Use of monitoring levels of soluble forms of cytokeratin 18 in the urine of patients with superficial bladder cancer following intravesical Ad-IFNα/Syn3 treatment in a phase l study

W. F. Benedict, M. Fisher, X. Q. Zhang, Z. Yang, M. F. Munsell, C. N.P. Dinney

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

A phase l study using intravesical Ad-IFNαSyn3 for patients with bacillus Calmette-Guérin-resistant superficial bladder cancer showed a complete remission (CR) of 43% at 90 days after treatment with high levels of interferon-α (IFNα) being produced. Ad-IFNα kills bladder cancer cells by two apoptotic and one necrotic mechanism that can be measured by soluble forms of cytokeratin 18 (CK18) using M30 and M65 ELISAs, assays for caspase-cleaved (apoptotic) and uncleaved (necrotic) cell death, respectively. Therefore, we determined whether M30 and M65 levels in the urine after treatment could document all three mechanisms of cancer cell kill and also predict having a CR. High levels of both M30 and M65 were found in all patients within 24 h after treatment with all three types of cancer cell death occurring. Moreover, the return of both M30 and M65 levels in the urine to normal levels within 5 days or more after treatment was strongly associated with obtaining a CR (P=0.003). This is the first time that such assays have been used to study response to therapy in the urine of patients with bladder cancer and in the future may prove valuable in predicting clinical outcome.

Original languageEnglish (US)
Pages (from-to)91-94
Number of pages4
JournalCancer gene therapy
Volume21
Issue number3
DOIs
StatePublished - Mar 2014
Externally publishedYes

Keywords

  • Adenoviral-mediated interferon α treatment
  • Bladder cancer
  • Phase l study
  • Urine cytokeratin 18 levels

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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