ovarian cancer in immunodeficient mice that can be used to assay for ovarian cancer stem cells
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2007: 376–76
View details for DOI 10.1016/j.ygyno.2007.08.045
View details for Web of Science ID 000250654900074
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Long-term survivors using intraoperative radiotherapy for recurrent gynecologic malignancies
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
2007; 69 (2): 504-511
Abstract
To analyze the outcomes of therapy and identify prognostic factors for patients treated with surgery followed by intraoperative radiotherapy (IORT) for gynecologic malignancies at a single institution.We performed a retrospective review of 36 consecutive patients treated with IORT to 44 sites with mean follow-up of 50 months. The primary site was the cervix in 47%, endometrium in 31%, vulva in 14%, vagina in 6%, and fallopian tubes in 3%. Previous RT had failed in 72% of patients, and 89% had recurrent disease. Of 38 IORT sessions, 84% included maximal cytoreductive surgery, including 18% exenterations. The mean age was 52 years (range, 30-74), mean tumor size was 5 cm (range, 0.5-12), previous disease-free interval was 32 months (range, 0-177), and mean IORT dose was 1,152 cGy (range, 600-1,750). RT and systemic therapy after IORT were given to 53% and 24% of the cohort, respectively. The outcomes measured were locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications.The Kaplan-Meier 5-year LRC, DMFS, and DSS probability for the whole group was 44%, 51%, and 47%, respectively. For cervical cancer patients, the Kaplan-Meier 5-year LRC, DMFS, and DSS estimate was 45%, 60%, and 46%, respectively. The prognostic factors found on multivariate analysis (p
View details for DOI 10.1016/j.ijrobp.2007.03.021
View details for Web of Science ID 000249796100026
View details for PubMedID 17560736
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Acute postoperative thrombotic thrombocytopenic purpura following hysterectomy and lymphadenectomy for endometrial cancer
GYNECOLOGIC ONCOLOGY
2007; 106 (2): 423-426
Abstract
Thrombotic thrombocytopenic purpura (TTP) in the acute postoperative setting is a recently recognized syndrome that, similar to classic or idiopathic TTP, presents variably with microangiopathic hemolytic anemia, thrombocytopenia, fever, renal failure, and mental status changes. Though most reports of postoperative TTP are in conjunction with cardiac or vascular surgery, it has also been reported following orthopedic and abdominal surgeries.We present a case of a 53 year-old female diagnosed with metastatic poorly differentiated endometrial cancer who developed TTP the day following her cytoreductive cancer surgery.To our knowledge, this represents the first reported case of postoperative TTP following gynecologic cancer surgery. Because the presentation can be confused with other early postoperative complications, awareness of this syndrome is essential as initiation of plasmapheresis can be life-saving.
View details for DOI 10.1016/j.ygyno.2007.04.005
View details for Web of Science ID 000248585700023
View details for PubMedID 17499845
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The potential therapeutic role of lymph node resection in epithelial ovarian cancer: a study of 13,918 patients
BRITISH JOURNAL OF CANCER
2007; 96 (12): 1817-1822
Abstract
The aim of the study is to determine the role of lymphadenectomy in advanced epithelial ovarian cancer. The data were obtained from the Surveillance, Epidemiology and End Results (SEER) program reported between 1988 and 2001. Kaplan-Meier estimates and Cox proportional hazards regression models were used for analysis. Of 13 918 women with stage III-IV epithelial ovarian cancer (median age: 64 years), 87.9% were Caucasian, 5.6% African Americans, and 4.4% Asians. A total of 4260 (30.6%) underwent lymph node dissections with a median number of six nodes reported. For all patients, a more extensive lymph node dissection (0, 1, 2-5, 6-10, 11-20, and >20 nodes) was associated with an improved 5-year disease-specific survival of 26.1, 35.2, 42.6, 48.4, 47.5, and 47.8%, respectively (P<0.001). Of the stage IIIC patients with nodal metastases, the extent of nodal resection (1, 2-5, 6-10, 11-20, and >20 nodes) was associated with improved survivals of 36.9, 45.0, 47.8, 48.7, and 51.1%, respectively (P=0.023). On multivariate analysis, the extent of lymph node dissection and number of positive nodes were significant independent prognosticators after adjusting for age, year at diagnosis, stage, and grade of disease. The extent of lymphadenectomy is associated with an improved disease-specific survival of women with advanced epithelial ovarian cancer.
View details for DOI 10.1038/sj.bjc.6603803
View details for Web of Science ID 000247218100007
View details for PubMedID 17519907
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Lymphadenectomy in endometrioid uterine cancer staging - How many lymph nodes are enough? A study of 11,443 patients
CANCER
2007; 109 (12): 2454-2460
Abstract
The purpose of the current study was investigate the association between the number of lymph nodes examined and the probability of detecting at least a single lymph node involved by metastatic disease in patients with endometrioid corpus cancer.Demographic, clinicopathologic, and surgical information were obtained from the National Cancer Institute between 1990 and 2001. A logistic regression model was used to investigate the relation between the number of lymph nodes identified and the probability of detecting at least a single positive lymph node.Of 11,443 patients, the median age was 64 years (range, 22-74 years). In all, 78.7% had stage I disease, 10.3% had stage II disease, and 11.0% had stage III disease; 31.5% had grade 1 histology, 40.6% had grade 2 histology, and 24.3% had grade 3 histology. The median number of lymph nodes reported was 9 (range, 1-90 lymph nodes). The median number of lymph nodes and the percent of patients with positive lymph nodes have increased from 1988 to 2001. An increasing number of lymph nodes removed was associated with a higher likelihood of identifying those with lymph node metastases. Based on the logistic regression model, the largest increase in probability of detecting at least a single positive lymph node was observed when 21 to 25 lymph nodes were resected (odds ratio [OR] of 1.45; 95% confidence interval [95% CI], 1.08-1.94 [P < .01]). Removing greater than 25 lymph nodes did not improve the statistical probability (OR of 1.23; 95% CI, 0.94-1.61 [P = .13]).The current study data suggest that the removal of 21 to 25 lymph nodes significantly increases the probability of detecting at least 1 positive lymph node in endometrioid uterine cancer. The definition of an adequate lymphadenectomy deserves further investigation.
View details for DOI 10.1002/cncr.22727
View details for Web of Science ID 000247113500009
View details for PubMedID 17503431
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Influence of the gynecologic oncologist on the survival of ovarian cancer patients
OBSTETRICS AND GYNECOLOGY
2007; 109 (6): 1342-1350
Abstract
To estimate the influence of gynecologic oncologists on the treatment and outcome of patients with ovarian cancer.Data were obtained from California Cancer Registry from 1994 to 1996. Kaplan-Meier and Cox proportional hazard methods were used for analyses.Of 1,491 patients, the median age was 65 years (range: 13-100). Only 34.1% received care by gynecologic oncologists (group A) while 65.9% were treated by others (group B). Women in group A were more affluent (P<.001), were more educated (P=.036), were classified as white-collar employees (P=.128), and lived in urban regions (P<.001) compared with group B. Patients who saw gynecologic oncologists were more likely to have surgery as their initial treatment (91.9% versus 69.1%; P<.001), present with advanced (stage III-IV) cancers (78.2% versus 70.5%; P<.001), have more grade 3 tumors (61.7% versus 39.9%; P=.048), and receive chemotherapy (90.0% versus 70.1%; P<.001). Women in group B had a fourfold higher risk of having unstaged cancers (8.0% versus 2.1%; P<.001). The 5-year disease-specific survival of group A patients was 38.6% compared with 30.3% in group B (P<.001). On multivariable analysis, early stage, lower grade, and treatment by gynecologic oncologists were independent prognostic factors for improved survival. After adjusting for surgery and chemotherapy, there was no improvement in survival associated with care by gynecologic oncologists (hazard ratio=0.90, 95% confidence interval 0.78-1.03; P=.133).In this study of 1,491 women, those who were treated by gynecologic oncologists were more likely to undergo primary staging surgery and receive chemotherapy. Stage, grade of disease, and treatment by gynecologic oncologists were important prognosticators.
View details for Web of Science ID 000247010200013
View details for PubMedID 17540806
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Prognostic factors for outcomes and complications for primary squamous cell carcinoma of the vagina treated with radiation
GYNECOLOGIC ONCOLOGY
2007; 105 (3): 641-649
Abstract
To analyze the results of treatment and identify prognostic factors for primary squamous cell carcinoma (SCCA) of the vagina managed with radiotherapy at a single institution.Seventy-eight patients were analyzed in this retrospective series. Mean characteristics: follow-up 89 months; age 65 years (range 33-99); tumor size 3.8 cm (0.3-10); treatment hemoglobin 12.4 g/dl (range 8.7-14.4); and tumor dose 72 Gy (range 6-127). In addition, 49% of our cohort had a prior hysterectomy. The FIGO stage distribution: I (42%); II (29%); III (17%); and IVA/B (11%). Sixty-two percent of patients were treated with a combination of external beam radiation (EBRT) and brachytherapy, 22% with EBRT alone and 13% with brachytherapy alone.Kaplan-Meier (KM) 5-year pelvic control, distant metastasis free survival and disease specific survival probabilities: stage I, 83%, 100%, and 92%; stage II, 76%, 95%, and 68%; stage III, 62%, 65%, and 44%; and stage IV, 30%, 18%, and 13%. On multivariate analysis: stage; treatment hemoglobin; and prior hysterectomy were prognostic for DSS (p<0.05). The KM 5-year grade 3/4 (G3/4) complication free estimate of our cohort was 84%. G3/4 complications: tumor size and tumor dose were independently predictive (p<0.05).Radiotherapy as a single modality for early stage primary vaginal SCCA produces good results. Advanced stage disease necessitates a combined modality approach and/or new methods. Treatment Hg levels appear to be clinically significant and studies on correction of anemia during treatment are warranted.
View details for DOI 10.1016/j.ygyno.2007.01.033
View details for Web of Science ID 000246815700014
View details for PubMedID 17363046
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Effects of human monoclonal antibody 216 on B-progenitor acute lymphoblastic leukemia in vitro
PEDIATRIC BLOOD & CANCER
2007; 48 (4): 380-386
Abstract
Human monoclonal antibody (mAb) 216 is a naturally occurring IgM cytotoxic mAb that binds to a glycosylated epitope on the surface of B-lymphocytes. This study investigated if this mAb could bind and kill acute lymphoblastic leukemia (ALL) B-progenitor lymphoblasts in vitro. ALL cell lines were used to determine if combining mAb 216 with chemotherapeutic drugs would enhance killing and cell lines were used to measure cytotoxicity by mAb 216 with human complement.Expression of cell surface markers and mAb 216 epitope on fresh and banked ALL bone marrow samples was determined by flow cytometry. Fresh lymphoblasts were incubated for 20 hr with mAb 216 without complement to measure cytotoxicity. Cytotoxicity of ALL cell lines incubated with mAb 216 and vincristine (VCR) or human complement was determined using flow cytometry.Pre-B-ALL cells but not T-ALL cells are bound and killed by mAb 216. The combination of mAb 216 and VCR at sub-therapeutic levels demonstrated enhanced cytotoxicity beyond that observed for either agent alone. Incubation of mAb 216 with human complement increased cytotoxicity of ALL cell lines.This increased cytotoxicity with chemotherapy and the functional ability of mAb 216 to use multiple pathways to induce cell death identify mAb 216 as a potentially novel therapeutic tool in the treatment of B-progenitor ALL. Based on the results from this preclinical study, a Phase I clinical trial with mAb 216 for the treatment of patients with relapsed or refractory B-lineage ALL is ongoing.
View details for DOI 10.1002/pbc.20770
View details for Web of Science ID 000244611500004
View details for PubMedID 16421902
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Racial disparities in the surgical treatment of epithelial ovarian cancer in the United States
55th Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists
LIPPINCOTT WILLIAMS & WILKINS. 2007: 9S–9S
View details for Web of Science ID 000246801600023
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Safety and efficacy of lenalidomide (Revlimid((R))) in recurrent ovarian and primary peritoneal carcinoma
GYNECOLOGIC ONCOLOGY
2007; 105 (1): 194-198
Abstract
To conduct a phase I trial to determine the safety and toxicity profile of a novel immunomodulatory drug, lenalidomide, in recurrent ovarian and primary peritoneal cancer. The secondary objective is to evaluate the efficacy profile and quality of life (QOL) parameters in patients receiving this treatment.Patients with recurrent ovarian or peritoneal cancer who received standard staging surgery and at least one prior platinum-based chemotherapy regimen were treated with single-agent oral lenalidomide 25 mg daily for 21 days of a 28-day cycle. Toxicities were monitored by patient report, physical exam, and laboratories. Response was assessed by imaging, physical exam, and CA-125. Therapy was discontinued with disease progression and/or unacceptable toxicity.20 patients with recurrent ovarian or peritoneal cancer were enrolled and received 70 completed 28-day cycles and 10 partial cycles of lenalidomide therapy. The majority of adverse events were grades 1-2, including fatigue (25/80 cycles), nausea/vomiting (23/80), constipation (13/80), abdominal pain (17/80), rash (12/80), neutropenia (12/80), and anemia (12/80). Grade 3 toxicities occurred in 12 of 80 cycles (14%) and no grade IV toxicities were observed. Eleven patients completed > or = 2 cycles and were evaluable for response. Nine achieved stable disease (SD) of at least 3 months, with four patients maintaining SD for > 6 months. The mean time to progression was 5.8 months (range 2-12 months).Overall, oral lenalidomide was well tolerated and may have some activity as a single agent in this heavily pre-treated population. Further studies combining lenalidomide with cytotoxic treatments may be warranted in this disease setting.
View details for DOI 10.1016/j.ygyno.2006.11.026
View details for Web of Science ID 000245559000030
View details for PubMedID 17257661
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Prognostic factors for uterine cancer in reproductive-aged women
OBSTETRICS AND GYNECOLOGY
2007; 109 (3): 655-662
Abstract
To determine the prognostic factors that influence the survival of younger women diagnosed with uterine cancer.Demographic and clinico-pathologic data were collected from the National Cancer Institute database between 1988 and 2001. Data were analyzed with Kaplan-Meier methods and Cox proportional hazards regression.Of the 51,471 women diagnosed with uterine cancer in the study period, 2,076 (4.0%) patients were aged 40 years or younger, and 49,395 (96.0%) were older than 40. The mean age in the younger group was 35.6 years, compared with 65.2 years of the older group. The overall distribution by stage was stage I 75.4%, II 8.1%, III 6.7%, and IV 9.8%. Younger patients were more likely to be nonwhite (42.4% versus 18.3%, P<.001) and have stage I disease (79.2% versus 75.3%, P<.001), grade 1 lesions (47.6% versus 35.6%, P<.001), and sarcomas (15.9% versus 8.2%, P<.001) compared with their older counterparts. The overall 5-year disease-specific survival for younger patients was significantly better than that of older women (93.2% versus 86.4%, P<.001). On multivariable analysis, younger age, earlier stage, lower grade, nonblack race, endometrioid histology, and surgical treatment remained as significant independent prognostic factors for improved survival.This large population-based study demonstrates that patients 40 years and younger have an overall survival advantage compared with women older than 40 years, independent of other clinico-pathologic prognosticators.III.
View details for Web of Science ID 000246771200011
View details for PubMedID 17329517
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A multivariate analysis of vulvar melanomas: A study of 359 patients
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2007: S5–S6
View details for Web of Science ID 000244834100010
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Racial disparities in the surgical treatment of epithelial ovarian cancer in the United States
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2007: S31–S31
View details for Web of Science ID 000244834100065
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Factors responsible for the increase in death rate of women diagnosed with uterine corpus cancer
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2007: S8–S8
View details for Web of Science ID 000244834100015
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Access to gynecologic oncologists and its impact on survival of women with epithelial ovarian cancer
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2007: S23–S23
View details for Web of Science ID 000244834100047
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Prognostic factors responsible for survival in sex cord stromal tumors of the ovary- An analysis of 376 women
GYNECOLOGIC ONCOLOGY
2007; 104 (2): 396-400
Abstract
To evaluate prognostic factors that impact on the survival of women with ovarian sex cord stromal tumors (SCST).Data including age at diagnosis, stage, histology, grade, treatment, and survival were extracted from the 1988-2001 Surveillance, Epidemiology, and End Results Program. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival.376 women (median age: 51) with ovarian sex cord stromal cell tumors were identified, including 339 with granulosa cell and 37 with Sertoli-Leydig cell tumors. 265 (71%) patients had stage I, 39 (10%) stage II, 40 (11%) stage III, and 32 (8%) had stage IV disease. Women with stage I-II disease had a 5-year disease-specific survival of 95% compared to 59% in those with stage III-IV cancers (p<0.001). Patients
50 years (93% vs. 84%, p<0.001). This age-associated survival advantage was observed for early (97% vs. 92%, p=0.003), but not for advanced-staged (68% vs. 53%, p=0.09) patients. 110 patients with stage I-II disease underwent conservative surgery without hysterectomy. The survival for this group was similar to patients who underwent a standard surgery including a hysterectomy (94.8% and 94.9%, p=0.38). On multivariate analysis, age View details for DOI 10.1016/j.ygyno.2006.08.032
View details for Web of Science ID 000244101200021
View details for PubMedID 17030354
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Association of lymphadenectomy and survival in stage I ovarian cancer patients
OBSTETRICS AND GYNECOLOGY
2007; 109 (1): 12-19
Abstract
To estimate the survival impact of lymphadenectomy in women diagnosed with clinical stage I ovarian cancer.Demographic and clinicopathologic information were obtained from the Surveillance, Epidemiology and End Results Program between 1988 and 2001. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression.A total of 6,686 women had clinical stage I ovarian cancer (median age 54 years, range 1-99). Of this total, 75.9% of patients were Caucasian, 8.3% were Hispanic, 5.8% were African American, and 7.3% were Asian. Epithelial tumors were present in 85.8% of the women, and 2,862 (42.8%) patients underwent lymphadenectomy. Patients aged 50 years or more were less likely to undergo lymphadenectomy compared with their younger cohorts (39.8% compared with 60.2%, P<.001). Only 32.7% of African-American women had lymphadenectomy compared with 42.7% of Caucasian women, 47.2% of Hispanics, and 48.8% of Asians (P<.001). Lymphadenectomy was associated with improved 5-year disease-specific survival of all patients from 87.0% to 92.6% (P<.001). More specifically, lymphadenectomy improved the survival in those with non-clear cell epithelial ovarian cancer (85.9% to 93.3%, P<.001) but not in those with clear cell carcinoma, germ cell tumors, sex cord stromal tumors, and sarcomas. Moreover, the extent of lymphadenectomy (0 nodes, less than 10 nodes, and 10 or more nodes) increased the survival rates from 87.0% to 91.9% to 93.8%, respectively (P<.001). On multivariable analysis, the extent of lymphadenectomy was a significant prognostic factor for improved survival, independently of other factors such as age, stage, histology, and grade of disease.Our data suggest that women with stage I non-clear cell ovarian cancers who underwent lymphadenectomy had a significant improvement in survival.II.
View details for Web of Science ID 000246771500003
View details for PubMedID 17197582
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Disruption of actin filaments by latrunculin B affects cell wall construction in Picea meyeri pollen tube by disturbing vesicle trafficking
PLANT AND CELL PHYSIOLOGY
2007; 48 (1): 19-30
Abstract
The involvement of actin filaments (AFs) in vesicle trafficking, cell wall construction and tip growth was investigated during pollen tube development of Picea meyeri. Pollen germination and tube elongation were inhibited in a dose-dependent manner by the latrunculin B (LatB) treatment. The fine AFs were broken down into disorganized fragments showing a tendency to aggregate. FM4-64 labeling revealed that the dynamic balance of vesicle trafficking was perturbed due to F-actin disruption and the fountain-like cytoplasmic pattern changed into disorganized Brownian movement. The configuration and/or distribution of cell wall components, such as pectins, callose and cellulose, as well as arabinogalactan proteins changed in obvious ways after the LatB application. Fourier transform infrared (FTIR) analysis further established significant changes in the chemical composition of the wall material. Our results indicate that depolymerization of AFs affects the distribution and configuration of cell wall components in Picea meyeri pollen tube by disturbing vesicle trafficking.
View details for DOI 10.1093/pcp/pc1036
View details for Web of Science ID 000243993900004
View details for PubMedID 17118947
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Mesonephric adenocarcinoma of the cervix: A case report and review of the literature
GYNECOLOGIC ONCOLOGY
2006; 103 (3): 1155-1158
Abstract
Malignant mesonephric tumor arising in the uterine cervix is an exceedingly uncommon variant of cervical adenocarcinoma with only 30 well-documented cases in the literature.We present a case of a 54-year-old woman with postmenopausal vaginal bleeding who was found to have a stage IB mesonephric adenocarcinoma of the cervix.At present there is no consensus on a standardized treatment protocol for malignant mesonephric tumors of the cervix. The present case suggests that a favorable outcome may be achieved for patients with stage IB tumors with aggressive initial therapy.
View details for DOI 10.1016/j.ygyno.2006.08.031
View details for Web of Science ID 000242809500065
View details for PubMedID 17023031
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The benefit of adjuvant radiation therapy in single-node-positive squamous cell vulvar carcinoma
GYNECOLOGIC ONCOLOGY
2006; 103 (3): 1095-1099
Abstract
To determine if adjuvant radiotherapy improves the survival of women with invasive squamous cell carcinoma of the vulva involving one inguinal node.Demographic, pathologic, and treatment information was obtained on patients with vulvar cancers from the Surveillance, Epidemiology, and End Results database between 1988 and 2001. Kaplan-Meier estimates and Cox-proportional hazards model were used for analyses.Of the 490 patients with stage III, node-positive vulvar cancers, 208 had a single positive inguinal node. The median age of this group was 71 years (range: 29-100). 82.2% of patients were White, 7.2% were Hispanic, 7.7% were Black, 1.4% were Asian, and 1.4% were Others. 91.8% of patients underwent a radical vulvectomy with a unilateral or bilateral inguinal lymphadenectomy. The median number of lymph nodes resected was 13 (range: 1-34). 102 women underwent adjuvant radiotherapy, while 106 did not receive any radiation treatment. Women who received adjuvant radiotherapy had a 5-year disease-specific survival of 77.0% compared to 61.2% in those without radiotherapy (p=0.02). After stratifying the study group based on the extent of lymphadenectomy, we found that radiation treatment improved the survival of those with
View details for DOI 10.1016/j.ygyno.2006.06.030
View details for Web of Science ID 000242809500053
View details for PubMedID 16889821
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Safety and efficacy of thalidomide in recurrent epithelial ovarian and peritoneal carcinoma
GYNECOLOGIC ONCOLOGY
2006; 103 (3): 919-923
Abstract
Thalidomide is an anti-angiogenesis agent that has shown activity in some solid tumors. We performed a phase I clinical trial to determine the toxicity and potential efficacy of Thalidomide in recurrent epithelial ovarian carcinoma.Patients with recurrent ovarian cancer were evaluated between 1998 and 2000. Data were evaluated using Kaplan-Meier and logistic regression analyses.17 heavily pretreated patients with recurrent epithelial ovarian cancer received oral Thalidomide starting at 100 mg/day, with dose escalations of 100 mg/day every 2 weeks, up to 1200 mg/day as tolerated. The median number of courses was four (range: 1-18 courses), and median dose was 200 mg/day (range: 100-600 mg/day). Treatment duration ranged from 2 to 48 months. Common grade 1 or 2 side effects included constipation (76%), neuropathy (71%), and fatigue (65%) with few grade 3 or 4 events. Three (18%) patients had partial responses, and six (35%) had stabilization of disease after 6 months. After 1 year of treatment, six of the nine patients with an initial partial response (n=2) or stable disease (n=4) remained in these response categories. Median time to progression was 10 months. Forty-seven percent of patients had a 50-70% decrease in CA125 levels. Using logistic regression and repeated measures analyses, CA125 levels decreased by 62 units/ml per month (p=0.07).Our study demonstrates the safety, tolerability, and potential efficacy of Thalidomide in recurrent and refractory epithelial ovarian cancers. Additional clinical trials are warranted.
View details for DOI 10.1016/j.ygyno.2006.05.035
View details for Web of Science ID 000242809500024
View details for PubMedID 16828852
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Ovarian cancer in younger vs older women: a population-based analysis
BRITISH JOURNAL OF CANCER
2006; 95 (10): 1314-1320
Abstract
To compare the clinico-pathologic prognostic factors and survival of younger vs older women diagnosed with epithelial ovarian cancer. Demographic, clinico-pathologic, treatment, and surgery information were obtained from patients with ovarian cancer from the Surveillance, Epidemiology, and End Results Program from 1988 to 2001 and analysed using Kaplan-Meier estimates. Of 28 165 patients, 400 were <30 years (very young), 11 601 were 30-60 (young), and 16 164 were >60 (older) years of age. Of the very young, young, and older patients, 261 (65.3%), 4664 (40.2%), and 3643 (22.5%) had stage I-II disease, respectively (P<0.001). Across all stages, very young women had a significant survival advantage over the young and older groups with 5-year disease-specific survival estimates at 78.8% vs 58.8 and 35.3%, respectively (P<0.001). This survival difference between the age groups persists even after adjusting for race, stage, grade, and surgical treatment. Reproductive age (16-40 years) women with stage I-II epithelial ovarian cancer who received uterine-sparing procedures had similar survivals compared to those who underwent standard surgery (93.3% vs 91.5%, P=0.26). Younger women with epithelial ovarian cancer have a survival advantage compared to older patients.
View details for DOI 10.1038/sj.bjc.6603457
View details for Web of Science ID 000242046700002
View details for PubMedID 17088903
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The effect of adjuvant chemotherapy versus whole abdominopelvic radiation on the survival of patients with advanced stage uterine papillary serous carcinoma
GYNECOLOGIC ONCOLOGY
2006; 103 (2): 679-683
Abstract
To compare the outcomes of stage III and IV uterine papillary serous carcinoma (UPSC) patients treated with platinum-based chemotherapy (PC) versus whole abdominopelvic irradiation (WAPI) after optimal cytoreductive surgery.Surgically staged patients with advanced stage UPSC diagnosed between 1981 and 2002 were identified from tumor registry databases at four hospitals. Survival analyses and predictors of outcome were analyzed using Kaplan-Meier methods.Of the 40 patients with advanced UPSC (median age: 64.5), 84% were Caucasian, 8% were African American, and 8% were Asian. The majority of patients (85%) presented with vaginal bleeding. Twenty-seven had stage III and 13 had stage IV disease. All patients were optimally debulked; 21 patients received adjuvant PC while 19 underwent WAPI. The median follow-up was 27 months (range: 5-209). The 3-year overall survival (OS) and progression-free survival (PFS) for the patients with stage III disease were 49% and 37% compared to 37% and 31% in those with stage IV disease (P = 0.23 for OS; P = 0.41 for PFS). Women who received PC had a 3-year OS and PFS of 43% and 31% compared to 45% and 41% in those receiving WAPI, respectively (P = 0.40 for OS; P = 0.84 for PFS).Platinum-based chemotherapy or whole abdominopelvic irradiation resulted in similar survival in this series of women with optimally cytoreduced UPSC. Given the overall poor prognosis of these patients, new treatment modalities are warranted.
View details for DOI 10.1016/j.ygyno.2006.05.005
View details for Web of Science ID 000241759600053
View details for PubMedID 16793126
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Therapeutic role of lymph node resection in endometrioid corpus cancer - A study of 12,333 patients
CANCER
2006; 107 (8): 1823-1830
Abstract
The purpose of the current study was to determine the potential therapeutic role of lymphadenectomy in women with endometrioid corpus cancer.Demographic and clinicopathologic information were obtained from the Surveillance, Epidemiology, and End Results Program between 1988-2001. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression.In all, 12,333 women (median age, 64) underwent surgical staging with lymph node assessment, including 9,009, 1,211, 1,223, and 890 with Stage I-IV disease. Over the time intervals 1988-1992, 1993-1997, and 1998-2001, the percentage of patients undergoing lymph node staging increased from 22.6%, 29.6%, to 40.9% (P < .001). In the intermediate/high-risk patients (Stage IB, Grade 3; Stage IC and II-IV, all grades), a more extensive lymph node resection (1, 2-5, 6-10, 11-20, and >20) was associated with improved 5-year disease-specific survivals across all 5 groups at 75.3%, 81.5%, 84.1%, 85.3%, and 86.8%, respectively (P < .001). For Stage IIIC-IV patients with nodal disease, the extent of node resection significantly improved the survival from 51.0%, 53.0%, 53.0%, 60.0%, to 72.0%, (P < .001). However, no significant benefit of lymph node resection in low-risk patients could be demonstrated (Stage IA, all grades; Stage IB, Grades 1 and 2 disease; P = .23). In multivariate analysis, a more extensive node resection remained a significant prognostic factor for improved survival in intermediate/high-risk patients after adjusting for other factors including age, year of diagnosis, stage, grade, adjuvant radiotherapy, and the presence of positive nodes (P < .001).The findings of the current study suggest that the extent of lymph node resection improves the survival of women with intermediate/high-risk endometrioid uterine cancer.
View details for DOI 10.1002/cncr.22185
View details for Web of Science ID 000241171300011
View details for PubMedID 16977653
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Ovarian cancer. Clinical practice guidelines in oncology.
Journal of the National Comprehensive Cancer Network
2006; 4 (9): 912-939
View details for PubMedID 17020669
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Outcomes of women with metachronous breast and ovarian carcinomas
GYNECOLOGIC ONCOLOGY
2006; 103 (1): 190-194
Abstract
Women with a history of breast cancer have a significantly increased risk of developing a second primary ovarian cancer and vice versa. We proposed to determine the characteristics and outcomes of women diagnosed with metachronous breast and ovarian cancer.Patients were identified from the Surveillance, Epidemiology, and End Results program database between 1988 and 2001. Kaplan-Meier and Cox proportional hazards regression tests were used to determine survival outcomes.Of 704 women, 526 developed breast cancer then ovarian cancer (B-O) and 178 developed ovarian cancer then breast cancer (O-B). The mean age at diagnosis of the first cancer in the B-O versus O-B group was 60.3 versus 58.9 years, respectively (P = 0.23). Twenty-five percent of women in the B-O group had stage I-II ovarian cancer versus 63% in the O-B group (P < 0.001). The percentage of those with stage I-II breast cancer was 94% and 91% in the B-O versus O-B group, respectively (P = 0.13). Women in the B-O group had more high grade of ovarian cancer compared to those in the O-B group (P < 0.001). The mean time interval between diagnoses of breast then ovarian versus ovarian then breast cancer was 58 versus 56 months, respectively (P = 0.42).In the largest series to date, we found that women diagnosed with ovarian cancer first had significantly more early stage and lower grade ovarian cancers with better survival compared to those with breast cancer followed by ovarian cancer. Since half of the women had their second cancer beyond 5 years, continued surveillance of these high risk patients is recommended.
View details for DOI 10.1016/j.ygyno.2006.02.022
View details for Web of Science ID 000240887100036
View details for PubMedID 16569424
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Breast cancer followed by corpus cancer: Is there a higher risk for aggressive histologic subtypes?
GYNECOLOGIC ONCOLOGY
2006; 102 (3): 508-512
Abstract
To analyze corpus cancer patients with a breast cancer history for risk of developing aggressive uterine histologic types.Corpus cancer patients with a history of breast cancer were identified from the Surveillance Epidemiology and End Results database from 1988 to 2001. Demographics, clinico-pathologic, and survival data were analyzed using Kaplan-Meier and logistic regression analyses.Of 52,109 women diagnosed with corpus cancer, 1922 had a history of breast cancer. Women with a history of breast cancer had a significantly higher proportion of uterine papillary serous carcinomas (UPSC) and sarcomas compared to those without a breast cancer history (9.4% vs. 6.3% for UPSC and 10.3% vs. 8.4% for sarcoma; P < 0.001). Patients with endometrioid or sarcoma of the uterus after breast cancer had significantly worse 5-year survivals than patients without a breast cancer history (84.4% vs. 90.5%; P < 0.001 and 49.0% vs. 63.6%, P < 0.001, respectively). Older age, advanced stage, lack of surgery and radiation treatment, poor histologic types, and history of breast cancer were independent prognostic factors for poorer survival.In this study, the proportional incidence of UPSC and sarcoma was significantly higher in women with a breast cancer history. These findings highlight the association of breast cancer and high-risk corpus cancer subtypes.
View details for DOI 10.1016/j.ygyno.2006.01.014
View details for Web of Science ID 000240871000017
View details for PubMedID 16483640
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Patterns and progress in ovarian cancer over 14 years
OBSTETRICS AND GYNECOLOGY
2006; 108 (3): 521-528
Abstract
To estimate the change in survival rates of women with ovarian cancer during the past 14 years.Women diagnosed with epithelial, germ cell, sarcomas, and sex-cord stromal ovarian tumors were identified from the Surveillance Epidemiology and End Results Database. Demographic and clinicopathologic factors, and survival information were extracted and tested using chi 2 and Kaplan-Meier and Cox regression analyses.A total of 30,246 women were diagnosed with ovarian cancer, including 26,753 non-clear cell epithelial, 1,411 clear cell, 818 sarcoma, 778 germ cell, and 486 sex-cord stromal tumors. The 5-year disease-specific survival rate across 1988-1992 and 1993-1997 improved from 45.4% to 48.6% (P < .001). The corresponding estimates show increases for non-clear cell epithelial carcinoma from 42.5% to 45.8% (P < .001), and for sarcomas from 33.5% to 38.8% (P = .07). However, improvements were not observed in those with clear cell, 64.3% to 63.9% (P = .82), and sex-cord stromal, 89.7% to 85.7% (P = .18), tumors of the ovary. In multivariable analyses, younger age, early stage, favorable histologic cell types, low-grade tumors, standard surgery, and recent time interval from 1993-1997 were independent prognostic factors for improved survival.In this large population-based study, there has been some improvement in the overall survival of women with ovarian cancers during a 14-year period. However, new treatment strategies are warranted for those with epithelial cancer and sarcomas of the ovary, given their overall poor prognosis. These results from our updated analyses might help to counsel women diagnosed with ovarian cancers.
View details for Web of Science ID 000246769000008
View details for PubMedID 16946210
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Awns play a dominant role in carbohydrate production during the grain-filling stages in wheat (Triticum aestivum)
PHYSIOLOGIA PLANTARUM
2006; 127 (4): 701-709
View details for DOI 10.1111/j.1399-3054.2006.00679.x
View details for Web of Science ID 000239561900017
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The number of lymph nodes with metastatic disease portends for a poorer prognosis in women with stage IIIC-IV endometrioid uterine cancer.
42nd Annual Meeting of the American-Society-of-Clinical-Oncology
AMER SOC CLINICAL ONCOLOGY. 2006: 265S–265S
View details for Web of Science ID 000239009401494
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Cellular immunotherapy redirected by bispecific antibodies in primary ovarian cancer cells: A preclinical study.
42nd Annual Meeting of the American-Society-of-Clinical-Oncology
AMER SOC CLINICAL ONCOLOGY. 2006: 104S–104S
View details for Web of Science ID 000239009400406
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The. role of extensive lymphadenectomy in stage I ovarian cancer.
42nd Annual Meeting of the American-Society-of-Clinical-Oncology
AMER SOC CLINICAL ONCOLOGY. 2006: 272S–272S
View details for Web of Science ID 000239009401523
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The impact of lymphadenectomy in women with endometrioid uterine cancer: A study of 39,396 women.
42nd Annual Meeting of the American-Society-of-Clinical-Oncology
AMER SOC CLINICAL ONCOLOGY. 2006: 256S–256S
View details for Web of Science ID 000239009401456
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The role of surgical staging in grade 1 endometrioid corpus cancer.
42nd Annual Meeting of the American-Society-of-Clinical-Oncology
AMER SOC CLINICAL ONCOLOGY. 2006: 258S–258S
View details for Web of Science ID 000239009401464
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Uterine cancers.
Journal of the National Comprehensive Cancer Network
2006; 4 (5): 438-462
View details for PubMedID 16687093
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Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: A preclinical study
CLINICAL CANCER RESEARCH
2006; 12 (6): 1859-1867
Abstract
Cytokine-induced killer (CIK) cells are ex vivo activated and expanded CD8+ natural killer T cells that have been shown to have antitumor activity. This is the first study exploring cell killing of primary ovarian carcinoma cells with and without bispecific antibodies. Primary cancer cells and autologous CIK cells were collected from women with epithelial ovarian cancer. Bispecific antibodies against cancer antigen-125 (BSAbxCA125) and Her2 (BSAbxHer2) were developed using chemical heteroconjugation. On fluorescence-activated cell sorting analysis, the expansion of CIK cells resulted in a significant increase of CD3+CD8+ and CD3+CD56+ T cells. With enhancement by bispecific antibodies, the mean percent lysis in a 51Cr release assay of fresh ovarian cancer cells exposed to autologous CIK cells increased from 21.7 +/- 0.3% to 89.4 +/- 2.1% at an E:T ratio of 100:1 (P < 0.001). Anti-NKG2D antibodies attenuated the CIK activity by 56.8% on primary cells (P < 0.001). In a xenograft severe combined immunodeficient mouse model, real-time tumor regression and progression was visualized using a noninvasive in vivo bioluminescence imaging system. Four hours after CIK cell injection, we were able to visualize CD8+NKG2D+ CIK cells infiltrating Her2-expressing cancer cells on fluorescence microscopy. Mice that underwent adoptive transfer of CIK cells redirected with BSAbxCA125 and BSAbxHer2 had significant reduction in tumor burden (P < 0.001 and P < 0.001) and improvement in survival (P = 0.05 and P = 0.006) versus those treated with CIK cells alone. Bispecific antibodies significantly enhanced the cytotoxicity of CIK cells in primary ovarian cancer cells and in our in vivo mouse model. The mechanism of cytolysis seems to be mediated in part by the NKG2D receptor.
View details for DOI 10.1158/1078-0432.CCR-05-2019
View details for PubMedID 16551871
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Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers
BRITISH JOURNAL OF CANCER
2006; 94 (5): 642-646
Abstract
To compare the survival of women with uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CC) to those with grade 3 endometrioid uterine carcinoma (G3EC). Demographic, pathologic, treatment, and survival information were obtained from the Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Data were analysed using Kaplan-Meier and Cox proportional hazards regression methods. Of 4180 women, 1473 had UPSC, 391 had CC, and 2316 had G3EC cancers. Uterine papillary serous carcinoma and CC patients were older (median age: 70 years and 68 vs 66 years, respectively; P<0.0001) and more likely to be black compared to G3EC (15 and 12% vs 7%; P<0.0001). A higher proportion of UPSC and CC patients had stage III-IV disease compared to G3EC patients (52 and 36% vs 29%; P<0.0001). Uterine papillary serous carcinoma, CC and G3EC patients represent 10, 3, and 15% of endometrial cancers but account for 39, 8, and 27% of cancer deaths, respectively. The 5-year disease-specific survivals for women with UPSC, CC and G3EC were 55, 68, and 77%, respectively (P<0.0001). The survival differences between UPSC, CC and G3EC persist after controlling for stage I-II (74, 82, and 86%; P<0.0001) and stage III-IV disease (33, 40, and 54; P<0.0001). On multivariate analysis, more favourable histology (G3EC), younger age, and earlier stage were independent predictors of improved survival. Women with UPSC and CC of the uterus have a significantly poorer prognosis compared to those with G3EC. These findings should be considered in the counselling, treating and designing of future trials for these high-risk patients.
View details for DOI 10.1038/sj.bjc.6603012
View details for Web of Science ID 000235868700007
View details for PubMedID 16495918
View details for PubMedCentralID PMC2361201
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Improved survival of Asians with corpus cancer compared with whites - An analysis of underlying factors
OBSTETRICS AND GYNECOLOGY
2006; 107 (2): 329-335
Abstract
To compare the clinicopathologic prognosticators and survival of Asians and whites with corpus cancer.Demographic, clinicopathologic, and survival data were obtained from the 1992-2001 Surveillance, Epidemiology, and End Results Program. Statistical analyses were performed by Kaplan-Meier methods and Cox proportional hazards model.A total of 2,144 Asians and 32,999 whites with corpus cancer were identified. The age-adjusted incidence of uterine cancer in Asians compared with whites was 16.8 compared with 26.1 per 100,000. Asians presented at a younger age (mean 58.4 years compared with 65.1; P < .01) and with more advanced stage disease than whites (21.5% compared with 15.4%; P < .01). The 5-year survival rate for Asians was 79.4% compared with 75.2% for whites (P < .01). Asians with stage I-II and III-IV cancers had 5-year survival rates of 89.3% and 41.2% compared with 82.3% and 34.0% for the whites, respectively (P < .01, early stage; P < .01, advanced stage). The survival advantage of Asians persists in endometrioid (P < .01) and uterine papillary serous carcinomas (P < .01), but not in clear cell carcinoma (P = .62) or sarcomas (P = .78). In multivariate analysis, younger age (P < .01), earlier stage (P < .01), favorable histology (P < .01), and lower grade (P < .01) remained as significant independent prognosticators for improved survival. However, race was not an important prognosticator.The overall survival advantage experienced by Asians with uterine cancer is attributable to their younger age at diagnosis. Because Asian women present at a younger age with more advanced disease, physicians should have an increased index of suspicion for malignancy in young Asian women with suspicious symptoms and consider a lower age threshold for biopsy in this group.II-2.
View details for Web of Science ID 000241295400019
View details for PubMedID 16449120
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Elevated CO2 induces physiological, biochemical and structural changes in leaves of Arabidopsis thaliana
NEW PHYTOLOGIST
2006; 172 (1): 92-103
Abstract
Leaves of Arabidopsis thaliana grown under elevated or ambient CO2 (700 or 370 micromol mol(-1), respectively) were examined for physiological, biochemical and structural changes. Stomatal characters, carbohydrate and mineral nutrient concentrations, leaf ultrastructure and plant hormone content were investigated using atomic absorption spectrophotometry, transmission electron microscopy and enzyme-linked immunosorbent assay (ELISA). Elevated CO2 reduced the stomatal density and stomatal index of leaves, and also reduced stomatal conductance and transpiration rate. Elevated CO2 increased chloroplast number, width and profile area, and starch grain size and number, but reduced the number of grana thylakoid membranes. Under elevated CO2, the concentrations of carbohydrates and plant hormones, with the exception of abscisic acid, increased whereas mineral nutrient concentrations declined. These results suggest that the changes in chloroplast ultrastructure may primarily be a consequence of increased starch accumulation. Accelerated A. thaliana growth and development in elevated CO2 could in part be attributed to increased foliar concentrations of plant hormones. The reductions in mineral nutrient concentrations may be a result of dilution by increased concentrations of carbohydrates and also of decreases in stomatal conductance and transpiration rate.
View details for DOI 10.1111/j.1469-8137.2006.01818.x
View details for Web of Science ID 000239988100011
View details for PubMedID 16945092
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Prognostic factors for outcomes and complications for primary squamous cell carcinoma of the vagina treated with radiation
48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO)
ELSEVIER SCIENCE INC. 2006: S160–S160
View details for Web of Science ID 000241221600267
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Bispecific antibody-redirected immunotherapy of Her2/neu-expressing uterine cancer.
Western Regional Meeting of the American-Federation-for-Medical-Research
LIPPINCOTT WILLIAMS & WILKINS. 2006: S104–S104
View details for Web of Science ID 000235301500152
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Immunotherapy of primary ovarian cancer using autologous cytokine induced killer cells retargeted with bispecific antibodies: A preclinical study.
47th Annual Meeting of the American-Society-of-Hematology
AMER SOC HEMATOLOGY. 2005: 669A–670A
View details for Web of Science ID 000233426004226
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Intraoperative radiation therapy in recurrent ovarian cancer
35th Annual Meeting of the Society-of-Gynecologic-Oncologists
ELSEVIER SCIENCE INC. 2005: 1114–21
Abstract
To evaluate disease outcomes and complications in patients with recurrent ovarian cancer treated with cytoreductive surgery and intraoperative radiation therapy (IORT).A retrospective study of 24 consecutive patients with ovarian carcinoma who underwent secondary cytoreduction and intraoperative radiation therapy at our institution between 1994 and 2002 was conducted. After optimal cytoreductive surgery, IORT was delivered with orthovoltage X-rays (200 kVp) using individually sized and beveled cone applications. Outcomes measures were local control of disease, progression-free interval, overall survival, and treatment-related complications.Of these 24 patients, 22 were available for follow-up analysis. Additional treatment at the time of and after IORT included whole abdominopelvic radiation, 9; pelvic or locoregional radiation, 5; chemotherapy, 6; and no adjuvant treatment, 2. IORT doses ranged from 9-14 Gy (median, 12 Gy). The anatomic sites treated were pelvis (sidewalls, vaginal cuff, presacral area, anterior pubis), para-aortic and paracaval lymph node beds, inguinal region, or porta hepatitis. At a median follow-up of 24 months, 5 patients remain free of disease, whereas 17 patients have recurred, of whom 4 are alive with disease and 13 died from disease. Five patients recurred within the radiation fields for a locoregional relapse rate of 32% and 12 patients recurred at distant sites with a median time to recurrence of 13.7 months. Five-year overall survival was 22% with a median survival of 26 months from time of IORT. Nine patients (41%) experienced Grade 3 toxicities from their treatments.In carefully selected patients with locally recurrent ovarian cancer, combined IORT and tumor reductive surgery is reasonably tolerated and may contribute to achieving local control and disease palliation.
View details for DOI 10.1016/j.ijrobp.2005.04.007
View details for Web of Science ID 000232943900020
View details for PubMedID 15964710
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Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
2005; 63 (3): 839-844
Abstract
To determine the efficacy of adjuvant therapy in patients with early-stage uterine papillary serous carcinoma.Data were collected on all surgically staged Stage I-II uterine papillary serous carcinoma patients. Statistical analyses were performed using the Kaplan-Meier and Cox proportional hazards regression methods.Of 68 patients, 50 had Stage I and 18 had Stage II disease; 35 underwent adjuvant treatment, including radiotherapy in 26, chemotherapy in 7, and combined RT and chemotherapy in 2. The remaining 33 were treated expectantly. The median follow-up was 56 months (range 1-173). The 5-year overall survival rate was 69%. Of 19 patients with disease limited to the endometrium, 10 received no additional therapy, 3 of whom developed recurrence. However, all 9 women who underwent adjuvant treatment remained free of disease. Patients receiving adjuvant therapy with chemotherapy or radiotherapy had a prolonged 5-year overall and disease-free survival compared with those who were treated expectantly (85% vs. 54%, p = 0.002 for overall survival and 85% vs. 49%, p = 0.01 for disease-free survival). In multivariate analysis, adjuvant therapy (p = 0.035) and the absence of lymphovascular space invasion (p = 0.001) remained as independent prognostic factors for improved survival.Adjuvant therapy with chemotherapy or radiotherapy improves the survival of women with early-stage uterine papillary serous carcinoma.
View details for DOI 10.1016/j.ijrobp.2005.03.028
View details for Web of Science ID 000232411600025
View details for PubMedID 16199314
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A modified technique for insertion of intraperitoneal port for chemotherapy
JOURNAL OF SURGICAL ONCOLOGY
2005; 90 (4): 247-248
Abstract
The clinical and pharmacological rationale of using intraperitoneal (IP) chemotherapy has been demonstrated in randomized clinical trials. However, IP chemotherapy is often discontinued secondary to catheter-related complications such as blockage, leakage, infection, and access difficulties. An effective method that provides a reliable access to the IP cavity is needed. In this report, we describe a novel technique of IP port placement that may prevent access problems and decrease patient discomfort.
View details for DOI 10.1002/jso.20255
View details for Web of Science ID 000229453300006
View details for PubMedID 15906367
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Factors responsible for improved survival in Asians with corpus cancer compared with whites
53rd Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists
LIPPINCOTT WILLIAMS & WILKINS. 2005: 117S–117S
View details for Web of Science ID 000228065900265
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Cervical cancer guidelines. Clinical practice guidelines in oncology.
Journal of the National Comprehensive Cancer Network
2004; 2 (6): 612-630
View details for PubMedID 19780304
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Cervical cancer screening clinical practice guidelines in oncology.
Journal of the National Comprehensive Cancer Network
2004; 2 (6): 570-587
View details for PubMedID 19780301
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Ovarian cancer clinical practice guidelines.
Journal of the National Comprehensive Cancer Network
2004; 2 (6): 526-547
View details for PubMedID 19780297
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Detection of pelvic lymph node micrometastasis in stage IA2-IB2 cervical cancer by immunohistochemical analysis
31st Annual Meeting of the Western-Association-of-Gynecologic-Oncologists
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2004: 107–11
Abstract
The objectives of this study were to (1) determine the incidence of lymph node micrometastasis in cervical cancer by immunohistochemical analysis and (2) determine if the presence of micrometastasis is a poor prognostic feature in early cervical cancer.We retrospectively reviewed the medical records of 62 patients who underwent radical hysterectomy and lymphadenectomy for FIGO stage IA2-IB2 cervical cancer at Stanford University Hospital from 1990 to 2000. Forty-nine patients with negative lymph nodes were identified. A total of 976 formalin-fixed paraffin-embedded pelvic lymphadenectomy specimens were serially sectioned and stained with anti-cytokeratin antibodies AE1 and AE1/CAM5.2.Six patients had stage IA2 disease, 37 had stage IB1, and 6 had IB2. The mean age of the patients was 44 years (range, 24-76). Seventy-one percent had squamous cell carcinomas, 22% had adenocarcinomas, and 6% had other types. Lymph node micrometastases were immunohistochemically detected in 4 of the 49 (8.1%) patients, comprising 4 of 976 (0.41%) pelvic lymph nodes examined. Twelve of 45 (15.6%) patients with negative nodes had lymph-vascular space invasion (LVSI) whereas 3 of 4 (75%) patients with micrometastases had LVSI. At a mean follow-up time of 39.4 months, 2 of 4 (50%) patients with micrometastasis had recurrent disease, while 3 of 45 (6.7%) patients without micrometastasis developed recurrent disease.These preliminary data suggest that immunohistochemical detection of pelvic lymph nodes is more frequent in patients with LVSI and may identify patients needing adjuvant chemoradiation.
View details for DOI 10.1016/j.ygyno.2003.11.033
View details for Web of Science ID 000220850800016
View details for PubMedID 15047221
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Secondary cytoreductive surgery for patients with relapsed epithelial ovarian carcinoma: Who benefits?
CANCER
2004; 100 (6): 1152-1161
Abstract
This study was performed to address patient selection criteria and the role of secondary cytoreductive surgery (SCR) in patients with epithelial ovarian carcinoma (EOC) who had relapsed tumors after a progression-free interval > or = 3 months.One hundred seventeen patients with relapsed EOC after a clinical complete remission duration > or = 3 months who underwent SCR were entered on this prospective trial. Survival curves were generated using the Kaplan-Meier method, and statistical comparisons were performed using log-rank tests, logistic stepwise regression analyses, and a Cox stepwise regression model.The median patient age at the time of relapse was 53 years (range, 20-78 years). The median survival was 22 months and the estimated 5-year survival rate for the entire cohort was 17.2%. Tumor was confined to a solitary site in 33 patients and to > or = 2 sites in 84 patients. After they underwent SCR, 11 patients were rendered macroscopically disease free, 61 patients had residual disease that measured < or = 1 cm in greatest dimension, and 45 patients had bulky intraabdominal residual disease. Survival was influenced by the extent of relapse disease (solitary site vs. multiple sites; P < 0.0001), the size of residual disease after SCR (0 cm vs. < or = 1 cm [P = 0.1211], < or = 1 cm vs. > 1 cm [P = 0.0002], and 0 cm vs. > 1 cm [P = 0.0011]), Eastern Cooperative Oncology Group performance status (0 vs. 1 [P = 0.134], 1 vs. 2 [P = 0.007], and 0 vs. 2 [P = 0.0012]), and the number of cycles of salvage chemotherapy (1-2 cycles vs. 3-5 cycles [P = 0.0144]; 1-2 cycles vs. > or = 6 cycles [P < 0.0001]; and 3-5 cycles vs. > or = 6 cycles [P = 0.0009]). The outcome of SCR was influenced by the extent of relapse disease (multiple sites [51.2%] vs. solitary sites [87.9%]; relative risk [RR] = 9.1237; P = 0.0002) and by the use of bowel resection (yes [60.9%] vs. no [37.5%]; RR = 0.3828; P = 0.0106).SCR was found to be safe for patients with relapsed EOC who achieved a clinical complete remission that lasted > or = 3 months, with resectability similar to that of primary debulking surgery. Optimal surgical outcomes were achieved easily in patients who apparently had solitary tumor sites, with bowel resection making it possible to remove bulky tumors that involved the intestine. A survival benefit was provided by optimal SCR, particularly when surgery was supported by multiple courses of salvage chemotherapy.
View details for DOI 10.1002/cncr.20106
View details for Web of Science ID 000220195200007
View details for PubMedID 15022281
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Platinum-based chemotherapy versus whole abdominopelvic irradiation in the treatment of advanced stage uterine papillary serous carcinoma.
51st Annual Meeting of the Society-for-Gynecologic-Investigation
ELSEVIER SCIENCE INC. 2004: 403A–403A
View details for Web of Science ID 000220184500969
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B cell lymphoproliferative disorders and VH4-34 gene encoded antibodies.
Human antibodies
2004; 13 (3): 63-68
Abstract
The VH4-34 represents an unusual Ig heavy chain variable region gene given that it is conserved and overexpressed despite its autoreactivity. Besides RBC 'I/i' recognition, a subset of VH4-34 encoded Igs bind and kill human B-lymphocytes via interaction with a cytoskeletally-associated ligand similar in structure to the cord RBC 'i' antigen. In vivo, secretion of VH4-34 gene encoded antibodies is minimal in healthy individuals. The turn on signal occurs in few clinical conditions such as, systemic lupus erythematosus, AIDS and infectious mononucleosis. Here we show that secretion of VH4-34 Abs is also switched on in hepatitis C and nasopharyngeal carcinoma; but not in diseases such as HPV-associated cervical carcinoma, multiple sclerosis and sarcoidosis. All syndromes with increased VH4-34 Igs appear to be associated with B cell hyperproliferation and B cell lymphotropic viruses, particularly EBV. The significance of the tightly controlled secretion of an autoreactive, conserved Ig gene is discussed.
View details for PubMedID 15598986
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Differential expression of CD40 and CD95 in ovarian carcinoma
EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY
2004; 25 (1): 27-32
Abstract
The role of CD95 (Fas) as a mediator of apoptosis has been well documented. CD40 ligation has been recently shown to initiate apoptosis and modulate CD95 mediated apoptosis in normal and some neoplastic tissues. Here we report the expression of CD95 and CD40 in cryopreserved cell suspensions from ovarian cancer associated ascites, fresh primary and recurrent ovarian carcinoma (OVCA) specimens, and ten established ovarian cancer cell lines. The effect of CD95 and CD40 receptor binding on apoptosis is described in two cell lines.Ascites specimens, fresh primary and recurrent OVCA specimens were dissociated to single cell suspensions. Expression of CD95 and CD40 was analyzed using flow cytometry. Apoptosis was determined via annexin uptake by flow cytometry following incubation with anti-CD95 antibody, CH11 and trimeric CD40L.Ascites showed the highest expression of both CD95 and CD40. Recurrent OVCA, in contrast, expressed low levels of CD95 and CD40. Primary OVCA showed moderate expression of both receptors. CD40 expression in ascites was significantly greater when compared to solid specimens (p < 0.05). Both CD40 and CD95 were strongly expressed in eight of ten cell lines studied. Binding of CD40L did not influence CD95 mediated apoptosis.CD40 is ubiquitously expressed in ovarian carcinomas and expression differs between ascites and solid tumor. There may be differential expression of both CD40 and CD95 in recurrent vs primary ovarian carcinoma, which may contribute to increased clinical malignancy of recurrent disease. In contrast to other epithelial malignancies, CD40 ligation does not appear to modulate CD95 mediated apoptosis.
View details for Web of Science ID 000189378400004
View details for PubMedID 15053058
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Epoxidation of chiral camphor N-enoylpyrazolidinones with methyl(trifluoromethyl)dioxirane and urea hydrogen peroxide/acid anhydride: Reversal of stereoselectivity
JOURNAL OF ORGANIC CHEMISTRY
2003; 68 (25): 9816-9818
Abstract
Both diastereomeric isomers of epoxides with high optical purity are obtained when camphor N-methacryloylpyrazolidinone (1a) and N-tigloylpyrazolidinone (1b) are treated with a urea hydrogen peroxide/TFAA and methyl(trifluoromethyl)dioxirane, respectively.
View details for DOI 10.1021/jo034807w
View details for Web of Science ID 000187016700037
View details for PubMedID 14656113
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Modification of the vertical rectus abdominis musculocutaneous (VRAM) flap for functional reconstruction of complex vulvoperineal defects
ANNALS OF PLASTIC SURGERY
2003; 51 (6): 556-560
Abstract
Radical vulvoperineal ablations present challenging reconstructive dilemmas, especially when local metastatic spread requires distal vaginal and anal resection. Despite advances in vaginal salvage and sphincteroplasty, surface recontouring remains elusive because of the necessity to resurface a large, complex area that includes the mons, vulva, and fourchette. We describe a modification of the inferior-based vertical rectus abdominis musculocutaneous (VRAM) flap where the superior portion is split longitudinally to produce "tongue" flaps, which can resurface complex vulvoperineal wounds. By splitting the flap, one can resurface the vulva, provide an edge to reattach the vaginal cuff, and recreate the fourchette and line the anoderm after anoplasty. This musculocutaneous flap provides adequate contour and protection against radiation injury. Splitting of the flap is based on the vascular territory of the superior epigastric branches and their perforators and can be carried down to the level of their anastomosis, with the inferior system at the level of the umbilicus. The split VRAM flap has been used successfully in 3 patients with complex perineal wounds with excellent results and maintenance of vaginal patency.
View details for DOI 10.1097/01.sap.0000096444.59573.87
View details for Web of Science ID 000187178600005
View details for PubMedID 14646647
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Monoclonal antibody 216 (MAb 216), a VH4-34 encoded antibody, is a novel cytotoxic agent for B-progenitor acute lymphoblastic leukemia (ALL).
AMER SOC HEMATOLOGY. 2003: 380A
View details for Web of Science ID 000186536701380
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Gene expression patterns in ovarian carcinomas
MOLECULAR BIOLOGY OF THE CELL
2003; 14 (11): 4376-4386
Abstract
We used DNA microarrays to characterize the global gene expression patterns in surface epithelial cancers of the ovary. We identified groups of genes that distinguished the clear cell subtype from other ovarian carcinomas, grade I and II from grade III serous papillary carcinomas, and ovarian from breast carcinomas. Six clear cell carcinomas were distinguished from 36 other ovarian carcinomas (predominantly serous papillary) based on their gene expression patterns. The differences may yield insights into the worse prognosis and therapeutic resistance associated with clear cell carcinomas. A comparison of the gene expression patterns in the ovarian cancers to published data of gene expression in breast cancers revealed a large number of differentially expressed genes. We identified a group of 62 genes that correctly classified all 125 breast and ovarian cancer specimens. Among the best discriminators more highly expressed in the ovarian carcinomas were PAX8 (paired box gene 8), mesothelin, and ephrin-B1 (EFNB1). Although estrogen receptor was expressed in both the ovarian and breast cancers, genes that are coregulated with the estrogen receptor in breast cancers, including GATA-3, LIV-1, and X-box binding protein 1, did not show a similar pattern of coexpression in the ovarian cancers.
View details for PubMedID 12960427
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Preoperative CT diagnosis of primary fallopian tube carcinoma in a patient with a history of total abdominal hysterectomy
JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
2003; 27 (3): 361-363
Abstract
Fallopian tube carcinoma is an unusual gynecologic malignancy that is rarely diagnosed preoperatively. We report a case of fallopian tube carcinoma occurring in a patient who had undergone a hysterectomy many years previously, in whom findings on computed tomography and ultrasound were highly suggestive of the diagnosis.
View details for PubMedID 12794600
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Protein expression study of ovarian surface epithelial neoplasms using tissue microarray analysis: Emergence of a clear cell signature profile
92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology
NATURE PUBLISHING GROUP. 2003: 181A–181A
View details for Web of Science ID 000180732500838
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Protein expression study of ovarian surface epithelial neoplasms using tissue microarray analysis: Emergence of a clear cell signature profile
92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology
NATURE PUBLISHING GROUP. 2003: 181A–181A
View details for Web of Science ID 000180720100835
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Liposomal doxorubicin for treatment of metastatic chemorefractory vulvar adenocarcinoma
GYNECOLOGIC ONCOLOGY
2002; 87 (3): 313-318
Abstract
Primaryadenocarcinoma of the vulva is a rare entity, and for widely metastatic vulvar adenocarcinoma, no effective treatment has been established.A 65-year-old woman was diagnosed with regionally advanced vulvar adenocarcinoma, with bulky involvement of bilateral groin lymph nodes, and associated extramammary Paget's disease. Initial therapy consisted of multiagent chemotherapy and vulvar and groin irradiation, followed by radical vulvectomy with groin and pelvic lymph node dissection. She subsequently developed widely metastatic disease including brain, pulmonary, hepatic, osseus, and subcutaneous lesions. Treatment with liposomal doxorubicin (Doxil) resulted in dramatic regression of metastatic lesions and marked improvement in quality-of-life. She remains clinically well, greater than 1 year since initiating Doxil treatment for widely metastatic vulvar adenocarcinoma, and has surpassed 5 years of survival since her initial diagnosis.We report the first case of Doxil used for the treatment of metastatic chemorefractory vulvar adenocarcinoma. We observed that Doxil was a well-tolerated and effective agent for this gynecologic malignancy, and warrants further investigation.
View details for DOI 10.1006/gyno.2002.6830
View details for Web of Science ID 000179842700015
View details for PubMedID 12468332
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VH4-34 encoded antibody in systemic lupus erythematosus: Effect of Isotype
JOURNAL OF RHEUMATOLOGY
2002; 29 (10): 2114-2121
Abstract
To determine the clinical significance of elevated serum levels of VH4-34 encoded IgM and IgG antibodies with respect to the clinical characteristics of systemic lupus erythematosus (SLE).VH4-34 encoded IgM and IgG immunoglobulin was measured in 95 patients with SLE by ELISA using antiidiotype monoclonal antibody (Mab) 9G4. SLE disease activity, severity, and damage were assessed by visual analog scales, Systemic Lupus Activity Measure, Lupus Severity of Disease Index, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Presence of VH4-34 encoded antibodies on patients' B lymphocytes was analyzed by flow cytometry using Mab 9G4.Fifty-two of 95 patients with SLE had elevated levels of VH4-34 encoded antibodies of IgG isotype; 17 patients with VH4-34 IgG had elevated VH4-34 of the IgM isotype. Forty-three of the 95 patients had normal levels of VH4-34 encoded antibodies. When disease severity was correlated to VH4-34 isotype, patients with circulating VH4-34 IgG but without IgM had significantly more severe disease compared to patients who had VH4-34 of both isotypes. Eighty-six percent of patients with SLE nephritis and 100% of those with central nervous system (CNS) lupus had VH4-34 IgG without IgM. In vivo, VH4-34 encoded antibodies were found to bind autologous B lymphocytes.Presence of VH4-34 IgG in the absence of VH4-34 IgM was the finding most strongly associated with severe SLE, nephritis, and CNS lupus, suggesting that isotype switching of VH4-34 encoded antibodies or loss of VH4-34 IgM encoded antibodies may influence the progression of disease in SLE.
View details for Web of Science ID 000178374000015
View details for PubMedID 12375320
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A new approach to enhancement of bone formation by electrically polarized hydroxyapatite
JOURNAL OF DENTAL RESEARCH
2001; 80 (10): 1925-1929
Abstract
An electrical field may affect osteogenesis. Since we found that hydroxyapatite (HA) ceramics may be polarizable, we hypothesized that electrically polarized HA may foster production of new bone in vivo. Both polarized and non-polarized HA ceramics were inserted into the subperiosteum spaces at the parietal bone area of rats. After 2, 4, and 8 weeks, the implant sites were examined histologically. Morphometric analysis revealed that new bone formation was accelerated on the negatively charged surface of the polarized HA (N-surface) at 2 weeks. The newly formed bone approached maturation at 4 weeks and was thicker on the N-surface than in the controls. By 8 weeks, newly formed bone in the controls was almost the same as that on the N-surface. These findings suggest that polarized HA is biocompatible and that bone formation on the N-surface is enhanced in the early stage of bone healing.
View details for Web of Science ID 000174684300012
View details for PubMedID 11706953
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Effect of 17 beta-estradiol or alendronate on the bone densitometry, bone histomorphometry and bone metabolism of ovariectomized rats
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
2001; 34 (8): 1015-1022
Abstract
The objective of the present study was to evaluate the effect of 17beta-estradiol or alendronate in preventing bone loss in 3-month-old ovariectomized Wistar rats. One group underwent sham ovariectomy (control, N = 10), and the remaining three underwent double ovariectomy. One ovariectomized group did not receive any treatment (OVX, N = 12). A second received subcutaneous 17beta-estradiol at a dose of 30 microg/kg for 6 weeks (OVX-E, N = 11) and a third, subcutaneous alendronate at a dose of 0.1 mg/kg for 6 weeks (OVX-A, N = 8). Histomorphometry, densitometry, osteocalcin and deoxypyridinoline measurements were applied to all groups. After 6 weeks there was a significant decrease in bone mineral density (BMD) at the trabecular site (distal femur) in OVX rats. Both alendronate and 17beta-estradiol increased the BMD of ovariectomized rats, with the BMD of the OVX-A group being higher than that of the OVX-E group. Histomorphometry of the distal femur showed a decrease in trabecular volume in the untreated group (OVX), and an increase in the two treated groups, principally in the alendronate group. In OVX-A there was a greater increase in trabecular number. An increase in trabecular thickness, however, was seen only in the OVX-E group. There was also a decrease in bone turnover in both OVX-E and OVX-A. The osteocalcin and deoxypyridinoline levels were decreased in both treated groups, mainly in OVX-A. Although both drugs were effective in inhibiting bone loss, alendronate proved to be more effective than estradiol at the doses used in increasing bone mass.
View details for Web of Science ID 000170731800007
View details for PubMedID 11471040
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Susceptibility of B-cell lymphoma to human antibodies encoded by the V4-34 gene
International Conference on Advances in Cancer Immunotherapy
ELSEVIER SCIENCE INC. 2001: 59–68
Abstract
Our previous studies have shown that mAbs derived from the human V4-34 gene bind and kill human B-lymphocytes via membrane disruption. This study demonstrates the cytotoxicity of two V4-34 encoded mAbs, 216 and Z2D2, towards human B-cell lymphoma. In vitro, 216 and Z2D2 are cytotoxic to a variety of B-cell lymphomas obtained from patient biopsies. In vivo, increased survival was observed with both mAbs in a lymphoma model developed in scid mice with human B-cell line Nalm-6. Studies in mice show that these mAbs are well tolerated with minimum side effects. Since 216 and Z2D2 show increased toxicity towards cycling cells, V4-34 mAb-based therapy can be additive with drugs that block cell-cycle progression. Stem cells that are V4-34 mAb ligand negative would not be depleted. Together, these studies recommend an evaluation of the two completely human mAbs in a phase I trial for B-cell lymphoma.
View details for Web of Science ID 000169725400007
View details for PubMedID 11418302
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Treatment of B cell lymphoma by V4-34 encoded antibodies.
AMER SOC HEMATOLOGY. 2000: 731A
View details for Web of Science ID 000165256103161
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Treatment of high-risk uterine cancer with whole abdominopelvic radiation therapy
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
2000; 48 (3): 767-778
Abstract
To evaluate the treatment outcomes in patients with optimally debulked Stage III and IV endometrial adenocarcinoma (ACA) or Stages I-IV uterine papillary serous (UPSC) or clear cell (CCC) carcinoma of the uterus, treated postoperatively with whole abdominopelvic irradiation (WAPI).Between 1979 and 1998, 48 patients received postoperative WAPI at our institution. Twenty-two patients had FIGO Stage III or Stage IV ACA and 26 patients had FIGO Stages I-IV UPSC or CCC. The median dose was 30 Gy to the upper abdomen and 49.8 Gy to the pelvis. Mean follow-up was 37 months (2.4-135 months).The 3-year estimated disease-free survival (DFS) and overall survival (OS) rates for the entire group were 60% and 77%, respectively. Patients with ACA had 3-year DFS and OS of 79% and 89%, respectively, compared with 47% and 68% in the UPSC/CCC group. Early-stage patients (I and II) with UPSC/CCC had 3-year DFS and OS of 87% compared with 32% and 61% in those with advanced (Stage III and IV) disease. The 3-year actuarial major complication rate was 7%, with no treatment-related deaths. All 4 failures in the ACA group were extra-abdominal and 6 of the 11 in the UPSC/CCC group had an extra-abdominal component. Age and UPSC/CCC histology were significant prognostic factors for DFS and OS. In addition, stage and number of extrauterine sites of disease were significant predictors for DFS in UPSC/CCC.WAPI is a safe, effective treatment for patients with optimally debulked advanced-stage uterine ACA or early-stage UPSC/CCC. Survival was significantly worse in advanced-stage UPSC/CCC patients. We recommend future trials of WAPI with concurrent, or subsequent systemic therapy in patients with advanced-stage UPSC or CCC.
View details for Web of Science ID 000089822600019
View details for PubMedID 11020574
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Malignant granular cell tumor of the vulva in a 17-year-old: Case report and literature review.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
2000; 10 (5): 429-434
Abstract
Granular cell tumors are uncommon soft tissue tumors. Although the majority of these tumors are benign, a rare malignant variant exists which is aggressive, with local recurrence rates up to 70% and 3-year survival rates of less than 50%. We present a case of malignant granular cell tumor of the vulva in a 17-year-old, the sixth such case to be reported at this site. She was treated with a left hemivulvectomy and ipsilateral groin node dissection followed by postoperative radiation therapy. She remains free of disease at 16 months. Patients with malignant granular cell tumor or granular cell tumor of malignant potential are best managed with wide local excision and regional lymph node dissection.
View details for PubMedID 11240710
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Malignant granular cell tumor of the vulva in a 17-year-old: Case report and literature review
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
2000; 10 (5): 429-434
View details for Web of Science ID 000165402900013
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Primary leiomyosarcoma of the vagina. A case report and literature review.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
2000; 10 (4): 340-347
Abstract
Primary vaginal leiomyosarcoma is a rare tumor. We report a unique case of a 27-year-old woman with stage I, high-grade primary leiomyosarcoma of the vagina treated with surgical resection and adjuvant radiation therapy. She returned within 6 months with an abdominal-pelvic recurrence and lung metastases. The patient died of disease 9 months after diagnosis. A comprehensive review of primary vaginal leiomyosarcoma was performed and factors affecting survival were analyzed. A Medline search of the English-language literature revealed 66 previously reported cases. Forty-eight of these had follow-up data. Survival probabilities were calculated using the Kaplan-Meier method, and the effects of age, stage, grade, tumor location, and treatment modality were analyzed. Stage III and IV data were combined. The overall 5-year survival rate was 43%. Patients more than 50 years of age had a 5-year survival rate of 26% compared with 51% for those less than 40 years. Five-year survival for stage I and II tumors was 55% and 44%, respectively. Patients with stage III/IV disease had 25% survival at 18 months. No patient treated primarily with chemotherapy or radiation therapy survived beyond 36 months. In contrast, patients treated primarily with surgery had a 5-year survival rate of 57%. Only stage remained an independent predictor of survival on Cox regression analysis. We continue to recommend surgical resection as primary treatment. Exenteration may be an option for select patients, but ultimately management should continue on a case-by-case basis.
View details for PubMedID 11240697
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Primary leiomyosarcoma of the vagina. A case report and literature review
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
2000; 10 (4): 340-347
View details for Web of Science ID 000089404800013
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Recognition of auto- and exoantigens by V4-34 gene encoded antibodies
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
2000; 51 (2): 134-140
Abstract
The antigenic specificities of 24 V4-34-encoded monoclonal antibodies were compared with the amino acid sequence. The specificities were divided into three categories, red blood cells, B lymphocytes and auto/exoantigens. Six anti-I monoclonal antibodies, with multiple substitutions in their VH region, did not bind B lymphocytes or auto/exoantigens. Reactivity to these two antigens segregated with the 16 anti-i monoclonal antibodies, which were derived from the near germline V4-34 gene. All anti-i monoclonal antibodies bound B lymphocytes, albeit with varying intensities. B-cell binding correlated with basic amino acids in the VH-CDR3. Reactivity to auto/exoantigens was demonstrated only by a subset anti-i monoclonal antibodies and did not correlate with B-lymphocyte or i-antigen binding. These anti-ssDNA reactive monoclonal antibodies had basic amino acids in the VH-CDR3, strongly supporting the suggested role of arginine in DNA binding. However, an arginine-rich CDR3 was not enough to ensure DNA reactivity, since six other anti-i monoclonal antibodies that fulfilled this criteria did not bind ssDNA. Thus it is possible that the anti-DNA reactivity of V4-34-encoded monoclonal antibodies is mediated by the classic antigen-binding groove generated by the CDRs of the heavy/light chains. In contrast, anti-B-cell/i-antigen reactivity is mediated, unconventionally, by the V4-34 protein with a dominant influence of the VH-CDR3.
View details for Web of Science ID 000085609000004
View details for PubMedID 10652159
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NCCN practice guidelines for endometrial carcinoma
ONCOLOGY-NEW YORK
1999; 13 (11A): 45-67
View details for Web of Science ID 000165178600004
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VH4-34 encoded antibodies in systemic lupus erythematosus: A specific diagnostic marker that correlates with clinical disease characteristics
JOURNAL OF RHEUMATOLOGY
1999; 26 (8): 1727-1733
Abstract
To determine the clinical significance of elevated serum levels of VH4-34 encoded antibodies (VH4-34 Ab) with respect to the diagnosis and clinical characteristics of systemic lupus erythematosus (SLE).Ninety-five patients with SLE and 344 controls were studied. The controls included 34 healthy individuals, 282 patients with nonautoimmune diseases, and 28 patients with autoimmune diseases other than SLE. VH4-34 Ab levels were measured by inhibition ELISA using anti-idiotope monoclonal antibody (9G4). SLE disease activity, severity, and damage were assessed by visual analog scales, Systemic Lupus Activity Measure, Lupus Severity of Disease Index, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index.Fifty-two of 95 patients with SLE had elevated levels of VH4-34 Ab compared to 18 of 344 controls (5%), giving a sensitivity of 55% and a specificity of 95% for elevated VH4-34 Ab as a serologic test for SLE. The positive predictive value of elevated VH4-34 under these conditions was 74-85%. In this study, anti-dsDNA was not VH4-34 encoded. Significant correlations between VH4-34 and disease activity and severity indices were observed (r = 0.29-0.50). The relative risk for severe disease in SLE patients with VH4-34 antibody level in the highest tertile compared to the lowest tertile was 5.25. Twenty-five of 29 patients with lupus nephritis and 6 of 6 patients with central nervous system (CNS) lupus had elevated VH4-34 Ab.With a specificity of 94-95%, the VH4-34 antibody assay may prove valuable as a confirmatory diagnostic test for SLE. In patients with known SLE, serum VH4-34 Ab levels correlate with overall disease severity and activity, but not damage, and with nephritis and CNS lupus.
View details for Web of Science ID 000081725000015
View details for PubMedID 10451069
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Clinical practice guidelines in the management of gynecologic malignancies
HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA
1999; 13 (1): 63-?
Abstract
The need for guidelines in managing gynecologic cancer is addressed in the first part of this article. Second, the guideline development process that enables the practitioner to judge the validity and usefulness of proffered guidelines is detailed. An important element in this discussion is an exploration of the shortcomings, either real or perceived, of the process. The last section focuses on issues relating to the implementation of guidelines and some of the obstacles that one may encounter as the programs evolve.
View details for Web of Science ID 000079144800005
View details for PubMedID 10080070
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Cytotoxicity of murine B lymphocytes induced by human VH4-34 (VH4.21) gene-encoded monoclonal antibodies
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
1997; 84 (3): 283-289
Abstract
We have previously described specific binding and cytotoxicity of human B lymphocytes by VH4-34 gene-derived anti-i cold agglutinin (CA) mAbs. Here we demonstrate that the carbohydrate ligand recognized by human VH4-34 anti-i CA mAbs is also expressed on murine B lymphocytes. Similar to human B cells, binding of murine B lymphocytes by VH4-34-derived anti-i CA mAbs leads to rapid cytotoxicity of target cells as tested both in vitro and in vivo. Moreover, the mechanism leading to murine B cell death is also similar to human B cells, since morphologically identical membrane pores were detected within 15 min of mAb exposure by scanning electron microscopy. The conservation of the carbohydrate ligand across species provides an ideal system to study the function of human VH4-34 gene derived Abs in immune regulation.
View details for Web of Science ID A1997XV88200007
View details for PubMedID 9281387
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Rapid cytotoxicity of human B lymphocytes induced by VH4-34 (VH4.21) gene-encoded monoclonal antibodies .2.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
1997; 108 (1): 151-159
Abstract
We have previously described complement-independent killing of human B lymphocytes by two IgM MoAbs derived from the VH4-34 (VH4.21) gene. Analysis of 17 independently derived VH4-34-encoded MoAbs shows that B cell toxicity is not limited to the two described MoAbs, but is a general property shared by a subset of MoAbs derived from the VH4-34 gene. As observed by two independent microscopy techniques, giant membrane pores were formed on target B cells within 10-15 min of exposure to cytotoxic VH4-34-derived MoAbs. Toxicity by individual MoAb correlated directly to its B cell binding intensity measured by FACS, i.e. stronger the binding greater the killing. Sequence analysis showed that V(H) region in germ-line or in near germ-line configuration was necessary but not sufficient for B cell binding. In addition, a particular sequence motif enriched in basic amino acids in the CDR3 may be required to supplement the reactivity mediated by the V(H) region of the MoAb molecule. VH4-34-encoded antibodies that fulfil the above sequence requirements have cold agglutinin activity towards the i antigen of cord erythrocytes. In vivo, such anti-i/anti-B cell antibodies are rarely detected in healthy adults, but serum levels are dramatically elevated in selective pathological conditions, such as systemic lupus erythematosus and infectious mononucleosis. This strict regulation may be related to the novel and rapid mechanism of human B cell toxicity demonstrated by antibodies encoded by a single human V(H) gene.
View details for Web of Science ID A1997WR92700022
View details for PubMedID 9097924
View details for PubMedCentralID PMC1904638
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Heavy chain variable gene usage by human B-1 lymphocytes and polyreactive autoantibodies.
Human antibodies
1997; 8 (3): 146-150
Abstract
To evaluate the role of B-1 cells and polyreactive autoantibodies in the development of adult immune repertoire, it is necessary to assess their immunoglobulin heavy chain variable-gene usage. We thus screened 28 independently derived human polyreactive MAbs from fetal and adult splenic B lymphocytes for their VH-region usage. We demonstrate that the polyreactivity of the IgM antibodies secreted by B-1 cells is not the result of the expression of particular variable region gene families. All six VH families are represented roughly in proportion to their estimated family size. Furthermore, the representation of the six families appears similar in polyreactive MAbs derived from fetal or adult lymphocytes.
View details for PubMedID 9322085
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V(H)4-34(V(H)4.21) gene expression in the chronic arthritides of childhood: Studies of associations with anti-lipid a antibodies, HLA antigens, and clinical features
JOURNAL OF RHEUMATOLOGY
1996; 23 (12): 2132-2139
Abstract
To determine if the germ line gene VH4-34 (VH4.21) encodes the antimonophosphoryl lipid A (MPL) polyspecific antibodies found in oligoarticular arthritis of childhood.Sera from a range of rheumatic diseases of childhood were assayed for VH4-34 derived antibodies by ELISA using the antiidiotype monoclonal antibody 9G4. Results were compared to assays for anti-MPL antibodies, C4d, and Bb, and for HLA type, joint count, and sedimentation rate.VH4-34 derived antibodies were elevated in all diseases studied except rheumatoid factor positive polyarticular disease. In oligoarticular arthritis, VH4-34 gene expression correlated with C4d concentration, and VH4-34 encoded globulins were more concentrated in synovial fluid than in blood. No association was found with HLA type. An association between VH4-34 expression and IgG anti-MPL was found in sera from patients from Cincinnati but not from Stanford. No other evidence supported a direct association between VH4-34 derived and anti-MPL antibodies in these children.The expression of VH4-34 is increased in several rheumatic diseases of childhood, but, as in adults, not in rheumatoid arthritis. VH4-34 expression is not associated with HLA type. The polyspecific autoantibody nature of some VH4-34 derived antibodies may explain the wide range of the unusual antibodies found in oligoarticular arthritis.
View details for Web of Science ID A1996VX84300022
View details for PubMedID 8970052
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Lymphangioleiomyomatosis of the uterus simulating high-stage endometrial stromal sarcoma
GYNECOLOGIC ONCOLOGY
1996; 63 (3): 404-410
Abstract
Symptomatic uterine lymphangioleiomyomatosis (LAM) simulating high-stage uterine sarcoma in a patient with tuberous sclerosis complex is reported. A 49-year-old female presented with abdominal pain and anemia. Preoperative workup revealed a uterine mass and a large amount of peritoneal free fluid and possible metastatic implant along the lateral edge of the liver. The patient also had a large right pleural effusion. A fungating anterior uterine fundal mass with apparent perforation and intraabdominal hemorrhage was found on laparotomy. A portion of the mass was excised and initially interpreted as an endometrial stromal sarcoma. Microscopic examination revealed multiple vascular epithelioid smooth muscle proliferations in the uterus and serosal surface of the fallopian tube and periaortic lymph node lymphangioleiomyomas. The uterine, fallopian tube, and nodal lesions were positive for smooth muscle actin, desmin, and HMB-45, findings characteristic of LAM. Additional examination of the patient revealed stigmata of tuberous sclerosis complex. Although uterine LAM is uncommon, it may be associated with pelvic and/or abdominal symptoms and may simulate a primary uterine mesenchymal neoplasm.
View details for Web of Science ID A1996VY31800021
View details for PubMedID 8946880
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NCCN Ovarian Cancer Practice Guidelines. The National Comprehensive Cancer Network.
Oncology (Williston Park, N.Y.)
1996; 10 (11): 293-310
View details for PubMedID 8953610
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Rapid cytotoxicity of human B lymphocytes induced by VH4-34 (VH4.21) gene-encoded monoclonal antibodies
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
1996; 105 (1): 183-190
Abstract
We have previously described two human cold agglutinin MoAbs 216 and A6(H4C5), that are derived from the VH4-34 (VH4.21) gene that bind specifically to a cell surface ligand on human B lymphocytes. In this study, we report that binding of 216 and A6(H4C5) leads to rapid killing of target B cells. This complement-independent cytotoxicity was measured by three independent assays, cell viability dye uptake on FACS, 3H-thymidine uptake, and the 3(4,5)-dimethylthiazol-2,5-diphenyl tetrazolium bromide (MTT) assay. Cytotoxicity was specific for CD20+ mononuclear cells in human spleen and peripheral blood. The MoAbs were also cytotoxic to human B cell lines Nalm-6, OCI-LY8, Arent and SUP-B8, but not to T cell lines HuT 78 and PEER. As observed by scanning electron microscopy, membrane pores were formed within 15 min of exposure to the MoAbs. Cytotoxic activity was dependent on MoAb concentration and temperature of exposure. Killing with greater at 4 degrees C than 37 degrees C. Sodium azide and EDTA did not block the cytotoxic activity. No DNA fragmentation typical of apoptosis was observed. This rapid cytotoxic activity, independent of physiologic cellular process and independent of complement, suggests a novel mechanism of all death via membrane perturbations.
View details for Web of Science ID A1996UU85000029
View details for PubMedID 8697629
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Phase 1 trial of intraperitoneal AD-32 in gynecologic malignancies
GYNECOLOGIC ONCOLOGY
1996; 61 (1): 90-93
Abstract
AD-32 (N-trifluoroacetyladriamycin-14-valerate), an analogue of doxorubicin, was examined for intraperitoneal (ip) administration in a phase 2 trial involving 25 patients with advanced gynecologic malignancies. At an AD-32 dose of 600 mg/m2, the limiting toxicity was grade 4 neutropenia (64% of patients), while severe abdominal pain was relatively uncommon (12%). Intraperitoneal AD-32 administration was associated with a 200-fold pharmacokinetic advantage for cavity exposure, compared to the systemic compartment. At the 600 mg/m2 dose level, 4 of 9 patients (44%) with ascites experienced control of malignant fluid reaccumulation. Based on the results of this phase 1 trial, further exploration of a possible role for the ip administration of AD-32 in individuals with gynecological malignancies appears indicated, particularly in patients with either small volume residual disease after initial systemic chemotherapy or in those with intractable ascites.
View details for Web of Science ID A1996UC96100017
View details for PubMedID 8626124
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Operative laparoscopy in the management of ovarian cancer
SURGICAL LAPAROSCOPY & ENDOSCOPY
1996; 6 (1): 38-45
Abstract
Advances in operative laparoscopic techniques have made possible the extension of this technology to the treatment of women with ovarian cancer. We present a detailed case series of eight patients with ovarian cancer who underwent a total of 11 operative laparoscopies for treatment of ovarian cancer ranging in stage from IA to IIIC. Three patients underwent initial laparoscopic staging and therapeutic debulking procedures. In three other cases that were incompletely staged via laparotomy, laparoscopy was used to complete the staging. Interval laparoscopic tumor debulking combined with second-look laparoscopy was performed in four cases. We describe our experience with these new applications of evolving techniques with particular regard to potential advantages, disadvantages, and complications. This detailed preliminary case series suggests the need for prospective clinical studies to establish the safety and efficacy of the approach.
View details for Web of Science ID A1996TR44000010
View details for PubMedID 8808559
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The female genital tract.
Pathology (Philadelphia, Pa.)
1996; 3 (2): 427-492
View details for PubMedID 8795830
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ANTIENDOTOXIN HUMAN MONOCLONAL-ANTIBODY A6H4C5 (HA-1A) UTILIZES THE VH4.21 GENE
Abraham I Braude Memorial Symposium on Infectious Diseases
UNIV CHICAGO PRESS. 1995: S186–S189
Abstract
Human IgM monoclonal antibody A6H4C5 was manufactured by Centocor (Malvern, PA) and used in clinical trials as HA-1A (Centoxin). In vitro, A6H4C6 binds to lipid A and rough-strain, gram-negative bacteria endotoxin. Further analysis of A6H4C5 has shown that it is a polyreactive, cold agglutinin that utilizes the VH4.21 gene segment in germline configuration. It is also a human antibody that binds to human B cells. We have characterized several other independently derived VH4.21 human monoclonal antibodies with the same characteristics as A6H4C5. This group of antibodies may represent a conserved host immune response.
View details for Web of Science ID A1995RZ52700011
View details for PubMedID 8845451
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HUMAN CD5+ B-LYMPHOCYTES (B-1 CELLS) DECREASE IN PERIPHERAL-BLOOD DURING PREGNANCY
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
1995; 28 (1): 53-60
Abstract
Pregnancy is a unique immunologic state where a natural homeostasis exists between antigenically different tissues. Several earlier studies have addressed the fluctuations in the number and/or function of lymphocytes, including B cells during pregnancy, but changes within the subsets of B lymphocytes, conventional (CD5-) and B-1 (CD5+), have not been addressed. Here we demonstrate that the frequency of B-1 cells decreases dramatically during pregnancy, whereas the frequency of conventional B cells remains relatively constant. The missing B-1 cells return to pre-pregnancy levels 8-10 weeks after parturition. The polyreactive autoantibodies secreted by B-1 cells have been implicated in autoimmunity and immune regulation. The possible role of B-1 cells during pregnancy will be discussed in that context.
View details for Web of Science ID A1995QH79400005
View details for PubMedID 7537825
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THE ROLE OF LAPAROSCOPY IN THE MANAGEMENT OF GYNECOLOGIC MALIGNANCY
SEMINARS IN SURGICAL ONCOLOGY
1994; 10 (6): 431-439
Abstract
With the advent of minimally invasive laparoscopic techniques, most gynecologic procedures for benign conditions can be performed in an outpatient setting. However, the role of such techniques in gynecologic oncology is not well defined. By reviewing the literature and presenting some new data, we attempt to elucidate the applications of operative videolaparoscopy in gynecologic oncology. Advanced laparoscopic techniques are utilized for the management of cervical cancer as well as the staging and treatment of endometrial and ovarian cancers. Such techniques are used in performing radical hysterectomy for early stage cervical cancer, pelvic and paraaortic lymphadenectomy, and second look laparoscopy following chemotherapy for ovarian cancer. Even though preliminary data are encouraging, large prospective controlled studies with long-term follow-up are necessary to better define the role and limitations of laparoscopy in the treatment of gynecologic malignancies.
View details for Web of Science ID A1994QH21200010
View details for PubMedID 7855480
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FACS ANALYSIS OF PERITONEAL LYMPHOCYTES IN OVARIAN-CANCER AND CONTROL PATIENTS
IMMUNOBIOLOGY
1994; 191 (1): 1-8
Abstract
In this study different lymphocyte populations in the malignant ascites of 10 patients with ovarian carcinoma and in the peritoneal fluid of 8 control patients (tubal ligation and benign conditions) were analyzed. A panel of monoclonal antibodies against the CD markers of lymphocytes was used to stain different populations and the cells were analyzed on a FACS II (fluorescence-activated cell sorter). The mean percentage of B lymphocytes in the peritoneal cavity of the OVCA patients was 0.18 +/- 0.5% and in the control patients 0.05 +/- 0.07%. There was no significant difference between the two groups. In the OVCA group and in the controls the percentage of T lymphocytes (CD5+) was 23.5% and 17.1% respectively with no significant difference between the groups. These results indicate that B lymphocytes are not present in the human peritoneal cavity. The small numbers of B cells found in this study could be due to contamination with peripheral blood. The human peritoneal cavity contains a cell population which differs from that present in peripheral blood. Significant numbers of B lymphocytes have been reported in the peritoneal cavity of mice. The difference between the lymphocyte population of the human peritoneal cavity and that of rodents implies that data on characterization and function of B lymphocytes in the mouse peritoneal cavity would not be applicable to humans.
View details for Web of Science ID A1994PE02100001
View details for PubMedID 7806256
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HUMAN ANTILIPID A MONOCLONAL-ANTIBODIES BIND TO HUMAN B-CELLS AND THE I-ANTIGEN ON CORD RED-BLOOD-CELLS
JOURNAL OF IMMUNOLOGY
1993; 151 (9): 5011-5021
Abstract
We describe two independently derived human mAb, A6(H4C5) and 216, initially selected for their reactivity to the lipid A domain of bacterial LPS, which also react with the following Ag: the i Ag present on cord RBC, a ligand on human B lymphocytes, and to certain autoantigens, defining these mAb as polyreactive. Both mAb have specific affinity for a carbohydrate epitope consisting minimally of a disaccharide with an acyl substitution at the 2-carbon position. Structural examination of the diverse Ag recognized by the two antibodies reveals the presence of this carbohydrate structure required for antibody binding. A6(H4C5) and 216 are IgM in isotype, but differ in their L chain expression. Molecular analysis shows that both the mAb are encoded by a highly conserved VH4 gene, designated VH4-21. This gene encodes a number of autoantibodies, particularly cold agglutinins. Specific recognition of lipid A and of a carbohydrate epitope on B lymphocytes by the two human mAb suggests a dual function for the highly conserved VH4-21 gene in antibacterial response and in B cell development and regulation.
View details for Web of Science ID A1993MD34900061
View details for PubMedID 7691963
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PERITONEAL IMPLANT ELIMINATION DURING CYTOREDUCTIVE SURGERY FOR OVARIAN-CANCER - IMPACT ON SURVIVAL
GYNECOLOGIC ONCOLOGY
1993; 51 (2): 224-229
Abstract
A case-control study was performed to evaluate the potential benefit of peritoneal and serosal implant elimination (PIE) during primary cytoreductive surgery for patients with Stage IIIC epithelial ovarian cancer. Peritoneal implant excision and/or ablation was accomplished with electrocautery, CO2 laser, sharp dissection, argon beam coagulator, and cavitron ultrasonic surgical aspirator. Three groups of patients were compared: Group A (7 patients); macroscopically disease-free after cytoreduction without needing PIE; Group B (26 patients); macroscopically disease-free after cytoreduction, including PIE; Group C (34 patients); macroscopic disease < or = 1 cm remaining exclusively on peritoneal surfaces with PIE not attempted. Each group had statistically equivalent mean ages, estimated blood loss, extent of disease, and variety of cytoreductive operations performed. Group B had a longer mean operating time than that of A or C (4.0 vs 2.8 hr P = 0.002). No serious morbidity occurred from PIE. Comparison of survival by log rank analysis and Cox proportional hazards regression shows a survival advantage for patients rendered free of macroscopic peritoneal implants (Group B vs Group C; P = 0.003). The result suggests that complete elimination of all visible peritoneal metastases might be of benefit during surgical cytoreduction for ovarian cancer if this renders the patient macroscopically disease-free. We also suggest the need of a randomized, prospective study to clarify the clinical role of PIE.
View details for Web of Science ID A1993MQ99300017
View details for PubMedID 8276298
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DOCUMENTATION OF COMPLETE RESOLUTION OF GESTATIONAL CHORIOCARCINOMA IN THE OOPHORECTOMIZED PATIENT
GYNECOLOGIC ONCOLOGY
1993; 51 (2): 261-265
Abstract
A 39-year-old woman with choriocarcinoma metastatic to the lungs and parametrium underwent total abdominal hysterectomy/bilateral salpingo-oophorectomy and follow-up chemotherapy with regression of the hCG assay, plateauing at 9 mIU/ml. Spinal fluid hCG assay was negative. An LH assay was performed which was 135 mIU/ml (2nd IRP-HMG). A quantitative hCG assay was performed on two sources of purified LH at varying concentrations to determine the contribution of LH cross-reactivity. When corrected for the LH contribution, the quantitative hCG was zero. Chemotherapy was discontinued. At 12-months follow-up the patient has remained in complete chemical remission and has an excellent performance status. Whenever a patient is oophorectomized, LH cross-reactivity should be ruled out as a cause for persistent low titers of hCG.
View details for Web of Science ID A1993MQ99300024
View details for PubMedID 8276305
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DETECTION OF FETAL TRISOMY-21 AND TRISOMY-18 FROM MATERNAL BLOOD USING TRIPLE GRADIENT AND MAGNETIC CELL SORTING
40th Annual Meeting of the Society-for-Gynecologic-Investigation
WILEY-BLACKWELL. 1993: 194–201
View details for Web of Science ID A1993MN38100020
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LIPOPOLYSACCHARIDE AND PEPTIDOGLYCAN SHARE BINDING-SITES ON HUMAN PERIPHERAL-BLOOD MONOCYTES
JOURNAL OF INFECTIOUS DISEASES
1993; 168 (1): 135-142
Abstract
p73, a binding site for lipopolysaccharide (LPS) on human peripheral blood monocytes was identified using the radiolabeled photoaffinity cross-linker sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1,3'-dithiopropionate (SASD). The 125I-labeled conjugate of SASD and LPS (125I-labeled ASD-LPS) was bound to monocytes and UV cross-linked, and the cellular extracts were analyzed with two-dimensional SDS-PAGE and autoradiography. In addition to the major binding site on human monocytes at 73 kDa, isoelectric point 5.95, there were multiple minor binding sites that recognized both smooth and rough LPS. Binding of 125I-labeled ASD-LPS to monocytes is concentration dependent, decreased in the absence of calcium and magnesium, and inhibited by either excess LPS or the low-molecular-weight soluble isolate of bacterial cell wall peptidoglycan (sPGN). However, sPGN only minimally stimulates tumor necrosis factor (TNF) secretion by human peripheral blood mononuclear cells. In contrast, the relatively insoluble high-molecular-weight peptidoglycan significantly stimulates TNF secretion.
View details for Web of Science ID A1993LH88000020
View details for PubMedID 8515100
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LONG-TERM SURVIVAL WITH ADJUVANT WHOLE ABDOMINOPELVIC IRRADIATION FOR UTERINE PAPILLARY SEROUS CARCINOMA
CANCER
1993; 71 (10): 3076-3081
Abstract
The optimum management of uterine papillary serous carcinoma (UPSC), a clinically aggressive histologic variant of endometrial adenocarcinoma, is a controversial issue.Ten patients with UPSC were reviewed who received whole abdominopelvic irradiation (WAP) as adjuvant therapy after a staging laparotomy and debulking surgery.Nine patients had clinical Stage I disease; the tumors in eight of them were upstaged based on laparotomy findings. There was greater than a 50% invasion of the myometrium in four of the hysterectomy specimens, and vascular space invasion was noted in seven patients. Peritoneal washings were positive in three of the nine specimens obtained; two others showed atypical cells. Five patients are alive with no evidence of disease at 102-133 months. Four patients are dead, and one patient is alive with disease. All recurrences were observed within 30 months of the initial diagnosis and were more common in the presence of deep myometrial invasion and vascular space involvement. Three of the four patients who died had pleural effusions that did not respond to hormonal and/or chemotherapy. Local irradiation produced long-term control of recurrences in two patients, including one with supraclavicular lymph node metastases who had no evidence of disease 117 months after radiation treatment to the involved nodes.These findings suggest that WAP be considered as an adjuvant therapy in the management of UPSC. The patients with the greatest benefit were those with early disease by surgical staging with or without positive peritoneal cytologic findings. For patients at high risk for pleural effusions and pulmonary metastasis, additional adjuvant therapy, such as innovative chemotherapy or low-dose lung irradiation, needs to be considered.
View details for Web of Science ID A1993LD04100029
View details for PubMedID 8490835
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ONE-STEP ENRICHMENT OF NUCLEATED RED-BLOOD-CELLS - A POTENTIAL APPLICATION IN PERINATAL DIAGNOSIS
JOURNAL OF IMMUNOLOGICAL METHODS
1993; 158 (2): 277-280
Abstract
We describe a discontinuous triple density gradient to obtain a 25-fold enrichment of nucleated red blood cells from mononuclear cells, granulocytes, and mature red blood cells in a single centrifugation step.
View details for Web of Science ID A1993KK44400016
View details for PubMedID 8094088
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Adenocarcinoma-reactive human monoclonal antibody MS2B6 defines an antigen in simple glandular epithelium.
Human antibodies and hybridomas
1992; 3 (3): 114-122
Abstract
A human monoclonal antibody (MAb), MS2B6, produced from splenocytes isolated from a patient with advanced papillary serous cystadenocarcinoma of the ovary, defines a unique human tumor-associated antigen. This antigen, EA2B6 (epithelial antigen 2B6), is expressed in a tissue-restricted manner on cultured and fresh human adenocarcinomas and some normal glandular epithelial tissues. EA2B6 is a 38-48 kD protein antigen that co-fractionates with the nuclear matrix-intermediate filament scaffold of simple glandular epithelial tissues. EA2B6 is a molecule with restricted solubility, and in vitro antigen-antibody binding is dependent on the antigen being presented on a solid support. To determine if EA2B6 is a cytokeratin, competition studies were undertaken with several cytokeratin-specific murine monoclonal antibodies. None of these antibodies inhibited the binding of human MAb MS2B6 to partially purified EA2B6. Less than 1% of HT29 colon adenocarcinoma cells and fresh ovarian adenocarcinoma ascites cells express EA2B6 on their surface. The majority of EA2B6 is intracellular. Because of the restricted tissue distribution of this antigen and stability of the antibody, we believe MS2B6 is a good candidate for MAb-mediated diagnosis and therapy of human adenocarcinomas.
View details for PubMedID 1382650
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HUMAN MONOCLONAL-ANTIBODY RECOGNIZING AN ANTIGEN ASSOCIATED WITH OVARIAN AND OTHER ADENOCARCINOMAS
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
1992; 166 (2): 634-645
Abstract
MS2B6, a human monoclonal antibody derived from a patient with advanced ovarian cancer, has been used to study the distribution and characteristics of its target antigen. The MS2B6 antigen was detected by immunoperoxidase studies in 41 of 41 epithelial ovarian cancers and in the majority of nonovarian adenocarcinomas. Among normal tissues the MS2B6 antigen was found in the adult epithelia of the fallopian tube, endometrium, endocervix, colon, bronchus, breast, sweat duct, and large renal ducts. No detectable antigen was found in peritoneal epithelia, tissue stromal cells, spleen, thymus, or blood-borne cells. Immunoblotting analysis showed that the MS2B6 epitope resides on polypeptides of 38, 44, and 60 kd. The cellular location of the MS2B6 antigen was studied with immunoperoxidase and immunofluorescent staining and immunoelectronmicroscopy of ovarian cancer ascites tumor cells. The results suggest that in ascites tumor cells the MS2B6 antigen is located in a layer of the peripheral cytoplasm beginning just below the cell membrane. MS2B6 may be useful as an imaging or therapeutic agent.
View details for Web of Science ID A1992HE65600038
View details for PubMedID 1371375
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THE ONTOGENY AND FUNCTIONAL-CHARACTERISTICS OF HUMAN B-1 (CD5+B) CELLS
INTERNATIONAL IMMUNOLOGY
1992; 4 (2): 243-252
Abstract
We demonstrate that, on average, greater than 90% of B lymphocytes in fetal spleen express CD5 at gestational ages of 17-23 weeks. Similarly, CD5+ B cells (B-1 cells) are the major B cell subset in umbilical cord blood. These findings depend on the optimization of fluorochrome conjugated anti-CD5 reagents for multiparameter fluorescent-activated cell sorter (FACS) analysis. From infancy through childhood the percentage of B-1 cells gradually diminishes in both spleen and peripheral blood. Stable adult levels, 25-35% of the total B cell population, are reached in late adolescence. The decrease in the percentage of B-1 cells in spleen is accompanied by an increase in conventional (CD5-) B cells, keeping the percentage of total B cells per mononuclear cells relatively constant. In contrast, in peripheral blood, the concentration of both B-1 cells and total B cells decreases, while T cells increase. At the functional level, we show that polyreactive IgM autoantibodies are produced by FACS-sorted CD5high B cells, but not by CD5- B cells from adolescent spleen. In contrast, fetal splenic CD5high and CD5- B cells appear functionally uniform, both producing IgM autoantibodies that are typical of B-1 cells. The apparent level of CD5- B cells in fetal spleen, on average 10% of total B cells, may still result from limitations of our reagent. The prominence of B-1 cells in fetal spleen and cord blood, the gradual reduction of B-1 cells with increasing age, and its characteristic repertoire, all suggest a role for this cell type in immunologically immature hosts.
View details for Web of Science ID A1992HF01700016
View details for PubMedID 1377947
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CRITICAL REASSESSMENT OF 2ND LOOK EXPLORATORY LAPAROTOMY FOR EPITHELIAL OVARIAN-CARCINOMA - MINIMAL DIAGNOSTIC AND THERAPEUTIC VALUE IN PATIENTS WITH PERSISTENT CANCER
CANCER
1992; 69 (2): 502-510
Abstract
From 1979 to 1984, 88 women with epithelial ovarian cancer were treated with surgery and chemotherapy, achieved a clinical complete response, and then had "second-look" exploratory laparotomy to assess the pathologic status of their disease. Persistent cancer was found in 50 (57%) patients: 34 of 50 (68%) had gross tumor, which was larger than 2 cm in 12 (24%) and smaller than 2 cm in 22 (44%), and 16 (32%) had microscopic disease. Salvage therapy was as follows for these patients: whole abdominal irradiation, 29 (58%); chemotherapy, 17 (34%); intraperitoneal chromic phosphate, 1 (2%); and no further therapy, 3 (6%). With a follow-up time of 4 to 8 years, 7 (14%) patients are alive without evidence of cancer, 7 (14%) are alive with disease, 35 (70%) are dead of disease, and 1 (2%) has died of treatment complications. At 5 years, the relapse-free rate was 18% and the survival rate was 25%. Seventy-two parameters of suspected prognostic significance and 64 potential sites of tumor involvement were correlated with survival in a univariate analysis. The factors favorably affecting survival included the following: lower grade; microscopic tumor versus gross disease at second-look laparotomy; removal of the uterus; removal of the omentum; pelvic and paraaortic lymph node biopsy; negative results of a right diaphragm biopsy; and radiation therapy at Stanford University Medical Center, Stanford, California. There was no survival advantage for whole abdomen irradiation compared with chemotherapy or for the patients who had their disease successfully debulked at second-look laparotomy. The above factors and others were evaluated by multivariate regression. The best model (P = 0.000004) for predicting survival included largest tumor mass (P = 0.0002), operative blood loss (P = 0.002), perioperative blood transfusion (P = 0.003), and grade (P = 0.004). The detection of persistent ovarian cancer by second-look exploratory laparotomy should identify a subgroup of patients whose conditions can be salvaged by a second-line therapy. Unfortunately, that subgroup is small (8%) and an effective salvage therapy remains to be identified.
View details for PubMedID 1728381
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MODIFIED POSTERIOR EXENTERATION FOR OVARIAN-CANCER
OBSTETRICS AND GYNECOLOGY
1991; 78 (5): 879-885
Abstract
The operative description of a modified posterior exenteration along with operative findings, other operative procedures, postoperative course, and follow-up information are presented for 47 patients (37 primary cytoreduction, ten secondary cytoreduction). All had stage IIIC or IV epithelial ovarian cancer with pelvic disease encasing the reproductive organs, pelvic peritoneum, cul-de-sac, and sigmoid colon. In addition to modified posterior exenteration, all patients had multiple other procedures performed as part of the cytoreductive efforts. Forty-five (95.7%) had optimal (less than 2 cm) cytoreduction and 18 (38.3%) had complete cytoreductive surgery. Thirty-four patients were ultimately rendered continent of feces (25 primarily and nine after colostomy reversal). Nine patients (19.1%) had serious morbidity and one (2.1%) died postoperatively. The median follow-up for those undergoing primary cytoreduction was 13.3 months (6-84). Nineteen (51.4%) were alive at the time of writing, 16 (43.2%) were dead, and two (5.4%) were lost to follow-up. Modified posterior exenteration effectively removes all visible pelvic disease with acceptable mortality. Hence, even patients with the most advanced cases of ovarian cancer may attain optimal cytoreduction and become ideal candidates for adjunctive therapy, with improved survival or a chance for cure.
View details for Web of Science ID A1991GL66900033
View details for PubMedID 1923216
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OPTICAL BIOSENSOR ASSAY (OBA)
23RD ANNUAL OAK RIDGE CONF ON ADVANCED ANALYTICAL CONCEPTS FOR THE CLINICAL LABORATORY : SENSITIVE ANALYTE DETECTION SYSTEMS
AMER ASSOC CLINICAL CHEMISTRY. 1991: 1502–5
Abstract
We describe a new biosensor immunoassay involving optical diffraction to detect clinically important analytes in human body fluids. A silicon wafer is used as a support for immobilization of antigen or antibody. The protein-coated surface is illuminated through a photo mask to create distinct periodic areas of active and inactive protein. When the surface is incubated with a positive sample, antigen-antibody binding occurs only on the active areas. Upon illumination with a light source such as a laser, the resulting biological diffraction grating diffracts the light. A negative sample does not result in diffraction because no antigen-antibody binding occurs to create the diffraction grating. The presence or absence of a diffraction signal differentiates between positive and negative samples, and the intensity of the signal provides a quantitative measure of the analyte concentration. The technique is demonstrated with a quantitative assay of choriogonadotropin in serum.
View details for Web of Science ID A1991GF97100007
View details for PubMedID 1893575
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QUANTITATIVE PROTEIN-CHANGES IN METASTATIC VERSUS PRIMARY EPITHELIAL OVARIAN-CARCINOMA
GYNECOLOGIC ONCOLOGY
1991; 41 (1): 22-27
Abstract
Primary and metastatic ovarian carcinomas from six patients were obtained during primary exploratory laparotomy. Tumor cells were synthetically radiolabeled with [35S]methionine. Radiolabeled cellular proteins of the primary and metastatic cells were examined by two-dimensional polyacrylamide gel electrophoresis followed by autoradiography. Computer assisted analysis of the resultant autoradiograms revealed that the amounts of only two proteins, p35 and p36, were consistently and significantly decreased in the metastatic tumor cells. No other consistent differences in protein synthesis between primary and metastatic tumors were detected.
View details for Web of Science ID A1991FN28400003
View details for PubMedID 2026354
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TREATMENT OF GRAM-NEGATIVE BACTEREMIA AND SEPTIC SHOCK WITH HA-1A HUMAN MONOCLONAL-ANTIBODY AGAINST ENDOTOXIN - A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
NEW ENGLAND JOURNAL OF MEDICINE
1991; 324 (7): 429-436
Abstract
HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia.To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection. The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin). Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol.Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture. For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017). Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients. Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038). No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia. For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24). All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected.HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.
View details for Web of Science ID A1991EX36300001
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Gynecologic factors in sexual dysfunction of the older woman.
Clinics in geriatric medicine
1991; 7 (1): 41-61
Abstract
Older women may experience sexual dysfunction due to many different causes. Some problems related to menopausal hormonal change may be easily treated with estrogen supplements. Other problems involve intricate interpersonal relations between the woman and her sexual partner and may require a combination of medical therapy and sexual counseling. Gynecologic cancer and cancer treatments are often accompanied by problems in sexual functioning. These problems may then impair relations and self-image, leading to a vicious circle of deteriorating social function. Some recommendations for the clinician follow. The clinician should maintain an attitude of openness to the possibility of sexual concerns in older women. Such concerns should be taken seriously and should not be dismissed as part of aging. Routine periodic health examinations can include a question such as "Do you have any concerns about your sexual life that you would like to discuss?" In follow-up visits for procedures with a high likelihood of causing sexual dysfunction, questions that would open the door to a discussion of sexuality should be asked. Sexual dysfunction should be recognized as a couple-oriented phenomenon. A woman's anxiety about her appearance, postoperative depression, or dyspareunia may be perceived by her partner as a sexual rejection and may initiate a cycle of decreasing contact or may even lead to erectile dysfunction. Sexual counseling should include both partners. When a surgical procedure that will probably have an impact on sexual function is contemplated, provide the patient and her partner with advance counseling. Descriptions of surgery should not be simply a statement of body parts to be removed but should specifically address the anticipated sexual effects. Counseling should include a description of basic anatomy and function of the genital organs. Illustrations and appropriate demonstration during the physical examination should be used to ensure the patient's understanding. Descriptions should be accurate without being either frightening or falsely reassuring. The patient should be counseled about the benefits of including her partner in discussions. Then, when possible, the sexual partner of the patient should be invited to sessions of advance counseling on contemplated procedures. Clinicians should remain open to the possibility that the sexual partner will be a nontraditional one, e.g., an unmarried male partner or another woman. The clinician should be alert to remediable causes of dysfunction. For example, decreased vaginal lubrication may be managed with use of water-soluble lubricants.(ABSTRACT TRUNCATED AT 400 WORDS)
View details for PubMedID 2004290
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WOMEN WITH PREECLAMPSIA HAVE HIGHER PLASMA ENDOTHELIN LEVELS THAN WOMEN WITH NORMAL PREGNANCIES
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
1990; 71 (6): 1675-1677
Abstract
Endothelin, a newly discovered endothelium-derived peptide, has potent vasoactive properties in vivo and in vitro. The actions of endothelin in clinical conditions of hypertension have not yet been defined. This study examined the possible role of endothelin in the vasospasm and hypertension associated with a well-defined syndrome of gestational hypertension, preeclampsia. Our results indicate that the concentration of immunoreactive endothelin is elevated significantly in plasma obtained from women with preeclampsia and rapidly returns to a normal pregnancy value within 48 hours of delivery, as predicted by the prompt clinical resolution of this disorder. The findings suggest that endothelin may contribute to the vasospasm associated with this syndrome and lend further support to the involvement of endothelial cells in the pathophysiology of preeclampsia.
View details for Web of Science ID A1990EL03300046
View details for PubMedID 2229324
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Synthesis and Characterization of Gentiobiose Heptaacetate Conjugate Vaccines That Produce Endotoxin-Neutralizing Antibodies
BIOCONJUGATE CHEMISTRY
1990; 1 (6): 375-380
Abstract
We have prepared aminoethyl (AE), aminopropyl (AP), and aminopentyl (APT) derivatives of gentiobiose heptaacetate (GH). These spacer compounds (AEGH, APGH, APTGH) have been coupled to succinylated diphtheria toxoid (Suc.DT) to produce conjugate vaccines. These conjugates all bind to the anti-lipid A human monoclonal antibody A6(H4C5) in an ELISA binding assay. Rabbits immunized with the APGH conjugate vaccine in either Freund's complete adjuvant or aluminum hydroxide gel produced antibody levels of 5120 and 3600 ELISA units, respectively, compared to an antibody level of less than 20 ELISA units for the prebleed sera. Sera from mice immunized with either the aminopropyl or the aminopentyl conjugate had antibody levels of 5120 and 2560 ELISA antibody units, respectively. These antibodies neutralized endotoxin in a Limulus lysate neutralization assay. Protection against the local Shwartzman reaction was demonstrated (p less than 0.05) in eight out of nine rabbits immunized with the Suc-DT-APGH conjugate vaccine compared to three out of 10 rabbits immunized with the carrier protein Suc-DT. Passive transfer experiments demonstrated that four out of five rabbits receiving immune serum were protected from Shwartzman reaction compared to one out of five rabbits receiving normal serum (p less than 0.1). These results indicated that epitopes contained in gentiobiose heptaacetate when properly presented as conjugate vaccines were capable of inducing neutralizing antibodies against endotoxin.
View details for Web of Science ID 000206175400002
View details for PubMedID 2099185
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STUDY OF THE SELECTIVE CYTOTOXIC PROPERTIES OF CATIONIC, LIPOPHILIC MITOCHONDRIAL-SPECIFIC COMPOUNDS IN GYNECOLOGIC MALIGNANCIES
GYNECOLOGIC ONCOLOGY
1990; 39 (1): 72-79
Abstract
Cationic lipophilic compounds have a unique cytotoxic mechanism of action which is dependent on mitochondrial-specific localization of these fluorescent dyes. We have demonstrated in vitro that carcinoma cells, which have a higher negative mitochondrial membrane potential than normal cells, have an increased accumulation and retention of two of these compounds. The compounds tested were rhodamine 123 and dequalinium (DECA). After the development of a reproducible murine intraperitoneal (ip) human ovarian cancer model, which maintained the biologic characteristics of the parent cell line, we undertook in vivo evaluation of DECA. Mice with intraperitoneal tumor inoculations were treated with cisplatin, and/or DECA. When compared to cisplatin, a chemotherapeutic agent known to be effective in the treatment of clinical ovarian cancer, DECA was significantly more efficacious and seemed less toxic in the murine model. Cisplatin and DECA used together were possibly synergistic. Cationic lipophilic compounds may prove to be an exciting new class of antineoplastic agents which exploit intracellular, mitochondrial differences between normal cells and cancer cells.
View details for Web of Science ID A1990EF79100011
View details for PubMedID 2227576
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ONE-STEP SEPARATION OF HUMAN FETAL LYMPHOCYTES FROM NUCLEATED RED-BLOOD-CELLS
JOURNAL OF IMMUNOLOGICAL METHODS
1990; 131 (1): 147-149
View details for Web of Science ID A1990DQ54300020
View details for PubMedID 2380562
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DELIVERY OF A NORMAL INFANT FOLLOWING CISPLATIN, VINBLASTINE, AND BLEOMYCIN (PVB) CHEMOTHERAPY FOR MALIGNANT TERATOMA OF THE OVARY DURING PREGNANCY
GYNECOLOGIC ONCOLOGY
1990; 37 (2): 292-295
Abstract
Pregnancy complicated by an immature teratoma is rare, with a reported incidence of 0.07%. A case report of a grade 3 immature teratoma measuring 18 x 20 cm, with operative intraabdominal rupture (FIGO stage IC), is reported. The poor prognosis of malignant germ cell tumors treated by surgery alone seems to indicate a need for adjunctive chemotherapy. One course of multiagent chemotherapy consisting of cisplatin, vinblastine, and bleomycin (PVB) was initiated during the midtrimester. After an uncomplicated vaginal delivery at term of a normal infant, the planned regimen of chemotherapy was resumed. Subsequent "second-look" laparotomy was negative for malignant disease. The actual risk of PVB chemotherapy in pregnancy cannot be assessed by a single case report. The delivery of a normal infant is encouraging.
View details for Web of Science ID A1990DE81300025
View details for PubMedID 1693127
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INITIAL EVALUATION OF A HUMAN IMMUNOGLOBULIN-M MONOCLONAL-ANTIBODY (HA-1A) IN HUMANS
JOURNAL OF BIOLOGICAL RESPONSE MODIFIERS
1990; 9 (2): 178-184
Abstract
A human monoclonal antibody (HA-1A) directed against bacterial endotoxin was administered to 15 patients with incurable malignant disease. No adverse effects were noted following single intravenous infusions of 0.05 to 100 mg. Pharmacokinetics were evaluated in nine patients receiving 10 mg (n = 3), 25 mg (n = 3), and 100 mg (n = 3). Seven of these patients had initial peak serum concentrations greater than 80% of predicted values with plasma disappearance curves fitting a one-compartment system and a plasma half-life of 31.5 h (range of 20.3-44.6 h). The peak serum concentrations and area under the curve values were proportional to the dose of HA-1A administered. One patient had a hypercatabolic state with low levels of serum albumin and IgM. He achieved 65% of the predicted value for peak serum concentration of HA-1A with a plasma half-life of 12.3 h. A second patient had detectable serum HA-1A for only 15 min following infusion without an adequate technical or biologic explanation. We were unable to demonstrate antibody to HA-1A in sera from these nine patients either prior to therapy or during 28 days postinfusion using a "double-antigen" radiometric assay. This study suggests that HA-1A human monoclonal antibody administration is well tolerated by patients. Phase I trials will need to be carried out to characterize further the pharmacokinetics and toxicity of HA-1A in patients with gram-negative sepsis.
View details for Web of Science ID A1990CZ55400007
View details for PubMedID 2341860
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PROSPECTIVE RANDOMIZED TRIAL OF TOPICAL ALPHA-INTERFERON (ALPHA-INTERFERON GELS) FOR THE TREATMENT OF VULVAR INTRAEPITHELIAL NEOPLASIA-3
GYNECOLOGIC ONCOLOGY
1990; 37 (1): 34-38
Abstract
Twenty-one patients were prospectively randomized into a blinded double-armed crossover study comparing alpha-interferon (alpha-IFN, 10(6) IU in a 3.5% aqueous methylcellulose base) with and without 1% nonoxynol-9. Nine and twelve patients were randomized to arms with (+N) and without (-N) 1% nonoxynol-9, respectively. Patients applied the gel to affected areas every 8 hr and were evaluated biweekly. Including those crossed over, 14 patients were treated with -N. Six of fourteen (43%) achieved complete responses: biopsy proven with at least 1 year follow-up (CR). One patient achieved a partial response with at least a 50% reduction in the total surface area of all lesions present (PR). Similarly, 13 patients were treated with +N. Two patients in this group were found to have invasive cancer and one to have HIV and thus were eliminated from statistical analysis. Of the remaining 10 patients, 3 had CRs (30%), 5 had PRs (50%), and 2 failed to respond. There was no significant difference in responses between the two groups. Overall, 14 of 18 (67%) patients demonstrated some response to alpha-IFN applied topically. These data support the conclusion that alpha-IFN is an active agent in the treatment of vulvar intraepithelial neoplasia III.
View details for Web of Science ID A1990DA10500008
View details for PubMedID 2182407
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A RANDOMIZED COMPARATIVE TRIAL OF CARBOPLATIN AND IPROPLATIN IN ADVANCED SQUAMOUS CARCINOMA OF THE UTERINE CERVIX - A GYNECOLOGIC ONCOLOGY GROUP-STUDY
JOURNAL OF CLINICAL ONCOLOGY
1989; 7 (10): 1462-1468
Abstract
A total of 394 patients with advanced, measurable squamous carcinoma of the uterine cervix and no prior chemotherapy were randomized to therapy with either carboplatin or iproplatin. There were 23 patients ineligible for the study and 10 patients who were not evaluable; the remaining 361 patients were evaluable for response and adverse effects. Randomization was well balanced for age, performance status, and prior therapy. Both platinum analogs were given every 28 days with starting doses of 400 mg/m2 for carboplatin (340 mg/m2 if the patient underwent prior radiation) and 270 mg/m2 for iproplatin (230 mg/m2 if the patient underwent prior radiation). These doses are equivalent to cisplatin doses of 75 to 100 mg/m2. Hematologic toxicity was dose-limiting, among which thrombocytopenia was slightly more common than leukopenia. Gastrointestinal toxicity was also prominent with both agents; however, iproplatin was significantly more toxic than carboplatin (P less than .001). Renal, otic, and peripheral nervous system toxicities were absent or infrequent with both analogs. No electrolyte abnormalities were observed. The percentage of planned dosages that were actually administered was 100% of carboplatin doses and 85% of iproplatin doses (P less than .0001). The reduction in iproplatin dose was apparently due to gastrointestinal toxicity. Response rates were similar for both agents (15% for carboplatin, 11% for iproplatin) and appear to be inferior to those noted with the parent compound, cisplatin.
View details for Web of Science ID A1989AR88400011
View details for PubMedID 2674333
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RADIATION-THERAPY FOR PRIMARY SQUAMOUS-CELL CARCINOMA OF THE VAGINA - STANFORD-UNIVERSITY EXPERIENCE
GYNECOLOGIC ONCOLOGY
1989; 35 (1): 20-26
Abstract
A retrospective analysis of 38 patients with primary squamous cell carcinoma of the vagina seen at Stanford University Medical Center from 1958 to 1984 was undertaken. Patients were analyzed with regard to symptoms, stage, treatment techniques, survival, patterns of failure, and complications. Eighteen patients were classified as FIGO Stage I, 5 as Stage II, 10 as Stage III, and 5 as Stage IV. The 5-year disease-free survival was 94% in Stage I, 80% in Stage II, 50% in Stage III, and 0% in Stage IV. Five patients (13%) had eight major complications secondary to treatment. Only 2 of 23 patients with Stage I or Stage II disease developed a recurrence. There was a significant correlation between dose and response in patients treated with radiotherapy.
View details for Web of Science ID A1989AT54200004
View details for PubMedID 2792898
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DELETION OF HISTO-BLOOD GROUP-A AND GROUP-B ANTIGENS AND EXPRESSION OF INCOMPATIBLE A-ANTIGEN IN OVARIAN-CANCER
JOURNAL OF THE NATIONAL CANCER INSTITUTE
1989; 81 (15): 1151-1157
Abstract
Expression of histo-blood group ABH antigens in 53 cases of ovarian cancer was examined by immunoperoxidase staining of Formalin-fixed as well as frozen histological sections with various monoclonal antibodies, including those defining type 1, 2, 3, and 4 chain A. Findings of major interest were (a) deletion of A and B determinants in tumors from histo-blood group A and B individuals, and a high incidence of H antigen deletion in tumors from group O individuals were observed and (b) strong expression of incompatible A antigen in two of 10 samples from group B patients and in two of nine samples from group O patients was demonstrated. A antigen expression was defined by monoclonal antibody AH21, which reacts with monofucosyl type 1 chain A (ALed), but not by other types of anti-A antibodies directed to difucosyl type 1 chain A (ALeb), mono- or difucosyl type 2 chain A, or type 3 or type 4 chain A. The reactivity of monoclonal antibody AH21 was abolished by alpha-N-acetylgalactosaminidase from chicken liver. These findings clearly identified the specific expression of incompatible A antigen with the structure monofucosyl type 1 chain A (ALed) in tumors from histo-blood group B and O individuals.
View details for Web of Science ID A1989AH03600005
View details for PubMedID 2664192
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EFFECTS OF ANTI-LIPID A HUMAN MONOCLONAL-ANTIBODY ON LIPOPOLYSACCHARIDE-INDUCED TOXICITY TO THE KIDNEY
JOURNAL OF UROLOGY
1989; 141 (6): 1463-1466
Abstract
Studies were done to evaluate the effects of the human monoclonal anti-lipid A IgM antibody A6(H4C5) on several components of the hemodynamic and renal toxicity of the cell wall lipopolysaccharide of E. coli 0111:B4. Antibody (0.25 to four mg./kg. BW) was administered 0.5 hour before, or premixed for one hour with, lipopolysaccharide (0.05 mg./kg., a 14 to 18% lethal dose), and the following measurements made over 0.5 to 3.5 hours of study: systemic arterial blood pressure, renal plasma flow, and glomerular filtration. The proximal tubular cell cytotoxicity of 90 mg./kg. of the cephalosporin cephaloridine was also quantified in similarly treated animals sacrificed 48 hours later. While one mg./kg. of antibody prevented the reduction by the lipopolysaccharide of renal plasma flow, it did not prevent the nephrotoxic synergy with cephaloridine, and four times the antibody dose did not prevent lipopolysaccharide-induced hypotension or reduced glomerular filtration. These amounts of this antibody protect leukopenic rabbits against the lethality of the slow onset bacteremic model of Pseudomonas conjunctivitis. It is suggested that the incompleteness of protection in this study may be the result of the sensitivity of the assay methods used and/or the acute endotoxemia produced in these animals.
View details for Web of Science ID A1989U850100052
View details for PubMedID 2657114
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TOPICAL INTERFERON FOR TREATING CONDYLOMA ACUMINATA IN WOMEN
JOURNAL OF INFECTIOUS DISEASES
1988; 158 (5): 934-939
Abstract
We conducted a randomized, double-blind, placebo-controlled trial of two forms of topical interferon therapy for condyloma acuminata in women. Gel containing 10(6) IU of leukocyte interferon/g, with or without nonoxynol-9, was compared with treatment with gel base alone. Eighty-nine patients applied the gel three times a day for four weeks and were studied for at least 16 w. Side effects were generally mild and limited to the site of application for all three drugs. Although a transient, statistically significant therapeutic effect was noted early in the course of treatment with both interferon gels as compared with placebo, this effect was lost by the end of the follow-up period, possibly because of a generally high response rate in patients receiving placebo. Hence, there was no overall difference in the number of patients with a partial or complete response to any of the agents by the end of therapy or by the end of the study.
View details for Web of Science ID A1988Q700100004
View details for PubMedID 2460568
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GENERATION OF HUMAN MONOCLONAL-ANTIBODIES TO CANCER-ASSOCIATED ANTIGENS USING LIMITED NUMBERS OF PATIENT LYMPHOCYTES
JOURNAL OF IMMUNOLOGICAL METHODS
1987; 105 (2): 263-273
Abstract
A limiting dilution method for the efficient transformation by Epstein-Barr virus (EBV) of human B lymphocytes has been applied to the production of human monoclonal antibodies to ovarian cancer-associated antigens. Limited numbers (e.g., 2 X 10(5)) of EBV-infected B lymphocytes from ovarian cancer patient spleen, lymph node, tumor, ascites and blood were successfully transformed using this method. An immunofiltration assay system was employed to identify EBV transformants secreting IgM antibody which reacted selectively with ovarian cancer patient ascites tumor cells, but not with a mixture of normal cell types. A miniature Western blot assay was utilized to screen for IgG reactivity to protein species in detergent extracts of ovarian cancer tumor cells. EBV-transformed cells selected after screening were then fused with heteromyeloma fusion partner SHM-D33 resulting in efficient recovery of hybridomas secreting MAb of the desired specificity. Human MAbs which selectively react with antigens associated with ovarian cancer tumor cells were obtained.
View details for Web of Science ID A1987L481200014
View details for PubMedID 2826600
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CARDIOVASCULAR EFFECT OF INTRAVENOUS LIPID-A IN RABBITS
CIRCULATORY SHOCK
1987; 23 (4): 285-293
Abstract
The in vivo cardiovascular effect of intravenous administration of monophosphoryl lipid A (mp-lipid A) and diphosphoryl lipid A (dp-lipid A) in awake New Zealand white rabbits was investigated. Observed changes were evaluated in comparison to a control group and an endotoxin-treated group. Rabbits given lipid A showed a significant depression in cardiac index (p less than .025), mean arterial pressure (p less than .025, dp-lipid A only), arterial carbon dioxide tension (p less than .025), and total leukocyte count (p less than .05) compared to controls. Animals receiving lipid A tended to respond overall in a manner closely matching that of the endotoxin group. Dosages of lipid A given were approximately 3.5 times larger than the endotoxin dosages with respect to actual number of molecules administered (1.25-2.0 times larger by mass). These results indicate that lipid A is active in producing the cardiovascular and leukopenic effects characteristic of experimental septic shock.
View details for PubMedID 3690820
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SINGLE-DOSE ACTINOMYCIN-D TREATMENT FOR NONMETASTATIC GESTATIONAL TROPHOBLASTIC DISEASE - A PROSPECTIVE PHASE-II TRIAL OF THE GYNECOLOGIC-ONCOLOGY-GROUP
CANCER
1987; 60 (9): 2173-2176
Abstract
The Gynecologic Oncology Group (GOG) conducted a prospective trial of single-dose Actinomycin-D (ACT-D) given intravenously (IV) at 1.25 mg/m2 every 2 weeks to patients with nonmetastatic gestational trophoblastic disease (NMGTD) in order to determine the efficacy of pulse scheduling and the frequency and severity of associated toxicity. Of 31 evaluable patients, 29 (94%) achieved remission after receiving a median of four courses of therapy. Two patients who failed to respond to pulse therapy were subsequently cured by alternative treatment. There were 93 toxic events in 133 cycles of therapy. Ninety-two percent of adverse effects were graded as mild or moderate, and 8% were graded as severe. No life-threatening toxicity occurred. Although single-dose ACT-D efficacy and toxicity is comparable to conventional therapy for NMGTD, the advantages of easier administration, greater patient convenience, and improved cost-effectiveness make it superior to other alternatives. On this basis it is recommended as the treatment of choice for NMGTD.
View details for Web of Science ID A1987K484400009
View details for PubMedID 2449942
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CLINICAL-APPLICATIONS OF MONOCLONAL-ANTIBODIES IN GYNECOLOGIC ONCOLOGY
CANCER
1987; 60 (8): 2068-2074
Abstract
The advances of both murine and human monoclonal antibody (MoAb) technology have allowed the development of several antibodies against gynecologic tumors. The goals are to produce effective and specific reagents for both immunodiagnosis and therapy. However, despite an extensive research effort, a clear demonstration of specific cancer-associated antigens in gynecologic malignancies, or of specific immune responses to such antigens has been elusive. Currently, most antibodies found are cross reactive with either oncofetal antigens or some normal adult tissues. Clinical usefulness of these MoAbs as a screening test in radioimaging or in immunotherapy remains to be proven. However, the use of MoAb technology in defined antigens/tumor markers such as beta-human chorionic gonadotropin, and alpha fetal proteins has provided convenient, reproducible and highly specific reagents. More recently, promising antibodies have been shown to detect tumor antigens in serum of patients with ovarian cancer.
View details for Web of Science ID A1987K299800019
View details for PubMedID 3308066
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TREATMENT OF PSEUDOMONAS BACTEREMIA IN NEUTROPENIC RABBITS WITH HUMAN MONOCLONAL IGM ANTIBODY AGAINST ESCHERICHIA-COLI LIPID-A
SLACK INC. 1987: A619–A619
View details for Web of Science ID A1987G986202187
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THE EFFECT OF HUMAN ANTIENDOTOXIN MONOCLONAL-ANTIBODIES ON ENDOTOXIN-INDUCED LUNG INJURY IN THE RAT
AMERICAN REVIEW OF RESPIRATORY DISEASE
1987; 135 (3): 665-670
Abstract
A model of endotoxin-induced lung injury was developed in the rat. We found that 24 h after intravenously administered endotoxin (3 mg/kg) there was increased clearance of the isotope 99mTcDTPA from the lung to blood, increased neutrophils in the lung in bronchoalveolar lavage, and increased levels of products of peroxidation of lipids and nucleic acid in the serum. Using this model, we evaluated the effect of pretreatment of rats with a human monoclonal antibody specific to the core glycolipid that is common to all endotoxins. We found that pretreatment prevented the increased clearance of 99mTcDTPA from the lung, as well as the increase in lipid peroxidation products in the serum. The antibody did not prevent increased neutrophil accumulation in the lung. The findings suggest that the administration of human antiendotoxin monoclonal antibodies prior to endotoxemia may prevent some of the changes in the lung associated with endotoxin.
View details for Web of Science ID A1987G356300029
View details for PubMedID 3548509
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EPITHELIAL OVARIAN-CARCINOMA IN PATIENTS WITH INTERSEX DISORDERS - THE ROLE OF PITUITARY GONADOTROPINS IN OVARIAN TUMORIGENESIS
GYNECOLOGIC ONCOLOGY
1986; 24 (3): 299-308
Abstract
The common epithelial tumors of the human ovary have rarely been found in the gonads of intersex patients with gonadal dysgenesis or true hermaphroditism. This report describes a patient with ovarian serous cystadenocarcinoma and mixed gonadal dysgenesis (45,X/46,XY) and reviews other reported cases. Intersex patients require early evaluation with treatment based on the karyotypic risk of malignant gonadal transformation. Epithelial ovarian tumors arising in dysgenetic gonads, which lack ova and are incapable of ovulating, provide a unique model for understanding the role of pituitary gonadotropins in ovarian epithelial tumorigenesis.
View details for Web of Science ID A1986D021200004
View details for PubMedID 2424810
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INFLUENCE OF AVIDITY AND IDIOTOPE RECOGNITION ON THE MODULATION OF SURFACE-IMMUNOGLOBULIN ON MALIGNANT HUMAN B-CELLS BY RAT MONOCLONAL ANTIIDIOTYPE ANTIBODIES
JOURNAL OF IMMUNOLOGY
1986; 136 (8): 2983-2988
Abstract
Immunoglobulin (Ig) was obtained from the tumor cells of patients with B cell malignancies by somatic cell hybridization to mouse-human heteromyeloma cells. The human Ig secreted by one of these hybridomas was used as an immunogen for the production of rat monoclonal antibodies (mAb). A panel of mAb specific for the idiotype (Id) was produced and characterized. Competitive binding studies that made use of [Se]-labeled anti-Id mAb (MAID) demonstrated several distinct yet topographically related Id on the Id-bearing Ig. These antibodies were shown to have avidities ranging from 0.38 to 45.3 X 10(8) l/mol. Additional studies demonstrated varying degrees of antigenic modulation of surface Id in vitro by MAID. The degree of modulation correlates with antibody avidity.
View details for Web of Science ID A1986C169100038
View details for PubMedID 3485677
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A CRITICAL REASSESSMENT OF 2ND-LOOK LAPAROTOMY IN EPITHELIAL OVARIAN-CARCINOMA
CANCER
1986; 57 (3): 530-535
Abstract
Eighty-eight women with epithelial ovarian carcinoma, treated by first-line chemotherapy, achieved a complete clinical response and underwent second-look laparotomy to assess the true pathologic status of their disease. Persistent tumor was found in 50 patients (57%). Thirty-two of these (36%) had obvious gross tumor, whereas, 16 (18%) had microscopic disease. Thirty-eight patients (43%) had no pathologic evidence of persistent ovarian carcinoma. With a follow-up of 6 to 60 months, 30 of these patients (79%) remain without evidence of recurrence. Multivariate logistic regression analysis revealed three covariates that were independently significant in predicting continued disease-free status. These included: the greatest diameter of the largest residual tumor left at the primary operation; histologic features of the tumor; and the diameter of the largest tumor aggregate found at initial operation. A mathematical model based on the most significant covariates was designed to assess the relative risk of any patient having persistent tumor at second-look laparotomy. A comparison of the predicted to actual outcome revealed a sensitivity of the model of 88%, a specificity of 71%, and an accuracy of 77%. Second-look laparotomy represents the basis on which potentially curative second-line salvage therapy can be initiated. With an increasing period of follow-up and with greater numbers of patients, it can potentially document a complete pathologic response to first-line therapy administered with curative intent, and identify patients for additional, adjunctive therapy, who are at risk of recurrence.
View details for Web of Science ID A1986AYC4300019
View details for PubMedID 3942985
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EVALUATION OF A HUMAN MONOCLONAL-ANTIBODY TO LIPID-A
EOS-RIVISTA DI IMMUNOLOGIA ED IMMUNOFARMACOLOGIA
1986; 6 (3): 139-141
View details for Web of Science ID A1986D845300046
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PROGNOSTIC FACTORS IN 2ND-LOOK LAPAROTOMY FOR EPITHELIAL OVARIAN-CARCINOMA
SURGICAL FORUM
1985; 36: 462-463
View details for Web of Science ID A1985AVR3900192
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ANTIBODIES TO PEPTIDES CORRESPONDING TO A CONSERVED SEQUENCE OF GONOCOCCAL PILINS BLOCK BACTERIAL ADHESION
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
1985; 82 (3): 915-919
Abstract
Antisera generated against each of seven synthetic peptides corresponding to constant and variable sequences of the pilin from gonococcal strain MS11 were assayed for their ability to crossreact with intact pili from both homologous and heterologous strains. The peptides elicited roughly equal antipeptide responses but varied substantially in their ability to elicit antisera that crossreacted with intact pili. Of the antisera to peptides corresponding to regions of conserved sequence, antisera directed against residues 69-84 were the most efficient in binding pili from all strains tested in both solid-phase assays and immunoblots. Anti-69-84 also efficiently precipitated a tryptic fragment of pilin known to bind human endocervical cells. Sera against the two peptides (121-134 and 135-151) previously shown to contain strain-specific epitopes crossreacted with MS11 pili equally well, but differed in their ability to bind pili from heterologous strains. Anti-121-134 was strain-specific whereas anti-135-151 bound all pilin tested. Each of the sera was examined for its ability to inhibit bacterial adhesion to a human endometrial carcinoma cell line. Sera generated against residues 41-50 and 69-84 successfully inhibited a heterologous gonococcal strain from binding. These peptides could be important components of an effective vaccine for the prevention of gonorrhea.
View details for Web of Science ID A1985ADL2400060
View details for PubMedID 3919385
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PROTECTION AGAINST GRAM-NEGATIVE BACTEREMIA AND ENDOTOXEMIA WITH HUMAN MONOCLONAL IGM ANTIBODIES
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
1985; 82 (6): 1790-1794
Abstract
Hybridomas producing human monoclonal IgM antibodies (mAbs) against bacterial lipopolysaccharide (LPS) were generated by fusion of B lymphocytes from sensitized human spleen with heteromyeloma cells. The splenocytes were from patients undergoing splenectomy during staging for Hodgkin disease after vaccination with the J5 mutant of Escherichia coli, which is deficient in O antigenic side chains. This deficiency exposes the core oligosaccharide, common to LPS of all Gram-negative bacteria. The mAbs cross-reacted strongly with endotoxins from a wide range of unrelated species of Gram-negative bacteria. The mAbs also gave strong protection against LPS in the dermal Shwartzman reaction and against lethal Gram-negative bacteremia in mice. These findings indicate that monoclonal IgM against LPS endotoxin can neutralize its toxicity in vivo and might be valuable for treatment of patients with Gram-negative bacteremia. Analysis of one of the hybridoma clones, A6(H4C5), showed that the IgM mAb is directed against the covalently bound lipid A, which represents the most conservative and least variable structural element of LPS.
View details for Web of Science ID A1985AED8800046
View details for PubMedID 3856860
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PRODUCTION OF HUMAN MONOCLONAL IGG ANTIBODIES AGAINST RHESUS (D) ANTIGEN
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
1984; 81 (10): 3214-3217
Abstract
An Epstein-Barr virus (EBV)-transformed human B-cell line ( LB4r ) producing anti-Rhesus [Rho(D) antigen] antibody was fused with a non-immunoglobulin-producing mouse-human heteromyeloma ( SHM - D33 ) and selected in hypoxanthine/aminopterin/thymidine medium containing 0.5 microM ouabain. Surviving hybrids found to secrete specific anti-Rho(D) antibody were cloned by limiting dilution. Two clones (D4-B2 and E10-C1) producing high levels (12 and 20 micrograms/ml per 10(6) cells per 24 hr, respectively) of monospecific antibody (IgG3, lambda chain) were selected for expansion and further characterization. Compared to the parental cell line ( LB4r ), these hybridoma cell lines presented several advantages: antibody production was increased 10-fold, cloning efficiency was improved, and the EBV genome was not retained. Antibody production has been stable for greater than 8 months. These human monoclonal anti-Rho(D) antibodies have demonstrated utility in routine blood-group typing. They may also prove useful in the biochemical and genetic characterization of the Rh antigen system. Most important, they offer a source of Rh-immune globulin for the prevention of Rh immunization and alloimmune hemolytic disease of the newborn.
View details for Web of Science ID A1984SU47600056
View details for PubMedID 6427767
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PARTIAL HYDATIDIFORM MOLE WITH DIPLOID KARYOTYPE - REPORT OF 3 CASES
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
1984; 150 (8): 961-964
Abstract
Recent studies suggest that a partial mole with a triploid karyotype has little tendency to invade and metastasize and usually requires no therapy other than evacuation. This report describes three patients with a mole of normal diploid karyotype coexisting with a living fetus. Each patient had persistent elevation of human chorionic gonadotropin. Two patients required chemotherapy; one of these had invasive mole. The partial mole with normal diploid karyotype is a distinct clinical entity with the potential for malignant sequelae. The possibility of twin gestation cannot be excluded.
View details for Web of Science ID A1984TX04400012
View details for PubMedID 6507534
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SOMATIC-CELL HYBRID SELECTION WITH A TRANSFECTABLE DOMINANT MARKER
SOMATIC CELL AND MOLECULAR GENETICS
1984; 10 (2): 123-127
Abstract
A recombinant plasmid vector, pSV2-neo, coding for resistance to neomycin and the related antibiotic G-418, was transfected into the mouse myeloma line X63-Ag8.653 by a modification of the protoplast fusion technique. The time interval required to obtain 10(6) G-418 resistant cells was 20 days and the efficiency was 10(-4)-10(-5), which represents a significant advantage over classical methods of selecting mutant cells bearing a dominant selection marker. To investigate the efficiency of this marker in somatic cell hybrid selection, these cells were fused to the human myeloma line U-266 and the hybrids were selected either in HAT + G-418 or HAT + ouabain. The pSV2-neo vector was as efficient as ouabain as a dominant marker with respect to the number of viable hybrid colonies selected and their levels of immunoglobulin secretion. The reciprocal experiment was also performed: HAT-sensitive, mutant U-266 cells were transfected with pSV2-neo, clones selected in G-418 and fused with X63-Ag8.653 cells, and hybrids selected in ouabain plus G-418, yielding HAT-sensitive hybrid "heteromyelomas" that were effective fusion partners with human B lymphocytes.
View details for Web of Science ID A1984SK09400002
View details for PubMedID 6324391
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2ND-LOOK LAPAROTOMY IN EPITHELIAL OVARIAN-CARCINOMA - PRECISE DEFINITION, SENSITIVITY, AND SPECIFICITY OF THE OPERATIVE PROCEDURE
GYNECOLOGIC ONCOLOGY
1984; 17 (2): 154-160
Abstract
Twenty-five women treated with chemotherapy for epithelial ovarian carcinoma underwent "second-look" laparotomy after thorough clinical and radiographic examinations failed to detect residual tumor. Chest roentgenogram, barium enema, upper gastrointestinal series with small-bowel follow through, and abdominopelvic CAT scan were obtained in all patients prior to operation. Inspection, palpation, and multiple biopsies were performed in accordance with precise and detailed protocol requirements. Eight patients (32%) had gross tumor found at laparotomy, while 6 (24%) had no suspicion of residual disease at operation but had cytologic or microscopic evidence of tumor found on review of submitted specimens. Eleven patients (44%) had no gross or microscopic evidence of residual ovarian carcinoma. After follow-up of from 4 to 25 months, 1 of these 11 patients (9%) has suffered a recurrence. The maximum sensitivity of "second-look" laparotomy is 85.7%, and the maximum specificity is 90.9% in this series. Any additional recurrences observed over time will decrease both the sensitivity and specificity of the operation. The sites of microscopic disease support rigid adherence to a precise operative procedure which should minimize the false negative rate.
View details for Web of Science ID A1984SE71100003
View details for PubMedID 6706223
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MONOCLONAL VERSUS POLYCLONAL ANTIBODY-RADIOIMMUNOASSAY AGAINST THE BETA-SUBUNIT OF HUMAN CHORIONIC-GONADOTROPIN IN PATIENTS WITH GESTATIONAL TROPHOBLASTIC NEOPLASIA
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
1983; 147 (7): 821-825
Abstract
The level of human chorionic gonadotropin (hCG) in series of sera from eight patients with gestational trophoblastic neoplasia was measured by monoclonal antibody and polyclonal antibody radioimmunoassay. A comparative analysis was performed. Three commercially available monoclonal anti-beta-subunit of hCG (beta-hCG) antibodies were evaluated and the most specific and sensitive one was chosen to develop a quantitative beta-hCG radioimmunoassay. beta-hCG radioimmunoassay kits from Nuclear Medical Systems, Inc., and Clinical Assays served as polyclonal antibody assays. Results obtained with the monoclonal antibody radioimmunoassays demonstrated a high degree of correlation (r greater than 0.95, p less than 0.01) with those obtained by the polyclonal antibody techniques; however, the sera from one patient continuously demonstrated a low level of hCG in the monoclonal antibody radioimmunoassay while registering undetectable levels in the polyclonal antibody assays. Although the monoclonal antibody radioimmunoassay appears to be specific and fairly sensitive, the results indicate that, with current technology, there is no special advantage to employing this assay to measure hCG in patients with gestational trophoblastic neoplasia.
View details for Web of Science ID A1983RU08900020
View details for PubMedID 6196974
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CONSTRUCTION AND TESTING OF MOUSE HUMAN HETEROMYELOMAS FOR HUMAN MONOCLONAL-ANTIBODY PRODUCTION
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
1983; 80 (23): 7308-7312
Abstract
FU-266, a mutant human myeloma cell line sensitive to hypoxanthine/aminopterin/thymidine (HAT), was transfected by protoplast fusion with DNA of the recombinant plasmid vector pSV2-neoR, thus acquiring a dominant marker conferring resistance to the antibiotic G-418. One of the resultant neoR clones, E-1, was fused to irradiated (500 rads) or unirradiated cells of the HAT-sensitive, G-418-sensitive, nonproducer mouse myeloma line X63-Ag8.653. Hybrid clones were selected in G-418 plus ouabain, thus preserving their HAT sensitivity. Small numbers of human chromosomes were retained in all such hybrids, but most of them ceased secreting human myeloma (IgE(lambda). Selected hybrid clones were then tested as malignant fusion partners in a series of fusions with polyclonally activated human B lymphocytes and with antigen-primed human B lymphocytes, in some instances after transformation of the latter with Epstein-Barr virus. The yield of viable chimeric hybridomas has been consistently high, as has the proportion of hybridomas secreting human immunoglobulin molecules unpermuted with mouse or human myeloma heavy or light chains. Secretion by many subcloned hybridomas has been stable for over 6 months, and several antigen-specific human monoclonal antibodies have been generated. Thus these heteromyeloma cell lines appear to have significant advantages for human monoclonal antibody production.
View details for Web of Science ID A1983RT73300054
View details for PubMedID 6316357
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CHARACTERIZATION OF AN ALPHA-BUNGAROTOXIN BINDING COMPONENT FROM DROSOPHILA - MELANOGASTER
JOURNAL OF NEUROCHEMISTRY
1977; 29 (6): 1013-1029
View details for Web of Science ID A1977EE17200009
View details for PubMedID 413880
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APPEARANCE OF ACETYLCHOLINE RECEPTORS IN CULTURED MYOBLASTS PRIOR TO FUSION
JOURNAL OF SUPRAMOLECULAR STRUCTURE
1976; 4 (3): 381-387
Abstract
The development of the acetylcholine receptors in chick embryo myoblasts from 11-day old embryos was studied in vitro. Using the purified alpha-bungarotoxin labeled with radioactive iodide, a high concentration of acetylcholine receptors was found in the prefusing myoblasts; most of these receptors were located in the interior of the myoblasts. However, upon the completion of myoblasts fusion, the majority of the acetylcholine receptors appeared on the external cell surface of the myotubes.
View details for Web of Science ID A1976BP46300008
View details for PubMedID 772316
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MITOGENICITY OF THROMBIN AND SURFACE ALTERATIONS ON MOUSE SPLENOCYTES
EXPERIMENTAL CELL RESEARCH
1976; 101 (1): 41-46
View details for Web of Science ID A1976CE09400005
View details for PubMedID 986310
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THROMBIN-SENSITIVE SURFACE PROTEIN OF CULTURED CHICK-EMBRYO CELLS
NATURE
1976; 259 (5544): 578-580
View details for Web of Science ID A1976BF69500042
View details for PubMedID 1250403
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ROLE OF SURFACE PROTEINS IN CELL-PROLIFERATION AS STUDIED WITH THROMBIN AND OTHER PROTEASES
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
1975; 72 (2): 413-417
Abstract
This communication explores the capacity of different proteases to stimulate DNA synthesis in resting chick embryo fibroblasts and to cause the removal of cell membrane proteins previosly postulated as important in the regulation of growth and division of cells. Thrombin, a highly specific protease and a known mitogen, was incubated with chick embryo fibroblasts, and analysis was made of the cell membrane proteins. Of particular interest were a protein of molecular weight 250,000, which is known to be readily removed by the action of trypsin and is not present in most transformed cells, and two other proteins, which are reduced in amount in transformed as compared to confluent resting cell cultures. None of these three proteins was removed by thrombin when the latter was added to confluent cells in concentrations sufficient to cause significant increase in DNA synthesis twelve hours after stimulation by the protease. The presence or absence of these proteins in the membranes of confluent resting or transformed cells of chick embryo fibroblasts does not seem to be directly related to the process of regulation of DNA synthesis and cellular division.
View details for Web of Science ID A1975V833700001
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HISTONES OF CHICK EMBRYONIC LENS NUCLEI
DEVELOPMENTAL BIOLOGY
1974; 41 (1): 72-76
View details for Web of Science ID A1974U648300007
View details for PubMedID 4474101
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MECHANISM OF ACTION OF PARA HYDROXYBENZOATE HYDROXYLASE FROM PSEUDOMONAS-PUTIDA .3. ENZYME-SUBSTRATE COMPLEX
JOURNAL OF BIOLOGICAL CHEMISTRY
1971; 246 (17): 5448-?
View details for Web of Science ID A1971K329400036
View details for PubMedID 4398470
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220-MHZ NUCLEAR MAGNETIC RESONANCE STUDY OF A SOLVENT-INDUCED CONFORMATIONAL CHANGE IN FLAVIN ADENINE DINUCLEOTIDE
JOURNAL OF BIOLOGICAL CHEMISTRY
1969; 244 (20): 5656-?
View details for Web of Science ID A1969E474900029
View details for PubMedID 5348605
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[PRELIMINARY STUDIES ON LIGHT ANESTHESIA WITH ETHER].
Zhonghua wai ke za zhi [Chinese journal of surgery]
1963; 11: 802-804
View details for PubMedID 14110578
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Poisoning: a four year survey.
Texas state journal of medicine
1957; 53 (7): 514-519
View details for PubMedID 13455566