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阿霉素联合肝肿瘤暂时性动脉闭塞有效性的体内和体外分析

In vivo and in vitro analysis of the effectiveness of doxorubicin combined with temporary arterial occlusion in liver tumors.

作者信息

Kruskal J B, Hlatky L, Hahnfeldt P, Teramoto K, Stokes K R, Clouse M E

机构信息

Department of Radiology, New England Deaconess Hospital, Boston, MA 02215.

出版信息

J Vasc Interv Radiol. 1993 Nov-Dec;4(6):741-7. doi: 10.1016/s1051-0443(93)71965-x.

DOI:10.1016/s1051-0443(93)71965-x
PMID:8280994
Abstract

PURPOSE

The authors evaluated the effects of daunomycin (daunorubicin)--an analogue of doxorubicin--ethiodized oil, and arterial occlusion on an in vitro hepatoma analogue and on in vivo rat liver tumors.

MATERIALS AND METHODS

A human Sk hepatoma cell monolayer sandwich system was used to determine uptake of 3H-daunomycin under normoxic/hypoxic conditions with use of autoradiography. Fluorescence microscopy was used to evaluate the biodistribution of doxorubicin in cell cultures (human Sk hepatoma and colon carcinoma). Microvascular flow adjacent to and within liver tumors and the intrahepatic effects of doxorubicin and ethiodized oil were studied with in vivo video microscopy on exteriorized rat livers containing peripheral hepatomas.

RESULTS

Increased uptake of 3H-daunomycin by hepatoma cells occurred under hypoxic conditions. Intrahepatic arterial administration of ethiodized oil caused temporary occlusion of peripheral sinusoids following passage through arterioportal anastomoses. Tumors received portal venous and neovascular blood supply and ethiodized oil occluded but did not enter the narrow neovasculature perfusing the tumors.

CONCLUSION

Hypoxia increases uptake of 3H-daunomycin by human Sk hepatoma and colon carcinoma cell cultures. Selective hepatic arterial occlusion (and perhaps the resultant hypoxia) may facilitate increased uptake of doxorubicin analogues into liver tumors. Hepatomas receive both arterial and portal venous blood supply, and ethiodized oil reaches the tumor via arterioportal anastomoses that perfuse the tumor periphery.

摘要

目的

作者评估了柔红霉素(道诺霉素)——一种阿霉素类似物——、碘化油和动脉闭塞对体外肝癌类似物及体内大鼠肝肿瘤的影响。

材料与方法

使用人Sk肝癌细胞单层夹心系统,通过放射自显影术测定常氧/低氧条件下3H-柔红霉素的摄取。利用荧光显微镜评估阿霉素在细胞培养物(人Sk肝癌和结肠癌细胞)中的生物分布。采用体内视频显微镜技术,对含有外周肝癌的大鼠离体肝脏进行研究,观察肝肿瘤周边及内部的微血管血流情况以及阿霉素和碘化油的肝内效应。

结果

在低氧条件下,肝癌细胞对3H-柔红霉素的摄取增加。肝动脉内注射碘化油经动脉门静脉吻合支进入后可导致外周肝血窦暂时闭塞。肿瘤接受门静脉和新生血管供血,碘化油可阻塞但无法进入灌注肿瘤的狭窄新生血管。

结论

低氧可增加人Sk肝癌和结肠癌细胞培养物对3H-柔红霉素的摄取。选择性肝动脉闭塞(以及由此可能导致的低氧)可能有助于阿霉素类似物增加对肝肿瘤的摄取。肝癌接受动脉和门静脉供血,碘化油通过灌注肿瘤周边的动脉门静脉吻合支到达肿瘤部位。

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