New therapeutic perspectives for proliferative prostate lesions treatment: immunotherapy P-MAPA associated with block angiogenesis

Abstract

The association between immunotherapy and antiangiogenic agents may be a promising combination in the development of treatments against prostate diseases. According to preview researches, the compost P-MAPA has a very important immunotherapy effect, and its association with the angiogenic inhibitor TNP-470 may represent a new treatment for these pathologies. How in the literature there is no such association, this study aims to characterize and compare the morphological and molecular effects of anti-angiogenic therapy associated with P-MAPA immunotherapy in the treatment of prostatic lesions chemically induced. From 25 Fischer 344 male rats, 5 will be considered as a control group and 20 will be chemically induced. Each of these rats will receive daily subcutaneous doses of 100 mg/Kg of Testosterone Cypionate and they will be treated with N-methyl-N-nitrosourea (MNU, 15 mg/Kg) inoculated in the capsule of the anterior prostate lobe (1 application on every 15 days, resulting in 2 administrations). One week after the last dose, the rats will receive subcutaneous doses of 5 mg/Kg of Testosterone cypionate, in alternating days, in a period of 120 days. Then, all the animals will be submitted to ultrasound scanning and divided in five groups with 5 animals each, which will receive the following subcutaneous treatment three times a week, for 30 days: Control Group (Group 1): 5 mL/Kg of 0.9% saline solution; MNU Group (with the prostate diseases, Group 2): the same treatment as group 1; MNU + P-MAPA Group (Group 3): 5 mg/Kg of P-MAPA; MNU+TNP-470 Group (Group 4): 15 mg/Kg of TNP-470; MNU+P-MAPA+TNP-470 Group (Group 5): 5 mg/Kg of P-MAPA and 15 mg/Kg of TNP-470. Passed 150 days of treatment, the anterior prostate of the 25 animals will be extracted for histopathological analysis, immunohistochemistry, and Western Blotting. (AU)