METRADISC-XL: a program for meta-analysis of multidimensional ranked discovery oriented datasets including microarrays.

A comprehensive software for performing meta-analysis of ranked discovery oriented datasets, such as those derived from microarrays or other high throughput technologies, and for testing between-study heterogeneity for biological variables (gene expression, microRNA, proteomic, or other high-dimensional data) is presented. The software can identify biological probes that have either very high average ranks (e.g.

The ubiquitin-proteasome system in glioma cell cycle control.

A major determinant of cell fate is regulation of cell cycle. Tight regulation of this process is lost during the course of development and progression of various tumors. The ubiquitin-proteasome system (UPS) constitutes a universal protein degradation pathway, essential for the consistent recycling of a plethora of proteins with distinct structural and functional roles within the cell, including cell cycle regulation.

Performance of MAX test and degree of dominance index in predicting the mode of inheritance.

We evaluate power performance to detect the correct mode of inheritance in gene-disease associations of two different approaches: the MAX test and the degree of dominance index or h-index. The MAX test is a special case of the conditional independence tests that simultaneously test for association and select the most likely genetic model based on a three-dimensional normal distribution. The h-index is based on the philosophy of using orthogonal contrasts to infer the mode of inheritance quantitatively.

Intravitreal bevacizumab for photodynamic therapy-induced massive macular detachment in acute central serous chorioretinopathy.

We present a long followed up case of acute central serous chorioretinopathy (CSC) complicated by a severe visual loss due to massive pigment epithelium detachment of the macula after a full-dose photodynamic therapy (PDT). Rapid anatomical and functional improvement was observed after a single intravitreal injection of bevacizumab. To our knowledge, we report the first case of PDT-treated CSC complicated by severe visual loss.

The reporting quality of studies investigating the diagnostic accuracy of anti-CCP antibody in rheumatoid arthritis and its impact on diagnostic estimates.

Background: Recently anti-CCP testing has become popular in the diagnosis of rheumatoid arthritis (RA). However, the inadequate reporting of the relevant diagnostic studies may overestimate and bias the results, directing scientists into making false decisions. The aim of the present study was to evaluate the reporting quality of studies used anti-CCP2 for the diagnosis of RA and to explore the impact of reporting quality on pooled estimates of diagnostic measures.

Expression of neutral endopeptidase, endothelin-1, and nuclear factor kappa B in prostate cancer: interrelations and associations with prostate-specific antigen recurrence after radical prostatectomy.

Objective. To study the impact of the neutral endopeptidase (NEP)/neuropeptides (NPs) axis and nuclear factor kappa B (NFκB) as predictors of prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Patients and Methods.

Central role of SREBP-2 in the pathogenesis of osteoarthritis.

Background: Recent studies have implied that osteoarthritis (OA) is a metabolic disease linked to deregulation of genes involved in lipid metabolism and cholesterol efflux. Sterol Regulatory Element Binding Proteins (SREBPs) are transcription factors regulating lipid metabolism with so far no association with OA. Our aim was to test the hypothesis that SREBP-2, a gene that plays a key role in cholesterol homeostasis, is crucially involved in OA pathogenesis and to identify possible mechanisms of action.

Gamma-aminobutyric acid A receptor, α-2 (GABRA2) variants as individual markers for alcoholism: a meta-analysis.

Objectives: The available evidence from the genetic association studies (GAS) published to date on the association between variants in the GABRA2 gene and alcoholism has produced inconclusive results. To interpret these results, a meticulous meta-analysis of all available studies was carried out.

Methods: The PubMed database and the HuGE Navigator were searched for published GAS-related variants in the GABRA2 gene with susceptibility to alcoholism.

Basic Concepts in Metastatic Cardiac Disease.

The involvement of the heart in metastatic cancer is a rare clinical diagnosis, as it may be asymptomatic or symptoms, when present, may be attributed to other causes. Issues regarding incidence, intracardiac location, clinical presentation, diagnosis and treatment of metastatic cardiac tumors will be discussed here.

Network analysis of randomized controlled trials in multiple sclerosis.

Background: The optimal treatment of multiple sclerosis (MS) is not yet well-defined.

Objective: To estimate the relative effectiveness of treatments in MS, we performed a network of multiple-treatments meta-analysis of randomized controlled trials (RCTs) for relapsing MS using three main efficacy outcomes: relapse-free patients, patients without disease progression, and patients without magnetic resonance imaging progression.

Methods: We systematically searched PubMed and the Cochrane Central Register of Controlled Trials to identify English-language articles with RCTs that compared pharmaceutical treatments using the terms multiple sclerosis and randomized controlled trial.

Bortezomib reverses the proliferative and antiapoptotic effect of neuropeptides on prostate cancer cells.

Objectives: Neuropeptides are important signal initiators in advanced prostate cancer, partially acting through activation of nuclear factor kappa B. Central to nuclear factor kappa B regulation is the ubiquitin-proteasome system, pharmacological inhibition of which has been proposed as an anticancer strategy. We investigated the putative role of the proteasome inhibitor bortezomib in neuropeptides signaling effects on prostate cancer cells.

CD10 is inversely associated with nuclear factor-kappa B and predicts biochemical recurrence after radical prostatectomy.

Introduction: The cell surface endopeptidase CD10 (neutral endopeptidase) and nuclear factor-κB (NF-κB) have been independently associated with prostate cancer (PC) progression. We investigated the correlations between these two factors and their prognostic relevance in terms of biochemical (prostate-specific antigen, PSA) relapse after radical prostatectomy (RP) for localized PC.

Patients And Methods: The immunohistochemical expression of CD10 and NF-κB in samples from 70 patients who underwent RP for localized PC was correlated with the preoperative PSA level, Gleason score, pathological stage and time to PSA failure.

Lack of prognostic significance of p16 and p27 after radical prostatectomy in hormone-naïve prostate cancer.

Background: Loss of normal cell cycle control is an early event in the evolution of cancer. The expression of cyclin-dependent kinase (CDK) inhibitors p16 and p27 has been previously associated with progression of prostate cancer (PC). 70 patients diagnosed with early stage PCwere treated with radical prostatectomy (RP) at our institution and their tumor specimens were immunohistochemically evaluated for expression of p16 and p27.

The Role of the Small Ubiquitin-Related Modifier (SUMO) Pathway in Prostate Cancer.

SUMO (small ubiquitin-related modifier) conjugation is a reversible three-step process of protein post-translational modifications mediating protein-protein interactions, subcellular compartmentalization and regulation of transcriptional events. Among divergent transcription factors regulated by SUMOylation and deSUMOylation, the androgen receptor (AR) is of exceptional significance, given its established role in prostate carcinogenesis. The enzymes of the SUMO pathway can have diverse effects on AR transcriptional activity, either via direct modification of the AR or through modification of AR co-regulators.

Estimating the mode of inheritance in genetic association studies of qualitative traits based on the degree of dominance index.

Background: The biological justification for the choice of the genetic mode in genetic association studies (GAS) is seldom available. Then, the mode of inheritance is approximated by investigating a number of non-orthogonal genetic contrasts making the interpretation of results difficult.

Methods: We propose to define the mode of inheritance by the significance of the deviance of the co-dominant contrast and the degree of dominance (h), which is a function of two orthogonal contrasts (the co-dominant and additive).

Neuroendocrine differentiation and the ubiquitin-proteasome system in cancer: Partners or enemies?

Neuroendocrine (NE) differentiation of cancer and deregulation of the ubiquitin-proteasome system (UPS) are two processes that have been independently linked to the development of aggressive and treatment-resistant tumors. Striking data suggest a plausible interconnection between these two mechanisms, based on indirect evidence of neuropeptide-induced effects on UPS, reversed by proteasome inhibition and deubiquitinase-like properties of NE markers. Deciphering the model of their exact interactions is one of the keys to targeting the NE malignant phenotype more effectively.

Variants of the MTHFR gene and susceptibility to acute lymphoblastic leukemia in children: a synthesis of genetic association studies.

Background: Acute lymphoblastic leukemia (ALL) is a complex disease with genetic background. The genetic association studies (GAS) that investigated the association between ALL and the MTHFR C677T and A1298C gene variants have produced contradictory or inconclusive results.

Materials And Methods: In order to decrease the uncertainty of estimated genetic risk effects, a meticulous meta-analysis of published GAS related the variants in the MTFHR gene with susceptibility to ALL was conducted.

Bone mineral density and genetic markers involved in three connected pathways (focal adhesion, actin cytoskeleton regulation and cell cycle): the CUMAGAS-BMD information system.

The focal adhesion, the actin cytoskeleton and cell-cycle are connected pathways and their genes are implicated in the pathogenesis of low BMD. Data from 211 studies that investigated the association between BMD and gene variants involved in these pathways were catalogued in a web-based information system and analyzed. In individual studies, significant association was found for 16 variants in lumbar spine, 11 in femoral neck and 5 in hip.

Polymorphisms of the endothelial nitric oxide synthase (NOS3) gene in preeclampsia: a candidate-gene association study.

Background: The endothelial nitric oxide synthase gene (NOS3) has been proposed as a candidate gene for preeclampsia. However, studies so far have produced conflicting results. This study examines the specific role of variants and haplotypes of the NOS3 gene in a population of Caucasian origin.

Baseline insulin-like growth factor-I plasma levels, systemic inflammation, weight loss and clinical outcome in metastatic non-small cell lung cancer patients.

Background: Cancer patients frequently suffer from weight loss and systemic inflammation in the context of advanced disease, which is related to adverse outcome. Insulin-like growth factor (IGF)-I is an anabolic molecule implicated in the maintenance of muscle mass and cancer growth. We investigated potential correlations of IGF-I with an inflammatory and weight loss status and with clinical outcome.

Is there evidence to claim or deny association between variants of the multidrug resistance gene (MDR1 or ABCB1) and inflammatory bowel disease?

Background: Inflammatory bowel disease (IBD) is a complex disease with a genetic background. Crohn's disease (CD) and ulcerative colitis (UC) are the two main types of IBD. There is indication that variants in the MDR1 gene are associated with development of IBD.

Evidence of association between methylenetetrahydrofolate reductase gene and susceptibility to breast cancer: a candidate-gene association study in a South-eastern European population.

The methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a candidate gene for breast cancer (BC). However, the specific role of MTHFR polymorphisms and haplotypes has not been fully clarified and replicated. We examined the association of two common MTHFR polymorphisms (C677T and A1298C) and their haplotypes in a candidate-gene association study, involving 300 female patients with BC and 283 healthy women.