Faculty Collaboration Database

Loss of bacillus Calmette-Guérin viability adversely affects the direct response of urothelial carcinoma cells to bacillus Calmette-Guérin exposure. J Urol 2014 Mar;191(3):823-9 PMID: 24035882 PMCID: PMC5798236

Pubmed ID

24035882

DOI

10.1016/j.juro.2013.09.012

Abstract

PURPOSE: The attenuated mycobacterium bacillus Calmette-Guérin is widely used as intravesical immunotherapy for nonmuscle invasive urothelial carcinoma. Previous studies demonstrated that in the laboratory and clinical settings bacillus Calmette-Guérin viability is a variable that correlates with antitumor efficacy. We evaluated how loss of viability impacted a number of molecular and phenotypic intermediate end points that characterize and/or contribute to the direct effect of bacillus Calmette-Guérin on urothelial carcinoma cells.

MATERIALS AND METHODS: We studied the effect of loss of bacillus Calmette-Guérin viability on the tumor cell response to the treatment in 2 human urothelial carcinoma cell lines. The cellular response to bacillus Calmette-Guérin rendered nonviable by heat killing was compared to the response to viable bacillus. Response end points 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 that of viable bacillus Calmette-Guérin for all measured end points. The decrease in response varied by cell line, ranging from 15% to 100% of the response to viable bacillus. While responses were quantitatively different, nonviable bacillus continued to induce responses that were qualitatively similar to those of bacillus Calmette-Guérin relative to that in untreated controls.

CONCLUSIONS: Bacillus Calmette-Guérin viability is an important variable influencing the direct tumor cell response to the treatment. Although the magnitude of its effects are attenuated, heat killed bacillus Calmette-Guérin remains active for the induction of bacillus Calmette-Guérin responsive biological end points.

Author List

Shah G, Zhang G, Chen F, Cao Y, Kalyanaraman B, See W

Authors

Balaraman Kalyanaraman PhD Chair, Professor in the Biophysics department at Medical College of Wisconsin
William A. See MD Chair, Professor in the Urologic Surgery department at Medical College of Wisconsin

Scopus

2-s2.0-84893823729   3 Citations

MESH terms used to index this publication - Major topics in bold

Adjuvants, Immunologic
BCG Vaccine
Carcinoma, Transitional Cell
Cell Line, Tumor
Enzyme-Linked Immunosorbent Assay
Gene Expression Regulation, Neoplastic
Humans
Oxidative Stress
Phenotype
Real-Time Polymerase Chain Reaction
Signal Transduction
Urinary Bladder Neoplasms