Prevention of hepatic and peritoneal metastases by the angiogenesis inhibitor fr-118487 after removal of growing tumor in mice.
Prevention of hepatic and peritoneal metastases by the angiogenesis inhibitor fr-118487 after removal of growing tumor in mice.
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DOI：
10.1111/j.1349-7006.2001.tb01052.x
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发表时间：
2001-01
期刊：
影响因子：
--
通讯作者：
Nakamura S
中科院分区：
文献类型：
--
作者：
Tanaka T;Konno H;Baba S;Kanai T;Matsumoto K;Matsuda I;Ohba K;Ohta M;Kamiya K;Nakamura S
我们建立了一个小鼠“原发性肿瘤切除模型”，在该模型中，在原位移植结直肠癌组织后切除移植的肿瘤，以评估血管生成抑制剂对转移的治疗效果。血管生成抑制剂FR-118487是烟曲霉素家族的成员。在此，通过渗透泵向裸鼠皮下给予1 mg/kg/天FR-118487，持续1周、2周或4周。在9只对照小鼠中的7只、在移植后2周进行肿瘤切除的6只小鼠中的2只（早期切除）和在移植后4周进行肿瘤切除的所有7只小鼠中（晚期切除）发生肝转移。在短期治疗试验中，早期切除术后立即给予FR-118487可完全抑制肝转移和腹膜转移，而晚期切除术后给予FR-118487对肝转移无影响。在延长治疗试验中，明确证明了FR-118487延长治疗对晚期切除术后肝转移和腹膜转移的抑制作用。单独切除组的小鼠在肿瘤接种后106天内全部死亡，原因是结肠癌转移。相比之下，接受切除术然后接受抗血管生成治疗的小鼠中有一半在观察期结束时（移植后160天）存活。结论：手术联合抗血管生成治疗可能有助于预防结直肠癌远处转移，改善结直肠癌患者的预后。
We established a mouse “primary tumor resection model” in which a transplanted tumor was resected after an orthotopic transplantation of colorectal cancer tissue to estimate the therapeutic effect of an angiogenesis inhibitor on metastasis. The angiogenesis inhibitor FR‐118487 is a member of the fumagUlin family. Here, 1 mg/kg/day of FR‐118487 was subcutaneously administered to nude mice for 1 week, 2 weeks, or 4 weeks through an osmotic pump. Liver metastasis developed in 7 of 9 control mice, 2 of 6 mice that underwent the tumor resection 2 weeks after transplantation (early resection), and in all 7 of the mice that underwent the tumor resection 4 weeks after transplantation (late resection). In the short treatment trial, the FR‐118487 administration immediately after the early resection completely inhibited both hepatic and peritoneal metastases, whereas its administration after the late resection had no effect on liver metastasis. In the prolonged treatment trial, inhibitory effects of prolonged treatment with FR‐118487 on both hepatic and peritoneal metastases after the late resection were clearly demonstrated. The mice of the resection‐alone group all died within 106 days after tumor inoculation, due to metastases of colon carcinoma. In contrast, half of the mice that underwent resection and then received antiangiogenic therapy were alive at the end of the observation period (160 days after transplantation). In conclusion, the combination of surgery and subsequent antiangiogenic therapy may be useful to prevent the distant metastasis of colorectal cancer and to improve the prognosis of patients with colorectal cancer.
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影响因子：
82.9
作者：
Gohongi, T;Fukumura, D;Jain, RK
通讯作者：
Jain, RK
影响因子：
2.2
作者：
Ahmed, MH;Konno, H;Baba, S
通讯作者：
Baba, S
影响因子：
56.9
作者：
Bergers, G;Javaherian, K;Hanahan, D
通讯作者：
Hanahan, D
影响因子：
82.9
作者：
HOLMGREN, L;OREILLY, MS;FOLKMAN, J
通讯作者：
FOLKMAN, J
DOI：
10.1111/j.1349-7006.1999.tb00817.x
发表时间：
1999-07
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Kamiya K;Konno H;Tanaka T;Baba M;Matsumoto K;Sakaguchi T;Yukita A;Asano M;Suzuki H;Arai T;Nakamura S
通讯作者：
Nakamura S