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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
3P50CA095060-10S3
Application #
8519616
Study Section
Special Emphasis Panel (ZCA1-GRB-I (O1))
Program Officer
Lin, Alison J
Project Start
2002-09-05
Project End
2014-03-31
Budget Start
2012-07-01
Budget End
2014-03-31
Support Year
10
Fiscal Year
2012
Total Cost
$88,491
Indirect Cost
$30,081
Name
University of Arizona
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Daryaei, Iman; Randtke, Edward A; Pagel, Mark D (2017) A biomarker-responsive T2ex MRI contrast agent. Magn Reson Med 77:1665-1670
Shkreta, Lulzim; Blanchette, Marco; Toutant, Johanne et al. (2017) Modulation of the splicing regulatory function of SRSF10 by a novel compound that impairs HIV-1 replication. Nucleic Acids Res 45:4051-4067
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
Liu, Lin; Messer, Karen; Baron, John A et al. (2016) A prognostic model for advanced colorectal neoplasia recurrence. Cancer Causes Control 27:1175-85
Chang, Hae Ryung; Nam, Seungyoon; Kook, Myeong-Cherl et al. (2016) HNF4? is a therapeutic target that links AMPK to WNT signalling in early-stage gastric cancer. Gut 65:19-32
Harpel, Kaitlin; Leung, Sarah; Rice, Photini Faith et al. (2016) Imaging colon cancer development in mice: IL-6 deficiency prevents adenoma in azoxymethane-treated Smad3 knockouts. Phys Med Biol 61:N60-9
Kobes, Joseph E; Daryaei, Iman; Howison, Christine M et al. (2016) Improved Treatment of Pancreatic Cancer With Drug Delivery Nanoparticles Loaded With a Novel AKT/PDK1 Inhibitor. Pancreas 45:1158-66
Kurzius-Spencer, Margaret; Harris, Robin B; Hartz, Vern et al. (2016) Relation of dietary inorganic arsenic to serum matrix metalloproteinase-9 (MMP-9) at different threshold concentrations of tap water arsenic. J Expo Sci Environ Epidemiol 26:445-51
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
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

Showing the most recent 10 out of 232 publications