ZD6126 inhibits orthotopic growth and peritoneal carcinomatosis in a mouse model of human gastric cancer
ZD6126 inhibits orthotopic growth and peritoneal carcinomatosis in a mouse model of human gastric cancer
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DOI：
10.1038/sj.bjc.6601490
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发表时间：
2004-02-09
影响因子：
8.8
通讯作者：
Ellis, LM
中科院分区：
文献类型：
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作者：
McCarty, MF;Takeda, A;Ellis, LM
本研究的目的是检查 ZD6126（一种新型血管靶向剂）对胃癌原位模型中肿瘤生长和血管生成的影响。将TMK-1人胃腺癌细胞注射到裸鼠胃壁中。肿瘤形成后（第14天），开始治疗。小鼠（n = 11-12/组）接受（a）媒介物，（b）ZD6126（100 mg kg day(-1) i.p.）。每周一次或 (c) ZD6126 100 mg kg day(-1) 腹膜内注射每周五次。在第38天处死时测定肿瘤质量、体积以及是否存在腹膜癌转移。对每组的肿瘤进行血管标记物、增殖和凋亡标记物染色。为了进一步确定 ZD6126 慢性治疗的血管靶向作用的时间范围，在第二个实验中再次将 TMK-1 细胞注射到小鼠胃壁中。第 14 天，单个 IP。注射ZD6126 100 mg kg(-1)小鼠(-1)或载体。在注射 ZD6126 后第 1、3 和 5 天，每组杀死三只小鼠并收获肿瘤。对肿瘤进行处理和染色以检测内皮细胞和肿瘤细胞的凋亡和增殖。 ZD6126 治疗未观察到明显的毒性。 ZD6126 显着抑制肿瘤生长（与对照相比减少 82%（P
The purpose of this study was to examine the effects of ZD6126, a novel vascular-targeting agent, on tumour growth and angiogenesis in an orthotopic model of gastric cancer. TMK-1 human gastric adenocarcinoma cells were injected into the gastric wall of nude mice. After the tumours were established (day 14), therapy was initiated. Mice (n = 11-12/group) received (a) vehicle, (b) ZD6126 at 100 mg kg day(-1) i.p. one time per week or (c) ZD6126 at 100 mg kg day(-1) i.p. five times per week. Tumour mass, volume and the presence or absence of peritoneal carcinomatosis were determined at sacrifice on day 38. Tumours from each group were stained for markers of blood vessels, proliferation and apoptosis. To further define the time frame of the vascular-targeting effects of chronic therapy with ZD6126, TMK-1 cells were again injected into the gastric wall of mice in a second experiment. On day 14, a single i.p. injection of ZD6126 100 mg kg(-1) mouse(-1) or vehicle was delivered. Groups of three mice each were killed and the tumours harvested at days 1, 3 and 5 post-ZD6126 injection. Tumours were processed and stained for endothelial and tumour cell apoptosis and proliferation. No overt toxicity was observed with ZD6126 therapy. ZD6126 led to a marked inhibition of tumour growth (82% decrease vs control (P