Objective:To investigate the effect of bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer on tumor markers, angiogenesis molecules and invasive growth molecules....Objective:To investigate the effect of bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer on tumor markers, angiogenesis molecules and invasive growth molecules.Methods:A total of 68 patients who were diagnosed with non-small cell lung cancer complicated by pleural effusion in the Affiliated T.C.M Hospital of Southwest Medical University between June 2013 and August 2016 were selected and randomly divided into two groups, the combined group received bevacizumab combined with carboplatin chemotherapy, and the carboplatin group received carboplatin chemotherapy. Before treatment as well as 3 cycles and 6 cycles after treatment, the contents of tumor markers, angiogenesis molecules and invasive growth molecules in pleural effusion were examined.Results:3 cycles and 6 cycles after treatment, CEA, SCCAg, CYFRA21-1, sHLA-G, VEGF, VEGFR, PTN, MMP7 and MMP10 contents in pleural effusion of both groups of patients were significantly lower than those before treatment while TIMP1 and TIMP2 contents were significantly higher than those before treatment, and CEA, SCCAg, CYFRA21-1, sHLA-G, VEGF, VEGFR, PTN, MMP7 and MMP10 contents in pleural effusion of combined group were significantly lower than those of carboplatin group while TIMP1 and TIMP2 contents were significantly higher than those of carboplatin group.Conclusion:Bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer can effectively kill cancer cells, and inhibit angiogenesis and cell invasion.展开更多
Objective:To evaluate the diagnostic value of endostatin(ES),vascular endothelial growth factor (VEGF) and careinoembryonie antigen(CEA) in both serum and pleural effusion of lung cancer patients.Methods:Levels of ES,...Objective:To evaluate the diagnostic value of endostatin(ES),vascular endothelial growth factor (VEGF) and careinoembryonie antigen(CEA) in both serum and pleural effusion of lung cancer patients.Methods:Levels of ES,VEGF and CEA in 52 malignant pleural effusion due to lung cancer and 50 patients with non-malignant disease were measured by using sandwich enzymelinked immunosorbent assay and microparticle enzyme immunoassay.Results:The ES.VEGF and CEA levels in pleural effusion and serum,and their ratio(F/S) were higher in lung cancer group than that in benign group,and the differences were statistically significant(P【0.05).The diagnostic efficiency of ES+VEGF for lung cancer was superior to either single detection.The diagnostic efficiency of ES+VEGK+CEA was superior to either ES+VEGF or ES+CEA.Conclusions: The results suggest that ES,VEGF and CEA might be useful in the differentiation between benign and malignant pleural effusion due to lung cancer.In comparison with either single determination of concentration in serum or pleural fluid,the couiljined detection of two or three markers is of important clinical significance in the diagnosis of lung cancer.展开更多
Objective To compare intra-pleural injection efficacy and safety between Endostar and bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth fa...Objective To compare intra-pleural injection efficacy and safety between Endostar and bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth factor receptor(EGFR)-/anaplastic lymphoma kinase(ALK)-lung adenocarcinoma. Methods Sixty-four pCVatients with EGFR-/ALK-lung adenocarcinoma with malignant pleural effusion(MPE) were admitted to the authors' hospital between January 2016 and June 2017. Patients were randomly divided into two groups: Endostar combined with pemetrexed/cisplatin(Endostar group); and bevacizumab plus pemetrexed/cisplatin(Bevacizumab group). They underwent thoracic puncture and catheterization, and MPE was drained as much as possible. Both groups were treated with pemetrexed 500 mg/m^2, intravenous drip(d1), cisplatin 37.5 mg/m^2 per time, intra-pleural injection(d1, d3). Patients in the Endostar group were treated with Endostar 30 mg per time, intra-pleural injection(d1, 3), and patients in the Bevacizumab group were treated with bevacizumab 5 mg/kg per time, intra-pleural injection(d1). Only one cycle of treatment was applied. MPE was extracted before treatment and on day 7 after treatment. The levels of vascular endothelial growth factor(VEGF) were determined using ELISA. Efficacy and side effects were evaluated according to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1, and National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE) version 3.0 criteria. Results The objective response rates in the Endostar and Bevacizumab groups were 50.0% and 56.3%, respectively; there was no statistical difference between the groups(P > 0.05). After one cycle of treatment, the mean VEGF levels in MPE in both groups decreased significantly, and there was no significant difference in the degree of decline between the two groups(P > 0.05). In both groups, pre-treatment VEGF levels for patients achieving complete response were significantly higher than those for patients achieving stable disease + progressive disease(P < 0.05). No specific side effects were recorded. Conclusion Endostar and Bevacizumab demonstrated similar efficacy in controlling MPE in patients with EGFR-/ALK-lung adenocarcinoma through an anti-angiogenesis pathway, with tolerable side effects. The levels of VEGF in MPE could predict the efficacy of intra-pleural injection of anti-angiogenesis drugs.展开更多
Objective:To study the effect of intrapleural endostatin and mannatide infusion on malignant molecule expression in pleural fluid of malignant pleural effusion.Methods:Patients with lung cancer and malignant pleural e...Objective:To study the effect of intrapleural endostatin and mannatide infusion on malignant molecule expression in pleural fluid of malignant pleural effusion.Methods:Patients with lung cancer and malignant pleural effusion treated in our hospital between April 2013 and December 2015 were selected and randomly divided into two groups, the observation group received intrapleural endostatin and mannatide infusion treatment and control group accepted routine intrapleural infusion treatment. 4 weeks after treatment, the pleural fluid samples were collected to determine the levels of tumor markers, invasion-related molecules, VEGF-related molecules and anti-tumor cytokines.Results:4 weeks after treatment, CEA, CYFRA21-1, NSE, SCC-Ag, CXCL12, CXCR4, MMP2, MMP9, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2 and VEGF-R3 levels in pleural fluid of observation group were significantly lower than those of control group while LASS2/TMSG-1, IFN-γ, IL-2, TNF-α, IL-17 and IL-23 levels were significantly higher than those of control group.Conclusion:Intrapleural endostatin and mannatide infusion treatment of malignant pleural effusion can more effectively kill cancer cells, inhibit cell invasion, angiogenesis and lymphangiogenesis, and enhance antitumor immune response.展开更多
Background:Non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutations or anaplastic lymphoma kinase(ALK)fusions show dramatic responses to specific tyrosine kinase inhibitors(TKIs);...Background:Non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutations or anaplastic lymphoma kinase(ALK)fusions show dramatic responses to specific tyrosine kinase inhibitors(TKIs);however,after 10-12 months,secondary mutations arise that confer resistance.We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK-and EGFR-targeted TKIs crizotinib and osimertinib,respectively.Methods:Genotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing(WES),and patients and xenograft-bearing mice received targeted treatment(crizotinib or osimertinib)accordingly.Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size.Finally,the pathology of patients biopsies and xenograft tumors were compared histologically.Results:The histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients.WES showed that the genotypes of the xenograft and patient tumors were similar(an echinoderm microtu-bule-associated protein-like 4-ALK(EML4-ALK)gene fusion(patient/xenograft:CTC15035EML4-ALK)and EGFR L858R and T790M mutations(patient/xenograft:CTC15063EGFR L858R,T790M)).After continuous crizotinib or osimertinib treatment,WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035EML4-ALK xenograft,while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v-RAF murine sarcoma viral oncogene homolog B(BRAF)G7V mutations and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha(PIK3C2A)A86fs frame shift mutations led to osimertinib resistance in the CTC15063EGFR L858R,T790M xenografts.Conclusions:We successfully developed a new method of generating drug resistance xenograft models from liquid biopsies using microfluidic technology,which might be a useful tool to investigate the mechanisms of drug resist-ance in NSCLC.展开更多
目的系统评价贝伐珠单抗联合顺铂胸腔灌注治疗非小细胞肺癌(NSCLC)合并恶性胸腔积液(MPE)的疗效及安全性。方法检索PubMed、Embase、The Cochrane Library、Web of Science、ProQuest、中国生物医学文献数据库、中国知网、维普、万方数...目的系统评价贝伐珠单抗联合顺铂胸腔灌注治疗非小细胞肺癌(NSCLC)合并恶性胸腔积液(MPE)的疗效及安全性。方法检索PubMed、Embase、The Cochrane Library、Web of Science、ProQuest、中国生物医学文献数据库、中国知网、维普、万方数据库中收录的关于贝伐珠单抗联合顺铂对比顺铂胸腔灌注治疗NSCLC合并MPE的随机对照试验,检索时间均从建库至2022年4月18日。依照Cochrane系统评价方法对纳入的随机对照试验进行质量评价,采用RevMan5.3和Stata15软件进行Meta分析。结果本研究最终纳入14项随机对照试验,共计932例患者。Meta分析结果显示,试验组患者总有效率(RR=1.42,95%CI:1.30~1.54,P﹤0.01)和生活质量改善率(RR=1.57,95%CI:1.27~1.94,P﹤0.01)均明显高于对照组,胸腔积液中血管内皮生长因子(VEGF)水平明显低于对照组(MD=-56.50,95%CI:-67.79~-45.21,P﹤0.01)。试验组和对照组患者胃肠道反应、骨髓抑制、肝肾功能异常、高血压、出血事件发生率比较,差异均无统计学意义(P﹥0.05)。结论贝伐珠单抗联合顺铂胸腔灌注治疗NSCLC合并MPE可提高疗效,抑制MPE生成,同时不增加不良反应发生率。展开更多
文摘Objective:To investigate the effect of bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer on tumor markers, angiogenesis molecules and invasive growth molecules.Methods:A total of 68 patients who were diagnosed with non-small cell lung cancer complicated by pleural effusion in the Affiliated T.C.M Hospital of Southwest Medical University between June 2013 and August 2016 were selected and randomly divided into two groups, the combined group received bevacizumab combined with carboplatin chemotherapy, and the carboplatin group received carboplatin chemotherapy. Before treatment as well as 3 cycles and 6 cycles after treatment, the contents of tumor markers, angiogenesis molecules and invasive growth molecules in pleural effusion were examined.Results:3 cycles and 6 cycles after treatment, CEA, SCCAg, CYFRA21-1, sHLA-G, VEGF, VEGFR, PTN, MMP7 and MMP10 contents in pleural effusion of both groups of patients were significantly lower than those before treatment while TIMP1 and TIMP2 contents were significantly higher than those before treatment, and CEA, SCCAg, CYFRA21-1, sHLA-G, VEGF, VEGFR, PTN, MMP7 and MMP10 contents in pleural effusion of combined group were significantly lower than those of carboplatin group while TIMP1 and TIMP2 contents were significantly higher than those of carboplatin group.Conclusion:Bevacizumab combined with carboplatin therapy for malignant pleural effusion of non-small cell lung cancer can effectively kill cancer cells, and inhibit angiogenesis and cell invasion.
文摘Objective:To evaluate the diagnostic value of endostatin(ES),vascular endothelial growth factor (VEGF) and careinoembryonie antigen(CEA) in both serum and pleural effusion of lung cancer patients.Methods:Levels of ES,VEGF and CEA in 52 malignant pleural effusion due to lung cancer and 50 patients with non-malignant disease were measured by using sandwich enzymelinked immunosorbent assay and microparticle enzyme immunoassay.Results:The ES.VEGF and CEA levels in pleural effusion and serum,and their ratio(F/S) were higher in lung cancer group than that in benign group,and the differences were statistically significant(P【0.05).The diagnostic efficiency of ES+VEGF for lung cancer was superior to either single detection.The diagnostic efficiency of ES+VEGK+CEA was superior to either ES+VEGF or ES+CEA.Conclusions: The results suggest that ES,VEGF and CEA might be useful in the differentiation between benign and malignant pleural effusion due to lung cancer.In comparison with either single determination of concentration in serum or pleural fluid,the couiljined detection of two or three markers is of important clinical significance in the diagnosis of lung cancer.
基金Supported by a grant from the Nature Science Foundation of Hubei Province,China(No.2017CFB472)
文摘Objective To compare intra-pleural injection efficacy and safety between Endostar and bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth factor receptor(EGFR)-/anaplastic lymphoma kinase(ALK)-lung adenocarcinoma. Methods Sixty-four pCVatients with EGFR-/ALK-lung adenocarcinoma with malignant pleural effusion(MPE) were admitted to the authors' hospital between January 2016 and June 2017. Patients were randomly divided into two groups: Endostar combined with pemetrexed/cisplatin(Endostar group); and bevacizumab plus pemetrexed/cisplatin(Bevacizumab group). They underwent thoracic puncture and catheterization, and MPE was drained as much as possible. Both groups were treated with pemetrexed 500 mg/m^2, intravenous drip(d1), cisplatin 37.5 mg/m^2 per time, intra-pleural injection(d1, d3). Patients in the Endostar group were treated with Endostar 30 mg per time, intra-pleural injection(d1, 3), and patients in the Bevacizumab group were treated with bevacizumab 5 mg/kg per time, intra-pleural injection(d1). Only one cycle of treatment was applied. MPE was extracted before treatment and on day 7 after treatment. The levels of vascular endothelial growth factor(VEGF) were determined using ELISA. Efficacy and side effects were evaluated according to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1, and National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE) version 3.0 criteria. Results The objective response rates in the Endostar and Bevacizumab groups were 50.0% and 56.3%, respectively; there was no statistical difference between the groups(P > 0.05). After one cycle of treatment, the mean VEGF levels in MPE in both groups decreased significantly, and there was no significant difference in the degree of decline between the two groups(P > 0.05). In both groups, pre-treatment VEGF levels for patients achieving complete response were significantly higher than those for patients achieving stable disease + progressive disease(P < 0.05). No specific side effects were recorded. Conclusion Endostar and Bevacizumab demonstrated similar efficacy in controlling MPE in patients with EGFR-/ALK-lung adenocarcinoma through an anti-angiogenesis pathway, with tolerable side effects. The levels of VEGF in MPE could predict the efficacy of intra-pleural injection of anti-angiogenesis drugs.
文摘Objective:To study the effect of intrapleural endostatin and mannatide infusion on malignant molecule expression in pleural fluid of malignant pleural effusion.Methods:Patients with lung cancer and malignant pleural effusion treated in our hospital between April 2013 and December 2015 were selected and randomly divided into two groups, the observation group received intrapleural endostatin and mannatide infusion treatment and control group accepted routine intrapleural infusion treatment. 4 weeks after treatment, the pleural fluid samples were collected to determine the levels of tumor markers, invasion-related molecules, VEGF-related molecules and anti-tumor cytokines.Results:4 weeks after treatment, CEA, CYFRA21-1, NSE, SCC-Ag, CXCL12, CXCR4, MMP2, MMP9, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2 and VEGF-R3 levels in pleural fluid of observation group were significantly lower than those of control group while LASS2/TMSG-1, IFN-γ, IL-2, TNF-α, IL-17 and IL-23 levels were significantly higher than those of control group.Conclusion:Intrapleural endostatin and mannatide infusion treatment of malignant pleural effusion can more effectively kill cancer cells, inhibit cell invasion, angiogenesis and lymphangiogenesis, and enhance antitumor immune response.
基金supported by grants from the Science and Technology Commission of Shanghai Municipality(STCSM)(14140902800 and 16140902800)the National Key R&D Program of China(2016YFC1303300)+1 种基金the National Natural Science Foundation of China(81672272)the Key Project of Shanghai Health&Family Planning Commission(201540365).
文摘Background:Non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)mutations or anaplastic lymphoma kinase(ALK)fusions show dramatic responses to specific tyrosine kinase inhibitors(TKIs);however,after 10-12 months,secondary mutations arise that confer resistance.We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK-and EGFR-targeted TKIs crizotinib and osimertinib,respectively.Methods:Genotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing(WES),and patients and xenograft-bearing mice received targeted treatment(crizotinib or osimertinib)accordingly.Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size.Finally,the pathology of patients biopsies and xenograft tumors were compared histologically.Results:The histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients.WES showed that the genotypes of the xenograft and patient tumors were similar(an echinoderm microtu-bule-associated protein-like 4-ALK(EML4-ALK)gene fusion(patient/xenograft:CTC15035EML4-ALK)and EGFR L858R and T790M mutations(patient/xenograft:CTC15063EGFR L858R,T790M)).After continuous crizotinib or osimertinib treatment,WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035EML4-ALK xenograft,while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v-RAF murine sarcoma viral oncogene homolog B(BRAF)G7V mutations and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha(PIK3C2A)A86fs frame shift mutations led to osimertinib resistance in the CTC15063EGFR L858R,T790M xenografts.Conclusions:We successfully developed a new method of generating drug resistance xenograft models from liquid biopsies using microfluidic technology,which might be a useful tool to investigate the mechanisms of drug resist-ance in NSCLC.
文摘目的系统评价贝伐珠单抗联合顺铂胸腔灌注治疗非小细胞肺癌(NSCLC)合并恶性胸腔积液(MPE)的疗效及安全性。方法检索PubMed、Embase、The Cochrane Library、Web of Science、ProQuest、中国生物医学文献数据库、中国知网、维普、万方数据库中收录的关于贝伐珠单抗联合顺铂对比顺铂胸腔灌注治疗NSCLC合并MPE的随机对照试验,检索时间均从建库至2022年4月18日。依照Cochrane系统评价方法对纳入的随机对照试验进行质量评价,采用RevMan5.3和Stata15软件进行Meta分析。结果本研究最终纳入14项随机对照试验,共计932例患者。Meta分析结果显示,试验组患者总有效率(RR=1.42,95%CI:1.30~1.54,P﹤0.01)和生活质量改善率(RR=1.57,95%CI:1.27~1.94,P﹤0.01)均明显高于对照组,胸腔积液中血管内皮生长因子(VEGF)水平明显低于对照组(MD=-56.50,95%CI:-67.79~-45.21,P﹤0.01)。试验组和对照组患者胃肠道反应、骨髓抑制、肝肾功能异常、高血压、出血事件发生率比较,差异均无统计学意义(P﹥0.05)。结论贝伐珠单抗联合顺铂胸腔灌注治疗NSCLC合并MPE可提高疗效,抑制MPE生成,同时不增加不良反应发生率。
