Analysis of the expression profile of growth factors and their relationship to markers of inflammation and angiogenesis in the pathogenesis of benign prostatic hyperplasia

• Grant number: 11/18409-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): January 01, 2012
• Effective date (End): December 31, 2012
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Alberto Azoubel Antunes
• Grantee: Ricardo Akihiro Kirihara
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Benign prostatic hyperplasia (BPH) is the most common benign neoplasm in men. Although widely studied, the pathogenesis of BPH has not been fully elucidated. Imagine, first, that the frames of benign hyperplasia could result from overproduction of testosterone. This idea prevailed for some time, since studies have shown that serum levels of this hormone decline with age. Similarly, the addition of dihydrotestosterone (DHT) in culture media containing only epithelial cells of the prostate does not increase the mitogenic activity or the proliferation of these cells. This observation led to research on other factors that could modulate the proliferation of prostate cells and the genesis of BPH. Growth factors (CF) are proteins that regulate growth, differentiation and programmed cell death. Numerous studies have shown that they are produced by stromal cells of the prostate and act through autocrine and paracrine mechanisms exerting a powerful stimulating action on the proliferation of these cells in vitro. Despite these data, the exact relationship of circulating and tissue levels of FC with the development and progression of BPH, as well as how they act in the prostate remains so far unclear. The relationship between the FC, the local inflammatory process and markers of angiogenesis are largely unknown. Lymphokines produced by inflammatory cells may influence the local production of CF and angiogenesis in prostate tissue, simulating the response that occurs in the process of wound healing. So, adequate knowledge of these relationships may contribute to a better understanding of the pathogenesis and to find new targeted therapies that can combat or prevent the occurrence of this disease. The objective is to assess the relationship between the expression profile of CF and markers of inflammation and angiogenesis in patients with BPH and prostatic different volumes. Will be included in the study 45 patients diagnosed with BPH and underwent surgery. Patients will be divided into three groups according to prostate volume. In group I, 15 patients will be included with prostate volume less than 30 grams; In group II, 15 patients will be included with prostate volume between 30 and 60 grams, and group III are included 15 patients with prostate volume greater than 60 grams. After surgery, will be removed from a fragment of material already resected prostate of the patient (the transition zone of the prostate) and frozen at -80 ° C. The frozen fragments will be used to analyze the expression of FC, markers of inflammation and angiogenesis through the technique of polymerase chain reaction real-time quantitative (qRT-PCR). The FC will be analyzed: EGF, FGF-2, IGF-I, TGF-²1 and PDF. Markers of inflammation are IL-2, IL-4, IL-6, IL-8 and IL-17. Markers of angiogenesis are VEGF and CD105.