neoplastic cell transformation

Summary

Summary: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.

Top Publications

  1. ncbi The hallmarks of cancer
    D Hanahan
    Department of Biochemistry, Hormone Research Institute, University of California at San Francisco, 94143, USA
    Cell 100:57-70. 2000
  2. ncbi Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma
    V Korinek
    Department of Immunology, University Hospital, Post Office Box 85500, 3508 GA Utrecht, Netherlands
    Science 275:1784-7. 1997
  3. ncbi Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication
    Raffaella Di Micco
    IFOM Foundation FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy
    Nature 444:638-42. 2006
  4. ncbi Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
    Vassilis G Gorgoulis
    Department of Histology and Embryology, School of Medicine, University of Athens, Athens GR 11527, Greece
    Nature 434:907-13. 2005
  5. ncbi Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, DK 2100 Copenhagen, Denmark
    Nature 444:633-7. 2006
  6. ncbi DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Nature 434:864-70. 2005
  7. ncbi Stat3 as an oncogene
    J F Bromberg
    Laboratory of Molecular Cell Biology, The Rockefeller University, New York, New York 10021 6399, USA
    Cell 98:295-303. 1999
  8. ncbi MicroRNA signatures in human cancers
    George A Calin
    Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210, USA
    Nat Rev Cancer 6:857-66. 2006
  9. ncbi Mutations of the BRAF gene in human cancer
    Helen Davies
    Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
    Nature 417:949-54. 2002
  10. ncbi Induction of tumors in mice by genomic hypomethylation
    François Gaudet
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Science 300:489-92. 2003

Research Grants

  1. Anticarcinogenic Mechanisms of Tea Constituents
    Zigang Dong; Fiscal Year: 2012
  2. Molecular Functions of the Adenovirus E1A Oncogene
    Maurice Green; Fiscal Year: 2006
  3. Hypoxia Signaling, Chromatin Remodeling and Nickel Carcinogenesis
    Max Costa; Fiscal Year: 2009
  4. INHIBITION OF CARCINOGENESIS BY TEA AND TEA CONSTITUENTS
    Zigang Dong; Fiscal Year: 2010
  5. CLINICAL STUDIES OF SIGNAL TRANSDUCTION INHIBITORS
    Alex Adjei; Fiscal Year: 2001
  6. HEPTOCYTE PROLIFERATION AND AFLATOXIN METABOLISM
    Stewart Sell; Fiscal Year: 2004
  7. STEM CELLS AND HEPATOCARCINOGENESIS
    Stewart Sell; Fiscal Year: 2009
  8. Role of HPV16 E7/E2F6 interaction in viral oncogenesis
    Margaret McLaughlin Drubin; Fiscal Year: 2006
  9. DIFFERENTIATION OF BLOOD STEM CELLS INTO LIVER CELLS
    Stewart Sell; Fiscal Year: 2005
  10. STEM CELLS AND AGING
    Stewart Sell; Fiscal Year: 2008

Detail Information

Publications303 found, 100 shown here

  1. ncbi The hallmarks of cancer
    D Hanahan
    Department of Biochemistry, Hormone Research Institute, University of California at San Francisco, 94143, USA
    Cell 100:57-70. 2000
  2. ncbi Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma
    V Korinek
    Department of Immunology, University Hospital, Post Office Box 85500, 3508 GA Utrecht, Netherlands
    Science 275:1784-7. 1997
    ..Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium...
  3. ncbi Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication
    Raffaella Di Micco
    IFOM Foundation FIRC Institute of Molecular Oncology Foundation, 20139 Milan, Italy
    Nature 444:638-42. 2006
    ..Last, we show that oncogene activation is associated with DDR activation in a mouse model in vivo. We propose that OIS results from the enforcement of a DDR triggered by oncogene-induced DNA hyper-replication...
  4. ncbi Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
    Vassilis G Gorgoulis
    Department of Histology and Embryology, School of Medicine, University of Athens, Athens GR 11527, Greece
    Nature 434:907-13. 2005
    ..We propose that, from its earliest stages, cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations...
  5. ncbi Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, DK 2100 Copenhagen, Denmark
    Nature 444:633-7. 2006
    ..Thus, senescence in human preneoplastic lesions is a manifestation of oncogene-induced DNA replication stress and, together with apoptosis, provides a barrier to malignant progression...
  6. ncbi DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
    Jirina Bartkova
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Nature 434:864-70. 2005
    ..Mutations compromising this checkpoint, including defects in the ATM-Chk2-p53 pathway, might allow cell proliferation, survival, increased genomic instability and tumour progression...
  7. ncbi Stat3 as an oncogene
    J F Bromberg
    Laboratory of Molecular Cell Biology, The Rockefeller University, New York, New York 10021 6399, USA
    Cell 98:295-303. 1999
    ..Thus, the activated Stat3 molecule by itself can mediate cellular transformation and the experiments focus attention on the importance of constitutive Stat3 activation in human tumors...
  8. ncbi MicroRNA signatures in human cancers
    George A Calin
    Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210, USA
    Nat Rev Cancer 6:857-66. 2006
    ..In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer...
  9. ncbi Mutations of the BRAF gene in human cancer
    Helen Davies
    Cancer Genome Project, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
    Nature 417:949-54. 2002
    ..As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma...
  10. ncbi Induction of tumors in mice by genomic hypomethylation
    François Gaudet
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
    Science 300:489-92. 2003
    ..These results indicate that DNA hypomethylation plays a causal role in tumor formation, possibly by promoting chromosomal instability...
  11. ncbi The emerging roles of forkhead box (Fox) proteins in cancer
    Stephen S Myatt
    Cancer Research UK Laboratories, Department of Oncology, MRC Cyclotron Building, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
    Nat Rev Cancer 7:847-59. 2007
    ....
  12. pmc Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis
    G Bergers
    Department of Biochemistry and Biophysics, University of California, 513 Parnassus Avenue, San Francisco, California 94143, USA
    Nat Cell Biol 2:737-44. 2000
    ..Absence of MMP-2 does not impair induction of angiogenesis, but retards tumour growth, whereas lack of urokinase has no effect. Our results show that MMP-9 is a component of the angiogenic switch...
  13. ncbi Linking colorectal cancer to Wnt signaling
    M Bienz
    MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Cell 103:311-20. 2000
  14. ncbi Stem cells, cancer, and cancer stem cells
    T Reya
    Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Palo Alto, California 94305, USA
    Nature 414:105-11. 2001
    ....
  15. ncbi STATs in oncogenesis
    T Bowman
    Molecular Oncology Program, H Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida, FL 33612, USA
    Oncogene 19:2474-88. 2000
    ..This review presents the evidence for critical roles of STATs in oncogenesis and discusses the potential for development of novel cancer therapies based on mechanistic understanding of STAT signaling. Oncogene (2000)...
  16. pmc Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells
    B Elenbaas
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Genes Dev 15:50-65. 2001
    ..Thus, these observations establish an experimental system for elucidating both the genetic and cell biological requirements for the development of breast cancer...
  17. ncbi ATM and related protein kinases: safeguarding genome integrity
    Yosef Shiloh
    The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Rev Cancer 3:155-68. 2003
    ..Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers...
  18. ncbi Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9
    Andrei V Krivtsov
    Division of Hematology Oncology, Children s Hospital, Boston, Massachusetts 02115, USA
    Nature 442:818-22. 2006
    ..Our findings define progression from normal progenitor to cancer stem cell, and suggest that targeting a self-renewal programme expressed in an abnormal context may be possible...
  19. ncbi Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers
    Elgene Lim
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    Nat Med 15:907-13. 2009
    ..Our findings suggest that an aberrant luminal progenitor population is a target for transformation in BRCA1-associated basal tumors ...
  20. ncbi RAS is regulated by the let-7 microRNA family
    Steven M Johnson
    Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, CT 06520, USA
    Cell 120:635-47. 2005
    ..let-7 expression is lower in lung tumors than in normal lung tissue, while RAS protein is significantly higher in lung tumors, providing a possible mechanism for let-7 in cancer...
  21. ncbi Identification of bronchioalveolar stem cells in normal lung and lung cancer
    Carla F Bender Kim
    Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cell 121:823-35. 2005
    ..Although bronchiolar cells and alveolar cells are proposed to be the precursor cells of adenocarcinoma, this work points to BASCs as the putative cells of origin for this subtype of lung cancer...
  22. ncbi Role of the INK4a locus in tumor suppression and cell mortality
    M Serrano
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York, 11724 USA
    Cell 85:27-37. 1996
    ..These findings directly demonstrate that the INK4a locus functions to suppress neoplastic growth...
  23. ncbi Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18
    D Bello
    Department of Medicine, Michigan State University, East Lansing 48824 1312, USA
    Carcinogenesis 18:1215-23. 1997
    ..The RWPE-1 cells, which show many normal cell characteristics, and the malignant RWPE-2 cells, provide useful cell culture models for studies on prostate growth regulation and carcinogenesis...
  24. ncbi Urothelial tumorigenesis: a tale of divergent pathways
    Xue ru Wu
    Department of Urology, New York University School of Medicine, New York, New York 10016, USA
    Nat Rev Cancer 5:713-25. 2005
    ..Correcting pathway-specific defects represents an attractive strategy for the molecular therapy of urothelial carcinomas...
  25. ncbi Epithelial-mesenchymal transitions in tumour progression
    Jean Paul Thiery
    Centre National Recherche Scientifique Unité Mixte Recherche, 144 Institut Curie, 26 Rue d Ulm, 75248 Paris Cedex 05, France
    Nat Rev Cancer 2:442-54. 2002
  26. ncbi The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells
    Marc van de Wetering
    Department of Immunology and Center for Biomedical Genetics, University Medical Center, 3584 CX, Utrecht, The Netherlands
    Cell 111:241-50. 2002
    ..Thus, the beta-catenin/TCF-4 complex constitutes the master switch that controls proliferation versus differentiation in healthy and malignant intestinal epithelial cells...
  27. pmc The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1
    W A May
    Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, University of California, Los Angeles
    Mol Cell Biol 13:7393-8. 1993
    ..EWS/FLI-1 could disrupt normal growth and differentiation either by more efficiently activating FLI-1 target genes or by inappropriately modulating genes normally not responsive to FLI-1...
  28. ncbi Identification and characterization of leukemia stem cells in murine MLL-AF9 acute myeloid leukemia
    Tim C P Somervaille
    Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA
    Cancer Cell 10:257-68. 2006
    ....
  29. ncbi Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis
    Reiji Kannagi
    Division of Molecular Pathology, Aichi Cancer Center Research Institute, Chikusa ku, Nagoya 464 8681, Japan
    Cancer Sci 95:377-84. 2004
    ..Considerable new knowledge has also been accumulated regarding the therapeutic implications for suppression of hematogenous metastasis targeting this cell adhesion system...
  30. ncbi hDOT1L links histone methylation to leukemogenesis
    Yuki Okada
    Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Cell 121:167-78. 2005
    ..Our studies thus establish that mistargeting of hDOT1L to Hoxa9 plays an important role in MLL-AF10-mediated leukemogenesis and suggests that the enzymatic activity of hDOT1L may provide a potential target for therapeutic intervention...
  31. ncbi Malignant transformation in a nontumorigenic human prostatic epithelial cell line
    S W Hayward
    Department of Urology, University of California San Francisco, San Francisco, CA 94143, USA
    Cancer Res 61:8135-42. 2001
    ..The cells continued to express SV40T antigen. These cell strains, which are all derived from a common nontumorigenic progenitor, represent a useful resource for examining genetic and phenotypic changes during carcinogenesis...
  32. ncbi Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis
    H van Dam
    Department of Molecular Cell Biology, Leiden University Medical Center, Sylvius Laboratories, PO Box 9503, 2300 RA Leiden, The Netherlands
    Oncogene 20:2453-64. 2001
    ..Further genetic studies with Jun dimerization mutants will be required to be precise and extend the specific roles of the Jun : Fos and Jun : ATF dimers during cancer progression in avian and mammalian systems...
  33. ncbi Cell adhesion and signalling by cadherins and Ig-CAMs in cancer
    Ugo Cavallaro
    Institute of Biochemistry and Genetics, Department of Clincal Biological Sciences, University of Basel Switzerland
    Nat Rev Cancer 4:118-32. 2004
  34. ncbi New functions for the matrix metalloproteinases in cancer progression
    Mikala Egeblad
    Department of Anatomy, University of California at San Francisco, 94143 0452, USA
    Nat Rev Cancer 2:161-74. 2002
    ..With this knowledge in hand, can we rethink the use of MMP inhibitors in the clinic?..
  35. ncbi Two genetic hits (more or less) to cancer
    A G Knudson
    Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Nat Rev Cancer 1:157-62. 2001
    ..Evidence from the recent molecular era also indicates that cancers can arise from small numbers of events that affect common cell birth and death processes...
  36. ncbi Friends or foes - bipolar effects of the tumour stroma in cancer
    Margareta M Mueller
    Group Tumor and Microenvironment, German Cancer Research Centre, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Nat Rev Cancer 4:839-49. 2004
    ..What have we recently learned from studying tumour-stroma interactions, and will this help to define new targets for therapy?..
  37. pmc MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis
    L M Coussens
    Cancer Research Institute, University of California, San Francisco 94143, USA
    Cell 103:481-90. 2000
    ..Thus, inflammatory cells can be coconspirators in carcinogenesis...
  38. ncbi Modelling glandular epithelial cancers in three-dimensional cultures
    Jayanta Debnath
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 5:675-88. 2005
    ..Here, we review the important features of epithelial structures grown in 3D basement membrane cultures, and how such models have been used to investigate the mechanisms associated with tumour initiation and progression...
  39. ncbi Hedgehog signalling in cancer formation and maintenance
    Marina Pasca di Magliano
    Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA
    Nat Rev Cancer 3:903-11. 2003
  40. pmc Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation
    Christine Mayr
    Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, and Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Science 315:1576-9. 2007
    ..Thus, losing miRNA-directed repression of an oncogene provides a mechanism for tumorigenesis, and disrupting a single miRNA-target interaction can produce an observable phenotype in mammalian cells...
  41. ncbi Aberrant activation of notch signaling in human breast cancer
    Spyros Stylianou
    Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Christie Hospital NHS Trust, Manchester M13 9PT, United Kingdom
    Cancer Res 66:1517-25. 2006
    ..More significantly, we show that attenuation of Notch signaling reverts the transformed phenotype of human breast cancer cell lines, suggesting that inhibition of Notch signaling may be a therapeutic strategy for this disease...
  42. ncbi Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene
    W J Muller
    Harvard Medical School Department of Genetics, Boston, Massachusetts 02115
    Cell 54:105-15. 1988
    ....
  43. pmc Multistage carcinogenesis and the incidence of colorectal cancer
    E Georg Luebeck
    Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, P O Box 19024, Seattle, WA 98109 1024, USA
    Proc Natl Acad Sci U S A 99:15095-100. 2002
    ..By contrast, interventions that decrease the rate of mutations at the adenomatous polyposis coli locus are much less effective in reducing the risk of colon cancer...
  44. ncbi AP-1: a double-edged sword in tumorigenesis
    Robert Eferl
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Nat Rev Cancer 3:859-68. 2003
  45. ncbi Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis
    Megan Cully
    The Campbell Family Institute for Breast Cancer Research, University Health Network, University of Toronto, Toronto, Ontario M5G 2C1, Canada
    Nat Rev Cancer 6:184-92. 2006
    ..How does the PI3K pathway integrate signals from numerous sources, and how can this information be used in the rational design of cancer therapies?..
  46. ncbi Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models
    Darren N Seril
    Susan L Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 8020, USA
    Carcinogenesis 24:353-62. 2003
    ..Based on this concept, iron over-nutrition is proposed as a risk factor and dietary antioxidants as protective factors for UC and associated carcinogenesis...
  47. ncbi Reversible tumorigenesis by MYC in hematopoietic lineages
    D W Felsher
    Department of Medicine, G W Hooper Foundation, San Francisco, California, USA
    Mol Cell 4:199-207. 1999
    ..We conclude that even though tumorigenesis is a multistep process, remediation of a single genetic lesion may be sufficient to reverse malignancy...
  48. pmc Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis
    Andrew J Holland
    Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, 9500 Gilman Drive, San Diego, La Jolla, California 92093 0670, USA
    Nat Rev Mol Cell Biol 10:478-87. 2009
    ..A clearer understanding of the tumour suppressive function of aneuploidy might reveal new avenues for anticancer therapy...
  49. ncbi p53 mutant mice that display early ageing-associated phenotypes
    Stuart D Tyner
    Cell and Molecular Biology Program, Baylor College of Medicine, Houston, TX 77030, USA
    Nature 415:45-53. 2002
    ..A second line of transgenic mice containing a temperature-sensitive mutant allele of p53 also exhibits early ageing phenotypes. These data suggest that p53 has a role in regulating organismal ageing...
  50. ncbi Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells
    Takeshi Fujiwara
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 437:1043-7. 2005
    ..MMP overexpression is linked to mammary tumours in humans and animal models. Thus, tetraploidy enhances the frequency of chromosomal alterations and promotes tumour development in p53-/- MMECs...
  51. ncbi An essential part for Rho-associated kinase in the transcellular invasion of tumor cells
    K Itoh
    Department of Tumor Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan
    Nat Med 5:221-5. 1999
    ..These results indicate that ROCK plays an essential part in tumor cell invasion, and demonstrate its potential as a therapeutic target for the prevention of cancer invasion and metastasis...
  52. ncbi Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma
    Richard Smith
    The Center for Children, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA
    Cancer Cell 9:405-16. 2006
    ..Thus, we developed a highly validated transcriptional profile for the EWS/FLI fusion protein and identified a critical target gene in Ewing's sarcoma development...
  53. 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...
  54. pmc Stat3 activation by Src induces specific gene regulation and is required for cell transformation
    J Turkson
    H Lee Moffitt Cancer Center and Research Institute, and Department of Biochemistry and Molecular Biology, University of South Florida College of Medicine, Tampa 33612, USA
    Mol Cell Biol 18:2545-52. 1998
    ..Our findings provide evidence that oncogenesis-associated activation of Stat3 signaling is part of the process of malignant transformation...
  55. ncbi Tumour biology: senescence in premalignant tumours
    Manuel Collado
    Spanish National Cancer Centre CNIO, Madrid 28029, Spain
    Nature 436:642. 2005
    ..Senescence is therefore a defining feature of premalignant tumours that could prove valuable in the diagnosis and prognosis of cancer...
  56. ncbi Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes
    S R Romanov
    Department of Pathology and UCSF Comprehensive Cancer Center, University of California at San Francisco, 94143-0506, USA
    Nature 409:633-7. 2001
    ..The differences between epithelial cells and fibroblasts provide new insights into the mechanistic basis of neoplastic transformation...
  57. ncbi Stem cells and breast cancer: A field in transit
    Matthew Smalley
    The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW3 6JB, UK
    Nat Rev Cancer 3:832-44. 2003
  58. ncbi TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia
    Neil A Bhowmick
    Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Science 303:848-51. 2004
    ..Thus, TGF-beta signaling in fibroblasts modulates the growth and oncogenic potential of adjacent epithelia in selected tissues...
  59. ncbi Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction?
    Stephen B Baylin
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Bunting Blaustein Cancer Research Building, 1650 Orleans Street, Suite 530, Baltimore, Maryland 21231, USA
    Nat Rev Cancer 6:107-16. 2006
    ..Strategies to reverse epigenetic gene silencing might therefore be useful in cancer prevention and therapy...
  60. ncbi Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation
    Nabeel Bardeesy
    Department of Adult Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 419:162-7. 2002
    ..Together, our data rationalize several features of PJS polyposis--notably its peculiar histopathological presentation and limited malignant potential--and place Lkb1 in a distinct class of tumour suppressors...
  61. pmc A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers
    J R Bischoff
    SUGEN, Inc, Redwood City, California 94063, USA
    EMBO J 17:3052-65. 1998
    ..These observations implicate aurora2 as a potential oncogene in many colon, breast and other solid tumors, and identify centrosome-associated proteins as novel targets for cancer therapy...
  62. ncbi Cancer susceptibility and the functions of BRCA1 and BRCA2
    Ashok R Venkitaraman
    University of Cambridge, CRC Department of Oncology, Hutchison MRC Research Centre, Hills Road, Cambridge CB2 2XZ, United Kingdom
    Cell 108:171-82. 2002
    ..Here, I examine what is known about the biological functions of the BRCA proteins and ask how their disruption can induce susceptibility to specific types of cancer...
  63. ncbi Oncogenic PI3K and its role in cancer
    Yardena Samuels
    The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University Medical Institutions, Baltimore, Maryland 21231, USA
    Curr Opin Oncol 18:77-82. 2006
    ..The purpose of this review is to examine the contribution of the PI3K signaling pathway to the development of human tumors and to propose further studies to elucidate how to develop therapeutics for patients with mutations in this pathway...
  64. pmc Constitutively active type I insulin-like growth factor receptor causes transformation and xenograft growth of immortalized mammary epithelial cells and is accompanied by an epithelial-to-mesenchymal transition mediated by NF-kappaB and snail
    Hyun Jung Kim
    Baylor College of Medicine, Breast Center MS 600, One Baylor Plaza, Room N1110, Houston, TX 77030, USA
    Mol Cell Biol 27:3165-75. 2007
    ..This study places IGF-IR among a small group of oncogenes that, when overexpressed alone, can confer in vivo tumorigenic growth of MCF10A cells and indicates the hierarchy in the mechanism of IGF-IR-induced EMT...
  65. ncbi Transcriptional regulation and transformation by Myc proteins
    Sovana Adhikary
    Institute for Molecular Biology and Tumour Research, University of Marburg, Emil Mannkopff Strasse 2, 35033 Marburg, Germany
    Nat Rev Mol Cell Biol 6:635-45. 2005
    ..Recently, a wealth of data has shed new light on the biochemical functions of Myc proteins and on the mechanisms through which they function in cellular transformation...
  66. ncbi RAS and RHO GTPases in G1-phase cell-cycle regulation
    Mathew L Coleman
    Abramson Family Cancer Research Institute, BRB II III, 421 Curie Boulevard, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6160, USA
    Nat Rev Mol Cell Biol 5:355-66. 2004
  67. pmc FOXM1 upregulation is an early event in human squamous cell carcinoma and it is enhanced by nicotine during malignant transformation
    Emilios Gemenetzidis
    Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
    PLoS ONE 4:e4849. 2009
    ..The survival of patients is very poor due to the lack of effective early biomarkers. FOXM1 overexpression is linked to the majority of human cancers but its mechanism remains unclear in head and neck squamous cell carcinoma (HNSCC)...
  68. ncbi Effects of cadmium on DNA-(Cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation
    Masufumi Takiguchi
    Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Exp Cell Res 286:355-65. 2003
    ..These results indicate that, while cadmium is an effective inhibitor of DNA MeTase and initially induces DNA hypomethylation, prolonged exposure results in DNA hypermethylation and enhanced DNA MeTase activity...
  69. ncbi The significance of unstable chromosomes in colorectal cancer
    Harith Rajagopalan
    Sidney Kimmel Comprehensive Cancer Center and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA
    Nat Rev Cancer 3:695-701. 2003
    ..Here, we explore experimental and theoretical evidence for the initiation of chromosomal instability in very early colorectal cancers, and reflect on the role that chromosomal instability could have in colorectal tumorigenesis...
  70. pmc Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability
    Derek C Radisky
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Nature 436:123-7. 2005
    ..These findings identify a previously undescribed pathway in which a component of the breast tumour microenvironment alters cellular structure in culture and tissue structure in vivo, leading to malignant transformation...
  71. pmc Inactivation of p53 and Pten promotes invasive bladder cancer
    Anna M Puzio-Kuter
    Department of Urology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA
    Genes Dev 23:675-80. 2009
    ..Our integrated analyses of mouse and human bladder cancer provide a rationale for investigating mTOR inhibition for treatment of patients with invasive disease...
  72. pmc Microenvironment determines lineage fate in a human model of MLL-AF9 leukemia
    Junping Wei
    Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Cancer Cell 13:483-95. 2008
    ..Targeting the Rac signaling pathway by pharmacologic or genetic means resulted in rapid and specific apoptosis of MLL-AF9 cells, suggesting that the Rac signaling pathway may be a valid therapeutic target in MLL-rearranged AML...
  73. pmc Opposite effects of the p52shc/p46shc and p66shc splicing isoforms on the EGF receptor-MAP kinase-fos signalling pathway
    E Migliaccio
    European Institute of Oncology, Department of Experimental Oncology, Milan, Italy
    EMBO J 16:706-16. 1997
    ..Regulation of p66shc expression might, therefore, influence the cellular response to growth factors...
  74. ncbi JunB deficiency leads to a myeloproliferative disorder arising from hematopoietic stem cells
    Emmanuelle Passegue
    Institute of Cancer and Stem Cell Biology and Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell 119:431-43. 2004
    ..These results demonstrate a stem cell-specific role for JunB in normal and leukemic hematopoiesis and provide experimental evidence that leukemic stem cells (LSC) can reside at the LT-HSC stage of development in a mouse model of MPD...
  75. ncbi NF-kappaB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: potential involvement of ZEB-1 and ZEB-2
    H L Chua
    Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
    Oncogene 26:711-24. 2007
    ..MCF10A cells chronically exposed to tumor necrosis factor alpha (TNFalpha), a potent NF-kappaB inducer, also exhibited the EMT-like phenotype and ZEB-1/ZEB-2 induction, both of which were reversed following TNFalpha withdrawal...
  76. ncbi Modeling the initiation and progression of human acute leukemia in mice
    Frédéric Barabé
    Division of Cell and Molecular Biology, University Health Network, Toronto, Ontario, M5G 1L7, Canada
    Science 316:600-4. 2007
    ..The L-ICs retained both myeloid and lymphoid lineage potential and remained responsive to microenvironmental cues. The properties of these cells provide a biological basis for several clinical hallmarks of MLL leukemias...
  77. ncbi PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum
    Silvia Marino
    Institute of Pathology, University Hospital, 8091 Zurich, Switzerland
    Development 129:3513-22. 2002
    ..However, PTEN is not required for cell differentiation and lack of PTEN is not sufficient to induce neoplastic transformation of neuronal or glial cells..
  78. ncbi Non-transcriptional control of DNA replication by c-Myc
    David Dominguez-Sola
    Institute for Cancer Genetics, Department of Genetics and Development and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York 10032, USA
    Nature 448:445-51. 2007
    ..These findings identify a critical function of c-Myc in DNA replication and suggest a novel mechanism for its normal and oncogenic functions...
  79. pmc Stat proteins and oncogenesis
    Jacqueline Bromberg
    Memorial Sloan Kettering Cancer Center, 1230 York Avenue, Box 397, New York, New York 10021, USA
    J Clin Invest 109:1139-42. 2002
  80. ncbi Atypical protein kinase Ciota plays a critical role in human lung cancer cell growth and tumorigenicity
    Roderick P Regala
    Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida 32224, USA
    J Biol Chem 280:31109-15. 2005
    ..Our data indicate that PKCiota may be an attractive molecular target for mechanism-based therapies for treatment of lung cancer...
  81. pmc The tumor suppressor PP2A Abeta regulates the RalA GTPase
    Anna A Sablina
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 129:969-82. 2007
    ..These observations identify PP2A Abeta as a tumor suppressor gene that transforms immortalized human cells by regulating the function of RalA...
  82. ncbi MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior
    Claudia Roldo
    Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA
    J Clin Oncol 24:4677-84. 2006
    ..Recent evidence indicates that microRNAs can contribute to tumor development and progression and may have diagnostic and prognostic value in several human malignancies...
  83. ncbi hTERT-immortalized prostate epithelial and stromal-derived cells: an authentic in vitro model for differentiation and carcinogenesis
    Ira Kogan
    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Cancer Res 66:3531-40. 2006
    ....
  84. pmc Transgenic mice demonstrate AP-1 (activator protein-1) transactivation is required for tumor promotion
    M R Young
    Basic Research Laboratory, National Cancer Institute, Frederick, MD 21702, USA
    Proc Natl Acad Sci U S A 96:9827-32. 1999
    ..We conclude that transactivation of a subset of AP-1-dependent genes is required for tumor promotion and may be targeted for cancer prevention...
  85. pmc E-cadherin as an indicator of mesenchymal to epithelial reverting transitions during the metastatic seeding of disseminated carcinomas
    Alan Wells
    Department of Pathology, Pittsburgh VA Medical Center and University of Pittsburgh, 3550 Terrace St, Scaife Hall, S 713, Pittsburgh, PA 15261, USA
    Clin Exp Metastasis 25:621-8. 2008
    ....
  86. pmc Phosphorylation by Cdk2 is required for Myc to repress Ras-induced senescence in cotransformation
    Per Hydbring
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE 171 77 Stockholm, Sweden
    Proc Natl Acad Sci U S A 107:58-63. 2010
    ..Finally, our findings highlight that pharmacological inhibition of Cdk2 activity is a potential therapeutical principle for cancer therapy, in particular for tumors with activated Myc or Ras...
  87. pmc Scribble mutants promote aPKC and JNK-dependent epithelial neoplasia independently of Crumbs
    Gregory R Leong
    Peter MacCallum Cancer Centre, Victoria, Australia
    BMC Biol 7:62. 2009
    ..Increasing evidence also implicates the loss of human Scrib in cancer. In this report, we investigate how loss of Scrib promotes epithelial tumourigenesis in Drosophila, both alone and in cooperation with oncogenic mutations...
  88. ncbi Spontaneous human adult stem cell transformation
    Daniel Rubio
    Department of Immunology and Oncology, Centro Nacional de Biotecnología Consejo Superior de Investigaciones Científicas, UAM Campus de Cantoblanco, Darwin, 3 E 28049 Madrid, Spain
    Cancer Res 65:3035-9. 2005
    ..Our findings indicate the importance of biosafety studies of mesenchymal stem cell biology to efficiently exploit their full clinical therapeutic potential...
  89. pmc Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development
    Meritxell Gironella
    Institut National de Santé et de Recherche Médicale, U624 Stress Cellulaire, F 13288 Marseille, France
    Proc Natl Acad Sci U S A 104:16170-5. 2007
    ..Finally, TP53INP1 expression is repressed by the oncogenic micro RNA miR-155, which is overexpressed in PDAC cells. TP53INP1 is a previously unknown miR-155 target presenting anti-tumoral activity...
  90. ncbi Sarcoma derived from cultured mesenchymal stem cells
    Jakub Tolar
    Department of Pediatrics, Division of Hematology Oncology, Blood and Marrow Transplant and Cancer Center, University of Minnesota Medical School, Minneapolis, Minnesota, USA
    Stem Cells 25:371-9. 2007
    ..More importantly, our study indicates that sarcoma can evolve from MSC cultures...
  91. ncbi Impaired microRNA processing enhances cellular transformation and tumorigenesis
    Madhu S Kumar
    MIT Center for Cancer Research, Cambridge, Massachusetts 02139, USA
    Nat Genet 39:673-7. 2007
    ..Furthermore, conditional deletion of Dicer1 enhanced tumor development in a K-Ras-induced mouse model of lung cancer. Overall, these studies indicate that abrogation of global miRNA processing promotes tumorigenesis...
  92. ncbi Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer
    Donghui Li
    Department of Gastrointestinal Medical Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Clin Cancer Res 9:991-7. 2003
    ..The purpose of this study was to investigate the expression and copy number alteration of STK15 in pancreatic cancer...
  93. pmc BRCA1 regulates human mammary stem/progenitor cell fate
    Suling Liu
    Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 105:1680-5. 2008
    ..Because BRCA1 also plays a role in DNA repair, our work suggests that loss of BRCA1 may result in the accumulation of genetically unstable breast stem cells, providing prime targets for further carcinogenic events...
  94. pmc Activated oncogenes promote and cooperate with chromosomal instability for neoplastic transformation
    Richard A Woo
    Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong
    Genes Dev 18:1317-30. 2004
    ..These data indicate that chromosomal instability could be a catalyst for oncogenic transformation, and bring together aspects of the chromosomal instability hypothesis and the gene mutation hypothesis for tumorigenesis...
  95. ncbi A human prostatic epithelial model of hormonal carcinogenesis
    Y Wang
    Department of Anatomy, University of California, San Francisco, California 94143, USA
    Cancer Res 61:6064-72. 2001
    ..In addition, the data demonstrate that the stromal environment plays an important role in mediating hormonal carcinogenesis...
  96. ncbi Telomere shortening and tumor formation by mouse cells lacking telomerase RNA
    M A Blasco
    Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 91:25-34. 1997
    ..These results indicate that telomerase is essential for telomere length maintenance but is not required for establishment of cell lines, oncogenic transformation, or tumor formation in mice...
  97. ncbi Linear model of colon cancer initiation
    Franziska Michor
    Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, USA
    Cell Cycle 3:358-62. 2004
    ..We study the consequences of mutations in different cell types and calculate the conditions for CIN to precede APC inactivation. We find that early emergence of CIN is very likely in colorectal tumorigenesis...
  98. ncbi Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: revisiting old hypotheses
    Jean S Fleming
    Eskitis Institute for Cell and Molecular Therapies, School of Biomolecular and Biomedical Sciences, Griffith University Nathan Campus, Nathan, QLD 4111, Australia
    Mol Cell Endocrinol 247:4-21. 2006
    ..The emergence of laser-capture microdissection and expression profiling by microarray technologies offers the promise of defining these pathways more accurately, as well as providing us with the tools for earlier diagnosis...
  99. ncbi Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence
    Akinori Takaoka
    Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Nature 424:516-23. 2003
    ..Our study reveals a hitherto unrecognized link between p53 and IFN-alpha/beta in tumour suppression and antiviral immunity, which may have therapeutic implications...
  100. ncbi MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors
    Brian J P Huntly
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cancer Cell 6:587-96. 2004
    ..These data demonstrate that some, but not all, leukemia oncogenes can confer properties of leukemic stem cells to hematopoietic progenitors destined to undergo apoptotic cell death...
  101. pmc Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers
    Tsuyoshi Etoh
    Pathology Division, National Cancer Center Research Institute, Tokyo, Japan
    Am J Pathol 164:689-99. 2004
    ..Furthermore, DNMT1 may play a significant role in the development of poorly differentiated gastric cancers by inducing frequent DNA hypermethylation of multiple CpG islands...

Research Grants67

  1. Anticarcinogenic Mechanisms of Tea Constituents
    Zigang Dong; Fiscal Year: 2012
    ..is based on our other published data and our preliminary data showing that (a) Pin-1 is critical for neoplastic cell transformation and tumorigenesis;(b) EGCG can bind with Pin-1;(c) EGCG and other tea polyphenols inhibit multiple ..
  2. Molecular Functions of the Adenovirus E1A Oncogene
    Maurice Green; Fiscal Year: 2006
    ..to the N-terminal domain (E1A 1-80) and is required for induction of cell cycle progression and neoplastic cell transformation. Our goals are to understand the mechanism of E1A repression in molecular detail and to identify the ..
  3. Hypoxia Signaling, Chromatin Remodeling and Nickel Carcinogenesis
    Max Costa; Fiscal Year: 2009
    ..These studies will allow us to understand the importance of hypoxia signaling and the HIF-1alpha transcription factor in promoting neoplastic cell transformation.
  4. INHIBITION OF CARCINOGENESIS BY TEA AND TEA CONSTITUENTS
    Zigang Dong; Fiscal Year: 2010
    ..Because these EGCG-binding proteins are critical for cell growth, neoplastic cell transformation and tumorigenicity, we hypothesize that the chemopreventive effect of the tea polyphenol EGCG and its ..
  5. CLINICAL STUDIES OF SIGNAL TRANSDUCTION INHIBITORS
    Alex Adjei; Fiscal Year: 2001
    DESCRIPTION: (Applicant's Description) Regulated cell signaling is critical in neoplastic cell transformation and proliferation. Novel anticancer agents interrupting different points in cell signaling pathways are entering the clinic...
  6. HEPTOCYTE PROLIFERATION AND AFLATOXIN METABOLISM
    Stewart Sell; Fiscal Year: 2004
    ..the effect Of HBV associated injury and AFB I hepatocarcinogensis in these mice. In Specific Aim 3, the effect of HBV associated injury and AFB1 hepatocarcinogenesis in these mice will be examined. ..
  7. STEM CELLS AND HEPATOCARCINOGENESIS
    Stewart Sell; Fiscal Year: 2009
    ..Knowledge of the cellular origin of cancer is critical for understanding how cancer evolves and for developing prevention strategies. ..
  8. Role of HPV16 E7/E2F6 interaction in viral oncogenesis
    Margaret McLaughlin Drubin; Fiscal Year: 2006
    ..These studies will further the understanding of how viral proteins interact with cellular factors to induce cancer. [unreadable] [unreadable] [unreadable] [unreadable]..
  9. DIFFERENTIATION OF BLOOD STEM CELLS INTO LIVER CELLS
    Stewart Sell; Fiscal Year: 2005
    ..If this project is successful, it would overcome a major hurdle in the possible use of hepatic stem cells for treatment of liver failure or ex vivo gene therapy. ..
  10. STEM CELLS AND AGING
    Stewart Sell; Fiscal Year: 2008
    ..The results of these experiments should provide critical proof for one of the most important hypothetical properties of adult stem cells. ..
  11. AFB1 AND P53 CARCINOGENESIS IN HBSAG TRANSGENIC MICE
    Stewart Sell; Fiscal Year: 2002
    ..These studies should lead to an understanding of how each of these risk factors affect hepatocyte proliferation and how these effects contribute to AFB1 hepatocarcinogenesis. ..
  12. O2 SENSING BY MITOCHONDRIA DURING INTERMITTENT HYPOXIA
    Paul Schumacker; Fiscal Year: 2003
    ..Collectively, these studies could identify a novel mechanism of O2 sensing in the lung, and provide a mechanistic explanation for the activation of gene transcritpion and cellular proliferation during intermittent hypoxia. ..
  13. Firefly Shared Instrument Grant
    Dean Felsher; Fiscal Year: 2008
    ..David Hirschberg. A vital additional component of our program involves the integration of data through support from Bioinformatics [see Letter, Amar Das]. [unreadable] [unreadable] [unreadable]..
  14. CYTOGENETIC MODELS FOR ASSESSING LOW DOSE RADIATION RISK
    Rainer Sachs; Fiscal Year: 2001
    ..By studying molecular, mechanisms relevant to low doses and low dose-rates quantitatively the project will help firm-up risk estimates and make them more credible. ..
  15. O2 Sensing in Hypoxic Pulmonary Vasoconstriction
    Paul Schumacker; Fiscal Year: 2009
    ..Collectively, these studies will test whether a common O2 sensing mechanism functions in PA myocytes and endothelial cells to trigger their diverse responses in HPV. ..
  16. Molecular and Cellular Basis of Oncogene Addiction
    Dean W Felsher; Fiscal Year: 2010
    ..The results of our proposed experiments will have important implications for the mechanisms by which the MYC oncogene maintains tumorigenesis and the development of new therapies for the treatment of cancer. ..
  17. Colon and liver anticarcinogenicity by acetaminophen
    Gary Williams; Fiscal Year: 2004
    ..In addition, these experiments will provide support for the epidemiological observations of reduced cancer risk associated with the use of APAP. ..
  18. C-MYC INDUCED TUMORIGENESIS AND GENOMIC INSTABILITY
    Dean Felsher; Fiscal Year: 2002
    ....
  19. Updating Chromosome Aberration Simulator (CAS) Software
    Rainer Sachs; Fiscal Year: 2006
    ..An interdisciplinary team has been assembled for this project. The grant would ensure that a computer resource important to the radiation cytogenetics community is kept fully current and readily available. ..
  20. OXYGEN SENSING AND CELL SIGNALING IN HYPOXIA
    Paul Schumacker; Fiscal Year: 2001
    ..These studies will identify a novel pathway of cellular O2 detection, and may help clarify understanding of how cells adapt to lowered O2 conditions. ..
  21. 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. ..
  22. Hormonal regulation of p53 activity in mammary tissue
    D Jerry; Fiscal Year: 2008
    ..The results will lead to identification of cellular mechanisms that regulate p53 function in the mammary epithelium. These pathways will provide novel targets for both treatment and prevention of breast cancer. ..
  23. Adult pancreatic progenitor cells as target of early oncogenic events
    CATHERINE CARRIERE; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  24. MURINE STK RECEPTOR AND MACROPHAGE ACTIVATION
    PAMELA CORRELL; Fiscal Year: 2002
    ..By understanding, in more detail, the regulation of macrophage activation, the PI hopes to begin to identify targets for suppression of the tissue-damaging effects of inflammation without compromising the host immune response. ..
  25. Chemical Antagonists of IAP-Family Anti-Apoptotic Proteins
    John Reed; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  26. Mitochondria and Apoptosis (revised GM60554)
    John Reed; Fiscal Year: 2009
    ..abstract_text> ..
  27. TARGET-GUIDED DEVELOPMENT OF SPECIFIC AKT INHIBITORS
    Peter Vogt; Fiscal Year: 2008
    ..4) Investigate the structure-activity relationship through in situ click chemistry and optimize inhibitors for potency, selectivity and cell-based activity ..
  28. PROTEIN TYROSINE DEPHOSPHORYLATION & SIGNAL TRANSDUCTION
    Nicholas Tonks; Fiscal Year: 2008
    ..Furthermore, proteomics-based strategies are being developed for PTP identification in biological samples, to define novel therapeutic targets for human disease. ..
  29. Metabolism of Vitamin A in the Prostate
    Lorraine Gudas; Fiscal Year: 2009
    ..The knowledge generated from these studies should allow us to devise better pharmacological strategies to reverse specific gene repression and to restore more normal retinoid signaling in malignant cells. ..
  30. Developmental Regulation of MacroH2A1 Chromatin Assembly
    Theodore Rasmussen; Fiscal Year: 2009
    ..Research proposed here will provide basic insights into differentiation biology and provide a framework for future attempts to achieve rationally-guided ES cell differentiation. ..
  31. The Werner Syndrome Protein in DNA Replication, Mutagenesis and Genomic Stability
    Lawrence A Loeb; Fiscal Year: 2010
    ..All of the procedures have been established and are ongoing in our laboratory and can be completed within two years. ..
  32. Regulation of Hepatic Excretion of Xenobiotics by Mrps
    Curtis D Klaassen; Fiscal Year: 2010
    ..Elucidation of the role of Nrf2 in the regulation of the efflux transport process will have significant ramifications in toxicology, xenobiotics disposition, drug-drug interaction, and cancer chemoprevention. ..
  33. PATHOGENESIS OF HEPATOCELLULAR CARCINOMA
    Nelson Fausto; Fiscal Year: 2010
    ..The proposed experiments will increase our understanding of the mechanisms of hepatocellular carcinogenesis, and test therapeutic strategies that might be applied to human tumors. ..
  34. SAG E3 ubiquitin ligase in angiogenesis & carcinogenesis
    Yi Sun; Fiscal Year: 2010
    ..Targeting SAG in cancer cells, via siRNA silencing or small molecule inhibitors, would, therefore, be a valid antianglogenesis therapy. ..
  35. The Role of MLL-AF9 in Acute Myeloid Leukemia
    James C Mulloy; Fiscal Year: 2010
    ..RELEVANCE (See instructions): We have recently shown that human blood stem cells can be induced to make leukemia upon introduction ..
  36. Mechanisms of chemopreventive effect of resveratrol
    Zigang Dong; Fiscal Year: 2009
    ..Our long-term goal is to identify the molecular mechanism explaining the anti-tumor effect exhibited by resveratrol. Such knowledge will help in developing better chemopreventive agents with fewer side effects. ..
  37. Adhesion signaling by a novel mitotic substrate of src
    Mark Moasser; Fiscal Year: 2009
    ..abstract_text> ..
  38. STRUCTURE AND FUNCTION OF HIV GAG PROTEIN
    MARILYN RESH; Fiscal Year: 2009
    ..Multicolor imaging with site-specific fluorescein derivatives (FLASH and ReAsH) will be used to determine the order in which Gag assembly sites are formed and maintained in the cell. ..
  39. Proteomic Validation of the Min Mouse Model of Colon Cancer
    Anthony Yeung; Fiscal Year: 2007
    ..The Min mouse model genetically mimics humans for colon cancer. The proposed work will demonstrate whether it is a perfect model for the human disease. ..
  40. Biology of Breast Cancers Arising in Older Women
    Christopher Benz; Fiscal Year: 2007
    ..abstract_text> ..
  41. CELL-SURFACE PROTEINS IN CAMPYLOBACTER FETUS VIRULENCE
    Martin Blaser; Fiscal Year: 2004
    ..Finally, the data generated can be used to develop a mathematical model of antigenic variation that focuses on the relationship between microbial recombination generating diversity and host selection determining the direction of change. ..
  42. MOLECULAR MECHANISMS OF MAMMALIAN CHECKPOINT PATHWAYS
    MICHAEL KASTAN; Fiscal Year: 2004
    ....
  43. THE ONCOGENICITY OF WINGED HELIX PROTEINS
    Peter Vogt; Fiscal Year: 2003
    ..The nature of activating mutations, the interactions with the preinitiation complex, and the identity and function of target genes will reveal novel molecular targets for therapeutic intervention. ..
  44. INTEGRATION OF FIBROBLAST FUNCTIONING IN WOUND HEALING
    Alan Wells; Fiscal Year: 2003
    ..Understanding the delicate balance of these molecular mechanisms is important for rationally designing interventions to achieve normal wound healing. ..
  45. GENES INVOLVED IN AIDS LYMPHOMAGENESIS
    Michael Teitell; Fiscal Year: 2002
    ..Genes with significant involvement in the etiology and/or progression of lymphomagenesis, or those with reproducible in vitro biochemical effects, will be further characterized by molecular methods. ..
  46. TGF BETA RECEPTOR MUTATIONS AND HUMAN CANCER
    William Grady; Fiscal Year: 2002
    ....
  47. MOLECULAR REGULATION OF SIGNALING BY IONIZING RADIATION
    Donald Kufe; Fiscal Year: 2002
    ....
  48. H PYLORI RECOMBINATION AND GASTRIC COLONIZATION
    Martin Blaser; Fiscal Year: 2001
    ..pylori infections. ..
  49. Role of AML1/ETO in Hematopoiesis and Leukemogenesis
    JAMES MULLOY; Fiscal Year: 2005
    ..The establishment of a small animal model of AML will greatly enhance our ability to develop and test treatment strategies and drugs that may be useful in the therapy of AML. ..
  50. Int5/Aromatase Effect of Breast Estrogen in Neoplasia
    RAJESHWAR TEKMAL; Fiscal Year: 2005
    ..abstract_text> ..
  51. Peptide Reagents for Detection of Colonic Dysplasia
    Thomas Wang; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  52. RUNX-fusion Target Genes in Normal and Leukemic Hematopoiesis
    JAMES MULLOY; Fiscal Year: 2007
    ..Understanding the modulation of the self-renewal process by these fusion proteins could give insight into the normal mechanisms of self-renewal employed by the stem cell. [unreadable] [unreadable]..
  53. Identification of Histone Gene Regulatory Sequences
    Gary Stein; Fiscal Year: 2006
    ..These studies will elucidate parameters of growth control that mediate competency for proliferation and cell cycle progression. [unreadable] [unreadable]..
  54. Liver Injury in Alpha-1-Antitrypsin Deficiency
    David Perlmutter; Fiscal Year: 2007
    ..Thus, the studies proposed in this competitive renewal application will address the novel concept that oxidative stress causes, or contributes to, liver cell injury in alpha-1-ATZ deficiency. ..
  55. Unique BRCA1 transcriptional response leading to repair
    Wafik El Deiry; Fiscal Year: 2006
    ..Our studies will increase our understanding of the mechanism of action of BRCA1 and may provide novel strategies for therapeutic design, for example by targeting DDB2. ..
  56. PTH (7-34) for Chemotherapy alopecia in Breast Cancer
    Michael Holick; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  57. dementias of the Alzheimer's Type
    George Martin; Fiscal Year: 2005
    ..abstract_text> ..
  58. KILLER/DR5 AND TUMORIGENESIS
    Wafik El Deiry; Fiscal Year: 2001
    ..These experiments could lead to novel strategies for anti-cancer therapy. ..
  59. ESOPHAGEAL ADENOCARCINOGENESIS AND ITS PREVENTION
    Chung Yang; Fiscal Year: 2007
    ..These studies are expected to fully elucidate the roles of oxidative stress and aberrant AA metabolism in the formation of EAC and help develop effective agents for its prevention. ..
  60. BIOLOGY OF KSHV/HHV8 G PROTEIN COUPLED RECEPTOR
    ENRIQUE MESRI; Fiscal Year: 2009
    ..abstract_text> ..
  61. HMG-1/Y AND NEOPLASTIC TRANSFORMATION
    Linda Resar; Fiscal Year: 2002
    ..Insight gained from these studies should advance our understanding of malignancies associated with increased c-myc and or HMG-I/Y expression and may lead to new treatment strategies. ..
  62. MOLECULAR MECHANISMS OF ARA-C THERAPY IN MAN
    Donald Kufe; Fiscal Year: 2005
    ..abstract_text> ..
  63. Exposure to beef growth promoter in breast cancer
    YOUNG LIN; Fiscal Year: 2003
    ....