Objective Colorectal cancer(CRC) is a heterogeneous disease in which both epigenetic alterations and gene mutations transform normal cells into cancer cells. Apart from a variety of standard treatments, there are few ...Objective Colorectal cancer(CRC) is a heterogeneous disease in which both epigenetic alterations and gene mutations transform normal cells into cancer cells. Apart from a variety of standard treatments, there are few options available to improve a CRC patient's overall survival(OS) and quality of a life. The objective of the present retrospective study was to analyze the response and toxicity associated with apatinib in patients with metastatic CRC(m CRC).Method Data on the use of apatinib as salvage therapy were collected from patients diagnosed with m CRC, Eastern Cooperative Oncology Group(ECOG) performance status ≤ 3, from the Luhe Hospital. A total of 17 patients with stage IV unresectable m CRC, who received at least one cycle of apatinib, between October 2015 and February 2017, were involved in this study. Our primary endpoints were the overall response rate(ORR) and disease control rate(DCR), and the secondary objectives were progression-free survival(PFS), OS and safety.Result Seventeen patients with a median age of 62 years(34–83 years) were enrolled. Twelve patients were male, and the location of the primary tumor was in the colon and the rectum in 9 and 8 patients, respectively. Liver metastasis was observed in 9 patients and lung metastasis in 5. The ECOG performance status was 0 to 2 in 13 patients. The ORR at the first evaluation was 17.6 %(3/17). The DCR was 82.4%(14/17). The median PFS was 3.0 months(95% confidence interval(CI): 1.924–4.076 months) and the median OS was 5.4 months(95% CI: 3.383–7.417 months). Grade 1–2 adverse events included hypertension(52.9%), fatigue(64.7%), anorexia(29.4%), hoarseness(23.5%), proteinuria(23.5%), and development of rashes(17.6%). Grade 3 adverse events included thrombocytopenia(5.9%) and proteinuria(5.9%). There were no Grade 4 adverse events in our analysis.Conclusions Apatinib was found to be both safe and effective in the treatment of advanced m CRC, and its associated toxicities were acceptable and manageable. However, further studies are required to validate these findings.展开更多
Background:Rotavirus(RV)is a major pathogen that causes severe gastroenteritis in infants and young animals.Endoplasmic reticulum(ER)stress and subsequent apoptosis play pivotal role in virus infection.However,the pro...Background:Rotavirus(RV)is a major pathogen that causes severe gastroenteritis in infants and young animals.Endoplasmic reticulum(ER)stress and subsequent apoptosis play pivotal role in virus infection.However,the protective mechanisms of intestinal damage caused by RV are poorly defined,especially the molecular pathways related to enterocytes apoptosis.Thus,the aim of this study was to investigate the protective effect and mechanism of sodium butyrate(SB)on RV-induced apoptosis of IPEC-J2 cells.Results:The RV infection led to significant cell apoptosis,increased the expression levels of ER stress(ERS)markers,phosphorylated protein kinase-like ER kinase(PERK),eukaryotic initiation factor 2 alpha(eIF2α),caspase9,and caspase3.Blocking PERK pathway using specific inhibitor GSK subsequently reversed RV-induced cell apoptosis.The SB treatment significantly inhibited RV-induced ERS by decreasing the expression of glucose regulated protein 78(GRP78),PERK,and eIF2α.In addition,SB treatment restrained the ERS-mediated apoptotic pathway,as indicated by downregulation of C/EBP homologous protein(CHOP)mRNA level,as well as decreased cleaved caspase9 and caspase3 protein levels.Furthermore,siRNA-induced GPR109a knockdown significantly suppressed the protective effect of SB on RV-induced cell apoptosis.Conclusions:These results indicate that SB exerts protective effects against RV-induced cell apoptosis through inhibiting ERS mediated apoptosis by regulating PERK-eIF2αsignaling pathway via GPR109a,which provide new ideas for the prevention and control of RV.展开更多
Various types of gene rearrangements have been discovered in the mitogenoes of the frog family Ranidae. In this study, we determined the complete mitogenome sequence of three Rana frogs. By combining the available mit...Various types of gene rearrangements have been discovered in the mitogenoes of the frog family Ranidae. In this study, we determined the complete mitogenome sequence of three Rana frogs. By combining the available mitogenomic data sets from GenBank, we evaluated the phylogenetic relationships of Ranidae at the mitogenome level and analyzed mitogenome rearrangement cases within Ranidae. The three frogs shared an identical mitogenome organization that was extremely similar to the typical Neobatrachian-type arrangement. Except for the genus Babina, the monophyly of each genus was well supported. The genus Amnirana occupied the most basal position among the Ranidae. The [Lithobates + Rana] was the closest sister group of Odorrana. The diversity of mitochondrial gene arrangements in ranid species was unexpectedly high, with 47 mitogenomes from 40 ranids being classified into 10 different gene rearrangement types. Some taxa owned their unique gene rearrangement characteristics, which had significant implication for their phylogeny analysis. All rearrangement events discovered in the Ranidae mitogenomes can be explained by the duplication and random loss model.展开更多
文摘Objective Colorectal cancer(CRC) is a heterogeneous disease in which both epigenetic alterations and gene mutations transform normal cells into cancer cells. Apart from a variety of standard treatments, there are few options available to improve a CRC patient's overall survival(OS) and quality of a life. The objective of the present retrospective study was to analyze the response and toxicity associated with apatinib in patients with metastatic CRC(m CRC).Method Data on the use of apatinib as salvage therapy were collected from patients diagnosed with m CRC, Eastern Cooperative Oncology Group(ECOG) performance status ≤ 3, from the Luhe Hospital. A total of 17 patients with stage IV unresectable m CRC, who received at least one cycle of apatinib, between October 2015 and February 2017, were involved in this study. Our primary endpoints were the overall response rate(ORR) and disease control rate(DCR), and the secondary objectives were progression-free survival(PFS), OS and safety.Result Seventeen patients with a median age of 62 years(34–83 years) were enrolled. Twelve patients were male, and the location of the primary tumor was in the colon and the rectum in 9 and 8 patients, respectively. Liver metastasis was observed in 9 patients and lung metastasis in 5. The ECOG performance status was 0 to 2 in 13 patients. The ORR at the first evaluation was 17.6 %(3/17). The DCR was 82.4%(14/17). The median PFS was 3.0 months(95% confidence interval(CI): 1.924–4.076 months) and the median OS was 5.4 months(95% CI: 3.383–7.417 months). Grade 1–2 adverse events included hypertension(52.9%), fatigue(64.7%), anorexia(29.4%), hoarseness(23.5%), proteinuria(23.5%), and development of rashes(17.6%). Grade 3 adverse events included thrombocytopenia(5.9%) and proteinuria(5.9%). There were no Grade 4 adverse events in our analysis.Conclusions Apatinib was found to be both safe and effective in the treatment of advanced m CRC, and its associated toxicities were acceptable and manageable. However, further studies are required to validate these findings.
基金supported by Key Program for the National Key Research&Development Program of China(2018YFD0501004)the National Natural Science Foundation of China(31730091)the Sichuan Science and Technology Support Program(2020YFN0147).
文摘Background:Rotavirus(RV)is a major pathogen that causes severe gastroenteritis in infants and young animals.Endoplasmic reticulum(ER)stress and subsequent apoptosis play pivotal role in virus infection.However,the protective mechanisms of intestinal damage caused by RV are poorly defined,especially the molecular pathways related to enterocytes apoptosis.Thus,the aim of this study was to investigate the protective effect and mechanism of sodium butyrate(SB)on RV-induced apoptosis of IPEC-J2 cells.Results:The RV infection led to significant cell apoptosis,increased the expression levels of ER stress(ERS)markers,phosphorylated protein kinase-like ER kinase(PERK),eukaryotic initiation factor 2 alpha(eIF2α),caspase9,and caspase3.Blocking PERK pathway using specific inhibitor GSK subsequently reversed RV-induced cell apoptosis.The SB treatment significantly inhibited RV-induced ERS by decreasing the expression of glucose regulated protein 78(GRP78),PERK,and eIF2α.In addition,SB treatment restrained the ERS-mediated apoptotic pathway,as indicated by downregulation of C/EBP homologous protein(CHOP)mRNA level,as well as decreased cleaved caspase9 and caspase3 protein levels.Furthermore,siRNA-induced GPR109a knockdown significantly suppressed the protective effect of SB on RV-induced cell apoptosis.Conclusions:These results indicate that SB exerts protective effects against RV-induced cell apoptosis through inhibiting ERS mediated apoptosis by regulating PERK-eIF2αsignaling pathway via GPR109a,which provide new ideas for the prevention and control of RV.
基金supported by the Innovative Research Team in University of Sichuan Bureau of Education (No.14TD0002)the Scientific Research Fund of Sichuan Provincial Education Department (No.11ZA077)
文摘Various types of gene rearrangements have been discovered in the mitogenoes of the frog family Ranidae. In this study, we determined the complete mitogenome sequence of three Rana frogs. By combining the available mitogenomic data sets from GenBank, we evaluated the phylogenetic relationships of Ranidae at the mitogenome level and analyzed mitogenome rearrangement cases within Ranidae. The three frogs shared an identical mitogenome organization that was extremely similar to the typical Neobatrachian-type arrangement. Except for the genus Babina, the monophyly of each genus was well supported. The genus Amnirana occupied the most basal position among the Ranidae. The [Lithobates + Rana] was the closest sister group of Odorrana. The diversity of mitochondrial gene arrangements in ranid species was unexpectedly high, with 47 mitogenomes from 40 ranids being classified into 10 different gene rearrangement types. Some taxa owned their unique gene rearrangement characteristics, which had significant implication for their phylogeny analysis. All rearrangement events discovered in the Ranidae mitogenomes can be explained by the duplication and random loss model.