In vivo effects of cavitation alone or in combination with chemotherapy in a peritoneal carcinomatosis in the rat.
In vivo effects of cavitation alone or in combination with chemotherapy in a peritoneal carcinomatosis in the rat.
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DOI：
10.1038/bjc.1993.279
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发表时间：
1993-07
影响因子：
8.8
通讯作者：
Cathignol, D
中科院分区：
文献类型：
--
作者：
Prat, F;Chapelon, J Y;el Fadil, F A;Theillere, Y;Ponchon, T;Cathignol, D
由冲击波（SW）和微泡（SWB）共同给药产生的空化（体积振荡和气泡塌陷）在体外诱导细胞毒性。此外，空化增强氟尿嘧啶（FUra）对结肠癌细胞的作用。我们的目标是在体内重现这种效果。通过腹膜内（IP）注射DHDK 12 PROb细胞在BDIX大鼠中诱导腹膜癌病。通过各种SW方案（250至750 SW）结合通过IP导管输注的气泡（空气/明胶乳剂）产生空化。在两个连续的实验中，将微肿瘤（细胞注射后第3天）以高剂量或低剂量进行空化和/或氟尿嘧啶（FUra）和顺铂（CDDP）的各种组合。30天后，对照组动物100%死亡或出现癌病伴腹水，而FUra 5 mg kg dy（第4天至第8天）组为60%，250次SWB（第4天和第6天）+ FUra 5 mg kg dy（第4天至第8天）组为0%（P < 0.001）; CDDP组也存在类似差异。低剂量FUra + SWB后的存活率与高剂量FUra（25 mg/kg，每天一次，直至第8天）相当，并且与低剂量FUra单独给药相比有所改善。只有高剂量FUra + SWB方案诱导40%的长期（> 150天）无病生存，但也有更高的不良毒性（1个月内40%的毒性死亡）。可以得出结论，空化在体内具有细胞毒性，并且它增强了FUra和CDDP在该动物模型中的作用。
Cavitation (volume oscillations and collapse of gas bubbles), as generated by a co-administration of shockwaves (SW) and microbubbles (SWB), induces cytotoxicity in vitro. Moreover, cavitation potentiates the effects of Fluorouracil (FUra) on colon cancer cells. We aimed at reproducing such effects in vivo. A peritoneal carcinomatosis was induced in BDIX rats by intraperitoneal (IP) injection of DHDK12PROb cells. Cavitation was produced by various SW regimens (250 to 750SW) combined with bubbles (air/gelatin emulsion) infused through an IP catheter. In two consecutive experiments, microtumours (day 3 after cell injection) were submitted to various combinations of cavitation and/or Fluorouracil (FUra) and Cisplatinum (CDDP) at either high or low doses. After 30 days, 100% of control animals were dead or presented carcinomatosis with ascites, vs 60% after FUra 5 mg kg dy, day 4 through 8, and 0% after 250 SWB, day 4 and 6 + FUra 5 mg kg dy, day 4 through 8 (P < 0.001); similar differences were found with CDDP. Survival after low dose FUra + SWB was comparable to high dose FUra (25 mg kg dy day through 8) and was improved as compared to low-dose FUra alone. Only a high dose FUra + SWB schedule induced 40% long term (> 150 days) disease-free survival, but also a higher undesirable toxicity (40% toxic deaths within 1 month). It is concluded that cavitation is cytotoxic in vivo and that it potentiates the effects of FUra and CDDP in this animal model.