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.
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.
|Samuel, Temesgen; Fadlalla, Khalda; Gales, Dominique N et al. (2014) Variable NF-?B pathway responses in colon cancer cells treated with chemotherapeutic drugs. BMC Cancer 14:599|
|Battle, Monica; Gillespie, Corey; Quarshie, Alexander et al. (2014) Obesity induced a leptin-Notch signaling axis in breast cancer. Int J Cancer 134:1605-16|
|Singh, Rajesh; Gupta, Pranav; Kloecker, Goetz H et al. (2014) Expression and clinical significance of CXCR5/CXCL13 in human non?small cell lung carcinoma. Int J Oncol 45:2232-40|
|Desai, Arpita; Xu, Jingyao; Aysola, Kartik et al. (2014) Epithelial ovarian cancer: An overview. World J Transl Med 3:1-8|
|Colbert, Laronna S; Wilson, Kaamilah; Kim, Sungjin et al. (2014) NILCO biomarkers in breast cancer from Chinese patients. BMC Cancer 14:249|
|Smith, Selina A; Blumenthal, Daniel S (2013) Efficacy to effectiveness transition of an Educational Program to Increase Colorectal Cancer Screening (EPICS): study protocol of a cluster randomized controlled trial. Implement Sci 8:86|
|Coleman Wallace, Debbie A; Baltrus, Peter T; Wallace, Tracey C et al. (2013) Black white disparities in receiving a physician recommendation for colorectal cancer screening and reasons for not undergoing screening. J Health Care Poor Underserved 24:1115-24|
|Qin, Yunlong; Xu, Jingyao; Aysola, Kartik et al. (2011) Ubc9 mediates nuclear localization and growth suppression of BRCA1 and BRCA1a proteins. J Cell Physiol 226:3355-67|
|Caplan, Lee; Stout, Charlotte; Blumenthal, Daniel S (2011) Training physicians to do office-based smoking cessation increases adherence to PHS guidelines. J Community Health 36:238-43|
|Fortson, Wendell S; Kayarthodi, Shubhalaxmi; Fujimura, Yasuo et al. (2011) Histone deacetylase inhibitors, valproic acid and trichostatin-A induce apoptosis and affect acetylation status of p53 in ERG-positive prostate cancer cells. Int J Oncol 39:111-9|
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