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Titolo:
Cellular sensitization to cisplatin and carboplatin with decreased removalof platinum-DNA adduct by glucose-regulated stress
Autore:
Yamada, M; Tomida, A; Yun, JS; Cai, B; Yoshikawa, H; Taketani, Y; Tsuruo, T;
Indirizzi:
Univ30032,, Biomed Res Lab, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 11 Univ Tokyo Tokyo Japan 1130032 ol & Cellular Biosci, Bunkyo Ku, Tokyo 11 Univ Tokyo, Dept Obstet & Gynecol, Fac Med, Bunkyo Ku, Tokyo 1130033, Japan Univ Tokyo Tokyo Japan 1130033 Fac Med, Bunkyo Ku, Tokyo 1130033, Japan Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Toshima Ku, Tokyo 170, JapanJapanese Fdn Canc Res Tokyo Japan 170 rapy, Toshima Ku, Tokyo 170, Japan
Titolo Testata:
CANCER CHEMOTHERAPY AND PHARMACOLOGY
fascicolo: 1, volume: 44, anno: 1999,
pagine: 59 - 64
SICI:
0344-5704(199907)44:1<59:CSTCAC>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN OVARIAN-CANCER; CHINESE-HAMSTER CELLS; DRUG ACCUMULATION; RESISTANCE; REPAIR; INDUCTION; PROTEINS; TUMORS; MECHANISMS; ADRIAMYCIN;
Keywords:
glucose-regulated stress; cisplatin; carboplatin; chemosensitization; DNA platination;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Tsuruo, T Univyoi,yo, Biomed Res Lab, Inst Mol & Cellular Biosci, Bunkyo Ku, 1-1-1 Ya Univ Tokyo 1-1-1 Yayoi Tokyo Japan 1130032 Bunkyo Ku, 1-1-1 Ya
Citazione:
M. Yamada et al., "Cellular sensitization to cisplatin and carboplatin with decreased removalof platinum-DNA adduct by glucose-regulated stress", CANC CHEMOT, 44(1), 1999, pp. 59-64

Abstract

Purpose: Stress conditions, such as glucose starvation and hypoxia, that induce glucose-regulated proteins (GRPs) in cells, are seen in most solid tumors. These conditions have been shown to cause cellular resistance to multiple anticancer drugs, such as etoposide, doxorubicin, and camptothecin. Weexamined the effect of the GRP-inducing conditions on cellular sensitivityto cisplatin and carboplatin, which are widely used drugs against solid tumors. Methods: We generated the GRP-inducing culture conditions by exposingcells to 2-deoxyglucose (2DG), calcium ionophore A23187 and tunicamycin, and examined cellular sensitivity to cisplatin and carboplatin under these conditions. We next measured platinum accumulation and DNA-bound platinum in2DG-stressed cells after cisplatin exposure. Results: The GRP-inducing stress conditions led to cellular sensitization to cisplatin and carboplatin. This sensitization was reversible, as the cellular sensitivity returned to normal levels 12 h after removal of 2DG. Platinum accumulation and DNA-bound platinum that were found immediately after exposure to cisplatin for Ih were slightly increased in 2DG-stressed cells as compared with nonstressed cells. After a drug-free recovery incubation of 8 h, the DNA-bound platinum in the nonstressed cells was reduced by 33% while the amount in the 2DG-stressed cells was sustained at the initial levels. Conclusions: These resultsindicated that the decreased removal of platinum-DNA adducts was associated with increased sensitivity to cisplatin and carboplatin in the stressed cells. The sensitization of cancer cells under the GRP-inducing stress conditions would explain, in part, the clinical potency of platinum drugs against solid tumors.

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Documento generato il 21/09/20 alle ore 02:28:28