环磷酰胺,阿霉素,顺铂联合用药与单一用药药动学的比较

对环磷酰胺、阿霉素、顺铂采用联合用药方案给药与单一给药进行家兔和癌症病人药动学的研究。结果表明，家兔联合用药方案中３种药物Ｔ＿（１／２）和在肾脏的ＡＵＣ均大于单一用药；联合用药方案中环磷酰胺、顺铂在肺脏的ＡＵＣ小于单一用药，只有阿霉素在肺脏ＡＵＣ大于单一用药，滞留时间也延长。病人药动学研究表明，由于清除率不同，ＡＵＣ差别显著。因此，抗癌药物联合用药时，应以ＡＵＣ、Ｔ＿（１／２）、Ｃ＿（ｓｓ）为指标调整给药方案。     

颐康冲剂对阿霉素、丝裂霉素、氟尿嘧啶的增效作用及其对毒性影响的实验研究

颐康冲剂由香菇、当归、红参等１６味药材提制而成。实验结果表明，颐康冲剂与阿霉素、丝裂霉素及氟尿嘧啶分别伍用，能明显提高对小鼠移植肿瘤Ｓ１８０、Ｈ２２及Ｌｅｗｉｓ抑瘤率，与单用３种化疗药物相比，Ｐ值＜０．０５～０．００１。对３种化疗药物所致免疫器官萎缩、巨噬细胞吞噬功能下降、染色体畸变及白细胞减少等均有显著保护作用，同时还能显著提高ＮＫ细胞活性。说明颐康冲剂不仅是一种有效的肿瘤化疗药物增效剂，而且能提高机体免疫功能，显著降低化疗药物的毒副反应。     

TNP-470与阿霉素联合使用治疗小鼠膀胱癌

目的观察血管形成抑制剂TNF-470与化疗药物阿霉素联合应用抑制小鼠膀胱癌的协同作用.方法分别予TNP-470、阿霉素、TNP-470 阿霉素治疗TN39膀胱癌荷瘤小鼠,观察肿瘤生长及血管形成、细胞凋亡情况.结果治疗后12 d,TNP-470、阿霉素及TNP-470 阿霉素治疗组抑瘤率分别为46.3%、21.4%及56.5%,TNP-470组微血管密度明显减少、凋亡指数增多,阿霉素组凋亡指数增多,TNP-470 阿霉素组凋亡指数进一步增加.结论TNP-470与阿霉素治疗小鼠膀胱肿瘤,有明显的抗肿瘤协同作用,其机理可能是通过抑制血管形成及化疗药物细胞毒性作用而促使肿瘤细胞凋亡进一步增加.     

卡托普利对阿霉素心脏毒性作用的影响

用离体大鼠心脏灌流模型观察了卡托普利（ｃａｐｔｏｐｒｉｌ，ＣＡＰ）对阿霉素（ａｄｒｉａｍｙｃｉｎ，ＡＤＭ）急性心肌毒性作用的影响。结果表明，ＡＤＭ（６ｍｇ／Ｌ）灌注能造成心肌收缩力的严重损害，冠脉灌注压的明显升高和心肌丙二醛含量的增加；治疗剂量的ＣＡＰ（４０ｍｇ／Ｌ）并不能保护心肌，反而加重了ＡＤＭ对心脏的毒性作用。作者认为，在防治ＡＤＭ所致的心功能不全时应慎用ＣＡＰ。     

A new superinvasive in vitro phenotype induced by selection of human breast carcinoma cells with the chemotherapeutic drugs paclitaxel and doxorubicin

Doxorubicin- and paclitaxel-selected variants of an in vitro invasive clonal population of the human breast cancer cell line, MDA-MB-435S, were established by pulse selection, and exhibited a novel 'superinvasive' phenotype. This phenotype is characterised by an ability to relocate to another surface following invasion through matrigel and membrane pores, by decreased adhesion to extracellular matrix proteins and by increased motility. This may represent an in vitro model of a step in the metastatic process occurring subsequent to invasion. The paclitaxel-resistant variants, MDA-MB-435S-F/Taxol-10p and MDA-MB-435S-F/Taxol-10p4p were resistant to paclitaxel, vincristine and docetaxel, but not to doxorubicin, carboplatin, etoposide or 5-fluorouracil. The doxorubicin-selected variants MDA-MB-435S-F/Adr-10p and MDA-MB-435S-F/Adr-10p10p, in contrast, exhibited only small increases in resistance to doxorubicin, although they were slightly resistant to VP-16 and docetaxel, and exhibited increased sensitivity to paclitaxel, carboplatin and 5-fluorouracil.     

Enhanced transfollicular delivery of adriamycin with a liposome and iontophoresis

To find a better way to deliver drugs into hair follicles, we tried two approaches: single topical application using various liposomes; and iontophoresis combined with topical application of ionic liposome. After delivery of adriamycin (ADR) to wax-depilated rat skin, the transport of the drug was examined under fluorescence microscopy. Most liposomal ADR showed more effective transdermal and transfollicular penetration than free ADR. Among tested liposomes, the non-ionic GDL liposome (GDL/CH/POE-10 = glycerol dilaulate/cholesterol/polyoxyethylene-10) was the most selective to hair follicles against skin, while the cationic liposome (GDL/CH/POE-10/DOTAP, dioleoyl trimethylammonium propane) containing monocationic DOTAP was less selective; however, it was better at improving the delivery amount and penetration of ADR into the follicles and skin. The DMPC/DMPG (7/3) formulation of anionic PC liposome (DMPC/DMPG = dimyristoyl-phosphocholine/-phospoglycerol) showed results similar to the cationic liposome. The DMPC/DMPG (3/7) formulation yielded poor results, however, probably because of its increased viscosity and anionic property. Although ADR delivery was enhanced by liposomal formulations, topical applications had some limitations in delivery capacity and speed. To accelerate delivery, iontophoresis was combined with the cationic liposome at positive 0.2-0.4 mA/cm(2) for 20-30 min. The resulting delivery of ADR through follicular routes was excellent. This combination method diffused ADR 3.0-fold more efficiently, rapidly and deeply than single topical application of cationic liposomal ADR. This system also achieved a 3.5-fold higher diffusive follicular delivery than a free ADR/iontophoresis combination. Furthermore, it was demonstrated that the tetracationic lipid DOSPER and hydrophile spermine could serve as a cationic additive instead of the monocationic DOTAP in the liposome. These results suggest that the combinative system of the topically applied cationic liposome followed by iontophoresis has a significant synergistic effect on the transfollicular delivery of ADR.     

Protective effect of melatonin against adriamycin toxicity in the rat

Adriamycin, an anthracyclinic antibiotic frequently used in quimioterapeutic treatments is highly toxic; it inhibits protein synthesis and provokes prooxidant effects. Melatonin has recently been shown to have high antioxidative properties. We tested if melatonin is able to neutralize the oxidative damage induced by a single dose (20 mg/kg, i.p.) of adriamycin preceded (3 days) and followed (7 days) by a low pharmacological dose (50 microg/kg, i.p.) of melatonin. After the administration of a single dose of adriamycin (20 mg/kg i.p.) to male Wistar rats, the reduced to oxidized glutathione (GSH/GSSG) ratio and the glutathione peroxidase (GPx, E.C. 1.11.1.9.) activity in the brain, intestine, heart, kidney, and lung were significantly reduced. When the treatment of adriamycin was preceded and followed by low pharmacological doses of melatonin, the decrease in the GSH/GSSG ratio was significantly reduced but the reduction in GPx activity was not attenuated. A significant increase in lipid peroxidation products was observed in brain, heart, and kidney tissues after a single administration of adriamycin, which was attenuated by pre- and post-treatment with a low pharmacological dose of melatonin. Our results demonstrate that oxidative damage induced by the antitumor drug, adriamycin, can be reduced by low pharmacological doses of melatonin.     

甘草酸表面修饰阿霉素壳聚糖纳米粒的制备及特性研究

目的:制备具有肝细胞靶向的甘草酸表面修饰阿霉素壳聚糖纳米粒,并考察其理化特性。方法:采用离子凝胶法制备阿霉素壳聚糖纳米粒,再以高碘酸盐氧化法制备甘草酸表面修饰阿霉素壳聚糖纳米粒。激光透射电子显微镜观察纳米粒的形态,马尔文激光粒度仪测定其粒径。RP-HPLC法间接测定纳米粒中甘草酸结合率和阿霉素包封率,并初步研究体外甘草酸的结合稳定性和阿霉素释药特性。结果:电镜显示纳米粒呈类球形,平均粒径为179.5 nm,甘草酸结合率达到80%以上,在释放介质中,12 h的甘草酸结合率仍保持(65.2±3.4)%;纳米粒中阿霉素包封率达90%以上,体外释药缓慢,无明显的"突释"现象,72 h的累计释放百分率为(28±4.6)%。结论:本方法制备的甘草酸表面修饰阿霉素纳米粒工艺简单,包封率高,且甘草酸表面结合稳定,有望提高阿霉素的肝细胞靶向性。     

Cystosarcoma phylloides: A case presentation

A case of cystosarcoma phylloides is presented here showing the natural history of this disease both clinically and pathologically from 1962 through 1979, and demonstrating the management of this disease by surgery and by chemotherapy with the use of adriamycin at 25 mg/m² daily, times three days, every 28 days, which to our knowledge has not been used in this particular setting.