Prevention of hepatic metastasis after surgery by angiogenesis inhibitor
血管生成抑制剂预防术后肝转移
基本信息
- 批准号:10671171
- 负责人:
- 金额:$ 1.98万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:1998
- 资助国家:日本
- 起止时间:1998 至 1999
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Hepatic metastasis after curative surgery is the most common type of recurrence of colorectal cancer. 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 liver metastasis. The angiogenesis inhibitor FR-118487, isolated from the fermentation products of Scolecobasidium arenarium F-2015 and modified chemically, was classified as a member of the fumagillin family. Here, one mg/kg/day of FR-118487 was subcutaneously administered to nude mice for one week, 2 weeks, or 4 weeks through an osmotic pump.The results of the experiment using the orthotopic transplantation model revealed that FR-118487 significantly inhibited the tumor growth and hepatic metastasis. 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 o … More f the mice that underwent the tumor resection 4 weeks after transplantation (late resection). Interestingly, peritoneal dissemination developed in all of the mice that underwent a tumor resection. In the short treatment trial, the FR-118487 administration immediately after the early resection completely inhibited both hepatic and peritoneal metastasis, whereas its administration after the late resection had no effect on liver metastasis, but significantly inhibited the peritoneal dissemination. 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 hepatic and peritoneal 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 observational period (160 days after transplantation).Antiangiogenic therapy is more effective against microtumor than against a mass of tumor. Thus, a mass of primary tumor is removed by surgery and remnant microtumors are controlled by antiangiogenic therapy. In conclusion, the combination of surgery and subsequent antiangiogenic therapy may be useful to prevent the distant metastasis of colorectal cancer and improve the prognosis of patients with colorectal cancer. Less
术后肝转移是结直肠癌最常见的复发类型。我们建立小鼠“原发肿瘤切除模型”,在原位大肠癌组织移植后切除移植肿瘤,以评估血管生成抑制剂对肝转移的治疗作用。血管生成抑制剂FR-118487是从猪头孢菌F-2015的发酵产物中分离得到并经化学修饰的,属于富马西林家族。本研究中,通过渗透泵给药1 mg/kg/天的FR-118487裸鼠皮下注射1周、2周或4周。原位移植模型实验结果显示FR-118487显著抑制肿瘤生长和肝转移。9只对照小鼠中有7只发生肝转移,6只移植后2周切除的小鼠中有2只发生肝转移(早期切除),7只移植后4周切除的小鼠中有2只发生肝转移(晚期切除)。有趣的是,所有接受肿瘤切除的小鼠都出现了腹膜播散。在短期治疗试验中,早期切除后立即给予FR-118487完全抑制肝转移和腹膜转移,而晚期切除后给予FR-118487对肝转移没有影响,但明显抑制腹膜播散。在延长治疗试验中,明确证明了FR-118487延长治疗对晚期切除后肝脏和腹膜转移的抑制作用。单独切除组小鼠均在肿瘤接种后106天内死亡,原因是结肠癌肝转移和腹膜转移。相比之下,在切除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。抗血管生成治疗对微肿瘤比对肿瘤团块更有效。因此,原发肿瘤通过手术切除,残余微肿瘤通过抗血管生成治疗得到控制。综上所述,手术联合后续抗血管生成治疗可能有助于预防结直肠癌的远处转移,改善结直肠癌患者的预后。少
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
田中達郎: "血管新生阻害物質TNP-470によるtumor dormancyの誘導"Tumor Dormancy Therapy. 2・2. 111-114 (2000)
田中达郎:“血管生成抑制剂TNP-470诱导肿瘤休眠”《肿瘤休眠疗法》111-114。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Tatuo Tanaka: "Induction of tumor dormancy by angiogenesis inhibitor TNP-470"Tumor Dormacy Therapy. 2. 111-114 (2000)
Tatuo Tanaka:“通过血管生成抑制剂 TNP-470 诱导肿瘤休眠”肿瘤休眠疗法。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
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NAKAMURA Toshio其他文献
NAKAMURA Toshio的其他文献
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{{ truncateString('NAKAMURA Toshio', 18)}}的其他基金
A modification of preparation method of ancient iron artifacts for radiocarbon dating
古代铁器放射性碳测年制备方法的改进
- 批准号:
24652155 - 财政年份:2012
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Precise 14C dating of wooden cultural properties treated for preservation with PEG
用 PEG 进行保存的木质文化财产的精确 14C 测年
- 批准号:
22652072 - 财政年份:2010
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
A study on estimation of calendar age for wooden cultural properties with high precision by wiggle matching
摆动匹配高精度估算木质文物历法研究
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19300300 - 财政年份:2007
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
A study of determining the tree-ring age with a precision of one year by 14C wiggle matching
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16320108 - 财政年份:2004
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$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Implication of intestinal lymphocytes in endotoxin-induced hepatic injury after partial hepatectomy in rats
肠淋巴细胞在大鼠肝部分切除术后内毒素性肝损伤中的意义
- 批准号:
15591396 - 财政年份:2003
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$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A study on accurate age determination of volcanic eruptions by high-precision 140 dating and a wiggle matching analysison charred wood from volcanic deposits
火山沉积物焦木高精度140测年及摆动匹配分析准确测定火山喷发年龄的研究
- 批准号:
13480020 - 财政年份:2001
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Kupffer cells modulate splenic, interleukin-10 production in endotoxin-induced liver injury after partial hepatectomy.
部分肝切除术后内毒素诱导的肝损伤中,库普弗细胞调节脾脏、白细胞介素 10 的产生。
- 批准号:
12671218 - 财政年份:2000
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A study on accurate age measurement of buried wood by high-precision 14C dating and 14C wiggle matching
高精度14C测年和14C摆动匹配准确测量埋藏木材年龄的研究
- 批准号:
10680174 - 财政年份:1998
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$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development and its application of anion sensor consist of polymer film for the use of nonaqueous solution
非水溶液用聚合物薄膜阴离子传感器的研制及其应用
- 批准号:
10640587 - 财政年份:1998
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
DEVELOPMENT OF AN ELECTROCHEMICAL MEASUREMENT METHODS ABOUT BIOFUNCTIONAL MATERIALS AND THEIR APPLICATION TO NONAQUEOUS SOLUTION SYSTEMS
生物功能材料电化学测量方法的开发及其在非水溶液体系中的应用
- 批准号:
06640778 - 财政年份:1994
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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