含奥沙利铂与含顺铂方案肝动脉栓塞化疗治疗中晚期肝癌的疗效

目的分析含奥沙利铂（L—OHP）与含顺铂（DDP）方案行肝动脉化疗栓塞术（TACE）对中晚期原发性肝癌（HCC）的治疗效果和不良反应。方法将108例中晚期HCC患者随机分成2组。治疗组55例,行含L—OHP方案介入治疗,L—OHP 130mg／m^2,替加氟（FT207）500～750mg／m^2,用葡萄糖溶液稀释后分别注入血管,根据肿瘤病灶的大小以多柔比星（ADM）40mg／m^2＋超液化碘油10～30ml乳化后进行血管栓塞。对照组53例,行含DDP方案介入治疗,DDP40mg／m^2,FT207500～750mg／m^2,用葡萄糖溶液稀释后分别注入血管,根据肿瘤病灶的大小以ADM40mg／m^2＋超液化碘油10～30ml乳化后进行血管栓塞,并予水化利尿。结果治疗组近期有效率为67.3％（37／55）,与对照组[47．2％（25／53）]比较,差异有统计学意义（P〈0．05）。治疗组甲胎蛋白（AFP）下降率为73．1％（31／43）,与对照组[44．7％（17／38）]比较,差异有统计学意义（P〈0．05）。主要不良反应为消化道反应,治疗组恶心、呕吐发生率较对照组低,差异有统计学意义（P〈0．05）。两组骨髓抑制、肝功能受损、末梢神经炎发生率差异无统计学意义。两组均未见心、肾损害。结论采用以L—OHP为主的方案行TACE治疗中晚期肝癌疗效肯定,安全性好,患者耐受好。     

黄芪注射液对奥沙利铂致海马神经细胞凋亡的抑制作用

目的:研究黄芪注射液对奥沙利铂(L-OHP)致海马神经细胞凋亡的作用。方法:在原代培养的新生24hSD大鼠海马神经细胞培养液中,加入不同浓度L-OHP(0、3、5和10μg/mL)和不同浓度黄芪注射液(0.05、0.2和0.5g/mL),观察各组细胞凋亡情况,并测定细胞外液神经生长因子(NGF)含量。结果:黄芪可浓度依赖性地减轻L-OHP引起的神经细胞凋亡(P<0.01)并能增加NGF含量(P<0.05)。结论:黄芪可能通过增加NGF含量抑制L-OHP导致的海马神经细胞凋亡。     

S-1 and Oxaliplatin Versus Tegafur-uracil and Leucovorin as Postoperative Adjuvant Chemotherapy in Patients With High-risk Stage III Colon Cancer (ACTS-CC 02): A Randomized,Open-label,Multicenter, Phase III Superiority Trial

BackgroundThe efficacy of S-1 plus oxaliplatin (SOX) as postoperative adjuvant chemotherapy for colon cancer has not been established. This randomized phase III study was designed to verify the superiority of SOX over tegafur-uracil and leucovorin (UFT/LV) in patients with high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries).Patients and MethodsPatients who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300 mg/m² of UFT and 75 mg/day of LV on days 1-28, every 35 days, 5 cycles) or SOX (100 mg/m² of oxaliplatin on day 1 and 80 mg/m² of S-1 on days 1-14, every 21 days, 8 cycles). The primary endpoint was disease-free survival (DFS).ResultsA total of 478 patients in the UFT/LV group and 477 patients in the SOX group were included in the primary analysis. The 3-year DFS was 60.6% (95% confidence interval [CI], 56.0%-64.9%) in the UFT/LV group and 62.7% (95% CI, 58.1%-66.9%) in the SOX group. The stratified hazard ratio for DFS was 0.90 (95% CI, 0.74-1.09; stratified log-rank test, P = .2780). In the N2b subgroup, the 3-year DFS was 46.0% (95% CI, 37.5%-54.0%) in the UFT/LV group and 54.7% (95% CI, 45.7%–62.7%) in the SOX group (hazard ratio, 0.76; 95% CI, 0.55-1.05).ConclusionAs postoperative adjuvant chemotherapy, SOX was not superior to UFT/LV in terms of DFS in patients with high-risk stage III colon cancer.     

益气活血中药联合化疗治疗晚期大肠癌的临床研究

目的观察益气活血中药联合草酸铂 CF 5-FU治疗晚期大肠癌的疗效。方法68例晚期大肠癌患者,分为治疗组(38例,益气活血中药联合化疗)和对照组(30例,单纯化疗),观察两组疗效。结果治疗组和对照组的临床受益率(CR PR SD)分别为78.9%、53.3%(P<0.05),1年生存率分别为73.7%、46.7%(P<0.05)。益气活血中药可减低患者的血液高凝状态、提高细胞免疫功能、缓解化疗药物的不良反应、改善患者的生活质量。结论益气活血中药联合草酸铂 CF 5-FU治疗晚期大肠癌有较好的疗效。     

人参皂苷Rh2对结肠癌耐药细胞HCT116/L-OHP侵袭迁移能力的影响

目的:观察人参皂苷Rh_2(ginsenoside Rh_2,GRh_2)对结肠癌耐药细胞HCT116/L-OHP迁移、侵袭的影响,并探讨其作用机制。方法:细胞计数试剂盒(cell counting kit-8,CCK-8)法检测不同质量浓度GRh_2(0,2. 5,5,10,20,40 mg·L~(-1))对HCT116/L-OHP细胞增殖抑制作用;划痕实验,Transwell实验及黏附实验分别检测GRh_2(0,2. 5,5,10 mg·L~(-1))对细胞迁移、侵袭及黏附能力的影响;蛋白免疫印迹法(Western blot)检测GRh_2(0,5,10,20,30 mg·L~(-1))对HCT116/L-OHP细胞上皮型钙黏蛋白(E-cadherin)和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)蛋白表达水平的影响。结果:与空白组比较,GRh_2(5,10,20,40 mg·L~(-1))可显著抑制HCT116/L-OHP耐药细胞的增殖能力(P 0. 05,P 0. 01),并且呈浓度依赖性;与空白组比较,GRh_2组(5,10 mg·L~(-1))划痕愈合率明显减小(P 0. 05,P 0. 01),GRh_2组穿过小室的细胞数量明显减少(P 0. 05,P 0. 01),细胞的迁移和侵袭能力受到显著抑制,并且呈浓度依赖性; GRh_2组黏附细胞数量显著减少(P 0. 05,P 0. 01),细胞的黏附能力受到显著抑制,并且呈浓度依赖性;与空白组比较,GRh_2(10,20,30 mg·L~(-1))促进了E-cadherin的蛋白表达(P 0. 05,P 0. 01),同时抑制了MMP-9蛋白表达(P 0. 01),呈一定的浓度依赖性。结论:GRh_2可显著抑制结肠癌耐药细胞HCT116/L-OHP的侵袭和迁移能力,其潜在机制可能与促进E-cadherin并抑制MMP-9的表达有关。     

周剂量多西紫杉醇联合希罗达治疗晚期胃癌的临床观察

目的观察周剂量多西紫杉醇联合希罗达治疗晚期胃癌的临床疗效和安全性。方法将93例晚期胃癌患者随机分组,观察组48例,采用周剂量多西紫杉醇联合希罗达化疗方案：多西紫杉醇35 mg/m2静脉滴注第1天、第8天,希罗达2 500 mg/m2,分2次口服,第1天至第14天;对照组45例采用奥沙利铂（L-OHP）联合希罗达治疗。结果观察组CR 4例,PR 23例,SD 15例,PD 6例,有效率为56.3%;对照组CR 4例,PR 21例,SD 14例,PD 6例,有效率为53.5%,差异无统计学意义（χ2=0.0013,P = 0.9714）。观察组中位TTP 6.5个月;对照组为5.2个月,差异有显著性（χ2=4.1655,P= 0.0413）。两组不良反应主要表现为骨髓抑制和胃肠道反应,差异无统计学意义（P〉 0.05）;观察组外周神经毒性较轻,差异有统计学意义（χ2=4.4524,P= 0.0349）。KPS评分增高率分别为54.2%和22.2%,差异有统计学意义（χ2=4.5072,P= 0.0338）。结论周剂量多西紫杉醇联合希罗达治疗晚期胃癌疗效较好,不良反应可以耐受,而在外周神经毒性、中位无进展时间及生存质量上优于对照组。     

奥沙利铂联合氟尿嘧啶亚叶酸钙治疗晚期胃癌

目的 观察奥沙利铂联合氟尿嘧啶、亚叶酸钙治疗晚期胃癌的疗效与不良反应。方法奥沙利铂130mg／m^2ivgtt dl，氟尿嘧啶450mg／m^2 ivgtt dl-5，亚叶酸钙120mg／m^2 ivgtt dl-5，3周为一周期，使用3周期后评价疗效及不良反应：结果入组46例中44例可评价疗效，PR15例(34．1％)，SD13例(29.5％)，PD16例(36．4％)，中位疾病进展时间7.5个月。不良反应主要为神经毒性，消化道反应及白细胞下降。结论奥沙利铂联合氟尿嘧啶、亚叶酸钙治疗晚期胃癌有效率较高，不良反应较轻，可作为首选方案之一。     

RNA干扰联合阻断MMS2和REV3基因表达减轻结肠癌细胞系THC8307/L-OHP对奥沙利铂的耐药性

目的 探讨沉默REV3和MMS2逆转结肠癌耐药细胞系THC8307/L-OHP细胞对奥沙利铂(L-OHP)的耐药性.方法 THC8307/L-OHP细胞转染含microRNA片段重组质粒后,用实时荧光定量PCR法(qRT-PCR)和免疫荧光法检测目的基因表达,选择低表达效率具有统计学意义的细胞作为实验组细胞.分别应用MTT法、罗丹明123实验、流式细胞术检测细胞对L-OHP药物敏感度和细胞凋亡.结果 与对照组相比,L-OHP对实验组细胞的半数抑制浓度(IC50)及耐药指数(Rl)减低(P＜0.05),实验组细胞经L-OHP处理后凋亡率显著增高(P＜0.05),实验组细胞MMS2和REV3蛋白表达水平降低(P＜0.05).结论 下调REV3和MMS2在逆转人结肠癌细胞对L-OHP的耐药性和促进肿瘤细胞的凋亡上有一定作用.     

草酸铂与时间调节5-氟脲嘧啶/亚叶酸钙治疗转移性结直肠癌疗效

目的:观察草酸铂(L-OHP)与时间调节5-氟脲嘧啶/亚叶酸钙(5-Fu/CF)治疗发生转移的结直肠癌疗效。方 法:对同周期经病理组织学或细胞学证实发生转移的结直肠腺癌44例,随机分为试验组和对照组,采用静脉多通道的时间编 程泵给药。试验组采用时辰化疗方法,L -OHP150mg/m2在用药第1天10时至16时给药,持续6小时静脉滴注,CF100mg/ m2d1～5,5-Fu500mg/m2d1～5,用药时间在每天22时15分至次日9时45分连续静脉滴注给药。对照组用药L-OHP150mg/m2 每日上午9时～12时静滴,CF100mg/m2d1～5,5-Fu500mg/m2d1～5,持续静脉滴注24小时。两组化疗前均给予恩丹西酮8mg 或格拉司琼3mg静注预防性止吐药。21天为1周期。在每个治疗周期开始前记录前1周期的毒性,并根据WHO标准分级。 每6个治疗周期后根据WHO标准评定疗效及毒副反应。结果:试验组22例,总有效率(CR+PR)54.5%。对照组22例,总 有效率(CR+PR)31.8%。两组疗效相比,有显著性差异(P<0.01)。毒副反应:外周静脉炎,试验组13.6%,对照组45.5%; 周围神经毒性,试验组36.4%,对照组81.8%,两组结果统计学处理有显著性差异(P<0.01);骨髓抑制、胃肠道反应、口腔溃 疡、脱发,两组结果无显著性差异(P>0.05);未见肝肾功、心功能损害。结论:草酸铂与时间调节5-Fu/CF治疗发生转移的结 直肠癌     

Risk factors for oxaliplatin-induced hypersensitivity reactions in Japanese patients with advanced colorectal cancer

Objective: Previously, we suggested that oxaliplatin (L-OHP)-related grade 3/4 hypersensitivity reactions occurred immediately after the initiation, but grade 1/2 reactions did not. This study was conducted to clarify the risk factors for L-OHP-related hypersensitivity reactions.Methods: Clinical data from 108 Japanese patients with colorectal cancer were analyzed, who were treated with L-OHP-containing regimens, FOLFOX4 and/or mFOLFOX6. The risk factors examined included demographic data, preexisting allergies, laboratory test data, treatment regimen, treatment line of therapy, pretreatment with steroids, total number of cycles and cumulative amount of L-OHP.Results: The incidence of grade 1/2 and grade 3/4 hypersensitivity reactions were found at 13.0% (14/108) and 9.3% (10/108), respectively. Female (P=0.037), preexisting allergies (P=0.004) and lower level of lactate dehydrogenase (P=0.003) were risk factors for grade 1/2 hypersensitivity reactions, and higher neutrophil count (P=0.043) and lower monocyte count (P=0.007) were for grade 3/4 reactions. Total number of cycles were larger in the patients with grade 3/4 reactions than those without reactions (P=0.049).Conclusions: Further extensive examination with a large number of patients is needed to establish a patient management strategy.