Crohn's disease (CD) and Ulcerative Colitis (UC) are Inflammatory Bowel Diseases (IBDs) of unknown etiology. Although the exact pathogenesis is poorly understood, there is evidence that it involves interactions between the immune system, genetic susceptibility and the environment. One of the complications of longstanding ulcerative colitis (UC) is the development of cancer. Understanding why some patients with long standing colitis develop dysplasia while others do not is an important question that remains unanswered. The central hypothesis of this proposal is that NK1R- and EGFR-signaling pathways play critical roles in the development of colitis-associated dysplasia.
The specific aims of the proposed plan are to: 1) to investigate the role of NK1 receptors in our model of colitis-associated dysplasia versus chronic inflammation;2) to analyze the role of EGFR in chronic inflammation and colitis-associated dysplasia;3) evaluate the effects of EGFR and COX-2 inhibitors on the occurrence of colitis-associated dysplasia. These studies will help to understand the involvement of the SP-NK1R-EGFR signaling pathways in UC-associated CRC and how inhibitors could eventually be used as a potential therapy in patients with long standing colitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31GM078951-04
Application #
7675317
Study Section
Minority Programs Review Committee (MPRC)
Program Officer
Toliver, Adolphus
Project Start
2006-09-01
Project End
2010-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
4
Fiscal Year
2009
Total Cost
$26,802
Indirect Cost
Name
Ponce School of Medicine
Department
Physiology
Type
Schools of Medicine
DUNS #
105742043
City
Ponce
State
PR
Country
United States
Zip Code
00732
Pagán, Beatriz; Isidro, Angel A; Cruz, Myrella L et al. (2011) Erlotinib inhibits progression to dysplasia in a colitis-associated colon cancer model. World J Gastroenterol 17:4858-66
Pagán, Beatriz; Isidro, Angel A; Coppola, Domenico et al. (2010) Effect of a neurokinin-1 receptor antagonist in a rat model of colitis-associated colon cancer. Anticancer Res 30:3345-53