The Effects of N-acetylcysteine on Ifosfamide Efficacy in a Mouse Xenograft Model

被引：0
作者：
Hanly, L. [1 ,2 ]
Figueredo, R. [3 ,4 ,5 ]
Rieder, M. J. [1 ,6 ,7 ]
Koropatnick, J. [1 ,3 ,4 ,5 ,8 ]
Koren, G. [1 ,2 ,6 ,9 ,10 ]
机构：
[1] Univ Western Ontario, Schulich Sch Med & Dent, Dept Physiol & Pharmacol, London, ON, Canada
[2] Univ Western Ontario, Schulich Sch Med & Dent, Ivey Chair Mol Toxicol, London, ON, Canada
[3] London Reg Canc Program, London, ON, Canada
[4] Lawson Hlth Res Inst, London, ON, Canada
[5] Univ Western Ontario, Dept Oncol, London, ON, Canada
[6] Univ Western Ontario, Dept Paediat, London, ON, Canada
[7] Childrens Hlth Res Inst, CIHR GSK Chair Paediat Clin Pharmacol, London, ON, Canada
[8] Univ Western Ontario, Dept Microbiol & Immunol, London, ON, Canada
[9] Hosp Sick Children, Div Clin Pharmacol & Toxicol, Toronto, ON M5G 1X8, Canada
[10] Univ Toronto, Fac Med, Dept Pharmacol, Toronto, ON, Canada
来源：
ANTICANCER RESEARCH | 2012年 / 32卷 / 09期
关键词：
N-acetylcysteine; ifosfamide; antitumour activity; xenograft; Ewing's sarcoma; nephrotoxicity; INDUCED FANCONI-SYNDROME; ACUTE LYMPHOBLASTIC-LEUKEMIA; METASTATIC RHABDOMYOSARCOMA; INDUCED NEPHROTOXICITY; STANDARD CHEMOTHERAPY; TUMOR; CYCLOPHOSPHAMIDE; METABOLISM; ETOPOSIDE; DECHLOROETHYLATION;
D O I：
暂无
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background/Aim: Nephrotoxicity is observed in 30% of children treated with ifosfamide. We have shown that n-acetylcysteine (NAC) successfully mitigates nephrotoxicity of ifosfamide in cell and rodent models. However, before this treatment is evaluated clinically, it must be established that NAC does not interfere with the efficacy of ifosfamide. Materials and Methods: Mice implanted with Ewing's sarcoma tumours received the following treatments: saline, ifosfamide, ifosfamide + NAC concurrently, pre-treatment with NAC + ifosfamide, or NAC alone. Results: Median volumes of EW-7 tumour xenografts in mice treated with ifosfamide (n=8), ifosfamide with concurrent NAC therapy (n=7), and NAC pre-treatment (n=6) (p<0.05) were significantly reduced compared to median tumour volumes of control mice (n=6). None of the NAC treatments affected ifosfamide-mediated reduction in tumour volumes. Conclusion: NAC does not interfere with the efficacy of ifosfamide in a EW-7 xenograft model. These results support the clinical evaluation of NAC as a strategy against ifosfamide-induced nephrotoxicity in children.
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收藏
页码：3791 / 3798
页数：8
相关论文
共 54 条
[31]  
Nissim I, 1990, J AM SOC NEPHROL, V1, P616
[32]  
NORPOTH K, 1976, CANCER TREAT REP, V60, P437
[33]   SIDE-CHAIN OXIDATION OF IFOSFAMIDE IN MAN [J].
NORPOTH, K ;
RAIDT, H ;
WITTING, U ;
MULLER, G ;
NORPOTH, R .
KLINISCHE WOCHENSCHRIFT, 1975, 53 (22) :1075-1076
[34]   Chronic health conditions in adult survivors of childhood cancer [J].
Oeffinger, Kevin C. ;
Mertens, Ann C. ;
Sklar, Charles A. ;
Kawashima, Toana ;
Hudson, Melissa M. ;
Meadows, Anna T. ;
Friedman, Debra L. ;
Marina, Neyssa ;
Hobbie, Wendy ;
Kadan-Lottick, Nina S. ;
Schwartz, Cindy L. ;
Leisenring, Wendy ;
Robison, Leslie L. .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (15) :1572-1582
[35]  
Pinkerton C R, 1989, Cancer Chemother Pharmacol, V24 Suppl 1, pS13
[36]  
Pratt C B, 1989, Cancer Chemother Pharmacol, V24 Suppl 1, pS24
[37]  
Pratt CB, 1996, MED PEDIATR ONCOL, V27, P145
[38]   IFOSFAMIDE, FANCONIS SYNDROME, AND RICKETS [J].
PRATT, CB ;
MEYER, WH ;
JENKINS, JJ ;
AVERY, L ;
MCKAY, CP ;
WYATT, RJ ;
HANCOCK, ML .
JOURNAL OF CLINICAL ONCOLOGY, 1991, 9 (08) :1495-1499
[39]   INTRAVENOUS N-ACETYLCYSTEINE - TREATMENT OF CHOICE FOR PARACETAMOL POISONING [J].
PRESCOTT, LF ;
ILLINGWORTH, RN ;
CRITCHLEY, JAJH ;
STEWART, MJ ;
ADAM, RD ;
PROUDFOOT, AT .
BRITISH MEDICAL JOURNAL, 1979, 2 (6198) :1097-1100
[40]  
Ries L., 2007, SEER CANC STAT REV 1
123456