This Full Project of the MSM/TU/UAB Partnership proposes to conduct preclinical translational studies in colorectal cancer to determine the prognostic and predictive value of a panel of novel molecular markers in colonic adenocarcinoma (CAC) tissues collected from African-American (AA) and non-Hispanic Caucasian (white) patients who underwent treatment at MSM and UAB hospitals. This proposal is also intended to develop the career of Dr. Temesgen Samuel, a junior faculty at Tuskegee Univeristy, who is seeking more experience in understanding the basis for cancer health disparities. Further, this project will continue the existing successful collaboration, established during the currently funded U54 Partnership award, between Dr. Harvey Bumpers of Morehouse School of Medicine and Dr. Upender Manne of UAB. The preliminary results of these collaborative studies show a disparity in gene expression profiles of aggressive microsatellite stable (MSS) phenotypes of CACs of AAs and whites. Based on these findings, the current hypothesis is that the MSS phenotypes of CACs from AAs and whites are different, and their value in assessing the clincal outcomes varies with tumor stage and location. To this hypothesis, Aim-1 will evaluate colon cancer specimens from 447 AAs and 563 whites for expression profiles of genes differentially expressed in colon cancers with MSS phenotypes. The expression profiles will be correlated with tumor stage, disease recurrence, overall and disease-specific survival, and response to therapy based on ethnicity;
Aim -2 will assess the mutational and expression status of S100A11 and RPH3AL in CACs of AAs and whites, and the mutational status and expression levels will be correlated with clinicopatholgoic features and with the clinical outcomes of AAs and whites;
and Aim -3 will determine the mechanistic functions of S100A11 and RPH3AL in colon cancer cells in vitro by generating colon cancer cells stably inhibiting S100A1 or expressing RPH3AL, in 3-dimensional tumor models. These studies will identify predictive/prognostic molecular signatures of MSS phenotypes of CACs of AAs and specifically elucidate the underiying molecular mechanisms of colon cancers of AAs and whites.

Public Health Relevance

Molecular signatures identified in this project will be useful in diagnosing aggressive forms of colon cancers and provide a basis for future validation studies;and, eventually, aid in minimizing the disparity In mortality of AA patients with colon cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA118638-07
Application #
8555496
Study Section
Special Emphasis Panel (ZCA1-SRLB-Y (O1))
Project Start
2005-09-29
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
7
Fiscal Year
2012
Total Cost
$26,603
Indirect Cost
$7,802
Name
Morehouse School of Medicine
Department
Type
DUNS #
102005451
City
Atlanta
State
GA
Country
United States
Zip Code
30310
Piyathilake, Chandrika J; Badiga, Suguna; Borak, Samuel G et al. (2017) A higher degree of expression of DNA methyl transferase 1 in cervical cancer is associated with poor survival outcome. Int J Womens Health 9:413-420
Williams, Samuel K; Braxton, Joanne M; Gosdin, Melissa et al. (2017) Evidence-Based Care for the Elderly: Uses of ""the Grandmother Principle"". J Health Care Poor Underserved 28:7
Ojeaga, Ashley; Alema-Mensah, Ernest; Rivers, Desiree et al. (2017) Racial Disparities in HPV-related Knowledge, Attitudes, and Beliefs Among African American and White Women in the USA. J Cancer Educ :
Stewart, Tarianna; Koval, William T; Molina, Samuel A et al. (2017) Calibrated flux measurements reveal a nanostructure-stimulated transcytotic pathway. Exp Cell Res 355:153-161
Tchio Mantho, Cynthia I; Harbuzariu, Adriana; Gonzalez-Perez, Ruben R (2017) Histone deacetylases, microRNA and leptin crosstalk in pancreatic cancer. World J Clin Oncol 8:178-189
Harmon, Tia; Harbuzariu, Adriana; Lanier, Viola et al. (2017) Nanoparticle-linked antagonist for leptin signaling inhibition in breast cancer. World J Clin Oncol 8:54-66
Joffe, Ari R; Bara, Meredith; Anton, Natalie et al. (2016) The ethics of animal research: a survey of the public and scientists in North America. BMC Med Ethics 17:17
Peng, Yin; Song, Lanying; Li, Ding et al. (2016) Sema6D acts downstream of bone morphogenetic protein signalling to promote atrioventricular cushion development in mice. Cardiovasc Res 112:532-542
Xu, J; Footman, A; Qin, Y et al. (2016) BRCA1 Mutation Leads to Deregulated Ubc9 Levels which Triggers Proliferation and Migration of Patient-Derived High Grade Serous Ovarian Cancer and Triple Negative Breast Cancer Cells. Int J Chronic Dis Ther 2:31-38
Zhang, Wei; Yi, Bin; Wang, Chao et al. (2016) Silencing of CD24 Enhances the PRIMA-1-Induced Restoration of Mutant p53 in Prostate Cancer Cells. Clin Cancer Res 22:2545-54

Showing the most recent 10 out of 95 publications