Antiangiogenic therapy of pancreatic cancer

胰腺癌的抗血管生成治疗

• 批准号: 6924633
• 负责人: Sareh Parangi
• 金额: $ 13.03万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-07 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6924633
• 关键词: BCL2 gene /protein; CD95 molecule; SCID mouse; angiogenesis inhibitors; apoptosis; biological signal transduction; cell line; combination chemotherapy; confocal scanning microscopy; cysteine endopeptidases; enzyme linked immunosorbent assay; fibroblast growth factor; gemcitabine; gene delivery system; immunoprecipitation; in situ hybridization; neoplasm /cancer chemotherapy; neoplastic growth; nonhuman therapy evaluation; pancreas neoplasms; polymerase chain reaction; terminal nick end labeling; thrombospondins; transfection /expression vector; xenotransplantation

DESCRIPTION (provided by applicant): Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. Unfortunately, this disease is often diagnosed at a late incurable stage, with less than 5% of patients surviving 5 years. Antiangiogenic therapy has not been well studied in this disease. The first specific aim of this study will help define the role of treatment with angiogenesis inhibitors in a mouse model of pancreatic cancer that closely resembles human disease. In specific aim 1 I will look at different combinations of antiangiogenic agents. Adenoassociated virus will be used to deliver novel antiangiogenic agents. Combinations of antiangiogenic agents and the chemotherapeutic agent, Gemcitabine, will also be tested. Preliminary data points to the importance of apoptosis during antiangiogenic therapy with recombinant Type I repeats of TSP-1 (TSR) in this model of pancreatic cancer. Therefore, in specific aim 2 the molecular mechanisms of the signal transduction pathways that are involved in mediating apoptosis by TSP-1 will be analyzed. Completion of this mentored project will allow me to gain in-depth expertise in areas such as novel delivery mechanisms such as gene therapy, detailed analysis of apoptotic pathways focusing on endothelial and tumor cell responses to antiangiogenic agents. This unique combination will allow me to complete the first phase of my career development and progress on to independent research.

描述（由申请人提供）：胰腺癌是美国癌症死亡的第四大原因。 不幸的是，这种疾病通常在晚期无法治愈的阶段被诊断出来，只有不到5%的患者存活5年。 抗血管生成治疗在这种疾病中尚未得到很好的研究。 这项研究的第一个具体目标将有助于确定血管生成抑制剂在与人类疾病非常相似的胰腺癌小鼠模型中的治疗作用。 在具体目标1中，我将研究抗血管生成剂的不同组合。 腺相关病毒将被用来提供新的抗血管生成剂。 还将测试抗血管生成剂和化疗剂吉西他滨的组合。 初步数据表明，在胰腺癌模型中，用重组TSP-1（TSR）I型重复序列进行抗血管生成治疗期间，细胞凋亡具有重要意义。 因此，在具体目标2中，将分析参与TSP-1介导细胞凋亡的信号转导途径的分子机制。 完成这个指导项目将使我能够获得深入的专业知识，如新的交付机制，如基因治疗，细胞凋亡途径的详细分析，重点是内皮细胞和肿瘤细胞对抗血管生成剂的反应。 这种独特的组合将使我能够完成我职业发展的第一阶段，并继续进行独立研究。