The Role of Hepatocyte Nuclear Factor-1Beta in the Pathogenesis of Endometriosi-Associated Ovarian Cancer

肝细胞核因子1β在子宫内膜异位症相关卵巢癌发病机制中的作用

• 批准号: 20591958
• 负责人: KOBAYASHI Hiroshi
• 金额: $ 3万
• 依托单位: Nara 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: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591958/
• 关键词: 子宮内膜症; 卵巣癌; 転写因子; HNF-1beta; 卵巣明細胞腺癌

Problem Clear cell carcinoma of the ovary (CCC) has a number of features distinguishing it from other epithelial ovarian carcinomas (EOC) because of its characteristic histology and biology, frequent concurrence with endometriotic lesion, and highly chemoresistant nature resulting in an extremely poor prognosis. The incidence of CCC has been steadily increasing in Japan. They comprise approximately 20% of all EOC. Understanding the mechanisms of CCC development and elucidating pathogenesis and pathophysiology are intrinsic to prevention and effective therapies for CCC. Method We have investigated the role of hepatocyte nuclear factor-1beta (HNF-1beta) for biology, pathogenesis, and pathophysiological studies on endometriosis-associated EOC. Several data are discussed in the context of endometriosis and CCC biology. Results Here, we show that 1) the expression of the genes involved in transcription, signaling, cell cycle, adhesion, matrix, proteinase, and detoxification was greatly incr … More eased in the CCC carcinogenesis ; 2) upregulation of HNF-1beta and Polo-like kinase (PLK)-Early mitotic inhibitor-1 (Emi1) as well as their downstream targets are specifically found in most CCC. The promising molecular targeting approach will emerge in the context of HNF-1beta and PLK-Emi1 biology ; and 3) several significant common pathways observed in CCC of the ovary overlap the datasets identified in CCC of the kidney. To improve the outcome in CCC therapy, we must learn various adaptive treatment strategies for renal CCC, although it is not supported by any preliminary clinical data. These studies based on genome-wide expression analysis technology have noted specific expression of transcription factor genes, HNF-1beta, in endometriosis and CCC, suggesting that early differentiation into the clear cell lineage takes place in the endometriosis. The HNF-1beta-dependent pathway of CCC will be discussed, which are providing new insights into regulation of apoptosis and glycogen synthesis and resistance of CCC to anticancer agents. Conclusion This study demonstrates recent advances in the HNF-1beta and its target genes, the potential challenges to the understanding of carcinogenesis, pathogenesis and pathophysiology of CCC, and a possible novel model is proposed. The inhibitors that target HNF-1beta and PLK-Emi1 and their downstream signaling molecules would be evaluated. The challenges accompanying the recent advance are described in this article. Less

卵巢（CCC）的清晰细胞癌具有许多特征，其特征与其他上皮卵巢癌（EOC）区分开来，因为其特征性的组织学和生物学，经常与子宫内膜病变一致，并且高度化学疗法导致预后极为差。在日本，CCC的事件一直在稳步增加。它们约占所有EOC的20％。了解CCC发育的机制以及阐明发病机理和病理生理学是CCC的预防和有效疗法的内在性。方法我们已经研究了肝细胞核因子-1BETA（HNF-1BETA）在生物学，发病机理和病理生理研究对子宫内膜异位相关的EOC中的作用。在子宫内膜异位症和CCC生物学的背景下讨论了几个数据。结果在这里，我们表明1）在CCC癌发生中，更容易更容易获得转录，信号，细胞周期，粘合剂，基质，蛋白酶和排毒的基因的表达； 2）在大多数CCC中特别发现了HNF-1BETA和POLO样激酶（PLK） - 过度有丝分裂抑制剂1（EMI1）及其下游靶标。在HNF-1BETA和PLK-EMI1生物学的背景下，有希望的分子靶向方法将出现。 3）在卵巢CCC中观察到的几种重要的公共途径与肾脏CCC中鉴定的数据集重叠。为了改善CCC治疗的结果，我们必须学习各种肾脏CCC的自适应治疗策略，尽管没有任何初步临床数据支持。这些基于全基因组表达分析技术的研究指出，子宫内膜异位症和CCC中转录因子基因HNF-1BETA的特定表达表明，在子宫内膜异位症中发生了早期分化为透明细胞谱系。将讨论CCC的HNF-1BETA依赖性途径，该途径正在为调节凋亡和糖原合成的调节以及CCC对抗癌剂的抗性提供新的见解。结论本研究表明，HNF-1BETA及其靶基因的最新进展，对CCC的癌变，发病机理和病理生理学的理解的潜在挑战，并提出了一种新的模型。将评估靶向HNF-1BETA和PLK-EMI1及其下游信号分子的抑制剂。在本文中描述了最近的进步挑战。较少的

项目成果

Angiopoietin-like Protein 2 (AngPTL2) in Human Maternal Serum, Amniotic Fluid and Term Placental Trophoblast in Pregnancy.

妊娠期人母体血清、羊水和足月胎盘滋养层中的血管生成素样蛋白 2 (AngPTL2)。

• 发表时间: 2009
• 作者: Naruse K;Endo M;Onogi A;Shigetomi H;Yoshizawa Y;Sado T;Oi H;Oike Y;Kobayashi H.
• 通讯作者: Kobayashi H.

Ultrasonic CTAR and PLI Indices Predict Neonatal Congestive Heart Failure in Monochorionic Twin Pregnancies

超声 CTAR 和 PLI 指数可预测单绒毛膜双胎妊娠中的新生儿充血性心力衰竭

• 发表时间: 2008
• 作者: Sakata M;Shigetomi H;Utsu M;Kobayashi H;Maeda K.
• 通讯作者: Maeda K.

A Neonate with Umbilical Arteriovenous Malformation Showing Hemorrhagic Shock from Massive Umbilical Hemorrhage.

脐部动静脉畸形新生儿因脐部大量出血而出现失血性休克。

• 发表时间: 2009
• 期刊: Am J Perinatol. 26(8)
• 作者: Shibata M;Kanehiro H;Shinkawa T;Fujita Y;Yada K;Kamamoto T;Arai I;Nishikubo T;Sakata M;Kobayashi H;Takeda M;Nonomura A;Takahashi Y.
• 通讯作者: Takahashi Y.

Giant abdominal tumor of the ovary.

腹部巨大卵巢肿瘤。

• 发表时间: 2008
• 期刊: J Obstet Gynaecol Res. 34
• 作者: Sakata M;Kobayashi H.
• 通讯作者: Kobayashi H.

Metodopramide does not prolong duration of action of landiolol attenuating the hemodynamic response to induction of anesthesia and tracheal intubation.

甲多普胺不会延长兰地洛尔的作用持续时间，从而减弱对麻醉诱导和气管插管的血流动力学反应。

• 发表时间: 2010
• 期刊: J Anesth
• 影响因子: 2.8
• 作者: Inoue S;Abe R;Kawaguchi M;Kobayashi H;Furuya H.
• 通讯作者: Furuya H.