論文 - 詳細
| RRC ID | 44070 |
|---|---|
| 著者 | Rahman MT, Nakayama K, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Nakayama S, Otsuki Y, Miyazaki K. |
| タイトル | Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer. |
| ジャーナル | Am J Clin Pathol |
| Abstract |
This study examined the clinical significance of Notch3 expression and assessed its usefulness as a potential therapeutic target in chemoresistant ovarian cancer. Notch3 expression was assessed with immunohistochemical examination, and clinical variables were collected with a retrospective chart review. Notch3 siRNA or γ-secretase inhibitor was used to assess Notch3 function in ovarian cancer cell lines. Notch3 overexpression correlated with shorter progression-free/overall survival in patients with advanced stage (stage III, IV) ovarian carcinoma treated with platinum and taxane. Three of 5 patients showed increased Notch3 immunostaining in recurrent tumors compared with corresponding primary tumors. Notch3 overexpression was observed in both the cisplatin-resistant KFr13 and cisplatin/paclitaxel-resistant KFr13Tx cells. Inactivation of Notch3 by γ-secretase inhibitor or siRNA decreased cell proliferation and induced apoptosis in the KFr13 and KFr13Tx cells. Our findings suggest that Notch3 expression may be related to chemoresistance and that the Notch3 pathway may represent a novel therapeutic target for advanced stage chemoresistant ovarian cancer. |
| 巻・号 | 138(4) |
| ページ | 535-44 |
| 公開日 | 2012-10-1 |
| DOI | 10.1309/AJCPKDLRQ8F3EWNS |
| PII | 138/4/535 |
| PMID | 23010708 |
| MeSH | Adenocarcinoma / diagnosis* Adenocarcinoma / genetics Adenocarcinoma / metabolism Adenocarcinoma / mortality Amyloid Precursor Protein Secretases / antagonists & inhibitors Antineoplastic Combined Chemotherapy Protocols Apoptosis / drug effects Cell Line, Tumor Cisplatin / pharmacology Disease Progression Drug Resistance, Neoplasm / genetics* Enzyme Inhibitors / pharmacology Female Gene Expression Regulation, Neoplastic / drug effects* Gene Knockdown Techniques Humans Japan / epidemiology Kaplan-Meier Estimate Middle Aged Neoplasm Recurrence, Local Neoplasm Staging Ovarian Neoplasms / drug therapy* Ovarian Neoplasms / genetics Ovarian Neoplasms / metabolism Ovarian Neoplasms / mortality Paclitaxel / pharmacology RNA, Small Interfering / genetics Receptor, Notch3 Receptors, Notch / genetics Receptors, Notch / metabolism* Retrospective Studies Survival Rate |
| IF | 2.094 |
| 引用数 | 39 |
| WOS 分野 | PATHOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | JHOC-9(RCB2226) JHOC-5(RCB1520) |