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An novel hematoporphyrin-anticancer drug conjugate for a therapy of lung metastasis of sarcoma.

一种新型血卟啉-抗癌药物缀合物，用于治疗肉瘤肺转移。

基本信息

批准号：
07671566
负责人：
OKADA Kyoji
金额：
$ 0.51万
依托单位：
Akita University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671566/
关键词：
hematoporphyrin lung metastasis porphyrin sarcoma Osteosarcoma metastasis マイトマイシンマイトマイシンC

项目摘要

1.Implantation of rat osteosarcoma, S-SLM : A appropriate focus of lung metastasis was selected, and implanted into the subcutaneous layr of F344 rat (male). We divided the rats into 5 groups as described below, each group included 10 rats.2.Preparation of hematoporphyrin-mitomycin C conjugate : Hematoporphyrin and mitomycin c were conjugated by dehydrated reaction under the DCC and 4-dimethylaminopyridine.3.Experimental group : A single intravenous administration was performed ineach group1) Control : Only DMSO2) Low MMC group : 8.97 * 10 -8 mol MMC3) Low Hp-MMC group : 8.97 * 10 -8 mol Hp-MMC4) MMC group : 8.97 * 10 -7 mol MMC5) Hp-MMC group : 8.97 * 10 -7 mol Hp-MMC4. Results :1) Survival rate : Low MMC group showed best survival rate 90%). However, survival rate of Low Hp-MMC group, MMC group, Hp-MMC group, were 50%, 20%, and 70%, respectively (p<0.001).2) Number of metastatic lung nodule : Low MMC group showed lowest lung nodules (average : 35). However, number of nodules of Low Hp-MMC group, MMC group, Hp-MMC group, were 120,35, and 80, respectively.3) Necrosis ratio of metastatic foci : Low MMC group showed best necrosis ratio (55%). However, necrosis ratio of Low Hp-MMC group, MMC group, Hp-MMC group, were significantly lower, which were 12%, 12%, and 34%, respectively (p<0.001).5.Conclusion : Hematoporphyrin-mitomycin C conjugate showed a lower anti tumor effect than that of mitomucin C.Side effects of hematoporphyrin-mitomycin C conjugate, however, has been more acceptable. Therefore we believe that hematoporphyrin-mitomycin C conjugate should be a novel anti tumor chemotherapy agent, if a better protocol would be established.

1.大鼠骨肉瘤S-SLM的种植：选择合适的肺转移灶，植入F344大鼠（雄性）皮下。将大鼠分为5组，每组10只。2.血卟啉-丝裂霉素C偶联物的制备：血卟啉和丝裂霉素C在DCC和4-二甲氨基吡啶下通过脱水反应进行偶联。3.实验组：每组单次静脉给药1）对照组：仅DMSO 2）低MMC组：4）MMC组：8.97 * 10 - 7mol MMC 5）Hp MMC组：8.97 * 10 - 7mol Hp MMC 4.结果：1）存活率：低MMC组存活率最高，达90%。而低Hp MMC组、MMC组、Hp MMC组的生存率分别为50%、20%、70%（p<0.001）。2）肺转移结节数：低MMC组肺转移结节数最少（平均35个）。而低浓度组、MMC组、Hp-MMC组的结节数分别为120、35、80个。3）转移灶坏死率：低浓度组坏死率最高（55%）。低Hp MMC组、MMC组、Hp MMC组的肿瘤坏死率分别为12%、12%、34%（P<0.001）。5.结论：血卟啉丝裂霉素C偶联物的抗肿瘤作用低于丝裂霉素C，但毒副作用较好。因此，我们认为血卟啉-丝裂霉素C偶联物有望成为一种新的抗肿瘤化疗药物，如能建立更好的方案。