TE方案与TEC方案在乳腺癌新辅助化疗中的疗效比较

[目的]对比分析多西他赛联合表柔比星加/不加环磷酰胺（TEC/TE）两种新辅助化疗方案治疗乳腺癌的近期疗效。[方法]回顾性分析2006~2009年收治的Ⅱ~Ⅲ期乳腺癌新辅助化疗患者108例的临床病理资料,分别术前接受新辅助化疗的TE方案（n=62）及TEC方案（n=46）,两组患者均在术前接受2~4个周期化疗。TE方案：多西他赛75mg/m2,第1天静脉滴注;表柔比星（EPI）60mg/m2,第1天静脉滴注。[结果]全组108例患者均可评价疗效,CR 10例（9.25%）,PR 75例（69.44%）。TE组有效率为75.81%,而TEC组有效率为82.61%,两组有效率无统计学差异（χ2=0.729,P=0.392）。Ⅱ期患者28例均生存。Ⅲ期患者80例3年生存率为82.4%,其中TE组44例3年生存率为74.6%;而TEC组36例3年生存率为91.8%,差异有统计学意义（χ2=4.149,P=0.042）。[结论]在Ⅱ~Ⅲ期乳腺癌患者新辅助化疗中,TE与TEC方案近期疗效相似,TEC组3年生存率较佳,有待于进一步加大样本量进行研究。     

右丙亚胺对表柔比星诱导大鼠心肌损伤干预机制研究

目的：比较不同剂量右丙亚胺对表柔比星诱导大鼠心肌损伤的干预作用及可能机制。方法：35只SD大鼠随机分5组,每组7只。对照组：于大鼠双侧腹腔分别注射生理盐水5mL/kg,间隔时间为30min,隔日1次,共4次（7d）;模型组（表柔比星＋生理盐水）：大鼠腹腔内注射表柔比星4.5mg/kg,隔日1次,共4次（7d）,注射表柔比星前30min于另一区域腹腔内注射生理盐水5mL/kg;表柔比星＋低、中、高剂量右丙亚胺组：大鼠腹腔内注射表柔比星4.5mg/kg,隔日1次,共4次（7d）,注射表柔比星前30min于另一区域腹腔内注射右丙亚胺45、67.5和90mg/kg,隔日1次,共4次（7d）。处死大鼠后检测各组大鼠心肌组织微量丙二醛（MDA）含量、总超氧化物歧化酶（T-SOD）活性、血浆乳酸脱氢酶（LDH）及肌钙蛋白I（cTnI）水平,观察心肌组织病理形态学改变及心肌细胞凋亡情况。结果：模型组较对照组SOD活性降低,分别为（75.10±5.14）和（101.81±13.21）U/mL,F=5.7,P=0.00;MDA含量升高,分别为（13.60±2.88）和（5.28±3.14）nmol/mg,F=7.31,P=0.00;血浆LDH升高,分别为（5.27±0.58）×103和（2.23±0.47）×103 U/L,F=23.7,P=0.00;cTnI升高,分别为（483.38±52.07）和（264.16±52.07）ρg/mL,F=20.13,P=0.00;心肌细胞病理评分升高,分别为2.70±0.20和0,F=8.65,P=0.00;凋亡指数明显升高,分别为（66.54±3.46）%和（1.55±0.74）%,F=126.86,P=0.00。而加用右丙亚胺各组均较模型组提高SOD活性,降低MDA、血浆LDH及cTnI含量,减少心肌病理评分及心肌细胞凋亡指数,P〈0.01或P〈0.05。结论：右丙亚胺对表柔比星诱导的大鼠心肌损伤有保护作用,其机制可能与减少氧自由基的产生、降低脂质过氧化物含量以及调节心肌细胞凋亡机制有关。     

乳腺癌细胞原位移植模型的建立及紫杉醇和表柔比星联合用药疗效

目的 建立乳腺癌细胞原位移植瘤模型,观察紫杉醇及联合表柔比星的抑瘤效果,为临床联合用药提供实验依据。方法 用乳腺癌细胞悬液接种于动物脂肪垫下建立荷瘤鼠,待瘤块直径≥1 cm时,处死动物剥离肿瘤,接种于裸小鼠脂肪垫下,建立原位移植的乳腺癌肿瘤模型。成模动物按瘤体积大小随机分为紫杉醇组、表柔比星组、联合用药组及模型对照组4组,连续给药3周后,观察各组小鼠的肿瘤生长情况,抑瘤率及肿瘤组织中P53蛋白的表达情况。结果 成功建立原位移植的乳腺癌肿瘤模型,成模小鼠给药3周后,与模型对照组相比,各给药组小鼠体重和瘤重均有显著下降（P<0.05）,其中,紫杉醇组抑瘤效果显著;给药后第8天,紫杉醇组小鼠肿瘤体积与模型对照组比较有显著性差异（P<0.05）,给药后第21天,紫杉醇组的抑瘤率达到82.53%;肿瘤组织中P53蛋白的表达情况,与模型对照组相比,紫杉醇组和联合给药组表达显著减弱（P<0.05）。结论 成功构建原位乳腺癌模型,实验结果显示紫杉醇及其与表柔比星的联合用药对肿瘤均有一定抑制作用。     

A phase 2 study of gemcitabine and epirubicin for the treatment of pleural mesothelioma: a North Central Cancer Treatment Study, N0021

BACKGROUND: The North Central Cancer Treatment Group (NCCTG) conducted a phase 2 study to evaluate the antitumor activity of the combination of gemcitabine and epirubicin in patients with pleural mesothelioma who received no more than 1 prior chemotherapy regimen. METHODS: A total of 23 patients were accrued between August 2001 and April 2002 and received gemcitabine at a dose of 1000 mg/m(2) intravenously over 30 minutes weekly every 2 weeks and epirubicin at a dose of 90 mg/m(2) intravenously on Day 1 on an every-21-days cycle (high-dose patient group). Between August 2002 and April 2004, an additional 45 patients were treated at a reduced dose of gemcitabine of 750 mg/m(2) and epirubicin at a dose of 70 mg/m(2) with the same schedule (low-dose patient group). RESULTS: In the high-dose patient group, the confirmed response rate was 13% (95% confidence interval [95% CI], 3-34%). The median survival was 9.3 months (95% CI, 7.4-10.7 months) and the median time to disease progression was 6.3 months (95% CI, 3.0-7.6 months). In the low-dose patient group, the confirmed response rate was 7% (95% CI, 0-28%). The median survival was 5.7 months (95% CI, 4.7-8.7 months) and the median time to disease progression was 4.2 months (95% CI, 2.7-5.6 months). Toxicity was moderate to severe. In the high-dose and low-dose groups, 87% and 60% of patients, respectively, experienced at least 1 adverse event of grade 4 or higher (according to National Cancer Institute Common Toxicity Criteria [version 2.0]). The quality of life remained similar from baseline to the end of the 2 cycles of treatment in the high-dose group but worsened in the low-dose group. CONCLUSIONS: In the current study, the combination regimen of gemcitabine and epirubicin was found to demonstrate minimal antitumor activity against pleural mesothelioma.     

人肝癌多药耐药细胞系BEL-7402/ADM的建立及耐药相关基因表达检测

目的：建立人肝癌多药耐药细胞系,研究其耐药特性及机制。 方法：应用人肝癌细胞株BEL-7402,采用阿霉素（ADM）大剂量间歇诱导法,建立多药耐药细胞系BEL-7402/ADM。相差显微镜观察细胞,用MTT法检测该耐药细胞株对多种化疗药物的多药耐药性,采用流式细胞术检测该耐药细胞表面多药耐药基因(MDR)的表达产物P糖蛋白(P-gp)、多药耐药相关蛋白(MRP)及谷胱甘肽硫转移系统(GSH／GST)的表达情况,应用RT-PCR检测MDR、MRP基因表达水平。 结果：BEL-7402/ADM对多种抗癌药物产生耐药,对ADM的耐药性(半数抑制浓度,IC₅₀)提高了17.31倍。流式细胞仪分析发现（65.5±5.8）%的BEL-7402/ADM细胞表面P-gp 表达阳性,而对照细胞BEL-7402表达仅为（31.3±4.3）%;（32.4±3.5）%的BEL-7402/ADM细胞表面MRP表达阳性,而对照细胞BEL-7402表达仅为（23.4±3.1）%,二者差异有显著性(P<0.01);BEL-7402/ADM和BEL-7402细胞的GSH／GST表达无明显变化（P>0.05）。RT-PCR检测发现BEL-7402/ADM中MDR及MRP mRNA高表达。 结论：BEL-7402/ADM具有明确的多药耐药性,其多药耐药相关基因MDR及MRP mRNA表达升高。     

高剂量表柔比星为主的联合化疗方案治疗48例晚期胸部恶性肿瘤

目的：评价高剂量表柔比星（表阿霉素）联合其他化疗药物治疗晚期胸部肿瘤的疗效及毒副反应。方法：48例可评价晚期胸部肿瘤中非小细胞癌32例;乳腺癌11例;纵隔恶性淋巴瘤5例。分别应用EMP[表柔比星（EPI）100mg/m^2联合丝裂霉素（MMC)6mg/m^2及顺铂（DDP）60mg/m^2]治疗非小细胞肺癌;应用CEF[环磷酰胺（CTX）600mg/m^2联合表柔比星100mg/m^2及氟尿嘧啶（5－FU）800mg/m^2]治疗乳腺癌。应用CEOP[环磷酰胺600mg/m^2联合表柔比星100mg/m^2、长春新碱（VCR）1mg/m^2及强的松60mg/m^2]治疗纵隔恶性淋巴瘤。3－4周重复。结果：非小细胞肺癌总有效率56．3％;乳腺癌总有效率72．7％;纵隔恶性淋巴瘤总有效率100％。白细胞减少为主要毒副反应,发生率为93．8％。未见明显心脏毒性。结论：高剂量表柔比星治疗晚期胸部恶性肿瘤安全有效。     

高剂量表阿霉素治疗非小细胞肺癌的随机研究

目的：观察以高剂量表阿霉素联合方案治疗非小细胞肺癌（NSCLC）的疗效和毒副反应。方法：每个病人给予两周期的EVpP方案治疗,每个周期表阿霉素（Eqinubicin)55mg/m2,cl1,2或d1,14;Vp16 100mg/d,d1-4,DDP 80mg/m2,d1。结果：可评价疗效20例患者中10例有效（PR）,总有效率50．0％,主要毒副反应为骨髓抑制,脱发,呕吐,口腔炎,结论：高剂量表阿霉素为主的联合化疗方案是治疗非小细胞肺癌有效的方案。     

Identification of the highest dose of docetaxel associable with active doses of epirubicin. Results from a dose-finding study in advanced breast cancer patients

Purpose:To determine the maximum tolerated dose (MTD) and thedose limiting toxicity (DLT) of docetaxel in combination with fixed doses ofepirubicin. Patients and methods:Women with locally advanced or metastaticbreast cancer were given docetaxel, 60 mg/m² in escalated doses bysteps of 10 mg/m², in association with two fixed doses ofepirubicin (90 mg/m², and 75 mg/m²). Since neutropeniawas foreseen to be the most likely DLT, a third group with prophylactic G-CSFsupport was planned to define the MTD of docetaxel with 90 mg/m²of epirubicin. Selected patients underwent pharmacokinetic evaluation ofdocetaxel. Results:Fifty-eight patients entered the study. At the first step(90 mg/m² of epirubicin) the MTD was obtained at 60mg/m² of docetaxel. At the second step (75 mg/m² ofepirubicin) the MTD of docetaxel was 80 mg/m². At the third step(epirubicin 90 mg/m²) G-CSF allowed a safe escalation of docetaxelup to 90 mg/m². Neutropenia was the most common hematologicaladverse event. Without G-CSF, grade 4 neutropenia occurred in 69% ofcycles, of which 11% was complicated by fever. In G-CSF group, grade4 neutropenia and neutropenic fever occurred in 31% and 3%,respectively. Most frequent non-hematological adverse effects were asthenia(45%), nausea (39%) and mucositis (36%). No patientdeveloped congestive heart failure. Two toxic deaths occurred. Overallresponse rate was 73% in 42 out of 58 patients, with no apparentepirubicin dose-related effect. No statistically significant effect of the twodoses of epirubicin was observed in docetaxel pharmacokinetics. Conclusions:On the basis of the toxicity profile, the docetaxelpharmacokinetics and the response rate observed, epirubicin 75mg/m² combined with docetaxel 80 mg/m² can berecommended for further studies.     

JNK3重组腺病毒促进表柔比星诱导的人成神经细胞瘤SH-SY5Y细胞凋亡

目的:构建人JNK3基因重组腺病毒,检测其对人成神经细胞瘤SH-SY5Y细胞增殖的影响;以表柔比星作为凋亡诱导剂,检测其对细胞凋亡的影响。方法:以pDBLeu-JNK3质粒为模板PCR扩增人JNK3基因全长,构建重组穿梭载体pAdTrack-CMV-JNK3,线性化后与骨架载体pAdEasy-1在细菌BJ5183内同源重组,在HEK293细胞中进行病毒包装和扩增,经PCR方法鉴定后,用包装后的病毒上清感染人成神经细胞瘤SH-SY5Y细胞,Western印迹方法检测JNK3蛋白的表达;MTT实验检测其对细胞增殖的影响;流式细胞术和琼脂糖凝胶电泳检测表柔比星诱导的细胞凋亡情况。结果:核酸测序和PCR鉴定表明成功构建Ad-JNK3,终点稀释试验测定扩增的腺病毒滴度为6.5×1010 pfu/ml;Ad-JNK3在SH-SY5Y细胞中表达JNK3蛋白;MTT检测结果表明Ad-JNK3可抑制SH-SY5Y细胞生长,抑制率为28.08%;流式细胞术结果表明Ad-JNK3可明显促进表柔比星诱导的细胞凋亡,琼脂糖凝胶电泳可观察到DNA梯形条带。结论:重组腺病毒Ad-JNK3能显著抑制SH-SY5Y细胞增殖,促进表柔比星诱导的SH-SY5Y细胞凋亡,为研究JNK3的作用机制及将其用于人成神经细胞瘤的基因治疗提供了条件。     

多西他赛联合表阿霉素治疗乳腺癌的疗效观察

目的 探讨多西他赛联合表阿霉素治疗乳腺癌的临床疗效和毒副反应.方法 将60例乳腺癌患者随机分为观察组和对照组,每组30例.观察组给予多西他赛联合表阿霉素治疗,对照组给予表阿霉素治疗,比较观察2组患者的临床疗效和毒副反应.结果 观察组和对照组的总有效率分别为96.67％和76.67％,观察组疗效明显优于对照组(P＜0.05);主要毒副反应为骨髓抑制、消化道反应,观察组发生率明显低于对照组(P＜0.05).结论 多西他赛联合表阿霉素治疗乳腺癌疗效显著,毒副反应可耐受.