Effect of intraperitoneal administration of docetaxel on peritoneal dissemination of gastric cancer.

Effect of intraperitoneal administration of docetaxel on peritoneal dissemination of gastric cancer.
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腹腔注射多西紫杉醇对胃癌腹膜播散的影响。

DOI:
10.1016/j.canlet.2004.03.018
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发表时间:
2004
期刊:
影响因子:
9.7
通讯作者:
P. Sugarbaker
P. Sugarbaker
中科院分区:
医学1区
文献类型:
--
作者:
Y. Yonemura;Y. Endou;E. Bando;K. Kuno;T. Kawamura;M. Kimura;T. Shimada;K. Miyamoto;Takuma Sasaki;P. Sugarbaker

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对携带胃癌细胞系 MKN-45-P 的无胸腺小鼠腹膜内 (i.p.) 施用多西紫杉醇的效果进行了抗癌活性临床前证据的评估,该细胞系显示裸鼠腹膜腔的高转移率。裸鼠腹膜内接种。与 107MKN-45-P 细胞。在肿瘤接种后第2、5、9、12、16和19天,对小鼠进行腹膜内注射治疗。注射多西紫杉醇。多西紫杉醇的治疗剂量为8mg/kg(N=7)、2mg/kg(N=7)和0.5mg/kg(N=7)。测定腹膜内癌胚抗原(CEA)水平、动物体重、死亡率和存活率。所有对照小鼠均出现腹水并在 19-40 天内死亡。对照组的中位生存时间为32天,而8、2和0.5 mg/kg治疗组的小鼠的中位生存时间分别为90、63和49.5天。用 8 mg/kg 多西紫杉醇治疗的 7 只小鼠中,有 1 只在第 12 天死于毒性。4 只小鼠在第 90 天时无肿瘤,但在第 90 天尸检时,两只小鼠腹部有肿瘤。用 2 mg/kg 治疗的一只小鼠在第 90 天被确定为无肿瘤。用 0.5 mg/kg 多西紫杉醇治疗的所有 7 只小鼠在 71 天内死于腹膜播散。结果表明腹腔内多西紫杉醇给药具有治疗胃癌腹膜播散的潜力。
The effect of intraperitoneal (i.p.) administration of docetaxel was evaluated for preclinical evidence of anticancer activity in athymic mice bearing a gastric cancer cell line, MKN-45-P that shows a high rate of metastasis to the peritoneal cavity of nude mice. Nude mice were inoculated i.p. with 107MKN-45-P cells. On days 2, 5, 9, 12, 16 and 19 after tumor inoculation, mice were treated with i.p. injection of docetaxel. Treatment doses of docetaxel were 8 mg/kg (N=7), 2 mg/kg (N=7) and 0.5 mg/kg (N=7). Intraperitoneal carcinoembryonic antigen (CEA) levels, animal body weight, mortality and survival were determined. All control mice developed ascites and died within 19–40 days. The median survival time in the control group was 32 days, while those of mice treated with 8, 2 and 0.5 mg/kg were 90, 63 and 49.5 days, respectively. One of seven mice treated with 8 mg/kg of docetaxel died of toxicity on day 12. Four mice were tumor-free on day 90, but two had tumors in the abdomen when autopsied on day 90. One mouse treated with 2 mg/kg was ascertained to be tumor-free on day 90. All seven mice treated with 0.5 mg/kg of docetaxel died of peritoneal dissemination within 71 days. The results suggest the potential of intraperitoneal docetaxel administration for the treatment of peritoneal dissemination of gastric cancer.