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A trial at developing molecular-targeted therapy of ovarian cancer using a molecular chaperon heat shock protein(Hsp) as the target

以分子伴侣热休克蛋白（Hsp）为靶点开发卵巢癌分子靶向治疗的试验

基本信息

批准号：
18591849
负责人：
KIGUCHI Kazushige
金额：
$ 2.48万
依托单位：
St.Marianna University School of Medicine
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-18591849/
关键词：
gynecologic oncology oncology protein proteomics pathology 婦人科学

项目摘要

Geldanamycin(GA) was administered to several strains highly expressive of various HER-2 to find whether GA, an Hsp90-selective inhibitor, can be administered to ovarian cancer as a molecular-targeted therapy. For a medium-to-high degree of expression of HER-2, GA administration resulted in a reduction in protein expression and an evident suppression of cell proliferation. On the other hand, Hsp70, in cooperation with Hsp60 and others, performed a protein chaperon function for Hsp90. It has been known that Hsp70 expression is exaggerated in conditions such as ovarian and breast tumors and osteosarcoma. We have conducted a proteomics analysis of the protein group that had undergone changes in the Ga-treated and control groups, in comparison with the ovarian cancer with high HER-2 expression, and learned that the Hsp70 content increased significantly after GA administration, in comparison with the control. It was presumed that GA administration releases Hsp90 from its bond with HSF-1(heat … More shock transcription factor 1) ; HSF-1 is activated, in turn causing the Hsp gene activation. In other words, one expects that the cancer cells cause the Hsp70 content to increase to cover the damage, in an effort to survive the onslaught by antineoplastic agent administration. The increase in Hsp70 is ultimately linked to the resistance to apoptosis and even to the development of drug resistance of these cells. Currently, a study is underway not only on the Hsp70 function as a molecular chaperon but also on its signal transduction function in apoptosis-suppressive effects so that the results may lead to a new molecular targeted therapy mainly for ovarian cancer. Currently, a study is being conducted to evaluate the extent of involvement of Hsp70 in proteolysis by preparing RNAi of Hsp70 and introducing the gene into the cells. Also included : to discover whether the addition of an Hsp70 inhibitor to a strain with a high expression of Hsp70 will resolve the anti-apoptosis action and ultimately result in overcoming the resistance to antineoplastic agents. Less

格尔德霉素（GA）的管理，以几个菌株的高表达的各种HER-2，以发现GA，热休克蛋白90的选择性抑制剂，是否可以作为一种分子靶向治疗卵巢癌。对于HER-2的中高表达程度，GA给药导致蛋白质表达的降低和细胞增殖的明显抑制。另一方面，Hsp70与Hsp60和其它蛋白质合作，对Hsp90执行蛋白质伴侣功能。已知Hsp70的表达在诸如卵巢和乳腺肿瘤以及骨肉瘤的病症中被夸大。我们对GA处理组和对照组中发生变化的蛋白质组进行了蛋白质组学分析，并与HER-2高表达的卵巢癌进行了比较，了解到GA给药后Hsp70含量与对照组相比显著增加。据推测，GA给药使Hsp90从其与HSF-1的结合中释放（热 ...更多信息休克转录因子1）; HSF-1被激活，进而引起Hsp基因激活。换句话说，预期癌细胞引起Hsp70含量增加以覆盖损伤，以努力在抗肿瘤剂施用的冲击下存活。Hsp70的增加最终与对细胞凋亡的抗性相关，甚至与这些细胞的耐药性的发展相关。目前，不仅正在研究Hsp70作为分子伴侣的功能，而且还在研究其抑制卵巢癌作用的信号转导功能，因此结果可能导致新的主要针对卵巢癌的分子靶向治疗。目前，正在进行一项研究，通过制备Hsp70的RNAi并将该基因导入细胞来评估Hsp70参与蛋白质水解的程度。还包括：以发现向具有高表达Hsp70的菌株中加入Hsp70抑制剂是否将解决抗凋亡作用并最终导致克服对抗凋亡剂的抗性。少

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cytology and histology of corpus uteri cancer.

子宫体癌的细胞学和组织学。

DOI：
发表时间：
2007
期刊：
Clinical Gynecology and Obstertrics 61
影响因子：
0
作者：
Costanzo R;Miwa T;H.Mineta;木口一成;三輪高喜;H.Mineta;三輪高喜;Masao Iwanmori;H.Mine ta;Kazushige Kiguchi
通讯作者：
Kazushige Kiguchi

Ubiquitonation of SPIN, an ovarian cancer-related protein, by BRCA1.

BRCA1 对卵巢癌相关蛋白 SPIN 进行泛素化。

DOI：
发表时间：
2006
期刊：
St. Maranna Medical Journal 34
影响因子：
0
作者：
Yoichi Kobayashi;et. al.;Yoichi Kobayyashi;Kazushige Kiguchi;Masao Iwanmori;Tatsuru Ohara;Yoshiko Okuda
通讯作者：
Yoshiko Okuda

治療に難渋した臨床的侵入奇胎の1例。

一例临床上难以治疗的侵袭性葡萄胎。