Low RKIP expression associates with poor prognosis in bladder cancer patients

Urothelial bladder cancer (UBC) is a heterogeneous type of disease. It is urgent to screen biomarkers of tumour aggressiveness in order to clarify the clinical behaviour and to personalize therapy in UBC patients. Raf kinase inhibitory protein (RKIP) is a metastasis suppressor, and its downregulation is associated with metastatic events in an increasing number of solid tumours. We evaluated the clinical and prognostic significance of RKIP expression in patients with high risk of progression UBC. Using immunohistochemistry, we determined RKIP expression levels in a series of 81 patients with high-grade pT1/pTis or muscle-invasive UBC. Staining of CD31 and D2-40 was used to assess blood and lymphatic vessels, in order to distinguish between blood and lymphatic vessel invasion (LVI). We found that 90 % of pT1/pTis tumours, 94 % of non-muscle invasive papillary tumours and 76 % of the cases without LVI occurrence expressed RKIP in >10 % of cells. In this group, we observed a subgroup of tumours (42 %) in which the tumour centre was significantly more intensely stained than the invasion front. This heterogeneous pattern was observed in 63 % of the cases with LVI. Low RKIP expression was associated with poorer 5-year disease-free and overall survival rates, and remained as an independent prognostic factor for disease-free survival. Loss of RKIP expression may be an important prognostic factor for patients with high risk of progression bladder cancer. © 2013 Springer-Verlag Berlin Heidelberg.

Simultaneity of the anthropometric markers of adiposity and chronic diseases in women

Aim. The aim of this paper was to investigate the relationship between the accumulation of different anthropometric indicators and the prevalence of some chronic diseases in women over 40 years of age. Methods. The sample was comprised of 562 women between 40 and 95 years of age (64.5 ± 11.4) attended by the research projects were carried out in two cities in southeastern Brazil. Anthropometric measurements were taken: weight, height, waist circumference, hip circumference, and the values of BMI and WHR were later calculated. The referenced morbidity questionnaire was also applied, based on the Standard Health Questionnaire (SHQ), which analyzes the presence of degenerative chronic diseases in the adult population. For the statistical treatment, the chi-square and binary logistic regression tests were performed, with significance set at 5%. Results. The relationship between three changes in the anthropometric indicators and the greater incidence of diseases continued significant for hypertension (OR=3.77 [95% CI: 2.14-6.65], =P=0.001), and for endocrine and metabolic diseases (OR=2.59 [95%: 1:47 to 4:32], =P=0.001), regardless of the effects of age and physical activities. Conclusion. The simultaneity of body fat indicators is more strongly associated with the prevalence of some chronic diseases (hypertension, endocrine, and metabolic), relative to the individualized use of anthropometric indicators.

Nanotechnology-based drug delivery systems for treatment of hyperproliferative skin diseases - a review

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

In vitro targeting of Polo-like kinase 1 in bladder carcinoma: Comparative effects of four potent inhibitors

Despite the improvements in neoadjuvant chemotherapy, the outcome of patients with advanced bladder cancer has changed very little over the past 30 years. In the present study we tested and compared the in vitro antitumor activities of four different inhibitors of Polo-like kinase 1 (PLK1) (BI 2536, BI 6727, GW843682X, and GSK461364), against 3 bladder carcinoma cell lines RT4, 5637 and T24. The impact on radiosensitivity and drug interactions in simultaneous treatments with cisplatin, methotrexate, and doxorubicin were also investigated. Our results showed that PLK1 inhibition prevented cell proliferation and clonogenicity, causing significant inhibition of invasion of tumor cells, though modest differences were observed between drugs. Moreover, all PLK1 inhibitors induced G2/M arrest, with the subsequent induction of death in all 3 cell lines. Drug interactions studies showed auspicious results for all PLK1 inhibitors when combined with the commonly used cisplatin and methotrexate, though combinations with doxorubicin showed mostly antagonistic effects. Comparably, the four PLK1 inhibitors efficiently sensitized cells to ionizing radiation. Our findings demonstrate that irrespective of the inhibitor used, the pharmacological inhibition of PLK1 constrains bladder cancer growth and dissemination, providing new opportunities for future therapeutic intervention. However, further laboratorial and preclinical tests are still needed to corroborate the usefulness of using them in combination with other commonly used chemotherapeutic drugs. © 2013 Landes Bioscience.

Chromosomal imbalances in successive moments of human bladder urothelial carcinoma

Objective: To understand developmental characteristics of urinary bladder carcinomas (UBC) by evaluating genomic alterations and p53 protein expression in primary tumors, their recurrences, and in the morphologically normal urothelium of UBC patients. Methods: Tumors and their respective recurrences, six low-grade and five high-grade cases, provided 19 samples that were submitted to laser microdissection capture followed by high resolution comparative genomic hybridization (HR-CGH). HR-CGH profiles went through two different analyses-all tumors combined or classified according to their respective histologic grades. In a supplementary analysis, 124 primary urothelial tumors, their recurrences, and normal urothelium biopsied during the period between tumor surgical resection and recurrence, were submitted to immunohistochemical analyses of the p53 protein. During the follow-up of at least 21 patients, urinary bladder washes citologically negative for neoplastic cells were submitted to fluorescence in situ hybridization (FISH) to detect copy number alterations in centromeres 7, 17, and 9p21 region. Results and Conclusions: HR-CGH indicated high frequencies (80%) of gains in 11p12 and losses in 16p12, in line with suggestions that these chromosome regions contain genes critical for urinary bladder carcinogenesis. Within a same patient, tumors and their respective recurrences showed common genomic losses and gains, which implies that the genomic profile acquired by primary tumors was relatively stable. There were exclusive genomic alterations in low and in high grade tumors. Genes mapped in these regions should be investigated on their involvement in the urinary bladder carcinogenesis. Successive tumors from same patient did not present similar levels of protein p53 expression; however, when cases were grouped according to tumor histologic grades, p53 expression was directly proportional to tumor grades. Biopsies taken during the follow-up of patients with history of previously resected UBC revealed that 5/15 patients with no histologic alterations had more than 25% of urothelial cells expressing the p53 protein, suggesting that the apparently normal urothelium was genomically unstable. No numerical alterations of the chromosomes 7, 17, and 9p21 region were found by FISH during the periods free-of-neoplasia. Our data are informative for further studies to better understand urinary bladder urothelial carcinogenesis. © 2013 Elsevier Inc.

The renin-angiotensin system plays a major role in voiding dysfunction of ovariectomized rats

Aims: The renin-angiotensin system (RAS) plays a major role in cardiovascular diseases in postmenopausal women, but little is known about its importance to lower urinary tract symptoms. In this study we have used the model of ovariectomized (OVX) estrogen-deficient rats to investigate the role of RAS in functional and molecular alterations in the urethra and bladder. Main methods: Responses to contractile and relaxant agents in isolated urethra and bladder, as well as cystometry were evaluated in 4-month OVX Sprague-Dawley rats. Angiotensin-converting enzyme activity and Western blotting for AT1/AT2 receptors were examined. Key findings: Cystometric evaluations in OVX rats showed increases in basal pressure, capacity and micturition frequency, as well as decreased voiding pressure. Angiotensin II and phenylephrine produced greater urethral contractions in OVX compared with Sham group. Carbachol-induced bladder contractions were significantly reduced in OVX group. Relaxations of urethra and bladder to sodium nitroprusside and BAY 41-2272 were unaffected by OVX. Angiotensin-converting enzyme activity was 2.6-fold greater (p < 0.05) in urethral tissue of OVX group, whereas enzyme activity in plasma and bladder remained unchanged. Expressions of AT1 and AT2 receptors in the urethra were markedly higher in OVX group. In bladder, AT1 receptors were not detected, whereas AT2 receptor expression was unchanged between groups. 17β-Estradiol replacement (0.1 mg/kg, weekly) or losartan (30 mg/kg/day) largely attenuated most of the alterations seen in OVX group. Significance: Prolonged estrogen deprivation leads to voiding dysfunction and urethral hypercontractility that are associated with increased ACE activity and up-regulation of angiotensin AT1/AT2 receptor in the urethral tissue. © 2013 Elsevier Inc. All rights reserved.

Variação da ecogenicidade difusa em parênquima hepático homogêneo relacionada aos achados bioquímicos e hematológicos em cães

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Modelo experimental de urolitíase em ovinos: estudo clinico, laboratorial e hemogasométrico

Pós-graduação em Medicina Veterinária - FMVZ

Avaliação histofuncional de matriz heteróloga acelular como scaffold para células de músculo liso para implante em uretra de coelhos

Pós-graduação em Bases Gerais da Cirurgia - FMB

Contribuição do estudo ultrassonográfico (Modo e Doppler) de órgãos abdominais em gatos do mato (Leopardus tigrinus) híbridos: valores de referência

Pós-graduação em Medicina Veterinária - FMVZ

Variação da ecogenicidade difusa em parênquima hepático homogêneo relacionada aos achados bioquímicos e hematológicos em cães

The present study evaluated the liver with homogeneous parenchyma in dogs, with diffuse reduced echogenicity (G1), increased echogenicity (G2) and normal echogenicity (G3) by ultrasound examination associating the findings on animal profile, liver size and hematology and biochemistry results. Blood samples obtained by cephalic or jugular venipunture were submitted for hemogram and ALT, ALP, total proteins, albumin, globulin, urea and creatinine analysis. Among the 30 dogs in G1, 30 (100%) presented portal venous and gall bladder wall clarity, 23 (76.67%) presented normal liver size and edges, 15 (50%) were from 1 to 6 years old and 8 (26.67%) belonged to the lhasa apso breed. No predispositions were found according to gender, as well as no significant alterations in biochemical and hematological exams were observed in G1. The most prevalent disease found in this group was gastroenteritis (43.33%). Among the 30 dogs in G2, 27 (90%) presented hepatomegaly and rounded hepatic edges, 18 (60%) were over 9 years old, 16 (53.33%) were female and 9 (30%) belonged to the poodle breed. The laboratorial findings related to this group were increased ALT and ALP serum activity, decreased levels of total protein, albumin, globulin, erythrocytes and hematocrit, as well as leukocytosis with neutrophilia and a left shift, eosinopenia, lymphopenia and monocytosis. The most prevalent diseases found in this group were metabolic disorders (54%), such as diabetes mellitus and hyperadrenocorticism, and chronic hepatopathies (17%) due to prolonged and continuous use of corticoid and anticonvulsive drugs. Among the 30 dogs in the control group (G3), normal liver size and edges were presented in 22 (73.33%). In this group, no alterations were seen in laboratorial exams.

Skin diseases reported by workers from UNESP campus at Rubiao Jr, Botucatu-SP (Brazil)

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