Exploring the association with disease recurrence of miRNAs predictive of colorectal cancer.

Introduction: Disease recurrence after surgery is a crucial predictor of poor prognosis in colorectal cancer, where disseminated disease at the time of intervention can also be observed in localized early-stage cases. We evaluated the ability to predict disease recurrence of miRNAs from two signatures that we have found linked to the presence of colorectal cancer (CL signature) or adenoma (HgA signature) in higher-risk subjects.

Methods: miRNAs from the signatures were studied longitudinally by quantitative real-time polymerase chain reaction in plasma from 24 patients with resectable colorectal cancer collected at the time of surgery and during scheduled follow-up across 36 months.

Plasma miRNA-based signatures in CRC screening programs.

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification.

Evaluation of SNPs in miR-146a, miR196a2 and miR-499 as low-penetrance alleles in German and Italian familial breast cancer cases.

Recently, the SNPs rs11614913 in hsa-mir-196a2 and rs3746444 in hsa-mir-499 were reported to be associated with increased breast cancer risk, and the SNP rs2910164 in hsa-mir-146a was shown to have an effect on age of breast cancer diagnosis. In order to further investigate the effect of these SNPs, we genotyped a total of 1894 breast cancer cases negative for disease-causing mutations or unclassified variants in BRCA1 and BRCA2, and 2760 controls from Germany and Italy. We compared the genotype and allele frequencies of rs2910164, rs11614913 and rs3746444 in cases versus controls of the German and Italian series, and of the two series combined; we also investigated the effect of the three SNPs on age at breast cancer diagnosis.

Survival prediction of stage I lung adenocarcinomas by expression of 10 genes.

Adenocarcinoma is the predominant histological subtype of lung cancer, the leading cause of cancer deaths in the world. At stage I, the tumor is cured by surgery alone in about 60% of cases. Markers are needed to stratify patients by prognostic outcomes and may help in devising more effective therapies for poor prognosis patients.

Myc-binding-site recognition in the human genome is determined by chromatin context.

Large-scale chromatin immunoprecipitation (ChIP) studies have been effective in unravelling the distribution of DNA-binding transcription factors along eukaryotic genomes, but specificity determinants remain elusive. Gene-regulatory regions display distinct histone variants and modifications (or marks). An attractive hypothesis is that these marks modulate protein recognition, but whether or not this applies to transcription factors remains unknown.

Acute myeloid leukemia bearing cytoplasmic nucleophosmin (NPMc+ AML) shows a distinct gene expression profile characterized by up-regulation of genes involved in stem-cell maintenance.

Approximately one third of acute myeloid leukemias (AMLs) are characterized by aberrant cytoplasmic localization of nucleophosmin (NPMc+ AML), consequent to mutations in the NPM putative nucleolar localization signal. These events are mutually exclusive with the major AML-associated chromosomal rearrangements, and are frequently associated with normal karyotype, FLT3 mutations, and multilineage involvement. We report the gene expression profiles of 78 de novo AMLs (72 with normal karyotype; 6 without major chromosomal abnormalities) that were characterized for the subcellular localization and mutation status of NPM.

Genetic polymorphisms of the renin-angiotensin-aldosterone system and renal insufficiency in essential hypertension.

Objective: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the control of renal function both in physiological and pathological conditions. The aim of the present study was to evaluate the relation between four genetic polymorphisms of the RAAS and renal insufficiency in a population of patients with essential hypertension living in north-east Italy.

Design And Methods: Eighty-six hypertensive patients with renal insufficiency and 172 hypertensive patients without renal damage matched for age and hypertension duration to within 2 years were evaluated.

Association between aldosterone synthase (CYP11B2) polymorphism and left ventricular mass in human essential hypertension.

Objectives: The aim of our study was to evaluate the relationship between aldosterone synthase gene polymorphism and cardiac dimensions in essential hypertension.

Background: Higher aldosterone synthase messenger ribonucleic acid levels in the human heart are accompanied by increased intracardiac aldosterone production, a phenomenon that is associated with cardiac fibrosis and hypertrophy. Recent evidence suggests that a polymorphism (-344C/T) in the promoter region of the aldosterone synthase gene is associated with increased constitutive aldosterone production.

Genetic polymorphism of the renin-angiotensin-aldosterone system and arterial hypertension in the Italian population: the GENIPER Project.

Objective: To detect the association of single polymorphisms of the renin-angiotensin-aldosterone system (RAAS), or different combinations thereof, with hypertension.

Design And Methods: The GENIPER database is the result of a collaborative effort of 13 Italian research centres to collect genomic DNA in subjects well characterized in terms of blood pressure status. A total of 2461 subjects (normotensive = 611; hypertensive = 1850) were selected and genotyped for the angiotensin-converting enzyme insertion/deletion (ACE I/D), angiotensinogen (AGT) T/C704, angiotensin receptor type 1 (AT1) A/C1166 and aldosterone synthase (ALDO) T/C-344 genetic variants.

Expression analysis of the human adducin gene family and evidence of ADD2 beta4 multiple splicing variants.

Adducin is a cytoskeleton heterodimeric protein. Its subunits are encoded by three related genes (ADD1, ADD2, and ADD3) which show alternative spliced variants. Adducin polymorphisms are involved in blood pressure regulation in humans and rats.