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 University, 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 / As and whites are different, and their value in assessing the clinical 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 SI 00A11 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 underlying 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.
|Karthikeyan, Chandrabose; Lee, Crystal; Moore, Joshua et al. (2015) IND-2, a pyrimido[1?,2?:1,5]pyrazolo[3,4-b]quinoline derivative, circumvents multi-drug resistance and causes apoptosis in colon cancer cells. Bioorg Med Chem 23:602-11|
|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|
|Wells, Kristen J; Lima, Diana S; Meade, Cathy D et al. (2014) Assessing needs and assets for building a regional network infrastructure to reduce cancer related health disparities. Eval Program Plann 44:14-25|
|Zhang, Huang-Ge; Grizzle, William E (2014) Exosomes: a novel pathway of local and distant intercellular communication that facilitates the growth and metastasis of neoplastic lesions. Am J Pathol 184:28-41|
|Richter, J R; Mahoney, M; Warram, J M et al. (2014) A dual-reporter, diagnostic vector for prostate cancer detection and tumor imaging. Gene Ther 21:897-902|
|Arora, Ritu; Yates, Clayton; Gary, Bernard D et al. (2014) Panepoxydone targets NF-kB and FOXM1 to inhibit proliferation, induce apoptosis and reverse epithelial to mesenchymal transition in breast cancer. PLoS One 9:e98370|
|Green, Hadiyah N; Crockett, Stephanie D; Martyshkin, Dmitry V et al. (2014) A histological evaluation and in vivo assessment of intratumoral near infrared photothermal nanotherapy-induced tumor regression. Int J Nanomedicine 9:5093-102|
|Khazal, Kamel F; Hill, Donald L; Grubbs, Clinton J (2014) Effect of Withania somnifera root extract on spontaneous estrogen receptor-negative mammary cancer in MMTV/Neu mice. Anticancer Res 34:6327-32|
|Jones, Jacqueline; Wang, Honghe; Karanam, Balasubramanyam et al. (2014) Nuclear localization of Kaiso promotes the poorly differentiated phenotype and EMT in infiltrating ductal carcinomas. Clin Exp Metastasis 31:497-510|
|Martin, Michelle Y; Fouad, Mona N; Oster, Robert A et al. (2014) What do cancer patients worry about when making decisions about treatment? Variation across racial/ethnic groups. Support Care Cancer 22:233-44|
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