Exploring the additive effects of stimulus quality and word frequency: The influence of local and list-wide prime relatedness

Stimulus quality and word frequency produce additive effects in lexical decision performance, whereas the semantic priming effect interacts with both stimulus quality and word frequency effects. This pattern places important constraints on models of visual word recognition. In Experiment 1, all three variables were investigated within a single speeded pronunciation study. The results indicated that the joint effects of stimulus quality and word frequency were dependent upon prime relatedness. In particular, an additive effect of stimulus quality and word frequency was found after related primes, and an interactive effect was found after unrelated primes. It was hypothesized that this pattern reflects an adaptive reliance on related prime information within the experimental context. In Experiment 2, related primes were eliminated from the list, and the interactive effects of stimulus quality and word frequency found following unrelated primes in Experiment 1 reverted to additive effects for the same unrelated prime conditions. The results are supportive of a flexible lexical processor that adapts to both local prime information and global list-wide context

p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas

Once melanoma metastasizes, no effective treatment modalities prolong survival in most patients. This notorious refractoriness to therapy challenges investigators to identify agents that overcome melanoma resistance to apoptosis. Whereas many survival pathways contribute to the death-defying phenotype in melanoma, a defect in apoptotic machinery previously highlighted inactivation of Apaf-1, an apoptosome component engaged after mitochondrial damage. During studies involving Notch signaling in melanoma, we observed a gamma-secretase tripeptide inhibitor (GSI; z-Leu-Leu-Nle-CHO), selected from a group of compounds originally used in Alzheimer's disease, induced apoptosis in nine of nine melanoma lines. GSI only induced G2-M growth arrest (but not killing) in five of five normal melanocyte cultures tested. Effective killing of melanoma cells by GSI involved new protein synthesis and a mitochondrial-based pathway mediated by up-regulation of BH3-only members (Bim and NOXA). p53 activation was not necessary for up-regulation of NOXA in melanoma cells. Blocking GSI-induced NOXA using an antisense (but not control) oligonucleotide significantly reduced the apoptotic response. GSI also killed melanoma cell lines with low Apaf-1 levels. We conclude that GSI is highly effective in killing melanoma cells while sparing normal melanocytes. Direct enhancement of BH3-only proteins executes an apoptotic program overcoming resistance of this lethal tumor. Identification of a p53-independent apoptotic pathway in melanoma cells, including cells with low Apaf-1, bypasses an impediment to current cytotoxic therapy and provides new targets for future therapeutic trials involving chemoresistant tumors

Video assisted esophagectomy for esophageal cancer

Video assisted surgery for esophageal cancer is an advanced surgical technique. It is being adopted with a concept of minimally invasive surgery. Since there are several options of the operative procedure for thoracic esophageal cancer, there are several laparoscopic approaches. The first VATS esophagectomy through a right thoracoscopic approach and the first transhiatal esophagectomy were reported in early 1990's. Mediastinoscope-assisted esophagectomy is also reported as a substitute of the blunt dissection of the esophagus. Moreover, video assisted Ivor-Lewis esophagectomy by right thoracotomy with intrathoracic anastomosis has also been tried. Furthermore, laparoscopic gastric mobilization and gastroplasty is also widely accepted as a substitution for open laparotomy. This article serves to review the literature on laparoscopic approaches for esophageal cancer