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: 8355085
• 负责人: KARAM F.A. SOLIMAN
• 金额: $ 16.48万
• 依托单位: FLORIDA AGRICULTURAL AND MECHANICAL UNIV
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-16 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8355085
• 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--癌细胞存活的低氧和无氧代谢调节：抗癌治疗的新分子靶点--K.F.Soliman H.Flores-Rozas，S.Darling和E.Mazzio： 在美国，非裔美国人仍然经历着许多不同类型癌症的最高死亡率。许多时候，社会经济上的不利条件使个人处于无法负担适当医疗费用的折衷境地，从而放弃了必要的早期发现和治疗。这带来了相当大的挑战，因为随着时间的推移，癌症会逐渐增强，转化为对化疗或放射没有反应的侵袭性恶性肿瘤。这一进化过程被认为是 是发生在原发实体瘤核心的事件的结果。随着肿瘤的生长，其中心核心暴露在低P02(低氧)下，导致遗传适应，促进一系列促进生存、生长、转移和血管生成的蛋白质的表达。缺氧阻止了HIF-1a蛋白酶体的降解，导致HIF-1a-HIF-1B二聚化并将其移位到细胞核，在那里缺氧反应元件(HRE)基因启动蛋白质的转录，从而维持生存。由于晚期癌症通常无法治愈，因此了解低氧肿瘤细胞中葡萄糖代谢的分子、遗传或功能调节是阐明靶向治疗方法的关键，这种治疗方法将在不损害宿主的情况下摧毁肿瘤。我们的初步数据显示，缺氧的肿瘤细胞使用 葡萄糖生产三磷酸腺苷的过程似乎超越了传统的