Polymorphisms in the AR and PSA Genes as Markers of Susceptibility and Aggressiveness in Prostate Cancer

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Malacoplakia or prostate cancer? Similarities and differences

Malacoplakia is a granulomatous inflammatory disorder clinically and ultrasonographically very similar to prostatic adenocarcinoma. Symptoms and physical findings are similar to prostatism and in half of the patients the differential diagnosis includes malignancy, mainly because of the presence of a hard nodule on digital rectal examination. Additionally, cases of malacoplakia can show hypoechoic nodes on transrectal ultrasound mimicking adenocarcinoma. We report a case of malacoplakia of the prostate with emphasis on its similarities and differences with prostate adenocarcinoma.

In vitro prostate cancer cell growth inhibition by Brazilian plant extracts

In the present study, 1220 plant extracts obtained from 352 plants belonging to 73 families that grow in the Amazon and Atlantic rain forests were screened for cytotoxicity against PC-3 prostate cancer cell lines. Extracts were tested in the single dose of 100 mu g/mL. Activity was observed in 17 aqueous or organic extracts belonging to Annonaceae, Apocynaceae, Araceae, Capparaceae, Commelinaceae, Flacourtiaceae, Lecythiclaceae, Leguminosae, Passifloraceae, Rutaceae, and Violaceae.

Results of prostate cancer screening in non-symptomatic men

Objectives: To verify prostate cancer prevalence in non-symptomatic men between 50 and 70 years old as well as cancer characteristics. Material and Methods: 2815 non-symptomatic men had total PSA and digital rectal examination performed between March 1998 and April 1998. Racial distribution was: 2331 Caucasians (83.9%), 373 Blacks (13.4%) and 75 Asiatic (2.7%). PSA was normal in 2554 (91.4%), 4 to 10 in 177 (6.3%) and greater than 10 in 64 (2.3%). DRE was normal in 2419 (86.3%), suspicious in 347 (12.4%) and characteristic for cancer in 37 (1.3%). Men with abnormal DRE and/or PSA had transrectal prostate biopsy indicated. Results: 461 biopsies were done and 78 tumors was detected (prevalence = 2.8%). Prevalence was progressively higher with age (p < 0.001), PSA level (p < 0.0001) and DRE findings (p = 0.0216). Cancer prevalence in Blacks was 1.65 times higher than in Caucasians (p > 0.05) and 94.9% of detected tumors were moderately or poorly differentiated. Sensibility, specificity, positive predictive value, negative predictive value and total accuracy for PSA were respectively: 66.6%; 89.7%; 51.7%; 94.2% and 86.5%. For DRE, the respective values were: 49.1%; 79.4%; 50.9%; 78.3% and 70.3%. Conclusions: prostate cancer prevalence in the studied population (2.8%) was similar to that of other countries populations. Cancer prevalence in blacks was 1.65 times higher than in Caucasians (difference was not statistically significant). Cancer prevalence becomes higher with aging. The association of DRE and PSA is of paramount importance for cancer diagnosis. The great majority of detected tumors (94.9%) was moderately and poorly differentiated. Brazil probably needs regional studies to better characterize prostate cancer epidemiology due to population heterogeneity.

Single testicular metastasis mimicking primary testicular neoplasm: A rare manifestation of prostate cancer

The incidence of secondary testicular tumors ranges from 0.02 to 2.5% among autopsies in general. With the exception of leukemias and lymphomas, prostate cancer is the most common primary site. It is diagnosed in autopsies or incidentally, following therapeutic orchiectomies in more advanced stages of the disease. In the present report, we show a case of testicular metastasis derived from prostate neoplasm whose clinical presentation as a single metastasis was similar to a primary testicular neoplasm. The diagnosis was evidenced after orchiectomy by histological examination and immunohistochemical tests.

Lack of reliability of nanotechnology in the of free plasma DNA in samples of patients with prostate cancer

Background: Several studies seek biological markers that give diagnostic and degree of tumor development. The aim of this study was to validate the determination of plasma DNA using nanotechnology (Nanovue™-NV) in samples of 80 patients with prostate cancer. Methods. Blood samples of 80 patients of the Urology Ambulatory of Faculdade de Medicina do ABC with prostate cancer confirmed by anatomical-pathology criteria were analyzed. DNA extraction was performed using a GFX TM kit (Amersham Pharmacia Biotech, Inc, USA) following the adapted protocol. Plasma was subjected to centrifugation. Results: There was a big difference between the first and the second value obtained by NanoVue Only two samples had no differences between duplicates. Maximum difference between duplicates was 38 μg/mL. Average variation between 51 samples was 10.29 μg/mL, although 21 samples had differences above this average. No correlation was observed between pDNA obtained by traditional spectrophotometry and by nanotechnology. Conclusion: Determination of plasma DNA by nanotechnology was not reproducible. © 2013 Moreno et al; licensee BioMed Central Ltd.

Fibronectin induces MMP2 expression in human prostate cancer cells

High-grade prostate cancers express high levels of matrix metalloproteinases (MMPs), major enzymes involved in tumor invasion and metastasis. However, the tumor cell lines commonly employed for prostate cancer research express only small amounts of MMPs when cultivated as monolayer cultures, in common culture media. The present study was conducted to ascertain whether culture conditions that include fibronectin can alter MMP2 and MMP9 expression by the human prostatic epithelial cell lines RWPE-1, LNCaP and PC-3. These cells were individually seeded at 2×104cells/cm2, cultivated until they reached 80% confluence, and then exposed for 4h to fibronectin, after which the conditioned medium was analyzed by gelatin zymography. Untreated cells were given common medium. Only RWPE-1 cells express detectable amounts of MMP9 when cultivated in common medium, whereas the addition of fibronectin induced high expression levels of pro and active forms of MMP2 in all tested cell lines. Our findings demonstrate that normal and tumor prostate cell lines express MMP2 activity when in contact with extracellular matrix components or blood plasma proteins such as fibronectin. Future studies of transcriptomes and proteomes in prostate cancer research using these cell lines should not neglect these important conclusions. © 2012 Elsevier Inc..

A new proposed rodent model of chemically induced prostate carcinogenesis: Distinct time-course prostate cancer progression in the dorsolateral and ventral lobes

Background. Characterization of novel rodent models for prostate cancer studies requires evaluation of either spontaneous and carcinogen-induced tumors as well as tumor incidence in different prostatic lobes. We propose a new short-term rodent model of chemically induced prostate carcinogenesis in which prostate cancer progression occurs differentially in the dorsolateral and ventral lobes. Methods. Adult gerbils were treated with MNU alone or associated with testosterone for 3 or 6 months of treatment. Tumor incidence, latency, localization, and immunohistochemistry (AR, PCNA, smooth muscle α-actin, p63, MGMT, and E-cadherin) were studied in both lobes. Results. Comparisons between both lobes revealed that lesions developed first in the DL while the VL presented longer tumor latency. However, after 6 months, there was a dramatic increase in tumor multiplicity in the VL, mainly in MNU-treated groups. Lesions clearly progressed from a premalignant to a malignant phenotype over time and tumor latency was decreased by MNU + testosterone administration. Three-dimensional reconstruction of the prostatic complex showed that the DL developed tumors exclusively in the periurethral area and showed intense AR, PCNA, and MGMT immunostaining. Moreover, VL lesions emerged throughout the entire lobe. MNU-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of E-cadherin, and high MGMT staining. Conclusions. There are distinct pathways involved in tumor progression in gerbil prostate lobes. This animal provides a good model for prostate cancer since it allows the investigation of advanced steps of carcinogenesis with shorter latency periods in both lobes. Copyright © 2013 Wiley Periodicals, Inc.

Finasteride Inhibits Human Prostate Cancer Cell Invasion through MMP2 and MMP9 Downregulation

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

Multi-scale lacunarity as an alternative to quantify and diagnose the behavior of prostate cancer

Prostate cancer is a serious public health problem accounting for up to 30% of clinical tumors in men. The diagnosis of this disease is made with clinical, laboratorial and radiological exams, which may indicate the need for transrectal biopsy. Prostate biopsies are discerningly evaluated by pathologists in an attempt to determine the most appropriate conduct. This paper presents a set of techniques for identifying and quantifying regions of interest in prostatic images. Analyses were performed using multi-scale lacunarity and distinct classification methods: decision tree, support vector machine and polynomial classifier. The performance evaluation measures were based on area under the receiver operating characteristic curve (AUC). The most appropriate region for distinguishing the different tissues (normal, hyperplastic and neoplasic) was defined: the corresponding lacunarity values and a rule's model were obtained considering combinations commonly explored by specialists in clinical practice. The best discriminative values (AUC) were 0.906, 0.891 and 0.859 between neoplasic versus normal, neoplasic versus hyperplastic and hyperplastic versus normal groups, respectively. The proposed protocol offers the advantage of making the findings comprehensible to pathologists. (C) 2014 Elsevier Ltd. All rights reserved.

Evidence of epithelial-mesenchymal transition in canine prostate cancer metastasis

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

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)

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)