Sakamoto Y, Fujita M, Sugiyama R, Ota J, Taguchi T
Dept. of Surgery, Osaka University.
Gan To Kagaku Ryoho. 1988 Aug;15(8 Pt 2):2573-7.
Enhancement of the antitumor effect of adriamycin (ADR) was investigated by using degradable starch microspheres (DSM) and pharmacokinetics of ADR in combination with DSM. An intra-arterial chemotherapy model of the nude rats transplanted of human cancer xenografts (H-154 gastric cancer) in the lower limbs was used for this study. Drug was administered through a catheter inserted into the carotid artery with the tip in the common iliac artery. DSM 30 mg/kg, which causes temporary arrest of blood flow in the tumor, had an only weak effect on tumor growth, whereas. DSM 30 mg/kg, mixed with ADR 3 mg/kg solution, was more effective than ADR solution. Furthermore, DSM 30 mg/kg mixed with ADR 3 mg/kg had a greater effect on the tumor growth than DSM 15 mg/kg mixed with ADR 3 mg/kg. In the pharmacological study, increase of the regional uptake of ADR and decrease of systemic distribution of ADR were recognized in some degree. It seems that embolization by DSM, retention of ADR in regional tissues and cytotoxic effect of ADR contributed to such a strong effect of ADR mixed with DSM on tumor growth.
通过使用可降解淀粉微球(DSM)以及阿霉素(ADR)与DSM联合用药的药代动力学来研究增强阿霉素的抗肿瘤效果。本研究采用人癌异种移植(H-154胃癌)裸鼠下肢动脉内化疗模型。通过插入颈动脉且尖端位于髂总动脉的导管给药。能使肿瘤血流暂时停滞的30mg/kg DSM对肿瘤生长仅有微弱作用,而30mg/kg DSM与3mg/kg ADR溶液混合使用比ADR溶液更有效。此外,30mg/kg DSM与3mg/kg ADR混合对肿瘤生长的影响比15mg/kg DSM与3mg/kg ADR混合更大。在药理学研究中,在一定程度上观察到ADR局部摄取增加和全身分布减少。DSM栓塞、ADR在局部组织中的滞留以及ADR的细胞毒性作用似乎促成了ADR与DSM混合对肿瘤生长的强大作用。