AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in v...AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in vivo.METHODS YLG-1 is a novel photosensitizer extracted from spirulina. Its phototoxicity, cellular uptake and localization, as well as its effect on reactive oxygen species(ROS) production, apoptosis, and expression of apoptosis-associated proteins were detected in vitro. An in vivo imaging system(IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were exploited to evaluate the drug delivery pathway and pancreatic cancer growth in vivo.RESULTS YLG-1 was localized to the mitochondria, and the appropriate incubation time was 6 h. Under 650 nm light irradiation, YLG-1-PDT exerted a potent cytotoxic effect on pancreatic cancer cells in vitro, which could be abolished by the ROS scavenger N-acetyl-L-cysteine(NAC). The death mode caused by YLG-1-PDT was apoptosis, accompanied by upregulated Bax and cleaved Caspase-3 and decreased Bcl-2 expression. The results from the IVIS images suggested that the optimal administration route was intratumoral(IT) injection and that the best time to conduct YLG-1-PDT was 2 h post-IT injection. Consistent with the results in vitro, YLG-1-PDT showed great growth inhibition effects on pancreatic cancer cells in a mouse model.CONCLUSION YLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are associated with inducing ROS and promoting apoptosis.展开更多
In order to overcome the elementary heterogeneous nucleation whileoctahydro trisodium salt of fructose- 1, 6-diphosphate (FDPNa_3·8H_2O) is crystallized with ethanol precipitation at low temperature,a new crystal...In order to overcome the elementary heterogeneous nucleation whileoctahydro trisodium salt of fructose- 1, 6-diphosphate (FDPNa_3·8H_2O) is crystallized with ethanol precipitation at low temperature,a new crystallization method with alcohol precipitation combined withsalt precipitation has been presented. The ethanol-sodium ac- etatesystem for crystallization of salt of fructose-1, 6-diphosphate isbased on the mechanism of crystallization of FDPNA_3·8H_2O in theethanol-low temperature system. It is found that crystal size may becontrolled by regulating Temperature of pH value of solution in thecrystallization process, and the crystal yield increases to 95/100from 78/100 Which obtained in the ethanol-low temperature system.展开更多
目的:建立胶原包裹挂线法家兔动脉血栓形成模型,并进行综合评价。方法:53只家兔随机分为正常组、挂线组、胶原包裹挂线组、胶原包裹挂线加阿司匹林处理组(阿司匹林组)、胶原包裹挂线加氯吡格雷处理组(氯吡格雷组)、胶原包裹挂线加阿司...目的:建立胶原包裹挂线法家兔动脉血栓形成模型,并进行综合评价。方法:53只家兔随机分为正常组、挂线组、胶原包裹挂线组、胶原包裹挂线加阿司匹林处理组(阿司匹林组)、胶原包裹挂线加氯吡格雷处理组(氯吡格雷组)、胶原包裹挂线加阿司匹林和氯吡格雷处理(阿司匹林和氯吡格雷组)6组,分别进行相应的处理,观察在不同情况下组织病理学改变。用ELISA法(enzym link immunology assay,ELISA)检测1,6-二磷酸果糖二钠盐(D-fructose-1,6-diphosphate trisodium salt octahydrate,FDP)、D-二聚体(D-dimer)和组织因子(tissue factor,TF)。结果:组织病理学检查发现胶原包裹挂线组较挂线组血栓形成明显,血管内弹力膜损伤严重,用阿司匹林及氯吡格雷干预后,动脉血栓有大部分软化、溶解、吸收;胶原包裹挂线组与正常组、挂线组相比较,血栓湿重、干重、D-dimer、FDP及TF明显增高(P<0.01);3组药物干预后血栓湿重、干重及D-dimer、FDP和TF血浆水平均显著降低(P<0.01);与阿司匹林组、氯吡格雷组相比较,阿司匹林加氯吡格雷组能显著降低血栓湿重、干重、D-dimer和FDP水平(P<0.01);与阿司匹林组比较,阿司匹林加氯吡格雷组TF水平明显降低(P<0.05)。结论:胶原包裹挂线法动脉血栓模型明显优于单挂线法,且直观可靠、重复性好、成功率高,可反映抗栓药的药效,是一个理想的研究动脉血栓形成的动物模型。展开更多
基金Supported by National Natural Science Foundation of China,No.81472844
文摘AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in vivo.METHODS YLG-1 is a novel photosensitizer extracted from spirulina. Its phototoxicity, cellular uptake and localization, as well as its effect on reactive oxygen species(ROS) production, apoptosis, and expression of apoptosis-associated proteins were detected in vitro. An in vivo imaging system(IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were exploited to evaluate the drug delivery pathway and pancreatic cancer growth in vivo.RESULTS YLG-1 was localized to the mitochondria, and the appropriate incubation time was 6 h. Under 650 nm light irradiation, YLG-1-PDT exerted a potent cytotoxic effect on pancreatic cancer cells in vitro, which could be abolished by the ROS scavenger N-acetyl-L-cysteine(NAC). The death mode caused by YLG-1-PDT was apoptosis, accompanied by upregulated Bax and cleaved Caspase-3 and decreased Bcl-2 expression. The results from the IVIS images suggested that the optimal administration route was intratumoral(IT) injection and that the best time to conduct YLG-1-PDT was 2 h post-IT injection. Consistent with the results in vitro, YLG-1-PDT showed great growth inhibition effects on pancreatic cancer cells in a mouse model.CONCLUSION YLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are associated with inducing ROS and promoting apoptosis.
基金Supported by the National Eighth Five-Year Key Project of China.
文摘In order to overcome the elementary heterogeneous nucleation whileoctahydro trisodium salt of fructose- 1, 6-diphosphate (FDPNa_3·8H_2O) is crystallized with ethanol precipitation at low temperature,a new crystallization method with alcohol precipitation combined withsalt precipitation has been presented. The ethanol-sodium ac- etatesystem for crystallization of salt of fructose-1, 6-diphosphate isbased on the mechanism of crystallization of FDPNA_3·8H_2O in theethanol-low temperature system. It is found that crystal size may becontrolled by regulating Temperature of pH value of solution in thecrystallization process, and the crystal yield increases to 95/100from 78/100 Which obtained in the ethanol-low temperature system.
文摘目的:建立胶原包裹挂线法家兔动脉血栓形成模型,并进行综合评价。方法:53只家兔随机分为正常组、挂线组、胶原包裹挂线组、胶原包裹挂线加阿司匹林处理组(阿司匹林组)、胶原包裹挂线加氯吡格雷处理组(氯吡格雷组)、胶原包裹挂线加阿司匹林和氯吡格雷处理(阿司匹林和氯吡格雷组)6组,分别进行相应的处理,观察在不同情况下组织病理学改变。用ELISA法(enzym link immunology assay,ELISA)检测1,6-二磷酸果糖二钠盐(D-fructose-1,6-diphosphate trisodium salt octahydrate,FDP)、D-二聚体(D-dimer)和组织因子(tissue factor,TF)。结果:组织病理学检查发现胶原包裹挂线组较挂线组血栓形成明显,血管内弹力膜损伤严重,用阿司匹林及氯吡格雷干预后,动脉血栓有大部分软化、溶解、吸收;胶原包裹挂线组与正常组、挂线组相比较,血栓湿重、干重、D-dimer、FDP及TF明显增高(P<0.01);3组药物干预后血栓湿重、干重及D-dimer、FDP和TF血浆水平均显著降低(P<0.01);与阿司匹林组、氯吡格雷组相比较,阿司匹林加氯吡格雷组能显著降低血栓湿重、干重、D-dimer和FDP水平(P<0.01);与阿司匹林组比较,阿司匹林加氯吡格雷组TF水平明显降低(P<0.05)。结论:胶原包裹挂线法动脉血栓模型明显优于单挂线法,且直观可靠、重复性好、成功率高,可反映抗栓药的药效,是一个理想的研究动脉血栓形成的动物模型。