Histopatological and molecular evaluation of dutasteride effects in the patients with and without prostatic lesions

• Grant number: 13/22734-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2014
• End date: July 31, 2015
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Patrick Vianna Garcia
• Grantee: Natasha Maia Pansani e Arantes
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The prostate morphology and physiology have been examined with particular attention because of different lesions that affect this organ. Among these stand out benign hyperplasia (BPH) and prostate cancer (PC). The low degree of effectiveness of therapies against prostate proliferative lesions may be related to the low effects of these therapies on the mechanisms of tissue repair and reactive oxygen species (ROS). The use of antiandrogens, such as inhibitors of 5±-reductase is a therapeutic option for BPH, demonstrating involution and shrinkage of the prostatic epithelium, with a consequent reduction in glandular size. Neoplastic prostatic tissue studies show that this pharmacological class led to tumor volume reduction and decrease of area compared to epithelial stroma. Although, little is known about the cellular repair mechanisms and reactive oxygen species with the use of inhibitors of 5±-reductase in prostate morphophysiology. Thus, the aim this study are to characterize and compare the histopathological and molecular effects of the dutasteride use on prostate of men with and without malignant lesion, involving inductive and reparative pathways of carcinogenesis and enzymes forming reactive oxygen species. In the present study will be used 21 samples of prostate tissue from group of patients from the Men's Health Clinic at the Hospital Municipal Paulinia (HMP) / Paulinia-SP. Prostate samples are divided into 4 groups: placebo (n = 7) in the peripheral zone of the prostate samples from normal patients who received placebo once daily for 12 months, dutasteride group (n = 7) in the peripheral zone of the prostate samples from normal patients who received dutasteride (0.5 mg) once daily for 12 months and Group dutasteride + cancer (n = 3) in the peripheral zone of the prostate samples from patients with cancer after 12 months of use of dutasteride; cancer + dutasteride group (n = 4) in the peripheral zone of the prostate samples from patients with early diagnosis of cancer in the first biopsy and subsequently treated with dutasteride for 12 months (with no tumor rebiopsy). Subsequently, prostatic different groups samples will be subjected to histopathological and immunohistochemical analyzes. From this project is expected to achieve a better knowledge of the effects of dutasteride on the cell repair mechanisms to provide more reliable information for adoption in chemoprevention or in the prostate cancer treatment.