羟基喜树碱与吡柔比星联合应用对膀胱癌5637细胞株影响的体外研究

目的：研究羟基喜树碱与吡柔比星联合应用对膀胱癌5637细胞生长的抑制作用。方法：将所培养的5637细胞分为五组．未加药5637细胞组、羟基喜树碱（HCPT）单药组、吡柔比星（THP）单药组、先羟基喜树碱后吡柔比星联合用药组、先吡柔比星后羟基喜树碱联合用药组。用RT-PCR检测残存细胞所表达的耐药基因（mrp-4，mrp-1，mdr-1），用MTT方法测定各组细胞的抑制情况。结果：联合使用对5637细胞增殖抑制作用优于单药THP和HCPT对肿瘤细胞的抑制作用。单用HCPT，残存的细胞中表达mrp-1和mdr-1。单用THP、残存的细胞中表达mrp-4和mdr-l。联合使用HCPT和THP后，残存细胞中仅表达mdr-1，两者联合应用起到了降低肿瘤细胞耐药性的目的。结论：HCPT和THP联合用于膀胱内灌注化疗具有联合化疗用药的合理性。     

高效液相色谱法检测吡柔比星的血药浓度

建立一种ＨＰＬＣ法分离和检测人血浆中吡柔比星的分析方法学。以柔红霉素为内标,１ｍｌ血浆加０．１ｍｌ（０．４ｍｏｌ／Ｌ,ｐＨ＝９．０）的氯化铵缓冲液碱化后以ＣＨＣＬ３：ＣＨ３ＯＨ（２：１）混合溶剂提取２次。在Ｐｈｅ－ｎｏｍｅｎｅｘ（Ｃ１８）柱上,以０．０４ｍｏｌ／Ｌ ＫＨ２ＰＯ４（ｐＨ＝３．０）：ＣＨ３ＣＮ＝６９：３２为流动相,荧光检测波和长４８０／５０ｎｍ（ＥＸ／Ｍ）。结果,血浆中吡柔比星的线性范     

吡柔比星诱导结肠癌细胞株SW-260的凋亡

目的：观察吡柔比星（pirarubicin,ＴＨＰ）对结肠癌细胞株ＳＷ－２６０凋亡的影响。 方法：将ＴＨＰ加入ＳＷ－２６０细胞培养液,Ｈoechst３３２５８荧光染色、透射电镜观察ＳＷ－２６０细胞形态学变化;ＤＮＡ抽提琼脂糖电泳观察ＤＮＡ的“梯状”条带;并测定细胞ＤＮＡ断裂百分率,以探讨ＴＨＰ能否引起人结肠癌细胞株ＳＷ－２６０发生凋亡。结果：不同浓度ＴＨＰ（５,１０,１５umol/Ｌ）作用于ＳＷ－２６０细胞２４小时及１     

三种药物对人乳腺癌细胞体外杀伤作用比较

目的比较吡柔比星(THP)和阿霉素(ADM)、表阿霉素(EPI)对人乳腺癌细胞的体外抑制及凋亡诱导作用,以及药物杀伤的时效关系.方法采用ATP生物荧光肿瘤体外药敏检测技术(ATP-TCA),比较吡柔比星和阿霉素、表阿霉素对人乳腺癌细胞系MCF-7、T-47D和Bcap-37的生长抑制作用,并绘制细胞存活率-时间曲线;用Annexin V凋亡检测技术检测药物诱导细胞凋亡的情况.结果3种药物对乳腺癌细胞系MCF-7、T-47D和Bcap-37的生长抑制作用呈现明显的剂量依赖性;吡柔比星对其生长抑制作用明显高于阿霉素和表阿霉素,其IC50仅相当于阿霉素和表阿霉素的1/3～1/6,与后两者的差异均具有显著意义(P＜0.01);阿霉素和表阿霉素的抑制作用相当,两者IC50无显著性差异(P＞0.05).三种药物对乳腺癌细胞的抑制作用均呈时间依赖关系,低浓度的吡柔比星在短时间内(12h)即具有生长抑制作用,而阿霉素和表阿霉素的起效时间较为迟缓(24～36h),72h后肿瘤细胞的存活率较吡柔比星高10%～20%.3种乳腺癌细胞分别经低浓度的吡柔比星、阿霉素和表阿霉素处理后均可诱导凋亡,其中吡柔比星组的细胞凋亡比例较其它两组为高.结论吡柔比星对乳腺癌细胞具有较好的生长抑制和凋亡诱导作用,其起效时间明显早于阿霉素和表阿霉素.该药良好的抑瘤效果和迅速的起效时间对于提高乳腺癌临床疗效,减轻不良反应有重要的参考和临床应用价值.     

不同溶剂配制吡柔比星在经尿道膀胱肿瘤电切术后膀胱灌注的疗效观察

目的评价生理盐水和注射用水配制吡柔比星在经尿道膀胱肿瘤电切(TUR-Bt)术后膀胱灌注的疗效和副反应.方法将TUR-Bt术后30例膀胱癌患者随机分为两组,分别用生理盐水和注射用水配制吡柔比星进行膀胱灌注,观察疗效并随访.结果两组随访12～18个月,均无肿瘤复发,术后3,6个月查肝肾功能和血常规均正常.生理盐水组有明显膀胱刺激症12例,术后3个月膀胱镜检查有溃疡形成6例,被迫停止灌药4例.注射用水组有明显膀胱刺激症5例,术后3个月膀胱镜检查有溃疡形成2例,被迫停止灌药1例.结论生理盐水和注射用水配制吡柔比星在TUR-Bt术后膀胱灌注均有较好的预防膀胱癌复发的疗效,但生理盐水组有明显膀胱刺激症,并可引起膀胱溃疡.     

The effect of pirarubicin chemotherapeutic regimen on osteosarcoma associated with lung metastasis and myocardial function assessment北大核心

Objective: To evaluate the clinical effect of pirarubicin (THP) chemotherapeutic regimen on osteosarcoma with lung metastasis, detect the heart function, and evaluate the adverse reactions induced by THP. Methods: For the 32 patients THP 50 mg/m2 was given on day 1 and cisplatin (DDP) was given for 2-3 d with total dosage of 80 mg/m2 or ifosfamide (IFO) was given for 4 d with total dosage of 8 g/m2. A color Doppler ultrasound echocardiography was used to measure the ejection ratio of left ventricle and the heart function parameters such as E/A value. Results: The survival time was (31.00 ±7.98) months and the disease free time was (13.00 ± 2.46) months. The objective remission rate was 46. 88% and the partial remission rate was 40.63 % in osteosarcoma patients with lung metastasis after combined THP chemotherapy. The side effects induced by THP treatment mainly involved gastrointestinal reaction and bone marrow depression. The left ventricular ejection fraction showed no significant difference between the groups who received various THP cumulative dosages. The E/A value was significantly decreased in high THP cumulative dosage group after chemotherapy (P < 0.05). Conclusion: The THP chemotherapeutic regimen is effective and safe in the treatment of osteosarcoma with lung metastasis, which could be served as a salvage chemotherapeutic regimen. Two dimensional and color Doppler echocardiography may be valuable to assess the early cardiotoxicity induced by anthracyclines.     

TEAA方案治疗难治性及复发性急性白血病疗效观察

目的:探讨治疗难治性复发性急性白血病(AL)的有效方案。方法:27例难治性复发性AL用吡柔比星(THP)、足叶乙甙(VP16)、安吖啶(AMSA)、阿糖胞苷(Ara-C)组成的TEAA方案治疗。用法:THP10mg/d,静脉滴注,第1~3天;VP16 100mg/d,静脉滴注,第1~4天,AMSA75mg/d,第1~3天,静脉滴注;Ara-C200mg/d,第1~7天,静脉滴注。结果:在1~3个疗程(平均1.4疗程,32.5d后)完全缓解16例(59.3%),部分缓解(PR)5例(18.5%),总有效率为77.8%。结论:TEAA方案是治疗难治性复发性AL较有效的方案。     

Stability and compatibility of four anthracyclines: doxorubicin, epirubicin, daunorubicin and pirarubicin with PVC infusion bags

A rapid isocratic technique was developed for the analysis of four anthracyclines (doxorubicin, epirubicin, daunorubicin and pirarubicin) in parenteral solutions using high pressure liquid chromatography (HPLC) with fluorescence detection and a C18 Hypersil ODS column. The availability and compatibility of these drugs from solutions infused via PVC infusion bags through PVC administration sets have been examined. No significant drug loss was observed during simulated infusions (n=4) for 24 h using PVC infusion bags and administration sets. No significant difference was found between infusion solutions (5% glucose or 0.9% NaCl), except for pirarubicin. The reconstitution of pirarubicin in 0.9% NaCl was impossible, because we observed a precipitation of the compound in solution. The stability of the drugs was also studied in solution, in PVC bags after storage at 4°C with protection from light. The results show the stability of doxorubicin, epirubicin and daunorubicin during 7 days of storage to be satisfactory, irrespective of the infusion solution (5% glucose or 0.9% NaCl). In the case of pirarubicin, the stability of the drug was satisfactory during 5 days of storage in 5% glucose, but beyond, we observed a degradation of the compound with formation of doxorubicin in the infusion solution.     

吡柔比星诱导膀胱癌细胞凋亡的实验研究及预防膀胱癌术后复发的效果

目的　探讨吡柔比星诱导膀胱癌细胞凋亡的机制和膀胱内灌注预防术后复发的效果。　方法　采用MTT法、流式细胞术和透射电子显微镜技术 ,研究不同浓度的吡柔比星对人膀胱癌细胞株T2 4的抑制作用。对 6 0例经尿道电切术的膀胱移行细胞癌患者 ,术后以 30～ 40mg吡柔比星膀胱内灌注 ,观察预防复发的效果。　结果　吡柔比星浓度为 10mg/L和 10 0mg/L时 ,对T2 4细胞生长的抑制率分别为 80 %和 94% ,G1期前出现明显的凋亡峰 ,可见胞浆内空泡形成、核染色质凝聚等典型细胞凋亡特征。当浓度为 10 0 0mg/L时 ,细胞出现坏死特征。共 5 8例完成 1个以上疗程 ,平均随访 18.8个月 ,复发 5例 (8.6 % )。　结论　抑制癌细胞生长和诱导细胞凋亡甚至死亡是吡柔比星抗肿瘤的机制之一。用吡柔比星进行膀胱内灌注预防膀胱癌术后复发安全、有效     

经尿道钬激光联合吡柔比星灌注治疗腺性膀胱炎

目的探讨经尿道钬激光联合吡柔比星灌注治疗腺性膀胱炎的方法及疗效。方法经膀胱镜检及活组织检查确诊38例腺性膀胱炎患者，均行经尿道钬激光切除，术后给予吡柔比星膀胱灌注治疗。结果38例获得8～40个月随访。27例治愈，8例好转，其中有3例6～12个月复发，无癌变。结论经尿道钬激光切除术后应用吡柔比星膀胱内灌注能减少腺性膀胱炎术后复发，且副反应少，安全性较高。