This interview is with Organic Chemistry Insights editorial board member Dr Uddhav Kelavkar. Organic Chemistry Insights is an open access journal published by Libertas Academica.

Editor in Chief Dr Hafiz Ahmed has recently issued a call for papers

What is the primary focus of your research?

Americans now consume substantially more processed plant fats and oils as compared with animal fats, and studies indicate that this high-fat diet likely plays a role in an increased risk for prostate cancer (PCa). Ideally, the ratio of omega (n)-3 to n-6 fatty acids should be 1-4:1, but many Americans ingest 10 to 20 times more n-6 than n-3 fatty acids, leading to an imbalanced ratio and higher cancer incidence of PCa. PCa remains the second most commonly diagnosed cancer in American men, with over 230,000 new cases predicted for 2005 alone. Specifically, consumption of omega (n)-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid (LA) and arachidonic acid (AA) from plant oils, correlates with increased risk whereas consumption of n-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oils, correlates with decreased risk. With the "baby boomer" generation approaching the target a ge for PCa screening, this number is expected to rise precipitously to 300,000 unless major advances in prevention become available.

Treatment options depend largely on the stage of the disease, the age and health of the patient, as well as whether the cancer has just been diagnosed or has recurred. Unfortunately though, many of these treatments can negatively impact the quality of life. Moreover, every year approximately 70,000 men present with recurrent disease and no curative therapy exists for advanced metastatic PCa. Given the long latency period for PCa progression along with the close association between aging and disease incidence, therapies that impede growth would make PCa clinically irrelevant. Thus, a major goal of our laboratory has been to identify key events that can be pro-actively targeted to slow PCa development. Our laboratory is studying the roles of polyunsaturated omega-6 fatty acid metabolism in PCa initiation and progression, particularly an enzyme called 15-lipoxygenase-1, using animal models and cell lines including a recently generated transgenic mouse model of prostate neoplasia. Other areas of interest are bladder cancer, epigenetics and molecular profiling.

What are the most exciting developments arising from current research in your area?

Our study will lay the groundwork and advance the field of chemoprevention by providing the suitability of early dietary n-3 PUFAs intervention to slow PCa progression in men. A positive outcome will provide a significant health benefit and quality of life for baby boomers and those who follow.

We also plan to develop a 15-LO-1 promoter methylation based assay for rapidly and accurately identifying cancer precursors early on, and then provide a rationale for appropriate treatment/s strategies that can be applied effectively to the patients when they are in the premalignant stage. Early treatment of these precancerous lesions would be of clinical benefit notwithstanding the potential for cancer prevention (for e.g., use of epigenetic modulators such as Zebularine, green tea major polyphenol (-)-epigallocatechin-3-gallate (EGCG), Procainamide etc., either alone or in combination). These epigenetic modulator/s can potentially silence tumor-promoting 15-LO-1 overexpression and induce tumor suppressors that can slow or even stop PCa initiation and/or progression. These clinical benefits would reduce morbidity, enhance the quality of life, delay surgery or radiation, and increase the interval for surveillance requiring invasive procedures. Overall, our study will provide a significant health benefit and quality of life for baby boomers and those who follow.

Who are your main collaborators? Please describe your work with them.

Thomas Eling, NIEHS: We showed for the first time the overxpression of 15-lipoxygenase-1 in prostate cancer.

Thomas Conrads, University of Pittsburgh: Mass spectrometry and metabolomics.

Beth Pflug, Indiana University: Fatty acid synthase and omega-3 fatty acids.

Dean Bacich, University of Pittsburgh: Tissue recombination model.

David Martin, Emory University: We generated the transgenic FLiMP mouse model that develops neoplasia in prostate when 15-LO-1 is overxpressed.

How did you come to be working in your research area?: Discovery that omega-6 metabolizing 15-lipoxygenase-1 is overexpressed in prostate cancer and maybe a link that high-fat diet consumption (more of omega-6 fatty acids)is linked to prostate cancer development.

What do you think about the development of open access publishing? Have you published in an open access journal? What motivated you to do so?

Yes, a journal called Carcinogenesis. Thought I will try.

What articles and/or books have you published recently?

Kelavkar UP, Hutzley J, Dhir R, Kim P, Allen K, McHugh K (2006). Prostate tumor growth and recurrence can be modulated by the omega (ω)-6: ω-3 ratio in diet: Athymic mouse xenograft model simulating radical prostatectomy. Neoplasia, 8: 112-124.

Kelavkar UP, Lin Y, Landsittel D, Chandran U, Dhir R (2006). The Yin and Yang of 15-lipoxygenase-1 and Delta-5-desaturase: Dietary omega-6 Linoleic acid metabolic pathway in prostate carcinogenesis. Journal of Carcinogenesis, 5:9.

Kelavkar UP, Parwani A, Shappell S, Martin W (2006). Conditional expression of human 15-lipoxygenase-1 in adult mouse prostate induces prostatic intraepithelial neoplasia: the FLiMP mouse model. Neoplasia, 8: 510-522.

Sen M, McHugh K, Dhir R, Hutzley J, Philips B, Parwani A, Kelavkar UP (2006). Forced overexpression of human 15-lipoxygenase (LO)-1, in the prostate of normal wild-type C57BL/6 mouse, causes neoplasia. Prostaglandins & other Lipid Mediators, 81: 1-13.

Kelavkar UP, Harya N, Hutzley J, Bacich DJ, Monzon FA, Chandran U, Dhir R and O’Keefe DS (2007). DNA methylation paradigm shift: 15-lipoxygenase-1 upregulation in prostatic intraepithelial neoplasia and prostate cancer by atypical promoter hypermethylation. Prostaglandins & other Lipid Mediators, 82: 185-197.

Philips B, Hutzley J, Dhir R, Sen M, Kelavkar UP (2008). 15-Lipoxygenase-1 expression in normal and cancerous human bladder. Applied Immunohistochemistry & Molecular Morphology, 16:159-164.

Kelavkar U, Hutzley J, McHugh K, Allen KGD, Parwani A (2009). Prostate tumor growth can be modulated by dietarily targeting the 15-lipoxygenase (LO)-1 and cyclooxygenase (COX)-2 enzymes. Neoplasia, In Press.

Invited Chapters:
“Human Genome Project”, Encyclopedia of The Human Genome (EHG)- Nature, London).