The long-term objective of our research plan is to reduce the disproportionate effects of prostate cancer on African American men. A guiding principle of our methodology is biochemical differences exist between prostate cancers of African American and European American origin and that these differences can explain, in part, prostate cancer health disparity. In this application, we propose to use the technique of metabolomic profiling to uncover these underlying differences. Metabolomics describes the science of quantifying the levels of metabolites (e.g., small molecules) that are the byproducts of cellular metabolism. That is to say, in this kind of analysis we are measuring the biochemical entities (or metabolites) that are produced by the functional machinery of the cell. With knowledge of the identity of specific metabolites we can infer the biological processes that produced them, thus gaining insight into a cell's metabolism. To date, a metabolomic analysis of prostate cancer health disparity has not been reported. In preliminary studies, we have profiled the metabolome of prostate cancers from African-American and European American men and have identified specific racially distinct metabololites as well as biological pathways associated with each. In this proposal, we will i) validate and refine the metabolomic profile of prostate cancers from African American and European American men, ii) evaluate the role of specific biochemical pathways in prostate cancers of African American and European American men and iii) develop urine based metabolic markers for high risk prostate cancer in African American and European American men. At the conclusion of this study, we will have developed a racially derived metabolomic model for prostate cancer as well as identified candidate pathways for future drug targeting.

Public Health Relevance

At present, it is not known how the prostate cancer metabolome contributes to health disparities. The information gleaned from this proposal could rapidly revolutionize current diagnostic, prognostic and therapeutic approaches by revealing the biological underpinnings of prostate cancer health disparity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01CA167234-02S1
Application #
8665538
Study Section
Special Emphasis Panel (ZRG1-OBT-A (55))
Program Officer
Ogunbiyi, Peter
Project Start
2012-08-01
Project End
2017-07-31
Budget Start
2013-08-29
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$103,544
Indirect Cost
$37,382
Name
Baylor College of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Xing, Zhen; Zhang, Yanyan; Liang, Ke et al. (2018) Expression of Long Noncoding RNA YIYA Promotes Glycolysis in Breast Cancer. Cancer Res 78:4524-4532
Piyarathna, Danthasinghe Waduge Badrajee; Rajendiran, Thekkelnaycke M; Putluri, Vasanta et al. (2018) Distinct Lipidomic Landscapes Associated with Clinical Stages of Urothelial Cancer of the Bladder. Eur Urol Focus 4:907-915
Ballester, Leomar Y; Lu, Guangrong; Zorofchian, Soheil et al. (2018) Analysis of cerebrospinal fluid metabolites in patients with primary or metastatic central nervous system tumors. Acta Neuropathol Commun 6:85
Yu, Wangie; Chen, Yunyun; Dubrulle, Julien et al. (2018) Cisplatin generates oxidative stress which is accompanied by rapid shifts in central carbon metabolism. Sci Rep 8:4306
Mishra, Prachi; Tang, Wei; Putluri, Vasanta et al. (2018) ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming. J Clin Invest 128:323-340
Coarfa, Christian; Florentin, Diego; Putluri, NagiReddy et al. (2018) Influence of the neural microenvironment on prostate cancer. Prostate 78:128-139
Jin, Feng; Thaiparambil, Jose; Donepudi, Sri Ramya et al. (2017) Tobacco-Specific Carcinogens Induce Hypermethylation, DNA Adducts, and DNA Damage in Bladder Cancer. Cancer Prev Res (Phila) 10:588-597
Kaushik, Akash K; Shojaie, Ali; Panzitt, Katrin et al. (2016) Inhibition of the hexosamine biosynthetic pathway promotes castration-resistant prostate cancer. Nat Commun 7:11612
Prueitt, Robyn L; Wallace, Tiffany A; Glynn, Sharon A et al. (2016) An Immune-Inflammation Gene Expression Signature in Prostate Tumors of Smokers. Cancer Res 76:1055-1065
Stossi, Fabio; Dandekar, Radhika D; Bolt, Michael J et al. (2016) High throughput microscopy identifies bisphenol AP, a bisphenol A analog, as a novel AR down-regulator. Oncotarget 7:16962-74

Showing the most recent 10 out of 21 publications