Article citationsMore>>
P. Rougier, R. Bugat, J. Y. Douillard, S. Culine, E. Suc, P. Brunet, Y. Becouarn, M. Ychou, M. Marty, J. M. Extra, J. Bonneterre, A. Adenis, J. F. Seitz, G. Ganem, M. Namer, T. Conroy, S. Negrier, Y. Merrouche, F. Burki, M. Mousseau, P. Herait and M. Mahjoubi, “Phase II Study of Irinotecan in the Treatment of Advanced Colorectal Cancer in Chemotherapy-Naive Patients and Patients Pretreated with Fluorouracil-Based Chemotherapy,” Journal of Clinical Oncology, Vol. 15, No. 1, 1997, pp. 251-260.
has been cited by the following article:
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TITLE:
Bicarbonate Attenuates Irinotecan-Induced Cytotoxicity through Regulation of Both Extracellular and Intracellular pHs in Intestine Cell Line
AUTHORS:
Teruo Miyazaki, Tadashi Ikegami, Yoshiaki Nagai, Amy Nguyen, Yasushi Matsuzaki, Kunihiko Kobayashi, Susan Ceryak
KEYWORDS:
Bicarbonate; SN-38; CPT-11; pHi; Anti-Cancer Drug; Intestine
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.5,
June
28,
2013
ABSTRACT:
The anti-cancer therapy of irinotecan (CPT-11) is often limited due to severe late-onset diarrhea. Because the higher toxic form of CPT-11/its active metabolite (SN-38) is produced at acidification, the usefulness of oral sodium bicarbonate treatment against the CPT-11/SN-38-induced intestinal injuries and diarrhea has been confirmed. However, the roles of bicarbonate have been suggested to affect not only intestinal pH environment but also intracellular pH and CPT-11/SN-38 dynamics. The present study proposed to clarify the hypothesis in CPT-11/SN-38-exposed colon cell line in various pH conditions adjusted by bicarbonate. HT29 cell pre-exposed to ~1.0 μM SN-38 lactone or carboxylate forms was incubated at different pH adjusted by either bicarbonate or HCl/NaOH. The degrees of SN-38-induced cell injury depended on the higher proportion of the toxic form (lactone) of SN-38 rather than mere pH condition of medium. Apoptosis and cell injury induced by SN-38 were significantly inhibited by bicarbonate in a dose-dependent manner. Intercellular pH acidification induced by SN-38 was significantly prevented by 30 mM bicarbonate. Cell cytotoxicity of SN-38 depended on not only extracellular but also intracellular pH that converts the SN-38 form, while the intracellular acidification was prevented by bicarbonate. The multiple regulations of bicarbonate on both exracellular and intracellular pH would be essential mechanism against intestinal cell injury by CPT-11/SN-38.
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