Investigation of Biological Behavior and Treatment Modality for Ovarian Clear Cell Adenocarcinoma

卵巢透明细胞腺癌的生物学行为和治疗方式的研究

基本信息

批准号：
09671667
负责人：
FUJIMURA Masaki
金额：
$ 1.86万
依托单位：
TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671667/
关键词：
Ovarianclearcell adenocarcmoma Chemo-resistant ovarian cancer Growth Faetor EGF-R HER2 neu Monoclonal antibody ZD1839 HERCEPTIN 明細胞腺癌卵巣癌チロシンキナーゼサイトカイン Clear cell adenocarcinoma Ovarian cancer Tyrosin Kinase Cytokine 薬剤

项目摘要

The basic anti-caner drug for treating ovarian clear cell adenocarcinoma (CCA) was revealed to be CPT-ll. Hyperthermia and Glycerol addition which were known as enhencer of anti-cancer drug, have insufficient effect on its clinically available condition. Estrogen receptor-α (ER α), and ER β were not expressed in clinically resected Ovarian CCA specimens and cultured CCAcell lines. EOF and TGF α stimulation through EGF-R, which was thought to be located at the lower stream of ERα, stimulated the growth and invasion of CCA cell lines by autocline system. Stimulation through HER2 was also involved in the growth of ovarian CCA cell lines. Then Iressa, a specific inhibitor of EGF-R phosphorylation, inhibited the growth and invasion of CCA cell lines dose dependently. Iressa also inhibit the growth of xenografted CCA(RMG-l) on the back of SCID mice. The mice in which Iressa was administered survived more longer than the mice in control group. Herceptin which is known as humanized anti-HER2 monoclonal antibody, also inhibited the growth of CCA cell line in vitro and in vivo. Also Herceptin administered mice survived more longer than the mice in control group.From these findings, Iressa and Herceptin were revealed to be potent inhibitors of CCA cell lines and could be a good candidate as one of clinically comprehensive treatment modality for CCA.

用于治疗卵巢透明细胞腺癌（CCA）的基本抗驱动药物是CPT-LL。被称为抗癌药物增强剂的高温和甘油添加对其临床可用状态的影响不足。雌激素受体-α（ERα）和ERβ在临床切除的卵巢CCA标本和培养的CCACELL系中未表达。 EOF和TGFα通过EGF-R刺激，重要的是要了解，位于ERα的下部很重要，刺激了Autocline System刺激CCA细胞系的生长和侵袭。通过HER2刺激还参与了卵巢CCA细胞系的生长。然后，EGF-R磷酸化的特定抑制剂IRESSA依赖于CCA细胞系剂量的生长和侵袭。 IRESSA还抑制异种移植的CCA（RMG-L）在SCID小鼠背面的生长。在对照组中，施用IRESSA的小鼠的生存比小鼠更长。赫斯汀被称为人源化抗HER2单克隆抗体，也抑制了CCA细胞系在体外和体内的生长。同样，赫斯汀的给药小鼠的存活比对照组的小鼠更长。从这些发现，Iressa和Herceptin被发现是CCA细胞系的有效抑制剂，并且可以作为CCA临床全面治疗方式之一。