Finasteride treatment alters MMP-2 and-9 gene expression and activity in the rat ventral prostate

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Combined effect of the finasteride and doxazosin on rat ventral prostate morphology and physiology

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tissue evidence of the testosterone role on the abnormal growth and aging effects reversion in the gerbil (Meriones unguiculatus) prostate

Prostate differentiation during embryogenesis and its further homeostatic state maintenance during adult life depend on androgens. Abundant biological data suggest that androgens play an important role in the development of the prostate cancer and other prostatic diseases. The objective of this work was to evaluate the effects of the testosterone supplementation in gerbil (a new experimental model) at different ages. Tissues from experimental animals were studied by histological and histochemistry procedures, androgen receptor immunohistochemistry assay, morphometric-stereological analysis, and transmission electron microscopy (TEM). After the treatment were observed increase of prostate weight and epithelium height in all ages studied. In some adult and aged treated animals, hyperplasic and displasic process were observed, including prostatic intraepithelial neoplasias and adenocarcinomas. Increase of the thickness of the smooth muscle cell (SMC) layer was observed in pubescent and adult animals and TEM revealed apparent SMC hypertrophy. An apparent increase in the frequency of blood vessels distributed by the subepithelial stroma in the treated animals was noticed. Reversion of the natural effects of aging on the prostate was observed in the aged treated animals in some acini of the gland. These data demonstrate that the gerbil prostate is susceptible to androgenic action at the studied ages and it can serve, for example, as experimental model to studies of prostate neoplasic process induction and hormonal therapy in aged animals.

Age-related histopathological lesions in the Mongolian gerbil ventral prostate as a good model for studies of spontaneous hormone-related disorders

The Meriones unguiculatus (Mongolian) gerbil has demonstrated significant prostatic responses to hormonal treatments, and to drugs against human prostatic hyperplasia Spontaneous neoplasia develops in the older animals. Thirty gerbils (age 18 months) were divided into non-affected and prostatic lesion bearers and the prostate lesions were evaluated morphologically, immunohistochemically and quantitatively. The most frequent changes were in epithelial sites and, namely prostatic intraepithelial neoplasias, microinvasive carcinomas and adenocarcinomas. In the stromal compartment, cellular hyperplasia, when verified, was always associated with the sites of anomalous epithelium. Additionally, larger deposition of collagen fibrils, generating stromal fibrosis, was found in all the old gerbils analysed. The quantitative analysis showed that prostatic tissue proportions differed in altered areas, being specific for each lesion type. Isolated nuclear and nucleolar parameters were not effective in diagnosing the malign potential of lesions. However, the cellular proliferation and death indexes indicated larger cellular turnover in invasive lesions such as carcinomas. With these analyses, it could be verified that old gerbils present high propensity to develop spontaneous prostate changes and this may aid in a better understanding of the biological behaviour of human prostate cancer.

Anatomy of smooth muscle cells in nonmalignant and malignant human prostate tissue

Differently graded areas of human prostate adenocarcinoma were examined after Masson's trichrome staining or immunohistochemistry for smooth muscle alpha-actin, type IV collagen and laminin. In addition, the ultrastructure of the prostatic smooth muscle cells (SMC) during glandular proliferation and epithelial invasion in selected tumors was studied. The SMC formed a thick layer below the epithelial structures in unaffected areas and were closely associated with each other in homotypic interactions. As the tumor grade increased, the SMC gradually lost interactions with each other and became atrophic. With the growth of the epithelial compartment, the SMC initially segregated to the tumor periphery and the intercellular spaces increased. In high grade tumors, the epithelial cancer cells invaded the spaces between the SMC. Immunohistochemical analysis of the basal membrane revealed increased disruption of the usually thick basal membrane, which became thinner and faintly stained with each of the antibodies used. We conclude that most SMC become atrophic following epithelial invasion in human tumors and that degradation of the basal membrane is an important factor in this process. At the ultrastructural level, different SMC phenotypes occur in prostatic tissues during epithelial invasion. Interconversion between these phenotypes is suggested and a probable relationship among them is proposed.

Tissue changes in senescent gerbil prostate after hormone deprivation leads to acquisition of androgen insensitivity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Androgen receptor in the Mongolian gerbil ventral prostate: Evaluation during different phases of postnatal development and following androgen blockage

The normal growth, differentiation and maintenance of the morphofunctional integrity of the prostate gland are dependent on the interaction of constant levels of androgens with their receptors. The need to study the responses to hormones under several conditions and the effect of their blockage is due to the fact that the human prostate is the site of a great number of age-related diseases, and the ones with a major medical importance are prostate cancer (Cap) and benign prostatic hyperplasia (BPH), which can both be treated with androgen suppression. Seventy-five male gerbils were divided, randomly, into 3 groups of 25 animals each, where each group corresponded to one phase of postnatal development. In each phase, it was possible to morphologically and stereologically analyze the compartments of prostatic ventral lobe, as well as to immunohistochemically analyze the degree of expression of androgen receptors (ARs) after the androgen blockage therapies. In addition, it was possible to establish the hormonal dosage of serum testosterone levels given the comparative approach of the expression of androgen receptors. There is a pattern of AR distribution in the prostatic ventral lobe throughout postnatal development, in which the younger the animal is the higher, the interaction of circulating androgens that stimulate the AR expression in both the epithelial and stromal compartments. The androgen blockage therapies decreased AR expression in the prostatic compartments, but the androgen reposition after these blockages was not sufficient to recover the glandular structure or stimulate the AR expression up to normal physiological conditions. Both the regulation and distribution of androgen receptors along the gerbil prostatic tissues are complex mechanisms that are likely to be genetically regulated by androgens prenatally or by other factors that are still unknown. This rodent species seems to be a valuable model in the attempt to improve the understanding of the morphophysiological and pathological behavior of this important gland in humans throughout aging and to stimulate new therapeutic ideas to fight prostate cancer. (C) 2008 Elsevier Ltd. All rights reserved.

Diabetes induces stromal remodelling and increase in chondroitin sulphate proteoglycans of the rat ventral prostate

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chronic Ethanol Consumption Alters All-Trans-Retinoic Acid Concentration and Expression of Their Receptors on the Prostate: A Possible Link Between Alcoholism and Prostate Damage

Background: Ethanol (EtOH) alters the all-trans-retinoic acid (ATRA) levels in some tissues. Retinol and ATRA are essential for cell proliferation, differentiation, and maintenance of prostate homeostasis. It has been suggested that disturbances in retinol/ATRA concentration as well as in the expression of retinoic acid receptors (RARs) contribute to benign prostate hyperplasia and prostate cancer. This study aimed to evaluate whether EtOH consumption is able to alter retinol and ATRA levels in the plasma and prostate tissue as well as the expression of RARs, cell proliferation, and apoptosis index. Methods: All animals were divided into 4 groups (n = 10/group). UChA: rats fed 10% (v/v) EtOH ad libitum; UChACo: EtOH-naïve rats without access to EtOH; UChB: rats fed 10% (v/v) EtOH ad libitum; UChBCo: EtOH-naïve rats without access to EtOH. Animals were euthanized by decapitation after 60 days of EtOH consumption for high-performance liquid chromatography and light microscopy analysis. Results: EtOH reduced plasma retinol concentration in both UChA and UChB groups, while the retinol concentration was not significantly different in prostate tissue. Conversely, plasma and prostate ATRA levels increased in UChB group compared with controls, beyond the up-regulation of RARβ and -γ in dorsal prostate lobe. Additionally, no alteration was found in cell proliferation and apoptosis index involving dorsal and lateral prostate lobe. Conclusions: We conclude that EtOH alters the plasma retinol concentrations proportionally to the amount of EtOH consumed. Moreover, high EtOH consumption increases the concentration of ATRA in plasma/prostate tissue and especially induces the RARβ and RARγ in the dorsal prostate lobe. EtOH consumption and increased ATRA levels were not associated with cell proliferation and apoptosis in the prostate. © 2012 by the Research Society on Alcoholism.

Unsupervised segmentation method for cuboidal cell nuclei in histological prostate images based on minimum cross entropy

This paper presents a novel segmentation method for cuboidal cell nuclei in images of prostate tissue stained with hematoxylin and eosin. The proposed method allows segmenting normal, hyperplastic and cancerous prostate images in three steps: pre-processing, segmentation of cuboidal cell nuclei and post-processing. The pre-processing step consists of applying contrast stretching to the red (R) channel to highlight the contrast of cuboidal cell nuclei. The aim of the second step is to apply global thresholding based on minimum cross entropy to generate a binary image with candidate regions for cuboidal cell nuclei. In the post-processing step, false positives are removed using the connected component method. The proposed segmentation method was applied to an image bank with 105 samples and measures of sensitivity, specificity and accuracy were compared with those provided by other segmentation approaches available in the specialized literature. The results are promising and demonstrate that the proposed method allows the segmentation of cuboidal cell nuclei with a mean accuracy of 97%. © 2013 Elsevier Ltd. All rights reserved.

Low frequency of human papillomavirus detection in prostate tissue from individuals from Northern Brazil

The presence of human papillomavirus (HPV) was evaluated in 65 samples of prostate tumours and six samples of prostates with benign prostatic hyperplasia from individuals from Northern Brazil. We used a highly sensitive test, the Linear Array HPV Genotyping Test, to detect 37 high and low-risk HPV types. In this study, only 3% of tumour samples showed HPV infection. Our findings support the conclusion that, despite the high incidence of HPV infection in the geographic regions studied, HPV was not associated with a higher risk of prostate cancer. To our knowledge, this is the first study evaluating the frequency of HPV detection in prostatic tissue of individuals from Brazil.

Key participants of the tumor microenvironment of the prostate: An approach of the structural dynamic of cellular elements and extracellular matrix components during epithelial-stromal transition

Cancer is a multistep process that begins with the transformation of normal epithelial cells and continues with tumor growth, stromal invasion and metastasis. The remodeling of the peritumoral environment is decisive for the onset of tumor invasiveness. This event is dependent on epithelial–stromal interactions, degradation of extracellular matrix components and reorganization of fibrillar components. Our research group has studied in a new proposed rodent model the participation of cellular and molecular components in the prostate microenvironment that contributes to cancer progression. Our group adopted the gerbil Meriones unguiculatus as an alternative experimental model for prostate cancer study. This model has presented significant responses to hormonal treatments and to development of spontaneous and induced neoplasias. The data obtained indicate reorganization of type I collagen fibers and reticular fibers, synthesis of new components such as tenascin and proteoglycans, degradation of basement membrane components and elastic fibers and increased expression of metalloproteinases. Fibroblasts that border the region, apparently participate in the stromal reaction. The roles of each of these events, as well as some signaling molecules, participants of neoplastic progression and factors that promote genetic reprogramming during epithelial–stromal transition are also discussed.

Segmentation of Cell Nuclei Regions in Epithelium of Prostate Glands

This paper proposes a method for segmentation of cell nuclei regions in epithelium of prostate glands. This structure provides information to diagnosis and prognosis of prostate cancer. In the initial step, the contrast stretching technique was applied in image in order to improve the contrast between regions of interest and other regions. After, the global thresholding technique was applied and the value of threshold was defined empirically. Finally, the false positive regions were removed using the connected components technique. The performance of the proposed method was compared with the Otsu technique and statistical measures of accuracy were calculated based on reference images (gold standard). The result of the mean value of accuracy of proposed method was 93% ± 0.07.

Short-term prophylaxis with ciprofloxacin in extended 16-core prostate biopsy

Objective: To evaluate the safety, efficacy and possible complications of 16-core transrectal prostate biopsies using two doses of ciprofloxacin for prophylaxis of infectious complications.Materials and Methods: Sixteen-core prostate biopsies were performed on a number of patients with different signs of potential prostate cancer. Complications were assessed both during the procedure and one week later. After the procedure, urine samples were collected for culture. The rate of post-biopsy complications, hospital visits and hospitalizations were also analyzed. Ciprofloxacin (500 mg) was administered two hours before, and eight hours after the procedure.Results: The overall rate of post-biopsy complications was 87.32%, being 5.4% of those considered major complications due to hemorrhage, or to urinary retention. Eight patients required hospital treatment post-biopsy. Fever occurred in just one patient (0.29%). There was no incidence of orchitis, epididymitis, prostatitis, septicemia, hospitalization, or death. The urine culture showed positive results in five patients (2.15%).Conclusion: One-day prophylaxis with ciprofloxacin proved to be safe and effective in the prevention of infectious complications following 16-core prostate biopsies.

Influence of melatonin on the proliferative and apoptotic responses of the prostate under normal and hyperglycemic conditions

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)