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マウス大腸癌肝転移に対する血管新生抑制機構を介した腫瘍増殖および肝転移抑制

通过血管生成抑制机制抑制小鼠结肠癌肝转移的肿瘤生长和肝转移

基本信息

批准号：
14770654
负责人：
小澤修太郎
金额：
$ 1.6万
依托单位：
Saitama Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14770654/
关键词：
VEGF サリドマイド血管新生大腸癌肝転移マウス

项目摘要

【目的】マウス大腸癌肝転移モデルに対するサリドマイドの全身投与を施行。この治療効果が血管新生制御を介した物であることを確認。更に本治療における最適の治療計画を確認。【方法Exp.1】マウス大腸癌CT-26細胞を脾臓に移植。移植後、7日目よりサリドマイドの腹腔内注射を4日間連日で施行(0mg、30mg、300mg/kg)。移植後14日目に肝転移数を各群で比較、転移性腫瘍を抗マウスCD-31,VEGF抗体を用いた免疫組織学的染色を用いて解析。【結果Exp.1】サリドマイド300mg/kg投与群は治療期間中に全て傾眠傾向の後、呼吸停止を呈して副作用死。30mg/kg投与群は治療期間中に4匹副作用死したがコントロール群(0mg/kg)に比べ肝転移発現抑制が見られた。免疫組織学的染色では腫瘍内の微小血管新生、VEGFの発現抑制が見られた。【結論Exp.1】サリドマイド連続投与により肝転移の抑制効果が見られた。効果はVEGF発現抑制を介した血管新生抑制と示唆された。多くのマウスが治療中に副作用死を生じたため今後、サリドマイドのdoseとtime scheduleを変えた更なる検討が必要と思われた。【方法Exp.2】前回と同様にマウス大腸癌CT-26細胞をマウス脾臓に移植。サリドマイドの腹腔内注射を隔日で施行(0mg、3mg、30mg/kg)治療終了後、肝転移数を各群で比較。又、転移性肝腫瘍をCD-31,VEGF抗体を用いた免疫組織学的染色で解析。【結果Exp.2】全マウスが本治療計画に耐えた。30mg/kg投与群はコントロール群に比し有意に肝転移の発現抑制が見られ、転移性肝腫瘍の免疫組織学的染色では腫瘍内微小血管新生の抑制、VEGFの発現抑制が見られた。【結論】30mg/kgの隔日サリドマイド投与は本モデルにおいて最適投与計画であった。同群で肝転移の抑制効果が見られ、この治療効果はVEGFの発現抑制を介した血管新生抑制によるものであると示唆された。以上の結果は今年度の第59回消化器外科学会総会にて発表予定である。

[objective] to investigate the effect of liver transfer of large cancer on the whole body. To treat the disease, the result is that the angiogenesis system has been confirmed. It is more important to confirm that the most effective treatment is the most effective. [methods] splenic transplantation of CT-26 cells from large breast cancer was carried out by Exp.1. On the 7th day after transplantation, the rats were injected intraperitoneally on the 4th day (0mg, 30mg, 300mg/kg). 14 days after transplantation, the number of liver metastases in each group was compared, and the anti-tumor CD-31,VEGF antibodies were analyzed by immunocytochemical staining. [results] during the period of treatment, total sleep apnea and respiratory arrest had side effects during the treatment of Exp.1. [results] during the period of treatment, there was a side effect of complete sleep and respiratory arrest during the period of treatment and treatment. During the treatment period of 30mg/kg and group therapy, 4 patients with side effects were killed in the treatment group (0mg/kg), and the liver transfer was compared to inhibit the death of patients. Immunohistochemical staining showed microangiogenesis and VEGF inhibition. [results] the link between Exp.1 and liver transfer suppressed the effect of liver transplantation. Results VEGF showed inhibition of angiogenesis and angiogenesis. It is necessary to think about the side effects in the treatment of multiple diseases, such as the death of side effects, and the [methods] the splenic transplantation was performed in patients with large intestinal cancer (CT-26). [methods] the spleen was transplanted into the spleen of patients with large cancer. [methods] the spleen was transplanted in the same way. Intraperitoneal injection (0mg, 3mg, 30mg/kg) was performed every other day. After treatment, the number of liver metastases was compared among groups. In addition, the CD-31,VEGF antibody of metastatic liver disease was analyzed by immunological staining. [results Exp.2] the whole treatment program was designed to tolerate the disease. Compared with the group of patients, 30mg/kg showed inhibition of microangiogenesis, and VEGF showed inhibition of angiogenesis in the immunology of liver metastasis. [results] every other day, 30mg/kg would like to invest in this project. In the same group, liver migration inhibits the occurrence of VEGF, induces angiogenesis inhibition, induces angiogenesis, and instigates the disease. As a result of the above results, the 59th Annual meeting of the Society of Digestive Surgeons is scheduled for this year.