JaLCDOI 10.18926/AMO/31598
フルテキストURL fulltext.pdf
著者 Kiura, Katsuyuki| Ohnoshi, Taisuke| Tabata, Masahiro| Shibayama, Takuo| Kimura, Ikuro|
抄録 A subline highly resistant to Adriamycin (SBC-3/ADM100) was isolated in vitro from the human small cell lung cancer cell line, SBC-3, by culturing in progressively higher concentrations of Adriamycin. The SBC-3/ADM100 cells were 106-fold more resistant to the drug than the parent cells in an inhibitory concentration of 50% determined by the MTT assay. The population-doubling time was much longer in SBC-3/ADM100 than in the parent cells. Northern blot hybridization revealed marked overexpression of the MDR1 mRNA in the resistant cells. P-glycoprotein overexpression and a decrease in intracellular accumulation of Adriamycin were demonstrated in SBC-3/ADM100, indicating that outward drug transport was the major mechanism of resistance in this subline. Additionally, a significant elevation of the intracellular glutathione content coupled with the glutathione S-transferase (GST) pi level and a decrease in DNA topoisomerase II (Topo II) activity were noted in this resistant subline. These results indicate that the mechanism of resistance to Adriamycin is multifactorial; involving altered growth characteristics, an enhanced outward transport, enhanced drug detoxification process, and decreased target enzyme activity. The resistant subline will serve as a useful tool in the search for ways to overcome drug resistance.
キーワード Adriamycin-resistant cell line MDR1 mRNA glutathione glutathione S-transferasse π DNA topoisomerase II
Amo Type Article
発行日 1993-06
出版物タイトル Acta Medica Okayama
47巻
3号
出版者 Okayama University Medical School
開始ページ 191
終了ページ 197
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
著作権者 Copyright © 1999 Okayama University Medical School
論文のバージョン publisher
査読 有り
PubMed ID 8104372
Web of Science KeyUT A1993LL12400008
関連URL http://ousar.lib.okayama-u.ac.jp/metadata/6296
JaLCDOI 10.18926/AMO/31590
フルテキストURL fulltext.pdf
著者 Segawa, Yoshihiko| Ohnoshi, Taisuke| Hiraki, Shunkichi| Ueoka, Hiroshi| Kiura, Katsuyuki| Kamei, Haruhito| Tabata, Masahiro| Shibayama, Takuo| Miyatake, Kazuyo| Genda, ken-ichi| Matsumura, Tadashi| Kimura, Ikuro|
抄録 <p>In an attempt to elucidate the tumor properties relating to responsiveness to chemotherapy, we examined immunohistochemically the expression of P-glycoprotein (P-gp) and carcinoembryonic antigen (CEA) in small cell lung cancer (SCLC) tumors. Tumor specimens from 33 patients were obtained at the time of diagnosis and relapse. Four patients expressed P-gp in their initial tumors, and 7 others did in recurrent tumors. The overall response rate to chemotherapy of the initial tumors was 75% for P-gp-positive initial tumors and 86% for P-gp-negative tumors, whereas the disease-free and overall survival times were significantly shorter in the former than the latter. Three patients showed CEA in their initial tumors, and 5 others did in recurrent tumors. The patients with CEA-positive initial tumors tended to relapse earlier than those with CEA-negative tumors. In addition, recurrent tumors expressing CEA were resistant to salvage chemotherapy. A clear correlation between CEA expression by tumors and the CEA level in the serum was observed at diagnosis as well as at relapse. These findings indicate that P-gp and/or CEA expression by a tumor and elevated CEA level in the serum may predict refractoriness of the tumor to chemotherapy.</p>
キーワード small cell lung cancer immunohistochemistry drug resistance P-glycoprotein carcinoembryonic antigen
Amo Type Article
発行日 1993-06
出版物タイトル Acta Medica Okayama
47巻
3号
出版者 Okayama University Medical School
開始ページ 181
終了ページ 189
ISSN 0386-300X
NCID AA00508441
資料タイプ 学術雑誌論文
言語 English
論文のバージョン publisher
査読 有り
PubMed ID 8104371
Web of Sience KeyUT A1993LL12400007