Evaluation of successful treatment of malignant pleural mesothelioma mouse model by intra-pleural new anti-drug (pemetrexed) administration

我们评价了顺铂、吉西他滨和培美曲塞单独使用以及与吉西他滨、培美曲塞联合使用对恶性胸膜间皮瘤细胞系（H28，211 H）的抗增殖作用。结果表明，在吉西他滨、培美曲塞联合用药时，没有发现额外的效应。我们将培美曲塞0、25、125、250、500、1000、1500 mg/kg注入小鼠胸腔。第二天，平均体重下降2.3%，此后平均体重顺利增加。这种趋势不依赖于培美曲塞的量。随后，我们将0、100、250、500、750、1000 mg/kg培美曲塞注射到小鼠胸腔内，每周一次，连续注射3周。各组平均体重均顺利增加，无显著差异。也就是说，我们没有发现胸膜内给药的体重减轻与培美曲塞量之间的相关性。这 ...更多信息 结果与我们以前评价的多西他赛的情况不同，我们将211 H注入小鼠胸腔。一周后开始重复给予培美曲塞或组蛋白去乙酰化酶抑制剂SB，每周1次，连续3周。胸腔内注射0、100、1000 mg/kg培美曲塞，SB 20 mg，100 mg/kg培美曲塞联合SB 20 mg，腹腔内注射100、1000 mg/kg培美曲塞。各组间总生存时间无显著差异。胸膜腔内注射100 mg/kg培美曲塞组和胸膜腔内注射1000 mg/kg培美曲塞组的平均体重无显著差异，但胸腔注射100 mg/kg培美曲塞组的平均体重明显高于注射100 mg/kg培美曲塞组这些结果可能表明，胸膜内给药培美曲塞的副作用小于腹腔内给药。少

We evaluated the anti-proliferative effects of cisplatin, gemcitabine and pemetrexed alone and in combination with gemcitabine, pemetrexed with malignant pleural mesothelioma cell line (H28, 211H). As a result, in combination with gemcitabine, pemetrexed, additional effect was not recognized.We injected 0, 25, 125, 250, 500, 1000, 1500 mg/kg pemetrexed into the pleural cavity of mouse. The next day, average body weight was decreased 2.3%, thereafter, average body weight increased favorably. This tendency was not depend on the amount of pemetrexed. Death by overdose of pemetrexed in single injection was not recognized.Next, we injected 0, 100, 250, 500, 750, 1000 mg/kg pemetrexed into the pleural cavity of mouse once a week for three consecutive weeks. The average weight of each group increased favorably and there was no significant difference. Namely, we could not find the correlation between the weight loss and the amount of pemetrexed by intra-pleural pemetrexed administration. This … More result is different from the case of docetaxel that we evaluated before.We injected 211H into the pleural cavity of mouse. After one week, we started repeated administration of pemetrexed or SB (one of histone deacetylase inhibitor (HDAC)) once a week for three consecutive weeks.We divided seven groups. We injected 0, 100, 1000 mg/kg pemetrexed, 20 mg SB, 100 mg/kg pemetrexed combined with 20 mg SB into the pleural cavity 100, 1000 mg/kg pemetrexed into abdominal cavity. Between each group, there was no significant difference in overall survival time. On the average body weight of the group that was injected pemetrexed into the pleural cavity 100 mg/kg and the group that was injected 1000 mg/kg pemetrexed injected into the pleural cavity, there was no significant difference.However, the average body weight of the group that was injected 100 mg/kg pemetrexed into the pleural cavity was significantly heavy than the group that was injected 100 mg/kg pemetrexed into the abdominal cavity.These results may suggest that the side effect of intra-pleural pemetrexed administration is less than that of intra-abdominal pemetrexed administration. Less