Effects of tirapazamine on experimental colorectal liver metastases after radiofrequency ablation

The British Journal of Surgery
Klaas M GovaertInne H M Borel Rinkes

Abstract

Radiofrequency ablation (RFA) is a common procedure for the management of colorectal liver metastases. RFA-generated lesions are surrounded by a rim of hypoxia that is associated with aggressive outgrowth of intrahepatic micrometastases. Hypoxia-activated prodrugs such as tirapazamine are designed selectively to induce apoptosis in tumour cells under hypoxic conditions. Therefore, it was hypothesized that tirapazamine may have therapeutic value in limiting hypoxia-associated tumour outgrowth following RFA. Murine C26 and MC38 colorectal cancer cells were grown under hypoxia and normal oxygenation in vitro, and treated with different concentrations of tirapazamine. Apoptosis and cell cycle distribution were assessed by western blot and fluorescence-activated cell sorting analysis. Proliferative capacity was tested by means of colony-formation assays. Mice harbouring microscopic colorectal liver metastases were treated with RFA, followed by a single injection of tirapazamine (60 mg/kg) or saline. Tumour load was assessed morphometrically 7 days later. Tirapazamine induced apoptosis of colorectal tumour cells under hypoxia in vitro. Under normal oxygenation, tirapazamine caused a G2 cell cycle arrest from which cells recovered par...Continue Reading

References

Jul 1, 1986·International Journal of Radiation Oncology, Biology, Physics·E M ZemanW W Lee
Jan 1, 1995·World Journal of Surgery·J ScheeleM Paul
Aug 11, 1998·Surgery Today·M NankoM Hara
Feb 9, 2000·Toxicology and Applied Pharmacology·A E Lee, W R Wilson
Mar 19, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Gregory D LeonardNancy E Kemeny
Feb 4, 2006·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Lynsey A HuxhamAndrew I Minchinton
Jul 22, 2006·Annals of Surgery·Sylvain ManfrediAnne-Marie Bouvier
Nov 23, 2006·Journal of Biomedical Materials Research. Part a·Brent D WeinbergJinming Gao
Feb 13, 2007·International Journal of Radiation Oncology, Biology, Physics·Ezra E W CohenJean Bourhis
Sep 26, 2007·Annals of Surgery·Allan E SipersteinRikesh T Parikh
Apr 15, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Quynh-Thu X LeDavid R Gandara
Oct 21, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sandra L WongAl B Benson
Jul 8, 2010·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Danny RischinAnthony Fyles

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Citations

Jan 30, 2014·Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract·K M GovaertI H M Borel Rinkes
Nov 21, 2013·Annals of Surgery·Klaas M GovaertInne H M Borel Rinkes
Aug 17, 2021·Frontiers in Oncology·Yue LiXiao-Feng Li

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