Identification of new targets for glioblastoma therapy based on a DNA expression microarray.

This study provides a comprehensive perspective on the deregulated pathways and impaired biological functions prevalent in human glioblastoma (GBM). In order to characterize differences in gene expression between individuals diagnosed with GBM and healthy brain tissue, we have designed and manufactured a specific, custom DNA microarray. The results obtained from differential gene expression analysis were validated by RT-qPCR.

Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation.

In Alzheimer's disease (AD), the reduction in acetylcholinesterase (AChE) enzymatic activity is not paralleled with changes in its protein levels, suggesting the presence of a considerable enzymatically inactive pool in the brain. In the present study, we validated previous findings, and, since inactive forms could result from post-translational modifications, we analyzed the glycosylation of AChE by lectin binding in brain samples from sporadic and familial AD (sAD and fAD). Most of the enzymatically active AChE was bound to lectins (Con A) and (LCA) that recognize terminal mannoses, whereas Western blot assays showed a very low percentage of AChE protein being recognized by the lectin.

CLytA-DAAO Chimeric Enzyme Bound to Magnetic Nanoparticles. A New Therapeutical Approach for Cancer Patients?

D-amino acid oxidase (DAAO) is an enzyme that catalyzes the oxidation of D-amino acids generating HO. The enzymatic chimera formed by DAAO bound to the choline-binding domain of N-acetylmuramoyl-L-alanine amidase (CLytA) induces cytotoxicity in several pancreatic and colorectal carcinoma and glioblastoma cell models. In the current work, we determined whether the effect of CLytA-DAAO immobilized in magnetic nanoparticles, gold nanoparticles, and alginate capsules offered some advantages as compared to the free CLytA-DAAO.

A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer.

Background: Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance.

Differential Effects of IGF-1R Small Molecule Tyrosine Kinase Inhibitors BMS-754807 and OSI-906 on Human Cancer Cell Lines.

We have determined the effects of the IGF-1R tyrosine kinase inhibitors BMS-754807 (BMS) and OSI-906 (OSI) on cell proliferation and cell-cycle phase distribution in human colon, pancreatic carcinoma, and glioblastoma cell lines and primary cultures. IGF-1R signaling was blocked by BMS and OSI at equivalent doses, although both inhibitors exhibited differential antiproliferative effects. In all pancreatic carcinoma cell lines tested, BMS exerted a strong antiproliferative effect, whereas OSI had a minimal effect.

Cell Death Mechanisms Induced by CLytA-DAAO Chimeric Enzyme in Human Tumor Cell Lines.

The combination of the choline binding domain of the amidase N-acetylmuramoyl-L-alanine (CLytA)-D-amino acid oxidase (DAAO) (CLytA-DAAO) and D-Alanine induces cell death in several pancreatic and colorectal carcinoma and glioblastoma cell lines. In glioblastoma cell lines, CLytA-DAAO-induced cell death was inhibited by a pan-caspase inhibitor, suggesting a classical apoptotic cell death. Meanwhile, the cell death induced in pancreatic and colon carcinoma cell lines is some type of programmed necrosis.

Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses.

Objectives: To characterise the association between type 2 diabetes mellitus (T2DM) subtypes (new-onset T2DM (NODM) or long-standing T2DM (LSDM)) and pancreatic cancer (PC) risk, to explore the direction of causation through Mendelian randomisation (MR) analysis and to assess the mediation role of body mass index (BMI).

Design: Information about T2DM and related factors was collected from 2018 PC cases and 1540 controls from the PanGenEU (European Study into Digestive Illnesses and Genetics) study. A subset of PC cases and controls had glycated haemoglobin, C-peptide and genotype data.

Pancreatic Cancer Risk in Relation to Lifetime Smoking Patterns, Tobacco Type, and Dose-Response Relationships.

Background: Despite smoking being a well-established risk factor for pancreatic cancer, there is a need to further characterize pancreatic cancer risk according to lifespan smoking patterns and other smoking features, such as tobacco type. Our aim was to deeply investigate them within a large European case-control study.

Methods: Tobacco smoking habits and other relevant information were obtained from 2,009 cases and 1,532 controls recruited in the PanGenEU study using standardized tools.

CLytA-DAAO, Free and Immobilized in Magnetic Nanoparticles, induces Cell Death in Human Cancer Cells.

D-amino acid oxidase (DAAO) catalyzes the oxidation of D-amino acids generating hydrogen peroxide, a potential producer of reactive oxygen species. In this study, we used a CLytA-DAAO chimera, both free and bound to magnetic nanoparticles, against colon carcinoma, pancreatic adenocarcinoma, and glioblastoma cell lines. We found that the enzyme induces cell death in most of the cell lines tested and its efficiency increases significantly when it is immobilized in nanoparticles.

Correction: Radiotherapy resistance acquisition in Glioblastoma. Role of SOCS1 and SOCS3.

[This corrects the article DOI: 10.1371/journal.pone.

Implementation of massive sequencing in the genetic diagnosis of hereditary cancer syndromes: diagnostic performance in the Hereditary Cancer Programme of the Valencia Community (FamCan-NGS).

Background: Approximately 5 to 10% of all cancers are caused by inherited germline mutations, many of which are associated with different Hereditary Cancer Syndromes (HCS). In the context of the Program of Hereditary Cancer of the Valencia Community, individuals belonging to specific HCS and their families receive genetic counselling and genetic testing according to internationally established guidelines. The current diagnostic approach is based on sequencing a few high-risk genes related to each HCS; however, this method is time-consuming, expensive and does not achieve a confirmatory genetic diagnosis in many cases.

DNA Methylation of Tumor Suppressor Genes in Pituitary Neuroendocrine Tumors.

Context: Epigenetic alterations may play a role in the development and behavior of pituitary neuroendocrine tumors (PitNETs).

Objective: To evaluate the effect of methylation of tumor suppressor genes (TSGs) on their gene expression and on the behavior of PitNETs.

Material And Methods: We used methylation-specific multiplex ligation-dependent probe amplification and quantitative real-time PCR techniques to analyze the DNA-promoter hypermethylation and gene expression of 35 TSGs in 105 PitNETs.

A phylogenetic approach to the Philippines endemic centipedes of the genus Scolopendra Linnaeus, 1758 (Scolopendromorpha, Scolopendridae), with the description of a new species.

The genus Scolopendra Linnaeus, 1758 is represented in the Philippines' fauna by five species, two of which are endemic. Mitochondrial DNA sequences of gene cytochrome c oxidase subunit I (COI) were obtained from six Scolopendra specimens belonging to two endemic species and a new one, described here as Scolopendra paradoxa Doménech sp. nov.

Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches.

Deciphering the underlying genetic basis behind pancreatic cancer (PC) and its associated multimorbidities will enhance our knowledge toward PC control. The study investigated the common genetic background of PC and different morbidities through a computational approach and further evaluated the less explored association between PC and autoimmune diseases (AIDs) through an epidemiological analysis. Gene-disease associations (GDAs) of 26 morbidities of interest and PC were obtained using the DisGeNET public discovery platform.

Lack of cytomegalovirus detection in human glioma.

Gliomas are the most common brain tumors and include a variety of histologic types and grades of malignancy. They arise from glial cells and represent approximately 70% of the primary brain tumors. According to the criteria of the World Health Organization (WHO), the majority of gliomas can be classified into four grades of malignancy (I-IV).

Streptococcus gallolyticus infection in colorectal cancer and association with biological and clinical factors.

There is an unambiguous association of Streptococcus gallolyticus infection with colorectal cancer, although there is limited information about epidemiology or interaction between molecular and environmental factors. We performed an original quantitative analysis of S. gallolyticus in unselected colorectal cancer patients (n = 190) and their association with clinical, pathological tumor molecular profiles (microsatellite instability, hypermethylator phenotype and chromosomal instability pathways), and other biological factors in colorectal tumor and normal tissues (cytomegalovirus and Epstein-Barr virus infection).

Prevalence of MLH1 constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer.

Background: The prevalence of MLH1 constitutional epimutations in the general population is unknown. We sought to analyse the prevalence of MLH1 constitutional epimutations in unselected and selected series of patients with colorectal cancer (CRC).

Methods: Patients with diagnoses of CRC (n=2123) were included in the unselected group.

HGUE-C-1 is an atypical and novel colon carcinoma cell line.

Background: Colorectal carcinoma is a common cause of cancer. Adjuvant treatments include: 5-fluorouracil administered together with folinic acid, or more recently, oral fluoropyrimidines such as capecitabine, in combination with oxaliplatin or irinotecan. Metastatic colorectal cancer patients can benefit from other additional treatments such as cetuximab or bevacizumab.

Prevalence of germline MUTYH mutations among Lynch-like syndrome patients.

Background And Aims: Individuals with tumours showing mismatch repair (MMR) deficiency not linked to germline mutations or somatic methylation of MMR genes have been recently referred as having 'Lynch-like syndrome' (LLS). The genetic basis of these LLS cases is unknown. MUTYH-associated polyposis patients show some phenotypic similarities to Lynch syndrome patients.

Risk of cancer in cases of suspected lynch syndrome without germline mutation.

Background & Aims: Colorectal cancers (CRCs) with microsatellite instability (MSI) and a mismatch repair (MMR) immunohistochemical deficit without hypermethylation of the MLH1 promoter are likely to be caused by Lynch syndrome. Some patients with these cancers have not been found to have pathogenic germline mutations and are considered to have Lynch-like syndrome (LLS). The aim of this study was to determine the risk of cancer in families of patients with LLS.

TGFBR1 intralocus epistatic interaction as a risk factor for colorectal cancer.

In colorectal cancer (CRC), an inherited susceptibility risk affects about 35% of patients, whereas high-penetrance germline mutations account for <6% of cases. A considerable proportion of sporadic tumors could be explained by the coinheritance of multiple low-penetrance variants, some of which are common. We assessed the susceptibility to CRC conferred by genetic variants at the TGFBR1 locus.

Comparison between universal molecular screening for Lynch syndrome and revised Bethesda guidelines in a large population-based cohort of patients with colorectal cancer.

Background: The selection of patients for genetic testing to rule out Lynch syndrome is currently based on fulfilment of at least one of the revised Bethesda criteria followed by mismatch repair (MMR) status analysis. A study was undertaken to compare the present approach with universal MMR study-based strategies to detect Lynch syndrome in a large series of patients with colorectal cancer (CRC).

Methods: 2093 patients with CRC from the EPICOLON I and II cohorts were included.

Methylation analysis of MLH1 improves the selection of patients for genetic testing in Lynch syndrome.

Inactivation of MLH1 due to promoter hypermethylation strongly suggests a sporadic origin, providing exclusion criteria for Lynch syndrome. The aim of this study is to compare the utility of methylation analysis of MLH1 and BRAF V600E mutations for the selection of patients with MLH1 negative colorectal cancer for genetic testing. MLH1 methylation status was evaluated by MethyLight and methylation-specific MLPA (MS-MLPA) in tumor DNA from 73 colorectal cancer patients with loss of MLH1 protein expression.

Biallelic MYH germline mutations as cause of Muir-Torre syndrome.

Muir-Torre syndrome is a rare, inherited disease predisposing of gastrointestinal and cutaneous tumours, such as keratoacanthomas and sebaceous gland adenomas. Muir-Torre syndrome is usually inherited in an autosomal dominant fashion and associated with mutations in the mismatch repair genes, predominantly in MLH1 and MSH2 genes. This report describes a man who has multiple adenomatous colon polyps, a gastric cancer, multiple colorectal cancers and sebaceous adenomas caused by biallelic MYH germline mutations.