A5026593581- Gastrointestinal Tumor Research and Treatment
- Sarcoma Diagnosis and Treatment
- Gastric Cancer Management and Outcomes
- Gastrointestinal disorders and treatments
- Cancer Genomics and Diagnostics
- Neurofibromatosis and Schwannoma Cases
- Soft tissue tumor case studies
- Chronic Myeloid Leukemia Treatments
- Pancreatic and Hepatic Oncology Research
- Mast cells and histamine
- Cancer, Hypoxia, and Metabolism
- Renal cell carcinoma treatment
- Cell Adhesion Molecules Research
- Genetic factors in colorectal cancer
- Cutaneous Melanoma Detection and Management
- Glioma Diagnosis and Treatment
- Hepatitis C virus research
- Prostate Cancer Treatment and Research
- Esophageal Cancer Research and Treatment
- Renal and related cancers
- Metastasis and carcinoma case studies
- Lung Cancer Treatments and Mutations
- Cytomegalovirus and herpesvirus research
- Eosinophilic Disorders and Syndromes
- Organ Transplantation Techniques and Outcomes
Oregon Health & Science University
2016-2025
OHSU Knight Cancer Institute
2014-2024
University of Portland
2008-2024
Fox Chase Cancer Center
2003-2023
Dana-Farber Cancer Institute
1996-2023
University of Turku
2003-2023
University of Helsinki
2003-2023
Oregon Health Authority
2023
Novartis (Switzerland)
2008-2023
Cancer Institute (WIA)
2006-2022
Constitutive activation of KIT receptor tyrosine kinase is critical in the pathogenesis gastrointestinal stromal tumors. Imatinib mesylate, a selective inhibitor, has been shown preclinical models and preliminary clinical studies to have activity against such
Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits kinase activity. Here we show that ∼35% (14 of 40) lacking intragenic activation related platelet-derived growth factor α ( PDGFRA ). Tumors expressing or oncoproteins were indistinguishable respect downstream signaling intermediates cytogenetic changes associated tumor progression. Thus, appear be alternative...
Purpose: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to was examined a group patients with advanced GIST. Patients Methods: GISTs from 127 enrolled onto phase II study were PDGFRA. Mutation types correlated outcome. Results: Activating...
The role of colonoscopy in screening for colorectal cancer is uncertain. At 13 Veterans Affairs medical centers, we performed to determine the prevalence and location advanced colonic neoplasms risk proximal neoplasia asymptomatic patients (age range, 50 75 years) with or without distal neoplasia. Advanced was defined as an adenoma that 10 mm more diameter, a villous adenoma, high-grade dysplasia, invasive cancer. In than one neoplastic lesion, classification based on most lesion.
The outcome of patients diagnosed with advanced gastrointestinal stromal tumor (GIST) and treated long-term imatinib mesylate is unknown. A previous report a randomized phase II trial in incurable GIST detailed high response rates at both the 400 600 mg/d dose levels. We conducted analysis on trial, including followed during an extension phase, to evaluate survival, patterns failure, potential prognostic factors, mutational status.Patients were enrolled onto open-label, multicenter randomly...
Purpose Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT or platelet-derived growth factor alpha (PDGFRA) kinases, which are targets for imatinib. In clinical studies, 75% to 90% patients with advanced GISTs experience benefit from However, imatinib resistance is an increasing problem. Patients and Methods One hundred forty-seven advanced, unresectable were enrolled onto a randomized, phase II study Specimens pretreatment and/or imatinib-resistant...
Most gastrointestinal stromal tumors (GISTs) harbor mutant KIT or platelet-derived growth factor receptor alpha (PDGFRA) kinases, which are imatinib targets. Sunitinib, targets KIT, PDGFRs, and several other has demonstrated efficacy in patients with GIST after they experience failure. We evaluated the impact of primary secondary kinase genotype on sunitinib activity.Tumor responses were assessed radiologically a phase I/II trial 97 metastatic, imatinib-resistant/intolerant GIST. KIT/PDGFRA...
Melanomas harbor aberrations in the c-Kit gene. We tested efficiency of tyrosine kinase inhibitor imatinib selected patients with metastatic melanoma harboring mutations or amplifications.Forty-three were enrolled on this phase II trial. Each patient received a continuous dose 400 mg/d unless intolerable toxicities disease progression occurred. Fifteen who experienced allowed to escalate 800 mg/d.Forty-three eligible for evaluation, and median follow-up time was 12.0 months. The...
Abstract Purpose: We recently identified a KIT exon 11 mutation in an anorectal melanoma of patient who had excellent response to treatment with imatinib. To determine the frequency mutations across subtypes, we surveyed large series tumors. Experimental Design: One hundred eighty-nine melanomas were screened for exons 11, 13, and 17. copy number was assessed by quantitative PCR. A subset cases evaluated BRAF NRAS mutations. Immunohistochemistry done assess (CD117) expression. Results:...
The NCCN Soft Tissue Sarcoma Guidelines include a subsection about treatment recommendations for gastrointestinal stromal tumors (GISTs). standard of practice rapidly changed after the introduction effective molecularly targeted therapy (such as imatinib and sunitinib) GIST. Because these changes, organized multidisciplinary panel composed experts in fields medical oncology, molecular diagnostics, pathology, radiation surgery to discuss optimal approach care patients with GIST at all stages...
Purpose Patients with advanced pancreas cancer present disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients cancer. This trial was conducted evaluate contribution of an EGFR-targeted agent standard gemcitabine therapy. Cetuximab a monoclonal antibody against ligand-binding domain receptor. Methods unresectable locally or metastatic pancreatic...
Imatinib mesylate is standard treatment for patients who have advanced gastrointestinal stromal tumor (GIST), but not all benefit equally. In previous studies, GIST genotype correlated with outcome and optimal imatinib dosing.We examined the relationship between kinase 428 enrolled on North American phase III study SWOG S0033/CALGB 150105 treated either 400 mg or 800 daily doses of imatinib.The presence KIT exon 11-mutant (n = 283) improved when compared 9-mutant 32) wild-type (WT; n 67)...
Fecal occult-blood testing and sigmoidoscopy have been recommended for screening colorectal cancer, but the sensitivity of such combined detecting neoplasia is uncertain. At 13 Veterans Affairs medical centers, we performed colonoscopy to determine prevalence one-time with a fecal test plus sigmoidoscopy.
Amplifications and mutations in the KIT proto-oncogene subsets of melanomas provide therapeutic opportunities.We conducted a multicenter phase II trial imatinib metastatic mucosal, acral, or chronically sun-damaged (CSD) melanoma with amplifications and/or mutations. Patients received 400 mg once per day twice if there was no initial response. Dose reductions were permitted for treatment-related toxicities. Additional oncogene mutation screening performed by mass spectroscopy.Twenty-five...
Tenosynovial giant-cell tumor (TGCT) and pigmented villonodular synovitis (PVNS) are related conditions with features of both reactive inflammatory disorders clonal neoplastic proliferations. Chromosomal translocations involving chromosome 1p13 have been reported in TGCT PVNS. We confirm that present a majority cases PVNS show CSF1 is the gene at breakpoint. In some PVNS, fused to COL6A3 (2q35). The result overexpression CSF1. carrying this translocation, it minority intratumoral cells,...
The diagnosis of gastrointestinal stromal tumor (GIST) is currently based on morphologic features and immunohistochemical demonstration KIT (CD117). However, some tumors (in our estimation approximately 4%) have clinicopathologic GIST but do not express KIT. To determine if these lesions are truly GISTs, we evaluated 25 with clinical histologic typical GIST, negative immunohistochemistry, for PDGFRA mutations using DNA extracted from paraffin-embedded tissue. Most originated in the stomach...