Clinical Associate Professor, Pediatrics - Hematology & Oncology
Honors & Awards
C.John Tupper Award for Excellence in Medical Education, University of California, Davis School of Medicine (1999)
M.D., Washington University, St.Louis, Medicine (1990)
B.S., Johns Hopkins University, Biology/Biomedical Engineering (1986)
- Independent Studies (5)
Genomic analysis of fibrolamellar hepatocellular carcinoma.
Human molecular genetics
2015; 24 (1): 50-63
Pediatric tumors are relatively infrequent but are often associated with significant lethality and lifelong morbidity. A major goal of pediatric cancer research has been to identify key drivers of tumorigenesis to eventually develop targeted therapies to enhance cure rate and minimize acute and long-term toxic effects. Here we used genomics approaches to identify biomarkers and candidate drivers for fibrolamellar hepatocellular carcinoma (FL-HCC), a very rare subtype of pediatric liver cancer for which limited therapeutic options exist. In-depth genomics analyses of one tumor followed by immunohistochemistry validation on seven other tumors showed expression of neuroendocrine markers in FL-HCC. DNA and RNA sequencing data further showed that common cancer pathways are not visibly altered in FL-HCC but identified two novel structural variants, both resulting in fusion transcripts. The first, a 400kb deletion, results in a DNAJ1-PRKCA fusion transcript, which leads to increased PKA activity in the index tumor case and other FL-HCC cases compared to normal liver. This PKA fusion protein is oncogenic in HCC cells. The second gene fusion event, a translocation between the CLPTML1 and GLIS3 genes, generates a transcript whose product also promotes cancer phenotypes in HCC cell lines. These experiments further highlight the tumorigenic role of gene fusions in the etiology of pediatric solid tumors and identify both candidate biomarkers and possible therapeutic targets for this lethal pediatric disease.
View details for DOI 10.1093/hmg/ddu418
View details for PubMedID 25122662
- Successful Treatment with Temozolomide Combined with Chemoradiotherapy and Surgery of a Metastatic Undifferentiated Soft Tissue Sarcoma with Relapse in the Central Nervous System of a Young Adult JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY 2014; 3 (2): 100-103
Increased utilization of pediatric specialty care: a population study of pediatric oncology inpatients in california.
Journal of pediatric hematology/oncology
2014; 36 (2): 99-107
To examine inpatient utilization of pediatric cancer specialty centers (PCSCs) by pediatric oncology patients.We performed a retrospective (1999 to 2010) population-based analysis of oncology hospitalizations for pediatric patients aged 0 through 18 years using the California Office of Statewide Health Planning and Development database. Logistic regression examined hospitalization at 29 PCSCs and variables of age, sex, tumor type, payer, race, income, and distance to admission site.Analysis of 103,961 pediatric oncology discharges revealed that 93% occurred at PCSCs. These sites experienced a 20% increase in pediatric oncology discharges, conversely non-PCSCs exhibited a 70% decrease (P<0.0001). Multivariate analyses revealed increased utilization with young age (odds ratio [OR], 4.58; 95% CI, 3.88-5.42), African American (OR, 1.26; 95% CI, 1.11-1.43), and middle income (OR, 1.36; 95% CI, 1.29-1.45). Decreased utilization was seen for females (OR, 0.88; 95% CI, 0.84-0.93) and Hispanics (OR, 0.72; 95% CI, 0.68-0.77). Payer and proximity were not significantly associated with change in utilization. Tumor types less likely to utilize a PCSC included germ cell, solid, and central nervous system tumors. Adolescents were >3 times less likely to be treated at a PCSC.Inpatient pediatric oncology care in California has become increasingly regionalized with the vast majority of patients accessing PCSCs. However, variability in hospitalizations of adolescent patients and children not treated in PCSCs deserve further evaluation.
View details for DOI 10.1097/01.mph.0000438027.07467.f1
View details for PubMedID 24517965
Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study
2013; 14 (9): 834-842
The objective of this study was to establish the efficacy and safety of a new treatment regimen consisting of dose-dense cisplatin-based chemotherapy and radical surgery in children with high-risk hepatoblastoma.SIOPEL-4 was a prospective single-arm feasibility study. Patients aged 18 years or younger with newly diagnosed hepatoblastoma with either metastatic disease, tumour in all liver segments, abdominal extrahepatic disease, major vascular invasion, low α fetoprotein, or tumour rupture were eligible. Treatment consisted of preoperative chemotherapy (cycles A1-A3: cisplatin 80 mg/m(2) per day intravenous in 24 h on day 1; cisplatin 70 mg/m(2) per day intravenous in 24 h on days 8, 15, 29, 36, 43, 57, and 64; and doxorubicin 30 mg/m(2) per day intravenous in 24 h on days 8, 9, 36, 37, 57, and 58) followed by surgical removal of all remaining tumour lesions if feasible (including liver transplantation and metastasectomy, if needed). Patients whose tumour remained unresectable received additional preoperative chemotherapy (cycle B: doxorubicin 25 mg/m(2) per day in 24 h on days 1-3 and 22-24, and carboplatin area under the curve [AUC] 10·6 mg/mL per min per day intravenous in 1 h on days 1 and 22) before surgery was attempted. After surgery, postoperative chemotherapy was given (cycle C: doxorubicin 20 mg/m(2) per day in 24 h on days 1, 2, 22, 23, 43, and 44, and carboplatin AUC 6·6 mg/mL per min per day in 1 h on days 1, 22, and 43) to patients who did not receive cycle B. The primary endpoint was the proportion of patients with complete remission at the end of treatment. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00077389.We report the final analysis of the trial. 62 eligible patients (39 with lung metastases) were included and analysed. 60 (98%, 95% CI 91-100) of 61 evaluable patients (one child underwent primary hepatectomy) had a partial response to preoperative chemotherapy. Complete resection of all tumour lesions was achieved in 46 patients (74%). At the end of therapy, 49 (79%, 95% CI 67-88) of 62 patients were in complete remission. With a median follow-up of 52 months, 3-year event-free survival was 76% (95% CI 65-87) and 3-year overall survival was 83% (73-93). 60 (97%) patients had grade 3-4 haematological toxicity (anaemia, neutropenia, or thrombocytopenia) and 44 (71%) had at least one episode of febrile neutropenia. Other main grade 3 or 4 toxicities were documented infections (17 patients, 27%), anorexia (22, 35%), and mucositis (seven, 11%). One child died of fungal infection in neutropenia. Moderate-to-severe ototoxicity was documented in 31 (50%) patients. 18 serious adverse events (including two deaths) reflecting the observed side-effects were reported in the trial (the most common was ototoxicity in five patients).The SIOPEL-4 treatment regimen is feasible and efficacious for complete remission at the end of treatment for patients with high-risk hepatoblastoma.Cancer Research UK and Cancer Research Switzerland/Oncosuisse.
View details for DOI 10.1016/S1470-2045(13)70272-9
View details for Web of Science ID 000323423400040
View details for PubMedID 23831416
Congenital Pancreatoblastoma: Report of an Atypical Case and Review of the Literature
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
2012; 34 (4): 310-315
Pancreatoblastoma is a rare malignant tumor of the pancreas mostly diagnosed in childhood. The clinical presentation and outcome of infantile and congenital pancreatoblastoma have not been clearly elucidated. This report describes our recent institutional experience with an unusual case of congenital pancreatoblastoma. Review of the scientific literature identifies approximately 200 cases of pancreatoblastoma. We describe the 9 infantile (aged 3 mo and younger) and 4 congenital cases previously reported and summarize their clinical presentation and outcome. We also define the close association of infantile/congenital pancreatoblastoma and Beckwith-Wiedemann syndrome (50%) versus all affected age groups (4.5%).
View details for DOI 10.1097/MPH.0b013e318239f4f6
View details for Web of Science ID 000303652500029
View details for PubMedID 22278199
Bcl-2 overexpression results in enhanced capacitative calcium entry and resistance to SKF-96395-induced apoptosis
2000; 60 (16): 4358-4361
Although there is evidence that changes in cellular ionic concentrations are important early events in apoptosis, the regulation of ion fluxes across the plasma membrane during this process is poorly understood. We report here that Bcl-2 overexpression results in up-regulation of capacitative Ca2+ entry (CCE) and that SKF-96365, an inhibitor of CCE, is a potent inducer of apoptosis. Cells that overexpress Bcl-2 are resistant to SKF-96365-mediated apoptosis and to its inhibition of CCE. Enhanced CCE can be reversed with ouabain, suggesting that Bcl-2-associated plasma membrane hyperpolarization plays a role in up-regulating CCE and may partially explain the antiapoptotic effect of Bcl-2.
View details for Web of Science ID 000088961100014
View details for PubMedID 10969777