Tumor necrosis factor-alpha-induced accentuation in cryoinjury: mechanisms in vitro and in vivo.

Molecular Cancer Therapeutics
Jing JiangJohn C Bischof

Abstract

Cryosurgical treatment of solid cancer can be greatly assisted by further translation of our finding that a cytokine adjuvant tumor necrosis factor-alpha (TNF-alpha) can achieve complete cancer destruction out to the intraoperatively imaged iceball edge (-0.5 degrees C) over the current clinical recommendation of reaching temperatures lower than -40 degrees C. The present study investigates the cellular and tissue level dose dependency and molecular mechanisms of TNF-alpha-induced enhancement in cryosurgical cancer destruction. Microvascular endothelial MVEC and human prostate cancer LNCaP Pro 5 (LNCaP) cells were frozen as monolayers in the presence of TNF-alpha. Normal skin and LNCaP tumor grown in a nude mouse model were also frozen at different TNF-alpha doses. Molecular mechanisms were investigated by using specific inhibitors to block nuclear factor-kappaB-mediated inflammatory or caspase-mediated apoptosis pathways. The amount of cryoinjury increased in a dose-dependent manner with TNF-alpha both in vitro and in vivo. MVEC were found to be more cryosensitive than LNCaP cells in both the presence and the absence of TNF-alpha. The augmentation in vivo was significantly greater than that in vitro, with complete cell death u...Continue Reading

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Citations

Nov 28, 2012·Annals of Biomedical Engineering·Zhenpeng QinJohn C Bischof
Jul 31, 2009·Journal of Biomechanical Engineering·Raghav GoelJohn C Bischof
May 6, 2011·Nanomedicine·Mithun M ShenoiJohn C Bischof
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