• Obesity, Insulin Resistance, IGFs, and Breast Cancer Risk in African-Americans

            Yong Cui, M.D., M.S.P.H. and Wei Zheng, M.D., Ph.D.
African-American women, compared to their Caucasian counterparts, have a higher incidence of early-onset breast cancer, are more frequently diagnosed with aggressive breast cancer, and suffer a higher mortality rate. This application will test several important etiological hypotheses of breast cancer risk related to obesity and insulin resistance. As part of the study, telephone interviews will be conducted to obtain dietary and other lifestyle information. Exfoliated buccal cell samples will also be collected from African American women to extract DNA for genotyping assays of polymorphisms in several major genes related to obesity, insulin resistance, and/or IGF-I effects in both randomly identified controls and newly diagnosed breast cancer patients.

• Energy Balance Intervention for Colorectal Cancer Prevention (Pilot)

            Maciej S. Buchowski, Ph.D. and Charles E. Matthews, Ph.D.
Substantial reductions in colorectal cancer risk have been noted for those reporting both high physical activity energy expenditures and/or low energy intakes. The specific molecular mechanisms underlying these associations, and the type and level of intervention needed to obtain a risk reduction, remain unknown. In this pilot, investigators will conduct a 16-wk randomized trial to test the feasibility of interventions comparing the effects of physical activity, dietary energy restriction, a combination of physical activity and dietary energy restriction, or no direct intervention (controls). As part of the study, they will quantify changes in both circulating biomarkers and tissue markers of cell proliferation, survival, and inflammation obtained from rectal biopsies post intervention. 

• COX-1 AND HDAC Inhibitors Suppress Ovarian Cancer Growth in Vitro and in Vivo (Pilot)   Dineo Khabele, M.D. and Sudhansu K. Dey, Ph.D.

In previous studies, cyclooxygenase-1 (COX-1) has been shown to be implicated in ovarian cancer. This labaoratory has also shown that histone deacetylases (HDACs) are highly expressed in ovarian malignancies.  Thus the goal of this research is to determine if inhibition of COX-1 and HDACs prevent tumor growth in ovarian cancers; further if these inhibitors are  synergistic both in vivo and in vitro in reducing tumor growth rate and size, making them excellent therapeutic targets for this disease.  In vitro experiments will be performed with the established ovarian cancer cell lines, OVCAR3 and SKOV3.  Parallel in vivo experiments will be performed in RAG2/γ-C mice injected with ovarian cancer cell lines OVCAR3 and SKOV3.
    

• Vitamin D and Mammographic Breast Density in African American Women (Pilot)

            Alecia Malin, Dr.Ph. and Kathleen M. Egan, Sc.D.
Vitamin D deficiency is emerging as a potentially important modifiable risk factor in breast carcinogenesis and limited data suggest that inadequate exposure to vitamin D is associated with increased breast density. This pilot will examine whether vitamin D deficiency, measured by serum vitamin D levels, correlates with a specific mammographic finding – ‘breast density’ – which in turn has been linked to an enhanced breast cancer risk, independent of breast size, body mass index (BMI) and other known risk factors. The population to be examined is a cohort of African American women undergoing mammography screening at Nashville General Hospital at Meharry. A secondary aim of the project is to examine whether polymorphic variations in genes critical to vitamin D signaling, or genes that play a central role in the synthesis and catabolism and therefore bioavailability of 25(OH)D3 are associated with the degree of breast density and other markers of risk.

• Identification of Serum Biomarkers in HNSCC (Pre-Pilot)

            Sabina P. Francis, M.D. and Wendell G. Yarbrough, M.D.
Head and neck squamous cell carcinoma (HNSCC) is the 5th most common tumor type in the US. Because there are no useful biomarkers for early detection of HNSCC, we propose to use state-of-the art analytic mass spectrometry to identify potential serum biomarkers for HNSCC. The proposed studies will use multidimensional liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to directly identify proteins and peptides present in serum from patients with and without HNSCC. Once predictive proteins are identified, future studies with absolute quantitation using mass spectrometry (AQUA) of these markers on individual samples will be performed to determine variations in serum concentrations and their predictive power.

• Biomarkers of Racial Disparity in Colorectal Cancer (Pre-Pilot)

            Ana M. Grau, M.D. and Nipun B. Merchant, M.D.
The central hypothesis is that molecular profiling of colorectal cancer (CRC) tissue will identify clinically relevant tumor subgroups between Caucasian and African-American patients and predict clinical outcomes in these patients.  In this pre-pilot, the investigators hope to validate a novel candidate biomarker of colorectal cancer.  The following specific aims are proposed: Specific Aim 1: To determine whether changes in gene expression profiles can be used to distinguish clinical outcomes between African-American and Caucasian patients with CRC.   Specific Aim 2: To determine whether the urinary metabolite of PGE2, PGE-M, can be used as a biomarker for CRC.