Molecular profiling and genomic microarrays in prostate cancer

In the present review article a global approach regarding the usefulness of genomic microarrays in prostate cancer management, is attempted. Cancer is a multistep process of mutations in key regulatory genes and epigenetic alterations that result in loss of balanced gene expression. A complete knowledge of the interaction between the genetic variability of the neoformation (tumor profiling) and the genetic variability of the host (inherited genome profiling), will be able to determine the better strategy against the cancer and the less toxicity for the patient. Alterations in the sequence of the hormone binding domain of the androgen receptor as well as mutations in some genes, determine radioresistance and resistance or sensitivity to some chemotherapeutic drugs. New therapies using monoclonal antibodies directed against specific extracellular binding domains of some receptors are based on molecular alterations observed in tumors.В обзоре обсуждается целесообразность применения геномных микрочипов для выявления рака предстательной железы. Рак является многоэтапным процессом мутаций в ключевых регуляторных генах и эпигенетических изменений, приводящих к утрате сбалансированной экспрессии генов. Фундаментальные знания о взаимосвязи между генетической вариабельностью опухолевых клеток (молекулярном профиле опухоли) и генетической вариабельностью хозяина (наследуемый геномный профиль) позволит выбрать наилучшую стратегию противоопухолевой терапии при низкой токсичности таковой. Изменения последовательности гормонсвязывающего домена рецептора андрогена наряду с мутациями некоторых генов определяют устойчивость к лучевой терапии и устойчивость или чувствительность к ряду химиопрепаратов. Новые виды терапии с использованием моноклональных антител против специфичных внеклеточных связывающих доменов ряда рецепторов основаны на данных о молекулярных особенностях новообразований

Micronuclei to detect in vivo chemotherapy damage in a p53 mutated solid tumour

Apoptosis induction and micronuclei formation were compared following cytotoxic treatments in two rat glioma differing in p53 integrity. In vitro, micronuclei emergence but not apoptosis was linked to the p53 mutated status. In vivo, micronuclei assays were more sensitive to evaluate DNA damage induced by chemotherapy in a p53-mutated solid tumour.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Emotional, behavioural problems and cigarette smoking in adolescence: findings of a Greek cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Although several studies have reported findings concerning the association between smoking and emotional/behavioural problems, little research has investigated this association after controlling for confounding factors which have been found to be significantly correlated with both cigarette smoking and emotional/behavioural problems and may have a strong effect on the relationship between adolescents' mental health and smoking. The present study attempted to assess the association between adolescents' smoking status and their emotional/behavioural problems after controlling for a number of possible confounders (i.e. age, gender, parental smoking status, exposure to family smoking, family socioeconomic status, adolescents' leisure time) in a Greek nation-wide school-based sample.</p> <p>Methods</p> <p>Participants completed a questionnaire which retrieved information about age, gender, family socioeconomic status, smoking status, parental smoking, adolescents' leisure time and emotional/behavioural problems. Data were modelled using multiple logistic regression analysis with adolescents' smoking status as the dependent variable.</p> <p>Results</p> <p>A total of 1194 (i.e. 63% response rate) of self-reported questionnaires (40.1% boys, 59.9% girls; 12-18 years old) were returned. Data from 1030 participants with full data were analyzed. Cigarette smoking was strongly associated with higher levels of emotional/behavioural problems (p < 0.001) and the association was not moderated (OR = 1.13, 95% CI: 1.08-1.18) after controlling for the effects of other covariates. Emotional symptoms, conduct problems and hyperactivity/inattention were all significantly associated with adolescents' current smoking.</p> <p>Conclusions</p> <p>This study supports the association between smoking and emotional/behavioural problems among adolescents. Addressing adolescents' needs regarding their emotional/behavioural health could be helpful in the development of effective anti-smoking strategies in school environment and elsewhere.</p

A new method to determine the elastopalstic properties of ductile materials by conical indentation

Based on load-displacement curves, indentation is widely used to extract the elastoplastic properties of materials. It is generally believed that such a measure is non-unique and a full stress-strain curve cannot be obtained using plural sharp and deep spherical indenters. In this paper we show that by introducing an additional dimensionless function of DA / A (the ratio of residual area to the area of an indenter profile) in the reverse analysis, the elastoplastic properties of several unknown materials that exhibit visually indistinguishable load-displacement curves can be uniquely determined with a sharp indentation

Multiple Interferon Stimulated Genes Synergize with the Zinc Finger Antiviral Protein to Mediate Anti-Alphavirus Activity

The zinc finger antiviral protein (ZAP) is a host factor that mediates inhibition of viruses in the Filoviridae, Retroviridae and Togaviridae families. We previously demonstrated that ZAP blocks replication of Sindbis virus (SINV), the prototype Alphavirus in the Togaviridae family at an early step prior to translation of the incoming genome and that synergy between ZAP and one or more interferon stimulated genes (ISGs) resulted in maximal inhibitory activity. The present study aimed to identify those ISGs that synergize with ZAP to mediate Alphavirus inhibition. Using a library of lentiviruses individually expressing more than 350 ISGs, we screened for inhibitory activity in interferon defective cells with or without ZAP overexpression. Confirmatory tests of the 23 ISGs demonstrating the largest infection reduction in combination with ZAP revealed that 16 were synergistic. Confirmatory tests of all potentially synergistic ISGs revealed 15 additional ISGs with a statistically significant synergistic effect in combination with ZAP. These 31 ISGs are candidates for further mechanistic studies. The number and diversity of the identified ZAP-synergistic ISGs lead us to speculate that ZAP may play an important role in priming the cell for optimal ISG function

Rapid Changes in Phospho-MAP/Tau Epitopes during Neuronal Stress: Cofilin-Actin Rods Primarily Recruit Microtubule Binding Domain Epitopes

Abnormal mitochondrial function is a widely reported contributor to neurodegenerative disease including Alzheimer's disease (AD), however, a mechanistic link between mitochondrial dysfunction and the initiation of neuropathology remains elusive. In AD, one of the earliest hallmark pathologies is neuropil threads comprising accumulated hyperphosphorylated microtubule-associated protein (MAP) tau in neurites. Rod-like aggregates of actin and its associated protein cofilin (AC rods) also occur in AD. Using a series of antibodies - AT270, AT8, AT100, S214, AT180, 12E8, S396, S404 and S422 - raised against different phosphoepitopes on tau, we characterize the pattern of expression and re-distribution in neurites of these phosphoepitope labels during mitochondrial inhibition. Employing chick primary neuron cultures, we demonstrate that epitopes recognized by the monoclonal antibody 12E8, are the only species rapidly recruited into AC rods. These results were recapitulated with the actin depolymerizing drug Latrunculin B, which induces AC rods and a concomitant increase in the 12E8 signal measured on Western blot. This suggests that AC rods may be one way in which MAP redistribution and phosphorylation is influenced in neurons during mitochondrial stress and potentially in the early pathogenesis of AD

A cross-sectional study of self-reported chemical-related sensitivity is associated with gene variants of drug-metabolizing enzymes

BACKGROUND: N-acetyltransferases (NAT) and glutathione S-transferases (GST) are involved in the metabolism of several ubiquitous chemical substances leading to the activation and detoxification of carcinogenic heterocyclic and aromatic amines. Since polymorphisms within these genes are described to influence the metabolism of ubiquitous chemicals, we conducted the present study to determine if individuals with self-reported chemical-related sensitivity differed from controls without self-reported chemical-related sensitivity with regard to the distribution of genotype frequencies of NAT2, GSTM1, GSTT1, and GSTP1 polymorphisms. METHODS: Out of 800 subjects who answered a questionnaire of ten items with regard to their severity of chemical sensitivity 521 unrelated individuals agreed to participate in the study. Subsequently, genetic variants of the NAT2, GSTM1, GSTT1, and GSTP1 genes were analyzed. RESULTS: The results show significant differences between individuals with and without self-reported chemical-related sensitivity with regard to the distribution of NAT2, GSTM1, and GSTT1 gene variants. Cases with self-reported chemical-related sensitivity were significantly more frequently NAT2 slow acetylators (controlled OR = 1.81, 95% CI = 1.27–2.59, P = 0.001). GSTM1 and GSTT1 genes were significantly more often homozygously deleted in those individuals reporting sensitivity to chemicals compared to controls (GSTM1: controlled OR 2.08, 95% CI = 1.46–2.96, P = 0.0001; GSTT1: controlled OR = 2.80, 95% CI = 1.65–4.75, P = 0.0001). Effects for GSTP1 gene variants were observed in conjunction with GSTM1, GSTT1 and NAT2 gene. CONCLUSION: The results from our study population show that individuals being slow acetylators and/or harbouring a homozygous GSTM1 and/or GSTT1 deletion reported chemical-related hypersensitivity more frequently

New insights into perinatal testicular torsion

Perinatal testicular torsion is a relatively rare event that remains unrecognized in many patients or is suspected and treated accordingly only after an avoidable loss of time. The authors report their own experience with several patients, some of them quite atypical but instructive. Missed bilateral torsion is an issue, as are partial torsion, possible antenatal signs, and late presentation. These data are discussed together with the existing literature and may help shed new light on the natural course of testicular torsion and its treatment. The most important conclusion is that a much higher index of suspicion based on clinical findings is needed for timely detection of perinatal torsion. It is the authors’ opinion that immediate surgery is mandatory not only in suspected bilateral torsions but also in cases of possible unilateral torsions. There is no place for a more fatalistic “wait-and-see” approach. Whenever possible, even necrotic testes should not be removed during surgery because some endocrine function may be retained