Gastrointestinal (Gl) cancers account for nearly 20 percent of cancer deaths in the United States of America in 2006 and colorectal cancer (CRC) continues to be the second leading cause of such deaths. The long-term objective of our SPORE in Gl Cancers is to decrease mortality due to Gl cancers by developing novel approaches for risk assessment, screening, chemoprevention and therapeutics. Four projects, three cores and developmental research and career development programs are proposed. Project 1 is entitled Genetic Variability as Prognostic or Predictive Factors in Colorectal Intraepithelial Neoplasia (IEN). The translational goal of this project is to demonstrate that tailoring prevention therapy in high-risk individuals, based on host and adenoma characteristics, will reduce the development of clinically significant colonic IEN. Project 2 is entitled Application and Development of Colonography for Colorectal Cancer Screening. The translational goal of this project is to combine minimal oral cleansing bowel preparation with lesion-specific targeting agents to detect large polyps and early cancers in asymptomatic subjects. Project 3 is entitled Mechanistic Translational Studies of the Stress Response in Gastrointestinal Cancer. The translational goal of this project is to exploit processes associated with altered blood perfusion in tumors for therapeutic benefit. Project 4 is entitled Drug Targeting of G-Quadraplex-NM23-H2 Complex in the c-MYC Promoter, and targets an important oncogene in Gl cancer development. The translational goal of both Projects 3 and 4 are to develop novel target-directed drugs for treatment of Gl cancers. The projects are supported by an extensive Human Gl Tissue Resource, which includes access to existing normal and neoplastic tissue specimens, including a subset of blood, urine and fecal samples, which have been gathered from approximately 6000 participants in colon polyp prevention trials, over 600 patients with Barrett's esophagus, and over 500 surgical patients who were treated for various Gl malignancies. A Statistical and Informatics Core will provide state-of-the-art statistical, computational and informatics support for all projects in our efforts to discover new prognostic markers and drug targets. The Evaluation and Administration Core is the critical feedback loop necessary for a productive SPORE. The Developmental Research Program will ensure that the most promising translational ideas are nurtured and funded. The complementary Career Development Program will support and mentor physicians and scientists in translational research. This competing renewal application builds on successes achieved during the previous funding period, including the development of several new target directed cancer therapies, and leverages resources at The University of Arizona, M.D. Anderson Cancer Center and the Translational Genomics Research Institute (TGEN) to offer unique opportunities to achieve our goal of reducing mortality due to Gl cancers in the United States.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
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Study Section
Special Emphasis Panel (ZCA1-GRB-I (O1))
Program Officer
Lin, Alison J
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University of Arizona
Anatomy/Cell Biology
Schools of Medicine
United States
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Jones, Kyle M; Pollard, Alyssa C; Pagel, Mark D (2018) Clinical applications of chemical exchange saturation transfer (CEST) MRI. J Magn Reson Imaging 47:11-27
Goldenberg, Joshua M; Cárdenas-Rodríguez, Julio; Pagel, Mark D (2018) Preliminary Results that Assess Metformin Treatment in a Preclinical Model of Pancreatic Cancer Using Simultaneous [18F]FDG PET and acidoCEST MRI. Mol Imaging Biol 20:575-583
Goldenberg, Joshua M; Pagel, Mark D; Cárdenas-Rodríguez, Julio (2018) Characterization of D-maltose as a T2 -exchange contrast agent for dynamic contrast-enhanced MRI. Magn Reson Med 80:1158-1164
Daryaei, Iman; Randtke, Edward A; Pagel, Mark D (2017) A biomarker-responsive T2exMRI contrast agent. Magn Reson Med 77:1665-1670
Daryaei, Iman; Jones, Kyle M; Pagel, Mark D (2017) Detection of DT-diaphorase Enzyme with a ParaCEST MRI Contrast Agent. Chemistry 23:6514-6517
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Tsikitis, Vassiliki L; Potter, Amiee; Mori, Motomi et al. (2016) MicroRNA Signatures of Colonic Polyps on Screening and Histology. Cancer Prev Res (Phila) 9:942-949
Hingorani, Dina V; Montano, Luis A; Randtke, Edward A et al. (2016) A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals. Contrast Media Mol Imaging 11:130-8
Fernández-Cuervo, Gabriela; Sinharay, Sanhita; Pagel, Mark D (2016) A CatalyCEST MRI Contrast Agent that Can Simultaneously Detect Two Enzyme Activities. Chembiochem 17:383-7

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