| RRC ID |
62250
|
| 著者 |
Shirota T, Ojima H, Hiraoka N, Shimada K, Rokutan H, Arai Y, Kanai Y, Miyagawa S, Shibata T.
|
| タイトル |
Heat Shock Protein 90 Is a Potential Therapeutic Target in Cholangiocarcinoma.
|
| ジャーナル |
Mol Cancer Ther
|
| Abstract |
Cholangiocarcinoma is an aggressive malignancy with a poor prognosis, with no effective therapy other than surgical resection. Heat shock protein 90 (HSP90) is a key component of a multichaperone complex involved in the posttranslational folding of a number of client proteins, many of which play essential roles in tumorigenesis. Here, we attempted to clarify its prognostic significance and potential utility as a therapeutic target in cholangiocarcinoma. Immunohistochemical expression of HSP90 was assessed retrospectively in 399 cholangiocarcinoma cases and 17 human cholangiocarcinoma cell lines, along with the effect of a small-molecule HSP90 inhibitor (NVP-AUY922) on cholangiocarcinoma tumor growth and angiogenesis in human cholangiocarcinoma cell lines and xenografts. The positivity of HSP90 was 44.6% in intrahepatic cholangiocarcinoma (IHCC) and 32.8% in extrahepatic cholangiocarcinoma (EHCC), respectively. HSP90 expression was significantly associated with the 5-year survival rate for IHCC (P < 0.001) and EHCC (P < 0.001). HSP90 inhibition showed potent antiproliferative activity and reduced growth-associated signaling in human cholangiocarcinoma cells in vitro. Furthermore, treatment of cholangiocarcinoma xenograft-bearing mice with NVP-AUY922 significantly inhibited growth at doses far below the maximum-tolerated dose. HSP90 overexpression is a prognostic marker for cholangiocarcinoma. HSP90-targeted therapy may be an option for a subset of cholangiocarcinoma.
|
| 巻・号 |
14(9)
|
| ページ |
1985-93
|
| 公開日 |
2015-9-1
|
| DOI |
10.1158/1535-7163.MCT-15-0069
|
| PII |
1535-7163.MCT-15-0069
|
| PMID |
26141945
|
| MeSH |
Adult
Aged
Aged, 80 and over
Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cholangiocarcinoma / drug therapy
Cholangiocarcinoma / metabolism*
Cholangiocarcinoma / mortality
Cholangiocarcinoma / pathology
Cholangiocarcinoma / surgery
Disease Models, Animal
Female
Follow-Up Studies
HSP90 Heat-Shock Proteins / antagonists & inhibitors*
HSP90 Heat-Shock Proteins / metabolism*
Humans
Immunohistochemistry
Isoxazoles / administration & dosage
Isoxazoles / pharmacology
Male
Mice
Middle Aged
Molecular Targeted Therapy
Neoplasm Staging
Prognosis
Resorcinols / administration & dosage
Resorcinols / pharmacology
Treatment Outcome
Xenograft Model Antitumor Assays
|
| IF |
5.615
|
| リソース情報 |
| ヒト・動物細胞 |
TKKK(RCB1907)
HuCCT1(RCB1960)
TGBC24TKB(RCB1196) |
