Ponce School of Medicine - Moffitt Cancer Center Partnership

庞塞医学院 - 莫菲特癌症中心合作伙伴关系

• 批准号: 7930659
• 负责人: Warren Jackson Pledger
• 金额: $ 45.47万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-26 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7930659
• 关键词: Affinity; Area; Biochemical; CD94 Antigen; Cancer Center; Cancerous; Chronic; Colitis; Colon Carcinoma; Colorectal Cancer; Crohn' s disease; Development; Disease; Dysplasia; Epidermal Growth Factor Receptor; Family; Female; Functional disorder; G Protein-Coupled Receptor Signaling; G-Protein-Coupled Receptors; Goals; Graduate Education; Grant; Growth Factor Receptors; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Institutes; Interleukins; Intestines; Lesion; Link; Lysophosphatidic Acid Receptors; Malignant Epithelial Cell; Malignant Neoplasms; Mediating; Mediator of activation protein; Minority; Modeling; Molecular; National Cancer Institute; Neuromedin K Receptor; Pathogenesis; Patients; Phosphotransferases; Play; Population; Premalignant; Preventive; Prostaglandins; Prostate; Puerto Rican; Rattus; Research Project Grants; Risk; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Substance P; Substance P Receptor; TAC1 gene; Testing; Therapeutic Intervention; Ulcerative Colitis; Up-Regulation; anticancer research; cyclooxygenase 2; cytokine; design; insight; male; malignant breast neoplasm; medical schools; neoplasm registry; novel; receptor; response; src-Family Kinases

DESCRIPTION (provided by applicant): Colorectal cancer is one of the leading cancers in Puerto Rican, second only to prostate and breast cancer. Inflammatory bowel diseases such as ulcerative colitis and Crohn's disease have been linked to the development of colorectal cancer. Evidence obtained by us and others have suggested that substance P (SP) and its high affinity receptor neurokinin-1 receptor (NK-1R, tachykinin receptor 1) play a pivotal role in inflammatory bowel diseases. Both NK-1R and cyclooxygenase-2 (Cox-2) are upregulated in patients with inflammatory bowel diseases. However, the roles of NK-1R-mediated signaling pathways in the pathogenesis of precancerous and cancerous lesions in ulcerative-associated colorectal cancer are not known. The long-term goals of this research project are to understand molecular mechanisms of ulcerative colitis-associated colorectal cancer and to target key signaling molecules in the development of ulcerative colitis-associated colorectal cancer for preventive and therapeutic intervention. The current study is designed to test the central hypothesis that NK-1R plays a key role in up regulation of Cox-2 in our rat model of colitis-associated dysplasia, and that the epidermal growth factor receptor (EGFR) and Src family tyrosine kinases (SFKs) are involved in NK-1R signaling in colon carcinoma cells, and in the development of precancerous lesions in this model of colitis-associated dysplasia. Three specific aims will be pursued in this collaborative research project that combines the strength of Dr. Appleyard in the rat model of ulcerative colitis-associated colorectal cancer and the expertise of Dr. Wu in growth factor receptor and G protein-coupled receptor (GPCR) signaling. In addition to giving novel insights into the roles of NK-1R and its mediators in the development of colorectal cancer, this collaborative research project will provide Dr. Appleyard with an excellent platform to strengthen her competitiveness in the areas of biochemical and molecular cancer research. This in turn will increase the likelihood for Dr. Appleyard in the Minority-Serving Institute (MSI) to successfully compete for a R01 grant from the National Cancer Institute (NCI) and will increase the quality of graduate education at the MSI.

描述（由申请人提供）：结直肠癌是波多黎各的主要癌症之一，仅次于前列腺癌和乳腺癌。炎症性肠病如溃疡性结肠炎和克罗恩病与结直肠癌的发生有关。我们和其他研究人员的研究表明，P物质（SP）及其高亲和力受体神经激肽1受体（NK-1 R，tachykinin receptor 1）在炎症性肠病中起关键作用。炎症性肠病患者NK-1 R和环氧合酶-2（考克斯-2）均上调。然而，NK-1 R介导的信号通路在溃疡相关结直肠癌的癌前病变和癌性病变的发病机制中的作用尚不清楚。该研究项目的长期目标是了解溃疡性结肠炎相关结直肠癌的分子机制，并针对溃疡性结肠炎相关结直肠癌发展中的关键信号分子进行预防和治疗干预。本研究旨在验证中心假设，即NK-1 R在我们的结肠炎相关异型增生大鼠模型中上调考克斯-2中起关键作用，表皮生长因子受体（EGFR）和Src家族酪氨酸激酶（SFKs）参与结肠癌细胞中NK-1 R信号传导，并参与结肠炎相关异型增生模型中癌前病变的发展。在这个合作研究项目中，将追求三个具体目标，该项目结合了Appleyard博士在溃疡性结肠炎相关结直肠癌大鼠模型中的优势以及Wu博士在生长因子受体和G蛋白偶联受体（GPCR）信号传导方面的专业知识。除了对NK-1 R及其介体在结直肠癌发展中的作用提供新的见解外，该合作研究项目还将为Appleyard博士提供一个极好的平台，以加强她在生物化学和分子癌症研究领域的竞争力。这反过来将增加少数民族服务研究所（MSI）的Appleyard博士成功竞争国家癌症研究所（NCI）R 01补助金的可能性，并将提高MSI的研究生教育质量。