Maggie Zhou

All Publications

• Recent advances in sarcoma therapy: new agents, strategies and predictive biomarkers. Journal of hematology & oncology Pan, M., Zhou, M., Xie, L., Bui, N., Ganjoo, K. 2024; 17 (1): 124

  Abstract

  Soft tissue and bone sarcomas are a heterogenous group of uncommon mesenchymal tumors with high unmet needs for novel therapeutic and diagnostic strategies. Despite many challenges that persist, innovative therapeutics are emerging. Here we provide a review of the studies presented at the 2024 American Society of Clinical Oncology annual meeting that were focused on sarcoma. There were many outstanding studies that were reported at the meeting. We begin by discussing the clinical studies on soft tissue sarcoma (STS) that included multiple histology subtypes, followed by highlighting developments in cellular therapy, before delving into specific STS histologic subtypes followed by a section covering the studies that were focused on predictive biomarkers. We conclude by discussing the studies in bone sarcomas. Some of the studies discussed here are likely to be practice changing. Some of the early-phase clinical trials have shown encouraging results.

  View details for DOI 10.1186/s13045-024-01650-6

  View details for PubMedID 39696530

  View details for PubMedCentralID PMC11656826

• Monitoring Response Using Circulating Tumor DNA in Undifferentiated Pleomorphic Sarcoma: A Case Report. Cureus Siy, A. B., Zhou, M., Boncompagni, A. C., Charville, G., Poultsides, G., Ganjoo, K. N. 2024; 16 (11): e74837

  Abstract

  Circulating tumor DNA (ctDNA) can be used to assess treatment response in patients with undifferentiated pleomorphic sarcoma (UPS). The importance of this is explored in our case of a 75-year-old man who was diagnosed with UPS of the right kidney. After a right nephrectomy and tumor resection, the patient was recovering well with initially undetectable, and then slightly elevated, circulating tumor DNA. Abdominal pain started shortly before a scheduled magnetic resonance imaging (MRI) which revealed a large mass in the resection bed invading the liver. The patient was treated with gemcitabine and docetaxel chemotherapy, and the ctDNA level rose dramatically before gradually decreasing and eventually becoming undetectable. At surgery, pathologic examination of the re-resection specimen revealed a complete pathological response. ctDNA monitoring may be a useful tool for early detection of response to chemotherapy in patients with UPS.

  View details for DOI 10.7759/cureus.74837

  View details for PubMedID 39737274

  View details for PubMedCentralID PMC11684465

• Circulating Tumor DNA in the Monitoring of Soft Tissue Sarcoma Treatment and Recurrence. Annals of surgical oncology Sun, B. J., Li, A. Y., Hur, D. G., Zhou, M., Poultsides, G. A., Delitto, D. J., Lee, B. 2024

  View details for DOI 10.1245/s10434-024-15902-9

  View details for PubMedID 39060690

  View details for PubMedCentralID 10119774

• Molecular residual disease (MRD) detection using bespoke circulating tumor DNA (ctDNA) assays in localized soft tissue sarcoma (STS): A multicenter study Alshibany, A., Zhou, M., Warren, E., Ganjoo, K. N., Demicco, E., Feeney, J., Lee, J., Shultz, D., Spickard, E., Bui, N., Cardona, K., Salawu, A., Razak, A. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557402695

• Sarcoma microenvironment cell states and ecosystems are associated with prognosis and predict response to immunotherapy. Nature cancer Subramanian, A., Nemat-Gorgani, N., Ellis-Caleo, T. J., van IJzendoorn, D. G., Sears, T. J., Somani, A., Luca, B. A., Zhou, M. Y., Bradic, M., Torres, I. A., Oladipo, E., New, C., Kenney, D. E., Avedian, R. S., Steffner, R. J., Binkley, M. S., Mohler, D. G., Tap, W. D., D'Angelo, S. P., van de Rijn, M., Ganjoo, K. N., Bui, N. Q., Charville, G. W., Newman, A. M., Moding, E. J. 2024

  Abstract

  Characterization of the diverse malignant and stromal cell states that make up soft tissue sarcomas and their correlation with patient outcomes has proven difficult using fixed clinical specimens. Here, we employed EcoTyper, a machine-learning framework, to identify the fundamental cell states and cellular ecosystems that make up sarcomas on a large scale using bulk transcriptomes with clinical annotations. We identified and validated 23 sarcoma-specific, transcriptionally defined cell states, many of which were highly prognostic of patient outcomes across independent datasets. We discovered three conserved cellular communities or ecotypes associated with underlying genomic alterations and distinct clinical outcomes. We show that one ecotype defined by tumor-associated macrophages and epithelial-like malignant cells predicts response to immune-checkpoint inhibition but not chemotherapy and validate our findings in an independent cohort. Our results may enable identification of patients with soft tissue sarcomas who could benefit from immunotherapy and help develop new therapeutic strategies.

  View details for DOI 10.1038/s43018-024-00743-y

  View details for PubMedID 38429415

  View details for PubMedCentralID 4486342

• PTEN pathogenic variants are associated with poor prognosis in patients with advanced soft tissue sarcoma. BJC reports Pan, M., Zhou, M. Y., Jiang, C., Zhang, Z., Bui, N., Bien, J., Siy, A., Achacoso, N., Solorzano, A. V., Tse, P., Chung, E., Hu, W., Thomas, S., Ganjoo, K., Habel, L. A. 2024; 2 (1): 9

  Abstract

  We aimed to examine whether PTEN pathogenic variants (mutPTEN) were associated with overall survival (OS) in patients with advanced soft tissue sarcoma (STS) with the presence of one or more of the most common genomic alterations including p53, CDKN2A, RB1, and ATRX pathogenic variants.This study included patients from Kaiser Permanente Northern California and Stanford Cancer Center with grade 2 or higher locally advanced and metastatic STS.A total of 174 patients had leiomyosarcoma (LMS), 136 had undifferentiated pleomorphic sarcoma (UPS), 78 had Liposarcoma (LPS), and 214 had other histology subtypes (Others). Among all patients with STS, OS was worse for those with mutPTEN versus wild-type PTEN (wtPTEN, adjusted HR [aHR] = 1.58 [95% CI, 1.11-2.23]), mutCDKN2A vs wtCDKN2A (aHR = 1.33 [95% CI .99-1.80]), and mutRB1 vs wtRB1 (aHR = 1.26 [95% CI 0.93-1.70[), while OS was similar for mutp53 vs wtp53 and mutATRX vs wtATRX. MutPTEN versus wtPTEN was consistently associated with worse OS in histologic subtypes including LMS and UPS and molecular subgroups.MutPTEN vs wtPTEN was associated with worse OS in advanced STS. If confirmed, our findings could be helpful for prognostic stratification in clinical practice and for further understanding the molecular mechanisms of STS.

  View details for DOI 10.1038/s44276-023-00029-3

  View details for PubMedID 39516677

  View details for PubMedCentralID 9200818

• Response to Immunotherapy in Sclerosing Epithelioid Fibrosarcoma: Case Report and Literature Review. Cureus Koerner, A. S., Zhou, M., Brook, A., Yoon, S. S., Ganjoo, K. N. 2023; 15 (12): e50967

  Abstract

  Sclerosing epithelioid fibrosarcoma (SEF) is an extremely rare subtype of sarcoma that appears histologically low-grade yet usually has a clinically aggressive course with a high rate of local recurrence and distant metastasis. However, these recurrences and metastases often occur years after initial treatment. Metastases can be to the lung as well as extra-pulmonary sites. In this case report, we discuss a patientwho developed SEF in the deep soft tissue with metastases. This patientunderwent checkpoint inhibitor therapy, with disease response. Thus, SEF is a sarcoma subtype with a unique tumor biology, and immunotherapy may be a promising avenue for treatment.

  View details for DOI 10.7759/cureus.50967

  View details for PubMedID 38259411

• Sex-Dependent Prognosis of Patients with Advanced Soft Tissue Sarcoma. Clinical cancer research : an official journal of the American Association for Cancer Research Pan, M., Zhou, M. Y., Jiang, C., Zhang, Z., Bui, N. Q., Bien, J., Siy, A., Achacoso, N., Solorzano, A. V., Tse, P., Chung, E., Thomas, S., Habel, L. A., Ganjoo, K. N. 2023

  Abstract

  To examine whether overall survival (OS) differs for male and female patients with advanced soft tissue sarcoma (STS).The study included patients from Kaiser Permanente Northern California and Stanford Cancer Center with grade 2 and 3 locally advanced or metastatic STS whose tumor underwent next-generation sequencing. We used Cox regression modeling to examine association of sex and OS adjusting for other important factors.Among 388 eligible patients, 174 had leiomyosarcoma (LMS), 136 had undifferentiated pleomorphic sarcoma (UPS), and 78 had LPS (Liposarcoma). OS for male versus female patients appeared to be slightly better among the full cohort (HR =0.89, [95% CI 0.66-1.20]); this association appeared to be stronger among the subsets of patients with LMS (HR = 0.76, [95% CI 0.39-1.49]) or LPS (HR = 0.74, [95% CI 0.32-1.70]). Better OS for male versus female patients was also observed among all molecular subgroups except mutRB1 and mutATRX, especially among patients whose tumor retained wtTP53 (HR = 0.73, [95% CI 0.44-1.18]), wtCDKN2A (HR = 0.85, [95% CI 0.59-1.23]), wtRB1 (HR = 0.73, [95% CI .51-1.04]) and among patients whose tumor had mutPTEN (HR = 0.37, [95% CI 0.09-1.62]). OS also appeared to be better for males in the MSK-IMPACT and TCGA datasets.A fairly consistent pattern of apparent better OS for males across histologic and molecular subgroups of STS was observed. If confirmed, our results could have implications for clinical practice for prognostic stratification and possibly treatment tailoring as well as for future clinical trials design.

  View details for DOI 10.1158/1078-0432.CCR-23-1990

  View details for PubMedID 37831066

• Epstein Barr Virus-Positive Lymphoproliferative Disorder Following Lymphodepletion for MAGE A4 Adoptive Cellular Therapy in a Patient with Synovial Sarcoma: A Case Report. Case reports in oncology Zhou, M., Jawed, G., Ganjoo, K. N. 2023; 16 (1): 886-892

  Abstract

  Lymphoproliferative disorder (LPD) associated with viral reactivation is a known risk of immunocompromised patients. With development of novel cellular therapies utilizing lymphodepletion regimens in advanced cancer, the risk of LPDs should be a consideration. Here, we report a case of a 61-year-old treated male with history of metastatic synovial sarcoma and multiple treatment lines treated with cell therapy (lymphodepleting chemotherapy and afami-cel, formerly ADP-A2M4, T-cell treatment) on clinical study that developed Epstein Barr virus-positive LPD. Patient was treated with rituximab and achieved a complete response. New cellular therapies present promising treatment options for patients and adverse events should be monitored carefully.

  View details for DOI 10.1159/000533129

  View details for PubMedID 37900845

  View details for PubMedCentralID PMC10601716

• Treatment of De-Differentiated Liposarcoma in the Era of Immunotherapy. International journal of molecular sciences Zhou, M. Y., Bui, N. Q., Charville, G. W., Ganjoo, K. N., Pan, M. 2023; 24 (11)

  Abstract

  Well-differentiated/de-differentiated liposarcoma (WDLPS/DDLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS); however, treatment options remain limited. WDLPS and DDLPS both exhibit the characteristic amplification of chromosome region 12q13-15, which contains the genes CDK4 and MDM2. DDLPS exhibits higher amplification ratios of these two and carries additional genomic lesions, including the amplification of chromosome region 1p32 and chromosome region 6q23, which may explain the more aggressive biology of DDLPS. WDLPS does not respond to systemic chemotherapy and is primarily managed with local therapy, including multiple resections and debulking procedures whenever clinically feasible. In contrast, DDLPS can respond to chemotherapy drugs and drug combinations, including doxorubicin (or doxorubicin in combination with ifosfamide), gemcitabine (or gemcitabine in combination with docetaxel), trabectedin, eribulin, and pazopanib. However, the response rate is generally low, and the response duration is usually short. This review highlights the clinical trials with developmental therapeutics that have been completed or are ongoing, including CDK4/6 inhibitors, MDM2 inhibitors, and immune checkpoint inhibitors. This review will also discuss the current landscape in assessing biomarkers for identifying tumors sensitive to immune checkpoint inhibitors.

  View details for DOI 10.3390/ijms24119571

  View details for PubMedID 37298520

• Feasibility of Longitudinal ctDNA Assessment in Patients with Uterine and Extra-Uterine Leiomyosarcoma. Cancers Zhou, M., Bui, N., Rathore, R., Sudhaman, S., George, G. V., Malashevich, A. K., Malhotra, M., Liu, M. C., Aleshin, A., Ganjoo, K. N. 2022; 15 (1)

  Abstract

  Background: Leiomyosarcomas (LMS) are aggressive malignancies with a propensity for early relapse. Current surveillance modalities include physical exam and imaging; however, radiological response to therapy may only manifest after 4-6 cycles of treatment. Herein, we evaluated the feasibility of longitudinal circulating tumor DNA (ctDNA) assessment in LMS patients to identify disease progression. Methods: We performed a retrospective review of patients with LMS who underwent treatment at Stanford Cancer Center between September 2019 and May 2022. ctDNA detection was performed using a personalized, tumor-informed ctDNA assay. Genomic analysis was conducted to characterize tumor mutation burden (TMB) and known driver mutations. Results: A total of 148 plasma samples were obtained from 34 patients with uterine (N = 21) and extrauterine (N = 13) LMS (median follow-up: 67.2 (19-346.3) weeks] and analyzed for ctDNA presence. Nineteen patients had metastatic disease. The most frequently mutated driver genes across sub-cohorts were TP53, RB1, and PTEN. Patients were stratified into four sub-cohorts (A-D) based on ctDNA kinetics. ctDNA levels tracked longitudinally with progression of disease and response to therapy. Conclusion: Our results indicate that while undetectable ctDNA may suggest a lower likelihood of relapse, ctDNA positivity may indicate progressive disease, enabling closer monitoring of patients for early clinical intervention.

  View details for DOI 10.3390/cancers15010157

  View details for PubMedID 36612153

• Current management and recent progress in desmoid tumors. Cancer treatment and research communications Zhou, M. Y., Bui, N. Q., Charville, G. W., Ghanouni, P., Ganjoo, K. N. 2022; 31: 100562

  Abstract

  Desmoid tumors are rare soft tissue tumors that can have aggressive infiltrative growth and relapse locally. Desmoid tumors can impact functionality and cause treatment-related morbidity and mortality. Here, the authors review current management strategies and avenues for further investigation. As part of the evolution of therapy away from primary surgical approaches to less invasive options, image-guided ablation has been accepted as less morbid and include cryoablation and high-intensity focused ultrasound. Systemic therapy options currently include hormonal agents, nonsteroidal anti-inflammatory drugs, tyrosine kinase inhibitors, and anthracycline-based regimens. Hormonal agents and nonsteroidal anti-inflammatory drugs have benign side effect profiles but generally limited efficacy. Anthracycline-based therapies are limited by the risk of secondary malignancies and cardiomyopathy. Tyrosine kinase inhibitors are well studied, and sorafenib is now one of the most utilized therapies, though limited by its side effect profile. Nirogacestat (PF-0308401) is an investigational small molecule gamma-secretase (GS) inhibitor that has demonstrated efficacy in phase 1 and II trials. A phase III trial investigating patients with desmoid tumors or aggressive fibromatosis is estimated to be completed December 2021 (NCT03785964). In addition to nirogacestat, the gamma-secretase inhibitor AL102 is being investigated for the treatment of patients with progressing desmoid tumors in the phase II/III RINGSIDE trial. Finally, the beta-catenin inhibitor Tegavivint (BC2059) is being investigated in a phase 1 open-label trial in patients with a proven primary or recurrent desmoid tumor that is unresectable and symptomatic or progressive.

  View details for DOI 10.1016/j.ctarc.2022.100562

  View details for PubMedID 35460976

• Safety and Feasibility of Cryoablation during Immunotherapy in Patients with Metastatic Soft Tissue Sarcoma. Journal of vascular and interventional radiology : JVIR Doshi, A., Zhou, M., Bui, N., Wang, D. S., Ganjoo, K., Hwang, G. L. 2021

  Abstract

  PURPOSE: Patients with metastatic soft tissue sarcoma (STS) undergo a wide array of treatments, including surgery, radiation, chemotherapy, immunotherapy, and ablative therapies, to control their disease. The combination of cryoablation and immunotherapy may lead to an enhanced anti-tumor immune response via the abscopal effect. It is hypothesized that the combination of cryoablation and immunotherapy in patients with metastatic STS is safe and feasible.MATERIALS/METHODS: A single-center retrospective analysis was performed on patients with metastatic STS who underwent cryoablation. Sixteen patients were treated with 27 cryoablation procedures while receiving ipilimumab and nivolumab from April 2017 to July 2020. RECIST 1.1 criteria was used to determine outcomes of non-target tumors. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of first cryoablation after initiating immunotherapy until progression or death.RESULTS: Thirty-four tumors were cryoablated, 23 of which were intentionally subtotal. Most common tumor subtype was liposarcoma (n = 4). Thirteen patients (81%) had previously demonstrated disease progression on multiple lines of chemotherapy. All tumors cryoablated with complete intention demonstrated complete response. Seven patients had clinical benefit, including 1 complete response, 1 partial response, and 5 with stable disease. The median OS was 14.1 months, with a median PFS of 2.3 months (95% CI 1.8-14.3). Five patients had post-cryoablation pneumothoraces, two of whom required chest tube placement. Eleven patients experienced adverse events related to immunotherapy, 10 of which were grade 1 or 2.CONCLUSION: Cryoablation in patients with metastatic soft tissue sarcoma undergoing immunotherapy is feasible and safe.

  View details for DOI 10.1016/j.jvir.2021.08.017

  View details for PubMedID 34478852

• Rare and fatal complication of immune checkpoint inhibition: a case report of haemophagocytic lymphohistiocytosis with severe lichenoid dermatitis. British journal of haematology Choi, S., Zhou, M., Bahrani, E., Martin, B. A., Ganjoo, K. N., Zaba, L. C. 2021

  View details for DOI 10.1111/bjh.17442

  View details for PubMedID 33954981

• Systemic Corticosteroid Use after Central Serous Chorioretinopathy Diagnosis OPHTHALMOLOGY Azad, A. D., Zhou, M., Afshar, A. R., Bakri, S. J., Pershing, S. 2021; 128 (1): 121–29

  View details for DOI 10.1016/j.opatha.2020.06.056

  View details for Web of Science ID 000600748500030

• Management Strategies for Patients With Epithelioid Hemangioendothelioma: Charting an Indolent Disease Course. American journal of clinical oncology Yurkiewicz, I. R., Zhou, M., Ganjoo, K. N., Charville, G. W., Bolleddu, S., Lohman, M., Bui, N. 2021

  Abstract

  Epithelioid hemangioendothelioma (EHE) is a malignant vascular neoplasm representing ∼1% of sarcomas. Due to its rarity, its clinical course is not well characterized and optimal treatment remains unknown.This was a retrospective review of patients with EHE treated at Stanford University between 1998 and 2020. Demographic characteristics, pathology results, treatment modalities, and clinical outcomes were collected from the electronic medical records.A total of 58 patients had a mean age of 50.6 years and a slight female predominance (52%). Primary disease sites were liver (33%), soft tissue (29%), lung (14%), bone (9%), and mediastinum (9%). A majority (55%) had advanced or metastatic disease. Median overall survival (OS) was 16.9 years, with OS 89% at 1 year, 68% at 5 years, and 64% at 10 years. The longest median OS was associated with soft tissue sites and shortest with lung and mediastinal disease (P=0.03). The localized disease had improved median OS compared with metastatic disease (P=0.02). There was no OS difference between tumors >3 cm and those equal or smaller (P=0.85). Surgery was a common treatment (71%), while radiation and ablation were sometimes used (28% and 9%, respectively). The median time to initiating therapy of any kind was 68 days. The median time to systemic therapy was 114 days.We report on the clinical characteristics and outcomes of patients with EHE at a large academic center. Treatment options included surgical excision, liver transplant, ablation, radiation, and systemic therapy. A subset of patients had indolent disease not requiring treatment upfront.

  View details for DOI 10.1097/COC.0000000000000827

  View details for PubMedID 34028371

• Surgical resection of leiomyosarcoma of the inferior vena cava: A case series and literature review. Surgical oncology Zhou, M., Javadi, C., Charville, G. W., Bui, N. Q., Harris, E. J., Poultsides, G. A., Norton, J. A., Visser, B., Lee, B., Dua, M. M., Ganjoo, K. N. 2021; 39: 101670

  Abstract

  We review our institution's experience in treating leiomyosarcomas involving the inferior vena cava, and we offer guidance on the management.A text-based search was performed to identify all patients who underwent surgical resection between January 2002 and October 2020. Clinicopathologic data, intraoperative variables, and outcomes were extracted from chart review.Twelve of 16 patients (75%) had localized disease; the remaining had limited metastatic disease. Seven of 16 patients (44%) received neoadjuvant chemotherapy or radiation; three patients had partial responses, and four patients had stable disease using RECIST 1.1 criteria. IVC reconstruction was performed in 14 of 16 patients (88%); IVC was ligated for the remaining two patients. Half of all patients had R0 resection on final pathology; the remaining had R1 resections. Progression-free survival (PFS) and overall survival (OS) were not statistically different between patients with R0 and R1 resection. Median PFS was 1.8 years (95% CI 0.89 - not reached); median OS was 6.5 years (1.8 - not reached). Only one patient (6%) experienced local disease recurrence; 4 of 16 patients (25%) experienced disease recurrence distally without local recurrence.Resection of IVC leiomyosarcomas at a sarcoma referral center with experience in vascular reconstruction can lead to many years of recurrence-free survival. Surgical resection should be offered to patients with a low volume of metastatic disease to reduce local complications from the primary tumor, many of which exert significant mass effect on surrounding organs. For patients with metastatic disease or large, high-risk tumors, neoadjuvant chemotherapy can provide a biologic test of disease stability prior to resection.

  View details for DOI 10.1016/j.suronc.2021.101670

  View details for PubMedID 34710646

• Long-Term Remission with Ipilimumab/Nivolumab in Two Patients with Different Soft Tissue Sarcoma Subtypes and No PD-L1 Expression. Case reports in oncology Zhou, M., Bui, N., Lohman, M., van de Rjin, M., Hwang, G., Ganjoo, K. 2021; 14 (1): 459–65

  Abstract

  Checkpoint inhibitor therapy has been shown to improve outcomes in multiple solid malignancies; however, data are limited in soft tissue sarcoma. We present two cases of patients with advanced soft tissue sarcoma of different subtypes (dedifferentiated liposarcoma and myxofibrosarcoma) with zero percent PD-L1 expression by immunohistochemistry who were treated with ipilimumab and nivolumab followed by maintenance nivolumab. Both patients had failed multiple lines of systemic treatment and experienced long-term remission after starting ipilimumab and nivolumab. Genetic testing revealed that no genetic mutations were found in common between the two cases. One patient received concurrent cryoablation, which may have sensitized his tumor to immunotherapy. Checkpoint inhibitor therapy may improve outcomes in soft tissue sarcoma regardless of PD-L1 status, especially when combined with cryoablation. Studies are needed to evaluate whether treatment response varies by sarcoma subtype and what molecular markers can be used to guide patient selection.

  View details for DOI 10.1159/000512828

  View details for PubMedID 33790767

• Nivolumab plus ipilimumab for soft tissue sarcoma: a single institution retrospective review IMMUNOTHERAPY Zhou, M., Bui, N., Bolleddu, S., Lohman, M., Becker, H., Ganjoo, K. 2020; 12 (18): 1303–12

  View details for DOI 10.2211/imt-2020-0155

  View details for Web of Science ID 000598571200001

• Sinonasal FUS-ERG-Rearranged Ewing's Sarcoma Mimicking Glomangiopericytoma. Case reports in oncology Zhou, M. n., Ko, Y. C., Charville, G. W., Ganjoo, K. N. 2020; 13 (3): 1393–96

  Abstract

  Ewing's sarcoma is a rare and aggressive tumor that typically arises in the long bones of the extremities. It belongs in the family of small round blue cell tumors and is characterized immunohistochemically by diffuse CD99 expression and molecularly by one of several oncogenic translocations, most commonly t(11;22)(q24;q12) between the EWSR1 gene and the FLI1 gene. Here we present a rare case of Ewing's sarcoma in the sinonasal tract with FUS-ERG gene arrangement that was regarded for almost a decade as a sinonasal-type hemangiopericytoma (glomangiopericytoma). This case illustrates the surprisingly prolonged natural history of Ewing's sarcoma that did not receive therapy for many years and the importance of considering alternative genetic translocations. Our experience suggests that the presence of diffuse CD99 membranous staining pattern in a small blue round cell tumor with morphology typical for Ewing's sarcoma but FISH negative for EWSR1 rearrangement should prompt consideration of FUS-ERG fusion.

  View details for DOI 10.1159/000511415

  View details for PubMedID 33442361

  View details for PubMedCentralID PMC7772862

• PD-1/PD-L1 Checkpoint Inhibitor Immunotherapy for Malignant Pleural Mesothelioma: Case Series and Literature Review. Clinical lung cancer Zhou, M. n., Joshi, N. n., Raj, K. P., Wakelee, H. n., Neal, J. W. 2020

  View details for DOI 10.1016/j.cllc.2020.05.012

  View details for PubMedID 32624413

• Risk factors for incident central serous retinopathy: case-control analysis of a US national managed care population BRITISH JOURNAL OF OPHTHALMOLOGY Zhou, M., Bakri, S. J., Pershing, S. 2019; 103 (12): 1784–88

  View details for DOI 10.1136/bjophthalmol-2018-313050

  View details for Web of Science ID 000501150600017

• Sleep duration, timing, variability and measures of adiposity among 8- to 12-year-old children with obesity. Obesity science & practice Zhou, M., Lalani, C., Banda, J. A., Robinson, T. N. 2018; 4 (6): 535–44

  Abstract

  Objectives: Sleep disruption in laboratory studies increases adiposity and decreases glucose tolerance. However, few epidemiological studies have used objective measures of sleep. This study aims to assess associations between sleep duration, timing and regularity with measures of adiposity.Methods: This is a cross-sectional study of 188 children with obesity (age: 10.50±1.39years; body mass index: 29.24±5.04kgm-2). Nightly sleep duration, bedtime and wake time were measured by multiple-day actigraphy and parent reports. Per cent overweight (per cent over median body mass index for age and sex) was chosen as the primary measure of obesity status. Objective measures of height, weight, waist circumference, blood pressure, fasting blood lipids, glucose, insulin, glycated haemoglobin and C-reactive protein were obtained. Television screen time and total caloric intake were assessed via parent questionnaire.Results: Each hour later in weekday bedtime was associated with an additional 6.17 per cent overweight (95% confidence interval [CI]: 1.42-10.92). Each hour greater in day-to-day variability in weekday bedtime and weekday wake time was associated with an additional 10.20 (95% CI: 0.50-19.91) and 10.02 (95% CI: 1.55-18.50) per cent overweight, respectively. Associations were similar after controlling for other obesity-related behaviours (television screen time, total caloric intake and physical activity.).Conclusions: Among children with obesity, later bedtime and greater variability in bedtime and wake time are associated with greater adiposity, independent of other obesity-related behaviours. Early bedtime and wake time and consistent day-to-day sleep timing may be strategies to reduce adiposity in high-risk children.

  View details for PubMedID 30574347

• Different Raf Protein Kinases Mediate Different Signaling Pathways to Stimulate E3 Ligase RFFL Gene Expression in Cell Migration Regulation JOURNAL OF BIOLOGICAL CHEMISTRY Gan, X., Wang, C., Patel, M., Kreutz, B., Zhou, M., Kozasa, T., Wu, D. 2013; 288 (47): 33978-33984

  Abstract

  We previously characterized a Gα12-specific signaling pathway that stimulates the transcription of the E3 ligase RFFL via the protein kinase ARAF and ERK. This pathway leads to persistent PKC activation and is important for sustaining fibroblast migration. However, questions remain regarding how Gα12 specifically activates ARAF, which transcription factor is involved in Gα12-mediated RFFL expression, and whether RFFL is important for cell migration stimulated by other signaling mechanisms that can activate ERK. In this study, we show that replacement of the Gα12 residue Arg-264 with Gln, which is the corresponding Gα13 residue, abrogates the ability of Gα12 to interact with or activate ARAF. We also show that Gα12 can no longer interact with and activate an ARAF mutant with its C-terminal sequence downstream of the kinase domain being replaced with the corresponding CRAF sequence. These results explain why Gα12, but not Gα13, specifically activates ARAF but not CRAF. Together with our finding that recombinant Gα12 is sufficient for stimulating the kinase activity of ARAF, this study reveals an ARAF activation mechanism that is different from that of CRAF. In addition, we show that this Gα12-ARAF-ERK pathway stimulates RFFL transcription through the transcription factor c-Myc. We further demonstrate that EGF, which signals through CRAF, and an activated BRAF mutant also activate PKC and stimulate cell migration through up-regulating RFFL expression. Thus, RFFL-mediated PKC activation has a broad significance in cell migration regulation.

  View details for DOI 10.1074/jbc.M113.477406

  View details for Web of Science ID 000327250200039

  View details for PubMedID 24114843

  View details for PubMedCentralID PMC3837137