Cisplatin(CDDP)-based chemotherapy is an effective strategy for the treatment of advanced nasopharyngeal carcinoma(NPC).However,serious toxic side effects of CDDP limit patient tolerance and treatment compliance,which...Cisplatin(CDDP)-based chemotherapy is an effective strategy for the treatment of advanced nasopharyngeal carcinoma(NPC).However,serious toxic side effects of CDDP limit patient tolerance and treatment compliance,which urgently needs to be addressed in clinical application.Liposomes have been considered ideal vehicles for reducing CDDP toxicity due to their high biocompatibility,low toxicity and passive targeting ability.Nevertheless,CDDP's poor water/lipid solubility usually results in a low liposome druglipid ratio,limiting tumor delivery ability.Herein,a CDDP-polyphenol complex liposome was designed to increase the drug loading capacity of CDDP to realize the reduction of toxicity and effective antitumor effect simultaneously.The complex was prepared via complexation reaction of different stoichiometric ratios of CDDP and polyphenolic substances(gallic acid,epigallocatechin gallate and tannic acid),followed by encapsulation of complex in liposomes to improve tumor targeting.Notably,the molecular interaction forces between CDDP and polyphenolic substances were intensively investigated through a binding force disruption assay.In vitro studies demonstrated that the optimal formulation of CDDP-epigallocatechin gallate complex liposome(CDDP-EGCG Lips) showed the highest CDDP encapsulation efficiency,favorable stability,pH-sensitive release,enhanced cellular uptake and apoptosis effect.In vivo studies revealed that CDDP-EGCG Lips retarded the elimination of CDDP to prolong their circulation time,inhibited the growth of tumors,and significantly reduced the toxic side effects compared to CDDP monotherapy.This delivery strategy holds great promise for improving the clinical use of platinum-based drugs.展开更多
目的:探讨扶正口服汤联合奥沙利铂及卡培他滨(Oxaliplatin and Capecitabine,XELOX)化疗方案对结直肠癌患者卡氏功能状态评分(Karnofsky performance status score,KPS)及毒副反应发生率的影响。方法:前瞻性选取2020年5月至2024年5月我...目的:探讨扶正口服汤联合奥沙利铂及卡培他滨(Oxaliplatin and Capecitabine,XELOX)化疗方案对结直肠癌患者卡氏功能状态评分(Karnofsky performance status score,KPS)及毒副反应发生率的影响。方法:前瞻性选取2020年5月至2024年5月我院收治的122例结直肠癌患作为研究对象。根据随机信封法将所有患者分为研究组和对照组,各61例。对照组采用XELOX化疗方案治疗,研究组在对照组的基础上加用扶正口服汤治疗,两组均持续治疗8个疗程。比较两组临床疗效,并于治疗前后采用中医证候积分及KPS评分评估两组临床症状及生存质量;比较两组的免疫功能(CD3^(+)、CD4^(+)/CD8^(+)、NK细胞、CD8^(+)),以及两组治疗期间的毒副反应发生情况。结果:研究组疾病控制率明显高于对照组(P<0.05)。治疗后,研究组中医证候积分、CD8^(+)、Ⅰ-Ⅱ级的毒副反应发生率明显低于对照组;研究组KPS评分、CD3^(+)、CD4^(+)/CD8^(+)、NK明显高于对照组(P<0.05)。结论:扶正口服汤联合XELOX化疗方案可有效提高结直肠癌患者疗效,改善免疫功能及KPS评分,减轻化疗毒副作用。展开更多
目的探讨特瑞普利单抗联合FOLFOX方案治疗进展期胃癌的效果及其免疫调节机制。方法选取2021年6月至2023年6月驻马店市中心医院收治的97例进展期胃癌患者纳入研究,按随机数表法分为观察组49例和对照组48例,其中对照组采用FOLFOX方案治疗...目的探讨特瑞普利单抗联合FOLFOX方案治疗进展期胃癌的效果及其免疫调节机制。方法选取2021年6月至2023年6月驻马店市中心医院收治的97例进展期胃癌患者纳入研究,按随机数表法分为观察组49例和对照组48例,其中对照组采用FOLFOX方案治疗者,观察组采用FOLFOX方案+特瑞普利单抗治疗,21 d为一个疗程,持续治疗6个疗程。比较两组患者治疗6个疗程后的治疗效果,以及治疗前、治疗3个疗程和6个疗程后的程序性细胞死亡受体-1(PD-1)/程序性细胞死亡配体-1(PD-L1)信号通路(PD-1蛋白、PD-1 m RNA、PD-L1蛋白、PD-L1 m RNA)、血管新生指标[低氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)、促血管生成素-2(Ang-2)、环氧合酶-2(COX-2)],同时比较两组患者治疗期间的毒副反应以及随访6个月的生存率。结果治疗6个疗程后,观察组患者的疾病控制率为63.27%,明显高于对照组的41.67%,差异有统计学意义(P<0.05)。治疗3个疗程、6个疗程后,观察组患者的PD-1蛋白分别为5.83±1.12、5.77±1.26,明显低于对照组的6.84±1.25、7.11±1.36,PD-1m RNA分别为6.12±1.33、6.01±1.34,明显低于对照组的6.91±1.34、7.20±1.30,PD-L1蛋白分别为6.30±1.05、6.19±1.11,明显低于对照组的7.02±1.33、6.88±1.40,PD-1 mRNA分别为6.41±1.24、6.33±1.25,明显低于对照组的7.19±1.36、7.10±1.38,差异有统计学意义(P<0.05)。治疗3个疗程、6个疗程后,观察组患者的VEGF分别为(224.46±25.25)ng/mL、(150.10±14.14)ng/mL,明显低于对照组的(279.79±30.44)ng/mL、(191.65±16.63)ng/mL,HIF-1α分别为(135.51±16.67)μg/L、(100.10±12.28)μg/L,明显低于对照组的(175.53±18.48)μg/L、(153.53±14.88)μg/L,Ang-2分别为(68.98±7.36)ng/mL、(46.68±5.13)ng/mL,明显低于对照组的(75.51±7.95)ng/mL、(56.64±6.11)ng/mL,COX-2分别为(31.48±4.12)ng/mL、(20.24±3.38)ng/mL,明显低于对照组的(36.64±4.20)ng/mL、(25.74±3.59)ng/mL;差异均有统计学意义(P<0.05)。两组患者治疗6个疗程后的毒副反应发生率与随访期间生存率比较差异均无统计学意义(P>0.05)。结论特瑞普利单抗联合FOLFOX方案治疗进展期胃癌,可阻断PD-1/PD-L1信号通路,增强肿瘤控制效果,且具有较好的安全性。展开更多
基金supported by the National Natural Science Foundation of China (Nos.81872823,82073782,and 82241002)the Key R&D Plan of Ganjiang New District of Jiangxi (No.2023010)。
文摘Cisplatin(CDDP)-based chemotherapy is an effective strategy for the treatment of advanced nasopharyngeal carcinoma(NPC).However,serious toxic side effects of CDDP limit patient tolerance and treatment compliance,which urgently needs to be addressed in clinical application.Liposomes have been considered ideal vehicles for reducing CDDP toxicity due to their high biocompatibility,low toxicity and passive targeting ability.Nevertheless,CDDP's poor water/lipid solubility usually results in a low liposome druglipid ratio,limiting tumor delivery ability.Herein,a CDDP-polyphenol complex liposome was designed to increase the drug loading capacity of CDDP to realize the reduction of toxicity and effective antitumor effect simultaneously.The complex was prepared via complexation reaction of different stoichiometric ratios of CDDP and polyphenolic substances(gallic acid,epigallocatechin gallate and tannic acid),followed by encapsulation of complex in liposomes to improve tumor targeting.Notably,the molecular interaction forces between CDDP and polyphenolic substances were intensively investigated through a binding force disruption assay.In vitro studies demonstrated that the optimal formulation of CDDP-epigallocatechin gallate complex liposome(CDDP-EGCG Lips) showed the highest CDDP encapsulation efficiency,favorable stability,pH-sensitive release,enhanced cellular uptake and apoptosis effect.In vivo studies revealed that CDDP-EGCG Lips retarded the elimination of CDDP to prolong their circulation time,inhibited the growth of tumors,and significantly reduced the toxic side effects compared to CDDP monotherapy.This delivery strategy holds great promise for improving the clinical use of platinum-based drugs.
文摘目的:探讨扶正口服汤联合奥沙利铂及卡培他滨(Oxaliplatin and Capecitabine,XELOX)化疗方案对结直肠癌患者卡氏功能状态评分(Karnofsky performance status score,KPS)及毒副反应发生率的影响。方法:前瞻性选取2020年5月至2024年5月我院收治的122例结直肠癌患作为研究对象。根据随机信封法将所有患者分为研究组和对照组,各61例。对照组采用XELOX化疗方案治疗,研究组在对照组的基础上加用扶正口服汤治疗,两组均持续治疗8个疗程。比较两组临床疗效,并于治疗前后采用中医证候积分及KPS评分评估两组临床症状及生存质量;比较两组的免疫功能(CD3^(+)、CD4^(+)/CD8^(+)、NK细胞、CD8^(+)),以及两组治疗期间的毒副反应发生情况。结果:研究组疾病控制率明显高于对照组(P<0.05)。治疗后,研究组中医证候积分、CD8^(+)、Ⅰ-Ⅱ级的毒副反应发生率明显低于对照组;研究组KPS评分、CD3^(+)、CD4^(+)/CD8^(+)、NK明显高于对照组(P<0.05)。结论:扶正口服汤联合XELOX化疗方案可有效提高结直肠癌患者疗效,改善免疫功能及KPS评分,减轻化疗毒副作用。
文摘目的探讨特瑞普利单抗联合FOLFOX方案治疗进展期胃癌的效果及其免疫调节机制。方法选取2021年6月至2023年6月驻马店市中心医院收治的97例进展期胃癌患者纳入研究,按随机数表法分为观察组49例和对照组48例,其中对照组采用FOLFOX方案治疗者,观察组采用FOLFOX方案+特瑞普利单抗治疗,21 d为一个疗程,持续治疗6个疗程。比较两组患者治疗6个疗程后的治疗效果,以及治疗前、治疗3个疗程和6个疗程后的程序性细胞死亡受体-1(PD-1)/程序性细胞死亡配体-1(PD-L1)信号通路(PD-1蛋白、PD-1 m RNA、PD-L1蛋白、PD-L1 m RNA)、血管新生指标[低氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)、促血管生成素-2(Ang-2)、环氧合酶-2(COX-2)],同时比较两组患者治疗期间的毒副反应以及随访6个月的生存率。结果治疗6个疗程后,观察组患者的疾病控制率为63.27%,明显高于对照组的41.67%,差异有统计学意义(P<0.05)。治疗3个疗程、6个疗程后,观察组患者的PD-1蛋白分别为5.83±1.12、5.77±1.26,明显低于对照组的6.84±1.25、7.11±1.36,PD-1m RNA分别为6.12±1.33、6.01±1.34,明显低于对照组的6.91±1.34、7.20±1.30,PD-L1蛋白分别为6.30±1.05、6.19±1.11,明显低于对照组的7.02±1.33、6.88±1.40,PD-1 mRNA分别为6.41±1.24、6.33±1.25,明显低于对照组的7.19±1.36、7.10±1.38,差异有统计学意义(P<0.05)。治疗3个疗程、6个疗程后,观察组患者的VEGF分别为(224.46±25.25)ng/mL、(150.10±14.14)ng/mL,明显低于对照组的(279.79±30.44)ng/mL、(191.65±16.63)ng/mL,HIF-1α分别为(135.51±16.67)μg/L、(100.10±12.28)μg/L,明显低于对照组的(175.53±18.48)μg/L、(153.53±14.88)μg/L,Ang-2分别为(68.98±7.36)ng/mL、(46.68±5.13)ng/mL,明显低于对照组的(75.51±7.95)ng/mL、(56.64±6.11)ng/mL,COX-2分别为(31.48±4.12)ng/mL、(20.24±3.38)ng/mL,明显低于对照组的(36.64±4.20)ng/mL、(25.74±3.59)ng/mL;差异均有统计学意义(P<0.05)。两组患者治疗6个疗程后的毒副反应发生率与随访期间生存率比较差异均无统计学意义(P>0.05)。结论特瑞普利单抗联合FOLFOX方案治疗进展期胃癌,可阻断PD-1/PD-L1信号通路,增强肿瘤控制效果,且具有较好的安全性。