权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

In vivo model mouse study to examine the effect of alteration of endogenous endocrine status in thyroid tumorigenesis

体内模型小鼠研究探讨内源性内分泌状态改变对甲状腺肿瘤发生的影响

基本信息

批准号：
18591030
负责人：
NAMBA Hiroyuki
金额：
$ 2.49万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591030/
关键词：
Thyroid cancer Radiation Oncogene Animal Model 動物モデル

项目摘要

The aim of the study is to establish transgenic mice that develop thyroid cancer and then to examine the effects of a novel selective nuclear factor kappa B(NF-κB)inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), which change various cytokines status in vivo, in the mouse model.First Experiment : We prepared two types of transgenic mice. One is BRAF transgenic mice and another is Ret/PTC transgenic mice. Both transgenic mice develop papillary thyroid cancer within 4 weeks after birth. We examined the effect of DHMEQ, which is novel NF-κB inhibitor, to thyroid carcinomas developed in BRAF or RET-transgenic mice in vivo.Results : Treatment with DHMEQ inhibited NF-κB DNA binding activity and induced apoptosis in dose and time dependent manner in thyroid carcinoma cells in vitro. However, in the in vivo study, DHMEQ could not suppress the NF-κB activity in thyroid carcinomas in the transgenic mice. Through the animal experiments, DHMEQ did not show any side effects in treated mice.Second Experiment : We tried to establish novel thyroid carcinoma model mice using Cre-Lox-P system, which is allowed to express the interest gene at any time we want. We could establish the double transgenic mice that have Cre gene and BRAF-Lox-P gene. However, the mice could not develop thyroid carcinoma after induction.

本研究的目的是建立甲状腺癌的转基因小鼠模型，并观察一种新型的选择性核因子kappaB(NF-κB)抑制剂脱羟甲基氧奎诺米星(DHMEQ)对小鼠体内多种细胞因子状态的影响。一组为BRAF转基因小鼠，另一组为Ret/PTC转基因小鼠。这两只转基因小鼠在出生后4周内都会患上乳头状甲状腺癌。结果：DHMEQ可抑制体外培养的甲状腺癌细胞的NF-κB结合活性，并以剂量和时间依赖的方式诱导甲状腺癌细胞的凋亡。但在体内实验中，二氢美其清不能抑制转基因小鼠甲状腺癌组织中核因子-κB的活性。通过动物实验，DHMEQ在治疗的小鼠身上没有表现出任何副作用。第二个实验：我们试图利用Cre-Lox-P系统建立新的甲状腺癌模型，该系统允许在我们想要的任何时间表达目的基因。我们可以建立Cre基因和BRAF-Lox-P基因的双转基因小鼠。然而，诱导后的小鼠不能形成甲状腺癌。