Five-alpha Reductase Inhibitor Influences Expression of Androgen Receptor and HOXB13 in Human Hyperplastic Prostate Tissue

Objectives Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells. Materials and Methods We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate tissue was evaluated by immunohistochemical staining. We tested the effect of 5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation assay, and ELISA. Results: Group 2 showed stronger reactivity for AR and HOXB13 than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI. At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR expression but it stimulated the expression of HOXB13. Conclusions These results demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells and human prostate tissue. In order to use 5ARI in chemoprevention of prostate cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic proteins and its regulation pathway. .

Identificación de factor de crecimiento vascular endotelial en células glandulares de tejido prostético maligno y benigno: Relación con la recidiva tumoral al año de la prostatectomía / Vascular endothelial growth factor in malignant and non malignant prostatic tissue: Association with tumor recurrence at one year after prostatectomy

Background: Prostate cancer (PC) is the second cause of death by cancer in men in Chile. Its behavior is so variable that it is necessary to search reliable prognostic markers. Vascular Endothelial Growth Factor (VEGF) is one of the most powerful pro-angiogenic factors. There is no agreement on its validity as a diagnostic or prognostic factor. Aim: To search for VEFG in prostatic tissue. Material and Methods: This study was performed in prostatectomy tissue coming from 41 patients with PC and 39 patients with benign prostatic hyperplasia (BPH). Specimens were studied using immunohistochemical staining for VEGF. The percentage of stained glandular cells per patient was calculated and associated with pathological diagnosis in cancer patients. Results: PC biopsies had a mean of 82% of VEGF (+) stained cells, while BPH had only 1.6% (p < 0.01). No relationship was found between the percentage of staining and recurrence at one year of follow-up in the case of PC. Conclusions: These results would rule out VEGF as a prognostic factor in this series of patients.

Tejido prostático en teratoma quístico maduro del ovario: Caso clínico / Prostatic tissue in a mature cystic teratoma of the ovary: Report of one case

Male accessory sexual glands arising in ovarian cystic teratoma are exceedingly rare. We report a 56-year-old female subjected to an ovariohysterectomy due to a left ovarian mass. The pathological study of the surgical piece revealed a tumor composed of different mature tissue elements and well defined nodules of benign prostatic tissue.

Parallel determination of NeuroD1, Chromogranin-A, KI67 and androgen receptor expression in surgically treated prostate cancers

PURPOSE: Neuroendocrine differentiation is a hallmark of prostate cancer. The aim of our study was the detection of the parallel expression of neuroendocrine related markers using a prostate tissue microarray (TMA). MATERIALS AND METHODS: Our study was aimed at detecting the parallel expression of NeuroD1, Chromogranin-A (ChrA), Androgen Receptor (AR) and Ki-67 by immunohistochemistry on prostate cancer tissue microarray. The data was analyzed using SAS version 8.2 (SAS Inc, Cary, NC). The relationships between NeuroD1, ChrA and AR expressions and patients' characteristics were investigated by multivariate logistic regression analysis. Progression and Overall Survival (OS) distributions were calculated using Kaplan-Meier method. RESULTS: Tissue reactivity for NeuroD1, ChrA and AR concerned 73 percent, 49 percent and 77 percent of the available cases, respectively. Regarding overall survival, there were 87 deaths and 295 patients alive/censored (6 years of median follow-up). Seventy-seven disease progressions occurred at the median follow-up 5.4y. A significant correlation between NeuroD1, ChrA and AR expression was observed (p < 0.001 and p < 0.03, respectively). Additionally, ChrA was strongly associated in multivariate analysis to Gleason score and Ki67 expression (p < 0.009 and p < 0.0052, respectively). Survival analysis showed no association between markers neither for overall nor for cancer-specific survival. CONCLUSIONS: The results highlight that NeuroD1, Chromogranin-A and Androgen Receptor are strongly associated, however their expression does not correlate with overall survival or disease progression.

Lycopene and ß-carotene protect in vivo iron-induced oxidative stress damage in rat prostate

It has been suggested that iron overload may be carcinogenic. In the present study, we evaluated the effect of plasma and prostate carotenoid concentration on oxidative DNA damage in 12-week-old Wistar rats treated with intraperitoneal (ip) ferric nitrilotriacetate (Fe-NTA) (10 mg Fe/kg). Plasma ß-carotene and lycopene concentrations were measured as a function of time after ip injection of carotenoids (10 mg kg-1 day-1 ß-carotene or lycopene) in rats. The highest total plasma concentration was reached 3 and 6 h after ip injection of lycopene or ß-carotene, respectively. After 5 days of carotenoid treatment, lycopene and ß-carotene were present in the 0.10-0.51 nmol/g wet tissue range in the prostate. Using a sensitive method to detected 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) by HPLC/EC, the level of 8-oxodGuo in rat prostate DNA was significantly higher (6.3 ± 0.6 residues/10(6) dGuo) 3 h after Fe-NTA injection compared with control rats (1.7 ± 0.3 residues/10(6) dGuo). Rats supplemented with lycopene or ß-carotene for 5 days prior to Fe-NTA treatment showed a reduction of about 70 percent in 8-oxodGuo levels to almost control levels. Compared with control rats, the prostate of Fe-NTA-treated animals showed a 78 percent increase in malondialdehyde accumulation. Lycopene or ß-carotene pre-treatment almost completely prevented lipid damage. Epidemiological studies have suggested a lower risk of prostate cancer in men reporting a higher consumption of tomato products. However, before associating this effect with tomato sauce constituents, more information is required. The results described here may contribute to the understanding of the protective effects of carotenoids against iron-induced oxidative stress.

Metallothioneim expression in human prostate gland

This study is conducted to detect metallothionein [MT] distribution in the epithelial cells of prostate gland from patients with benign prostatic hypertrophy and adenocarcinoma. Prostatic tissues from patients with benign prostatic hypertrophy and adenocarcinoma were processed for immunocytochemistry using indirect peroxidase antiperoxidase procedure and primary antibody against MT. The samples were collected over a period of 2-3 years and were processed at Jordan University of Science and Technology, Irbid, Jordan in the year 2002. All prostatic tissues showed a positive reaction for MT. In benign prostatic hypertrophy, MT was mainly localized in the nuclei of epithelial cells while in the adenocarcinoma; MT was mainly localized in the cytoplasm of the epithelial cells. Metallothionein expression may be affected by the pathological status of the prostate. In addition, these findings could be used in diagnosing and evaluating the prognosis of different pathological conditions of the prostate

Effect of gossypol on pituitary reproductive axis: ultrastructural and biochemical studies.

Oral administration of gossypol induced sterility in male rats by 10 weeks, at a dose of 15 mg/kg body weight/day. The pituitary FSH gonadotroph cells showed dilated endoplasmic reticulum and accumulation of secretory granules in the cytoplasm. LH cells were degranulated. The Leydig cells showed enhanced synthetic activity. There was no change in testis weight and testicular RNA, lipids and cholesterol in the treated group while significant increase was observed in DNA content. Testicular sialic acid content decreased significantly over controls. The Sertoli cells, spermatogonia, spermatocytes and early spermatids were not affected after the treatment. The weights of prostate, seminal vesicle were recorded normal and there were no ultrastructural variations. The levels of acid and alkaline phosphatase and RNA in prostatic tissue were insignificant as compared with controls. However, DNA content of prostate gland showed a significant increase. Sialic acid of seminal vesicle + coagulating gland were within the control range. A marked reduction in fructose values from the same organ was noted.