Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death among American men. Better detection of prostate tumors is now possible through prostate specific antigen tests, but diagnosis continues to rely upon the evaluation of biopsy samples, with treatment regimes based upon histopathological grade and clinical stage. Most newly diagnosed patients, however, have moderately differentiated adenocarcinomas, are likely to have an indolent disease course, and could live with the disease. Such patients need close clinical monitoring, but not necessarily treatment. By contrast, some patients with moderately differentiated adenocarcinomas will experience a morbid disease course and die if not promptly treated with radical prostatectomy, radiation therapy, and/or novel protocols. At present, no means for evaluating the likely biological behavior of individual prostate tumors exists, a matter made crucial because aggressive local treatment is itself complicated by morbidity and compromised quality of life. A method able to evaluate a tumor's likely potential for aggressiveness would provide an important new tool for the clinical management of prostate cancer. To facilitate this ultimate objective, the applicants here propose to test the feasibility of a recently developed spectroscopic method for identifying cellular metabolic abnormalities that can serve as diagnostic markers. This proposal seeks to quantify cellular metabolic changes associated with the development of human prostate cancer by using high-resolution magic angle spinning (HRMAS) proton magnetic resonance spectroscopy (1HMRS). The capability of HRMAS 1HMRS to measure cellular metabolic changes in intact human tissue specimens, while preserving histopathological structures, has been demonstrated. Here, study objectives are to test the feasibility of quantifying prostate tumor cellular metabolites by using this methodology, to correlate the metabolic concentrations thus obtained with histopathological features measured in the same intact tissues, to identify and characterize metabolic markers, and to establish preliminary biochemical databases that may serve as an adjunct to histopathology for use in the grading and staging of prostate tumors. Tissue metabolites of newly acquired biopsy and surgical specimens, as well as stored frozen tissues, will be quantified with HRMAS 1HMRS. Observed metabolic markers that correlate with histopathology will be used to create a prostate cancer metabolic database. He results of this study of tumor metabolic characteristics should yield information ultimately useful to improvements n the clinical management of prostate tumor patients.
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