Purpose:To study the effectiveness and toxicity of venorelbine combined with fluorouracil/leucovorin in patients with nasopharyngeal carcinoma(NPC) refractory to platinum based chemotherapy.Methods:The chemotherapy regimen consisted of bimonthly intravenous infusion of venorelbine 25 mg/m 2 plus 2-hour infusion of leucovorin 200 mg/m 2 followed by 48-hour infusion of 5-FU 3.0 g/m 2 using an ambulatory pump. Results:Among 30 patients entered into the study,1 patient achieved complete response,15 patients achieved partial response with an overall response rate of 53.3% and 10 had stable disease with clinical benefit rate of 86.7% respectively. 4 patients had disease progression. Median time to progression was 7 months(range:2.0-20.0 months) and the 1-year survival rate was 51%. The main toxicities were diarrhea and myelotoxicity.Conclusions:The results indicate that venorelbine combined with fluorouracil/leucovorin in patients with nasopharyngeal carcinoma refractory to platinum based chemotherapy has moderate activity but comparatively mild toxicity.

BACKGROUNDPaclitaxel plus cisplatin is an effective regimen in the treatment of non-small cell lung cancer (NSCLC), but it has severe adverse toxicities. The aim of this clinical trial is to evaluate the effect and safety of paclitaxel plus oxaliplatin compared with paclitaxel plus cisplatin in the treatment of advanced NSCLC.

METHODSFrom January, 2002 to October, 2004, 83 initially treated patients with advanced NSCLC were randomized into two groups: the trial group was treated with paclitaxel 175mg/m², and oxaliplatin 130mg/m² on day 1;and the control group was treated with paclitaxel 175mg/m² and cisplatin 80mg/m² on day 1. Both of them were repeated every 21 days and 2-6 cycles were given to patients. The evaluation of efficacy and safety was performed after chemotherapy regularly.

RESULTSAll patients were evaluable and received 2 cycles chemotherapy at least. The response rate of the trial group and control group was 34.1% (14/41) and 33.3% (14/42) respectively, median time to progression of them was 6.0 months and 5.5 months, median survival time was 10.7 months and 10.5 months, 1-year survival was 39.0% (16/41) and 40.5% (17/42) respectively. The following adverse effects of the two groups were different: the incidence rate of III+IV leukopenia was 4.9% and 28.6% in the trial group and the control group respectively, III+IV thrombocytopemia was 0 and 14.3%, III+IV nausea and vomiting was 7.3% and 26.2%. The difference of the incidence rate of III+IV nerve abnormality (9.8% and 9.5%), imparied renal function (0 and 7.1%), myalgia and anthralgia (0 and 2.4%) was insignificant.

CONCLUSIONSThe regimen of paclitaxel plus oxaliplatin have the similar efficacy and less adverse toxicities as compared to Paclitaxel plus Cisplatin in treatment of advanced NSCLC.

Primitive mammalian heart transforms from a single tube to a four-chambered muscular organ during a short developmental window. We found that knocking out global microRNA by deleting Dgcr8 microprocessor in Mesp1 cardiovascular progenitor cells lead to the formation of extremely dilated and enlarged heart due to defective cardiomyocyte (CM) differentiation. Transcriptome analysis revealed unusual upregulation of vascular gene expression in Dgcr8 cKO hearts. Single cell RNA sequencing study further confirmed the increase of angiogenesis genes in single Dgcr8 cKO CM. We also performed global microRNA profiling of E9.5 heart for the first time, and identified that miR-541 was transiently highly expressed in E9.5 hearts. Interestingly, introducing miR-541 back into microRNA-free CMs partially rescued their defects, downregulated angiogenesis genes and significantly upregulated cardiac genes. Moreover, miR-541 can target Ctgf and inhibit endothelial function. Our results suggest that microRNAs are required to suppress abnormal angiogenesis gene program to maintain CM differentiation.