DNA Methylation of PITX2 and PANCR Is Prognostic for Overall Survival in Patients with Resected Adenocarcinomas of the Biliary Tract.

Biliary tract cancers (BTC) are rare but highly aggressive malignant epithelial tumors. In order to improve the outcome in this lethal disease, novel biomarkers for diagnosis, prognosis, and therapy response prediction are urgently needed. DNA promoter methylation of PITX2 variants (PITX2ab, PITX2c) and intragenic methylation of the PITX2 adjacent non-coding RNA (PANCR) were investigated by methylations-specific qPCR assays in formalin-fixed paraffin-embedded tissue from 80 patients after resection for BTC.

PITX2 and PANCR DNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma.

Background: Squamous cell carcinoma of the head and neck region (HNSCC) is a common malignant disease accompanied by a high risk of local or distant recurrence after curative-intent treatment. Biomarkers that allow for the prediction of disease outcome can guide clinicians with respect to treatment and surveillance strategies. Here, the methylation status of PITX2 and an adjacent lncRNA (PANCR) were evaluated for their ability to predict overall survival in HNSCC patients.

Prospective multicenter registration study of colorectal cancer: significant variations in radicality and oncosurgical quality-Swiss Group for Clinical Cancer Research Protocol SAKK 40/00.

Purpose: This study aimed to investigate in a multicenter cohort study the radicality of colorectal cancer resections, to assess the oncosurgical quality of colorectal specimens, and to compare the performance between centers.

Methods: One German and nine Swiss hospitals agreed to prospectively register all patients with primary colorectal cancer resected between September 2001 and June 2005. The median number of eligible patients with one primary tumor included per center was 95 (range 12-204).

Scientific principles for the identification of endocrine-disrupting chemicals: a consensus statement.

Endocrine disruption is a specific form of toxicity, where natural and/or anthropogenic chemicals, known as "endocrine disruptors" (EDs), trigger adverse health effects by disrupting the endogenous hormone system. There is need to harmonize guidance on the regulation of EDs, but this has been hampered by what appeared as a lack of consensus among scientists. This publication provides summary information about a consensus reached by a group of world-leading scientists that can serve as the basis for the development of ED criteria in relevant EU legislation.

promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients after radical prostatectomy.

Background: Molecular biomarkers that might help to distinguish between more aggressive and clinically insignificant prostate cancers (PCa) are still urgently needed. Aberrant DNA methylation as a common molecular alteration in PCa seems to be a promising source for such biomarkers. In this study, DNA methylation () and its potential role as a prognostic biomarker were investigated.

CDO1 promoter methylation is associated with gene silencing and is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients.

Molecular biomarkers may facilitate the distinction between aggressive and clinically insignificant prostate cancer (PCa), thereby potentially aiding individualized treatment. We analyzed cysteine dioxygenase 1 (CDO1) promoter methylation and mRNA expression in order to evaluate its potential as prognostic biomarker. CDO1 methylation and mRNA expression were determined in cell lines and formalin-fixed paraffin-embedded prostatectomy specimens from a first cohort of 300 PCa patients using methylation-specific qPCR and qRT-PCR.

and DNA methylation status and its utility in the diagnosis of colonic adenomas and colorectal adenocarcinomas.

Background: Colorectal cancer (CRC) appear to arise from precursor lesions in a well-characterized adenoma-carcinoma sequence. Significant efforts have been invested to develop biomarkers that identify early adenocarcinomas and adenomas with high-grade dysplasia, since these are believed to harbor a particularly high risk for malignant transition and thus require resection. Promoter methylation of and has been suggested as a biomarker for various solid malignant tumors.

The emerging role of non-coding circulating RNA as a biomarker in renal cell carcinoma.

Bodily fluids like serum and plasma contain significant amounts of tumor-derived circulating cell-free RNA, which holds the potential to serve as diagnostic biomarker. Consequently, liquid biopsies comprising circulating cell-free RNA might help to facilitate personalized treatment strategies for patients with renal cell carcinoma (RCC). Areas covered: The present review provides a summary of the literature obtained by a PubMed search and covers the current knowledge on circulating non-coding cell-free RNA in patients with RCC.

NG2 glial cells integrate synaptic input in global and dendritic calcium signals.

Synaptic signaling to NG2-expressing oligodendrocyte precursor cells (NG2 cells) could be key to rendering myelination of axons dependent on neuronal activity, but it has remained unclear whether NG2 glial cells integrate and respond to synaptic input. Here we show that NG2 cells perform linear integration of glutamatergic synaptic inputs and respond with increasing dendritic calcium elevations. Synaptic activity induces rapid Ca signals mediated by low-voltage activated Ca channels under strict inhibitory control of voltage-gated A-type K channels.

CXCL12 promoter methylation and PD-L1 expression as prognostic biomarkers in prostate cancer patients.

Background: The CXCR4/CXCL12 axis plays a central role in systemic metastasis of prostate carcinoma (PCa), thereby representing a promising target for future therapies. Recent data suggest that the CXCR4/CXCL12 axis is functionally linked to the PD-1/PD-L1 immune checkpoint. We evaluated the prognostic value of aberrant CXCL12 DNA methylation with respect to PD-L1 expression in primary PCa.

Interleukin-36 potently stimulates human M2 macrophages, Langerhans cells and keratinocytes to produce pro-inflammatory cytokines.

Interleukin (IL)-36 cytokines belong to the IL-1 family and include three agonists, IL-36 α, β and γ and one inhibitor, IL-36 receptor antagonist (IL-36Ra). IL-36 and IL-1 (α and β) activate similar intracellular pathways via their related heterodimeric receptors, IL-36R/IL-1RAcP and IL-1R1/IL-1RAcP, respectively. However, excessive IL-36 versus IL-1 signaling induces different phenotypes in humans, which may be related to differential expression of their respective receptors.

Bevacizumab Continuation Versus Treatment Holidays After First-Line Chemotherapy With Bevacizumab in Patients With Metastatic Colorectal Cancer: A Health Economic Analysis of a Randomized Phase 3 Trial (SAKK 41/06).

Background: Bevacizumab (BEV)-containing therapies are costly. We performed a health economic analysis of a randomized phase 3 study (SAKK 41/06) that compared BEV continuation as a single agent (BEV) with treatment holidays (no BEV) after completing 4 to 6 cycles of first-line chemotherapy plus BEV in metastatic colorectal cancer patients.

Patients And Methods: Costs for first-line chemotherapy with BEV, BEV continuation therapy, hospitalizations (length of stay), control visits, diagnostic tests, and second-line and later rounds of chemotherapy were collected.

SOCS3 Modulates the Response to Enzalutamide and Is Regulated by Androgen Receptor Signaling and CpG Methylation in Prostate Cancer Cells.

Unlabelled: The proinflammatory cytokine IL6 is associated with bad prognosis in prostate cancer and implicated in progression to castration resistance. Suppressor of cytokine signaling 3 (SOCS3) is an IL6-induced negative feedback regulator of the IL6/Janus kinase (JAK)/STAT3 pathway. This study reveals that the SOCS3 promoter is hypermethylated in cancerous regions compared with adjacent benign tissue in prostate cancer using methylation-specific qPCR.

Dynamic posterior stabilization for degenerative lumbar spine disease: a large consecutive case series with long-term follow-up by additional postal survey.

Introduction: Dynamic stabilization of the degenerated spine was invented to overcome the negative side effects of fusion surgery like adjacent segment degeneration. Amongst various different implants DSS(®) is a pedicle-based dynamic device for stabilizing the spine and preserving motion. Nearly no clinical data of the implant have been reported so far.

Elemental bioimaging and speciation analysis for the investigation of Wilson's disease using μXRF and XANES.

A liver biopsy specimen from a Wilson's disease (WD) patient was analyzed by means of micro-X-ray fluorescence (μXRF) spectroscopy to determine the elemental distribution. First, bench-top μXRF was utilized for a coarse scan of the sample under laboratory conditions. The resulting distribution maps of copper and iron enabled the determination of a region of interest (ROI) for further analysis.

The beneficial and detrimental effects of major depression on intuitive decision-making.

Intuitions play a central role in everyday life decision-making but little is known regarding this capacity during depression. Thus, in Study 1, N = 39 depressed in-patients completed two well-established tasks, assessing intuitions of visual and semantic coherence. In the semantic coherence task, patients judged whether presented words triads were coherent (e.

Novel insights into renal D-amino acid oxidase accumulation: propiverine changes DAAO localization and peroxisomal size in vivo.

Chronic exposure to propiverine, a frequently prescribed pharmaceutical for treatment of overactive bladder and incontinence, provokes massive protein accumulation in the cytosol and nucleus of renal proximal tubule epithelial cells in rats. Previously, the accumulating protein was identified as D-amino acid oxidase (DAAO), a peroxisomal flavoenzyme expressed in kidney, liver and brain. The cellular mechanism of propiverine-induced DAAO accumulation, however, remains unexplained and poorly characterized.

Diagnostic and prognostic value of SHOX2 and SEPT9 DNA methylation and cytology in benign, paramalignant, and malignant ascites.

Background: Cytology remains the gold standard for the detection of malignant cells in ascites. However, its sensitivity is limited. The aim of this study was to evaluate DNA methylation biomarkers for the differential diagnosis of benign (ascites in patients without malignancy), malignant (ascites in cancer patients directly caused by malignancy), and paramalignant (ascites in cancer patients caused by comorbidities but not by malignancy) ascites.