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- W2157433648 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 up to the iceball edge in tumor tissue at local TNF-alpha doses greater than 200 ng. The inhibition assays showed contrasting results with caspase-mediated apoptosis as the dominant mechanism in MVEC in vitro and nuclear factor-kappaB-mediated inflammatory mechanisms within the microvasculatures the dominant mechanism in vivo. These results suggest the involvement of endothelial-mediated injury and inflammation as the critical mechanisms in cryoinjury and the use of vascular-targeting molecules such as TNF-alpha to enhance tumor killing and achieve the clinical goal of complete cell death within an iceball." @default.
- W2157433648 created "2016-06-24" @default.
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- W2157433648 date "2008-08-01" @default.
- W2157433648 modified "2023-10-12" @default.
- W2157433648 title "Tumor necrosis factor-α–induced accentuation in cryoinjury: mechanisms <i>in vitro</i> and <i>in vivo</i>" @default.
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- W2157433648 doi "https://doi.org/10.1158/1535-7163.mct-07-2421" @default.
- W2157433648 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2583962" @default.
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