不同术后辅助化疗方案对胃癌患者远期生存的影响

目的：比较奥沙利铂（L—OHP）联合5-FU／LV与羟基喜树碱（HCPT）联合5-FU／LV两种不同辅助化疗方案对可切除胃癌术后远期生存的影响。方法：85例I-Ⅳ期胃癌术后（R0切除）患者接受治疗,其中奥沙利铂组（L—OHP组）43例,羟基喜树碱组（HCPT组）42例,比较两组不良反应和生存率。结果：不良反应两组血小板减少、外周神经毒性及腹泻有显著性差异（P〈0．05）,其它不良反应无统计学差异（P〉0．05）。L—OHP组及HCPT组1、3、5年总生存率（OS）分别为95．4％、67．4％、18．6％和92．9％、64．3％、21．4％,两组比较无显著性差异（P〉Q05）,L—OHP组及HCPT组1、3、5年无病生存率（DFS）分别为83．7％、41．9％、9．3％和80．5％、45．2％、19．1％,随着时间延长,HCPT组5年DFS似有升高趋势,但均无统计学差异（P〉0．05）。结论：两种化疗方案均可作为胃癌患者术后辅助治疗的选择。     

HCPT联合L-OHP方案治疗进展期结直肠癌的近期临床疗效

Objective： Although 5-fluarouracil-based chemotherapy has become a standard regimen for treatment of advanced colorectal cancer, the efficacy, as second line therapy, is not high. It is necessary to find a new regimen as a substitute for these patients. The study was to evaluate the short-time effects and toxicity of combination of HCPT plus L-OHP regimen in treatment of advanced colorectal cancer. Methods： Forty-seven patients with pathological evidence of advanced colorectal cancer were enrolled and were treated with HCPT plus L-OHP regimen for 86 cycles. All patients were treated with L-OHP 130 mg/m^2 day 1 and HCPT 6 mg/m^2day 1-4, the chemotherapy was repeated every 3 weeks as a cycle. The Short-time efficats and side effects were evaluated after 2 cycles for each patient. Results： 38 cases can be evaluated to short-time effects and achieved the overall response rate （CR＋PR） was 36.8%. KPS improved in 20 cases （52.6%）. In the total 86 cycles, the leucopenia occurred in 59 cycles （68.6%）,18 cycles （30.5%） in grade Ⅲ and Ⅳ and the diarrhea occurred in 48 cycles （55.8%）, 18 cycles （37.5%） in grade Ⅲ and Ⅳ. Conclusion： A satisfied response rate was obtained in advanced colorectal cancer patients treated by HCPT plus L-OHP regimen, especially who were the failure of first-line chemotherapy with 5-FU. The limited-dose toxicity was leucopenia and diarrhea.     

羟基喜树碱与5-氟脲嘧啶联合治疗晚期胃肠道肿瘤近期疗效观察

目的 观察羟基喜树碱(HCPT)和5-氟脲嘧啶(5-Fu)联合化疗治疗晚期胃肠道肿瘤的近期疗效和毒副反应。方法HCPT10mg／d,静脉点滴,连用10天;5-Fu0．75mg／d,静脉点滴年,连用5天。21天为-个周期,二至三个周期观察疗效。结果20例胃癌CR1例,PR9例,NC6例,PD4例,总有效率(CR PR)为50％;结肠癌15例中CR2例,PR6例,NC5例,PD2例,(CR PR)为53．3％。毒副反应多为胃肠道反应及骨髓毒性,多为1～2级。结论以HCPT和5-Fu联合治疗晚期胃肠道肿瘤疗效较好,且毒副反应可以耐受。     

奥沙利铂和羟基喜树碱分别联合5-氟尿嘧啶/亚叶酸钙治疗晚期大肠癌的对照研究

目的 对照研究奥沙利铂(LOHP)和羟基喜树碱(HCPT)分别联合5-氟尿嘧啶/亚叶酸钙(5-Fu/CF)治疗晚期大肠癌的临床效果.方法 将符合入选条件的59 例晚期大肠癌患者随机分为观察组30例(含LOHP方案)及对照组29例(含HCPT方案),每3周重复,两组均完成3个疗程化疗.对照观察两组的近期疗效及不良反应.结果 观察组完全缓解(CR)1例,部分缓解(PR)12例,总有效率(CR+PR)为43.3%;对照组CR 0例,PR 7例,总有效率(CR+PR)为24.1%,差异有统计学意义(P<0.05).观察组神经毒性及腹泻发生率较高,对照组粒细胞减少发生率较高,但两组恶心、呕吐、脱发等不良反应发生率差异无统计学意义.结论 LOHP联合 5-Fu/CF是治疗大肠癌的有效化疗方案,特别适宜晚期大肠癌以及对 5-Fu 耐药的患者.     

羟基喜树碱联合热疗抑制人肝癌细胞SMMC-7721体外增殖作用的研究

目的探讨羟基喜树碱联合热疗体外抑制人肝癌细胞增殖的效果,以确定联合方案是否具有协同效应。方法使用MTT法测定单独或联合应用羟基喜树碱与热疗对人肝癌SMMC7721细胞的体外增殖的抑制作用,使用流式细胞仪检测不同方案对SMMC7721细胞凋亡率的影响。结果联合应用热疗可以显著提高羟基喜树碱引起的细胞增殖抑制及细胞凋亡。以亚毒性剂量浓度的羟基喜树碱为例,对照组、化疗组、热疗组、热化疗组的细胞增殖抑制率分别为0%、13.65%、32.46%、71.89%;细胞倍增时间分别为40.54、86.35、106.85、187.90h;细胞凋亡率分别为2.19%、3.96%、10.16%、20.42%。结论联合应用热疗与羟基喜树碱,对SMMC-7721细胞体外增殖的抑制及诱导细胞凋亡具有显著的协同作用。     

羟基喜树碱对肝纤维化大鼠肝组织Bax、Bcl-2基因和α-SMA蛋白表达及肝纤维化的影响

目的 考察羟基喜树碱（hydroxycamptothecin,HCPT）对肝纤维化大鼠肝组织中Bax、Bcl-2基因和α-平滑肌肌动蛋白（α-SMA）表达及肝纤维化的影响。方法 64只SD大鼠随机分为5组：正常组、模型组、低剂量 HCPT治疗组、中剂量HCPT治疗组、高剂量HCPT治疗组。采用40%四氯化碳（CCl₄）诱导大鼠肝纤维化模型。正常组给予生理盐水腹腔注射;3个治疗组在造模同时分别给予0.25、0.5、1.0 mg/kg HCPT腹腔注射,3次/周,共8周。各组分别在第8周末取肝脏组织,行H-E、Masson染色观察肝脏组织病理学改变;RT-PCR检测肝脏组织中Bax、Bcl-2 mRNA表达并计算Bax/Bcl-2 mRNA比值;免疫组化染色检测肝脏组织中α-SMA蛋白表达;TUNEL染色观察细胞凋亡情况。结果 模型组大鼠出现明显的肝纤维化（Ⅲ期2例,Ⅳ期8例）,各HCPT治疗组的肝纤维化程度较模型组减轻（低剂量组Ⅱ期1例,Ⅲ期8例,Ⅳ期1例;中剂量组Ⅱ期7例,Ⅲ期3例;高剂量组Ⅰ期1例,Ⅱ期7例,Ⅲ期2例）,差异有统计学意义（P均<0.05）。RT-PCR检测显示模型组Bax、Bcl-2 mRNA较正常组升高,而各HCPT治疗组较模型组降低（P均<0.05）;模型组Bax/Bcl-2 mRNA比值低于各HCPT治疗组（P均<0.05）。免疫组化染色检测显示模型组α-SMA蛋白表达水平高于中、高剂量HCPT组（P<0.05）。TUNEL染色结果显示正常组、模型组无明显阳性染色,各HCPT治疗组均有阳性染色。结论 HCPT对CCl₄诱导的肝纤维化大鼠模型具有防治作用,抑制肝星状细胞活化增殖,上调Bax/Bcl-2 mRNA比值可能是HCPT抗肝纤维化的部分机制。     

羟基喜树碱对MUTZ-1细胞凋亡中survivin基因及蛋白质表达的影响

摘要：目的：探讨羟基喜树碱（HCPT）对人骨髓增生异常综合征（MDS）细胞系MUTZ-1细胞凋亡中生存素（survivin）基因及蛋白质表达的影响。 方法：MUTZ-1细胞与0、1、2、4 μg/mL HCPT共育6 h,用流式细胞术（FCM）检测其细胞凋亡率,RT-PCR检测survivin mRNA的表达水平,免疫细胞化学及western blot检测survivin蛋白质的表达水平。 结果：MUTZ-1细胞与0、1、2、4 μg/mL HCPT共育后,细胞凋亡率升高,分别为（8.58±0.18）%、（12.10±1.04）%、（14.49±0.87）% 和（27.34±1.38）%（F=158.7,P<0.05）;survivin mRNA 表达水平下调,分别为0.87±0.08、0.76±0.03、0.67±0.03和0.45±0.04（F=97.65,P<0.05）;细胞凋亡率与survivin mRNA表达水平呈负相关（r=-0.85,P<0.01）;survivin蛋白质积分值降低,分别为2.36±0.19、1.50±0.11、1.49±0.18和1.06±0.04（F=14.57,P<0.05）;survivin蛋白质表达减少,分别为0.80±0.09、0.34±0.04、0.25±0.02和0.05±0.01（F=37.42,P<0.05）。 结论：HCPT可能通过下调survivin基因转录及蛋白质表达,诱导MUTZ-1细胞凋亡。     

羟基喜树碱联合化疗治疗晚期非小细胞肺癌的临床观察

目的　观察以羟基喜树碱 (HPT)为主的HEP和HTP方案治疗晚期非小细胞肺癌的疗效及其毒副反应。方法　 2 2例晚期非小细胞肺癌患者分别应用HEP方案 (VM -2 610 0mg ,d1-5;静脉滴注 :HPT 10mg ,d1-5,静脉滴注 :PDD 2 0mg ,d1-5,静脉滴注 )或HEP方案 (VP 1610 0mg ,d1-5:静脉滴注 :HPT 10mg ,d1-5,静脉滴注 :PDD 2 0mg ,d1-5,静脉滴注 )联合化疗 ,4周重复 ,2周期后按WHO标准进行评价。结果　 2 2例患者中CR 1例 ,PR 8例 ,总有效率 40 .9% ;主要毒副反应为骨髓抑制和消化道反应。结论　以羟基喜树碱为主的HEP和HTP方案治疗晚期非小细胞肺癌的疗效较高 ,毒副反应可以耐受 ,值得临床进一步观察。     

拓扑替康、羟喜树碱治疗脑转移癌的临床安全性观察

目的：观察和评价拓扑替康和羟喜树碱治疗脑转移癌的安全性。方法：2004年4月至2007年12月临床诊断为脑转移癌的86例患者纳入研究。患者的原发癌为小细胞肺癌（26例）、非小细胞肺癌（32例）及乳腺癌（28例）。86例患者随机分为2个治疗组：拓扑替康组（44例）和羟喜树碱组（42例）。拓扑替康组患者在第1～5天用拓扑替康0.8～1.0mg／（m^2·d）加入0．9％氯化钠注射液或5％葡萄糖注射液100～150ml静脉滴注，30min滴完。羟喜树碱组患者在第1～5天用羟喜树碱4．0～6．0mg／（m^2·d）加入0．9％氯化钠注射液或5％葡萄糖注射液100～150ml中静脉滴注，30min滴完。21d为1个周期，化疗为2个周期。在第2周期末评价疗效，比较2组治疗有效率和临床获益率以及不良反应。结果：共84例患者完成2个周期化疗和疗效评价，完成率为97.67％。拓扑替康和羟喜树碱组的临床有效率分别为37.21％和36．59％，临床获益率分别为81．40％和73．17％。组间比较无统计学差异（P〉0.05）。血液毒性反应主要为白细胞和血小板减少。拓扑替康组Ⅲ～Ⅳ度的白细胞减少和血小板减少，分别为29．55％和13.64％，羟喜树碱组分别为7.14％和2.38％。组间比较有统计学差异（P〈0．05）。未见明显的非血液毒性反应。结论：低剂量拓扑替康和羟基喜树碱在脑转移癌治疗中具有较为良好的疗效、安全性和耐受性。     

Clinical study of combining chemotherapy of oxaliplatin or 5-fluorouracil/leucovorin with hydroxycamptothecine for advanced colorectal cancer

OBJECTIVE To estimate effects, survival rate after the short-time efficacy, side the treatment of combining chemotherapy of oxaliplatin or 5-fluorouracil/leucovorin with hydroxycamptothecine （HCPT） for the patients with advanced colorectal cancer.
METHODS From January 2002 to November 2005, 59 patients with advanced colorectal cancer confirmed by pathology were enrolled into this study in the department of medical oncology, in the Sixth People＇s Hospital of Shanghai Jiaotong University, Shanghai. Patients＇ characteristics in two groups were similarly confirmed by statistic. All 37 patients in OH group received oxalip21atin （130 mg/m^2 d1） plus hydroxycamptothecine （6 mg/m d1-4）, and all 22 patients in the HLF group received hydroxycamptothecine （6 mg/m^2 d1-4） plus leucovorin （300 mg d1-5） and 5-fluorouracil （0.375 g/m^2 d1-5）. The regimens in both groups were 21-day cycle that was repeated three weeks. The side effects were evaluated. The efficacy was estimated after two cycles of chemotherapy for each patient.
RESULTS The efficacy of the treatment in the OH group with 37 patients and in the HLF group with 22 patients was estimated. The overall response rate （CR ＋ PR） was 32.4% in the OH group and 22.7% in the HLF group. There was no complete response （CR） and there was no statistical significantly difference （%2= 0.876, P = 0.704） in two groups. The 1-year survival rate was 30.98% in the OH group and 15.02% in the HLF group, and it had no significant difference between the two groups. The median PSF and OS were 5.83 months and 11.17 months in the OH group vs. 7.40 months and 10.48 months in the HLF group, and it had no significant differences between the two groups （P 〉 0.05）. The major side effects of grade III and IV in the two groups were myelosuppression and gastrointestinal reactions. The statistically significant difference in side effects appeared in leukopenia （χ^2= 17.173, P = 0.001）, nausea/vomiting （χ^2= 6.426, P = 0.039）, diarrhea （χ^2= 16.245, P = 0.000） and peripheral neuropathy. CONCLUSION The efficacy was almost equal between the OH and the HLF groups, and the two regimens can be used as the second-line treatments for the patients with colorectal cancer. Leucopenia, nausea, diarrhea and peripheral neuropathy appeared more in OH group, and anemia and thrombocytopenia were almost equal between the OH and the HLF groups.