Hypoxia and anaerobic metabolism regulation of cancer cell survival: a novel mol

缺氧和无氧代谢调节癌细胞存活：一种新的分子机制

• 批准号: 8552024
• 负责人: KARAM F.A. SOLIMAN
• 金额: $ 7.37万
• 依托单位: FLORIDA AGRICULTURAL AND MECHANICAL UNIV
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8552024
• 关键词: Address; African American; Caring; Cell Nucleus; Cell Survival; Community Services; Data; Death Rate; Diagnostic Neoplasm Staging; Dimerization; Disadvantaged; Disease; Early Diagnosis; Early treatment; Event; Fostering; Genes; Genetic; Genetic Transcription; Glucose; Goals; Growth; Hypoxia; Individual; Instruction; Malignant Neoplasms; Medical; Metabolism; Molecular Genetics; Molecular Target; Neoplasm Metastasis; Positioning Attribute; Process; Protein Array; Proteins; Radiation; Regulation; Research; Research Project Grants; Research Training; Resistance; Response Elements; Solid Neoplasm; Staging; Time; Tumor Pathology; angiogenesis; anti-cancer therapeutic; anticancer research; cancer cell; cancer therapy; cancer type; chemotherapy; experience; glucose metabolism; health disparity; neoplastic cell; novel; prevent; socioeconomics; therapeutic target; tumor

Research Project 2 - Hypoxia and anaerobic metabolism regulation of cancer cell survival: a novel molecular target for anticancer therapeutics - K.F. Soliman H. Flores-Rozas, S. Darling and E. Mazzio: In the US, African Americans still continue to experience highest death rates from many different types of cancers. Often times, socioeconomic disadvantage places individuals in a compromising position of not being able to afford proper medical care thereby forgoing necessary early detection and treatment. This poses considerable challenge because a cancer can gain strength over time transforming into aggressive malignancy, which is non-responsive to chemotherapy or radiation. This evolutionary process is believed to be the result of events occurring at the core of a primary solid tumor mass. As a tumor grows, its central core becomes exposed to low p02 (hypoxia) resulting In genetic adaptations which foster expression of a diverse array of proteins that promote survival, growth, metastasis and angiogenesis. A lack of O2 prevents HIF-1 a proteosomal degradation, leading to HIF-1 a-HIF-1B dimerization and its translocation to the nucleus where hypoxic response element (HRE) genes initiate transcription of proteins that perpetuate survival. Because late stage cancers are often untreatable, the understanding of molecular, genetic or functional regulation of glucose metabolism in hypoxic tumor cells are critical in order to elucidate targeted therapeutic treatments that will destroy the tumor without harm to the host.. Our preliminary data show that hypoxic tumor cells use glucose to produce ATP in a process that appears to expand beyond the traditional

研究项目2-癌细胞存活的缺氧和厌氧代谢调节：抗癌疗法的新型分子靶标-K.F。 Soliman H. Flores-Rozas，S。Darling和E. Mazzio： 在美国，非洲裔美国人仍然继续从许多不同类型的癌症中经历最高的死亡率。通常，社会经济的劣势使个人处于无法负担适当医疗的妥协状态，从而放弃了必要的早期发现和治疗。这构成了巨大的挑战，因为癌症可以随着时间的流逝而增强力量，从而将其转化为侵略性恶性肿瘤，这对化学疗法或放射线无反应。人们认为这个进化过程 是发生在原发性实体肿块核心的事件的结果。随着肿瘤的生长，其中心核心暴露于低P02（缺氧），导致遗传适应性，从而促进了各种蛋白质的表达，从而促进了促进生存，生长，转移和血管生成。缺乏O2阻止了HIF-1 A蛋白体降解，从而导致HIF-1 A-HIF-1B二聚化及其转移到核中，其中低氧反应元件（HRE）基因引发了蛋白质的转录，从而使生存永久存在。因为晚期癌症通常是不可治疗的，所以对低氧肿瘤细胞中葡萄糖代谢的分子，遗传或功能调节的理解至关重要，对于阐明靶向的治疗治疗而不会损害宿主而不会损害宿主。 葡萄糖在似乎超越传统的过程中生产ATP