Core B: ImmunoAnalysis and Tumor Management Core B will serve two primary functions to the three projects. First, Core B will be involved in all aspects of clinical specimen and prostate cancer xenograft management. Core personnel will obtain, process and store clinical specimens of recurrent prostate cancer obtained from men with advanced prostate cancer who present with urinary retention due to local recurrence. Nude mice will be implanted with fresh surgical specimens of benign and malignant prostate, the androgen-dependent CWR22 and LAPC-4 human prostate cancer xenografts, androgen deprivation therapy performed and research specimens obtained at various intervals after castration. Treatments will be administered using antisense and gene therapy and tumors measured and research specimens obtained. Secondly, Core B will provide research specimens to the investigators and assist with identification, immunostaining and image analysis. Research specimens will be used to construct tissue microarrays or laser capture microdissected for biochemical measurements of tissue androgens. Paraffin-embedded sections will be provided from original tumors or tissue arrays and used to 1) confirm tissue histology using routine H&E;2) analyze apoptosis using caspace-3, proliferation using MIB-1 detection of Ki-67 or BrdU incorporation and androgen receptor using monoclonal antibodies by standard, descriptive immunohistochemistry and quantitative video color image analysis;and 3) identification of steroid receptor co-activators, androgen metabolism enzymes, androgen-regulated gene products (PSA, Nkx3.1 and hK2), general transcription factors, growth factors and their receptors and stem cell, neuroendocrine cell and angiogenesis markers using immunohistochemistry. Drs. Mohler and Smith will co-direct the facility and supervise the activities of individuals who already possess high levels of expertise and currently perform these functions for the P01. Core B will draw upon resources currently available but, due to the increased use of xenograft models in all Projects and the large number of fresh prostate cancer xenografts required for Project 3, the capability to manage our tumor models will be enhanced.
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