M C Heinrich

Summary

Affiliation: Oregon Health and Science University
Country: USA

Publications

  1. pmc Gene expression of the IGF pathway family distinguishes subsets of gastrointestinal stromal tumors wild type for KIT and PDGFRA
    Carol Beadling
    Knight Cancer Institute, Oregon Health and Science University Portland, Oregon Division of Hematology and Oncology, Oregon Health and Science University Portland, Oregon
    Cancer Med 2:21-31. 2013
  2. ncbi request reprint Regorafenib for treatment of advanced gastrointestinal stromal tumors
    Lindsay C Overton
    Portland VA Medical Center, Oregon Helath and Science University and OHSU Knight Cancer Institute, 3710 SW US Veterans Hospital Rd, Building 103 Lab E223, R and D 19, Portland OR 97239 2999, USA 1 503 220 3405 1 503 273 5158
    Expert Opin Pharmacother 15:549-58. 2014
  3. pmc Cell cycle-dependent activity of the novel dual PI3K-MTORC1/2 inhibitor NVP-BGT226 in acute leukemia
    Kerstin Maria Kampa-Schittenhelm
    Department of Hematology, Oncology, Rheumatology, Immunology and Pulmology, University Hospital Tubingen, Otfried Müller Straße 10, 72076, Tubingen, Germany
    Mol Cancer 12:46. 2013
  4. pmc Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms
    Kerstin Maria Kampa-Schittenhelm
    Department of Hematology, Oncology, Rheumatology, Immunology and Pulmology, University Hospital Tubingen, Tubingen, Germany
    Mol Cancer 12:19. 2013
  5. doi request reprint Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors
    Michael C Heinrich
    Portland VA Medical Center, Portland, OR, USA
    Clin Cancer Res 18:4375-84. 2012
  6. doi request reprint Sorafenib inhibits many kinase mutations associated with drug-resistant gastrointestinal stromal tumors
    Michael C Heinrich
    Division of Hematology Oncology, Department of Medicine, Portland VA Medical Center and OHSU Knight Cancer Institute, Oregon Health and Science University, R and D 19 3710 U S Veterans Hospital Road, Portland, OR 97239, USA
    Mol Cancer Ther 11:1770-80. 2012
  7. ncbi request reprint Molecular correlates of imatinib resistance in gastrointestinal stromal tumors
    Michael C Heinrich
    Division of Hematology Oncology, Department of Pathology, Oregon Health and Science University Cancer Institute, Oregon Health and Science University, Portland, OR, USA
    J Clin Oncol 24:4764-74. 2006
  8. ncbi request reprint PDGFRA activating mutations in gastrointestinal stromal tumors
    Michael C Heinrich
    Department of Medicine, Department of Pathology, Oregon Health and Science University Cancer Institute and Portland VA Medical Center, Portland, OR 97201, USA
    Science 299:708-10. 2003
  9. pmc Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Gr
    Michael C Heinrich
    Division of Hematology Oncology, Department of Medicine and Cell and Developmental Biology, Portland Veterans Affairs Medical Center and Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    J Clin Oncol 26:5360-7. 2008
  10. ncbi request reprint Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor)
    Michael C Heinrich
    Oregon Health and Science University Cancer Institute and Portland VA Medical Center, Portland, OR, USA
    J Clin Oncol 24:1195-203. 2006

Detail Information

Publications102 found, 100 shown here

  1. pmc Gene expression of the IGF pathway family distinguishes subsets of gastrointestinal stromal tumors wild type for KIT and PDGFRA
    Carol Beadling
    Knight Cancer Institute, Oregon Health and Science University Portland, Oregon Division of Hematology and Oncology, Oregon Health and Science University Portland, Oregon
    Cancer Med 2:21-31. 2013
    ..These results underscore the complexity and heterogeneity of wild-type GISTs that will need to be factored into molecularly-targeted therapeutic strategies...
  2. ncbi request reprint Regorafenib for treatment of advanced gastrointestinal stromal tumors
    Lindsay C Overton
    Portland VA Medical Center, Oregon Helath and Science University and OHSU Knight Cancer Institute, 3710 SW US Veterans Hospital Rd, Building 103 Lab E223, R and D 19, Portland OR 97239 2999, USA 1 503 220 3405 1 503 273 5158
    Expert Opin Pharmacother 15:549-58. 2014
    ..The toxicity profile is similar to other oral kinase inhibitors with anti-VEGFR activity. Regorafenib is mainly metabolized by CYP3A4, and concomitant use of strong inducers/inhibitors of this enzyme should be avoided. ..
  3. pmc Cell cycle-dependent activity of the novel dual PI3K-MTORC1/2 inhibitor NVP-BGT226 in acute leukemia
    Kerstin Maria Kampa-Schittenhelm
    Department of Hematology, Oncology, Rheumatology, Immunology and Pulmology, University Hospital Tubingen, Otfried Müller Straße 10, 72076, Tubingen, Germany
    Mol Cancer 12:46. 2013
    ..We now evaluated the antitumor efficacy of NVP-BGT226, a novel dual pan-PI3K and MTORC1/2 inhibitor, in acute leukemia...
  4. pmc Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms
    Kerstin Maria Kampa-Schittenhelm
    Department of Hematology, Oncology, Rheumatology, Immunology and Pulmology, University Hospital Tubingen, Tubingen, Germany
    Mol Cancer 12:19. 2013
    ..In vitro kinase assays have suggested that in addition to FLT3, quizartinib also targets related class III RTK isoforms...
  5. doi request reprint Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors
    Michael C Heinrich
    Portland VA Medical Center, Portland, OR, USA
    Clin Cancer Res 18:4375-84. 2012
    ..To determine the potential of crenolanib, a potent inhibitor of PDGFRA, to treat malignancies driven by mutant PDGFRA...
  6. doi request reprint Sorafenib inhibits many kinase mutations associated with drug-resistant gastrointestinal stromal tumors
    Michael C Heinrich
    Division of Hematology Oncology, Department of Medicine, Portland VA Medical Center and OHSU Knight Cancer Institute, Oregon Health and Science University, R and D 19 3710 U S Veterans Hospital Road, Portland, OR 97239, USA
    Mol Cancer Ther 11:1770-80. 2012
    ..These results have implications for the further development of treatments for drug-resistant GIST...
  7. ncbi request reprint Molecular correlates of imatinib resistance in gastrointestinal stromal tumors
    Michael C Heinrich
    Division of Hematology Oncology, Department of Pathology, Oregon Health and Science University Cancer Institute, Oregon Health and Science University, Portland, OR, USA
    J Clin Oncol 24:4764-74. 2006
    ..In clinical studies, 75% to 90% of patients with advanced GISTs experience clinical benefit from imatinib. However, imatinib resistance is an increasing clinical problem...
  8. ncbi request reprint PDGFRA activating mutations in gastrointestinal stromal tumors
    Michael C Heinrich
    Department of Medicine, Department of Pathology, Oregon Health and Science University Cancer Institute and Portland VA Medical Center, Portland, OR 97201, USA
    Science 299:708-10. 2003
    ..Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs...
  9. pmc Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Gr
    Michael C Heinrich
    Division of Hematology Oncology, Department of Medicine and Cell and Developmental Biology, Portland Veterans Affairs Medical Center and Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    J Clin Oncol 26:5360-7. 2008
    ..In previous studies, GIST genotype correlated with treatment outcome and optimal imatinib dosing...
  10. ncbi request reprint Clinical and molecular studies of the effect of imatinib on advanced aggressive fibromatosis (desmoid tumor)
    Michael C Heinrich
    Oregon Health and Science University Cancer Institute and Portland VA Medical Center, Portland, OR, USA
    J Clin Oncol 24:1195-203. 2006
    ..To determine the clinical efficacy of imatinib in patients with advanced aggressive fibromatosis (AF) and to identify the molecular basis of response/nonresponse to this agent...
  11. doi request reprint Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases
    Michael C Heinrich
    Department of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute and Portland VA Medical Center, Portland, Oregon 97239 3098, USA
    Clin Cancer Res 14:2717-25. 2008
    ..To evaluate the activity of imatinib in treating advanced, life-threatening malignancies expressing one or more imatinib-sensitive tyrosine kinases...
  12. ncbi request reprint Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor
    Michael C Heinrich
    R and D 19 3710 SW US Veterans Hospital Rd, Portland, OR 97207, USA
    J Clin Oncol 21:4342-9. 2003
    ..The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST...
  13. ncbi request reprint Gastric GI stromal tumors (GISTs): the role of surgery in the era of targeted therapy
    Michael C Heinrich
    OHSU Cancer Institute, Oregon Health and Science University and VA Medical Center, Portland, Oregon 97239, USA
    J Surg Oncol 90:195-207; discussion 207. 2005
    ..The importance of a multi-disciplinary approach using both surgery and imatinib therapy is emphasized...
  14. pmc Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor
    Michael C Heinrich
    Division of Hematology Oncology, Department of Medicine and Cell and Developmental Biology, Portland Veterans Affairs Medical Center and Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    J Clin Oncol 26:5352-9. 2008
    ..We evaluated the impact of primary and secondary kinase genotype on sunitinib activity...
  15. ncbi request reprint Targeting FLT3 kinase in acute myelogenous leukemia: progress, perils, and prospects
    Michael C Heinrich
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute and Portland VA Medical Center, Portland, OR 97201, USA
    Mini Rev Med Chem 4:255-71. 2004
    ..Inhibition of FLT3 kinase activity by small molecule inhibitors has been proposed as a novel therapeutic approach AML. The pre-clinical and clinical development of candidate FLT3 inhibitors will be reviewed...
  16. ncbi request reprint Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies
    Michael C Heinrich
    Department of Medicine, Division of Hematology Oncology, Oregon Health and Science University, USA
    J Clin Oncol 20:1692-703. 2002
    ..In this review, we discuss the rationale for and development of KIT tyrosine kinase inhibitors for the treatment of human malignancies...
  17. ncbi request reprint Is KIT an important therapeutic target in small cell lung cancer?
    Michael C Heinrich
    Oregon Health and Science University Cancer Institute and Portland Veterans Affairs Medical Center, Portland, Oregon 97201, USA
    Clin Cancer Res 9:5825-8. 2003
  18. ncbi request reprint Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor
    M C Heinrich
    Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health Sciences University, and Portland Veterans Affairs Medical Center, USA
    Blood 96:925-32. 2000
    ..This compound may be useful in treating cancers associated with increased c-kit kinase activity...
  19. ncbi request reprint Posttranscriptional cell cycle-dependent regulation of human FANCC expression
    M C Heinrich
    Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health Sciences University and Portland Veterans Affairs Medical Center, Portland, OR 97207, USA
    Blood 95:3970-7. 2000
    ..Our observation of dynamic control of FANCC expression by the proteasome has important implications for understanding the molecular regulation of the multiprotein complex. (Blood. 2000;95:3970-3977)..
  20. ncbi request reprint Mutations of the BCR-ABL-kinase domain occur in a minority of patients with stable complete cytogenetic response to imatinib
    D W Sherbenou
    Cell and Developmental Biology, Oregon Health and Science University, Portland, OR 97239, USA
    Leukemia 21:489-93. 2007
    ..BCR-ABL-kinase domain mutations in patients with a stable CCR are infrequent, and their detection does not consistently predict relapse. Alternative mechanisms must be responsible for disease persistence in the majority of patients...
  21. ncbi request reprint PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib
    Christopher L Corless
    Department of Pathology, Division of Hematology and Oncology, Oregon Health and Science University Cancer Institute, Portland, OR 97201, USA
    J Clin Oncol 23:5357-64. 2005
    ..Little is known of the other types of PDGFRA mutations that occur in GISTs...
  22. ncbi request reprint Transforming growth factor beta 1 inhibits expression of the gene products for steel factor and its receptor (c-kit)
    M C Heinrich
    Department of Medicine, Oregon Health Sciences University, Portland, USA
    Blood 85:1769-80. 1995
    ....
  23. pmc Heterogeneity of kinase inhibitor resistance mechanisms in GIST
    B Liegl
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Pathol 216:64-74. 2008
    ..Our observations underscore the heterogeneity of clinical TKI resistance, and highlight the therapeutic challenges involved in salvaging patients after clinical progression on TKI monotherapies...
  24. ncbi request reprint The Fanconi anemia group C gene product is located in both the nucleus and cytoplasm of human cells
    M E Hoatlin
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland, OR 97201, USA
    Blood 91:1418-25. 1998
    ..Therefore, while cytoplasmic localization of this protein appears to be functionally important, it may also exert some essential nuclear function...
  25. ncbi request reprint Germ cell defects and hematopoietic hypersensitivity to gamma-interferon in mice with a targeted disruption of the Fanconi anemia C gene
    M A Whitney
    Department of Molecular and Medical Genetics, Vollum Institute, Oregon Regional Primate Center, Portland, USA
    Blood 88:49-58. 1996
    ..Progenitor cells from fac knock-out mice were hypersensitive to interferon gamma. This previously unrecognized phenotype may form the basis for BM failure in human FA...
  26. ncbi request reprint Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies
    Marcus M Schittenhelm
    Department of Medicine, Division of Hematology Oncology, Oregon Health and Science University, Portland, USA
    Cancer Res 66:473-81. 2006
    ..Our studies suggest that dasatinib may have clinical efficacy against human neoplasms that are associated with gain-of-function KIT mutations...
  27. ncbi request reprint Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c-kit
    A E Rader
    Department of Pathology, Oregon Health Sciences University, Portland, Oregon 97201 3098, USA
    Cancer 93:269-75. 2001
    ..The aim of the current study was to employ immunocytochemistry and mutational analysis of the c-kit gene to aid in the diagnosis of GISTs on FNAB...
  28. ncbi request reprint KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications
    Fabiola Medeiros
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Am J Surg Pathol 28:889-94. 2004
    ..Notably, some KIT-negative GISTs contain imatinib-sensitive KIT or PDGFRA mutations; therefore, patients with KIT-negative GISTs should not, a priori, be denied imatinib therapy...
  29. ncbi request reprint SU5416 and SU5614 inhibit kinase activity of wild-type and mutant FLT3 receptor tyrosine kinase
    Kevin W H Yee
    Department of Medicine, Division of Hematology and Medical Oncology, Oregon Health and Science University, and Portland Veterans Affairs Medical Center, Portland, OR 97201, USA
    Blood 100:2941-9. 2002
    ..We conclude that SU5416 and SU5614 are potent inhibitors of FLT3. Our finding that inhibition of FLT3 induces apoptosis of leukemic cells supports the feasibility of targeting FLT3 as a novel treatment strategy for AML...
  30. ncbi request reprint A functional genomics approach to Kaposi's sarcoma
    Ashlee V Moses
    Vaccine and Gene Therapy Institute and Department of Molecular Microbiology and Immunology, Oregon Health Science University, Portland, Oregon 97239, USA
    Ann N Y Acad Sci 975:180-91. 2002
    ..J. Virol. 76(16): 8383-8399). These data demonstrate that microarrays are useful for the identification of pharmacological targets essential for KS tumorigenesis...
  31. ncbi request reprint Activating alleles of JAK3 in acute megakaryoblastic leukemia
    Denise K Walters
    Howard Hughes Medical Institute, Portland, Oregon 97239, USA
    Cancer Cell 10:65-75. 2006
    ..These findings illustrate the biological importance of gain-of-function JAK3 mutations in leukemogenesis and demonstrate the utility of proteomic approaches to identifying clinically relevant mutations...
  32. ncbi request reprint Gastrointestinal stromal tumors
    C D Blanke
    Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health and Science University and Portland Veterans Affairs Medical Center, MC OP28, 3181 S W Sam Jackson Park Road, Portland, OR 97201, USA
    Curr Treat Options Oncol 2:485-91. 2001
    ..Its use can serve as a paradigm for designing molecularly targeted therapies for other malignancies...
  33. ncbi request reprint Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles
    Subbaya Subramanian
    Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA
    Oncogene 23:7780-90. 2004
    ..These gene products could serve as highly selective therapeutic targets in GISTs containing the KIT or PDGFRA mutational types with which they are associated...
  34. ncbi request reprint Protein Kinase C theta (PKCtheta) expression and constitutive activation in gastrointestinal stromal tumors (GISTs)
    Anette Duensing
    Department of Pathology, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Cancer Res 64:5127-31. 2004
    ..PKCtheta is strongly activated in most GISTs and hence may serve, along with KIT/PDGFRA, as a novel therapeutic target...
  35. ncbi request reprint Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis
    Ian J Griswold
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland 97239, USA
    Blood 104:2912-8. 2004
    ..In analogy to imatinib mesylate in BCR-ABL-positive acute leukemia, MLN518-induced remissions may not be durable. Our studies provide the basis for integrating this compound into chemotherapy and transplantation protocols...
  36. ncbi request reprint Detection of ABL kinase domain mutations with denaturing high-performance liquid chromatography
    M W N Deininger
    Oregon Health and Science University Cancer Institute, Portland, OR 97201 L592, USA
    Leukemia 18:864-71. 2004
    ..Early detection of emerging mutant clones may aid in guiding decisions regarding alternative treatment options...
  37. ncbi request reprint A single nucleotide polymorphism in the coding region of ABL and its effects on sensitivity to imatinib
    L C Crossman
    Oregon Health and Science University Cancer Institute, Portland, OR, USA
    Leukemia 19:1859-62. 2005
    ..Clinicians should be aware that possession of the arginine allele of K247R does not reflect a mutation that necessitates a change in the therapeutic strategy, unless there are other signs of inadequate response to drug...
  38. ncbi request reprint FLT3 K663Q is a novel AML-associated oncogenic kinase: Determination of biochemical properties and sensitivity to Sunitinib (SU11248)
    M M Schittenhelm
    Department of Pathology and Medicine, Oregon Health and Science University Cancer Institute and Portland Veterans Affairs Medical Center, Portland, OR 97239, USA
    Leukemia 20:2008-14. 2006
    ..We conclude that FLT3 mutations in AML can involve novel regions of the TK1. Future studies are needed to define the incidence and prognostic significance of FLT3 mutations outside the well-established JM and AL regions...
  39. ncbi request reprint Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations
    Michael C Heinrich
    Department of Medicine, Division of Hematology Oncology, Oregon Health Sciences University and Portland VA Medical Center, USA
    Hum Pathol 33:484-95. 2002
    ..These cytogenetic aberrations are undoubtedly important in GIST pathogenesis, but currently they do not play a key role as diagnostic adjuncts...
  40. ncbi request reprint In vitro and in vivo activity of ATP-based kinase inhibitors AP23464 and AP23848 against activation-loop mutants of Kit
    Amie S Corbin
    Oregon Health and Science University, Cancer Institute, L592, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 106:227-34. 2005
    ..Thus, AP23464 and AP23848 potently and selectively target activation-loop mutants of Kit in vitro and in vivo and could have therapeutic potential against D816V-expressing malignancies...
  41. ncbi request reprint Primary extragastrointestinal stromal tumor of the pleura: report of a unique case with genetic confirmation
    Kevin B Long
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Am J Surg Pathol 34:907-12. 2010
    ..This seems to be the first EGIST arising above the diaphragm. This case shows a potential diagnostic pitfall with therapeutic consequences...
  42. ncbi request reprint Biology of gastrointestinal stromal tumors
    Christopher L Corless
    Oregon Health and Science University Cancer Institute, Department of Pathology, Portland, OR, USA
    J Clin Oncol 22:3813-25. 2004
    ..In addition, the role of mutation screening in KIT and PDGFRA as a diagnostic and prognostic aid is emphasized in this review...
  43. ncbi request reprint Pediatric KIT wild-type and platelet-derived growth factor receptor alpha-wild-type gastrointestinal stromal tumors share KIT activation but not mechanisms of genetic progression with adult gastrointestinal stromal tumors
    Katherine A Janeway
    Department of Medicine, Children s Hospital Boston, MA, USA
    Cancer Res 67:9084-8. 2007
    ..KIT activation levels in pediatric KIT-wild-type GISTs are comparable with those in KIT-mutant GISTs. Therapies that inhibit KIT activation, or crucial KIT signaling intermediates, should be explored in pediatric KIT-wild-type GIST...
  44. ncbi request reprint Targeting mutant kinases in gastrointestinal stromal tumors: a paradigm for molecular therapy of other sarcomas
    Michael C Heinrich
    Department of Medicine, Oregon Health Science University Cancer Institute, Portland VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, OR 97201, USA
    Cancer Treat Res 120:129-50. 2004
  45. ncbi request reprint Biology of gastrointestinal stromal tumors: KIT mutations and beyond
    Anette Duensing
    Department of Pathology, Brigham and Women s Hospital, 75 Francis St, Boston, MA 02115, USA
    Cancer Invest 22:106-16. 2004
    ..This review focuses on the biological and molecular genetic principles of GISTs, and particularly the role of mutant KIT as a therapeutic target...
  46. ncbi request reprint Phase II study of imatinib mesylate in chemotherapy refractory germ cell tumors expressing KIT
    Lawrence H Einhorn
    Department of Medicine, Division of Hematology Oncology, Indiana University, Indianapolis, Indiana and Walther Cancer Institute, Indianapolis, IN, USA
    Am J Clin Oncol 29:12-3. 2006
    ..This phase II study was conducted to determine the activity of imatinib (gleevec) in heavily pretreated patients with KIT-positive metastatic germ cell tumor...
  47. pmc KIT mutations are common in testicular seminomas
    Kathleen Kemmer
    Division of Hematology and Oncology, Oregon Health and Science University Cancer Institute and Portland Veterans Affairs Medical Center, Portland, Oregon 97239, USA
    Am J Pathol 164:305-13. 2004
    ..These findings suggest that activating KIT mutations may contribute to tumorigenesis in a subset of seminomas, but are not involved in NSGCT...
  48. ncbi request reprint BRAF in papillary thyroid carcinoma of ovary (struma ovarii)
    Jason Schmidt
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Am J Surg Pathol 31:1337-43. 2007
    ..In this study, we explored the possible role of these genes in the development of BSO and MSO...
  49. ncbi request reprint The gene expression profile of extraskeletal myxoid chondrosarcoma
    Subbaya Subramanian
    Department of Pathology, Stanford University Medical Center, Stanford, CA 94035, USA
    J Pathol 206:433-44. 2005
    ..Small molecule inhibitors for PPARG exist and PPARG could be a potential therapeutic target for EMC...
  50. ncbi request reprint Sensitivity of oncogenic KIT mutants to the kinase inhibitors MLN518 and PD180970
    Amie S Corbin
    Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Blood 104:3754-7. 2004
    ..As phase 1 clinical trials of MLN518 in AML have shown little toxicity, our data suggest MLN518 is a promising candidate for the treatment of SM or AML with KIT mutations...
  51. pmc Repression of Fanconi anemia gene (FACC) expression inhibits growth of hematopoietic progenitor cells
    G M Segal
    Department of Medicine, Oregon Health Sciences University, Portland 97201 3098
    J Clin Invest 94:846-52. 1994
    ..We conclude that, while the FACC gene product plays a role in defining cellular tolerance to cross-linking agents, it also functions to regulate growth, differentiation, and/or survival of normal hematopoietic progenitor cells...
  52. ncbi request reprint In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, Portland 97239, USA
    Cancer Res 65:4500-5. 2005
    ..Thus, both inhibitors hold promise for treating imatinib-refractory CML...
  53. pmc The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status
    Robert B West
    Department of Pathology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA
    Am J Pathol 165:107-13. 2004
    ..Reactivity for DOG1 may aid in the diagnosis of GISTs, including PDGFRA mutants that fail to express KIT antigen, and lead to appropriate treatment with imatinib mesylate, an inhibitor of the KIT tyrosine kinase...
  54. pmc MET receptor sequence variants R970C and T992I lack transforming capacity
    Jeffrey W Tyner
    Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, Oregon 97239, USA
    Cancer Res 70:6233-7. 2010
    ....
  55. pmc Allele-specific polymerase chain reaction for the imatinib-resistant KIT D816V and D816F mutations in mastocytosis and acute myelogenous leukemia
    Christopher L Corless
    OHSU Dept of Pathology L471, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
    J Mol Diagn 8:604-12. 2006
    ..Thus, the assay may be useful in confirming the diagnosis of SM...
  56. doi request reprint Phosphatidylinositol-3-kinase and AKT1 mutations occur early in breast carcinoma
    Jennifer Dunlap
    Department of Pathology, Oregon Health and Science University, L471, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA
    Breast Cancer Res Treat 120:409-18. 2010
    ....
  57. pmc RNAi screen for rapid therapeutic target identification in leukemia patients
    Jeffrey W Tyner
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Proc Natl Acad Sci U S A 106:8695-700. 2009
    ..Combination of this technique with whole-genome sequencing will represent an ideal tool for oncogenic target identification such that specific therapies can be matched with individual patients...
  58. doi request reprint Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033
    Charles D Blanke
    Oregon Health and Science University Cancer Institute, 3181 SW Sam Jackson Park Rd, L 586, Portland, OR 97239, USA
    J Clin Oncol 26:626-32. 2008
    ....
  59. doi request reprint High prevalence of PIK3CA/AKT pathway mutations in papillary neoplasms of the breast
    Megan L Troxell
    Department of Pathology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA
    Mod Pathol 23:27-37. 2010
    ..These findings indicate that approximately two-thirds of papillomas are driven by mutations in the PI3CA/AKT pathway. Some papillary carcinomas may arise from these lesions, but others may have different molecular origins...
  60. ncbi request reprint Synergistic effect of SU11248 with cytarabine or daunorubicin on FLT3 ITD-positive leukemic cells
    Kevin W H Yee
    Oregon Health and Sciences University Cancer Institute and Portland Veterans Affairs Medical Center, Portland, OR, USA
    Blood 104:4202-9. 2004
    ..These data suggest that the addition of potent FLT3 inhibitors such as SU11248 to AML chemotherapy regimens could result in improved treatment results...
  61. pmc Kaposi's sarcoma-associated herpesvirus-induced upregulation of the c-kit proto-oncogene, as identified by gene expression profiling, is essential for the transformation of endothelial cells
    Ashlee V Moses
    Vaccine and Gene Therapy Institute, Portland, Oregon 97201, USA
    J Virol 76:8383-99. 2002
    ..Furthermore, overexpression studies showed that c-Kit was sufficient to induce spindle cell formation. Together, these data demonstrate an essential role for c-Kit in KS tumorigenesis and reveal a target for pharmacological intervention...
  62. pmc KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size
    Christopher L Corless
    Department of Pathology, Division of Hematology Oncology, Oregon Health and Science University, Portland, 97201, USA
    Am J Pathol 160:1567-72. 2002
    ..The findings suggest that KIT mutations per se are of little prognostic importance in GISTs...
  63. pmc KIT gene deletions at the intron 10-exon 11 boundary in GI stromal tumors
    Christopher L Corless
    Department of Pathology, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    J Mol Diagn 6:366-70. 2004
    ..Laboratories that offer clinical screening for KIT mutations in GI stromal tumors should be aware of this class of mutations...
  64. ncbi request reprint Phosphoproteomic analysis of AML cell lines identifies leukemic oncogenes
    Denise K Walters
    Department of Hematology and Oncology, Howard Hughes Medical Institute, Oregon Health and Science University Cancer Institute, 3181 Sam Jackson Park Road, and Portland VA Medical Center, Portland, OR 97239, USA
    Leuk Res 30:1097-104. 2006
    ..This study illustrates the benefit of LC-MS/MS mass spectrometry and siRNA for the identification of novel targets and mutations...
  65. ncbi request reprint RNAi-induced down-regulation of FLT3 expression in AML cell lines increases sensitivity to MLN518
    Denise K Walters
    Department of Hematology and Oncology, Howard Hughes Medical Institute, Oregon Health and Science University, and Portland Veterans Affairs VA Medical Center, 3181 Sam Jackson Park Rd, Portland, OR 97239, USA
    Blood 105:2952-4. 2005
    ..Furthermore, siRNA-induced down-regulation of FLT3 increased the sensitivity of both cell lines to treatment with the FLT3 inhibitor MLN518. This illustrates the potential benefit of combined therapeutic approaches...
  66. doi request reprint Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT
    Charles D Blanke
    Oregon Health and Science University Cancer Center and Portland Veterans Affairs Hospital, Portland, OR, USA
    J Clin Oncol 26:620-5. 2008
    ..We conducted a long-term analysis of patients treated on the trial, including patients followed during an extension phase, to evaluate survival, patterns of failure, and potential prognostic factors, including tumor mutational status...
  67. ncbi request reprint Pure red cell aplasia associated with parvovirus B19 infection occurring late after allogeneic bone marrow transplantation
    Brandon Hayes-Lattin
    Adult Bone Marrow Transplant Program, Division of Hematology and Medical Oncology, Oregon Health and Science University, The OHSU Cancer Institute, Portland, Oregon 97239, USA
    Am J Hematol 75:142-5. 2004
    ..Characteristics of parvovirus B19 infection and the immunosuppressed state after allogeneic stem cell transplantation are reviewed...
  68. ncbi request reprint Combined Abl inhibitor therapy for minimizing drug resistance in chronic myeloid leukemia: Src/Abl inhibitors are compatible with imatinib
    Thomas O'Hare
    Howard Hughes Medical Institute, Oregon Health and Science University, Portland 97239, USA
    Clin Cancer Res 11:6987-93. 2005
    ..As combination therapy is frequently used to prevent emergence of resistance, the combination of imatinib with an inhibitor of imatinib-resistant Bcr-Abl mutants (e.g., Src/Abl inhibitors AP23848 and BMS-354825) was investigated...
  69. ncbi request reprint Molecular pathobiology of gastrointestinal stromal sarcomas
    Christopher L Corless
    Department of Pathology, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Annu Rev Pathol 3:557-86. 2008
    ....
  70. doi request reprint A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors
    Inigo Espinosa
    Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA
    Am J Surg Pathol 32:210-8. 2008
    ..5%) synovial sarcomas among the 935 soft tissue tumors examined showed positive immunostaining for DOG1.1. In addition, DOG1.1 immunoreactivity was seen in fewer cases of carcinoma, melanoma, and seminoma as compared with KIT...
  71. pmc Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation
    Jason Gotlib
    Department of Medicine, Division of Hematology, Stanford University, Stanford Cancer Center, 875 Blake Wilbur Dr, Rm 2327B, Stanford, CA 94305 5821, USA
    Blood 106:2865-70. 2005
    ..This case indicates that KIT tyrosine kinase inhibition is a feasible approach in SM, but single-agent clinical efficacy may be limited by clonal evolution in the advanced leukemic phase of this disease...
  72. ncbi request reprint STI571: a paradigm of new agents for cancer therapeutics
    Michael J Mauro
    Leukemia Program, Division of Hematology and Medical Oncology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97201, USA
    J Clin Oncol 20:325-34. 2002
    ..Lastly, the potential use of STI571 in other malignancies and the translation of this paradigm to other malignancies are explored...
  73. pmc RNAi screening of the tyrosine kinome identifies therapeutic targets in acute myeloid leukemia
    Jeffrey W Tyner
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, Portland, USA
    Blood 111:2238-45. 2008
    ..This technique, with additional development, might eventually offer the potential to match specific therapies with individual patients based on a functional assay...
  74. ncbi request reprint A human gene coding for a membrane-associated nucleic acid-binding protein
    D C Siess
    Departments of Immunology, Pulmonology and Hematology, Veterans Affairs Medical Center, Portland, Oregon 97201, USA
    J Biol Chem 275:33655-62. 2000
    ..Characterization of the MNAB protein as a cell-surface DNA-binding protein, critical in binding and internalization of extracellular DNA, awaits confirmation of its localization to cell surfaces...
  75. doi request reprint KIT gene mutations and copy number in melanoma subtypes
    Carol Beadling
    Oregon Cancer Institute, Oregon Health and Science University, Portland, Oregon 97239, USA
    Clin Cancer Res 14:6821-8. 2008
    ..To determine the frequency of KIT mutations across melanoma subtypes, we surveyed a large series of tumors...
  76. ncbi request reprint The effects of the Fanconi anemia zinc finger (FAZF) on cell cycle, apoptosis, and proliferation are differentiation stage-specific
    Mu Shui Dai
    Division of Molecular Medicine, Oregon Health and Science University, Portland, Oregon 97201, USA
    J Biol Chem 277:26327-34. 2002
    ..These results suggest an essential role for FAZF during the proliferative stages of primitive hematopoietic progenitors, possibly acting in concert with (a subset of) the Fanconi anemia proteins...
  77. doi request reprint Chemotherapy and dasatinib induce long-term hematologic and molecular remission in systemic mastocytosis with acute myeloid leukemia with KIT D816V
    Celalettin Ustun
    Medical College of Georgia, Department of Medicine, Section of Hematology Oncology, Augusta, GA 30912 3125, USA
    Leuk Res 33:735-41. 2009
    ..Along with chemotherapy, dasatinib should be considered in these patients particularly if they cannot undergo allogeneic stem cell transplantation for this poor prognostic AML...
  78. pmc Ménétrier disease and gastrointestinal stromal tumors: hyperproliferative disorders of the stomach
    Robert J Coffey
    Department of Medicine, Vanderbilt University Medical Center and Nashville Veterans Affairs Medical Center, Nashville, Tennessee, USA
    J Clin Invest 117:70-80. 2007
    ....
  79. ncbi request reprint Dermatofibrosarcoma protuberans: a partial response to imatinib therapy
    Khosrow Mehrany
    Department of Dermatology, Oregon Health and Science University, and Oregon Health and Cancer Institute, Portland, Oregon 97239, USA
    Dermatol Surg 32:456-9. 2006
  80. ncbi request reprint MicroRNA expression signature of human sarcomas
    S Subramanian
    Department of Pathology, Stanford University, Stanford, CA 94305, USA
    Oncogene 27:2015-26. 2008
    ..The identification of unique miRNA signatures in each tumor type may indicate their role in tumorigenesis and may aid in diagnosis of soft tissue sarcomas...
  81. pmc High-throughput sequence analysis of the tyrosine kinome in acute myeloid leukemia
    Marc M Loriaux
    Division of Hematology and Medical Oncology, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Blood 111:4788-96. 2008
    ....
  82. pmc High-throughput sequencing screen reveals novel, transforming RAS mutations in myeloid leukemia patients
    Jeffrey W Tyner
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Blood 113:1749-55. 2009
    ....
  83. ncbi request reprint Absence of BRAF and NRAS mutations in uveal melanoma
    Frank Cruz
    Oregon Health and Science University OHSU Cancer Institute, Department of Pathology, OHSU and Portland Veterans Affairs Medical Center, Portland, Oregon 97239, USA
    Cancer Res 63:5761-6. 2003
    ..No NRAS exon 1 mutations were detected in either type of melanoma. We conclude that UMs arise independent of oncogenic BRAF and NRAS mutations, an observation that may have implications for therapies targeted to the NRAS-BRAF pathway...
  84. ncbi request reprint Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: Imatinib Target Exploration Consortium Study B2225
    Grant A McArthur
    Peter MacCallum Cancer Centre, East Melbourne, Australia
    J Clin Oncol 23:866-73. 2005
    ..The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib...
  85. ncbi request reprint Gastrointestinal stromal tumors: insights from a new familial GIST kindred with unusual genetic and pathologic features
    Ciarán O'Riain
    Department of Histopathology, St Vincent s University Hospital, Elm Park, Dublin, Ireland
    Am J Surg Pathol 29:1680-3. 2005
    ..Two smaller lesions from this patient were heterozygous for the mutation. This phenomenon has been observed in up to 8% of sporadic malignant GISTs but has not been documented in familial disease...
  86. ncbi request reprint Familial gastrointestinal stromal tumor syndrome: phenotypic and molecular features in a kindred
    Frederick P Li
    Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    J Clin Oncol 23:2735-43. 2005
    ..A tumor from the proband was analyzed to compare features with sporadic GISTs...
  87. ncbi request reprint Extragastrointestinal stromal tumors presenting as vulvovaginal/rectovaginal septal masses: a diagnostic pitfall
    Maggie M Lam
    Department of Anatomic Pathology, University of Washington Medical Center, Seattle, WA 98195, USA
    Int J Gynecol Pathol 25:288-92. 2006
    ..Thus, it is imperative to consider EGISTs in the differential diagnosis of mesenchymal neoplasms in the vulvovaginal/rectovaginal septum...
  88. pmc Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics
    Daniel J DeAngelo
    Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Blood 108:3674-81. 2006
    ..Tandutinib at the MTD (525 mg twice daily) should be evaluated more extensively in patients with AML with FLT3-ITD mutations to better define its antileukemic activity...
  89. pmc Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects
    Christophe Borg
    Department of Clinical Biology, Equipe de Recherche Mixte 0208, INSERM, Institut Gustave Roussy, Villejuif, France
    J Clin Invest 114:379-88. 2004
    ..These data point to a novel mode of antitumor action for Gleevec...
  90. ncbi request reprint Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial
    George D Demetri
    Ludwig Center at Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Lancet 368:1329-38. 2006
    ....
  91. ncbi request reprint Clinical management of gastrointestinal stromal tumors: before and after STI-571
    Ronald P Dematteo
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Hum Pathol 33:466-77. 2002
    ..The advent of STI-571 has markedly altered the clinical approach to GIST. It has proven to be effective in metastatic GIST and is also under investigation as a neoadjuvant and adjuvant therapy...
  92. ncbi request reprint An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients
    Anne Marie O'Farrell
    SUGEN Inc, South San Francisco, California, USA
    Clin Cancer Res 9:5465-76. 2003
    ..Study drug-related adverse events occurred in 31% of patients, mainly grade 1 or 2 diarrhea and nausea, at higher dose levels...
  93. ncbi request reprint Clonal evolution of resistance to imatinib in patients with metastatic gastrointestinal stromal tumors
    Jayesh Desai
    Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Clin Cancer Res 13:5398-405. 2007
    ..The objective of this study was to correlate molecular and radiologic patterns of imitinib-refractory disease with existing conventional criteria for disease progression...
  94. ncbi request reprint Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib
    Petri Bono
    Department of Oncology, University Central Hospital of Helsinki, Helsinki, Finland
    Blood 103:2929-35. 2004
    ..1-259-fold). A high serum SCF/KIT ratio may increase SCF-induced cell signaling with prolonged imatinib treatment, at the time when imatinib treatment is withdrawn, and in patients whose GIST has wild-type receptors...
  95. doi request reprint Clinicopathologic profile of gastrointestinal stromal tumors (GISTs) with primary KIT exon 13 or exon 17 mutations: a multicenter study on 54 cases
    Jerzy Lasota
    Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306 6000, USA
    Mod Pathol 21:476-84. 2008
    ..The latter is also true for all KIT exon 17 mutant GISTs...
  96. ncbi request reprint Epithelioid gastric stromal tumours of the antrum in young females with the Carney triad: a report of three new cases with mutational analysis and comparative genomic hybridization
    Abbas Agaimy
    Institute of Pathology, Klinikum Nürnberg, 90419 Nurnberg, Germany
    Oncol Rep 18:9-15. 2007
    ....
  97. ncbi request reprint Response to imatinib mesylate of a gastrointestinal stromal tumor with very low expression of KIT
    Sebastian Bauer
    Department of Internal Medicine Cancer Research, University of Essen Medical School, Germany
    Cancer Chemother Pharmacol 51:261-5. 2003
    ..Our experience with this patient suggests that even GISTs with very low levels of KIT expression may respond to imatinib mesylate therapy...
  98. pmc Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study
    Eric Raymond
    Service inter hospitalier de cancérologie, Beaujon University Hospital, Clichy
    J Clin Oncol 26:4659-65. 2008
    ..To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas...
  99. ncbi request reprint SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo
    Anne Marie O'Farrell
    Preclinical Research and Exploratory Development, SUGEN, South San Francisco, CA 94080, USA
    Blood 101:3597-605. 2003
    ..These results suggest that further exploration of SU11248 activity in AML patients is warranted...
  100. ncbi request reprint Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors
    George D Demetri
    Dana Farber Cancer Institute and Harvard Cancer Center, Boston, MA 02115, USA
    N Engl J Med 347:472-80. 2002
    ..Imatinib mesylate, a selective tyrosine kinase inhibitor, has been shown in preclinical models and preliminary clinical studies to have activity against such tumors...
  101. ncbi request reprint Gastrointestinal stromal tumour
    Brian P Rubin
    Department of Anatomic Pathology, Taussig Cancer Center and the Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Lancet 369:1731-41. 2007
    ..The important interplay between the molecular genetics of gastrontestinal stromal tumour and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumours...