Case GI SPORE

案例 GI 孢子

• 批准号: 9753939
• 负责人: SANFORD D. MARKOWITZ
• 金额: $ 232.5万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-14 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9753939
• 关键词: Adenocarcinoma; African American; Aspirin; Barrett Esophagus; Basic Science; Biological; Biological Markers; Cancer Center; Cancer Etiology; Cessation of life; Chemoprevention; Clinical Investigator; Clinical Trials; Colon; Colon Carcinoma; Colorectal Adenocarcinoma; Colorectal Cancer; Communication; Comprehensive Cancer Center; Coupled; DNA; Deglutition; Detection; Development; Devices; Dinoprostone; Disease; Dysplasia; Early Diagnosis; Endoscopy; Esophageal; Esophageal Adenocarcinoma; Esophagus; Evaluation; Experimental Pathology; Faculty; Fluorouracil; Formalin; Fostering; Funding; GPT2 gene; Genes; Glutaminase; Glutamine; Histologic; Human; Incidence; Individual; Industrialization; Infrastructure; Lesion; Life Style; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of gastrointestinal tract; Metabolism; Molecular; Morbidity - disease rate; Mutation; Nature; Neoplasms; Outcome; PIK3CA gene; Pathway interactions; Patients; Play; Population; Populations at Risk; Prevention; Prevention strategy; Publications; Recording of previous events; Research; Research Personnel; Research Project Grants; Resistance; Resources; Risk Factors; Risk stratification; Role; Sampling Studies; Science; Series; Services; Solid Neoplasm; Somatic Mutation; Specialized Program of Research Excellence; Statistical Methods; Stem cells; Survival Rate; Testing; Translational Research; Tumor Suppressor Genes; Tumor Suppressor Proteins; United States; United States National Academy of Sciences; Vimentin; base; cancer biomarkers; cancer chemoprevention; cancer epidemiology; cancer health disparity; cancer risk; cancer subtypes; career; clinically significant; colon cancer prevention; colon cancer risk; colorectal cancer prevention; colorectal cancer risk; drug discovery; early screening; inhibitor/antagonist; innovation; invention; molecular marker; mortality; mutant; named group; next generation sequencing; novel; novel strategies; novel therapeutic intervention; novel therapeutics; personalized medicine; predicting response; programs; recruit; response; screening; translational medicine; translational scientist; treatment strategy; tumor

OVERALL SUMMARY/ABSTRACT This Case GI SPORE renewal application provides for a cutting edged Specialized Program of Research Excellence in gastrointestinal malignancies with emphasis on colorectal cancers and adenocarcinoma of the esophagus. This comprehensive program builds on the resources of the Case Comprehensive Cancer Center to propose 4 translational Research Projects to bring new molecular advances to patients with GI Cancers. A series of 3 core resources support these projects and also establish a strong programmatic infrastructure for translational research in GI cancers. We have further developed a comprehensive infrastructure for identifying new Developmental Research Projects from basic science and clinical investigators from across the Case Cancer Center. Drawing on our strong track record of developing new faculty who emphasize translational research in GI cancers, we have also developed a targeted Career Enhancement Program to further advance and recruit to the translational research cadre of SPORE faculty. The 4 SPORE translational research projects constitute novel and cutting edge approaches to GI cancers and include studies of: i) Targeting the 15-PGDH colon cancer tumor suppressor pathway for prediction of cancer risk, prediction of response to chemoprevention with aspirin, and development of new colon cancer prevention and treatment strategies (Project 1, Drs. Markowitz, Li, and Berger); ii) Elucidating the basis for and the clinical significance of a mutational signature of African American colon cancer (Project 2, Drs. Willis, Li, and Wang); iii) Development of molecular markers of and non-endoscopic detection of Barrett's esophagus and early esophageal adenocarcinomas (Project 3, Drs. Chak, Guda, and Markowitz); and iv) Development of personalized treatment of PIK3CA mutant colon cancers using targeted inhibitors of glutamine metabolism (Project 4, Drs. Wang and Meropol). These projects are built on major advances from the SPORE's first funding period that include: i) publication in Science that 15-PGDH regulates colon crypt stem cells; ii) publication in Science Translational Medicine that individual's 15-PGDH levels regulate whether taking aspirin will or will not reduce their colon cancer risk; iii) publication in Proceedings of the National Academy of Sciences of genes preferentially targeted for somatic mutations in colorectal cancers of African Americans; iv) publication on the cover of Cancer Epidemiology, Biomarkers and Prevention that testing for methylated vimentin DNA in esophageal brushings could detect over 90% of Barrett's esophagus and esophageal adenocarcinomas; v) publication in Nature Communications that PIK3CA mutant cancers are addicted to glutamine and sensitive to inhibitors of glutamine metabolism. These projects are advantaged by special populations and scientific resources developed for evaluation of GI cancer biomarkers, new drug discovery, Next-Generation sequencing of formalin fixed tumor samples, and studies of Barrett's esophagus. The strength of these investigators and the resources at their disposal will insure this program leads to significant important translational advances.

总体摘要/摘要 此案GI孢子更新应用程序提供了一项切割的专业研究计划 胃肠道恶性肿瘤的卓越性，重点是结直肠癌和腺癌 食管。这个全面的计划以案例综合癌症中心的资源为基础 提出4个转化研究项目，以将新分子进步带给GI癌症患者。一个 一系列3个核心资源支持这些项目，还建立了强大的程序基础架构 GI癌的翻译研究。我们进一步开发了一个全面的基础设施来识别 来自案件的基础科学和临床研究人员的新发展研究项目 癌症中心。借鉴我们发展新教师的强大记录，他们强调翻译 GI癌的研究，我们还制定了一个有针对性的职业增强计划，以进一步促进 并招募孢子教师的转化研究干部。 4个孢子翻译研究项目 构成GI癌的新颖和最前沿方法，包括：i）针对15-PGDH的研究 结肠癌肿瘤抑制途径预测癌症风险，预测反应 随着阿司匹林以及新的结肠癌预防和治疗策略的发展（项目1，Drs。 Markowitz，Li和Berger）； ii）阐明突变特征的基础和临床意义 非洲裔美国结肠癌（第2个项目，威利斯博士，李和王）； iii）开发分子标记 以及对巴雷特食管和早期食道腺癌的非镜观察（项目3，Drs。 Chak，Guda和Markowitz）; iv）开发PIK3CA突变结肠癌的个性化处理 使用谷氨酰胺代谢的靶向抑制剂（项目4，Wang和Meropol博士）。这些项目是建立的 从孢子的第一个融资期开始的主要进步，其中包括：i）科学出版物15-pgdh 调节结肠隐窝干细胞； ii）科学转化医学中的出版物15-PGDH 水平调节服用阿司匹林是否会降低其结肠癌的风险； iii）诉讼中的出版 基因的国家科学院优先针对结直肠癌的体细胞突变 非裔美国人； iv）出版有关癌症流行病学，生物标志物和预防的封面 在食管刷子中测试甲基化的波形蛋白DNA可以检测到Barrett食管的90％以上 食管腺癌； v）PIK3CA突变癌的自然传播中的出版 沉迷于谷氨酰胺，对谷氨酰胺代谢的抑制剂敏感。这些项目优势 开发了用于评估GI癌症生物标志物，新药的特殊人群和科学资源 发现，福尔马林固定肿瘤样品的下一代测序以及对巴雷特食管的研究。 这些调查人员的优势及其可用的资源将确保该计划导致重大 重要的翻译进展。