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lüll Pathophysiological response to hypoxia - from the molecular mechanisms of malady to drug discovery:hypoxia-inducible factor-1 (HIF-1)-active cells as a target for cancer therapy Kizaka-Kondoh S; Kuchimaru T; Kadonosono TJ Pharmacol Sci 2011[]; 115 (4): 440-5The microenvironment of solid tumors is characterized by low pO(2) that is well below physiological levels. Intratumoral hypoxia is a major factor contributing to cancer progression and is exacerbated as a result of oxygen consumption by rapidly proliferating tumor cells near blood vessels, poor lymphatic drainage resulting in high interstitial pressure, and irregular blood supply through immature tumor vasculature. Hypoxia-inducible factor-1 (HIF-1) is the main transcription factor that regulates cellular responses to hypoxia. Cellular changes induced by HIF-1 are extremely important targets for cancer therapy. Therefore, targeting strategies to counteract HIF-1-active cells are essential for cancer therapy. In this study, we introduce a novel strategy for targeting HIF-1-active cells.|Animals[MESH]|Cytostatic Agents/pharmacology/therapeutic use[MESH]|Drug Discovery/*methods[MESH]|Humans[MESH]|Hypoxia-Inducible Factor 1/*antagonists & inhibitors[MESH]|Hypoxia/*physiopathology[MESH]|Models, Biological[MESH]|Molecular Imaging/methods[MESH]|Molecular Targeted Therapy/*methods[MESH]|Neoplasms/*drug therapy[MESH]|Oxidation-Reduction[MESH]|Prodrugs/pharmacology[MESH]|Transplantation, Heterologous[MESH]|Tumor Microenvironment/*drug effects[MESH] |