This Case Gl SPORE proposal provides for a cutting edge Specialized Program of Research Excellence in gastrointestinal malignancies with emphasis on colorectal cancers and with additional attention to 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 Gl Cancers. A series of 4 core resources support these research projects and also establish a strong programmatic infrastructure for translational research in Gl cancers. We further have developed a comprehensive infrastructure for identifying new Developmental Research Projects from basic science and clinical investigators from across the Case Cancer Center. Moreover, drawing on our strong track record of developing new faculty who emphasize translational research in Gl cancers, we propose a targeted Career Development Program to further enhance the translational research cadre of SPORE faculty. The 4 SPORE translational research projects constitute novel and cutting edge approaches to Gl cancers and include studies of: the predictive, prognostic, and therapeutic applications of the new 15-PGDH colon cancer suppressor pathway (Project 1, Drs. Markowitz and Willson);the noninvasive early detection of advanced colon adenomas through stool DNA testing for methylated DNA (Project 2, Drs. Cooper and Li);the comprehensive evaluation of colon cancer gene mutations as predictors of clinical outcome, via use of high throughput Next Generation genomic sequencing (Project 3, Drs. Willis and Wang);and the identification of esophageal adenocarcinoma susceptibility genes (Project 4, Drs. Chak and Elston). These projects are advantaged by special population and scientific resources developed by our SPORE faculty for: evaluation of colon cancer biomarkers, for high throughput screening for new drug discovery, for evaluation of colon cancer screening modalities, for Next Generation sequencing from archived formalin fixed tissue samples, and for study of familial Barrett's and adenocarcinomas of the esophagus. The strength of these investigators and the resources at their disposal will ensure this program leads to important advances.

Public Health Relevance

Colon cancers are the second leading cause of cancer death in adult Americans, and esophageal adenocarcinomas are the most rapidly increasing cause of cancer deaths in adult Americans. This Case Gl SPORE proposal focuses cutting edge scientific resources on the theme of identifying and clinically applying molecular cancer biomarkers in order to reduce deaths from these diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
1P50CA150964-01A1
Application #
8147466
Study Section
Special Emphasis Panel (ZCA1-RPRB-M (M1))
Program Officer
Agarwal, Rajeev K
Project Start
2011-09-14
Project End
2016-08-31
Budget Start
2011-09-14
Budget End
2012-08-31
Support Year
1
Fiscal Year
2011
Total Cost
$2,140,500
Indirect Cost
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Cooper, Gregory S; Markowitz, Sanford D; Chen, Zhengyi et al. (2018) Evaluation of Patients with an Apparent False Positive Stool DNA Test: The Role of Repeat Stool DNA Testing. Dig Dis Sci 63:1449-1453
Somasundaram, Saigopal; Forrest, Megan E; Moinova, Helen et al. (2018) The DNMT1-associated lincRNA DACOR1 reprograms genome-wide DNA methylation in colon cancer. Clin Epigenetics 10:127
Codipilly, Don Chamil; Chandar, Apoorva Krishna; Singh, Siddharth et al. (2018) The Effect of Endoscopic Surveillance in Patients With Barrett's Esophagus: A Systematic Review and Meta-analysis. Gastroenterology 154:2068-2086.e5
Petersen, Christine P; Meyer, Anne R; De Salvo, Carlo et al. (2018) A signalling cascade of IL-33 to IL-13 regulates metaplasia in the mouse stomach. Gut 67:805-817
Evans, Daniel R; Venkitachalam, Srividya; Revoredo, Leslie et al. (2018) Evidence for GALNT12 as a moderate penetrance gene for colorectal cancer. Hum Mutat 39:1092-1101
Otegbeye, Folashade; Ojo, Evelyn; Moreton, Stephen et al. (2018) Inhibiting TGF-beta signaling preserves the function of highly activated, in vitro expanded natural killer cells in AML and colon cancer models. PLoS One 13:e0191358
Desai, Amar; Zhang, Yongyou; Park, Youngsoo et al. (2018) A second-generation 15-PGDH inhibitor promotes bone marrow transplant recovery independently of age, transplant dose and granulocyte colony-stimulating factor support. Haematologica 103:1054-1064
Chan, M Q; Blum, A E; Chandar, A K et al. (2018) Association of sporadic and familial Barrett's esophagus with breast cancer. Dis Esophagus 31:
Cummings III, Kenneth C; Zimmerman, Nicole M; Maheshwari, Kamal et al. (2018) Epidural compared with non-epidural analgesia and cardiopulmonary complications after colectomy: A retrospective cohort study of 20,880 patients using a national quality database. J Clin Anesth 47:12-18
Guo, Xuan; Zhao, Yiqing; Nguyen, Hieu et al. (2018) Quantitative Analysis of Alternative Pre-mRNA Splicing in Mouse Brain Sections Using RNA In Situ Hybridization Assay. J Vis Exp :

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