| RRC ID |
41459
|
| 著者 |
Nakajima Y, Miyake S, Nagai K, Kawano T, Iwai T.
|
| タイトル |
CPT-11 may provide therapeutic efficacy for esophageal squamous cell cancer and the effects correlate with the level of DNA topoisomerase I protein.
|
| ジャーナル |
Jpn J Cancer Res
|
| Abstract |
CPT-11 is a potent anti-cancer drug and a specific inhibitor of DNA topoisomerase I (Topo I). In this study, we aim to evaluate the effects of CPT-11 on esophageal squamous cell cancers (ESCC) and to determine the correlation between the effects and the levels of Topo I expression. We examined the growth-inhibitory effect caused by SN-38, an active metabolite of CPT-11, in 14 human ESCC cell lines established from 10 primary and 4 metastatic lesions. CPT-11 was considered effective against 5 cell lines from primary lesions and one from metastatic lesions, and thus may show therapeutic efficacy against both primary and metastatic ESCC tumors. Although Topo I mRNA levels in these 14 ESCC cell lines, as quantitated by northern blot analysis, showed no correlation with the IC(50) values, Topo I protein levels, as quantitated by western blot analysis, showed an inverse correlation with the IC(50) values. Topo I protein levels could be an indicator of sensitivity to CPT-11. We also determined Topo I protein levels in 40 ESCC tumors and matched normal mucosae. Thirty-four tumors showed 1.2 - 22.3-fold increases in Topo I levels. Two patients receiving pre-operative chemotherapy and one receiving radiotherapy exhibited increased Topo I protein levels in their tumor lesions. It appeared that CPT-11 could provide selective therapeutic efficacy against ESCC tumors. CPT-11 may be effective for the treatment of metastatic ESCC tumors and as a second-line anti-cancer drug for ESCC.
|
| 巻・号 |
92(12)
|
| ページ |
1335-41
|
| 公開日 |
2001-12-1
|
| DOI |
10.1111/j.1349-7006.2001.tb02158.x
|
| PMID |
11749700
|
| PMC |
PMC5926676
|
| MeSH |
Blotting, Western
Camptothecin / analogs & derivatives
Camptothecin / pharmacology
Camptothecin / therapeutic use*
Cell Division / drug effects
DNA Topoisomerases, Type I / metabolism*
Dose-Response Relationship, Drug
Esophageal Neoplasms / drug therapy*
Esophageal Neoplasms / enzymology*
Humans
Irinotecan
Neoplasms, Squamous Cell / drug therapy*
Neoplasms, Squamous Cell / enzymology*
RNA, Messenger / metabolism
Tumor Cells, Cultured
|
| 引用数 |
12
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
EC-GI-10(RCB0774) |
