Related Experiment Video
Updated: May 18, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
The Effects of N-acetylcysteine on ifosfamide efficacy in a mouse xenograft model
L Hanly1, R Figueredo, M J Rieder
1Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
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.
Insights
N-acetylcysteine (NAC) effectively protects against ifosfamide-induced kidney damage without compromising the chemotherapy
Area of Science:
- Oncology
- Pharmacology
- Toxicology
Background:
- Ifosfamide chemotherapy causes nephrotoxicity in 30% of pediatric patients.
- N-acetylcysteine (NAC) has demonstrated protective effects against ifosfamide nephrotoxicity in preclinical models.
- Clinical application of NAC requires confirmation that it does not reduce ifosfamide's anti-cancer efficacy.
Purpose of the Study:
- To evaluate if N-acetylcysteine (NAC) interferes with the anti-tumour efficacy of ifosfamide.
- To assess the impact of NAC on ifosfamide's effectiveness in a Ewing's sarcoma xenograft model.
Main Methods:
- Ewing's sarcoma tumour xenografts were established in mice.
- Mice received treatments including saline, ifosfamide, ifosfamide + NAC concurrently, NAC pre-treatment, or NAC alone.
- Tumour volumes were measured to assess treatment efficacy.
Main Results:
- Ifosfamide significantly reduced tumour volumes compared to controls.
- Concurrent NAC therapy and NAC pre-treatment did not alter ifosfamide's tumour-reducing effects.
- NAC alone did not impact tumour volumes.
Conclusions:
- N-acetylcysteine (NAC) does not interfere with the anti-tumour efficacy of ifosfamide.
- These findings support the clinical investigation of NAC for mitigating ifosfamide-induced nephrotoxicity in children.
- NAC represents a potential co-therapy to improve ifosfamide treatment outcomes.
More Related Videos
05:11Construction of An Orthotopic Xenograft Model of Non-Small Cell Lung Cancer Mimicking Disease Progression and Predicting Drug Activities
Published on: May 10, 2024
08:17A Human Peripheral Blood Mononuclear Cell (PBMC) Engrafted Humanized Xenograft Model for Translational Immuno-oncology (I-O) Research
Published on: August 15, 2019