INTRODUCTION: The attenuated mycobacterium Bacille Calmette Guerin (BCG) is widely utilized as intravesical "immunotherapy" for the treatment of non-muscle invasive urothelial carcinoma.
Previous studies have demonstrated that in both the laboratory and clinical setting, BCG viability is a variable that correlates with anti-tumor efficacy. This study evaluated how loss of BCG viability impacted a number of molecular and phenotypic intermediate endpoints that characterize, and/or contribute to, the direct effect of BCG on Urothelial carcinoma (UC) cells.
MATERIALS AND METHODS: Two human UC cell lines were used to study the effect of loss of BCG viability on the tumor cell response to BCG. The cellular response to BCG rendered non-viable by heat killing (hk) was compared to the response to viable BCG. The response endpoints evaluated included the induction of oxidative stress, activation of intracellular signaling pathways, gene transactivation, and phenotypic changes.
RESULTS: Loss of viability resulted in a quantitative decrease in the tumor cell response, relative to viable BCG, for all of the measured endpoints. The decrease in response varied by cell line, ranging from 15% to 100% of the response to viable BCG. While quantitatively different, non-viable BCG continued to induce responses that were qualitatively similar to BCG relative to untreated controls.
CONCLUSIONS: BCG viability is an important variable influencing the direct tumor cell response to BCG. Although the magnitude of it effects are attenuated, hkBCG remains active for the induction of BCG responsive biologic endpoints.
Written by:
Shah G, Zhang G, Chen F, Cao Y, Kalyanaraman B, See W. Are you the author?
Department of Urology, Medical College of Wisconsin, Milwaukee, WI.
Reference: J Urol. 2013 Sep 10. pii: S0022-5347(13)05381-0.
doi: 10.1016/j.juro.2013.09.012
PubMed Abstract
PMID: 24035882
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