Study of the ventral prostate of Wistar rats treated with Heteropterys tomentosa (A. Juss.)

Heteropterys tomentosa is a Brazilian plant traditionally used as an aphrodisiac and stimulant. Previous studies suggested possible androgenic and antioxidant effects after long term administration of H. tomentosa infusion. The aim of the present study was to evaluate the effects of this plant infusion on the rat ventral prostate: an androgen responsive organ. Wistar rats were treated, by gavage, with H. tomentosa roots infusion (treated group, n=6) or water (control group, n=6) for 56 days. Morphological, morphometrical and stereological analyses were employed to study the ventral prostate tissue, as well as androgen receptor and apoptotic cell staining. The ultrastructure of the prostatic epithelium was also analyzed. No alteration was observed in the stereological and morphometrical analyses. The pattern of androgen receptor expression and the apoptotic index were identical in the control and treated group. Ultrastructural analysis showed no alterations caused by H. tomentosa. These results suggested that treatment with H. tomentosa infusion, although considered a strong aphrodisiac, did not cause any major damage nor benefit to the prostate tissue.

Prenatal exposure to testosterone masculinises the female gerbil and promotes the development of lesions in the prostate (Skene

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

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.

Prostate hyperplasia caused by long-term obesity is characterized by high deposition of extracellular matrix and increased content of MMP-9 and VEGF

Recent studies have shown a positive association of cancer and obesity, but the morphological and molecular mechanisms involved in this relationship are still unknown. This study analysed the impact of long-term obesity on rat prostate, focusing on stromal changes. Male adult Wistar rats were treated with high-fat diet to induce obesity, while the control group received a balanced diet. After 30 weeks of feeding, the ventral prostate was analysed by immunohistochemistry for cell proliferation, smooth muscle α-actin, vimentin, chondroitin sulphate and metalloproteinases (MMP-2 and 9). The content of androgen receptor (AR), oestrogen receptors (ERs) and vascular endothelial growth factor (VEGF) was measured by Western blotting, and activity of catalase and Glutathione-S-Transferase (GST) were quantified by enzymatic assay. Long-term obesity decreased testosterone plasma levels by 70% and resulted in stromal prostate hyperplasia, as evidenced by increased collagen fibres. Such stromal hyperplasia was associated with increased number of blood vessels and raised VEGF content, and increased expression of chondroitin sulphate, vimentin, α-actin and MMP-9. In spite of the high cell density in prostate, the proliferative activity was lower in the prostates of obese rats, indicating that hyperplasia was established during the early phases in this obesity model. AR levels increased significantly, whereas the ERα decreased in this group. Moreover, the levels of catalase and GST were changed considerably. These findings indicate that long-term obesity, besides disturbing the antioxidant control, causes intense stromal remodelling and release of factors that create an environment that can promote proliferative disorders in the gland, culminating with diffuse hyperplasia.

Evidence of epithelial-mesenchymal transition in canine prostate cancer metastasis

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

Ethanol modulates the synthesis and catabolism of retinoic acid in the rat prostate

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

The effects of high doses of nandrolone decanoate and exercise on prostate microvasculature of adult and older rats

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

Androgen therapy reverses injuries caused by ethanol consumption in the prostate: testosterone as a possible target to ethanol-related disorders

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

Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis

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

Acoustic radiation force impulse elastography of prostate and testes of healthy dogs: preliminary results

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

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.

Epithelial-mesenchymal transition occurs in preneoplastic and neoplastic lesions of canine prostate

Background: The epithelial-mesenchymal transition (EMT) is an essential process in the tumor progression and metastasis. In human prostate carcinoma (PCa), the upregulation of cytokeratin and E-cadherin and down-regulation of vimentin have been associated with aggressive phenotype and poor prognosis. Due to the importance of canine cancer model it was evaluated the immunoexpression of AE1/AE3, E-cadherin and vimentin in canine prostatic lesions. Patients and Methods: A total of 75 prostatic tissues formalin-fixed paraffin embedded from dogs was selected: 10 normal prostatic tissues, 20 benign prostatic hyperplasia (BPH), 25 proliferative inflammatory atrophy (PIA) and 20 PCa. AE1/AE3 was detected with a monoclonal antibody (Invitrogen, 180132) at a 1:300 dilution, applied for 45 min at room temperature (RT). The antibody against Vimentin (V9, Invitrogen) and E-cadherin (NCH-38, Dako cytomatiomn) were monoclonal mouse antibodies, used at a 1:300 and 1:200, respectively, for 45 min at RT. The immunolabelling was performed by a polymer method (Histofine, Nichirei Biosciences,). A negative control was performed for all antibodies by omitting the primary antibody and substituting with Tris-buffered saline. The percentage of C-MYC, E-cadherin, and p63- positive cells per lesion was evaluated according to Prowatke et al. (2007). The samples were scored separately according to staining intensity and graded semi-quantitatively as negative, weakly positive, moderately positive, and strongly positive. The score was done in one 400 magnification field, considering only the lesion, since this was done in a TMA core of 1 mm. For statistical analyses, the immunostaining classifications were reduced to two categories: negative and positive. The negative category included negative and weakly positive staining. Chi-square or Fisher exact test was used to determine the association between the categorical variables. Results: All prostatic normal and BPH tissue were positive for cytokeratin, E-cadherin and negative for vimentin. Similarly, all PIA samples were positive for AE1/AE3. From those samples, 48% (12/25) were also positive for vimentin. 55% of PCa (11/25) was positive for vimentin and among these samples 75% (6/11) was also positive for AE1/AE3 and 45% (5/11) was negative for AE1/AE3. PIA and PCa presented a higher number of vimentin positive cells when compared with normal tissue (p=0.032). E-cadherin expression had no statistical difference among diagnosis groups, but we found a higher number of positive cases, with more than 51% of positive immunostaining in BPH and PIA (81.25% and 78.60% of the cases, respectively) than in PCa (55.55%). Conclusion: The carcinogenesis process regarding prostatic epithelial cells in dogs showed higher vimentin protein expression associated with concomitant loss of the cytokeratin and E-cadherin, similar in humans.

Sedoanalgesia with midazolam and fentanyl citrate controls probe pain during prostate biopsy by transrectal ultrasound

To assess the pain intensity of patients administered midazolam and fentanyl citrate before undergoing transrectal ultrasound-guided prostate biopsy. This was a study in patients with different indications for prostate biopsy in whom 5 mg of midazolam and 50 µg of fentanyl citrate was administered intravenously 3 minutes before the procedure. After biopsy, pain was assessed by use of a visual analogue scale (VAS) in three stages: VAS 1, during probe introduction; VAS 2, during needle penetration into prostate tissue; and VAS 3, in the weeks following the exam. Pain intensity at these different times was tested with stratification by age, race, education, prostate volume, rebiopsy, and anxiety before biopsy. Pain was ranked according to the following scores: 0 (no pain), 1-3 (mild pain), 4-7 (moderate pain), and 8-10 (severe pain). Statistical analysis was performed by using Kruskal-Wallis and Wilcoxon two-tailed tests with a significance of 5%. Pain intensity was not influenced by any risk factors. The mean VAS 1 score was 1.95±1.98, the mean VAS 2 score was 2.73±2.55, and the mean VAS 3 score was 0.3±0.9, showing greater pain at the time of needle penetration than in other situations (VAS 2>VAS 1>VAS 3, p=0.0013, p=0.0001, respectively). Seventy-five percent of patients reported a VAS pain scale of less than 3.1 or mild pain. Intravenous sedation and analgesia with midazolam and fentanyl citrate is a good method for reducing pain caused by prostate biopsy, even during probe insertion.