Investigation of the molecular pathology of the differentiation mechanism by the Notch signaling pathway in colon carcinogenesis process.

结肠癌发生过程中Notch信号通路分化机制的分子病理学研究。

• 批准号: 19590397
• 负责人: MORIOKA Takamitsu
• 金额: $ 3万
• 依托单位: University of the Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19590397/
• 关键词: 粘液枯渇巣; Notch; 大腸癌; ラット大腸発癌モデル; ヒト大腸粘膜; Notch1; K1f4; 大腸陰窩変異巣; ヒト大腸粘液

The aim of this study is to investigate the relation of Notch signaling pathway on colon carcinogenesis by using the rats colon carcinogenic model. We found that the expression of Notch1 in colon tumor was significantly increased compared to the normal mucosa. In contrast, the expression of Klf4 in colon tumor was significantly decreased compared the normal mucosa. These results suggested that increased expression of Notch1 and decreased expression of Klf4 could be associated with the rat colon carcinogenesis. We also examined the identification of mucin-depleted foci (MDF) by using alcian blue pH2.5 stain in human colon mucosa of 57 subjects. We found that MDF existed in human colon mucosa. Histologically, MDF and OLL (Overlapped lesion with ACF) recognized the loss of goblet cells, nucleus swelling, nuclear stratification, and infiltrate of lymphocyte to stroma. The some of OLL represented the crypt with serrated change. These results suggested that MDF existed even in humans and it may be preneoplastic lesions and could be useful biomarker of human colon carcinogenesis.

本研究旨在通过大鼠结肠癌模型探讨Notch信号通路与结肠癌发生的关系。我们发现Notch 1在结肠肿瘤中的表达较正常粘膜显著增加。Klf 4在结肠癌组织中的表达明显低于正常粘膜组织。提示Notch 1的高表达和Klf 4的低表达可能与大鼠结肠癌的发生有关。我们还检查了57例受试者的结肠粘膜中使用阿辛蓝pH2.5染色的粘蛋白耗尽灶（mucin-depleted focuses，ESTA）的识别。我们发现人结肠粘膜中存在着一种蛋白质。组织学检查发现，肿瘤组织中杯状细胞丢失，细胞核肿胀，细胞核分层，淋巴细胞向间质浸润。OLL的部分代表锯齿状变化的地穴。这些结果表明，大肠癌组织中也存在大肠癌前病变，可能是大肠癌发生发展的一个有用的生物标志物。

项目成果

ヒト大腸粘膜におけるムチン枯渇巣の検索

寻找人结肠粘膜中的粘蛋白消耗灶

• 发表时间: 2008
• 作者: 森岡孝満;吉見直己
• 通讯作者: 吉見直己

Inhibitory effect of rice bran-derived crude glycosphingolipid on colon reneoplastic biomarker lesions induced by azoxymethane in male F344 rats

米糠粗鞘糖脂对氧化偶氮甲烷诱导的雄性 F344 大鼠结肠再生生物标志物病变的抑制作用

• 发表时间: 2009
• 期刊: Molecular Medicine Peports 2
• 作者: Kamao T;Miyazaki T;Soga Y;Komori H;Terada M;Nose M;et.al.;Nao Sunagawa
• 通讯作者: Nao Sunagawa

Effects of synthetic and natural in vivo inhibitors of β-glucuronidase on azoxymethane-induced colon carcinogeneis.

β-葡萄糖醛酸酶的合成和天然体内抑制剂对氧化偶氮甲烷诱导的结肠癌的影响。

• 发表时间: 2008
• 期刊: Mole Med Reports
• 作者: Morita N;Walaszek Z;Kinjo T;Nishimaki T;Hanausek M;Slaga TJ;Mori H;Yoshimi N
• 通讯作者: Yoshimi N

Histological examination and distributional analysis of mucin-depleted foci(MDF)in the human colon mucosa

人结肠粘膜粘蛋白耗尽灶（MDF）的组织学检查和分布分析

• 发表时间: 2009
• 作者: Yutori H;Semba S;Komori T;Yokozaki H;森岡孝満
• 通讯作者: 森岡孝満

ラット大腸腫瘍における Notchl 及びKlf4遺伝子のmRNA発現に関する検討

大鼠结肠肿瘤中Notch1和Klf4基因mRNA表达的研究

• 发表时间: 2009
• 作者: 森岡孝満;崔長旭;森田奈苗;吉見直己;Matsumoto H;森岡孝満
• 通讯作者: 森岡孝満