A5068831986- Gastrointestinal Tumor Research and Treatment
- Cancer Genomics and Diagnostics
- Gastrointestinal disorders and treatments
- Neurofibromatosis and Schwannoma Cases
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Sarcoma Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- Metastasis and carcinoma case studies
- Lung Cancer Treatments and Mutations
- Cancer Treatment and Pharmacology
- Mast cells and histamine
- Advanced Breast Cancer Therapies
- Radiomics and Machine Learning in Medical Imaging
- Ferroptosis and cancer prognosis
- PI3K/AKT/mTOR signaling in cancer
- Soft tissue tumor case studies
- Anatomy and Medical Technology
- Cutaneous Melanoma Detection and Management
- Reconstructive Surgery and Microvascular Techniques
- Platelet Disorders and Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer and Skin Lesions
- Breast Cancer Treatment Studies
- Polyamine Metabolism and Applications
University of Nevada, Las Vegas
2025
Oregon Health & Science University
2009-2022
OHSU Knight Cancer Institute
2009-2019
Portland VA Medical Center
2012-2019
VA Portland Health Care System
2018-2019
Kōchi University
2012
Arog Pharmaceuticals (United States)
2012
Brigham and Women's Hospital
2012
KU Leuven
2012
Cancer Institute (WIA)
2008
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:...
Abstract Purpose: To determine the potential of crenolanib, a potent inhibitor PDGFRA, to treat malignancies driven by mutant PDGFRA. Experimental Design: The biochemical activity crenolanib was compared with imatinib using panel PDGFRA-mutant kinases expressed in several different cell line models, including primary gastrointestinal stromal tumors (GIST) cells. antiproliferative also studied lines PDGFRA-dependent growth. Results: Crenolanib significantly more than inhibiting kinase...
Mechanisms of therapeutic resistance and vulnerability evolve in metastatic cancers as tumor cells extrinsic microenvironmental influences change during treatment. To support the development methods for identifying these mechanisms individual people, here we present an omic multidimensional spatial (OMS) atlas generated from four serial biopsies with breast cancer 3.5 years therapy. This resource links detailed, longitudinal clinical metadata that includes treatment times doses, anatomic...
There is an immediate and critical need for a rapid, broad-based genotyping method that can evaluate multiple mutations simultaneously in clinical cancer specimens identify patients most likely to benefit from targeted agents now use or late-stage development. We have implemented prospective approach characterize the frequency spectrum of amenable drug targeting present urothelial, colorectal, endometrioid, thyroid carcinomas melanoma. Cancer were enrolled Personalized Medicine Registry...
Abstract Sorafenib has substantial clinical activity as third- or fourth-line treatment of imatinib- and sunitinib-resistant gastrointestinal stromal tumors (GIST). Because sorafenib targets both angiogenesis-related kinases (VEGFR) the pathogenetic found in GIST (KIT PDGFRA), molecular basis for efficacy this setting remains unknown. We sought to determine spectrum against different mutant associated with drug-sensitive drug-resistant GIST. compared imatinib transiently expressed forms KIT...
Activating mutations of the receptor tyrosine kinase KIT are early events in development most gastrointestinal stromal tumors (GISTs). Although GISTs generally remain dependent on oncogenic during tumor progression, alone insufficient to induce malignant behavior. This is evidenced by KIT-mutant micro-GISTs, which present up one-third normal individuals, but virtually never progress malignancy. We performed whole exome sequencing 29 obtained from 21 patients with high grade or metastatic...
Molecular heterogeneity in metastatic breast cancer presents multiple clinical challenges accurately characterizing and treating the disease. Current diagnostic approaches offer limited ability to assess that exists among lesions throughout treatment course. We developed a precision oncology platform combines serial biopsies, multi-omic analysis, longitudinal patient monitoring, molecular tumor boards, with goal of improving management through enhanced understanding entire ecosystem within...
Gastrointestinal stromal tumors (GIST) carrying the D842V activating mutation in platelet-derived growth factor receptor alpha (PDGFRA) gene are a very rare subgroup of GIST (about 10%) known to be resistant conventional tyrosine kinase inhibitors (TKIs) and show an indolent behavior. In this study, we performed integrated molecular characterization mutant by whole-transcriptome whole-exome sequencing coupled with protein-ligand interaction modelling identify signature any additional...
Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of Cajal (ICCs) and are most common mesenchymal neoplasm gastrointestinal tract. While majority GISTs harbor activating mutations in either v-kit Hardy-Zuckerman feline sarcoma viral oncogene homolog (KIT) or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinases, approximately 10-15% adult 85% pediatric lack such mutations. These "wild-type" have been reported to express high levels insulin-like 1...
Abstract Resistant KIT mutations have hindered the development of kinase inhibitors for treatment patients with systemic mastocytosis. The goal this research was to characterize synergistic effects a novel combination therapy involving inhibition and calcineurin phosphatase, nuclear factor activated T cells (NFAT) regulator, using panel KIT-mutant mast cell lines. monotherapy or on cellular viability/survival were evaluated. In addition, NFAT-dependent transcriptional activity monitored in...
Summary Mechanisms of therapeutic resistance manifest in metastatic cancers as tumor cell intrinsic alterations and extrinsic microenvironmental influences that can change during treatment. To support the development methods for identification these mechanisms individual patients, we present here an Omic Multidimensional Spatial (OMS) Atlas generated from four serial biopsies a breast cancer patient 3.5 years therapy. This resource links detailed, longitudinal clinical metadata including...
10509 Background: Ponatinib (PO) is a multi-targeted tyrosine kinase inhibitor with potent pan-BCR-ABL activity that has recently been approved for treatment of CML and Ph + ALL. PO also inhibits the KIT. Approximately 80% gastrointestinal stromal tumors (GIST) contain primary activating KIT mutations, majority which cluster in exon 11. Imatinib (IM) 1 st line GIST; however, patients frequently relapse due to acquisition secondary resistance mutations located either ATP-binding pocket or...
• We present the clinical, roentgenographic, light-microscopic, immunohistochemical, and ultrastructural findings in two children with cranial fasciitis. A 7-year-old boy a 3-year-old girl presented rapidly expanding masses on scalp. Roentgenographic studies showed erosion of underlying cranium one case. Both lesions proliferations elongated spindle cells focally myxoid matrix, together areas hemorrhage, vascular proliferation, chronic inflammation. Occasional atypical nuclei were observed,...
e13514 Background: Dasatinib is a small molecule inhibitor of multiple oncogenic tyrosine kinase families, including SRC. Ixabepilone novel microtubule-stabilizing epothilone that has shown clinical activity in solid tumors. Preclinical data shows synergy between SRC inhibitors and agents. This phase I study evaluated the safety tolerability ixabepilone dasatinib patients with advanced Methods: Standard eligibility criteria cycle 1 dose-limiting toxicity (DLT) definitions were used. (Ixa)...
Comprehensive characterization of an individual's cancer using multi-omic analyses and expanding list targeted therapies is providing opportunity to uncover therapeutic vulnerabilities rationally target multiple driving alterations in the tumor. To leverage this opportunity, a multi-disciplinary team required unravel complexity tumor behavior genomic variant information, integrate data from assays, exploit potential synergies combination therapy while avoiding toxicity, all which occurs...