Actualités thérapeutiques de la sclérose en plaques

Since commercialisation of the first immunomodulatory drug (IMD) for multiple sclerosis (subcutaneous interféron beta-1b) in 1995, three new IMD have been on the market: two interferons (intramuscular interferon beta-1a and subcutaneous interferon beta-1a) and glatiramer acetate. These four immunomodulatory drugs have a similar efficiency: they reduce by about 30% the relapse rate of treated patients compared to untreated patients. Their effect on disability is moderate mainly due to the reduced relapse rate. Lately, in 2002, mitoxantrone was approved for aggressive relapsing-remitting MS and in 2007 the first monoclonal antibody (natalizumab) was approved for active relapsing-remitting MS.     

长春新碱治疗乳腺癌的临床疗效观察

目的：探讨长春新碱在乳腺癌患者中的临床疗效。方法：选取2004年1月~2010年5月的184例乳腺癌患者为研究对象,将其根据化疗方式不同分为对照组（米托蒽醌组）92例和观察组（米托蒽醌联合长春新碱组）92例,后将两组患者的治疗总有效率、不良反应发生率及治疗后1个月和3个月的生存质量评分进行统计比较。结果：观察组的治疗总有效率及治疗后1个月和3个月的生存质量评分均高于对照组,P均〈0.05,差异有统计学意义,但两组患者不良反应发生率比较,P〉0.05,差异无统计学意义。结论：长春新碱在乳腺癌患者中的临床疗效好,不良反应未见升高,可改善患者的生存质量。     

国内米托蒽醌治疗急性白血病疗效的Meta分析

目的:系统评价国内米托蒽醌治疗急性白血病的疗效。方法:计算机检索中国期刊全文数据库(1979-2010)、中国生物医学文献数据库(1989-2010),并手工检索所有纳入的参考文献,纳入米托蒽醌治疗急性白血病的随机对照试验(RCT)。评价纳入研究的方法学质量并进行资料提取后,采用RevMan4.2软件进行Meta分析。结果:共纳入5项RCT,包括341例患者。Meta分析结果显示,米托蒽醌联合化疗方案与柔红霉素联合化疗方案比较,其总有效率[RR=1.26,95%CI(1.12,1.41)]和完全缓解率[RR=1.36,95%CI(1.17,1.57)]差异均有统计学意义。结论:与柔红霉素相比,米托蒽醌能提高急性白血病治疗的总有效率和完全缓解率,但由于纳入研究样本量小,上述结论尚需要大样本、高质量的随机双盲对照试验加以证实。     

Bioreductive activation of mitoxantrone by NADPH cytochrome P450 reductase. Implications for increasing its ability to inhibit the growth of sensitive and multidrug resistant leukaemia HL60 cells

The aim of this study was to examine the role of reductive activation of mitoxantrone (MX) by human liver NADPH cytochrome P450 reductase (CPR) in increasing its ability to inhibit the growth of human promyelocytic sensitive leukaemia HL60 cell line as well as its MDR sublines exhibiting two different phenotypes of MDR related to the overexpression of P-glycoprotein (HL60/VINC) or MRP1 (HL60/DOX). Our assays showed that the reduction of MX by exogenously added CPR in the presence of low NADPH concentration had no effect in increasing its ability to inhibit the growth of sensitive and MDR tumour cells. In contrast, an important increase in antiproliferative activity of MX after its reductive activation by CPR at high NADPH concentration was observed against HL60/VINC as well as HL60/DOX cells.     

米西宁灌注预防膀胱癌术后复发的临床观察（附84例报告）

目的探讨膀胱癌术后复发的有效预防方法。方法手术治疗的84例膀胱癌患。术后采用米西宁(MTZ)行膀胱灌注治疗，并做随访和疗效观察。结果所有患均获6～24个月的随访。平均16．4个月，复发率为7．14％(6／84)，优于其他药物灌注的预防效果，并发症和副作用极轻。结论米西宁膀胱灌注预防膀胱癌术后复发有较好的效果，毒副作用少而轻，长期效果有待进一步研究。     

以米托蒽醌为主的联合化疗治疗急性白血病的临床观察

以米托恩醌为主组成联合化疗方案治疗急性白血病３０例，用ＶＭＰ方案治疗ＡＬＬ１０舍例，ＭＡ方案治疗ＡＮＬＬ２０例。结果表明，ＣＲ１３／３０中４３．３％；ＰＲ１０／３０，占３３．３％；总缓解率７６．６％。我们认为以米托蒽醌为主的化疗方案（ＶＭＰ、ＭＡ）治疗菜效。副作用不大，人均能耐受     

Expression of vaccinia-related kinase 1 (VRK1) accelerates cell proliferation but overcomes cell adhesion mediated drug resistance (CAM-DR) in multiple myeloma

Objective: Vaccinia-related kinase 1 (VRK1) has been reported to participate in the development of a variety of tumors. However, the role of VRK1 in multiple myeloma (MM) has not been investigated. The present study was undertaken to determine the expression and biologic function of VRK1 in human MM.

Methods: First, we constructed a model of cell adhesion in MM, the mRNA and protein level of VRK1 in suspension and adhesion model was analyzed by RT-PCR and western blot. Then, flow cytometry assay and western blot were used to investigate the mechanism of VRK1 in the proliferation of MM cells. In vitro, following using shRNA interfering VRK1 expression, we performed adhesion assay and cell viability assay to determine the effect of VRK1 on adhesive rate and drug sensitivity.

Results: VRK1 was lowly expressed in adherent MM cells and highly expressed in suspended cells. In addition, VRK1 was positively correlated with the proliferation of MM cells by regulating the expression of cell cycle-related protein, such as cyclinD1, CDK2 and p27^kip1. Furthermore, VRK1 could reverse cell adhesion mediated drug resistance (CAM-DR) by down-regulating the ability of cell adhesion.

Conclusion and discussion: Our data supports a role for VRK1 in MM cell proliferation, adhesion, and drug resistance, and it may pave the way for a novel therapeutic approach for CAM-DR in MM.     

米托蒽醌对HL-60细胞生长的影响

目的：探索米托蒽醌（MTN）对HL－60细胞生长的影响。方法：取对数生长期HL－60细胞，不同浓度MTN作用不同时间后，利用MTT法观察MTN对HL－60细胞的抑制效应，透射电镜，DNA电泳观察MTN作用HL－60细胞后其形态学及DNA的变化。结果：（1）毫微克级的MTN对HL－60细胞有明显的抑制效应。且此效应具有时间，剂量依赖关系。（2）MTN作用后的HL－60细胞透射电镜观察胞膜完整，出现核碎裂，凋亡小体等形态学特征。DNA电泳出现200bp左右的梯形条带。结论：MTN对HP－60细胞有明显的抑制作用。小剂量的MTN对HL－60细胞以诱导细胞凋亡为主，大剂量的MTN对HL－60细胞以细胞毒作用为主。     

含米托蒽醌化疗方案治疗血液恶性肿瘤的毒副作用临床观察

本文应用含米托蒽醌的化疗方案治疗37例血液恶性肿瘤，观察其毒副作用。结果表明，含米托蒽醌的方案毒副作用有骨髓抑制、胃肠道反应、心肝肾脏器损害、发热等。这些毒副作用症状大多轻微，且易耐受。最为严重的副作用是骨髓抑制，4例死于骨髓抑制后的出血和感染。作者认为，定期复查骨髓象、外周血象和心电图等，加强预防性措施，则可避免其毒性所造成的严重后果，提高血液系统恶性肿瘤的缓解率。     

柱切换HPLC法研究米托蒽醌毫微粒冻干静脉注射剂的药代动力学

建立了血浆中米托蒽醌的柱切换高效液相色谱测定法,测定和比较了米托蒽醌溶液型注射剂和毫微粒冻干静脉注射剂在家兔体内的血药曲线,并研究比较了二者的药代动力学参数。米托恩醌毫微粒冻干注射剂使米托蒽醌在血中浓度大为降低,血中分布容积增大了近5倍,体内平均驻留时间延长了2倍多。表明米托蒽醌毫微粒有明显的体内长效作用,结合其体内分布试验研究结果,表明其具有明显肝靶向分布作用。