Gefitinib is a new molecular targeted antitumor drug and recently used widely in lung cancer treatment in China. But when used for an average ten-month period, patient show resistance to gefitinib and this resistance ...Gefitinib is a new molecular targeted antitumor drug and recently used widely in lung cancer treatment in China. But when used for an average ten-month period, patient show resistance to gefitinib and this resistance limit its con- tinued use. Low-molecular-weight heparin （LMWH） has potent inhibitory action on experimental metastasis. In present study, we are trying to find whether LMWH combined with gefitinib could sensitize its antitumor effects and potential relieve its resistance phenomenon in fifo and in vitro. Enoxaparin （one kind of LMWH） combined with gefitinib inhibited the growth of xenografl A549-1uc-C5 tumors in nude mice and reduced lung colony formation compared with gefitinib alone.展开更多
Objective: To investigate the inhibitory effects of LMWH suppressing the expression of Livin and inducing the apoptosis of the osteosarcoma cells. Methods: Osteosarcoma cells line MG-63 was cultured in vitro. MTT assa...Objective: To investigate the inhibitory effects of LMWH suppressing the expression of Livin and inducing the apoptosis of the osteosarcoma cells. Methods: Osteosarcoma cells line MG-63 was cultured in vitro. MTT assay and flow cytometry were used to study the effect of LMWH with different concentration suppressed the prolifetation and induced apop- tosis in osteosarcoma cells line MG-63. The expression of Livin of osteosarcoma cells line MG-63 was analysed by the im- munohistochemistrical method and PT-PCR. Results: Low molecular weight heparin could inhibit the growth of osteosarcoma cell line MG-63. With the LMWH's increasing, the apoptosis rate was increased significantly. Immunohistochemistrical method and PT-PCR showed that the expression of Livin of osteosarcoma cells line MG-63 declined obviously than that before medi- cation. Conclusion: LMWH has very strong anti-tumor effect in vitro. The possible mechanisms of LMWH anti-tumor effect are associate with the effect of suppressing the expression of Livin and inducing cell apoptosis.展开更多
急性呼吸窘迫综合征(ARDS)是新冠病毒肺炎(COVID-19)较为常见的致命性并发症,而凝血/纤溶系统功能的紊乱是COVID-19患者的一个重要特征,常提示其预后不良,抗凝治疗可能是新冠病毒肺炎导致ARDS患者治疗的一个新靶点。低分子肝素(LMWH)具...急性呼吸窘迫综合征(ARDS)是新冠病毒肺炎(COVID-19)较为常见的致命性并发症,而凝血/纤溶系统功能的紊乱是COVID-19患者的一个重要特征,常提示其预后不良,抗凝治疗可能是新冠病毒肺炎导致ARDS患者治疗的一个新靶点。低分子肝素(LMWH)具有抗凝、抗炎、抗氧化等多重药理作用,但应用低分子肝素进行抗凝治疗的相关临床研究均局限于小样本、单中心,尚缺乏大规模、多中心的临床研究,且研究结局不甚统一,尚无准确的结论,因此低分子肝素对新冠肺炎所致ARDS的抗凝治疗作用有待进一步研究。本文从新冠病毒肺炎致ARDS的病理生理学机制及临床特点等方面入手,探寻低分子肝素对该类患者的抗凝治疗策略及存在的问题。Acute respiratory distress syndrome (ARDS) is a relatively common fatal complication of coronavirus pneumonia (COVID-19), and dysfunction of coagulation/fibrinolysis system is an important feature of COVID-19 patients, which often indicates poor prognosis. Anticoagulation therapy may be a new target for the treatment of ARDS patients caused by COVID-19. Low molecular weight heparin (LMWH) has multiple pharmacological effects such as anticoagulation, anti-inflammatory, antioxidant, etc. However, clinical studies related to the application of LMWH in anticoagulation therapy are limited to small samples and single centers, and there is still a lack of large-scale and multi-center clinical studies with inconsistent outcomes and no accurate conclusions. Therefore, the anticoagulant effect of low molecular weight heparin on ARDS induced by COVID-19 needs further study. In this paper, the pathophysiological mechanism and clinical characteristics of ARDS caused by novel coronavirus pneumonia were discussed to explore the anticoagulant treatment strategy and existing problems of low molecular weight heparin in these patients.展开更多
Chemotherapy agents have been widely used for cancer treatment,while the insolubility,instability and toxicity seriously restrict their efficacy.Thus,prodrug strategy was devised.Since some prodrugs are still with poo...Chemotherapy agents have been widely used for cancer treatment,while the insolubility,instability and toxicity seriously restrict their efficacy.Thus,prodrug strategy was devised.Since some prodrugs are still with poor solubility or stability,a synergy strategy is needed to enhance their efficacy.Gemcitabine(GEM)is a prescribed anticancer drug,however,the rapid clearance,growing resistance and serious side effects limit its clinical efficacy.Conjugating GEM with D-a-tocopherol succinate(TOS)is an effective solution,while the GEM-TOS(GT)is unstable in aqueous solution.D-a-Tocopherol polyethylene glycol succinate(TPGS)has been used to enhance the stability,but GT stabilized by TPGS(GTT)has limited effect on tumor metastases.Tumor metastases lead to high mortality in patients suffering from cancers.In order to further achieve antimetastatic effect,an amphiphilic polymer(LT)was synthesized by connecting low-molecular-weight heparin(LMWH)with TOS,and eventually obtained desired selfdelivery micellar NPs(GLT)by co-assembly GT with LT.The GLT not only possessed excellent stability,but also inhibited the metastases by acting on different phases of the metastatic cascade.The hydrophobic TOS inhibited the secretion of matrix metalloproteinase-9(MMP-9),the hydrophilic LMWH inhibited the interaction between tumor cells and platelets.As a result,GLT reduced tumor cells entering the blood and implanting at the distant organs,leading to a much more excellent inhibitory effect on the lung metastasis than GEM and GTT.展开更多
文摘Gefitinib is a new molecular targeted antitumor drug and recently used widely in lung cancer treatment in China. But when used for an average ten-month period, patient show resistance to gefitinib and this resistance limit its con- tinued use. Low-molecular-weight heparin （LMWH） has potent inhibitory action on experimental metastasis. In present study, we are trying to find whether LMWH combined with gefitinib could sensitize its antitumor effects and potential relieve its resistance phenomenon in fifo and in vitro. Enoxaparin （one kind of LMWH） combined with gefitinib inhibited the growth of xenografl A549-1uc-C5 tumors in nude mice and reduced lung colony formation compared with gefitinib alone.
文摘Objective: To investigate the inhibitory effects of LMWH suppressing the expression of Livin and inducing the apoptosis of the osteosarcoma cells. Methods: Osteosarcoma cells line MG-63 was cultured in vitro. MTT assay and flow cytometry were used to study the effect of LMWH with different concentration suppressed the prolifetation and induced apop- tosis in osteosarcoma cells line MG-63. The expression of Livin of osteosarcoma cells line MG-63 was analysed by the im- munohistochemistrical method and PT-PCR. Results: Low molecular weight heparin could inhibit the growth of osteosarcoma cell line MG-63. With the LMWH's increasing, the apoptosis rate was increased significantly. Immunohistochemistrical method and PT-PCR showed that the expression of Livin of osteosarcoma cells line MG-63 declined obviously than that before medi- cation. Conclusion: LMWH has very strong anti-tumor effect in vitro. The possible mechanisms of LMWH anti-tumor effect are associate with the effect of suppressing the expression of Livin and inducing cell apoptosis.
文摘急性呼吸窘迫综合征(ARDS)是新冠病毒肺炎(COVID-19)较为常见的致命性并发症,而凝血/纤溶系统功能的紊乱是COVID-19患者的一个重要特征,常提示其预后不良,抗凝治疗可能是新冠病毒肺炎导致ARDS患者治疗的一个新靶点。低分子肝素(LMWH)具有抗凝、抗炎、抗氧化等多重药理作用,但应用低分子肝素进行抗凝治疗的相关临床研究均局限于小样本、单中心,尚缺乏大规模、多中心的临床研究,且研究结局不甚统一,尚无准确的结论,因此低分子肝素对新冠肺炎所致ARDS的抗凝治疗作用有待进一步研究。本文从新冠病毒肺炎致ARDS的病理生理学机制及临床特点等方面入手,探寻低分子肝素对该类患者的抗凝治疗策略及存在的问题。Acute respiratory distress syndrome (ARDS) is a relatively common fatal complication of coronavirus pneumonia (COVID-19), and dysfunction of coagulation/fibrinolysis system is an important feature of COVID-19 patients, which often indicates poor prognosis. Anticoagulation therapy may be a new target for the treatment of ARDS patients caused by COVID-19. Low molecular weight heparin (LMWH) has multiple pharmacological effects such as anticoagulation, anti-inflammatory, antioxidant, etc. However, clinical studies related to the application of LMWH in anticoagulation therapy are limited to small samples and single centers, and there is still a lack of large-scale and multi-center clinical studies with inconsistent outcomes and no accurate conclusions. Therefore, the anticoagulant effect of low molecular weight heparin on ARDS induced by COVID-19 needs further study. In this paper, the pathophysiological mechanism and clinical characteristics of ARDS caused by novel coronavirus pneumonia were discussed to explore the anticoagulant treatment strategy and existing problems of low molecular weight heparin in these patients.
基金supported by Major Projects of the National Natural Science Foundation of China(81690261)Sichuan Science and Technology Program(2018RZ0136,China)
文摘Chemotherapy agents have been widely used for cancer treatment,while the insolubility,instability and toxicity seriously restrict their efficacy.Thus,prodrug strategy was devised.Since some prodrugs are still with poor solubility or stability,a synergy strategy is needed to enhance their efficacy.Gemcitabine(GEM)is a prescribed anticancer drug,however,the rapid clearance,growing resistance and serious side effects limit its clinical efficacy.Conjugating GEM with D-a-tocopherol succinate(TOS)is an effective solution,while the GEM-TOS(GT)is unstable in aqueous solution.D-a-Tocopherol polyethylene glycol succinate(TPGS)has been used to enhance the stability,but GT stabilized by TPGS(GTT)has limited effect on tumor metastases.Tumor metastases lead to high mortality in patients suffering from cancers.In order to further achieve antimetastatic effect,an amphiphilic polymer(LT)was synthesized by connecting low-molecular-weight heparin(LMWH)with TOS,and eventually obtained desired selfdelivery micellar NPs(GLT)by co-assembly GT with LT.The GLT not only possessed excellent stability,but also inhibited the metastases by acting on different phases of the metastatic cascade.The hydrophobic TOS inhibited the secretion of matrix metalloproteinase-9(MMP-9),the hydrophilic LMWH inhibited the interaction between tumor cells and platelets.As a result,GLT reduced tumor cells entering the blood and implanting at the distant organs,leading to a much more excellent inhibitory effect on the lung metastasis than GEM and GTT.
