Do Multidisciplinary Team (MDT) processes influence survival in patients with colorectal cancer? A population-based experience

BACKGROUND: MDT (multidisciplinary team) meetings are considered an essential component of care for patients with cancer. However there is remarkably little direct evidence that such meetings improve outcomes. We assessed whether or not MDT (multidisciplinary team) processes influenced survival in a cohort of patients with colorectal cancer. METHODS: Observational study of a population-based cohort of 586 consecutive patients with colorectal cancer diagnosed in Tayside (Scotland) during 2006 and 2007. RESULTS: Recommendations from MDT meetings were implemented in 411/586 (70.1 %) of patients, the MDT+ group. The remaining175/586 (29.9 %) were either never discussed at an MDT, or recommendations were not implemented, MDT- group. The 5-year cause-specific survival (CSS) rates were 63.1 % (MDT+) and 48.2 % (MDT-), p < 0.0001. In analysis confined to patients who survived >6 weeks after diagnosis, the rates were 63.2 % (MDT+) and 57.7 % (MDT-), p = 0.064. The adjusted hazard rate (HR) for death from colorectal cancer was 0.73 (0.53 to 1.00, p = 0.047) in the MDT+ group compared to the MDT- group, in patients surviving >6 weeks the adjusted HR was 1.00 (0.70 to 1.42, p = 0.987). Any benefit from the MDT process was largely confined to patients with advanced disease: adjusted HR ((early)) 1.32 (0.69 to 2.49, p = 0.401); adjusted HR((advanced)) 0.65 (0.45 to 0.96, p = 0.031). CONCLUSIONS: Adequate MDT processes are associated with improved survival for patients with colorectal cancer. However, some of this effect may be more apparent than real – simply reflecting selection bias. The MDT process predominantly benefits the 40 % of patients who present with advanced disease and conveys little demonstrable advantage to patients with early tumours. These results call into question the current belief that all new patients with colorectal cancer should be discussed at an MDT meeting

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

SCF Ensures Meiotic Chromosome Segregation Through a Resolution of Meiotic Recombination Intermediates

The SCF (Skp1-Cul1-F-box) complex contributes to a variety of cellular events including meiotic cell cycle control, but its function during meiosis is not understood well. Here we describe a novel function of SCF/Skp1 in meiotic recombination and subsequent chromosome segregation. The skp1 temperature-sensitive mutant exhibited abnormal distribution of spindle microtubules in meiosis II, which turned out to originate from abnormal bending of the spindle in meiosis I. Bent spindles were reported in mitosis of this mutant, but it remained unknown how SCF could affect spindle morphology. We found that the meiotic bent spindle in skp1 cells was due to a hypertension generated by chromosome entanglement. The spindle bending was suppressed by inhibiting double strand break (DSB) formation, indicating that the entanglement was generated by the meiotic recombination machinery. Consistently, Rhp51/Rad51-Rad22/Rad52 foci persisted until meiosis I in skp1 cells, proving accumulation of recombination intermediates. Intriguingly bent spindles were also observed in the mutant of Fbh1, an F-box protein containing the DNA helicase domain, which is involved in meiotic recombination. Genetic evidence suggested its cooperation with SCF/Skp1. Thus, SCF/Skp1 together with Fbh1 is likely to function in the resolution of meiotic recombination intermediates, thereby ensuring proper chromosome segregation

MicroRNAs Up-Regulated by CagA of Helicobacter pylori Induce Intestinal Metaplasia of Gastric Epithelial Cells

CagA of Helicobacter pylori is a bacterium-derived oncogenic protein closely associated with the development of gastric cancers. MicroRNAs (miRNAs) are a class of widespread non-coding RNAs, many of which are involved in cell growth, cell differentiation and tumorigenesis. The relationship between CagA protein and miRNAs is unclear. Using mammalian miRNA profile microarrays, we found that miRNA-584 and miRNA-1290 expression was up-regulated in CagA-transformed cells, miRNA-1290 was up-regulated in an Erk1/2-dependent manner, and miRNA-584 was activated by NF-κB. miRNA-584 sustained Erk1/2 activities through inhibition of PPP2a activities, and miRNA-1290 activated NF-κB by knockdown of NKRF. Foxa1 was revealed to be an important target of miRNA-584 and miRNA-1290. Knockdown of Foxa1 promoted the epithelial-mesenchymal transition significantly. Overexpression of miRNA-584 and miRNA-1290 induced intestinal metaplasia of gastric epithelial cells in knock-in mice. These results indicate that miRNA-584 and miRNA-1290 interfere with cell differentiation and remodel the tissues. Thus, the miRNA pathway is a new pathogenic mechanism of CagA

Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism

Malignant pleural mesothelioma (MPM) is an aggressive human cancer and miRNAs can play a key-role for this disease. In order to broaden the knowledge in this field, the miRNA expression was investigated in a large series of MPM to discover new pathways helpful in diagnosis, prognosis and therapy. We employed nanoString nCounter system for miRNA profiling on 105 MPM samples and 10 healthy pleura. The analysis was followed by the validation of the most significantly deregulated miRNAs by RT-qPCR in an independent sample set. We identified 63 miRNAs deregulated in a statistically significant way. MiR-185, miR-197, and miR-299 were confirmed differentially expressed, after validation study. In addition, the results of the microarray analysis corroborated previous findings concerning miR-15b-5p, miR-126-3p, and miR-145-5p. Kaplan-Meier curves were used to explore the association between miRNA expression and overall survival (OS) and identified a 2-miRNA prognostic signature (Let-7c-5p and miR-151a-5p) related to hypoxia and energy metabolism respectively. In silico analyses with DIANA-microT-CDS highlighted 5 putative targets in common between two miRNAs. With the present work we showed that the pattern of miRNAs expression is highly deregulated in MPM and that a 2-miRNA signature can be a new useful tool for prognosis in MPM

Expression of miRNAs miR-133b and miR-206 in the Il17a/f Locus Is Co-Regulated with IL-17 Production in αβ and γδ T Cells

Differentiation of T helper 17 cells (Th17) is a multistep process that involves the cytokines IL-6, TGF-β, and IL-23 as well as IL-1β, IL-21, and TNF-α. Thereby, robust induction of the capacity to produce IL-17 involves epigenetic modifications of the syntenic Il17a/f locus. Using inbred mouse strains, we identified co-regulation of gene transcription at the Il17a/f locus with the nearby microRNAs miR-133b and miR-206 that are clustered approximately 45 kb upstream of Il17a/f. Expression of these microRNAs was specific for Th17 as compared to other CD4+ T cell subsets and this was equally valid for in vitro polarized and ex vivo derived cells. From all factors analyzed, IL-23 was the most important cytokine for the in vitro induction of miR-133b and miR-206 in naive CD4+ T cells of wild type mice. However, analysis of IL-23R deficient mice revealed that IL-23R signaling was not essential for the induction of miR-133b and miR-206. Importantly, we found a similar co-regulation in CCR6+ and other γδ T cell subsets that are predisposed to production of IL-17. Taken together, we discovered a novel feature of T cell differentiation towards an IL-17-producing phenotype that is shared between αβ and γδ T cells. Notably, the specific co-regulation of miR-133b and miR-206 with the Il17a/f locus also extended to human Th17 cells. This qualifies expression of miR-133b and miR-206 in T cells as novel biomarkers for Th17-type immune reactions

Prediction of Associations between microRNAs and Gene Expression in Glioma Biology

Despite progress in the determination of miR interactions, their regulatory role in cancer is only beginning to be unraveled. Utilizing gene expression data from 27 glioblastoma samples we found that the mere knowledge of physical interactions between specific mRNAs and miRs can be used to determine associated regulatory interactions, allowing us to identify 626 associated interactions, involving 128 miRs that putatively modulate the expression of 246 mRNAs. Experimentally determining the expression of miRs, we found an over-representation of over(under)-expressed miRs with various predicted mRNA target sequences. Such significantly associated miRs that putatively bind over-expressed genes strongly tend to have binding sites nearby the 3′UTR of the corresponding mRNAs, suggesting that the presence of the miRs near the translation stop site may be a factor in their regulatory ability. Our analysis predicted a significant association between miR-128 and the protein kinase WEE1, which we subsequently validated experimentally by showing that the over-expression of the naturally under-expressed miR-128 in glioma cells resulted in the inhibition of WEE1 in glioblastoma cells

Predictors of binge drinking in adolescents: ultimate and distal factors - a representative study

<p>Abstract</p> <p>Background</p> <p>As epidemiological surveys have shown, binge drinking is a constant and wide-spread problem behavior in adolescents. It is not rare to find that more than half of all adolescents engage in this behavior when assessing only the last 4 weeks of time independent of the urbanity of the region they live in. There have been several reviews on predictors of substance consumption in adolescents in general, but there has been less high quality research on predictors of binge drinking, and most studies have not been theoretically based. The current study aimed to analyze the ultimate and distal factors predicting substance consumption according to Petraitis' theory of triadic influence. We assessed the predictive value of these factors with respect to binge drinking in German adolescents, including the identification of influence direction.</p> <p>Methods</p> <p>In the years 2007/2008, a representative written survey of N = 44,610 students in the 9^thgrade of different school types in Germany was carried out (net sample). The return rate of questionnaires was 88% regarding all students whose teachers or school directors had agreed to participate in the study. In this survey, prevalence of binge drinking was investigated as well as potential predictors from the social/interpersonal, the attitudinal/environmental, and the intrapersonal fields (3 factors of Petraitis). In a multivariate logistic regression analysis, these variables were included after testing for multicollinearity in order to assess their ability to predict binge drinking.</p> <p>Results</p> <p>Prevalence of binge drinking in the last 30 days was 52.3% for the surveyed adolescents with a higher prevalence for boys (56.9%) than for girls (47.5%). The two most influential factors found to protect against binge drinking with <it>p </it>< .001 were low economic status and importance of religion. The four most relevant risk factors for binge drinking (<it>p </it>< .001) were life-time prevalence of school absenteeism/truancy, academic failure, suicidal thoughts, and violence at school in the form of aggressive behavior of teachers. The model of Petraitis was partly confirmed for Binge Drinking in German adolescents and the direction of influence factors was clarified.</p> <p>Conclusions</p> <p>Whereas some of the risk and protective factors for binge drinking are not surprising since they are known for substance abuse in general, there are two points that could be targeted in interventions that do not focus on adolescents alone: (a) training teachers in positive, reassuring behavior and constructive criticism and (b) a focus on high risk adolescents either because they have a lack of coping strategies when in a negative mood or because of their low academic achievement in combination with absenteeism from school.</p

The Yeast Pif1 Helicase Prevents Genomic Instability Caused by G-Quadruplex-Forming CEB1 Sequences In Vivo

In budding yeast, the Pif1 DNA helicase is involved in the maintenance of both nuclear and mitochondrial genomes, but its role in these processes is still poorly understood. Here, we provide evidence for a new Pif1 function by demonstrating that its absence promotes genetic instability of alleles of the G-rich human minisatellite CEB1 inserted in the Saccharomyces cerevisiae genome, but not of other tandem repeats. Inactivation of other DNA helicases, including Sgs1, had no effect on CEB1 stability. In vitro, we show that CEB1 repeats formed stable G-quadruplex (G4) secondary structures and the Pif1 protein unwinds these structures more efficiently than regular B-DNA. Finally, synthetic CEB1 arrays in which we mutated the potential G4-forming sequences were no longer destabilized in pif1Δ cells. Hence, we conclude that CEB1 instability in pif1Δ cells depends on the potential to form G-quadruplex structures, suggesting that Pif1 could play a role in the metabolism of G4-forming sequences