Telomere-specific reverse transcriptase (hTERT) and cell-free RNA in plasma as predictors of pathologic tumor response in rectal cancer patients receiving neoadjuvant chemoradiotherapy.

Purpose: To investigate whether the plasma levels of cell-free RNA (cfRNA) and telomere-specific reverse transcriptase mRNA (hTERT) are associated with tumor response in rectal cancer patients who received preoperative chemoradiotherapy (pCRT).

Methods: Patients who underwent pCRT for rectal cancer and for whom baseline and paired post-pCRT blood samples were available were studied. On the basis of tumor regression score, patients were classified as having response or having no response.

Relative expression of TAp73 and ΔNp73 isoforms.

The transcription factor p73 belongs to the p53 family of tumour suppressors and similar to other family members, transcribed as different isoforms with opposing pro- and anti-apoptotic functions. Unlike p53, p73 mutations are extremely rare in cancers. Instead, the pro-apoptotic activities of transcriptionally active p73 isoforms are commonly inhibited by over-expression of the dominant negative p73 isoforms.

Diagnostics of the ITER neutral beam test facility.

The ITER heating neutral beam (HNB) injector, based on negative ions accelerated at 1 MV, will be tested and optimized in the SPIDER source and MITICA full injector prototypes, using a set of diagnostics not available on the ITER HNB. The RF source, where the H(-)∕D(-) production is enhanced by cesium evaporation, will be monitored with thermocouples, electrostatic probes, optical emission spectroscopy, cavity ring down, and laser absorption spectroscopy. The beam is analyzed by cooling water calorimetry, a short pulse instrumented calorimeter, beam emission spectroscopy, visible tomography, and neutron imaging.

Clinical and molecular detection of inherited colorectal cancers in northeast Italy: a first prospective study of incidence of Lynch syndrome and MUTYH-related colorectal cancer in Italy.

The reported incidence of hereditary colorectal cancers (CRCs) is widely variable. The principal aim of the study was to prospectively evaluate the incidence of familial CRCs in a region of northern Italy using a standardized method. Consecutive CRC patients were prospectively enrolled from October 2002 to December 2003.

APC I1307K mutations and forkhead box gene (FOXO1A): another piece of an interesting correlation.

Purpose: Germline nonsense and frameshift mutations in the adenomatous polyposis coli (APC) gene are found in approximately 90% of individuals affected by familial adenomatous polyposis (FAP) and a genotype-phenotype relationship has been observed. Missense mutations have also been found in a few cases, even if their role in FAP is still unknown. An association between a missense mutation, APC I1307K, and the risk of sporadic colorectal cancer (CRC) has been reported.

A mutation in the thyroid hormone receptor alpha gene.

Thyroid hormones exert their effects through alpha (TRα1) and beta (TRβ1 and TRβ2) receptors. Here we describe a child with classic features of hypothyroidism (growth retardation, developmental retardation, skeletal dysplasia, and severe constipation) but only borderline-abnormal thyroid hormone levels. Using whole-exome sequencing, we identified a de novo heterozygous nonsense mutation in a gene encoding thyroid hormone receptor alpha (THRA) and generating a mutant protein that inhibits wild-type receptor action in a dominant negative manner.

microRNA-34a regulates neurite outgrowth, spinal morphology, and function.

The p53 family member TAp73 is a transcription factor that plays a key role in many biological processes, including neuronal development. In particular, we have shown that p73 drives the expression of miR-34a, but not miR-34b and c, in mouse cortical neurons. miR-34a in turn modulates the expression of synaptic targets including synaptotagmin-1 and syntaxin-1A.

Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets.

The p53-family member TAp73 is a transcription factor that plays a key role in many biological processes. Here, we show that p73 drives the expression of microRNA (miR)-34a, but not miR-34b and -c, by acting on specific binding sites on the miR-34a promoter. Expression of miR-34a is modulated in parallel with that of TAp73 during in vitro differentiation of neuroblastoma cells and cortical neurons.

Cell death pathology: perspective for human diseases.

Apoptosis, a genetically regulated form of cell death with distinct biochemical and morphological features, plays a relevant physiological and pathological role in the organism, being pivotal in the maintenance of tissue development and homeostasis in the adult as well as in the regulation of immune responses. Deregulation of this process causes several human disorders including cancer, autoimmune and neurodegenerative diseases. Thus, modulation of the apoptotic process and of cell death in general, is a potential therapeutic approach for the treatment of several human pathologies.

Molecular events associated with ciclosporin A-induced gingival overgrowth are attenuated by Smad7 overexpression in fibroblasts.

Background And Objective: Ciclosporin A (CsA)-induced gingival overgrowth is attributed to an exaggerated accumulation of extracellular matrix, which is mainly due to an increased expression of transforming growth factor-β1 (TGF-β1). Herein, the in vitro investigation of effects of overexpression of Smad7, a TGF-β1 signaling inhibitor, in the events associated with CsA-induced extracellular matrix accumulation was performed.

Material And Methods: The effects of Smad7 were assessed by stable overexpression of Smad7 in fibroblasts from normal gingiva.

p63 in tooth development.

Recent findings have shown that the development of teeth involves a complex sequence of molecular events in which the p53 family member p63 is involved. Indeed, mice lacking p63 do not have teeth and humans bearing mutations in p63 suffer developmental syndromes that affect tooth morphology and number. Several isoforms of p63 have been described: the use of two different promoters produces longer TAp63 isoforms, or shorter, 5' truncated isoforms known as ΔNp63.

p73 in Cancer.

p73 is a tumor suppressor belonging to the p53 family of transcription factors. Distinct isoforms are transcribed from the p73 locus. The use of 2 promoters at the N-terminus allows the expression of an isoform containing (TAp73) or not containing (ΔNp73) a complete N-terminal transactivation domain, with the latter isoform capable of a dominant negative effect over the former.

Assessment of dermal exposure to bitumen condensate among road paving and mastic crews with an observational method.

Objective: To assess dermal exposure to bitumen condensate among road pavers and indoor mastic workers in multiple crews using a semi-quantitative observational method [DeRmal Exposure Assessment Method (DREAM)].

Methods: Two skilled observers assessed dermal exposure to bitumen condensate among 85 asphalt workers from 12 crews from nine companies active within four European countries using the DREAM methodology, which produces an estimate of exposure expressed in dimensionless DREAM units. Both observers independently evaluated each crew member's job (N = 14 jobs) for road paving and mastic applications.

miR-146a is modulated in human endothelial cell with aging.

Background: Increasing evidence has demonstrated that the senescence of vascular endothelial cells has critical roles in the pathogenesis of vascular dysfunction such as atherosclerosis and thrombosis. MicroRNA (miR) are small non-coding RNAs that inhibit gene expression by binding to complementary sequences in the 3'UTR of their target mRNAs. MiRs modulate a variety of biological functions such as cell development, cell differentiation, and apoptosis.

Exposure to rubber process dust and fume since 1970s in the United Kingdom; influence of origin of measurement data.

The objective of this study was to compare measured concentrations of rubber process dust and rubber fume originating from different sources in the British rubber manufacturing industry. Almost 8000 exposure measurements were obtained from industry-based survey results collected by the British Rubber Manufacturers' Association (BRMA), and covering the years 1977 to 2002, and from a series of small surveys contained in the Health and Safety Executive's (HSE) National Exposure Database (HSE-NEDB) from 1980 to 2002. The analysis investigated temporal trends in the exposure concentrations and the underlying main factors responsible for these changes.

Axon cap morphology of the sea robin (Prionotus carolinus): Mauthner cell is correlated with the presence of "signature" field potentials and a C-type startle response.

Studies on the Mauthner cell (M-cell) of goldfish, Carassius auratus, have facilitated our understanding of how sensory information is integrated in the hindbrain to initiate C-type fast startle responses (C-starts). The goldfish M-cell initial segment/axon hillock is surrounded by a composite axon cap consisting of a central core and a peripheral zone covered by a glial cell layer. The high resistivity of the axon cap results in "signature" field potentials recorded on activation of the M-cell, allowing unequivocal physiological identification of the M-cell and of its feedback and reciprocal inhibitory networks that are crucial in ensuring that only one M-cell is active and that it fires only once.

Circulating cell-free DNA: a promising marker of pathologic tumor response in rectal cancer patients receiving preoperative chemoradiotherapy.

Purpose: The circulating cell-free DNA (cfDNA) in plasma has been reported to be a marker of cancer detection. The aim of this study was to investigate whether the cfDNA has a role as response biomarker in patients receiving preoperative chemoradiotherapy (CRT) for rectal cancer.

Methods: Sixty-seven patients (median age 61 years; male/female 42/25) who underwent CRT for rectal cancer were evaluated.

p73: a multifunctional protein in neurobiology.

p73, a transcription factor of the p53 family, plays a key role in many biological processes including neuronal development. Indeed, mice deficient for both TAp73 and ΔNp73 isoforms display neuronal pathologies, including hydrocephalus and hippocampal dysgenesis, with defects in the CA1-CA3 pyramidal cell layers and the dentate gyrus. TAp73 expression increases in parallel with neuronal differentiation and its ectopic expression induces neurite outgrowth and expression of neuronal markers in neuroblastoma cell lines and neural stem cells, suggesting that it has a pro-differentiation role.

Collagen-coated polypropylene mesh in vaginal prolapse surgery: an observational study.

Objective: We evaluated the efficacy and safety of a collagen-coated polypropylene mesh with a trans-obturator approach for cystocele repair.

Study Design: We considered as eligible for our study 97 patients with a stage ≥ 2 cystocele according to the Pelvic Organ Prolapse Staging System (POP-Q), with or without associated apical or posterior vaginal wall prolapse. They were also evaluated pre- and post-operatively using validated questionnaires (P-QoL, Wexner and PISQ-12).

Warm-blood cardioplegia with low or high magnesium for coronary bypass surgery: a randomised controlled trial.

Objective: Magnesium (Mg²⁺) is cardioprotective and has been routinely used to supplement cardioplegic solutions during coronary artery bypass graft (CABG) surgery. However, there is no consensus about the Mg²⁺ concentration that should be used. The aim of this study was to compare the effects of intermittent antegrade warm-blood cardioplegia supplemented with either low- or high-concentration Mg²⁺.

Integrated analysis of unclassified variants in mismatch repair genes.

Purpose: Lynch syndrome is a genetic disease that predisposes to colorectal tumors, caused by mutation in mismatch repair genes. The use of genetic tests to identify mutation carriers does not always give perfectly clear results, as happens when an unclassified variant is found. This study aimed to define the pathogenic role of 35 variants present in MSH2, MLH1, MSH6, and PMS2 genes identified in our 15-year case study.

Ageing, neuronal connectivity and brain disorders: an unsolved ripple effect.

Cognitive decline associated with ageing and age-related disorders emerges as one of the greatest health challenges in the next decades. To date, the molecular mechanisms underlying the onset of neuronal physiological changes in the central nervous system remain unclear. Functional MRI and PET studies have indicated the decline in working memory performance in older adults.

Circulating cell-free DNA: a promising marker of regional lymphonode metastasis in breast cancer patients.

Purpose: We undertook the current study with untreated breast cancer to (1) role the variations in the plasma levels of cfDNA and the size distribution in early stage, (2) determine the frequency in plasma of methylation of three candidate genes, RASSF1A, MAL, and SFRP1, and (3) to determine whether detection of cfDNA variations and methylation changes in plasma might have specific clinical utility.

Methods And Materials: Thirty-nine patients woman patients (median age 64 years; range, 36-90 years) who underwent surgery for primary BR and 49 healthy females' subjects (control group without any breast lesion) were evaluated. The cfDNA levels were analyzed using quantitative real-time polymerase chain reaction of β-globin.

Rectum-sparing surgery may be appropriate for biallelic MutYH-associated polyposis.

Purpose: The risk of cancer or severe polyposis of the rectal stump after total colectomy for MutYH-associated polyposis is scarcely defined. To evaluate this risk, we describe the findings of endoscopic surveillance of the rectal stump in a series of patients with biallelic MutYH mutations and polyposis.

Methods: This is a retrospective, observational, multicenter case series derived from 2 familial cancer registries.

Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans.

Selenium, a trace element that is fundamental to human health, is incorporated into some proteins as selenocysteine (Sec), generating a family of selenoproteins. Sec incorporation is mediated by a multiprotein complex that includes Sec insertion sequence-binding protein 2 (SECISBP2; also known as SBP2). Here, we describe subjects with compound heterozygous defects in the SECISBP2 gene.