BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic cancer.However,the excessive accumulation of poly ADP-ribose(PAR)...BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic cancer.However,the excessive accumulation of poly ADP-ribose(PAR)induces apoptosis-inducing factor(AIF)release from mitochondria and energy deprivation resulting in the caspase-independent death of cancer cells.AIM To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR accumulation.METHODS Two pancreatic cancer cell lines,AsPC-1 and CFPAC-1 were used for the study.Calcium influx and mitochondrial reactive oxygen species(ROS)were observed by fluorescence staining.Changes in enzyme levels,as well as PAR accumulation and energy metabolism,were measured using assay kits.AIF-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium administration.RESULTS Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer cells.Then,excess PAR accumulation,decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels,and energy deprivation were observed.In vitro and in vivo antitumor effects were confirmed to accompany elevated AIF levels.CONCLUSION This study visualized the potential anticancer effects of excessive PAR accumulation by sustained calcium supply on pancreatic cancer,however elucidating a clear mode of action remains a challenge,and it should be accompanied by further studies to assess its potential for clinical application.展开更多
目的:系统评价PARPi治疗转移性去势抵抗性前列腺癌(mCRPC)的有效性及安全性,以期为临床决策供循证医学证据。方法:依据纳入和排除标准,网络检索2015年1月~2023年6月PubMed、Web of Science、Embace、Clinicial.gov中有关PARPi治疗mCRPC...目的:系统评价PARPi治疗转移性去势抵抗性前列腺癌(mCRPC)的有效性及安全性,以期为临床决策供循证医学证据。方法:依据纳入和排除标准,网络检索2015年1月~2023年6月PubMed、Web of Science、Embace、Clinicial.gov中有关PARPi治疗mCRPC的随机对照试验文献,使用RevMan5.4及Stata17.0软件对数据进行Meta分析。结果:纳入7篇随机对照试验文献,共1888例患者。Meta分析结果表明,与非PARPi组比较,PARPi组(PARPi联合或不联合抗激素治疗)可提高mCRPC的放射学无进展生存期(HR=0.52,95%CI=0.34~0.78)和总生存期(HR=0.72,95%CI=0.60~0.86),差异均有统计学意义(P<0.05)。在安全性方面,PARPi组1~2级骨痛、背痛、贫血、中性粒细胞减少、恶心、呕吐、腹泻、乏力不良反应发生率明显高于非PARPi组,差异均有统计学意义(P<0.05);≥3级上述不良反应中与非PARPi组比较,PARPi组中只有恶心和贫血不良反应发生率较高,差异均有统计学意义(P<0.05),而骨痛、背痛、中性粒细胞减少、呕吐、腹泻、乏力两组间比较差异均无统计学意义(P>0.05)。结论:与非PARPi比较,PARPi联合或不联合抗激素治疗可提高mCRPC的放射学无进展生存期和总生存期,3级及以上不良反应发生率低,值得在临床上推广应用。展开更多
目的研究连豆清脉方对大鼠动脉粥样硬化(AS)形成的预防作用,以及对核因子-κB(NF-κB)炎症信号通路中Toll样受体-4(TLR-4)、NF-κB、多聚二磷酸腺苷核糖聚合酶-1(PARP-1)的影响。方法 50只大鼠随机分为基础组10只、空白预防组(空预组)1...目的研究连豆清脉方对大鼠动脉粥样硬化(AS)形成的预防作用,以及对核因子-κB(NF-κB)炎症信号通路中Toll样受体-4(TLR-4)、NF-κB、多聚二磷酸腺苷核糖聚合酶-1(PARP-1)的影响。方法 50只大鼠随机分为基础组10只、空白预防组(空预组)10只、模型组10只、辛伐他汀预防组(辛预组)10只、连豆清脉方预防组(连预组)10只;后4组大鼠通过高脂饲料喂养建立早期AS模型,同步采用连豆清脉方、辛伐他汀,分别对大鼠AS模型进行预防性干预。并对主动脉血管壁厚度、组织PARP-1阳性细胞表达率、外周血单个核细胞TLR-4 m RNA表达、血清NF-κB水平检测计算。结果 1)光镜下大鼠主动脉血管壁厚度存在差异(P<0.01),连预组和辛预组大鼠主动脉血管壁厚度明显薄于模型组(P<0.01),但是和空预组比较差异无统计学意义。免疫组化染色光镜下大鼠左心室组织PARP-1表达具有显著差异,PARP-1阳性细胞表达率存在统计学差异(P<0.01),连预组和辛预组PARP-1阳性细胞表达率明显低于模型组(P<0.01),但是明显高于空预组(P<0.01),具有统计学差异。2)大鼠外周血单个核细胞TLR-4 m RNA表达各组间存在统计学差异(P<0.01),连预组和辛预组TLR-4 m RNA表达明显低于模型组(P<0.01),且连预组低于空预组(P<0.05)。大鼠血清NF-κB水平各组间存在差异(P=0.001);其中连预组NF-κB水平明显低于模型组(P<0.01),但与空预组比较差异无统计学意义。结论连豆清脉方可预防高脂饮食导致的AS形成;其机制与抑制NF-κB炎症信号通路PARP-1、TLR-4、NF-κB等环节有关。展开更多
文摘BACKGROUND The biochemical phenomenon defined as poly adenosine diphosphate(ADP)-ribosylation(PARylation)is essential for the progression of pancreatic cancer.However,the excessive accumulation of poly ADP-ribose(PAR)induces apoptosis-inducing factor(AIF)release from mitochondria and energy deprivation resulting in the caspase-independent death of cancer cells.AIM To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR accumulation.METHODS Two pancreatic cancer cell lines,AsPC-1 and CFPAC-1 were used for the study.Calcium influx and mitochondrial reactive oxygen species(ROS)were observed by fluorescence staining.Changes in enzyme levels,as well as PAR accumulation and energy metabolism,were measured using assay kits.AIF-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium administration.RESULTS Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer cells.Then,excess PAR accumulation,decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels,and energy deprivation were observed.In vitro and in vivo antitumor effects were confirmed to accompany elevated AIF levels.CONCLUSION This study visualized the potential anticancer effects of excessive PAR accumulation by sustained calcium supply on pancreatic cancer,however elucidating a clear mode of action remains a challenge,and it should be accompanied by further studies to assess its potential for clinical application.
文摘目的:系统评价PARPi治疗转移性去势抵抗性前列腺癌(mCRPC)的有效性及安全性,以期为临床决策供循证医学证据。方法:依据纳入和排除标准,网络检索2015年1月~2023年6月PubMed、Web of Science、Embace、Clinicial.gov中有关PARPi治疗mCRPC的随机对照试验文献,使用RevMan5.4及Stata17.0软件对数据进行Meta分析。结果:纳入7篇随机对照试验文献,共1888例患者。Meta分析结果表明,与非PARPi组比较,PARPi组(PARPi联合或不联合抗激素治疗)可提高mCRPC的放射学无进展生存期(HR=0.52,95%CI=0.34~0.78)和总生存期(HR=0.72,95%CI=0.60~0.86),差异均有统计学意义(P<0.05)。在安全性方面,PARPi组1~2级骨痛、背痛、贫血、中性粒细胞减少、恶心、呕吐、腹泻、乏力不良反应发生率明显高于非PARPi组,差异均有统计学意义(P<0.05);≥3级上述不良反应中与非PARPi组比较,PARPi组中只有恶心和贫血不良反应发生率较高,差异均有统计学意义(P<0.05),而骨痛、背痛、中性粒细胞减少、呕吐、腹泻、乏力两组间比较差异均无统计学意义(P>0.05)。结论:与非PARPi比较,PARPi联合或不联合抗激素治疗可提高mCRPC的放射学无进展生存期和总生存期,3级及以上不良反应发生率低,值得在临床上推广应用。
文摘目的研究连豆清脉方对大鼠动脉粥样硬化(AS)形成的预防作用,以及对核因子-κB(NF-κB)炎症信号通路中Toll样受体-4(TLR-4)、NF-κB、多聚二磷酸腺苷核糖聚合酶-1(PARP-1)的影响。方法 50只大鼠随机分为基础组10只、空白预防组(空预组)10只、模型组10只、辛伐他汀预防组(辛预组)10只、连豆清脉方预防组(连预组)10只;后4组大鼠通过高脂饲料喂养建立早期AS模型,同步采用连豆清脉方、辛伐他汀,分别对大鼠AS模型进行预防性干预。并对主动脉血管壁厚度、组织PARP-1阳性细胞表达率、外周血单个核细胞TLR-4 m RNA表达、血清NF-κB水平检测计算。结果 1)光镜下大鼠主动脉血管壁厚度存在差异(P<0.01),连预组和辛预组大鼠主动脉血管壁厚度明显薄于模型组(P<0.01),但是和空预组比较差异无统计学意义。免疫组化染色光镜下大鼠左心室组织PARP-1表达具有显著差异,PARP-1阳性细胞表达率存在统计学差异(P<0.01),连预组和辛预组PARP-1阳性细胞表达率明显低于模型组(P<0.01),但是明显高于空预组(P<0.01),具有统计学差异。2)大鼠外周血单个核细胞TLR-4 m RNA表达各组间存在统计学差异(P<0.01),连预组和辛预组TLR-4 m RNA表达明显低于模型组(P<0.01),且连预组低于空预组(P<0.05)。大鼠血清NF-κB水平各组间存在差异(P=0.001);其中连预组NF-κB水平明显低于模型组(P<0.01),但与空预组比较差异无统计学意义。结论连豆清脉方可预防高脂饮食导致的AS形成;其机制与抑制NF-κB炎症信号通路PARP-1、TLR-4、NF-κB等环节有关。
