In vivo optical pathology of paclitaxel efficacy on the peritoneal metastatic xenograft model of gastric cancer using two-photon laser scanning microscopy

In vivo optical pathology of paclitaxel efficacy on the peritoneal metastatic xenograft model of gastric cancer using two-photon laser scanning microscopy
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使用双光子激光扫描显微镜观察紫杉醇对胃癌腹膜转移异种移植模型的体内光学病理学疗效

DOI:
10.1007/s10120-013-0334-y
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发表时间:
2014
期刊:
影响因子:
7.4
通讯作者:
Kusunoki M
Kusunoki M
中科院分区:
医学1区
文献类型:
--
作者:
Shimura T;Tanaka K;Toiyama Y;Okigami M;Ide S;Kitajima T;Kondo S;Saigusa S;Ohi M;Araki T;Inoue Y;Uchida K;Mohri Y;Mizoguchi A;Kusunoki M

文献摘要

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背景我们先前使用活体实时和时间序列活体双光子激光扫描显微镜(TPLSM)在结肠直肠肝转移性异种移植模型中观察了体内对化疗的反应。在这项研究中,我们建立了评价腹膜异种移植物的转移性胃癌化疗反应的方法,使用活体TPLSM.MethodsRed荧光蛋白表达的胃癌细胞(NUGC 4)接种到腹膜腔的绿色荧光蛋白nude mice. Results剖腹探查发现,接种后2周,肉眼腹膜转移结节形成。第一次活体TPLSM疗程显示它们由红色肿瘤细胞簇和周围的绿色基质组成。治疗组在首次TPLSM后腹腔注射紫杉醇,每周3次,共7天。在第二次剖腹手术时,治疗组小鼠的结节明显少于对照组。第二次活体TPLSM显示转移性结节中的肿瘤细胞碎裂、肿胀和核凝聚-对化疗的反应。有多核肿瘤细胞在紫杉醇治疗的活mice.ConclusionsOur方法可能成为一个强大的工具,用于评估新的抗胃癌药物的疗效在临床前小鼠模型与最小的个体间变异。
BackgroundWe previously visualized in vivo responses to chemotherapy in a colorectal liver metastatic xenograft model using in vivo real-time and time-series intravital two-photon laser scanning microscopy (TPLSM). In this study, we established the method for evaluating the response of peritoneal xenografts to chemotherapy of metastatic gastric cancer using intravital TPLSM.MethodsRed fluorescent protein-expressing gastric cancer cells (NUGC4) were inoculated into the peritoneal cavity of green fluorescent protein nude mice.ResultsLaparotomy revealed that 2 weeks after inoculation, macroscopic peritoneal metastatic nodules were formed. The first intravital TPLSM session revealed that they were composed of red tumor cell clusters and green surrounding stroma. Paclitaxel was administered intraperitoneally after the first TPLSM three times a week for 7 days in the treatment group. At the second laparotomy, there were significantly fewer and smaller nodules in the treated mice than in the controls. The second intravital TPLSM session showed tumor cell fragmentation, swelling, and nuclear condensation in the metastatic nodules—a response to chemotherapy. There were multinuclear tumor cells in the paclitaxel-treated living mice.ConclusionsOur method may become a powerful tool for evaluating the efficacy of novel anti-gastric cancer drugs in a preclinical murine model with minimum interindividual variation.