Do any microcirculation changes reflect the malignant transformation in the intestinal tract during the multistep carcinogenesis?

在多步癌变过程中，微循环的变化是否反映了肠道的恶性转化？

• 批准号: 22791304
• 负责人: KITAHARA Shuji
• 金额: $ 2.5万
• 依托单位: Tokyo Women's 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: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791304/
• 关键词: 血管新生; 腫瘍血管; 消化器腫瘍; 多段階発癌; 自然発症腫瘍; 癌微小環境; 消化器癌; 消化管腫瘍

Apc^(Min/+) mice provide a unique orthotopic model for the development of spontaneous adenomatous polyposis and subsequent carcinomas, termed the adenoma-carcinoma sequence. In the current study, we sought to clarify the relationship between the patterns of tumor angiogenesis and the sequence of neoplastic transformation in intestinal epithelia, by the morphological characterization of this tumor models. We found that structural abnormalities of tumor vessels and the pattern of tumor angiogenesis in benign tumors resembled that in malignant tumors. Several angiogenic markers, such as VEGF were overexpressed in pre-neoplastic intestinal lesions from very early stages during the adenoma-carcinoma sequence in both mice and humans. A novel intrinsic angiogenic factor, Vasohibin-2 protein was detected around tumor blood vessels in adenocarcinomas in situ, but was absent from adenomas during early stages of Apc^(Min/+) tumors. These results indicated that malignant changes in local vascular networks occurred earlier than malignant transformation of the intestinal epithelia. Therefore, we suggest that microvascular changes in preneoplastic adenomatous polyposis may be an important diagnostic sign for the progression of intestinal adenocarcinoma and may be useful to predict the transformation of tumors from a benign to a malignant state

Apc^(Min/+)小鼠为自发性腺瘤性息肉病和随后的癌的发展提供了独特的原位模型，称为腺瘤-癌序列。在当前的研究中，我们试图通过该肿瘤模型的形态特征来阐明肿瘤血管生成模式与肠上皮肿瘤转化序列之间的关系。我们发现良性肿瘤的肿瘤血管结构异常和肿瘤血管生成模式与恶性肿瘤相似。在小鼠和人类的腺瘤-癌序列的早期阶段，几种血管生成标记物（例如 VEGF）在肿瘤前肠道病变中过度表达。 Vasohibin-2 蛋白是一种新的内在血管生成因子，在原位腺癌的肿瘤血管周围检测到，但在 Apc^(Min/+) 肿瘤的早期阶段在腺瘤中不存在。这些结果表明，局部血管网络的恶性变化发生早于肠上皮的恶性转化。因此，我们认为癌前腺瘤性息肉病的微血管变化可能是肠腺癌进展的重要诊断标志，并可能有助于预测肿瘤从良性状态向恶性状态的转变。

项目成果

新生児期肺障害モデルにおける肺胞および肺胞微小循環系の再生過程の解析

新生儿肺损伤模型肺泡及肺泡微循环系统再生过程分析

• 发表时间: 2012
• 作者: T. Kawamoto;et al.;Kitahara Shuji;北原秀治;Kitahara Shuji;北原秀治;北原秀治;北原秀治;北原秀治;菊田幸子;板垣裕子;中西秀彦
• 通讯作者: 中西秀彦

消化管腫瘍を用いた多段階発癌に伴う微小循環系の解析

利用胃肠道肿瘤分析与多阶段癌变相关的微循环系统

• 发表时间: 2010
• 作者: T. Kawamoto;et al.;Kitahara Shuji;北原秀治;Kitahara Shuji;北原秀治;北原秀治;北原秀治;北原秀治;菊田幸子;板垣裕子;中西秀彦;北原秀治;森島正恵;吉井明日香;Shuji KITAHARA;Hidehiko Nakanishi;Shuji KITAHARA;北原秀治;北原秀治;Shuji Kitahara;Shuji Kitahara;北原秀治;中西秀彦;吉井明日香;北原秀治;北原秀治;北原秀治;桃木裕美子;Kitahara S;Itagaki H;北原秀治;北原秀治;北原秀治;森美由紀;森美由紀;北原秀治
• 通讯作者: 北原秀治

Do any vascular change reflect the neoplastic transformation in the intestinal tract during the adenoma-carcinoma sequence?

在腺瘤-癌过程中，是否有任何血管变化反映了肠道的肿瘤转化？

• 发表时间: 2010
• 作者: T. Kawamoto;et al.;Kitahara Shuji;北原秀治;Kitahara Shuji;北原秀治;北原秀治;北原秀治;北原秀治;菊田幸子;板垣裕子;中西秀彦;北原秀治;森島正恵;吉井明日香;Shuji KITAHARA;Hidehiko Nakanishi;Shuji KITAHARA;北原秀治;北原秀治;Shuji Kitahara;Shuji Kitahara;北原秀治;中西秀彦;吉井明日香;北原秀治;北原秀治;北原秀治;桃木裕美子;Kitahara S;Itagaki H;北原秀治;北原秀治;北原秀治;森美由紀;森美由紀;北原秀治;桃木裕美子;北原秀治;Kitahara Shuji
• 通讯作者: Kitahara Shuji

Establishment of a normalized revascularization mouse model using tumor transplantation

肿瘤移植标准化血运重建小鼠模型的建立

• DOI: 10.1016/j.ajoms.2013.02.004
• 发表时间: 2013
• 期刊: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
• 作者: Shimizu K;Asakura M;Shinga J;Sato Y;Kitaha Hoshino K;Kaisho T;Schoenberger SP;Ezaki T;Fujii S;Yumiko Momokia
• 通讯作者: Yumiko Momokia

腫瘍血管を標的とする放射線耐性口腔癌治療の有効性

针对肿瘤血管的抗放射口腔癌治疗的疗效

• 发表时间: 2010
• 作者: T. Kawamoto;et al.;Kitahara Shuji;北原秀治;Kitahara Shuji;北原秀治;北原秀治;北原秀治;北原秀治;菊田幸子;板垣裕子;中西秀彦;北原秀治;森島正恵;吉井明日香;Shuji KITAHARA;Hidehiko Nakanishi;Shuji KITAHARA;北原秀治;北原秀治;Shuji Kitahara;Shuji Kitahara;北原秀治;中西秀彦;吉井明日香;北原秀治;北原秀治;北原秀治;桃木裕美子;Kitahara S;Itagaki H;北原秀治;北原秀治;北原秀治;森美由紀
• 通讯作者: 森美由紀