Castration-resistant prostate cancer: systemic therapy in 2012

Prostate cancer is the most common non-cutaneous neoplasm in the male population worldwide. It is typically diagnosed in its early stages, and the disease exhibits a relatively indolent course in most patients. Despite the curability of localized disease with prostatectomy and radiation therapy, some patients develop metastatic disease and die. Although androgen deprivation is present in the majority of patients with metastatic prostate cancer, a state of androgen resistance eventually develops. Castration-resistant prostate cancer, defined when there is progression of disease despite low levels of testosterone, requires specialized care, and improved communication between medical and urologic oncologists has been identified as a key component in delivering effective therapy. Despite being considered a chemoresistant tumor in the past, the use of a prostate-specific antigen has paved the way for a new generation of trials for castration-resistant prostate cancer. Docetaxel is a life-prolonging chemotherapy that has been established as the standard first-line agent in two phase III clinical trials. Cabazitaxel, a novel taxane with activity in cancer models resistant to paclitaxel and docetaxel, is the only agent that has been compared to a chemotherapy control in a phase III clinical trial as a second-line therapy; it was found to prolong the overall survival of patients with castration-resistant prostate cancer previously treated with docetaxel when compared to mitoxantrone. Other agents used in this setting include abiraterone and sipuleucel-T, and novel therapies are continually being investigated in an attempt to improve the outcome for patients with castration-resistant prostate cancer

Molecular Profiles of HCV Cirrhotic Tissues Derived in a Panel of Markers with Clinical Utility for Hepatocellular Carcinoma Surveillance

Background Early hepatocellular carcinoma (HCC) detection is difficult because low accuracy of surveillance tests. Genome-wide analyses were performed using HCV-cirrhosis with HCC to identify predictive signatures. Methodology/Principal Findings Cirrhotic liver tissue was collected from 107 HCV-infected patients with diagnosis of HCC at pre-transplantation and confirmed in explanted livers. Study groups included: 1) microarray hybridization set (n = 80) including patients without (woHCC = 45) and with (wHCC = 24) HCC, and with incidental HCC (iHCC = 11); 2) independent validation set (n = 27; woHCC = 16, wHCC = 11). Pairwise comparisons were performed using moderated t-test. FDR\u3c1% was considered significant. L1-penalized logistic regression model was fit for woHCC and wHCC microarrays, and tested against iHCC. Prediction model genes were validated in independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progressing to mitosis; unregulated DNA damage check-points, and apoptosis. The prediction model included 17 molecules demonstrated 98.6% of accuracy and correctly classified 6 out of 11 undiagnosed iHCC cases. The best model performed even better in the additional independent set. Conclusions/Significances The molecular analysis of HCV-cirrhotic tissue conducted to a prediction model with good performance and high potential for HCC surveillance

Genes Involved in Viral Carcinogenesis and Tumor Initiation in Hepatitis C Virus–Induced Hepatocellular Carcinoma

The role of chronic hepatitis C virus (HCV) in the pathogenesis of HCV-associated hepatocellular carcinoma (HCC) remains controversial. To understand the transition from benign to malignant, we studied the gene expression patterns in liver tissues at different stages, including normal, cirrhosis, and different HCC stages. We studied 108 liver tissue samples obtained from 88 distinct patients (41 HCV-cirrhotic tissues, 17 HCV-cirrhotic tissues from patients with HCC, and 47 HCV-HCC tissues). Differentially expressed genes (DEG) were studied by use of high-density oligonucleotide arrays. Among probe sets identified as differentially expressed via the F test, all pairwise comparisons were performed. Cirrhotic tissues with and without concomitant HCC were further evaluated, and a classifier was used to predict whether the tissue type was associated with HCC. Differential expression profiles were analyzed using Interaction Networks and Functional Analysis. Characteristic gene signatures were identified when normal tissue was compared with cirrhosis, cirrhosis with early HCC, and normal with HCC. Pathway analysis classified the cellular and biological functions of the DEG as related to cellular growth and proliferation, cell death and inflammatory disease in cirrhosis; cell death, cell cycle, DNA replication, and immune response in early HCCs; and cell death, cell growth and proliferation, cell cycle, and DNA repair in advanced HCCs. Characteristic gene signatures were identified at different stages of HCV-HCC progression. A set of genes were identified to predict whether the cirrhotic tissue was associated with HCC

Evaluation of the physical and antifungal effects of chlorhexidine diacetate incorporated into polymethyl methacrylate

This study aimed to evaluate the physical properties and antifungal activities of polymethyl methacrylate (PMMA) acrylic resins after the incorporation of chlorhexidine diacetate salt (CDA). Methodology: First, acrylic resin specimens were fabricated with Vipi Cor® and DuraLay® resins with and without the incorporation of 0.5%, 1.0% or 2.0% CDA. The residual monomer and CDA release were measured at intervals ranging from 2 hours to 28 days using ultraviolet spectrometry combined with high-performance liquid chromatography. The antifungal activity against C. albicans was evaluated with the agar diffusion method. Fourier transform infrared spectroscopy was used to analyze the degree of resin conversion. Finally, the water sorption values of the resins were also measured. Results: The incorporated CDA concentration significantly changed the rate of CDA release (p<0.0001); however, the brand of the material appeared to have no significant influence on drug release. Subsequently, the inhibition zones were compared between the tested groups and within the same brand, and only the comparisons between the CDA 2% and CDA 1% groups and between the CDA 1% and CDA 0.5% groups failed to yield significant differences. Regarding the degrees of conversion, the differences were not significant and were lower only in the CDA 2% groups. Water sorption was significantly increased at the 1.0% and 2.0% concentrations. Conclusions: We concluded that the incorporation of CDA into PMMA-based resins enabled the inhibition of C. albicans growth rate, did not alter the degrees of conversion of the tested resins and did not change the release of residual monomers

Dentin-bonding agents

New dental restorative materials have been developed to meet not only the functional demands, but esthetics as well, and in the last few years an enormous range of new materials has appeared for use in dentistry. Among them, several adhesive systems, and different operative techniques for each group materials. Therefore, is indispensable for the professional to know about the properties, characteristics, and association of these materials with the dental structures, in order to select and use them correctly. Should conventional self-etching adhesive systems be used? This question encouraged this literature review to be conducted, with the aim of comparing the conventional adhesive systems with the self-etching systems and to look for scientific data that would help professionals to choose which adhesive system to use. When compared to conventional systems, it was noted that the self-etching systems show less sensitivity to technique, especially as regards errors the operator could commit. The self-etching systems, particularly the 2-step type, have shown equivalent values of bond strength, marginal microleakage and performance, therefore, will be an option for direct composite resin restorations in posterior teeth

Tipos, setores, nacionalidade e experiência: o que importa para o sucesso das estratégias de fusão e aquisição?

This study characterizes the Mergers and Acquisitions (M&As) processes that achieved better performances in internal value and synergy generation. The M&A theme is not particularly new in the strategy literature, which does not mean that it is consolidated, at least not from the point of view of these strategies results. Academic literature on the topic stablishes that the search for synergies is the key reason for these strategies, although the measurement of these synergies is not a simple task. This study evaluated 154 M&As processes using three variables related to market value creation and operational efficiencies creation. The M&A processes were classified according to the type of agglomerative process, economic sector, nationality and positioning of companies in the production chain. Statistic data were analyzed with descriptive statistics, variance analysis and cluster analysis. The results indicate that most of the cases resulted in mild negative or positive results, with no significant differences between the results of processes carried out in different sectors of the economy. The cases that achieved better results were those in which companies already had previous experience in M&A and held knowledge of the acquired enterprise, which reiterates the need for prior planning and analysis to the generation of the expected synergies and value creation.Este estudo caracterizou os processos de Fusões e Aquisições (F&A) que criaram maior valor interno e sinergia. O tema de F&A não é novo na literatura de estratégia, o que não significa, que ele esteja consolidado, ao menos não do ponto de vista dos resultados que essa estratégia traz. O que se percebe é que existem momentos onde essa estratégia é mais comumente adotada, e em alguns setores onde ela é prevalente. A literatura traz a criação de sinergias como uma das principais razões para sua implementação, embora a aferição dessas sinergias não seja uma tarefa simples. Nesse sentido, o presente estudo avaliou 154 processos de F&A, a partir de três indicadores relacionados à criação de valor de mercado e de eficiências operacionais. Os dados foram analisados com estatística descritiva, análise de variância e análise de cluster. Os resultados encontrados indicam que a maioria dos casos pesquisados apresentaram resultados positivos discretos ou negativos, não havendo diferenças significativas entre aqueles realizados em diferentes setores da economia. Os casos que apresentaram melhor desempenho foram aqueles em que as empresas já contavam com experiência prévia em F&A e detinham conhecimento a respeito do negócio, o que reitera a necessidade de planejamento e análise a priori para a geração de sinergias e para a criação de valor, a partir dessa estratégia

Tomato Breeding for Insect-Pest Resistance

The tomato is susceptible to pest attacks that can lead to damages throughout the crop cycle. Pest control is carried out, mainly, by insecticide and chemical acaricide spraying. However, the use of chemical pest control can cause severe damage to the environment, biological imbalances and deleterious effects on farmers and consumer health, as well as increased production costs. An interesting alternative to minimizing the problems arising from the agrochemical application and maintaining pest populations below the economic damage level is the development of tomato plants displaying resistance to insect and arachnid pests. In this context, the main purpose of this chapter is to provide a review of the techniques applied in this regard, major progresses to date and future prospects for tomato pest-resistance breeding. This chapter is divided into five sections: (1) wild pest-resistant tomato species, (2) allelochemicals that confer pest resistance, (3) techniques used for the introgression of pest resistance genes (4) overview, challenges and prospects for pest-resistant tomato breeding and (5) final considerations

Specifications, sectors, nationality and experience: what matters for the success of mergers and acquisitions strategy?

Este estudo caracterizou os processos de Fusões e Aquisições (F&A) que criaram maior valor interno e sinergia. O tema de F&A não é novo na literatura de estratégia, o que não significa, que ele esteja consolidado, ao menos não do ponto de vista dos resultados que essa estratégia traz. O que se percebe é que existem momentos onde essa estratégia é mais comumente adotada, e em alguns setores onde ela é prevalente. A literatura traz a criação de sinergias como uma das principais razões para sua implementação, embora a aferição dessas sinergias não seja uma tarefa simples. Nesse sentido, o presente estudo avaliou 154 processos de F&A, a partir de três indicadores relacionados à criação de valor de mercado e de eficiências operacionais. Os dados foram analisados com estatística descritiva, análise de variância e análise de cluster. Os resultados encontrados indicam que a maioria dos casos pesquisados apresentaram resultados positivos discretos ou negativos, não havendo diferenças significativas entre aqueles realizados em diferentes setores da economia. Os casos que apresentaram melhor desempenho foram aqueles em que as empresas já contavam com experiência prévia em F&A e detinham conhecimento a respeito do negócio, o que reitera a necessidade de planejamento e análise a priori para a geração de sinergias e para a criação de valor, a partir dessa estratégia.This study characterizes the Mergers and Acquisitions (M&As) processes that achieved better performances in internal value and synergy generation. The M&A theme is not particularly new in the strategy literature, which does not mean that it is consolidated, at least not from the point of view of these strategies results. Academic literature on the topic stablishes that the search for synergies is the key reason for these strategies, although the measurement of these synergies is not a simple task. This study evaluated 154 M&As processes using three variables related to market value creation and operational efficiencies creation. The M&A processes were classified according to the type of agglomerative process, economic sector, nationality and positioning of companies in the production chain. Statistic data were analyzed with descriptive statistics, variance analysis and cluster analysis. The results indicate that most of the cases resulted in mild negative or positive results, with no significant differences between the results of processes carried out in different sectors of the economy. The cases that achieved better results were those in which companies already had previous experience in M&A and held knowledge of the acquired enterprise, which reiterates the need for prior planning and analysis to the generation of the expected synergies and value creation