Cyclin H expression is increased in GIST with very-high risk of malignancy

<p>Abstract</p> <p>Background</p> <p>Risk estimation of gastrointestinal stromal tumours (GIST) is based on tumour size and mitotic rate according to the National Institutes of Health consensus classification. The indication for adjuvant treatment of patients with high risk GIST after R₀resection with small molecule inhibitors is still a controversial issue, since these patients represent a highly heterogeneous population. Therefore, additional prognostic indicators are needed. Here, we evaluated the prognostic value of cyclin H expression in GIST.</p> <p>Methods</p> <p>In order to identify prognostic factors of GIST we evaluated a single centre cohort of ninety-five GIST patients. First, GISTs were classified with regard to tumour size, mitotic rate and localisation according to the NIH consensus and to three additional suggested risk classifications. Second, Cyclin H expression was analysed.</p> <p>Results</p> <p>Of ninety-five patients with GIST (53 female/42 male; median age: 66.78a; range 17-94a) risk classification revealed: 42% high risk, 20% intermediate risk, 23% low risk and 15% very low risk GIST. In patients with high risk GIST, the expression of cyclin H was highly predictive for reduced disease-specific survival (p = 0.038). A combination of cyclin H expression level and high risk classification yielded the strongest prognostic indicator for disease-specific and disease-free survival (p ≤ 0.001). Moreover, in patients with tumour recurrence and/or metastases, cyclin H positivity was significantly associated with reduced disease-specific survival (p = 0.016) regardless of risk-classification.</p> <p>Conclusion</p> <p>Our data suggest that, in addition to high risk classification, cyclin H expression might be an indicator for "very-high risk" GIST.</p

Adaptive Value of Phenological Traits in Stressful Environments: Predictions Based on Seed Production and Laboratory Natural Selection

Phenological traits often show variation within and among natural populations of annual plants. Nevertheless, the adaptive value of post-anthesis traits is seldom tested. In this study, we estimated the adaptive values of pre- and post-anthesis traits in two stressful environments (water stress and interspecific competition), using the selfing annual species Arabidopsis thaliana. By estimating seed production and by performing laboratory natural selection (LNS), we assessed the strength and nature (directional, disruptive and stabilizing) of selection acting on phenological traits in A. thaliana under the two tested stress conditions, each with four intensities. Both the type of stress and its intensity affected the strength and nature of selection, as did genetic constraints among phenological traits. Under water stress, both experimental approaches demonstrated directional selection for a shorter life cycle, although bolting time imposes a genetic constraint on the length of the interval between bolting and anthesis. Under interspecific competition, results from the two experimental approaches showed discrepancies. Estimation of seed production predicted directional selection toward early pre-anthesis traits and long post-anthesis periods. In contrast, the LNS approach suggested neutrality for all phenological traits. This study opens questions on adaptation in complex natural environment where many selective pressures act simultaneously

Systematic review with meta-analysis of the epidemiological evidence relating smoking to COPD, chronic bronchitis and emphysema

<p>Abstract</p> <p>Background</p> <p>Smoking is a known cause of the outcomes COPD, chronic bronchitis (CB) and emphysema, but no previous systematic review exists. We summarize evidence for various smoking indices.</p> <p>Methods</p> <p>Based on MEDLINE searches and other sources we obtained papers published to 2006 describing epidemiological studies relating incidence or prevalence of these outcomes to smoking. Studies in children or adolescents, or in populations at high respiratory disease risk or with co-existing diseases were excluded. Study-specific data were extracted on design, exposures and outcomes considered, and confounder adjustment. For each outcome RRs/ORs and 95% CIs were extracted for ever, current and ex smoking and various dose response indices, and meta-analyses and meta-regressions conducted to determine how relationships were modified by various study and RR characteristics.</p> <p>Results</p> <p>Of 218 studies identified, 133 provide data for COPD, 101 for CB and 28 for emphysema. RR estimates are markedly heterogeneous. Based on random-effects meta-analyses of most-adjusted RR/ORs, estimates are elevated for ever smoking (COPD 2.89, CI 2.63-3.17, n = 129 RRs; CB 2.69, 2.50-2.90, n = 114; emphysema 4.51, 3.38-6.02, n = 28), current smoking (COPD 3.51, 3.08-3.99; CB 3.41, 3.13-3.72; emphysema 4.87, 2.83-8.41) and ex smoking (COPD 2.35, 2.11-2.63; CB 1.63, 1.50-1.78; emphysema 3.52, 2.51-4.94). For COPD, RRs are higher for males, for studies conducted in North America, for cigarette smoking rather than any product smoking, and where the unexposed base is never smoking any product, and are markedly lower when asthma is included in the COPD definition. Variations by sex, continent, smoking product and unexposed group are in the same direction for CB, but less clearly demonstrated. For all outcomes RRs are higher when based on mortality, and for COPD are markedly lower when based on lung function. For all outcomes, risk increases with amount smoked and pack-years. Limited data show risk decreases with increasing starting age for COPD and CB and with increasing quitting duration for COPD. No clear relationship is seen with duration of smoking.</p> <p>Conclusions</p> <p>The results confirm and quantify the causal relationships with smoking.</p