Atonal homolog 1 Is a Tumor Suppressor Gene

Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1. ATOH1 antagonizes tumor formation and growth by regulating proliferation and apoptosis, likely via activation of the Jun N-terminal kinase signaling pathway. Furthermore, colorectal cancer and Merkel cell carcinoma patients show genetic and epigenetic ATOH1 loss-of-function mutations. Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation

Redirecting research efforts on the diversification-performance linkage: The search for synergy

We review the literature on the diversification-performance (D-P) relationship to a) propose that the time is ripe for a renewed attack on understanding the relationship between diversification and firm performance, and b) outline a new approach to attacking the question. Our paper makes four main contributions. First, through a review of the literature we establish the inherent complexities in the D-P relationship and the methodological challenges confronted by the literature in reaching its current conclusion of a non-linear relationship between diversification and performance. Second, we argue that to better guide managers the literature needs to develop along a complementary path – whereas past research has often focused on answering the big question of does diversification affect firm performance, this second path would focus more on identifying the precise micro-mechanisms through which diversification adds or subtracts value. Third, we outline a new approach to the investigation of this topic, based on (a) identifying the precise underlying mechanisms through which diversification affects performance; (b) identifying performance outcomes that are “proximate” to the mechanism that the researcher is studying, and (c) identifying an appropriate research design that can enable a causal claim. Finally, we outline a set of directions for future research

Extended Versus Standard Lymphadenectomy for Pancreatic Head Cancer: Meta-Analysis of Randomized Controlled Trials

INTRODUCTION: The evidence for improved prognostic assessment and long-term survival for extended pancreatoduodenectomy (EPD) compared to standard pancreatoduodenectomy (SPD) in patients with carcinoma of the head of the pancreas has not been considered from only randomized controlled trials (RCTs).METHODS: The aim of this study was to conduct a systematic review and meta-analysis of the outcomes comparing SPD and EPD in RCTs. Searches were performed on MEDLINE, Embase and Cochrane databases using MeSH keyword combinations: 'pancreatic cancer', 'pancreaticoduodenectomy', 'extended', 'randomized' and 'lymphadenectomy'. RCTs published up to 2014 were included. Overall post-operative survival, morbidity, 30-day mortality and length of hospital stay were the outcomes assessed.RESULTS: Five eligible RCTs with 546 participants were included (EPD = 276 and SPD = 270). EPD was associated with a significantly higher number of excised lymph nodes (LNs) compared to SPD (mean difference = 15.73, 95 % confidence interval (CI) = 9.41-22.04; P &lt; 0.00001; I (2) = 88 %). LN metastasis was detected in 58-68 and 55-70 % of patients who had EPD and SPD, respectively. EPD did not improve overall survival (hazard ratio (HR) = 0.88, 95 % CI = 0.75-1.03; P = 0.11) but did worsen post-operative morbidity compared to SPD (risk ratio (RR) = 1.23; 95 % CI = 1.01-1.50; P = 0.004; I (2) = 9 %). There were no differences in the 30-day mortality (RR = 0.81; 95 % CI = 0.32-2.06; P = 0.66; I (2) = 0 %) or length of hospital stay (mean difference = 1.39, 95 % CI = -2.31 to 5.09; P = 0.46; I (2) = 67 %).CONCLUSION: SPD is associated with reduced morbidity, but equivalent long-term benefits compared to patients undergoing EPD.</p