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.

Genistein reduces the noxious effects of in utero bisphenol A exposure on the rat prostate gland at weaning and in adulthood

Bisphenol A (BPA) is one hormonally active chemical with potential deleterious effects on reproductive organs, including breast and prostate. In contrast, genistein (GEN) is the major phytoestrogen of soy that presents potential protective effects against hormone-dependent cancers, including that of the prostate. Thus, pregnant Sprague-Dawley rats were treated with BPA at 25 or 250 μg/kg/day by gavage from gestational day (GD) 10-21 with or without dietary GEN at 250 mg/kg/chow (∼5.5 mg/kg/day). Then, male offspring from different litters were euthanized on post-natal day (PND) 21 and 180. At PND21, BPA 25 exposure induced early prostatic changes while dietary GEN attenuated some deleterious actions this xenoestrogen on epithelial cell proliferation levels, androgen receptor expression and prostatic architecture in male offspring. At PND180, a significant increase in incidence of prostatic multifocal inflammation/reactive hyperplasia and atypical hyperplasia were observed in male offspring from dams that received BPA 25. On the other hand, maternal GEN feeding attenuated some the adverse effects of BPA 25 on prostate disease at late-in-life. This way, the present findings point to preventive action of dietary GEN on deleterious effects of gestational BPA exposure in both early and late prostate development in offspring F1.

A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy

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

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)

Prepubertal exposure to bisphenol-A induces ERα upregulation and hyperplasia in adult gerbil female prostate

Prostate physiology is highly dependent on oestrogenic and androgenic homeostasis. Interferences in this equilibrium, especially in early periods of life, may disrupt the prostate and increase the susceptibility to the development of diseases with ageing. Taking this into account, and considering the increase of environmental chemicals with endocrine-disrupting potential such as bisphenol-A (BPA), this study aimed to evaluate the prostates of adult female gerbils exposed to BPA and BPA plus testosterone from pubertal to adult periods. Morphological, stereological and chemical analyses revealed that long-term BPA exposure, even in environmental dosages, increases the proliferative status of the prostate, increases the number of ERα-positive stromal cells and elicits the development of prostatic hyperplasia in adult female gerbils. Moreover, we also observed that the association with testosterone did not increase the proliferative status of the gland, which shows that low levels of BPA are enough to cause an oestrogenic disruption of the prostate in young adults. This evidence suggests that this oestrogenic endocrine disruptor may increase the susceptibility to prostatic disorders with ageing.

Gestational and lactational exposition to Di-N-butyl-phthalate (DBP) increases inflammation and preneoplastic lesions in prostate of wistar rats after carcinogenic N-methyl-N-nitrosourea (MNU) plus testosterone protocol

In the present study, it was evaluated the susceptibility of prostatic lesions in male adult rats exposed to Di-N-butyl-phthalate during fetal and lactational periods and submitted to MNU plus testosterone carcinogenesis protocol. Pregnant females were distributed into four experimental groups: CN (negative control); CMNU (MNU control); TDBP100 (100 mg/kg of DBP); TDBP500 (500 mg/kg of DBP). Females from the TDBP groups received DBP, by gavage, from gestation day 15 (GD15) to postnatal day 21 (DPN21), while C animals received the vehicle (corn oil). CMNU, TDBP100, and TDBP500 groups received a single intraperitoneal injection of MNU (50 mg/kg) on the sixth postnatal week. After that, testosterone cypionate was administered subcutaneously two times a week (2 mg/kg) for 24 weeks. The animals were euthanized on PND220. Distal segment fragments of the ventral (VP) and dorsolateral prostate (DLP) were fixed and processed for histopathological analysis. Protein extracts from ventral prostate were obtained, and western blotting was performed to AR, ERα, MAPK (ERK1/2), and pan-AKT. Stereological analysis showed an increase in the epithelial compartment in TDBP100 and TDBP500 compared to CN. In general, there was increase in the incidence of inflammation and metaplasia/dysplasia in the DBP-treated groups, mainly in DLP, compared to CN and CMNU. Proliferation index was significant higher in TDBP500 and PIN (prostatic intraepithelial neoplasia) was more frequent in this group compared to CMNU. Western blot assays showed an increase in the expressions of AR and MAPK (ERK1/2) in the TDBP100 compared to CN, and ERα and AKT expressions were higher in the TDBP500 group compared do CN. These results showed that different doses of DBP during prostate organogenesis in Wistar rats could increase the incidence of premalignant lesions in initiated rats inducing distinct biological responses in the adulthood. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.

Epigenetic and oncogenic regulation of SLC16A7 (MCT2) results in protein over-expression, impacting on signalling and cellular phenotypes in prostate cancer

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

Intrauterine exposure to bisphenol A promotes different effects in both neonatal and adult prostate of male and female gerbils (Meriones unguiculatus)

Substances that mimic endogenous hormones may alter the cell signaling that govern prostate development and predispose it to developing lesions in adult and senile life. Bisphenol A is able to mimic estrogens, and studies have demonstrated that low levels of exposure to this compound have caused alterations during prostate development. The aim of this study was to describe the prostate development in both male and female neonatal gerbils in normal conditions and under exposure to BPA during intrauterine life, and also to analyze whether the effects of intrauterine exposure to BPA remain in adulthood. Morphological, stereological, three-dimensional reconstruction, and immunohistochemical methods were employed. The results demonstrated that in 1-day-old normal gerbils, the female paraurethral glands and the male ventral lobe are morphologically similar, although its tissue components-epithelial buds (EB), periurethral mesenchyme (PeM), paraurethral mesenchyme (PaM) or ventral mesenchymal pad (VMP), and smooth muscle (SM)-have presented different immunolabeling pattern for androgen receptor (AR), and for proliferating cell nuclear antigen (PCNA). Moreover, we observed a differential response of male and female prostate to intrauterine BPA exposure. In 1-day-old males, the intrauterine exposure to BPA caused a decrease of AR-positive cells in the PeM and SM, and a decrease of the proliferative status in the EB. In contrast, no morphological alterations were observed in ventral prostate of adult males. In 1-day-old females, BPA exposure promoted an increase of estrogen receptor alpha (ERα) positive cells in PeM and PaM, a decrease of AR-positive cells in EB and PeM, besides a reduction of cell proliferation in EB. Additionally, the adult female prostate of BPA-exposed animals presented an increase of AR- and PCNA-positive cells. These results suggest that the prostate of female gerbils were more susceptible to the intrauterine BPA effects, since they became more proliferative in adult life. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.

Evaluation of prognostic factors and survival rates in malignant feline mammary gland neoplasms

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

Bisphenol-A promotes antiproliferative effects during neonatal prostate development in male and female gerbils

Conselho Nacional de Desenvolvimento Científico e Tecnol[ogico (CNPq)

CD10 (Neutral Endopeptidase) expression in myoepithelial cells of salivary neoplasms

CD10 is a cell surface peptidase expressed in a wide variety of normal and neoplastic tissues, including breast myoepithelial cells. In salivary glands, expression of CD10 has only been used to identify neoplastic myoepithelial cells of pleomorphic adenomas and myoepithelial carcinomas. However, its accuracy in other salivary tumors with myoepithelial component has yet to be analyzed. We examined 72 salivary tumors with myoepithelial differentiation using immunohistochemical technique to detect CD10. In salivary glands, CD10 expression was not detected in myoepithelial cells. Only fibrocytes within the intralobular stroma were CD10 positive. In neoplastic myoepithelial cells, CD10 expression was found in 25.71% of benign and 32.43% of malignant neoplasms. When the different groups of tumors were compared, epithelial-myoepithelial carcinomas (EMEC) showed a stark contrast with the others (83.3% of cases with CD10 expression). Surprisingly, adenoid cystic carcinomas and basal cell adenomas were negative in 100% of the cases. Myoepitheliomas, pleomorphic adenomas, and myoepithelial carcinomas were positive in 27.7%, 30.0%, and 40% of the cases, respectively. In conclusion, salivary neoplastic myoepithelial cells gain CD10 expression in relation to their normal counterparts. However, the gain of this protein is not a sensitive marker for detecting myoepithelial cells in the majority of the tumors, except for EMEC. The high expression of CD10 by this carcinoma can be a valuable tool to separate EMEC from the tubular variant of adenoid cystic carcinomas in small incisional biopsies, where the precise diagnosis may be impossible.

Expressão diferencial de microRNAs no câncer de próstata

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

Role of ATM and PTEN in prostatic carcinogenic dog prostate: validation of aCGH results

The canis lupus familiares is the only species besides human that spontaneously develop prostatic carcinoma (PCa). In addition, the metastatic sites are similar to those frequently reported in men. For these reasons, the dog is the best natural model to study the molecular mechanisms in PCa development providing a natural animal model for treatment by molecular targets. Previously, we investigated copy number alterations by arrayCGH (Canine Genome CGH Microarray 4x44K-G2519F, Agilent Technologies) in canine prostatic lesions: 3 benign prostatic hyperplasias (BPH), 4 proliferative inflammatory atrophies (PIA), and 14 PCa. Five histologically normal prostatic tissues were used as reference. Genomic alterations were evaluated using Genomic Workbench Standard Edition 5.0.14. This previous study revealed significant copy number losses of Atm and Pten exclusively in PCa. In the present study, ATM and PTEN immunoexpression were investigated using a tissue microarray (TMA) containing 149 canine prostatic paraffin-embedded lesions (BPH, PIA and PCa) collected from 67 animals. Immunohistochemical reactions were performed using the polyclonal rabbit antibody anti-PTEN (Santa Cruz Biotech, 1:50) and anti-ATM (Abcam, 1:50). The sections were developed with diaminobenzidine (DAB) and peroxidase. The immunohistochemical staining was assessed in each core by the distribution of positive cells for each antibody per lesion (score 1: <25% cells positive, 2: 26% to 50%, 3: being 51% and 75% and 4:> 75%) and intensity (1: weak, 2: moderate, 3: intense). Chi-square or Fisher exact test was used to determine the association between the categorical variables using GraphPad Prism 5 (GraphPad Software Inc., La Jolla, CA). Distribution of positive cells did not differ among lesions. PCa and PIA showed more samples with weak intensity for ATM when compared to normal prostatic tissue and BPH (PCa: p=0,032 and PIA: p=0,025). Benign prostatic hyperplasia and normal samples presented intense PTEN immunostaining than PCa (p=0,021) and PIA (p=0,0013). These results suggest that ATM and PTEN proteins expression in canine prostatic carcinoma are downregulated possibly by copy number losses. These findings are similar from those described in prostate carcinomas from human corroborating for the use of dogs as a natural model to study prostatic disease in men.

Modeling spatial distribution of cancer incidence in Cordoba, Argentina

Background: Cancer is the second leading cause of death in Argentina, and there is little knowledge about its incidence. The first study based on population-based cancer registry described spatial incidence and indicated that there existed at least county-level aggregation. The aim of the present work is to model the incidence patterns for the most incidence cancer in Córdoba Province, Argentina, using information from the Córdoba Cancer Registry by performing multilevel mixed model approach to deal with dependence and unobserved heterogeneity coming from the geo-reference cancer occurrence. Methods: Standardized incidence rates (world standard population) (SIR) by sex based on 5-year age groups were calculated for 109 districts nested on 26 counties for the most incidence cancers in Cordoba using 2004 database. A Poisson twolevel random effect model representing unobserved heterogeneity between first level-districts and second level-counties was fitted to assess the spatial distribution of the overall and site specific cancer incidence rates. Results: SIR cancer at Córdoba province shown an average of 263.53±138.34 and 200.45±98.30 for men and women, respectively. Considering the ratio site specific mean SIR to the total mean, breast cancer ratio was 0.25±0.19, prostate cancer ratio was 0.12±0.10 and lower values for lung and colon cancer for both sexes. The Poisson two-level random intercepts model fitted for SIR data distributed with overdispersion shown significant hierarchical structure for the cancer incidence distribution. Conclusions: a strong spatial-nested effect for the cancer incidence in Córdoba was observed and will help to begin the study of the factors associated with it.