proto oncogene proteins c kit

Summary

Alias: proto oncogene protein c kit
Summary: A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.

Top Publications

  1. ncbi Bone marrow cells regenerate infarcted myocardium
    D Orlic
    Hematopoiesis Section, Genetics and Molecular Biology Branch, NHGRI, NIH, Bethesda, MD 20892, USA
    Nature 410:701-5. 2001
  2. ncbi Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain
    Lixin Sun
    Neuro Oncology Branch, National Cancer Institute National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cancer Cell 9:287-300. 2006
  3. ncbi Motesanib diphosphate in progressive differentiated thyroid cancer
    Steven I Sherman
    Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M D Anderson Cancer Center, Houston 77230 1402, USA
    N Engl J Med 359:31-42. 2008
  4. ncbi Diagnosis of gastrointestinal stromal tumors: A consensus approach
    Christopher D M Fletcher
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston MA 02115, USA
    Hum Pathol 33:459-65. 2002
  5. ncbi Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis
    Markku Miettinen
    Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306 6000, USA
    Arch Pathol Lab Med 130:1466-78. 2006
  6. ncbi 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
  7. ncbi Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors
    S Hirota
    Department of Pathology, Osaka University Medical School, Yamada oka 2 2, Suita 565, Japan
    Science 279:577-80. 1998
  8. pmc Mast cell-deficient W-sash c-kit mutant Kit W-sh/W-sh mice as a model for investigating mast cell biology in vivo
    Michele A Grimbaldeston
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305 5324, USA
    Am J Pathol 167:835-48. 2005
  9. ncbi W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity
    J D Huizinga
    Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
    Nature 373:347-9. 1995
  10. pmc Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis
    V H Secor
    Graduate Program in Immunology and Molecular Pathogenesis, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Exp Med 191:813-22. 2000

Detail Information

Publications267 found, 100 shown here

  1. ncbi Bone marrow cells regenerate infarcted myocardium
    D Orlic
    Hematopoiesis Section, Genetics and Molecular Biology Branch, NHGRI, NIH, Bethesda, MD 20892, USA
    Nature 410:701-5. 2001
    ..The developing tissue comprised proliferating myocytes and vascular structures. Our studies indicate that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease...
  2. ncbi Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain
    Lixin Sun
    Neuro Oncology Branch, National Cancer Institute National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cancer Cell 9:287-300. 2006
    ..Thus, the SCF/c-Kit pathway plays an important role in tumor- and normal host cell-induced angiogenesis within the brain...
  3. ncbi Motesanib diphosphate in progressive differentiated thyroid cancer
    Steven I Sherman
    Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M D Anderson Cancer Center, Houston 77230 1402, USA
    N Engl J Med 359:31-42. 2008
    ..Motesanib diphosphate (AMG 706) is a novel oral inhibitor of VEGF receptors, platelet-derived growth-factor receptor, and KIT...
  4. ncbi Diagnosis of gastrointestinal stromal tumors: A consensus approach
    Christopher D M Fletcher
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston MA 02115, USA
    Hum Pathol 33:459-65. 2002
    ....
  5. ncbi Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis
    Markku Miettinen
    Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306 6000, USA
    Arch Pathol Lab Med 130:1466-78. 2006
    ..They are believed to originate from interstitial cells of Cajal or related stem cells...
  6. ncbi 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...
  7. ncbi Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors
    S Hirota
    Department of Pathology, Osaka University Medical School, Yamada oka 2 2, Suita 565, Japan
    Science 279:577-80. 1998
    ..GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34...
  8. pmc Mast cell-deficient W-sash c-kit mutant Kit W-sh/W-sh mice as a model for investigating mast cell biology in vivo
    Michele A Grimbaldeston
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305 5324, USA
    Am J Pathol 167:835-48. 2005
    ..Thus, Kit(W-sh/W-sh) mice represent a useful model for mast cell research, especially for analyzing mast cell function in vivo...
  9. ncbi W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity
    J D Huizinga
    Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
    Nature 373:347-9. 1995
    ....
  10. pmc Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis
    V H Secor
    Graduate Program in Immunology and Molecular Pathogenesis, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Exp Med 191:813-22. 2000
    ..These data provide a new mechanism for immune destruction in EAE and indicate that mast cells play a broader role in neurologic inflammation...
  11. ncbi 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...
  12. ncbi Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors
    Seiichi Hirota
    Department of Pathology, Osaka University Medical School, Suita, Japan
    Gastroenterology 125:660-7. 2003
    ..We investigated the cause of GISTs without KIT mutations. Because GISTs apparently expressed platelet-derived growth factor receptor (PDGFR) alpha, we examined whether GISTs without KIT mutations had a mutation of PDGFR alpha...
  13. ncbi KIT activation is a ubiquitous feature of gastrointestinal stromal tumors
    B P Rubin
    Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
    Cancer Res 61:8118-21. 2001
    ..These studies underscore the role of KIT activation in GIST pathogenesis, and they suggest that activated KIT might represent a universal therapeutic target in GISTs...
  14. ncbi The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations
    Yongsheng Ma
    Department of Dermatology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Blood 99:1741-4. 2002
    ..Furthermore, these results help establish a general paradigm whereby classification of mutations affecting oncogenic enzymes as RT or EST may be useful in predicting tumor sensitivity or resistance to inhibitory drugs...
  15. ncbi Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation
    Cristina R Antonescu
    Department of Pathology, Sloan Kettering Institute, New York, New York, USA
    Clin Cancer Res 11:4182-90. 2005
    ..That acquired resistance to imatinib in GIST commonly occurs via secondary gene mutation in the KIT kinase domain has implications for strategies to delay or prevent imatinib resistance and to employ newer targeted therapies...
  16. ncbi Signal transduction via the stem cell factor receptor/c-Kit
    L Ronnstrand
    Experimental Clinical Chemistry, Wallenberg Laboratory, Lund University, Malmo University Hospital, 205 02, Malmo, Sweden
    Cell Mol Life Sci 61:2535-48. 2004
    ..This review discusses our current knowledge of signal transduction molecules and signal transduction pathways activated by c-Kit and how their activation can be connected to the physiological outcome of c-Kit signaling...
  17. ncbi Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus: a clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases
    M Miettinen
    Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306 6000, USA
    Am J Surg Pathol 25:1121-33. 2001
    ..Intramural LMs are exceptional, and true LMSs are rare, and similar to colonic ones, often present as intraluminal polypoid masses that appear to have a better prognosis than GISTs with similar mitotic rates...
  18. ncbi 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...
  19. ncbi KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation
    Markku Miettinen
    Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306 6000, USA
    Appl Immunohistochem Mol Morphol 13:205-20. 2005
    ....
  20. ncbi Proof of target for SU11654: inhibition of KIT phosphorylation in canine mast cell tumors
    Nancy K Pryer
    SUGEN, Inc, South San Francisco, California 94080, USA
    Clin Cancer Res 9:5729-34. 2003
    ....
  21. ncbi Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor
    K M Zsebo
    Amgen Inc, Amgen Center, Thousand Oaks, California 91320
    Cell 63:213-24. 1990
    ..In vivo administration of SCF can reverse the macrocytic anemia and locally repair the mast cell deficiency of Sl/Sld mice. We have also provided biological and physical evidence that SCF is a ligand for the c-kit receptor...
  22. ncbi The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus
    B Chabot
    Division of Molecular and Developmental Biology, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada
    Nature 335:88-9. 1988
    ..In addition, these observations provide the first example of a germ-line mutation in a mammalian proto-oncogene and implicate the c-kit gene as a candidate for the W locus...
  23. ncbi Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group
    M Debiec-Rychter
    Department of Human Genetics, Oncology and Pathology, UZ Gasthuisberg, Catholic University of Leuven, Herestraat 49, B 3000 Leuven, Belgium
    Eur J Cancer 40:689-95. 2004
    ..These findings indicate that the mutational status of the c-KIT/PDGFRA oncoproteins could be useful to predict the clinical response of patients imatinib therapy...
  24. pmc Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand
    Y Yarden
    Department of Developmental Biology, Genentech, Inc, South San Francisco 94080
    EMBO J 6:3341-51. 1987
    ..Furthermore, carboxy- and amino-terminal truncations that occurred during the viral transduction process are likely to have generated the transformation potential of v-kit...
  25. ncbi Embryonic expression of a haematopoietic growth factor encoded by the Sl locus and the ligand for c-kit
    Y Matsui
    Department of Cell Biology, Vanderbilt University Medical School, Nashville, Tennessee 37232 2172
    Nature 347:667-9. 1990
    ..Both SCF and c-kit are also expressed in a variety of other tissues, including the brain and spinal cord, suggesting that the receptor-ligand system has additional roles in embryogenesis...
  26. ncbi Gene expression in gastrointestinal stromal tumors is distinguished by KIT genotype and anatomic site
    Cristina R Antonescu
    Departments of Pathology, Memorial Sloan Kettering Cancer Center, and Molecular Biology, Computational Biology Center, Sloan Kettering Institute, New York, New York 10021, USA
    Clin Cancer Res 10:3282-90. 2004
    ..We tested the hypothesis that the gene expression profile in GISTs might be related to KIT genotype and possibly to other clinicopathological factors...
  27. ncbi A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib
    Cem Akin
    Laboratory of Allergic Diseases, National Instititute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 103:3222-5. 2004
    ....
  28. ncbi Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs
    Sue Downing
    Veterinary Cancer Referral Group, 1044 South Robertson Blvd, Los Angeles, CA 90035, USA
    Am J Vet Res 63:1718-23. 2002
    ..To determine the prevalence of activating internal tandem duplications (ITDs) in exons 11 and 12 of c-kit in mast cell tumors (MCTs) of dogs and to correlate these mutations with prognosis...
  29. ncbi Spontaneous canine mast cell tumors express tandem duplications in the proto-oncogene c-kit
    C A London
    Department of Pathology, Brigham and Women s Hospital, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
    Exp Hematol 27:689-97. 1999
    ....
  30. ncbi Lack of KIT or FMS internal tandem duplications but co-expression with ligands in AML
    Rui Zheng
    Department of Pediatric Oncology, Johns Hopkins University School of Medicine, Room 253, Bunting Blaustein Cancer Research Building, Baltimore, MD 21231 1000, USA
    Leuk Res 28:121-6. 2004
    ....
  31. ncbi Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST)
    Ronald P Dematteo
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cancer 112:608-15. 2008
    ..Although the efficacy of tyrosine kinase inhibitors in metastatic GIST depends on tumor mutation status, there have been conflicting reports on the prognostic importance of KIT mutation in primary GIST...
  32. ncbi Growth stimulation of colorectal carcinoma cells via the c-kit receptor is inhibited by TGF-beta 1
    G Bellone
    Department of Clinical Physiopathology, University of Torino, Italy
    J Cell Physiol 172:1-11. 1997
    ..In summary, expression of the potential autocrine SCF/ c-kit axis is a tumor-associated phenomenon in colorectal cancer that can be suppressed by TGF-beta 1 in TGF-beta-responsive CRC cells...
  33. ncbi Coexpression of the c-kit receptor and the stem cell factor in gynecological tumors
    M Inoue
    Department of Obstetrics and Gynecology, School of Medicine, Osaka University, Japan
    Cancer Res 54:3049-53. 1994
    ..The present study suggests that the c-kit/SCF system may play an important role in the carcinogenesis of the female genital tract...
  34. ncbi Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3-CD4-CD8- thymocyte differentiation
    D I Godfrey
    DNAX Research Institute, Palo Alto, CA 94304
    J Immunol 152:4783-92. 1994
    ....
  35. ncbi Follicle-stimulating hormone regulates oocyte growth by modulation of expression of oocyte and granulosa cell factors
    Fiona H Thomas
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada K1H 1C4
    Endocrinology 146:941-9. 2005
    ..05), suggesting that lowered KL-1/KL-2 ratio is important for oocyte growth. In summary, the correct concentration of FSH is crucial for appropriate modulation of KL and BMP-15 to promote oocyte growth...
  36. ncbi KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours
    Maria Debiec-Rychter
    Department of Human Genetics, University of Leuven and University Hospital Gasthuisberg, O and N Gasthuisberg, Herestraat 49, B 3000 Leuven, Belgium
    Eur J Cancer 42:1093-103. 2006
    ..Our findings suggest the need for differential treatment of patients with GISTs, with KIT exon 9 mutant patients benefiting the most from the 800 mg daily dose of the drug...
  37. ncbi Stem cell factor and hematopoiesis
    V C Broudy
    Department of Medicine, University of Washington, Seattle 98195 7710, USA
    Blood 90:1345-64. 1997
  38. pmc Sequence occurrence and structural uniqueness of a G-quadruplex in the human c-kit promoter
    Alan K Todd
    Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
    Nucleic Acids Res 35:5799-808. 2007
    ..The c-kit87 quadruplex thus fulfils a fundamental criterion of a 'good' drug target, in that it possesses distinctive three-dimensional structural features that are only present in at most a handful of other genes...
  39. ncbi Expression of c-ABL, c-KIT, and platelet-derived growth factor receptor-beta in ovarian serous carcinoma and normal ovarian surface epithelium
    Rosemarie E Schmandt
    Department of Gynecologic Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 98:758-64. 2003
    ..Immunohistochemical expression of c-ABL, PDGFR-beta, and c-KIT was evaluated in ovarian carcinomas to determine whether treatment with imatinib mesylate might be feasible...
  40. ncbi Chimerism of the transplanted heart
    Federico Quaini
    Department of Medicine, New York Medical College, Valhalla 10595, USA
    N Engl J Med 346:5-15. 2002
    ..The Y chromosome can be used to detect migrated undifferentiated cells expressing stem-cell antigens and to discriminate between primitive cells derived from the recipient and those derived from the donor...
  41. ncbi Mutations in the juxtamembrane domain of c-KIT are associated with higher grade mast cell tumors in dogs
    D Zemke
    Department of Microbiology and Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing 48824, USA
    Vet Pathol 39:529-35. 2002
    ..A significant association was found between the presence of a mutation and a higher grade of tumor but not between breed and grade or between breed and the presence of a mutation...
  42. ncbi The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus
    E Huang
    Molecular Biology Program, Sloan Kettering Institute, New York, New York
    Cell 63:225-33. 1990
    ..Linkage analysis maps the KL gene to the Sl locus on mouse chromosome 10, and KL sequences are deleted in the genome of the Sl mouse. These results indicate that the Sl locus encodes the ligand of the c-kit receptor, KL...
  43. ncbi Diagnostic criteria and classification of mastocytosis: a consensus proposal
    P Valent
    Department of Internal Medicine I, Division of Hematology, University of Vienna, Währinger Gürtel 18 20 Vienna, Austria
    Leuk Res 25:603-25. 2001
    ..Criteria proposed in this article should be helpful in this regard...
  44. ncbi Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies
    Cheryl A London
    School of Veterinary Medicine, University of California, Davis, Davis, California 95616, USA
    Clin Cancer Res 9:2755-68. 2003
    ....
  45. ncbi Demonstration that human mast cells arise from a progenitor cell population that is CD34(+), c-kit(+), and expresses aminopeptidase N (CD13)
    A S Kirshenbaum
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
    Blood 94:2333-42. 1999
    ..Thus, human mast cells and a population of monocytes arise from precursor cells that express CD34, c-kit, and CD13; and within which, are mast cell, monocyte, and mast/monocyte (bipotential) precursors...
  46. ncbi Hypoxia-inducible factor (HIF)-1 alpha directly enhances the transcriptional activity of stem cell factor (SCF) in response to hypoxia and epidermal growth factor (EGF)
    Zhi Bo Han
    The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin 300020, China
    Carcinogenesis 29:1853-61. 2008
    ..Hypoxia and epidermal growth factor receptor signal coexisted in the tumor microenvironment and might promote angiogenesis through HIF-1 alpha-mediated upregulation of SCF and other angiogenic factors...
  47. pmc Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder
    H Nagata
    Allergic Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 92:10560-4. 1995
    ....
  48. ncbi Human malignant melanoma: detection of BRAF- and c-kit-activating mutations by high-resolution amplicon melting analysis
    Carlynn Willmore-Payne
    Department of Pathology, University of Utah, Salt Lake City, 84108, USA
    Hum Pathol 36:486-93. 2005
    ....
  49. ncbi Characterization of cells in the developing human liver
    Silvia Nava
    Division of Transplantation Surgery B56, Karolinska University Hospital Huddinge, S 141 86 Stockholm, Sweden
    Differentiation 73:249-60. 2005
    ..Cells that differentiate into Alb+ or CK19+ can be isolated from early FLs and may be appropriate progenitors for establishing novel systems to investigate basic mechanisms for cell therapy...
  50. pmc Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product
    T Furitsu
    Second Department of Internal Medicine, Osaka University Medical School, Suita, Japan
    J Clin Invest 92:1736-44. 1993
    ..These results suggest that conversion of Asp-816 to Val in human c-kitR may be an activating mutation and responsible for the constitutive activation of c-kitR in HMC-1 cells...
  51. ncbi Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate
    Eva Wardelmann
    Department of Pathology, University of Bonn Medical School, Bonn, Germany
    Clin Cancer Res 12:1743-9. 2006
    ..According to our results, the identification of newly acquired KIT mutations in addition to the primary mutation is dependent on the number of tissue samples analyzed and has high implications for further therapeutic strategies...
  52. ncbi c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue)
    Hidetaka Yamamoto
    Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
    Am J Surg Pathol 28:479-88. 2004
    ..Furthermore, STI-571, targeting c-kit and PDGFR tyrosine kinase, seems to be a possible therapeutic strategy for EGISTs, especially advanced cases...
  53. ncbi Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis
    M Miettinen
    Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306 6000, USA
    Virchows Arch 438:1-12. 2001
    ..Angiosarcomas and metastatic melanomas, both of which are often KIT-positive, should not be confused with GISTs...
  54. ncbi Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases
    Markku Miettinen
    Department of Soft Tissue Pathology, Armed Forces Institute of Patholgy, Washington, DC 20306 6000, USA
    Am J Surg Pathol 27:625-41. 2003
    ..The great majority of duodenal mesenchymal tumors are GISTs, which have a spectrum from small indolent tumors to overt sarcomas. LMs and LMSs are rare...
  55. pmc Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates
    Scott E Woodman
    Department of Melanoma Medical Oncology and Department of Systems Biology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA
    Mol Cancer Ther 8:2079-85. 2009
    ..These data support the selective inhibitory effect of dasatinib against cells harboring the most common KIT mutation in melanoma, and thus has therapeutic implications for acrallentiginous, chronic sun-damaged, and mucosal melanomas...
  56. ncbi Deletions affecting codons 557-558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS)
    Javier Martin
    Department of Oncology, Hospital Universitario de Son Dureta, C Andrea Doria 55, 07014 Palma de Mallorca Baleares, Spain
    J Clin Oncol 23:6190-8. 2005
    ..We have investigated the prognostic relevance of the type and position of the mutations, in addition to other clinicopathologic factors, in a large series of patients with GIST...
  57. pmc A G-rich sequence within the c-kit oncogene promoter forms a parallel G-quadruplex having asymmetric G-tetrad dynamics
    Shang Te Danny Hsu
    University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, United Kingdom
    J Am Chem Soc 131:13399-409. 2009
    ....
  58. ncbi SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer
    Tinya J Abrams
    Preclinical Research and Exploratory Development, SUGEN, Inc, South San Francisco, California 94080, USA
    Mol Cancer Ther 2:471-8. 2003
    ....
  59. 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...
  60. ncbi The biology of stem cell factor and its receptor C-kit
    L K Ashman
    Division of Haematology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, SA, Australia
    Int J Biochem Cell Biol 31:1037-51. 1999
    ....
  61. ncbi Structure of a c-kit product complex reveals the basis for kinase transactivation
    Clifford D Mol
    Syrrx, Inc, San Diego, California 92121, USA
    J Biol Chem 278:31461-4. 2003
    ....
  62. ncbi Induction of stem cell factor/c-Kit/slug signal transduction in multidrug-resistant malignant mesothelioma cells
    Alfonso Catalano
    Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona 60131, Italy
    J Biol Chem 279:46706-14. 2004
    ....
  63. ncbi Soluble and cell-bound forms of steel factor activity play distinct roles in melanocyte precursor dispersal and survival on the lateral neural crest migration pathway
    B Wehrle-Haller
    Institute of Neuroscience, University of Oregon, Eugene 97403
    Development 121:731-42. 1995
    ..In contrast, membrane-bound Steel factor appears to promote melanocyte precursor survival in the dermis...
  64. 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...
  65. pmc Molecular basis for the dominant white phenotype in the domestic pig
    S Marklund
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala Biomedical Centre, S 75124 Uppsala, Sweden
    Genome Res 8:826-33. 1998
    ..The EMBL accession numbers for porcine KIT1*0101, KIT1*0202, KIT2*0202, and KIT2*0101 are AJ223228-AJ223231, respectively.]..
  66. pmc Genetic aberrations of gastrointestinal stromal tumors
    Jilong Yang
    Department of Bone and Soft Tissue Tumors, Tianjin Cancer Hospital and Institute, Tianjin Medical University, Tianjin, China
    Cancer 113:1532-43. 2008
    ..A new paradigm of classification, integrating the standard clinical and pathological criteria with molecular aberrations, may permit personalized prognosis and treatment...
  67. ncbi Pigs with the dominant white coat color phenotype carry a duplication of the KIT gene encoding the mast/stem cell growth factor receptor
    M Johansson Moller
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden
    Mamm Genome 7:822-30. 1996
    ..5 cM) serum albumin (ALB) locus has previously been in situ mapped to the long arm (8q12). Pig Chr 8 shares extensive conserved synteny with human Chr 4, but the gene order is rearranged...
  68. ncbi KIT activating mutations: incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication
    Alessandro Beghini
    Department of Biology and Genetics for Medical Sciences, Medical Faculty, University of Milan, Italy
    Haematologica 89:920-5. 2004
    ..We evaluated the incidence of KIT mutation in 52 adult patients with de novo CBFL and in 49 FLT3/ITD-negative childhood patients with de novo acute myeloid leukemia (AML), excluding cases of acute promyelocytic leukemia...
  69. ncbi Activation of the receptor tyrosine kinase Kit is required for the proliferation of melanoblasts in the mouse embryo
    M A MacKenzie
    MRC Human Genetics Unit, Western General Hospital, Edinburgh, EH4 2XU, United Kingdom
    Dev Biol 192:99-107. 1997
    ..Our data do not describe a dependence upon Kit for melanoblast migration or differentiation...
  70. ncbi Prevalence of KIT expression in human tumors
    Philip Th Went
    Institute of Pathology, University of Basel, Basel, Switzerland
    J Clin Oncol 22:4514-22. 2004
    ..Because recent studies in GISTs suggest that KIT-activating mutations predict response to imatinib therapy, we also sequenced a subset of positive tumors...
  71. ncbi Structure of an unprecedented G-quadruplex scaffold in the human c-kit promoter
    Anh Tuân Phan
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Am Chem Soc 129:4386-92. 2007
    ..This unique structural scaffold provides a highly specific platform for the future design of ligands specifically targeted to the promoter DNA of c-kit...
  72. ncbi Morphology and localization of interstitial cells in the guinea pig bladder: structural relationships with smooth muscle and neurons
    Ross A Davidson
    Centre for Biophotonics, University of Strathclyde, Glasgow, Scotland, United Kingdom
    J Urol 173:1385-90. 2005
    ..In the current study we examined the location of interstitial cell of Cajal (ICC)-like cells in the guinea pig bladder wall and studied their structural interactions with nerves and smooth muscle cells...
  73. ncbi 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...
  74. pmc Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient Kit(W-sh)/Kit(W-sh) sash mice
    P J Wolters
    Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, CA 94143 0911, USA
    Clin Exp Allergy 35:82-8. 2005
    ..However, because they are compound heterozygotes in a mixed genetic background and are infertile, they cannot be crossed easily with other mice...
  75. ncbi KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs)
    Jerzy Lasota
    Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306 6000, USA
    Semin Diagn Pathol 23:91-102. 2006
    ..Mutation genotyping is a tool in GIST diagnosis and in assessment of sensitivity to kinase inhibitors. This is a US government work. There are no restrictions on its use...
  76. ncbi Rapamycin inhibits growth and survival of D816V-mutated c-kit mast cells
    Marion Gabillot-Carré
    CNRS UMR 8147, Universite Rene Descartes Paris V, Hopital Necker, 161 rue de Sevres, 75743 Paris Cedex 15, France
    Blood 108:1065-72. 2006
    ..The data presented here provide a rationale to test whether rapamycin could be a possible treatment for SM and other hematologic malignancies with the D816V mutation...
  77. ncbi Effect of tyrosine kinase inhibitor STI571 on the kinase activity of wild-type and various mutated c-kit receptors found in mast cell neoplasms
    Yael Zermati
    CNRS UMR 8603, Hopital Necker, Universite Rene Descartes, Paris, France
    Oncogene 22:660-4. 2003
    ..Therefore, STI571 is not a good candidate to treat SM and specific kinase inhibitors should be designed to inhibit constitutive activating mutations at codon 816...
  78. ncbi Regulation of hematopoietic stem cells by the steel factor/KIT signaling pathway
    David Kent
    Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada
    Clin Cancer Res 14:1926-30. 2008
    ....
  79. ncbi The selective tyrosine kinase inhibitor STI571 inhibits small cell lung cancer growth
    G W Krystal
    Department of Medicine, Virginia Commonwealth University, McGuire Veterans Affairs Medical Center, Richmond 23249, USA
    Clin Cancer Res 6:3319-26. 2000
    ....
  80. ncbi Expression of stem cell factor and c-kit in human neuroblastoma. The Children's Cancer Group
    P S Cohen
    Department of Pediatrics, Harbor UCLA Medical Center, Torrance, CA
    Blood 84:3465-72. 1994
    ..Simultaneous expression of SCF and c-kit mRNA in both neuroblastoma cell lines and tumors implies that c-kit may act as part of an autocrine growth loop in conjunction with endogenous production of SCF in this disease...
  81. ncbi Src family kinases are involved in the differential signaling from two splice forms of c-Kit
    Olexandr Voytyuk
    Ludwig Institute for Cancer Research, Biomedical Center, SE 751 24 Uppsala, Sweden, Sweden
    J Biol Chem 278:9159-66. 2003
    ..In summary, the two splice forms show, despite only a four-amino acid sequence difference, remarkable differences in their signaling capabilities...
  82. ncbi Imatinib inhibits proliferation of Ewing tumor cells mediated by the stem cell factor/KIT receptor pathway, and sensitizes cells to vincristine and doxorubicin-induced apoptosis
    Iranzu Gonzalez
    Department of Histology and Pathology, School of Medicine Universidad de Navarra, Pamplona, Spain
    Clin Cancer Res 10:751-61. 2004
    ..The stem cell factor/KIT receptor loop may represent a novel target for molecular-based therapies of Ewing tumor. We analyzed the in vitro impact of KIT blockade by imatinib in Ewing tumor cell lines...
  83. ncbi Gastrointestinal stromal tumours
    E M Connolly
    Department of Surgery, St James Hospital and Trinity College Dublin, Dublin 8, Ireland
    Br J Surg 90:1178-86. 2003
    ..GISTs are notoriously unresponsive to chemotherapy and, until the recent introduction of the KIT inhibitor imatinib, there has been no effective therapy for advanced, metastatic disease...
  84. 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...
  85. ncbi Gastrointestinal stromal tumors (GIST): C-kit mutations, CD117 expression, differential diagnosis and targeted cancer therapy with Imatinib
    Chandu M V de Silva
    University Department of Pathology, Western Infirmary, Glasgow, G11 6NT, UK
    Pathol Oncol Res 9:13-9. 2003
    ..This review summarises recent advances in knowledge regarding the histogenesis, pathology, molecular biology, genetics and differential diagnosis of GISTs and the basis for the novel targeted cancer therapy with imatinib...
  86. pmc Molecular bases of dominant negative and loss of function mutations at the murine c-kit/white spotting locus: W37, Wv, W41 and W
    K Nocka
    Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021
    EMBO J 9:1805-13. 1990
    ..A 125 kd c-kit protein was detected in homozygous W/W mast cells which lacks kinase activity and is not expressed on the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS)..
  87. ncbi Mastocytosis: molecular mechanisms and clinical disease heterogeneity
    D D Metcalfe
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 10, Rm. 11C205, 10 Center Drive MSC 1881, Bethesda, MD 20892-1881, USA
    Leuk Res 25:577-82. 2001
    ....
  88. ncbi Developmental and molecular aberrations associated with deterioration of oogenesis during complete or partial follicle-stimulating hormone receptor deficiency in mice
    Yinzhi Yang
    Molecular Reproduction Research Laboratory, Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W 1R7
    Biol Reprod 69:1294-302. 2003
    ..We believe that these data provide an experimental paradigm to explore the mechanisms responsible for preserving the structural integrity and quality of oocytes at different ages...
  89. ncbi Pro-thymocyte expansion by c-kit and the common cytokine receptor gamma chain is essential for repertoire formation
    H R Rodewald
    Basel Institute for Immunology, Switzerland
    Immunity 6:265-72. 1997
    ....
  90. ncbi Effects of mutations at the W locus (c-kit) on inner ear pigmentation and function in the mouse
    J Cable
    MRC Institute of Hearing Research, University Park, Nottingham, U K
    Pigment Cell Res 7:17-32. 1994
    ..Injection of normal neural crest cells into 9.5-day-old mutant embryos increased the extent of skin pigmentation on the head and coat of adult chimeras and was associated with a small increase in the proportion of pigmented strias...
  91. ncbi c-KIT expression and correlation with chemotherapy resistance in ovarian carcinoma: an immunocytochemical study
    M R Raspollini
    Department of Human Pathology and Oncology, University of Florence, Florence, Italy
    Ann Oncol 15:594-7. 2004
    ..The aim of this study was to determine the incidence and correlation with chemotherapy resistance of c-KIT expression in advanced serous, low grade of differentiation, ovarian carcinoma...
  92. ncbi Classes of c-KIT activating mutations: proposed mechanisms of action and implications for disease classification and therapy
    B J Longley
    Department of Dermatology and Pathology, Columbia University, 630 West 168th Street, VC-15-202, New York, NY 10031, USA
    Leuk Res 25:571-6. 2001
    ....
  93. pmc Candidate ligand for the c-kit transmembrane kinase receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors
    K Nocka
    Molecular Biology, Sloan Kettering Institute, New York, NY 10021
    EMBO J 9:3287-94. 1990
    ..abstract truncated at 250 words)..
  94. ncbi Imatinib inhibits c-Kit-induced hypoxia-inducible factor-1alpha activity and vascular endothelial growth factor expression in small cell lung cancer cells
    Julie Litz
    Department of Medicine, Virginia Commonwealth University and McGuire Veterans Affairs Medical Center, Richmond, VA, USA
    Mol Cancer Ther 5:1415-22. 2006
    ..These data indicate that activation of c-Kit by SCF leads to a predominantly HIF-1alpha-mediated enhancement of VEGF expression and that inhibition of c-Kit signaling with imatinib could result in inhibition of tumor angiogenesis...
  95. pmc AML1-ETO and C-KIT mutation/overexpression in t(8;21) leukemia: implication in stepwise leukemogenesis and response to Gleevec
    Yue Ying Wang
    State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Department of Medical Laboratory Science, Ruijin Medical College, Rui Jin Hospital Affiliated to Shanghai Second Medical University, 197 Rui Jin Road II, Shanghai 200025, China
    Proc Natl Acad Sci U S A 102:1104-9. 2005
    ..Gleevec also exerted a synergic effect in apoptosis induction with cytarabine, thus providing a potential therapeutic for t(8;21) leukemia...
  96. ncbi Immunohistochemical staining for KIT (CD117) in soft tissue sarcomas is very limited in distribution
    Jason L Hornick
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Am J Clin Pathol 117:188-93. 2002
    ..Since treatment eligibility for selective tyrosine kinase inhibitors such as STI571 hinges on positive immunostaining, standardization and reproducibility of meaningful results are critically important...
  97. ncbi 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...
  98. ncbi Expression of c-kit and kit ligand proteins in normal human tissues
    A Lammie
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10021
    J Histochem Cytochem 42:1417-25. 1994
    ..In the central nervous system, KL expression was confined to Golgi and Purkinje cells in the cerebellum. These results suggest a role for this receptor and its ligand in the maintenance of a variety of fully differentiated tissues...
  99. ncbi Anal mucosal melanoma with KIT-activating mutation and response to imatinib therapy--case report and review of the literature
    Imke Satzger
    Skin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany satzger imke mh hannover de
    Dermatology 220:77-81. 2010
    ..We report here on one of our patients with KIT-activating mutation in metastatic anal mucosal melanoma, who showed a response to imatinib therapy and summarize the available literature regarding this new therapeutic option...
  100. ncbi Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal tumor
    Sebastian Bauer
    Department of Pathology, Brigham and Women s Hospital, Center for Sarcoma and Bone Oncology, Dana Farber Cancer Institute, and Ludwig Center at Dana Farber Harvard Cancer Center, Boston, Massachusetts 02115, USA
    Cancer Res 66:9153-61. 2006
    ..The dramatic inactivation of imatinib-resistant KIT oncoproteins suggests that HSP90 inhibition provides a therapeutic solution to the challenge of heterogeneous imatinib resistance mutations in GIST patients...
  101. ncbi Mast cells promote homeostasis by limiting endothelin-1-induced toxicity
    Marcus Maurer
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 432:512-6. 2004
    ..These findings identify a new biological function for mast cells: promotion of homeostasis by limiting the toxicity associated with an endogenous mediator...

Research Grants68

  1. Mechanisms Regulating Reduced c-Kit-Dependent EAE Susceptibility in Male SJL Mice
    MELISSA ANN BROWN; Fiscal Year: 2013
    ..These mice provide a perfect system to explore the how c-kit signaling, in concert with influences from male sex hormones, confers neuroprotection and may lead to better therapies for this devastating CNS disease. ..
  2. Rac1 and Rac2 Guanosine Triphosphatases in Erythroid Function and Differentiation
    THEODOSIA ANASTASIOS KALFA; Fiscal Year: 2012
    ..abstract_text> ..
  3. Hematopoietic stem cell cytokine control of developmental vascularization
    George E Davis; Fiscal Year: 2013
    ..Specific Aim #3. To determine how SCF, IL-3 and SDF-1[unreadable] act to regulate pericyte-induced EC sprouting responses and vasculogenic EC-pericyte tube coassembly in 3D extracellular matrices. ..
  4. Structural biology of oncogenic receptor tyrosine kinases
    Xiaolin He; Fiscal Year: 2010
    ..These studies will elucidate novel structural mechanisms that will lay the groundwork for therapeutic development to treat class III-RTK-related cancers. ..
  5. STEM CELL FACTOR ACTION IN NEURAL CREST DEVELOPMENT
    Maya Sieber Blum; Fiscal Year: 2003
    ..However, the newly detected additional roles of SCF in maintaining stem cells, up-regulating neurotrophin receptors and promoting sensory neurogenesis suggest additional defects in human piebaldism that remain to be elucidated. ..
  6. MOLECULAR PATHWAYS IN MYELOPROLIFERATIVE DISEASE
    George Daley; Fiscal Year: 2002
    ....
  7. REGULATION OF MAST CELL DEVELOPMENT AND FUNCTION
    STEPHEN JOSEPH GALLI; Fiscal Year: 2010
    ..abstract_text> ..
  8. KIT GROWTH CONTROL OF MELANOCYTIC TUMORS
    James Grichnik; Fiscal Year: 2002
    ..The proposed experiments will define to what extent manipulation of the KIT pathway will be useful for the therapeutic treatment of proliferative melanocytic disease processes. ..
  9. Genetic networks that regulate the mast lineage
    Clifford Takemoto; Fiscal Year: 2009
    ..This proposal will provide insights into the mechanisms of lineage-selection during mast cell development and may lead to therapeutic targets for mast cell-related diseases. ..
  10. Stat5 Function in proliferation and Leukemogensis
    John Ryan; Fiscal Year: 2005
    ..As such, the resulting data will be important to the understanding and treatment of cancer. ..
  11. Natural Killer Dendritic Cells in Listeria Infection
    Ronald DeMatteo; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  12. STI571 Therapy for Gastrointestinal Stromal Tumors
    Ronald DeMatteo; Fiscal Year: 2002
    ..The results are essential to advance our understanding of GIST biology and determine the therapeutic value and limitations of STI571. ..
  13. FTI Biology & Treatment of Myeloproliferative Disorders
    Jason Gotlib; Fiscal Year: 2005
    ..If clinically efficacious, further studies of R115777 in MPDs will be warranted...
  14. KGF and Protection from Hyperoxic Lung Injury
    Prabir Ray; Fiscal Year: 2009
    ..Collectively, these studies will address the mechanisms by which KGF induces anti-apoptotic and anti-inflammatory effects. ..
  15. Chemokines and Immune Regulation in the Lung
    Prabir Ray; Fiscal Year: 2008
    ....
  16. Protein Packing Defects as Functional Markers and Drug Targets
    Ariel Fernandez; Fiscal Year: 2008
    ..Thus, the novel design concept of "drug inhibitor as a wrapper of functional packing defects" will be explored and validated. ..
  17. Cardiac Stem Cell Growth, Aging and Death
    Jan Kajstura; Fiscal Year: 2008
    ..Conversely, inhibitors of the cell cycle and marker of cellular senescence increase in combination with oxidative DNA damage, potentiating the endogenous cell death pathway. ..
  18. Maintainance of Organ Function Following Injury
    Irshad Chaudry; Fiscal Year: 2008
    ..abstract_text> ..
  19. Bladder transcriptome in experimental inflammation
    Ricardo Saban; Fiscal Year: 2007
    ..Following target validation of SSH-selected genes, a custom array will be developed. This micro array will be used to determine how the bladder transcriptome is altered by BCG therapy. ..
  20. Lineage decision in blood stem and progenitor cells
    Koichi Akashi; Fiscal Year: 2007
    ..Thus, we hope these studies will help understand mechanistic effects of these transcription factors on lineage decision in normal and malignant hematopoietic development. ..
  21. STEM CELL THERAPY IN ACUTE RENAL FAILURE
    Fangming Lin; Fiscal Year: 2007
    ....
  22. Ras-PI3K Pathway in Nf1-/-Hematopoiesis and Leukemia
    David Ingram; Fiscal Year: 2007
    ..abstract_text> ..
  23. Activity & resistance of Gleevec in GI stromal tumors
    Jonathan Trent; Fiscal Year: 2008
    ..The study of GIST is an exciting opportunity for career development and to focus on the study of a disease that has been effectively treated by targeted therapy. ..
  24. Encapsulated siRNAs for treatment of urological disease
    Robert Weiss; Fiscal Year: 2008
    ..Thus, we can determine the therapeutic potential of siRNA for treatment of urologic diseases. [unreadable] [unreadable] [unreadable]..
  25. Mechanisms of dynamin family GTPases
    Mark A Lemmon; Fiscal Year: 2010
    ..We will also investigate the structural basis for cardiolipin recognition. Together, these studies promise to provide valuable insight into the mechanisms of action of these important large GTPases. ..
  26. Pathways governing survival of neural crest derivatives
    ROBERT AARON CORNELL; Fiscal Year: 2010
    ..These pathways are potential entry points for therapies against malignant melanoma and other neural crest diseases. ..
  27. SPECIFICITY OF DOMAIN INTERACTIONS IN CELL SIGNALING
    Mark A Lemmon; Fiscal Year: 2010
    ..In parallel, we will map orthologous interactions in mammalian cells, establishing a new paradigm for PH domains that resembles the role of SH2, and SH3 domains. ..
  28. Targeting COX-2 Expressing Myofibroblasts in Colorectal Cancer (CRC)
    DON WATSON POWELL; Fiscal Year: 2010
    ..We hypothesize that CMF-derived PGE2 regulates Wnt/f3-catenin/TCF signaling within the malignant epit helium by regulating the stability, nuclear translocation and transcriptional activity of /3- catenin. ..
  29. Biology of Imatinib-Resistant Mutants of BCR-ABL
    Michael Deininger; Fiscal Year: 2009
    ..Such crucial proteins may then be exploited as drug targets for the treatment of chronic myeloid leukemia, and further, for other types of cancer. ..
  30. Mechanisms of mast cell influence on EAE disease course
    MELISSA ANN BROWN; Fiscal Year: 2010
    ..at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page 1 Description, ..
  31. Mechanisms of adhesion and growth control in stem cells
    Reuben Kapur; Fiscal Year: 2008
    ..Our proposed studies will provide unique insights into the physiologic significance of the in vivo interactions between class IA PI3K, PTEN and ROCK1 in regulating growth and survival in SC/Ps. ..
  32. Developmental Checkpoints of Murine Mast Cells
    Koichi Akashi; Fiscal Year: 2009
    ..Results obtained from this project will be critical to study mast cell biology, which eventually will help develop new therapeutic strategies for a variety of allergic and autoimmune disorders. ..
  33. The Role of HIV-1 Vpu in the Regulation of CD40
    Ashlee Moses; Fiscal Year: 2009
    ..Successful completion of these Aims will lead to an increased understanding of both CD40 regulation and Vpu function, and may identify targets of immune modulatory and/or anti-viral significance. ..
  34. Stem Cells
    Catherine Verfaillie; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  35. Protein Therapy for Junctional Epidermolysis Bullosa
    Vitali Alexeev; Fiscal Year: 2006
    ..abstract_text> ..
  36. Significance of Genetic Alterations in Neuroblastoma
    John Maris; Fiscal Year: 2006
    ..It is expected that these will be of prognostic importance and serve as specific targets for developmental therapeutics. ..
  37. Regulation of Prostaglandins in Periovulatory Follicles
    JOANNE FORTUNE; Fiscal Year: 2005
    ..Together these experiments will provide new knowledge about the regulation of, and relationship between, these two essential mediators of ovulation and their receptors. ..
  38. Silibinin in Prostate Cancer Chemoprevention & Treatment
    Michael Pollak; Fiscal Year: 2004
    ..The work is justified by the favorable toxicity profile of silibinin, together with prior positive laboratory studies reported by our group and other investigators. ..
  39. NEUROECTODERM DIFFERENTIATION FROM MESENCHYMAL STEM CELL
    Catherine Verfaillie; Fiscal Year: 2004
    ..abstract_text> ..
  40. FERTILITY AND SERTOLI CELL DEVELOPMENT
    Joanne Orth; Fiscal Year: 2004
    ..abstract_text> ..
  41. Feline Model of an Inherited Craniofacial Abnormality
    Leslie Lyons; Fiscal Year: 2004
    ..Once identified, mutation analyses of these genes in the cat or other species will lead to understanding the genetics of facial development in humans. ..
  42. Identifying cellular genes as anti-HIV drug targets
    Ashlee Moses; Fiscal Year: 2003
    ..The company intends to develop intellectual property protection for the use of novel validated genes in antiviral drug assays, and pursue the development of such drugs. ..
  43. MIGRATION AND ADHESION OF CHRONIC MYELOGNEOUS LEUKEMIA C
    Catherine Verfaillie; Fiscal Year: 2003
    ..SA 3. Examine effect of p210-Bcr/Abl on the function and interactions of GTPases, PI3-K, and Pyk2 leading to the decreased adhesion and enhanced migration characteristic of CML. ..
  44. FACS Vantage SE
    Catherine Verfaillie; Fiscal Year: 2003
    ..abstract_text> ..
  45. HIV INFECTED ENDOTHELIUM AND NONHODGKINS LYMPHOMA
    Ashlee Moses; Fiscal Year: 2002
    ..Identification of these mechanisms may suggest therapeutic targets to prevent development of extranodal B cell neoplasms. ..
  46. GENETIC STUDIES OF MARGARITA ISLAND ECTODERMAL DYSPLASIA
    Richard Spritz; Fiscal Year: 2002
    ..The last aim is to initiate studies to determine the function of the ED4 gene. ..
  47. Wnt Signaling in IBD-Related Colon Cancer
    RANDALL HOLCOMBE; Fiscal Year: 2005
    ..The precise effects of FIPs on Wnt signaling will be defined in vitro, with attention to the potentially disparate responses of different, specific, Fz receptor subtypes. ..
  48. FAS/APO-1 MEDIATED APOPTOSIS
    Robert Fine; Fiscal Year: 2002
    ..Thus, the selective and rapid induction of apoptosis occurring only in cancer cells carrying p53 abnormalities could be a powerful therapeutic modality for the treatment of cancer. ..
  49. ISOLATION OF THE NEUROBLASTOMA PREDISPOSITION GENE
    John Maris; Fiscal Year: 2006
    ..Ultimately, these experiments should lead to the identification of a common pathway to neuroblastoma tumorigenesis that will be an outstanding target for rationally designed therapeutics. ..
  50. Genetic analysis of Kit ligand of mice
    MARY BEDELL; Fiscal Year: 2006
    ..Together, these studies will provide new insights into Kitl function and may lead to novel strategies for the development of more effective cytokines. ..
  51. TRAINING PROGRAM IN BREAST CANCER RESEARCH
    Carlos Arteaga; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  52. Missing Mutations in Oculocutaneous and Ocular Albinism
    Richard Spritz; Fiscal Year: 2006
    ..Together, these studies should provide a greatly improved understanding of the molecular pathogenesis of oculocutaneous and ocular albinism. [unreadable] [unreadable]..
  53. A Phase 1 Study of CCI-779 in Combination with Imatnib *
    RANDALL HOLCOMBE; Fiscal Year: 2006
    ..Since deregulated kinase activity is known to contribute to a wide range of malignancies, these studies will have applicability to cancer therapy in general. [unreadable] [unreadable]..
  54. Mesenchymal Stem Cell Therapy a1 antitrypsin deficiency
    Catherine Verfaillie; Fiscal Year: 2006
    ....
  55. Phase II Trial of Thalidomide in Primary Amyloidosis
    Angela Dispenzieri; Fiscal Year: 2002
    ..The ultimate goal of the proposed studies is to improve the prognosis of patient with this fatal disease. ..
  56. Multipotent Stem Cells in Post Natal Bone Marrow
    Catherine Verfaillie; Fiscal Year: 2006
    ..We will test whether MAPC differentiate in vivo to tissue specific cells and whether this is enhanced when organs are damaged. ..
  57. Examination of FLT3 Mutations in Acute Myeloid Leukemia
    Derek Stirewalt; Fiscal Year: 2006
    ..Together, the research proposal and educational program provide Dc Stirewalt with the skills to become an independent clinical investigator. ..
  58. DOSE RESPONSE EFFECTS OF ALCOHOL ON BONE METABOLISM
    Russell Turner; Fiscal Year: 2006
    ....
  59. ESTROGEN METABOLITES EFFECTS ON BONE
    Russell Turner; Fiscal Year: 2002
    ..abstract_text> ..
  60. Phase II Study of 44Gy from 131I-81C6 for CNS Tumors
    David Reardon; Fiscal Year: 2004
    ..To further define the toxicity of this approach and Specific Aim 3.To determine the impact of this therapy on quality of life. ..
  61. Etiology and Treatment of Parathyroid Bone Disease
    Russell Turner; Fiscal Year: 2005
    ..Since PDGF antagonists such as trapidil are available for human use, positive results could be quickly extended to clinical practice. ..
  62. Venous thromboembolism among California cancer patients
    Helen Chew; Fiscal Year: 2003
    ..abstract_text> ..
  63. Clofarabine: Cytarabine Activation for Leukemia Response
    Stefan Faderl; Fiscal Year: 2004
    ..abstract_text> ..
  64. Mast cells' contribution to T cell immunity
    Melissa Brown; Fiscal Year: 2007
    ..3. 3. To assess the changes in mast cell phenotype during rLM33 infection and determine their relationship to alterations in T cell responses ..
  65. Mast cell effects on islet cell destruction in NOD mice
    Melissa Brown; Fiscal Year: 2007
    ..To examine the consequencess of mast cell-deficiency on the development of spontaneous insulitis and diabetes. 3. To determine the sites of mast cell influence on diabetes development. [unreadable] [unreadable] [unreadable]..
  66. Mast cell regulation of CD8+ T cell responses
    Melissa Brown; Fiscal Year: 2008
    ..2) To examine the influence of mast cells on dendritic cell maturation, migration and T cell stimulatory function in LCMV-infected mice. [unreadable] [unreadable]..
  67. INDUCIBLE IL4 GENE TRANSCRIPTION IN T AND MAST CELLS
    Melissa Brown; Fiscal Year: 2004
    ..3. To identify other sequences that influence transcription of IL-4 and/or IL-13 in both T and mast cells. 4. To examine the molecular basis of strain-specific differences in murine IL-4 gene expression. ..