Adipocyte Secreted Factors Enhance Aggressiveness of Prostate Carcinoma Cells

Obesity has been associated with increased incidence and risk of mortality of prostate cancer. One of the proposed mechanisms underlying this risk association is the change in adipokines expression that could promote the development and progression of the prostate tumor cells. The main goal of this study was to evaluate the effect of preadipocyte and adipocyte secretome in the proliferation, migration and invasion of androgen independent prostate carcinoma cells (RM1) and to assess cell proliferation in the presence of the adiposity signals leptin and insulin. RM1 cells were co-cultured in with preadipocytes, adipocytes or cultured in their respective conditioned medium. Cell proliferation was assessed by flow cytometry and XTT viability test. Cell migration was evaluated using a wound healing injury assay of RM1 cells cultured with conditioned media. Cellular invasion of RM1 cells co-cultured with adipocytes and preadipocytes was assessed using matrigel membranes. Preadipocyte conditioned medium was associated with a small increase in RM1 proliferation, while adipocytes conditioned media significantly increased RM1 cell proliferation (p<0.01). Adipocytes also significantly increased the RM1 cells proliferation in co-culture (p <0.01). Cell migration was higher in RM1 cells cultured with preadipocyte and adipocyte conditioned medium. RM1 cell invasion was significantly increased after co-culture with preadipocytes and adipocytes (p <0.05). Insulin also increased significantly the cell proliferation in contrast to leptin, which showed no effect. In conclusion, prostate carcinoma cells seem to be influenced by factors secreted by adipocytes that are able to increase their ability to proliferate, migrate and invade.

Agressividade e índice de Apgar

A agressividade é o comportamento que surge transversalmente como queixa isolada ou a par de outras queixas na maioria das crianças com e sem doença, que procuram apoio em saúde mental infantil. Nessas crianças, e a partir da recolha dos dados anamnesicos, tem-se verificado a constância de registo, no Livro do Bebé, de Índice de Apgar ≤ 9 ao primeiro minuto. Este estudo exploratório pretendeu analisar a hipótese teórica de que o Índice de Apgar abaixo de 10 ao primeiro minuto pode ser representativo de sofrimento fetal intraparto ou perinatal e assim fragilizar os circuitos neuronais das emoções tendo como consequência o surgimento, ao longo do desenvolvimento infantil e juvenil, de dificuldades na capacidade de gestão ou controlo das emoções, com comportamentos opositivos e/ou agressivos, como resposta defensiva de luta e fuga. Utilizou-se uma amostra de crianças inscritas no serviço de consulta externa de saúde mental infantil e juvenil, e verificou-se se as queixas de perturbação do comportamento com agressividade, formuladas no momento do acolhimento ao serviço, estão relacionadas com o Índice de Apgar ≤ 9 ao primeiro minuto e/ou com os registos de sofrimento fetal. Procurou-se, numa amostra aleatória de crianças sem queixa formulada no serviço de consulta externa de saúde mental infantil e juvenil, perceber as diferenças ou semelhanças dos registos de nascimento relativamente à amostra de crianças inscritas. Foi ainda auscultada a opinião dos profissionais dos serviços de obstetrícia e neonatologia – pediatria, mediante a aplicação de um questionário, no sentido de recolher as opiniões dos profissionais de saúde que lidam com o parto, que avaliam o Índice de Apgar dos recém – nascidos e que os seguem durante as primeiras horas ou dias de vida. Das conclusões a que chegamos, salienta-se que o sofrimento fetal intraparto pode ser predictor de dificuldades de controlo emocional traduzidas em alterações do comportamento com agressividade em situações de stress. Não se conclui que o Índice de Apgar ≤ 9 pode ser predictor de alterações do comportamento com agressividade em situações de stress, uma vez que os registos de ocorrências de sofrimento fetal intraparto e os registos do Índice de Apgar ao primeiro minuto são, na amostra de crianças com queixa, díspares, relacionando-se no entanto de modo estatisticamente significativo na amostra de crianças sem queixa. III No entanto, e apesar das dificuldades metodológicas, fica a certeza de haver mais percursos a percorrer nesta direcção para a compreensão dos distúrbios emocionais e a agressividade.

Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). METHODS: In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. RESULTS: From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death. CONCLUSION: s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy.

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.

Melhoria no processo de vendas na empresa bombas Grundfos Portugal S.A.

A situação económica instável vivida atualmente, aliada à crescente agressividade concorrencial obriga as organizações a evoluírem continuamente, melhorando a sua forma de trabalhar e de se apresentar ao mercado. Com a elaboração deste trabalho pretendeu-se analisar o processo de vendas, com maior enfoque no segmento de clientes Indústria, de modo a identificar possíveis desperdícios que ocorrem ao longo do processo, e criar um plano de ações corretivas e de melhoria, utilizando, para isso, ferramentas da qualidade. Neste relatório, descreve-se o processo atual na empresa, fazendo um estudo exaustivo ao mesmo. Com os dados recolhidos, desenvolveu-se um plano de ações para melhorar os vários processos com o objetivo de eliminar ou reduzir os desperdícios encontrados. Todas as ações corretivas que foram implementadas foram sujeitas a uma avaliação de desempenho, constatando-se uma melhoria do desempenho dos subprocessos tanto de forma quantitativa como qualitativa.

SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3

Prostate cancer (PCa) is one of the most incident cancers worldwide but clinical and pathological parameters have limited ability to discriminate between clinically significant and indolent PCa. Altered expression of histone methyltransferases and histone methylation patterns are involved in prostate carcinogenesis. SMYD3 transcript levels have prognostic value and discriminate among PCa with different clinical aggressiveness, so we decided to investigate its putative oncogenic role on PCa.We silenced SMYD3 and assess its impact through in vitro (cell viability, cell cycle, apoptosis, migration, invasion assays) and in vivo (tumor formation, angiogenesis). We evaluated SET domain's impact in PCa cells' phenotype. Histone marks deposition on SMYD3 putative target genes was assessed by ChIP analysis.Knockdown of SMYD3 attenuated malignant phenotype of LNCaP and PC3 cell lines. Deletions affecting the SET domain showed phenotypic impact similar to SMYD3 silencing, suggesting that tumorigenic effect is mediated through its histone methyltransferase activity. Moreover, CCND2 was identified as a putative target gene for SMYD3 transcriptional regulation, through trimethylation of H4K20.Our results support a proto-oncogenic role for SMYD3 in prostate carcinogenesis, mainly due to its methyltransferase enzymatic activity. Thus, SMYD3 overexpression is a potential biomarker for clinically aggressive disease and an attractive therapeutic target in PCa.