A5047649028- Gastrointestinal Tumor Research and Treatment
- Sarcoma Diagnosis and Treatment
- Neurofibromatosis and Schwannoma Cases
- Cardiac tumors and thrombi
- Chronic Myeloid Leukemia Treatments
- Bone Tumor Diagnosis and Treatments
- Vascular Tumors and Angiosarcomas
- Gastrointestinal disorders and treatments
- Oral and Maxillofacial Pathology
- Bone health and treatments
- Platelet Disorders and Treatments
- Pituitary Gland Disorders and Treatments
- Immune Cell Function and Interaction
- Soft tissue tumor case studies
- Cutaneous Melanoma Detection and Management
- Cancer Immunotherapy and Biomarkers
- Cell Adhesion Molecules Research
- Myasthenia Gravis and Thymoma
Memorial Sloan Kettering Cancer Center
2007-2011
Memorial Hospital
2011
Cornell University
2009
Translational Research in Oncology
2009
Abstract Most gastrointestinal stromal tumors (GIST) have an activating mutation in either KIT or PDGFRA. Imatinib is a selective tyrosine kinase inhibitor and achieves partial response stable disease about 80% of patients with metastatic GIST. It now clear that some GIST develop resistance to imatinib during chronic therapy. To identify the mechanism resistance, we studied 31 who were treated then underwent surgical resection. There 13 nonresistant imatinib, 3 primary 15 acquired after...
Abstract BRAF and NRAS are commonly mutated in cancer represent the most frequent genetic events malignant melanoma. More recently, a subset of melanomas was shown to overexpress KIT harbor mutations. Although gastrointestinal stromal tumors (GISTs) exhibit activating mutations either or PDGFRA , about 10% cases lack these genes. It is our hypothesis following melanoma model that may play role wild‐type GIST pathogenesis. Alterations RAS/MEK/ERK pathway also be involved development imatinib...
Abstract Angiosarcoma (AS) is a distinct group of sarcomas characterized by upregulation vascular‐specific receptor tyrosine kinases, including TIE1 , KDR TEK and FLT1. In keeping with the clinical heterogeneity, gene‐expression profiling distinguishes two AS genomic clusters, which correlate anatomical location prior exposure to radiation. Furthermore, high percentage secondary AS, but not primary shows 8q24 chromosomal gains, due MYC amplification. this study, we mined transcriptional...
Abstract Angiosarcomas (AS) represent a heterogeneous group of malignant vascular tumors occurring not only in different anatomic locations but also distinct clinical settings, such as radiation or associated chronic lymphedema. Although representing 1% to 2% soft tissue sarcomas, sarcomas provide unique insight into the general process tumor angiogenesis. However, no molecular candidates have been identified guide specific therapeutic intervention. By expression profiling, AS show...
Abstract Purpose: Pediatric gastrointestinal stromal tumors (GIST) are rare and occur preferentially in females as multifocal gastric tumors, typically lacking mutations KIT PDGFRA. As oncoprotein is consistently overexpressed pediatric GIST, we sought to investigate the activation of downstream targets alterations KIT/PDGFRA gene copy number, mine novel therapeutic by expression, test tyrosine kinase receptor proteomic profiling. Experimental Design: Seventeen GISTs were investigated for...
Abstract Activating mutations in either BRAF or NRAS are seen a significant number of malignant melanomas, but their incidence appears to be dependent ultraviolet light exposure. Thus, have the highest non‐chronic sun damaged (CSD), and uncommon acral, mucosal CSD melanomas. More recently, activating KIT been described rare cases metastatic melanoma, without further reference clinical phenotypes. This finding is intriguing since expression downregulated most melanomas progressing more...
Thymomas and thymic carcinomas are rare intrathoracic malignancies that can be invasive refractory to conventional treatment. Because these tumors both originate from the thymus, they often grouped together clinically. However, whether underlying biology of warrants such clustering is unclear, optimum treatment either entity unknown.All were profiled for mutations in genes encoding components EGFR KIT signaling pathways, assessed expression by immunohistochemistry, analyzed array-based...
Abstract Purpose: Resistance is commonly acquired in patients with metastatic gastrointestinal stromal tumor who are treated imatinib mesylate, often due to the development of secondary mutations KIT kinase domain. We sought investigate efficacy second-line tyrosine inhibitors, such as sorafenib, dasatinib, and nilotinib, against observed imatinib-resistant (KITV654A, KITT670I, KITD820Y, KITN822K) expressed Ba/F3 cellular system. Experimental Design: In vitro drug screening stable mutants...
Abstract Purpose: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of intestinal tract. Nearly all tumors express KIT protein, and have an activating mutation in either or PDGFRA. Therapy with selective tyrosine kinase inhibitors achieves a partial response stable disease ∼80% patients advanced GIST. However, after initial clinical response, some develop imatinib resistance. Our goal was to investigate spectrum pathologic molecular alterations group GIST patients, clinically...
Abstract Purpose: Although tyrosine kinase inhibitors have improved survival in advanced gastrointestinal stromal tumor (GIST), complete response is rare and most patients eventually fail the first-line treatment with imatinib. Sunitinib malate only approved second-line therapy for imatinib-resistant or imatinib-intolerant GIST. The clinical benefit of sunitinib genotype-dependent regards to both primary secondary mutations, GIST harboring KITAY502-3ins exon 9 mutation being sensitive....
Abstract Although imatinib mesylate has been a major breakthrough in the treatment of advanced gastrointestinal stromal tumors (GIST), complete responses are rare and most patients eventually develop resistance to drug. Thus, possibility an imatinib‐insensitive cell subpopulation within GIST tumors, harboring stem characteristics, may be responsible for clinical failures. However, existence cancer component not yet established. This study was aimed determine whether expression commonly used...