BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.Howev...BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.展开更多
肝细胞癌(hepatocellular carcinoma,HCC)是全球高发的恶性肿瘤。程序性死亡蛋白-1(programmed death protein-1,PD-1)/程序性死亡蛋白配体-1(programmed death protein ligand-1,PD-L1)抑制剂可通过阻断T细胞负调节信号,抑制肿瘤细胞...肝细胞癌(hepatocellular carcinoma,HCC)是全球高发的恶性肿瘤。程序性死亡蛋白-1(programmed death protein-1,PD-1)/程序性死亡蛋白配体-1(programmed death protein ligand-1,PD-L1)抑制剂可通过阻断T细胞负调节信号,抑制肿瘤细胞免疫逃逸途径,重新激活抗肿瘤免疫应答过程,成为晚期HCC治疗的新手段。然而,长期临床结果显示,采用PD-1/PD-L1抑制剂单药治疗晚期HCC的病人仍存在较高的复发率和转移率。免疫联合疗法是目前针对晚期HCC患者的新的治疗策略,其中PD-1/PD-L1抑制剂联合抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物在晚期HCC治疗中显示出了良好的疗效和安全性。PD-1/PD-L1抑制剂联合抗VEGF药物可通过参与癌症免疫循环途径抑制肝癌细胞的生长。该文就PD-1/PD-L1抑制剂联合抗VEGF药物在晚期HCC治疗中的临床研究作一综述。展开更多
OBJECTIVE To investigate the expression of urokinase-typeplasminogen (uPA), its inhibitor-1 (PAI-1) mRNA and its proteinin human gastric cancer and to find out the relationship among thetumor differentiation, angiogen...OBJECTIVE To investigate the expression of urokinase-typeplasminogen (uPA), its inhibitor-1 (PAI-1) mRNA and its proteinin human gastric cancer and to find out the relationship among thetumor differentiation, angiogenesis, and other clinical pathologicfactors.METHODS In situ hybridization (ISH) was used to get the uPA,PAI-1mRNA in 110 cases with human gastric cancer in 2-tissuemicroarray (TMA). Immunohistochemical staining (S-P method)for uPA, PAI-1 protein and CD34 were performed in the 110 casesin 2 TMA.RESULTS The expression of the uPA, PAI-1mRNA and theirprotein happened in the cytoplasm of gastric cancer cells wereinduced by the poor differentiation of the GC, and the expressionof uPA had an increasing trend while the expression of the PAI-1had a decreasing trend. The microvessel density (MVD) had apositive correlation with the clinical stages and the significantrelationship with the lymph node metastasis (P < 0.05). The MVDin uPA positive group was significantly higher than those inuPA negative group (P < 0.05). The expression of PAI-1 has nocorrelation neither with the clinical stages nor the lymph nodemetastasis.CONCLUSION The uPA play an important role in invasion andmetastasis of GC through promoting angiogenesis. Interdictingthe secretion and function of the uPA may allow the target therapyagainst the tumor invasion. As a new high-throughput technology,the tissue microarray is a valuable way to be used in clinicaltreatment.展开更多
Summary： This study aimed to evaluate the effects of Pinl inhibitor Juglone on proliferation, migration and the angiogenic ability of breast cancer cell line MCF7Adr. MCF7Adr ceils were cultured and sepa- rately trea...Summary： This study aimed to evaluate the effects of Pinl inhibitor Juglone on proliferation, migration and the angiogenic ability of breast cancer cell line MCF7Adr. MCF7Adr ceils were cultured and sepa- rately treated with Pinl inhibitor Juglone （treatment group） and DMEM without drug （control group）. The cell cycle was examined by flow cytometry. Cell migration was measured by wound-healing assay. Cyclin E protein content was detected by Western blotting. The angiogenesis factor vascular endothelial growth factor （VEGF） in cell media was determined by enzyme linked immunosorbent assay. The re- suits showed that the percentage of cells in GJM phase in treatment group was significantly higher than that in control group （25.5% vs. 10.1%, P〈0.05）, and that in G0/G1 phase and S stage in treatment group was significantly lower than that in control group （40.5% vs. 48.2%, and 33.7% vs. 41.7%, P〈0：05）. Cyclin E protein content in treatment group was significantly lower than that in control group （39.2±7.4 vs. 100±23.1, P〈0.05）. （A0-A24）/A0 value in treatment group was significantly lower than that in control group （23.9±3.8 vs. 100±14.4, P〈0.05）. VEGF-A, -B, and -C contents in cell media of treatment group were significantly lower than those in control group （P〈0.05）. It was suggested that Pinl inhibitor Juglone can effectively inhibit the proliferation, migration and the angiogenic ability of MCF7Adr cells, and can be used as an alternative drug therapy for breast cancer.展开更多
Epinephrine is often used for the treatment of patients with heart failure, low cardiac output and cardiac arrest. It can acutely improve hemodynamic parameters; however, it does not seem to improve longer term clinic...Epinephrine is often used for the treatment of patients with heart failure, low cardiac output and cardiac arrest. It can acutely improve hemodynamic parameters; however, it does not seem to improve longer term clinical outcomes. Therefore, we hypothesized that epinephrine may induce unfavorable changes in gene expression of cardiomyocyte. Thus, we investigated effects of epinephrine exposure on the mediation or modulation of gene expression of cultured cardiomyocytes at a genome-wide scale. Our investigation revealed that exposure of cardiomyocytes to epinephrine in an in vitro environment can up-regulate the expression ofangiopoietin-2 gene （~ 2.1 times）, and down-regulate the gene expression of neuregulin 1 （-3.7 times）, plasminogen activator inhibitor-1 （-2.4 times） and SPARC-related modular calcium-binding protein-2 （-4.5 times）. These changes suggest that epinephrine exposure may induce inhibition of angiogenesis-related gene expressions in cultured rat cardiomyocytes. The precise clinical significance of these changes in gene expression, which was induced by epinephrine exposure, warrants further experimental and clinical investigations.展开更多
目的探讨人基质金属蛋白酶组织抑制物-1(tissue inhibitor of metalloproteinase-1,TIMP-1)对肾脏器官衰老过程血管生成的影响。方法对3、12、24月龄人TIMP-1转基因小鼠和野生型小鼠肾组织石蜡切片行PASM染色,观察肾组织内微血管密度变...目的探讨人基质金属蛋白酶组织抑制物-1(tissue inhibitor of metalloproteinase-1,TIMP-1)对肾脏器官衰老过程血管生成的影响。方法对3、12、24月龄人TIMP-1转基因小鼠和野生型小鼠肾组织石蜡切片行PASM染色,观察肾组织内微血管密度变化;Western免疫印迹检测TIMP-1、TIMP-2、基质金属蛋白酶(matrix metalloproteinase,MMP)-2、MMP-9、血管内皮细胞生长因子(VEGF)、Ⅲ型和Ⅳ型胶原蛋白质表达;明胶酶谱和反向酶谱分别检测明胶酶和TIMP-1的活性。结果24月龄时与野生型小鼠相比,转基因小鼠肾小球和肾小管周围的微血管密度降低(P<0.05);TIMP-1、Ⅲ型和Ⅳ型胶原蛋白质表达增多(P<0.05),而MMP-2、MMP-9和VEGF的表达降低(P<0.05);明胶酶谱和反向酶谱结果显示,明胶酶的活性下调(P<0.05),而TIMP-1的活性则上调(P<0.05)。结论TIMP-1可能通过影响血管生成而促进肾脏器官衰老。展开更多
目的本研究拟探讨程序性死亡受体1(Programmed cell death 1,PD-1)抑制剂联合抗血管生成药物及化疗二线治疗晚期肺腺癌的临床对比分析。方法回顾性分析河北北方学院附属第一医院2017年1月1日—2020年12月31日期间收治的99例晚期肺腺癌...目的本研究拟探讨程序性死亡受体1(Programmed cell death 1,PD-1)抑制剂联合抗血管生成药物及化疗二线治疗晚期肺腺癌的临床对比分析。方法回顾性分析河北北方学院附属第一医院2017年1月1日—2020年12月31日期间收治的99例晚期肺腺癌患者临床资料,根据不同治疗方法将患者分为单纯化疗组(n=35)、化疗联合抗血管生成药物组(n=34)和化疗联合抗血管生成药物联合免疫治疗组(n=30)。比较三组患者治疗后的临床疗效及不良反应发生情况。结果三组的疾病控制率(Disease control rate,DCR)分别为48.6%、55.9%和80.0%,差异有统计学意义(P=0.028);客观缓解率(Objective response rate,ORR)分别为11.4%、8.8%和23.3%,差异无统计学意义(P=0.273)。三组中位无进展生存期(Progression-free survival,PFS)分别为2.4个月、4.3个月和6.2个月,差异有统计学意义(P<0.001)。治疗期间三组最常见的不良反应有白细胞减少、恶心呕吐、转氨酶升高、乏力等,大多为1~2级。单因素分析显示临床分期是影响PFS的独立因素。在考虑分组因素情况下,多因素Cox回归分析显示脑转移是PFS的独立影响因素。结论三组对比分析显示二线应用PD-1抑制剂联合抗血管生成药物及化疗治疗晚期肺腺癌的疗效确切且安全性良好。展开更多
基金Supported by Natural Science Foundation of Guangdong Province,No.2020A1515011539.
文摘BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.
文摘肝细胞癌(hepatocellular carcinoma,HCC)是全球高发的恶性肿瘤。程序性死亡蛋白-1(programmed death protein-1,PD-1)/程序性死亡蛋白配体-1(programmed death protein ligand-1,PD-L1)抑制剂可通过阻断T细胞负调节信号,抑制肿瘤细胞免疫逃逸途径,重新激活抗肿瘤免疫应答过程,成为晚期HCC治疗的新手段。然而,长期临床结果显示,采用PD-1/PD-L1抑制剂单药治疗晚期HCC的病人仍存在较高的复发率和转移率。免疫联合疗法是目前针对晚期HCC患者的新的治疗策略,其中PD-1/PD-L1抑制剂联合抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物在晚期HCC治疗中显示出了良好的疗效和安全性。PD-1/PD-L1抑制剂联合抗VEGF药物可通过参与癌症免疫循环途径抑制肝癌细胞的生长。该文就PD-1/PD-L1抑制剂联合抗VEGF药物在晚期HCC治疗中的临床研究作一综述。
基金supported by a grant from Educational Commission of Anhui Province,China(No.kj2007A029).
文摘OBJECTIVE To investigate the expression of urokinase-typeplasminogen (uPA), its inhibitor-1 (PAI-1) mRNA and its proteinin human gastric cancer and to find out the relationship among thetumor differentiation, angiogenesis, and other clinical pathologicfactors.METHODS In situ hybridization (ISH) was used to get the uPA,PAI-1mRNA in 110 cases with human gastric cancer in 2-tissuemicroarray (TMA). Immunohistochemical staining (S-P method)for uPA, PAI-1 protein and CD34 were performed in the 110 casesin 2 TMA.RESULTS The expression of the uPA, PAI-1mRNA and theirprotein happened in the cytoplasm of gastric cancer cells wereinduced by the poor differentiation of the GC, and the expressionof uPA had an increasing trend while the expression of the PAI-1had a decreasing trend. The microvessel density (MVD) had apositive correlation with the clinical stages and the significantrelationship with the lymph node metastasis (P < 0.05). The MVDin uPA positive group was significantly higher than those inuPA negative group (P < 0.05). The expression of PAI-1 has nocorrelation neither with the clinical stages nor the lymph nodemetastasis.CONCLUSION The uPA play an important role in invasion andmetastasis of GC through promoting angiogenesis. Interdictingthe secretion and function of the uPA may allow the target therapyagainst the tumor invasion. As a new high-throughput technology,the tissue microarray is a valuable way to be used in clinicaltreatment.
文摘Summary： This study aimed to evaluate the effects of Pinl inhibitor Juglone on proliferation, migration and the angiogenic ability of breast cancer cell line MCF7Adr. MCF7Adr ceils were cultured and sepa- rately treated with Pinl inhibitor Juglone （treatment group） and DMEM without drug （control group）. The cell cycle was examined by flow cytometry. Cell migration was measured by wound-healing assay. Cyclin E protein content was detected by Western blotting. The angiogenesis factor vascular endothelial growth factor （VEGF） in cell media was determined by enzyme linked immunosorbent assay. The re- suits showed that the percentage of cells in GJM phase in treatment group was significantly higher than that in control group （25.5% vs. 10.1%, P〈0.05）, and that in G0/G1 phase and S stage in treatment group was significantly lower than that in control group （40.5% vs. 48.2%, and 33.7% vs. 41.7%, P〈0：05）. Cyclin E protein content in treatment group was significantly lower than that in control group （39.2±7.4 vs. 100±23.1, P〈0.05）. （A0-A24）/A0 value in treatment group was significantly lower than that in control group （23.9±3.8 vs. 100±14.4, P〈0.05）. VEGF-A, -B, and -C contents in cell media of treatment group were significantly lower than those in control group （P〈0.05）. It was suggested that Pinl inhibitor Juglone can effectively inhibit the proliferation, migration and the angiogenic ability of MCF7Adr cells, and can be used as an alternative drug therapy for breast cancer.
基金supported by internal funding from the Department of Anesthesiology and Perioperative Medicine
文摘Epinephrine is often used for the treatment of patients with heart failure, low cardiac output and cardiac arrest. It can acutely improve hemodynamic parameters; however, it does not seem to improve longer term clinical outcomes. Therefore, we hypothesized that epinephrine may induce unfavorable changes in gene expression of cardiomyocyte. Thus, we investigated effects of epinephrine exposure on the mediation or modulation of gene expression of cultured cardiomyocytes at a genome-wide scale. Our investigation revealed that exposure of cardiomyocytes to epinephrine in an in vitro environment can up-regulate the expression ofangiopoietin-2 gene （~ 2.1 times）, and down-regulate the gene expression of neuregulin 1 （-3.7 times）, plasminogen activator inhibitor-1 （-2.4 times） and SPARC-related modular calcium-binding protein-2 （-4.5 times）. These changes suggest that epinephrine exposure may induce inhibition of angiogenesis-related gene expressions in cultured rat cardiomyocytes. The precise clinical significance of these changes in gene expression, which was induced by epinephrine exposure, warrants further experimental and clinical investigations.
文摘目的探讨人基质金属蛋白酶组织抑制物-1(tissue inhibitor of metalloproteinase-1,TIMP-1)对肾脏器官衰老过程血管生成的影响。方法对3、12、24月龄人TIMP-1转基因小鼠和野生型小鼠肾组织石蜡切片行PASM染色,观察肾组织内微血管密度变化;Western免疫印迹检测TIMP-1、TIMP-2、基质金属蛋白酶(matrix metalloproteinase,MMP)-2、MMP-9、血管内皮细胞生长因子(VEGF)、Ⅲ型和Ⅳ型胶原蛋白质表达;明胶酶谱和反向酶谱分别检测明胶酶和TIMP-1的活性。结果24月龄时与野生型小鼠相比,转基因小鼠肾小球和肾小管周围的微血管密度降低(P<0.05);TIMP-1、Ⅲ型和Ⅳ型胶原蛋白质表达增多(P<0.05),而MMP-2、MMP-9和VEGF的表达降低(P<0.05);明胶酶谱和反向酶谱结果显示,明胶酶的活性下调(P<0.05),而TIMP-1的活性则上调(P<0.05)。结论TIMP-1可能通过影响血管生成而促进肾脏器官衰老。
文摘目的本研究拟探讨程序性死亡受体1(Programmed cell death 1,PD-1)抑制剂联合抗血管生成药物及化疗二线治疗晚期肺腺癌的临床对比分析。方法回顾性分析河北北方学院附属第一医院2017年1月1日—2020年12月31日期间收治的99例晚期肺腺癌患者临床资料,根据不同治疗方法将患者分为单纯化疗组(n=35)、化疗联合抗血管生成药物组(n=34)和化疗联合抗血管生成药物联合免疫治疗组(n=30)。比较三组患者治疗后的临床疗效及不良反应发生情况。结果三组的疾病控制率(Disease control rate,DCR)分别为48.6%、55.9%和80.0%,差异有统计学意义(P=0.028);客观缓解率(Objective response rate,ORR)分别为11.4%、8.8%和23.3%,差异无统计学意义(P=0.273)。三组中位无进展生存期(Progression-free survival,PFS)分别为2.4个月、4.3个月和6.2个月,差异有统计学意义(P<0.001)。治疗期间三组最常见的不良反应有白细胞减少、恶心呕吐、转氨酶升高、乏力等,大多为1~2级。单因素分析显示临床分期是影响PFS的独立因素。在考虑分组因素情况下,多因素Cox回归分析显示脑转移是PFS的独立影响因素。结论三组对比分析显示二线应用PD-1抑制剂联合抗血管生成药物及化疗治疗晚期肺腺癌的疗效确切且安全性良好。
