Interestingly, the CaM knockdown primarily JNJ-26481585 order activated genes that are preferentially expressed in caudal brain regions, whereas it repressed genes in rostral brain regions. Consistent with this correlation, quantifications of protein levels in adult mice uncovered an inverse relationship of CaM
and synaptotagmin-2 levels in mouse forebrain, brain stem, and spinal cord. Finally, we employed molecular replacement experiments using a knockdown rescue approach to show that Ca(2+) binding to the C-lobe but not the N-lobe of CaM is required for suppression of synaptotagmin-2 expression in cortical neurons. Our data describe a previously unknown, Ca(2+)/CaM-dependent regulatory pathway that controls the expression of synaptic proteins in the rostral-caudal neuraxis.”
“Background: In patients with advanced non-small cell lung cancer (NSCLC) aged more than 70 years, the benefit-to-risk ratio of doublet chemotherapy vs single-agent is not established.\n\nMethods: We performed a meta-analysis (MA), with a PubMed query using keywords simultaneously (Randomized controlled trial,
Aged, Anti-neoplastic combined chemotherapy protocols/therapeutic APR-246 molecular weight use, Carcinoma, Non-small cell lung/drug therapy). Abstracts from ASCO, WCLC, and ESMO proceedings were reviewed. Articles were also obtained by cross-checking references. Third-generation agents (gemcitabine, vinorelbine, paclitaxel, docetaxel) in combination with or without platinum were included. The efficacy outcomes were Overall Response Rate (ORR) and 1-Year Overall Survival (OS). We used EasyMA software and a random-effect model in case of heterogeneity.\n\nResults: This MA comprised 10 studies including 2605 patients (mean age 74; 1866 men and 620 women; 654 stage IIIB and 1677 stage W; 839 squamous cell cancers, 968 adenocarcinomas, 521 other pathological types). One-year OS (including the last trial by Abe) did not significantly improve
for doublets compared with single-agents (HR 0.92; 95% confidence Interval or CI: 0.82-1.03) whereas it improved significantly before inclusion of this last study, when the study by Quoix et al., the most favorable to doublets, was included. However, doublet chemotherapy significantly improved ORR Selleck GSK2245840 after inclusion of Abe study (TAR 1.51; 1.22-1.86; p<0.001). OS was not significantly improved, neither by doublets including platinum (HR 0.90, 0.70-1.16), nor by those without platinum (HR 0.94, 0.84-1.07). ORR, but not OS, was improved by doublets including a taxane (docetaxel and paclitaxel) (HR 1.72; 1.28-2.33) except for paclitaxel with a significant OS and ORR benefit. All-grade neutropenia thrombocytopenia and anemia were significantly more frequent with doublets than with single-agents (HR 1.26, 1.15-1.39; 1.75, 1.11-2.77 and 1.33, 1.17-1.52 respectively).