IL-2联合吡柔比星膀胱灌注预防膀胱癌复发

目的：探讨生物制剂联合化疗药物膀胱灌注预防膀胱癌术后复发的机制。方法：对比研究白细胞介素2（IL－2）和吡柔比星联合膀胱灌注与单用吡柔比星膀胱灌注前后患者血、尿肿瘤坏死因子（TNF）和血IL－2受体的动态变化。结果：联合膀胱灌注组的TNF和IL－2受体水平显著高于吡柔比星组（P＜0．01）。结论：联合灌注组机体的细胞免疫功能得到更好改善,IL－2增加肿瘤细胞对免疫反应的应答,两者间有免疫促进及协同作用。     

Multimodal therapy with intravenous biweekly leucovorin, 5-fluorouracil and irinotecan combined with hepatic arterial infusion pirarubicin in non-resectable hepatic metastases from colorectal cancer (a European Association for Research in Oncology trial).

BACKGROUND: The purpose of this study was to evaluate the tolerance and efficacy of combining i.v. irinotecan, 5-fluorouracil (5-FU) and leucovorin (LV) with hepatic arterial infusion (HAI) of pirarubicin in non-resectable liver metastases from colorectal cancer. PATIENTS AND METHODS: Thirty-one patients were included in a phase II trial with i.v. irinotecan/5-FU/LV administered every 2 weeks, combined with HAI pirarubicin 60 mg/m(2) on day 1 every 4 weeks. In most cases HAI was administered via a percutaneous catheter. RESULTS: The main grade 3/4 toxicity was neutropenia, encountered in 78% of the patients. When all patients were considered in the analysis, tumour response rate was 15 out of 31 [48%; 95% confidence interval (CI) 32% to 65%]. Liver resection was made possible in 11 patients (35%; 95% CI 21% to 53%). There were no toxic death. Median overall survival was 20.5 months, and median progression-free survival was 9.1 months. In patients with completely resected metastases, median overall survival was not reached and median progression-free survival was 20.2 months. CONCLUSION: The multimodality approach used in the present study was well-tolerated and yielded dramatic responses. An aggressive approach combining i.v. and HAI chemotherapy deserves further investigation.     

骨肉瘤常用化疗药物作用的分子机制及用药方法选择

目的 研究常用骨肉瘤化疗药物作用的分子机制,对临床用药方式提供指导.方法 将骨肉瘤细胞混悬液与不同浓度吡柔比星、顺铂、卡铂、甲氨蝶呤、异环磷酰胺分别作用24、48、72 h后,用倒置显微镜观察细胞生长情况.用MTT法测定每一孔的吸光度值OD,制作生长曲线,并求出药物的IC50.用IC50浓度的药物分别作用于骨肉瘤细胞24、48和72 h后用流式细胞仪进行细胞周期分析,了解细胞的周期分布及细胞的增殖活性.免疫印迹技术观察细胞的PCNA、Bcl-2、Bax、cyclin D1、cyclin E的表达.结果 在倒置显微镜下观察不同药物浓度作用于的骨肉瘤细胞,比较细胞死亡数量于时间关系.MTT实验:不同时间组及不同浓度组与对照组相比,对MG-63细胞的生长抑制作用差异均具有显著性(P＜0.05),呈现不同剂量-时间效应关系.细胞周期分析:在细胞各期可见明显凋亡峰,细胞周期各期所占比例无明显变化,抑制作用呈剂量依赖性.蛋白免疫印迹:PCNA在不同药物组骨肉瘤表达与对照组相比明显不同,不同药物组Bax表达与对照组明显增加,Bcl-2表达减少.cyclin D1、cyclin E的表达明显减少.结论 吡柔比星对MG-63细胞的抑制率和时间关系密切,和浓度有一定的关系.同样剂量吡柔比星5d的效果比3d好.卡铂具有与顺铂类似的效应,但卡铂如果替代顺铂在化疗中的作用,卡铂的量必须是顺铂的25倍以上.甲氨蝶呤作用于骨肉瘤细胞MG-63后,随着药物浓度的增加和时间的延长,作用逐渐增强,尤其是用量和效果有明显关系.异环磷酰胺在体外对骨肉瘤细胞无明显抑制作用.     

TACE术中灌注氟尿嘧啶、奥沙利铂及吡柔比星治疗原发性肝癌的临床效果分析

目的观察评价肝动脉化疗栓塞（TACE）联合灌注奥沙利铂（OXA）、氟尿嘧啶（5-Fu）及吡柔比星（THP）方案治疗原发性肝癌的疗效和安全性。方法回顾分析采用TACE术中动脉灌注OXA/5-Fu/THP化疗药物治疗的原发性肝癌患者65例,及同期行单纯肝动脉栓塞（TAE）治疗的原发性肝癌患者21例,分为TACE组和TAE组。对TACE灌注OXA/5-Fu/THP的疗效、不良反应发生率、无进展生存时间（PFS）及总生存期（OS）进行综合评价,并与单纯肝动脉栓塞进行对比分析研究。结果 TACE联合OXA/5-Fu/THP治疗的65例患者中,客观缓解率（ORR）55.4%,疾病控制率（DCR）81.5%;患者的中位PFS时间为11.5个月,中位OS时间为18.5个月;单因素分析中,Child-Pugh A级、无门脉癌栓、无肿瘤转移、肿瘤直径小及TACE治疗次数多的患者预后较好,差异有统计学意义（P＜0.05）;巴塞罗那分期（BCLC）B期的患者预后优于C期的患者,差异有统计学意义（P=0.000）;Cox多因素分析中门脉癌栓及肿瘤远处转移是患者预后的独立危险因素。与单纯TAE 相比,TACE 联合OXA/5-Fu/THP 可提高患者的mPFS。结论TACE术中动脉灌注OXA/5-Fu/THP治疗原发性肝癌的疗效较好,不良反应少。     

应用雷替曲塞经肝动脉化疗栓塞治疗中晚期原发性肝癌的临床疗效

目的 应用雷替曲塞与碘化油混合乳剂行TACE治疗中晚期原发性肝癌,观察其临床效果及安全性。方法 对我院收治的不能手术切除的原发性中晚期肝癌患者80例的临床资料进行研究,按治疗方案分为治疗组与对照组,每组40例。观察两组患者近期(术后1个月)疗效,包括中位疾病进展时间及1年、2年生存率、患者血清肿瘤标记物(AFP、CA19-9)、转氨酶及胆红素变化,不良反应发生情况。结果 治疗组术后3个月RR、DCR均高于对照(P<0.01);治疗组的1年与2年生存率分别为81.6%、57.5%,显著高于对照组的67.0%和35.9%(P<0.05);治疗组中位生存期为11.6个月,高于对照组7.3个月(P<0.05);治疗组术后1个月AFP、CEA、转氨酶、胆红素水平下降的例数多于对照组(P<0.05);两组间不良反应发生率比较显示无统计学意义(P>0.05)。结论 应用雷替曲塞与碘化油经肝动脉内栓塞治疗中晚期原发性肝癌临床效果显著,安全性良好。     

术后膀胱灌注联合生物制剂预防膀胱癌复发的临床观察

目的：总结吡柔比星（THP）膀胱灌注联合乌苯美司片预防浅表性膀胱癌术后复发的疗效及安全性。方法：2008年10月～20n年10月对103例浅表性膀胱尿路上皮癌患者行经尿道膀胱肿瘤切除（TURBT）术,术后分成两组,其中THP膀胱灌注联合鸟苯美司片组56例,单纯THP膀胱灌注组47例。THP灌注方法为30mg／次,每次膀胱内保留30min,每周1次共8次,然后每月1次共8次;乌苯美司片服法30mg／d,早晨顿服,连用10个月。定期行膀胱镜检查。结果：103例患者获得随访,平均随访（12．5±6．28）个月,THP联合乌苯美司组1年和2年复发率分别为8．9％和10．7％;单纯THP组1年和2年复发率分别为12．8％和19．1％,差异有统计学意义。THP联合乌苯美司组副作用主要为膀胱刺激征及轻微血尿,全身副作用少,症状轻,较单纯THP组无明显差异。结论：THP膀胱灌注联合乌苯美司片预防浅表性膀胱癌术后复发疗效满意,副作用以下尿路局部症状为主,安全性好。     

Cardioprotective effects of rutin in rats exposed to pirarubicin toxicity

We established both an acute and chronic cardiac toxicity rat model, which showed pretreatment with rutin attenuated pirarubicin-induced myocardial histopathological injury, electrocardiogram abnormalities, and cardiac dysfunction. Rutin also significantly reduced serum levels of MDA, BNP, CK-MB, CTnT, and LDH and increased serum SOD levels. Treatment with rutin and dexrazoxane resulted in an increase in Bcl-2/Bax ratio (p < 0.05) and reduction in JNK and Caspase-3 protein levels, compared to the pirarubicin group (all p < 0.05). Furthermore, rutin at a dose of 50 mg/kg significantly attenuated the above-mentioned alterations. Our study suggests the antioxidant and anti-apoptotic properties of rutin may be responsible for the cardioprotective effects observed.     

长春地辛、吡柔比星、环磷酰胺、地塞米松联合治疗非霍奇金淋巴瘤的疗效观察

目的观察应用长春地辛(VDS)、吡柔比星(THP)、环磷酰胺(CTX)、地塞米松(DXM)联合治疗非霍奇金淋巴瘤的疗效及不良反应。方法患者予以VDS 2.5 mg.m-2,d1,8;THP 25 mg.m-2,d1,8;CTX 0.6 g.m-2,d1,8;DXM 10 mg.d-1,d1-10。28 d重复,2个疗程予以评价。结果总有效率(CR PR)为82.1%,不良反应为血液毒性,经G-CSF治疗可恢复,未见明显的外周神经毒性。结论VDS、THP、CTX和DXM联合治疗淋巴瘤安全有效。     

吡柔比星预防浅表性膀胱癌术后复发的效果观察

目的探讨吡柔比星预防浅表性膀胱癌术后复发效果厦其副作用。方法55例浅表性膀胱癌患者经尿道电切术后随机分为观察组29例和对照组26例，观察组；吡柔比星30mg＋蒸馏水30ml；对照组：塞替哌60mg＋蒸馏水30ml，术后立即膀胱灌注1次,保留30min。术后1周继续灌注．每周1次。共8次，之后每月1次。比较二组术后复发及不髓反应情况。结果观察组4例复发（13．8％）；对照组7例复发（26．9%）。复发后肿瘤临床分期；观察组4例均为T1前期；对照组7例分别为Ta期3例、T1期1例、T2期3例。复发肿瘤病理分级：观察组G1级3例、G2级1例；对照组G1级3例、G2级1例、G3级3例。二组复发及不良反应情况比较差异有统计学意义,P〈0．001。结论浅表性膀胱癌术后THP膀胱灌注能有效抑制肿瘤复发，提高患者生存率。     

The role of structural factors in the kinetics of cellular uptake of pyrazoloacridines and pyrazolopyrimidoacridines: implications for overcoming multidrug resistance towards leukaemia K562/DOX cells

The appearance of multidrug resistance (MDR) of tumour cells to a wide array of antitumour drugs, structurally diverse and having different mechanisms of action, constitutes the major obstacle to the successful treatment of cancer. Our approach to search for non-cross resistant antitumour agents is based on the rational design of derivatives, which have a high kinetics of passive cellular uptake rendering their active efflux by MDR exporting pumps inefficient. Recently, two families of acridine cytotoxic agents were obtained, pyrazoloacridines (PACs) and pyrazolopyrimidoacridines (PPACs). The aim of this study was to examine molecular basis of the reported differences in retaining cytotoxic activity of these derivatives at cellular level against resistant erythroleukaemia K562/DOX (overexpressing P-glycoprotein) cell line. The study was performed using a spectrofluorometric method, which allows continuous monitoring of the uptake and efflux of fluorescent molecules by living cells. It was demonstrated that the presence of two additional rings, pyrazole and pyrimidine, fused to the acridine chromophore structure (PPAC) favoured more rapid cellular diffusion than the presence of only one additional pyrazole ring (PAC). The presence of hydrophobic substituent OCH3 markedly favoured the cellular uptake of pyrazoloacridines and pyrazolopyrimidoacridines while compounds having hydrophilic substituent OH exhibited very low kinetics of cellular uptake. In contrast, it was found that neither structure of the ring system nor the hydrophobic/hydrophilic character of examined substituents determined the rate of active efflux of these compounds by P-glycoprotein. Our data showed that a nearly linear relation exists between the resistance factor (RF) and lnV+ reflecting the impact of the cellular uptake rate (V+) on the ability of these compounds to overcome MDR.