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premalignant cervical explants;induction of apoptosis Article Summary

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A robust ex vivo model for evaluation of induction of apoptosis by rhTRAIL in combination with proteasome inhibitor MG132 in human premalignant cervical explants
International Journal of Cancer, 06/26/08
Print     Email This Article     Save in My Library   Free Abstract
Hougardy BMT et al. - In a study to develop an ex vivo model for CIN II/III and to investigate the apoptosis-inducing effect of rhTRAIL and/or MG132 in cervical explants from CIN II/III pts, it was found that this ex vivo model system allows preclinical evaluation of (topical) medical therapies for CIN II/III

Methods
  • Short-term ex vivo culture system was optimized for cervical biopsies, in which explants from normal cervix and CIN II/III lesions were exposed to either rhTRAIL, MG132 or the combination and compared to untreated explants for apoptosis induction
  • 90 normal cervix and 24 CIN II/III explants could be reproducibly put in culture and kept viable for up to 7 days using a transwell membrane system

Results
  • 5 CIN II/III explants were highly sensitive to rhTRAIL plus MG132 compared with 10 normal cervix treated with rhTRAIL plus MG132, while monotherapy with either rhTRAIL, MG132, or medium resulted in a mean % apoptosis <10 in both CIN II/III and normal cervix

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