cell hypoxia

Summary

Summary: A condition of decreased oxygen content at the cellular level.

Top Publications

  1. ncbi Hypoxia--a key regulatory factor in tumour growth
    Adrian L Harris
    Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
    Nat Rev Cancer 2:38-47. 2002
  2. pmc Notch signaling mediates hypoxia-induced tumor cell migration and invasion
    Cecilia Sahlgren
    Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, SE 171 77 Stockholm, Sweden
    Proc Natl Acad Sci U S A 105:6392-7. 2008
  3. ncbi HIF-1 and HIF-2 transcription factors--similar but not identical
    Agnieszka Loboda
    Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
    Mol Cells 29:435-42. 2010
  4. pmc Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension
    G L Wang
    Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287 3914, USA
    Proc Natl Acad Sci U S A 92:5510-4. 1995
  5. ncbi Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation
    P Jaakkola
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
    Science 292:468-72. 2001
  6. pmc Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
    J A Forsythe
    Department of Physiology, University of Maryland School of Medicine, Baltimore, 21201, USA
    Mol Cell Biol 16:4604-13. 1996
  7. ncbi The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
    P H Maxwell
    Wellcome Trust Centre for Human Genetics, Oxford, UK
    Nature 399:271-5. 1999
  8. pmc A microRNA signature of hypoxia
    Ritu Kulshreshtha
    Molecular Oncology Research Institute, Tufts New England Medical Center, Boston, Massachusetts 02111, USA
    Mol Cell Biol 27:1859-67. 2007
  9. ncbi HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing
    M Ivan
    Dana Farber Cancer Institute and Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Science 292:464-8. 2001
  10. pmc Hypoxia-inducible factors and the response to hypoxic stress
    Amar J Majmundar
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Mol Cell 40:294-309. 2010

Detail Information

Publications260 found, 100 shown here

  1. ncbi Hypoxia--a key regulatory factor in tumour growth
    Adrian L Harris
    Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
    Nat Rev Cancer 2:38-47. 2002
    ..Many elements of the hypoxia-response pathway are therefore good candidates for therapeutic targeting...
  2. pmc Notch signaling mediates hypoxia-induced tumor cell migration and invasion
    Cecilia Sahlgren
    Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, SE 171 77 Stockholm, Sweden
    Proc Natl Acad Sci U S A 105:6392-7. 2008
    ..In sum, these data demonstrate a complex integration of the hypoxia and Notch signaling pathways in regulation of EMT and open up perspectives for pharmacological intervention with hypoxiainduced EMT and cell invasiveness in tumors...
  3. ncbi HIF-1 and HIF-2 transcription factors--similar but not identical
    Agnieszka Loboda
    Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
    Mol Cells 29:435-42. 2010
    ..Finally, recent data showing link between HIFs and specific microRNA have been presented...
  4. pmc Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension
    G L Wang
    Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287 3914, USA
    Proc Natl Acad Sci U S A 92:5510-4. 1995
    ....
  5. ncbi Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation
    P Jaakkola
    The Henry Wellcome Building of Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
    Science 292:468-72. 2001
    ..An absolute requirement for dioxygen as a cosubstrate and iron as cofactor suggests that HIF-PH functions directly as a cellular oxygen sensor...
  6. pmc Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
    J A Forsythe
    Department of Physiology, University of Maryland School of Medicine, Baltimore, 21201, USA
    Mol Cell Biol 16:4604-13. 1996
    ..VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. These findings implicate HIF-1 in the activation of VEGF transcription in hypoxic cells...
  7. ncbi The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
    P H Maxwell
    Wellcome Trust Centre for Human Genetics, Oxford, UK
    Nature 399:271-5. 1999
    ..Thus, constitutive HIF-1 activation may underlie the angiogenic phenotype of VHL-associated tumours. The pVHL/HIF-1 interaction provides a new focus for understanding cellular oxygen sensing...
  8. pmc A microRNA signature of hypoxia
    Ritu Kulshreshtha
    Molecular Oncology Research Institute, Tufts New England Medical Center, Boston, Massachusetts 02111, USA
    Mol Cell Biol 27:1859-67. 2007
    ..Interestingly, the vast majority of hypoxia-induced microRNAs are also overexpressed in a variety of human tumors...
  9. ncbi HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing
    M Ivan
    Dana Farber Cancer Institute and Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Science 292:464-8. 2001
    ..Because proline hydroxylation requires molecular oxygen and Fe(2+), this protein modification may play a key role in mammalian oxygen sensing...
  10. pmc Hypoxia-inducible factors and the response to hypoxic stress
    Amar J Majmundar
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Mol Cell 40:294-309. 2010
    ..These transcription factors function in normal tissue homeostasis and impinge on critical aspects of disease progression and recovery. Insights from basic HIF biology are being translated into pharmaceuticals targeting the HIF pathway...
  11. ncbi Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1
    Daniel J Ceradini
    Laboratory of Microvascular Research and Vascular Tissue Engineering, Institute of Reconstructive Plastic Surgery, New York University School of Medicine, New York, New York 10016, USA
    Nat Med 10:858-64. 2004
    ..These data show that the recruitment of CXCR4-positive progenitor cells to regenerating tissues is mediated by hypoxic gradients via HIF-1-induced expression of SDF-1...
  12. ncbi Hypoxia in cancer: significance and impact on clinical outcome
    Peter Vaupel
    Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, 55099 Mainz, Germany
    Cancer Metastasis Rev 26:225-39. 2007
    ..g., different immunohistochemical staining procedures) may compromise the power of the prognostic parameter used...
  13. pmc Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation
    Xin Huang
    Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94025, USA
    Mol Cell 35:856-67. 2009
    ..Taken together, these data implicate an important role for mir-210 in regulating the hypoxic response of tumor cells and tumor growth...
  14. pmc MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3
    Pasquale Fasanaro
    Laboratorio di Patologia Vascolare, Istituto Dermopatico dell Immacolata, IRCCS, 00167 Rome
    J Biol Chem 283:15878-83. 2008
    ..We conclude that miR-210 up-regulation is a crucial element of endothelial cell response to hypoxia, affecting cell survival, migration, and differentiation...
  15. ncbi Targeting hypoxia in cancer therapy
    William R Wilson
    Auckland Cancer Society Research Centre, The University of Auckland, Auckland, New Zealand
    Nat Rev Cancer 11:393-410. 2011
    ..We address the particular challenges and opportunities these overlapping strategies present, and discuss the central importance of emerging diagnostic tools for patient stratification in targeting hypoxia...
  16. pmc HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion
    Rose Du
    Department of Neurological Surgery, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA
    Cancer Cell 13:206-20. 2008
    ..VEGF also directly regulates tumor cell invasiveness. When VEGF activity is impaired, tumor cells invade deep into the brain in the perivascular compartment...
  17. ncbi Oxygen in stem cell biology: a critical component of the stem cell niche
    Ahmed Mohyeldin
    Department of Neurosurgery and Oncology, Brain Tumor Stem Cell Laboratory, The Johns Hopkins School of Medicine, Baltimore, MD 21231, USA
    Cell Stem Cell 7:150-61. 2010
    ..These findings have important implications on our understanding of development, disease, and tissue-engineering practices and furthermore elucidate an added dimension of stem cell control within the niche...
  18. pmc The impact of O2 availability on human cancer
    Jessica A Bertout
    Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Cancer 8:967-75. 2008
    ..The central role played by intra-tumoural hypoxia and HIF in these processes has made them attractive therapeutic targets in the treatment of multiple human malignancies...
  19. pmc Hypoxia-inducible factors, stem cells, and cancer
    Brian Keith
    Abramson Family Cancer Research Institute, University of Pennsylvania, 453 BRB II III, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Cell 129:465-72. 2007
    ..As many cancers are thought to develop from a small number of transformed, self-renewing, and multipotent "cancer stem cells," these results suggest new roles for HIFs in tumor progression...
  20. ncbi HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia
    Jung whan Kim
    Graduate Program of Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Cell Metab 3:177-85. 2006
    ..These studies reveal a hypoxia-induced metabolic switch that shunts glucose metabolites from the mitochondria to glycolysis to maintain ATP production and to prevent toxic ROS production...
  21. ncbi Oxygen sensing by HIF hydroxylases
    Christopher J Schofield
    The Oxford Centre for Molecular Sciences and The Dyson Perrins Laboratory, Department of Chemistry, South Parks Road, Oxford OX1 3QY, UK
    Nat Rev Mol Cell Biol 5:343-54. 2004
  22. pmc Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1
    Weibo Luo
    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 145:732-44. 2011
    ..Thus, PKM2 participates in a positive feedback loop that promotes HIF-1 transactivation and reprograms glucose metabolism in cancer cells...
  23. ncbi Hypoxia, HIF1 and glucose metabolism in the solid tumour
    Nicholas C Denko
    Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nat Rev Cancer 8:705-13. 2008
    ..As discussed in this Perspective, new data suggests that this metabolic switch may provide a benefit to the tumour not by increasing glycolysis but by decreasing mitochondrial activity...
  24. ncbi Exploiting tumour hypoxia in cancer treatment
    J Martin Brown
    Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford, California 94305, USA
    Nat Rev Cancer 4:437-47. 2004
  25. ncbi Lysyl oxidase is essential for hypoxia-induced metastasis
    Janine T Erler
    Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 440:1222-6. 2006
    ..Furthermore, LOX may be required to create a niche permissive for metastatic growth. Our findings indicate that LOX is essential for hypoxia-induced metastasis and is a good therapeutic target for preventing and treating metastases...
  26. pmc HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression
    E Laughner
    Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3914, USA
    Mol Cell Biol 21:3995-4004. 2001
    ..These data provide a molecular basis for VEGF induction and tumor angiogenesis by heregulin-HER2 signaling and establish a novel mechanism for the regulation of HIF-1alpha expression...
  27. pmc HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth
    Kelly L Covello
    Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 20:557-70. 2006
    ....
  28. pmc Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells
    Zhizhong Li
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Cancer Cell 15:501-13. 2009
    ..Our results demonstrate that GSCs differentially respond to hypoxia with distinct HIF induction patterns, and HIF2alpha might represent a promising target for antiglioblastoma therapies...
  29. pmc NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha
    Jordi Rius
    Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0723, USA
    Nature 453:807-11. 2008
    ..IKK-beta is also essential for HIF-1alpha accumulation in macrophages experiencing a bacterial infection. Hence, IKK-beta is an important physiological contributor to the hypoxic response, linking it to innate immunity and inflammation...
  30. ncbi Drug resistance and the solid tumor microenvironment
    Olivier Tredan
    Division of Applied Molecular Oncology and Department of Medical Oncology and Hematology, Princess Margaret Hospital, 610 University Ave, Toronto, ON M5G 2M9, Canada
    J Natl Cancer Inst 99:1441-54. 2007
    ....
  31. pmc MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia
    Zhong Hua
    Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China
    PLoS ONE 1:e116. 2006
    ..The competitive principle, differential regulation, multi-miRNA binding sites, and false positive miRNAs might be useful strategies in the avoidance of unwanted cross-action among genes targeted by miRNAs with multiple targets...
  32. pmc MicroRNA-210: a unique and pleiotropic hypoxamir
    Stephen Y Chan
    Harvard Medical School Boston, MA
    Cell Cycle 9:1072-83. 2010
    ..Thus, reflecting the pleiotropic actions of HIF-α, miR-210 appears to function as a "master microRNA" relevant for the control of diverse functions in the hypoxic state...
  33. ncbi Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1
    G L Semenza
    Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
    Annu Rev Cell Dev Biol 15:551-78. 1999
    ..HIF-1 thus appears to function as a master regulator of O2 homeostasis that plays essential roles in cellular and systemic physiology, development, and pathophysiology...
  34. ncbi Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules
    Benjamin J Moeller
    Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    Cancer Cell 5:429-41. 2004
    ..These data describe novel pathways contributing significantly to our understanding of HIF-1 regulation which may be major determinants of tumor radiosensitivity, potentially having high clinical relevance...
  35. ncbi Hypoxia signalling through mTOR and the unfolded protein response in cancer
    Bradly G Wouters
    Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada
    Nat Rev Cancer 8:851-64. 2008
    ....
  36. pmc MicroRNA regulation of DNA repair gene expression in hypoxic stress
    Meredith E Crosby
    Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520 8040, USA
    Cancer Res 69:1221-9. 2009
    ....
  37. pmc miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity
    M P Puissegur
    Institut de Pharmacologie Moleculaire et Cellulaire, CNRS UMR6097, Sophia Antipolis, France
    Cell Death Differ 18:465-78. 2011
    ..These observations help explain contradictory data regarding miR-210 expression and its putative function in solid tumors...
  38. pmc The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype
    John M Heddleston
    Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH, USA
    Cell Cycle 8:3274-84. 2009
    ....
  39. pmc The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5
    Kasper M A Rouschop
    Department of Radiation Oncology Maastro Lab, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
    J Clin Invest 120:127-41. 2010
    ..Our data therefore demonstrate that the UPR is an important mediator of the hypoxic tumor microenvironment and that it contributes to resistance to treatment through its ability to facilitate autophagy...
  40. pmc A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation
    G L Semenza
    Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
    Mol Cell Biol 12:5447-54. 1992
    ..We have thus defined a functionally tripartite, 50-nt hypoxia-inducible enhancer which binds several nuclear factors, one of which is induced by hypoxia via de novo protein synthesis...
  41. ncbi Direct regulation of TWIST by HIF-1alpha promotes metastasis
    Muh Hwa Yang
    Institutes of Biochemistry and Molecular Biology, National Yang Ming University, No 155, Sec 2, Li Niong Street, Peitou, Taipei 112, Taiwan
    Nat Cell Biol 10:295-305. 2008
    ..These results provide evidence of a key signalling pathway involving HIF-1alpha and TWIST that promotes metastasis in response to intratumoural hypoxia...
  42. pmc Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin
    Christine C Hudson
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 22:7004-14. 2002
    ..These studies position mTOR as an upstream activator of HIF-1 function in cancer cells and suggest that the antitumor activity of rapamycin is mediated, in part, through the inhibition of cellular responses to hypoxic stress...
  43. ncbi Hypoxia and cancer
    M Christiane Brahimi-Horn
    Institute of Signaling, Developmental Biology and Cancer Research, University of Nice, CNRS UMR 6543, Centre A Lacassagne, 33 Avenue Valombrose, 06189, Nice, France
    J Mol Med (Berl) 85:1301-7. 2007
    ..It is hoped that a better understanding of the mechanisms implicated will lead to alternative and more efficient therapeutic approaches...
  44. ncbi Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling
    Ryota Uemura
    Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267 0529, USA
    Circ Res 98:1414-21. 2006
    ..Preconditioning of BMSCs enhanced their survival and ability to attenuate LV remodeling, which was attributable, in part, to paracrine effects...
  45. ncbi HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells
    Ryo Fukuda
    Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 129:111-22. 2007
    ..Thus, mammalian cells respond to hypoxia by altering COX subunit composition, as previously observed in yeast, but by a completely different molecular mechanism...
  46. ncbi Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha
    A Soeda
    Brain Tumor Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA
    Oncogene 28:3949-59. 2009
    ..This study illustrates the importance of the tumor microenvironment in determining cellular behavior...
  47. pmc Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains
    Gregory Bellot
    Institute of Developmental Biology and Cancer Research, University of Nice, CNRS UMR 6543, Lacassagne, 33 Avenue de Valombrose, 06189 Nice, France
    Mol Cell Biol 29:2570-81. 2009
    ..Hypoxia-induced autophagy via BNIP3 and BNIP3L is clearly a survival mechanism that promotes tumor progression...
  48. pmc Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2
    Ha Won Kim
    Department of Pathology, University of Cincinnati, Cincinnati, Ohio 45267, USA
    J Biol Chem 284:33161-8. 2009
    ..These results highlighted that IP by multiple short episodes of I/R is a novel strategy to promote stem cell survival...
  49. pmc Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation
    Cheng Jun Hu
    Abramson Family Cancer Research Institute Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Mol Cell Biol 23:9361-74. 2003
    ..Importantly, HIF-1alpha (and not HIF-2alpha) stimulates glycolytic gene expression in both types of cells, clearly showing for the first time that HIF-1alpha and HIF-2alpha have unique targets...
  50. pmc HIF-1 alpha is required for solid tumor formation and embryonic vascularization
    H E Ryan
    Department of Biology, University of California, San Diego, La Jolla, CA 92093 0366, USA
    EMBO J 17:3005-15. 1998
    ..These data demonstrate the essential role of HIF-1alpha in controlling both embryonic and tumorigenic responses to variations in microenvironmental oxygenation...
  51. ncbi MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT
    Zhan Zhang
    Rosetta Inpharmatics LLC, Seattle, WA, USA
    Cell Cycle 8:2756-68. 2009
    ..Thus, miR-210 influences the hypoxia response in tumor cells through targeting a key transcriptional repressor of the MYC-MAX network...
  52. ncbi Concordant regulation of gene expression by hypoxia and 2-oxoglutarate-dependent dioxygenase inhibition: the role of HIF-1alpha, HIF-2alpha, and other pathways
    Gareth P Elvidge
    Oxygen Sensing Group, The Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford OX3 7BN
    J Biol Chem 281:15215-26. 2006
    ..Nevertheless, the definition of genes regulated by both hypoxia and DMOG, but not HIF, distinguished other pathways most likely involving the action of 2-OG-dependent dioxygenases on non-HIF substrates...
  53. ncbi Biology of HIF-1alpha
    A Weidemann
    Division of Biological Sciences, Molecular Biology Section, University of California, San Diego, La Jolla, CA 92093, USA
    Cell Death Differ 15:621-7. 2008
    ..The transcriptional complex hypoxia-inducible factor has emerged as a key regulator of the molecular hypoxic response, mediating a wide range of physiological and cellular mechanisms necessary to adapt to reduced oxygen...
  54. pmc Low O2 tensions and the prevention of differentiation of hES cells
    Toshihiko Ezashi
    Department of Animal Sciences, University of Missouri, Columbia, MO 65211, USA
    Proc Natl Acad Sci U S A 102:4783-8. 2005
    ..In addition, hES cell growth under hypoxia provided enhanced formation of embryoid bodies. Hypoxic culture would appear to be necessary to maintain full pluripotency of hES cells...
  55. ncbi Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways
    Nadine Rohwer
    Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charite Universitatsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
    Drug Resist Updat 14:191-201. 2011
    ..Specifically, we will highlight the multifaceted interaction of HIF with apoptosis, senescence, autophagy, p53 and mitochondrial activity and outline how these are at the heart of HIF-mediated therapy failure...
  56. ncbi Reactive species mechanisms of cellular hypoxia-reoxygenation injury
    Chuanyu Li
    Department of Veterans Affairs Medical Center, Birmingham 35233, USA
    Am J Physiol Cell Physiol 282:C227-41. 2002
    ..This review focuses on the specific roles of ROS and RNS in the cellular response to hypoxia and subsequent cytolytic injury during reoxygenation...
  57. ncbi Hypoxia-driven selection of the metastatic phenotype
    Richard Sullivan
    Department of Anatomy and Cell Biology, Queen s University, Kingston, ON K7L 3N6, Canada
    Cancer Metastasis Rev 26:319-31. 2007
    ..Through regulation of these critical molecular targets, hypoxia promotes each step of the metastatic cascade and selects tumor cell populations that are able to escape the unfavorable microenvironment of the primary tumor...
  58. pmc HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity
    John D Gordan
    Abramson Family Cancer Research Institute, School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Cancer Cell 11:335-47. 2007
    ..Enhanced c-Myc activity likely contributes to HIF-2alpha-mediated neoplastic progression following loss of the VHL tumor suppressor and influences the behavior of hypoxic tumor cells...
  59. pmc Hypoxia-inducible factor-1 alpha-dependent induction of FoxP3 drives regulatory T-cell abundance and function during inflammatory hypoxia of the mucosa
    Eric T Clambey
    Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO 80045, USA
    Proc Natl Acad Sci U S A 109:E2784-93. 2012
    ..These studies demonstrate that hypoxia is an intrinsic molecular cue that promotes FoxP3 expression, in turn eliciting potent anti-inflammatory mechanisms to limit tissue damage in conditions of reduced oxygen availability...
  60. ncbi Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha
    Ji Hong Lim
    Department of Pharmacology, Ischemic Hypoxic Disease Institute, Seoul National University College of Medicine, 28 Yongon Dong, Chongno Gu, Seoul 110 799, Korea
    Mol Cell 38:864-78. 2010
    ..Our results suggest that crosstalk between oxygen- and redox-responsive signal transducers occurs through the SIRT1-HIF-1alpha interaction...
  61. pmc Passing the baton: the HIF switch
    Mei Yee Koh
    Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    Trends Biochem Sci 37:364-72. 2012
    ..Here, we review the significance of the HIF switch and the relation between HIF-1 and HIF-2 under both physiological and pathophysiological conditions...
  62. pmc Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes
    Jung Eun Park
    School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore
    Mol Cell Proteomics 9:1085-99. 2010
    ..Two tetraspanins, CD9 and CD81, co-immunoprecipitated. Together, these data suggested that tumor cells secrete proteins and exosomes with the potential to modulate their microenvironment and facilitate angiogenesis and metastasis...
  63. pmc Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts
    David R Mole
    Henry Wellcome Building of Molecular Physiology, University of Oxford, Oxford OX3 7BN, United Kingdom
    J Biol Chem 284:16767-75. 2009
    ..Given emerging evidence for biologically distinct functions of HIF-1alpha versus HIF-2alpha understanding the mechanisms restricting HIF-2alpha activity will be of interest...
  64. pmc HIF induces human embryonic stem cell markers in cancer cells
    Julie Mathieu
    Department of Biochemistry, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA
    Cancer Res 71:4640-52. 2011
    ..In primary glioma-derived CD133 negative cells, hypoxia was able to induce neurospheres and hESC markers. Together, these findings suggest that HIF targets may act as key inducers of a dynamic state of stemness in pathologic conditions...
  65. pmc P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis
    Munekazu Yamakuchi
    Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Proc Natl Acad Sci U S A 107:6334-9. 2010
    ..Finally, in human colon cancer specimens, expression of miR-107 is inversely associated with expression of HIF-1beta. Taken together these data suggest that miR-107 can mediate p53 regulation of hypoxic signaling and tumor angiogenesis...
  66. pmc MicroRNA-210 as a novel therapy for treatment of ischemic heart disease
    Shijun Hu
    Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA 94305 5111, USA
    Circulation 122:S124-31. 2010
    ..We hypothesize that microRNA-210 can rescue cardiac function after myocardial infarction by upregulation of angiogenesis and inhibition of cellular apoptosis in the heart...
  67. ncbi Hypoxia inhibits senescence and maintains mesenchymal stem cell properties through down-regulation of E2A-p21 by HIF-TWIST
    Chih Chien Tsai
    Institute of Pharmacology, National Yang Ming University, Taipei, Taiwan
    Blood 117:459-69. 2011
    ..These results support low-density hypoxic culture as a method for efficiently expanding MSCs without losing stem cell properties or increasing tumorigenicity...
  68. ncbi Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study
    Marianne Nordsmark
    Department of Experimental Clinical Oncology, Aarhus University Hospital, DK, Denmark
    Radiother Oncol 77:18-24. 2005
    ..To analyze the relationship between pre-treatment measurements of tumor oxygen tension (pO2) and survival in advanced head and neck cancer...
  69. ncbi Interdependence of hypoxic and innate immune responses
    Victor Nizet
    Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Nat Rev Immunol 9:609-17. 2009
    ..In turn, HIF-driven innate immune responses have important consequences for both the pathogen and the host, such that the tissue microenvironment fundamentally influences susceptibility to infectious disease...
  70. ncbi Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects
    M Hockel
    Department of Obstetrics and Gynecology, University of Leipzig, Germany
    J Natl Cancer Inst 93:266-76. 2001
    ..Instead, alternative definitions based on clinical, biologic, and molecular effects that are observed at O(2) partial pressures below a critical level have to be applied...
  71. pmc Gene expression programs in response to hypoxia: cell type specificity and prognostic significance in human cancers
    Jen Tsan Chi
    Department of Biochemistry, Stanford University School of Medicine, Palo Alto, California, United States of America
    PLoS Med 3:e47. 2006
    ....
  72. pmc Treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the effect of radiation therapy
    H Harada
    Department of Radiation Oncology and Image Applied Therapy, Kyoto University Graduate School of Medicine, Sakyo ku, Japan
    Br J Cancer 100:747-57. 2009
    ....
  73. ncbi Regulation of hypoxia-inducible factor 2alpha signaling by the stress-responsive deacetylase sirtuin 1
    Elhadji M Dioum
    Veterans Affairs North Texas Health Care System, Department of Medicine, 4500 South Lancaster Road, Dallas, TX 75216, USA
    Science 324:1289-93. 2009
    ..Thus, Sirt1 promotes HIF-2 signaling during hypoxia and likely other environmental stresses...
  74. ncbi Tumor hypoxia and cancer progression
    Jie Zhou
    Institute of Biochemistry I, Faculty of Medicine, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Cancer Lett 237:10-21. 2006
    ....
  75. pmc Ecto-5'-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia
    Kristin Synnestvedt
    Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 110:993-1002. 2002
    ..These results identify an HIF-1-dependent regulatory pathway for CD73 and indicate the likelihood that CD39/CD73 protects the epithelial barrier during hypoxia...
  76. pmc An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia
    Yair Benita
    Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Nucleic Acids Res 37:4587-602. 2009
    ..Together these analyses demonstrate the potential to recover novel HIF-1-target genes and the discovery of mammalian-regulatory elements operative in the context of microarray data sets...
  77. ncbi Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia
    Rui Hua Xu
    Department of Molecular Pathology, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cancer Res 65:613-21. 2005
    ..Because the Warburg effect and hypoxia are frequently seen in human cancers, these findings may have broad clinical implications...
  78. ncbi Activation of the PI3-K/AKT pathway and implications for radioresistance mechanisms in head and neck cancer
    Johan Bussink
    Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Netherlands
    Lancet Oncol 9:288-96. 2008
    ..Thus, the activation status of this pathway might be a key element for the prediction of treatment response and for therapeutic targeting in head and neck cancer...
  79. pmc Anti-apoptotic role of HIF-1 and AP-1 in paclitaxel exposed breast cancer cells under hypoxia
    Lionel Flamant
    Laboratory of Biochemistry and Cellular Biology URBC, NARILIS NAmur Research Institute for LIfe Sciences FUNDP University of Namur, 5000 Namur, Belgium
    Mol Cancer 9:191. 2010
    ..Hypoxia is a hallmark of solid tumors and is associated with metastases, therapeutic resistance and poor patient survival...
  80. pmc Genome-wide identification of hypoxia-inducible factor binding sites and target genes by a probabilistic model integrating transcription-profiling data and in silico binding site prediction
    Amaya Ortiz-Barahona
    Department of Biochemistry, Universidad Autónoma de Madrid Instituto de Investigaciones Biomédicas CSIC, Madrid, Spain
    Nucleic Acids Res 38:2332-45. 2010
    ....
  81. pmc Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response
    Mark W Dewhirst
    Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nat Rev Cancer 8:425-37. 2008
    ..HIF1 can then promote endothelial and tumour cell survival. As discussed here, a constant theme emerges: inhibition of HIF1 activity will have therapeutic benefit...
  82. pmc Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition
    Debra F Higgins
    Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 117:3810-20. 2007
    ....
  83. ncbi Theoretical simulation of tumour oxygenation and results from acute and chronic hypoxia
    Alexandru Daşu
    Department of Radiation Sciences, Umea University, S 901 85 Umea, Sweden
    Phys Med Biol 48:2829-42. 2003
    ..All these suggest that theoretical modelling of tissue oxygenation starting from the basic principles is a robust method that can be used to quantify the tissue oxygenation and to provide input parameters for other simulations...
  84. ncbi Hypoxia signalling in cancer and approaches to enforce tumour regression
    Jacques Pouyssegur
    Institute of Signalling, Developmental Biology and Cancer Research, CNRS UMR 6543, University of Nice, Centre Antoine Lacassagne, 33 Avenue Valombrose, 06189 Nice, France
    Nature 441:437-43. 2006
    ..There are new approaches to enforce necrotic cell death and tumour regression by targeting tumour metabolism and pH(i)-control systems...
  85. pmc Hypoxia-inducible factors as essential regulators of inflammation
    Hongxia Z Imtiyaz
    Abramson Family Cancer Research Institute, University of Pennsylvania, 438 BRB II III, 421 Curie Boulevard, Philadelphia, PA 19104 6160, USA
    Curr Top Microbiol Immunol 345:105-20. 2010
    ..We will also discuss how hypoxia and HIFs control properties of tumor-associated macrophages and their relationship to tumor formation and progression...
  86. pmc A hypoxia-induced positive feedback loop promotes hypoxia-inducible factor 1alpha stability through miR-210 suppression of glycerol-3-phosphate dehydrogenase 1-like
    Timothy J Kelly
    Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Mol Cell Biol 31:2696-706. 2011
    ..We propose a model in which hypoxia-induced miR-210 represses GPD1L, contributing to suppression of PHD activity, and increases of HIF-1α protein levels...
  87. ncbi Tumor microenvironmental physiology and its implications for radiation oncology
    Peter Vaupel
    Institute of Physiology and Pathophysiology, Johannes Gutenberg University, Mainz, Germany
    Semin Radiat Oncol 14:198-206. 2004
    ..Because of a relatively high risk of local relapse or distant metastasis, patients with hypoxic and/or "high-lactate" tumors should undergo close surveillance...
  88. pmc Hypoxia, inflammation, and the tumor microenvironment in metastatic disease
    Elizabeth C Finger
    Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, CA, USA
    Cancer Metastasis Rev 29:285-93. 2010
    ..Central players involved in this process and discussed in this review include integrins, matrix metalloproteinases, and soluble growth factors/matrix proteins, including the connective tissue growth factor and lysyl oxidase...
  89. ncbi Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma
    D M Brizel
    Department of Radiation Oncology, Duke University Comprehensive Cancer Center, Durham, North Carolina, 27710, USA
    Cancer Res 56:941-3. 1996
    ..Median pO2 was 7.5 mm Hg for metastasizing tumors versus 20 mm Hg for nonmetastasizing tumors (P=0.03). Potential mechanisms and implications for clinical trial design are discussed...
  90. pmc Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity
    Eoin P Cummins
    Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    Proc Natl Acad Sci U S A 103:18154-9. 2006
    ....
  91. ncbi Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms
    T Kinnaird
    Cardiovascular Research Institute, Washington Hospital Center, Washington, DC 20010, USA
    Circ Res 94:678-85. 2004
    ..These data indicate that paracrine signaling is an important mediator of bone marrow cell therapy in tissue ischemia, and that cell incorporation into vessels is not a prerequisite for their effects...
  92. ncbi Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha
    W G An
    Department of Cell and Cancer Biology, Medicine Branch, NCI, NIH, Bethesda, Maryland 20892, USA
    Nature 392:405-8. 1998
    ..Our results suggest that hypoxic induction of transcriptionally active wild-type p53 is achieved as a result of the stabilization of p53 by its association with HIF-1alpha...
  93. ncbi Clinical and biological factors affecting response to radiotherapy in patients with head and neck cancer: a review
    P Silva
    Academic Department of Radiation Oncology, The University of Manchester, Manchester, UK
    Clin Otolaryngol 32:337-45. 2007
    ....
  94. ncbi HIF-1alpha and cancer therapy
    Mei Yee Koh
    Department of Experimental Therapeutics, M D Anderson Cancer Center, Houston, TX 77030, USA
    Recent Results Cancer Res 180:15-34. 2010
    ..In this chapter, we summarize recent findings regarding the regulation of HIF-1alpha and the progress made in identifying new therapeutic agents that inhibit HIF-1alpha...
  95. ncbi DNA cross-links in human tumor cells exposed to the prodrug PR-104A: relationships to hypoxia, bioreductive metabolism, and cytotoxicity
    Rachelle S Singleton
    Auckland Cancer Society Research Centre, The University of Auckland, Auckland, New Zealand
    Cancer Res 69:3884-91. 2009
    ....
  96. ncbi Adipose stromal cells stimulate angiogenesis via promoting progenitor cell differentiation, secretion of angiogenic factors, and enhancing vessel maturation
    Kseniya Rubina
    Department of Biological and Medical Chemistry, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia
    Tissue Eng Part A 15:2039-50. 2009
    ..All these mechanisms of actions could be beneficial for the stimulation of angiogenesis in ischemic tissues by ASCs administration...
  97. ncbi Hypoxia and the malignant glioma microenvironment: regulation and implications for therapy
    L Oliver
    Institut de Recherche Thérapeutique de l Université de Nantes, CRCNA INSERM UMR892 Université de Nantes, Nantes Cedex 1, France
    Curr Mol Pharmacol 2:263-84. 2009
    ..In this review we will summarize the role of hypoxia in GBM with regard to drug therapy and toxicity and attempt to describe the possible interactions between hypoxia and apoptosis...
  98. pmc SUMOylation participates in induction of ischemic tolerance
    Yang ja Lee
    Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    J Neurochem 109:257-67. 2009
    ..These findings suggest that maintenance of a globally elevated SUMO-1 (and maybe SUMO-2/3) conjugation level as revealed by immunoblot assays is a component of ischemic tolerance...
  99. pmc Hypoxia-inducible factors: central regulators of the tumor phenotype
    John D Gordan
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, PA, USA
    Curr Opin Genet Dev 17:71-7. 2007
    ..New targets and novel mechanisms of dysregulation place the HIFs in an ever more central role in tumor biology and have led to development of pharmacological inhibitors of their activity...
  100. ncbi Hypoxic chondrogenic differentiation of human embryonic stem cells enhances cartilage protein synthesis and biomechanical functionality
    E J Koay
    Department of Bioengineering, Rice University, Houston, TX 77251 1892, USA
    Osteoarthritis Cartilage 16:1450-6. 2008
    ..Hypoxia has effects on many cellular processes, though few investigations with hypoxia provide quantitative functional data on engineered cartilage...
  101. ncbi Mechanisms of adaptive angiogenesis to tissue hypoxia
    Guo Hua Fong
    Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030 3501, USA
    Angiogenesis 11:121-40. 2008
    ....

Research Grants62

  1. Predicting Radiation Response by Tumor pO2
    Cameron Koch; Fiscal Year: 2006
    ..DDFP may thus be the first PFC emulsion practical and safe for use in multifraction clinical regimens. ..
  2. IMAGING T CELLS BY POSITRON EMISSION TOMOGRAPHY
    Shahriar Yaghoubi; Fiscal Year: 2013
    ..T-cell hypoxia will be assessed by introducing a molecular sensor for oxygen to test whether sr39tk can report low oxygen ..
  3. MR Dynamic Imaging and Spectroscopy in Head & Neck Cancers
    AMITA DAVE; Fiscal Year: 2010
    ..Microenvironment parameters that have shown to be relevant for treatment outcome include tumor cell hypoxia and proliferation...
  4. Exploiting tumor stroma interactions for cancer therapy
    Garth Powis; Fiscal Year: 2013
    ..of the pancreatic cancer cell to hypoxia to develop novel small molecule inhibitors that can break the tumor cell hypoxia/stroma desmoplasia cycle leading to new and more effective ways of treating pancreatic cancer...
  5. TUMOR PHYSIOLOGICAL EFFECTS OF ANGIOGENESIS INHIBITION
    William Lee; Fiscal Year: 2002
    ..treated tumors reveals that a mechanism by which it controls tumor growth involves induction of severe tumor cell hypoxia and hypoxia-induced apoptosis...
  6. Regulation of Renal Oxygenation and Blood Pressure
    Pin Lan Li; Fiscal Year: 2006
    ..found highly expressed in the renal medulla and upregulated in response to decrease in tissue oxygenation or cell hypoxia. Inhibition of HIF-1alpha in this kidney region resulted in increase in arterial blood pressure and enhancement ..
  7. MRI BIOMARKERS OF ANGIOGENESIS AND CELL INJURY IN RETINOPATHY OF PREMATURITY
    Junjie Chen; Fiscal Year: 2009
    ..if successful, will provide novel MRI biomarkers for early diagnosis of retinal neovascularization that feature cell hypoxia and angiogenesis...
  8. Endothelial Cell Hypoxia Tolerance: Role of Plasmalogens
    Harrison Farber; Fiscal Year: 2006
    ..Once the biochemistry of plasmalogens in EC has been clarified, studies to determine their biological importance can be undertaken. [unreadable] [unreadable]..
  9. ENDOTHELIAL CELL HYPOXIA ASSOCIATED PROTEINS
    Harrison Farber; Fiscal Year: 2000
    ....
  10. Hypoxia-Inducible Factor 1 and Oxygen Homeostasis
    Gregg Semenza; Fiscal Year: 2009
    ....
  11. EXPRESSION OF HUMAN ERYTHROPOIETIN GENE
    Gregg Semenza; Fiscal Year: 2002
    ..abstract_text> ..
  12. DEVELOPMENT OF NEW HYPOXIC CYTOTOXINS FOR CANCER THERAPY
    John Brown; Fiscal Year: 2008
    ..abstract_text> ..
  13. Yeast Gene Ontology by Phenotypic Profiling
    John Brown; Fiscal Year: 2007
    ..abstract_text> ..
  14. Experimental Radiotherapy and Chemotherapy With a Potent New Hypoxic Cytotoxin
    JOHN MARTIN BROWN; Fiscal Year: 2010
    ....
  15. EXPERIMENTAL RADIOTHERAPY--BASIS AND MODIFICATION
    John Brown; Fiscal Year: 2002
    ..To test this hypothesis we will employ inhibitors of the topo II catalytic cycle as well as cells induced to express high levels of topo II following TPZ treatment ..
  16. Interactions of Black Cohosh with Cancer Therapy
    Sara Rockwell; Fiscal Year: 2005
    ..This project will assess these possibilities. The findings will show whether this herb is inactive and harmless, potentially dangerous to breast cancer patients, or of potential value in the treatment of this disease. ..
  17. Monitoring Oxygen Repeatedly for Hypoxic Tumor Therapy
    Mohammad Khan; Fiscal Year: 2007
    ..If successful, this approach potentially could be immediately extended for clinical applications. [unreadable] [unreadable] [unreadable]..
  18. Development of EPR and NIR Oximetry for Diabetic Foot
    Mohammad Khan; Fiscal Year: 2007
    ..If the promise of these techniques is fulfilled, clinicians will have a new powerful tool for management of peripheral vascular disease, based on fundamental pathophysiology. [unreadable] [unreadable] [unreadable]..
  19. Oxygen Guided Hypofractionated Radiotherapy for Gliomas
    Nadeem Khan; Fiscal Year: 2010
    ....
  20. Oxidative Damage to DNA Repair Pathways
    Cameron Koch; Fiscal Year: 2006
    ..Specific Aim 3 will investigate other aspects of DNA repair and DNA structural organization to determine their sensitivity to redox regulation. ..
  21. HYPOXIA AND GENE REPRESSION
    Amato Giaccia; Fiscal Year: 2009
    ..We will test these hypotheses through a combination of genetic and biochemical approaches in cell lines and in mice. ..
  22. CTGF in Pancreatic Tumor Growth
    Amato J Giaccia; Fiscal Year: 2010
    ..In summary, the proposed studies are intended to address an important mechanism by which CTGF affects tumor progression in pancreatic cancers and to determine how effective it is in combination therapy to bring it to the clinic. ..
  23. PET Imaging of Hypoxia with EF5
    Cameron Koch; Fiscal Year: 2009
    ..In summary, the aims of this grant will extend and advance our overall laboratory interest in quantifying the degree and extent of clinically relevant hypoxia in the tumor microenvironment. ..
  24. Study of anti-angiogenesis enhanced radiotherapy
    Robert Griffin; Fiscal Year: 2008
    ..The information to be obtained in this study will be a vital part of design and implementation of large animal and human clinical trials. ..
  25. Targeting Akt/NF-kappa beta for Pancreatic Cancer Therapy
    Fazlul Sarkar; Fiscal Year: 2007
    ..These results will provide mechanistic as well as pre-clinical data in support of our hypotheses and may open new and novel avenues for the treatment of human pancreatic cancer. ..
  26. A novel technology to generate conditionally inactivated alleles in mice
    Guo Hua Fong; Fiscal Year: 2008
    ..This project aims at developing a novel technology that will significantly simplify this procedure and therefore accelerate biomedical research. [unreadable] [unreadable] [unreadable]..
  27. Combination fusion toxin and cytarabine therapy of AML
    ARTHUR FRANKEL; Fiscal Year: 2002
    ..We anticipate these studies should provide the basis for the design and implementation of pivotal multi-institutional phase II and III trials of DTGM/cytarabine therapy for relapsed/refractory AML. ..
  28. REDOX MECHANISMS OF RESPIRATORY MUSCLE STRESS ADAPTATION
    Thomas Clanton; Fiscal Year: 2009
    ..This basic science investigation will give new insights into fundamental skeletal muscle biology that will have applications to a variety of muscle disorders related to O2 transport limitation. ..
  29. 3 D HOLOGRAPHIC VIDEO RECORDING IN BIOLOGICAL TISSUE
    David Nolte; Fiscal Year: 2001
    ....
  30. Lung Cell Genomic Threats from Physiological Signals
    Mark Gillespie; Fiscal Year: 2009
    ..Such a finding could point to new pathways leading to somatic mutation and thus lead to a better understanding of cancer, aging, and other disorders wherein ROS are believed to play pathogenic roles. ..
  31. REACTIVE OXYGEN SPECIES AND VASCULAR O2 SENSING
    Michael S Wolin; Fiscal Year: 2010
    ..These studies should help define the origins of differences in physiological responses of pulmonary and coronary arteries to changes in O2 tension. ..
  32. PULMONARY VASODILATION AND GUANYLATE CYCLASE REGULATION
    Michael S Wolin; Fiscal Year: 2010
    ....
  33. Sertoli Cell Mediated Engulfment of Apoptotic Germ Cells
    Kodi S Ravichandran; Fiscal Year: 2010
    ..abstract_text> ..
  34. Predictive Markers of Glioblastoma Response to VEGF Trap
    John de Groot; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  35. Mechanisms of ATP Release from RBC's
    Randy Sprague; Fiscal Year: 2007
    ..abstract_text> ..
  36. ROLE OF SURFACTANT PROTEIN B IN INNATE AIRWAY DEFENSE
    JOHN BAATZ; Fiscal Year: 2004
    ..Results from the proposed experiments will lay the foundation for therapeutic use of SP-B for eradication of bacterial lung infections. ..
  37. Targeting of the Androgen Receptor in Prostate Cancer
    John Isaacs; Fiscal Year: 2005
    ..These peptide prodrugs will be designed so that they are substrates for the enzymatic activity of either Prostate Specific Antigen. ..
  38. Adult Forebrain Neural Stem Cell Response to Ischemia
    Jack Parent; Fiscal Year: 2005
    ..Progress in these Aims will advance our understanding of adult SVZ neurogenesis in the normal and ischemic brain, and may provide insight into the potential use of neural stem cells for stroke therapy. ..
  39. Diphtheria fusion protein therapy of AML
    ARTHUR FRANKEL; Fiscal Year: 2006
    ..These studies should lead to the design of pivotal phase II clinical trials to determine the role of this therapeutic in AML management. ..
  40. Adenoviral vectors to target cells
    Patricia Yotnda; Fiscal Year: 2006
    ..At the conclusion of this study we will have in place an approach that could be implemented to allow truly targeted delivery of therapeutic vectors to disseminated malignancies. ..
  41. Is There a Link Between Alzheimer's and Atheroclerosis
    Paula Grammas; Fiscal Year: 2007
    ..abstract_text> ..
  42. Free Fatty Acids and Hepatic Insulin Resistance
    Guenther Boden; Fiscal Year: 2007
    ..These studies will hopefully provide much needed information relative to important details and mechanisms of FFA induced hepatic insulin resistance. [unreadable] [unreadable]..
  43. SLS: Molecular Basis and Role in Invasive GAS Disease
    Victor Nizet; Fiscal Year: 2006
    ..These hypotheses will be tested by molecular genetic studies, attempts protein purification and antibody development, and the use of targeted SLS mutants in in vitro assays of phagocytic function and our in vivo mouse model of GAS NF. ..
  44. OXYGEN SENSING AND REGULATION OF YEAST GENES
    ROBERT POYTON; Fiscal Year: 2002
    ..some other redox-sensitive oxygen binding protein involved in OCD gene expression? Aim 3: Does oxygen affect transcript turnover rate? Aim 4: What cis promoter sites mediate the OCD expression of COX6, COX5a, and CYC1? ..
  45. Function of FMRP in the Mouse Olfactory System
    John Larson; Fiscal Year: 2007
    ..Such new information would be vital for evaluating novel treatment strategies for a class of developmental disabilities. [unreadable] [unreadable]..
  46. RENAL INJURY AND ADAPTATION TO HEME PROTEINS
    Karl Nath; Fiscal Year: 2001
    ..Our proposed application thus continues to pursue the functionality of HO-1, as it utilized a new strategy, transgenic mice, and as it defines a new area of involvement namely, renal inflammation. ..
  47. OXYGEN SENSING AND SIGNAL TRANSDUCTION
    H Bunn; Fiscal Year: 2003
    ..abstract_text> ..
  48. The Role of NC2 in Gene Repression by Tumor Hypoxia
    Nicholas Denko; Fiscal Year: 2007
    ..These studies will determine if hypoxic gene repression through NC2 activity could be a potential therapeutic target for future molecular therapeutics in the treatment of human cancers. ..
  49. IGF-I and its binding proteins in vascular smooth muscle cells
    Cunming Duan; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  50. Sialic Acid O-Acetylation in GBS Pathogenesis & Immunity
    Victor Nizet; Fiscal Year: 2010
    ..Companion analyses will be performed on GBS isolates and human sera from recent prospective seroepidemiologic studies. ..
  51. IMMUNE RESPONSES IN LUNG ALLOGRAFT REJECTION
    David Wilkes; Fiscal Year: 2006
    ..Gene therapy will also be utilized to over express IDO in allograft donor lungs prior to transplantation followed by an assessment of the rejection response. ..
  52. MICROVASCULAR OCCLUSION IN ACUTE FOCAL CEREBRAL ISCHEMIA
    Gregory Del Zoppo; Fiscal Year: 2004
    ..These studies are a direct extension of completed work of this proposal, and are expected to add greatly to the understanding of how vascular ischemia affects neuron integrity with testable treatment strategies. ..
  53. SEX STEROID REGULATION OF IGF-I EXPRESSION IN BONE
    Thomas McCarthy; Fiscal Year: 2003
    ..Bone mass studies will be conducted using peripheral quantitative computer tomography, and will be correlated with basal and activated skeletal IGF-I expression. ..
  54. Hyperbaric Oxygenation May Increase Lung Injury
    Michail Sitkovsky; Fiscal Year: 2007
    ..unreadable]..
  55. Chemokine Signaling and Colitis in Gia2 Deficient Mice
    Robert Edwards; Fiscal Year: 2006
    ..This application has the support of outstanding mentors at two institutions, and funding of this application will foster Dr Edwards' continued development as a physician-scientist. ..
  56. The Role of BCL-2 in Corneal Epithelial Cell Shedding
    DANIELLE ROBERTSON; Fiscal Year: 2008
    ..4) That events leading to increased apoptosis such as UV light signal surface cell apoptosis through the phosphorylation of BCL-2. ..
  57. Fat Induced Insulin Resistance and Atherosclerosis
    Guenther Boden; Fiscal Year: 2007
    ..We believe that these studies will provide important new information relative to the mechanism by which obesity and FFAs cause IR and ASVD in human subjects. ..
  58. RNAi Mediated Gene Disruption in Caenorhabditis Elegans
    Wayne Van Voorhies; Fiscal Year: 2006
    ..Such worms could identify candidate genes affecting processes that act "downstream" from the metabolic rate and provide valuable insights into the causes of aging and mechanisms by which it can be attenuated. ..
  59. Augmentation of Neurogenesis and Recovery After Stroke
    Jack Parent; Fiscal Year: 2007
    ..Progress in these aims will advance our understanding of mechanisms underlying neural stem cell regulation and rehabilitative plasticity after brain injury, and may lead to novel regenerative therapies for stroke. ..
  60. DNA modifications in primary pulmonary hypertension
    Mark Gillespie; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..