Prediction of superficial bladder cancer chemosensitivity

I. K. Walsh*, S. R. Johnston, S. R. McKeown, V. J. McKelvey-Martin, J. J. McAleer

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Introduction: It is difficult to predict the most effective intravesical agent for managing each patient's superficial bladder cancer. To predict individual patient tumour response to chemotherapy we have used a gel electrophoresis assay (GEA), which quantifies nuclear DNA damage and repair. Materials and methods: Cell suspensions of 40 freshly resected superficial bladder TCC tumours were exposed to a panel of standard intravesical chemotherapeutic agents (doxorubicin. epirubicin. mitomycin and thiotepa). The cells were then embedded in agarose. cell membranes lysed and the nuclei subjected to alkaline electrophoresis. Nuclear DNA was stained with ethidium bromide and nuclear damage measured using Fenestra™ image-analysis equipment. Results: For eight tumours, a dose-response curve was derived for each agent and the DNA repair kinetics were examined in 12 tumour suspensions. When DNA repair occurred, it was complete by 120 nun. For each of 20 tumours, there was a differential, unique sensitivity to the panel of intravesical agents; 14 of these tumour suspensions showed a response to at least one agent. Mitomycin caused the greatest nuclear damage in 10 tumours, thiotepa the greatest damage in six. doxorubicin in two and epirubicin in two. These results were statistically significant (Mann-Whitney U-test, P =0.01). The in vitro correlation with the observed clinical chemoresponse was 87%. Conclusion: The results indicate that GEA is an accurate ex vivo method for quantifying the response of superficial bladder tumours to different agents. We have shown that the highest in vitro and in vivo chemoresponse was with mitomycin. GEA shows great potential for indicating the most effective agent for the management of an individual patient's bladder tumour.

Original languageEnglish
Number of pages1
JournalBritish journal of urology
Volume79
Issue numberSUPPL. 4
Publication statusPublished - 01 Dec 1997
Externally publishedYes

ASJC Scopus subject areas

  • Urology

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