Analysis of hypoxia-inducible factors in ovarian tumors focusing on individual-based treatment

卵巢肿瘤缺氧诱发因素分析，注重个体化治疗

• 批准号: 21590404
• 负责人: YASUDA Masanori
• 金额: $ 2.58万
• 依托单位: Saitama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590404/
• 关键词: 分子病理; 医歯薬学; 基礎医学; 人体病理学; 基歴医学

Everolimus(a derivative of rapamycin)-treated cells and non-treated cells were found not to show any difference in mTOR expression. But, phosphorylated-mTOR(p-mTOR) expression significantly decreased in the treated cells, and mTOR-related factors such as phosphorylated-4E-BP1(p-4E-BP1), HIF-1α, and vascular endothelial growth factor(VEGF) in the downstream region of mTOR revealed a marked decrease in expression. The analysis of influences of the drug on the HIF-1αdegradation system showed an increase in von-Hippel Lindau(VHL) expression in the treated cells. Increase of cleaved caspase-3, one of key factors involved in apoptosis, was also shown in the treated cells. In the next step, using nude mice implanted with RMG-1 cells, a decrease in tumor size was demonstrated in 4 of the 7 mice which were orally administered with everolimus. As a result, it was suggested that everolimus administration would be helpful as an anti-tumor therapy for CCA not only via down-regulation of p-mTOR but also degradation of HIF-1αby VHL and induction of apoptosis by cleaved caspase-3.

发现依维莫司（雷帕霉素的衍生物）处理的细胞和未处理的细胞在mTOR表达方面没有显示出任何差异。但磷酸化mTOR（p-mTOR）的表达在处理的细胞中显著降低，并且mTOR下游区域的mTOR相关因子如磷酸化-4 E-BP 1（p-4 E-BP 1）、HIF-1α和血管内皮生长因子（VEGF）的表达显著降低。药物对HIF-1α降解系统的影响分析显示，在处理的细胞中von-Hippel Lindau（VHL）表达增加。在处理的细胞中还显示了参与凋亡的关键因子之一的切割的caspase-3的增加。在下一步中，使用植入RMG-1细胞的裸鼠，在口服给予依维莫司的7只小鼠中的4只中证实肿瘤大小减小。结果表明，依维莫司给药不仅通过下调p-mTOR，而且通过VHL降解HIF-1α和通过切割的caspase-3诱导凋亡，有助于CCA的抗肿瘤治疗。

项目成果

Clear Cell Adenocarcinoma Arising From Adenomyosis

• DOI: 10.1097/pgp.0b013e31818e101f
• 发表时间: 2009-05-01
• 期刊: INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY
• 影响因子: 2.4
• 作者: Hirabayashi, Kenichi;Yasuda, Masanori;Osamura, Robert Yoshiyuki
• 通讯作者: Osamura, Robert Yoshiyuki

Ghost cell odontogenic carcinoma arising in calcifying odontogenic cyst

钙化性牙源性囊肿中出现的影细胞牙源性癌

• 发表时间: 2009
• 期刊: Ann Diagn Pathol
• 影响因子: 2
• 作者: Motosugi U;Ogawa I;Yasuda M;et al
• 通讯作者: et al

婦人科領域の組織化学(≒免疫組織化学)

妇科领域的组织化学（≒免疫组织化学）

• 发表时间: 2011
• 作者: 鳥越俊彦;廣橋良彦;佐藤昇志;安田政実
• 通讯作者: 安田政実

閉経後AFP産生卵巣腫瘍11例の臨床病理学的検討:明細胞腺癌および他の組織型と卵黄嚢腫瘍との異同

11例绝经后产AFP卵巢肿瘤的临床病理学检查：透明细胞腺癌、其他组织学类型及卵黄囊肿瘤的差异

• 发表时间: 2011
• 作者: Tomoeda M;Yuki M;Kubo C;Yoshizawa H;Kitamura M;Nagata S;Nishizawa Y;Tomita Y;安田政実
• 通讯作者: 安田政実

Cellular proliferation and apoptosis in ascetic cytology : the clinicopathological significance in uterine body cancer.

禁欲细胞学中的细胞增殖和凋亡：子宫体癌的临床病理学意义。

• 发表时间: 2011
• 作者: 倉持雅己;山岡賢俊;小林敬祐;井口けさ人;菊池慎二;酒井光昭;後藤行延;鬼塚正孝;佐藤幸夫;薄井真悟;南優子;野口雅之;Yasuda M.
• 通讯作者: Yasuda M.