title: 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.
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.
authors: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: W F
authors: WF
authors: Benedict
authors: Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: M
authors: M
authors: Fisher
authors: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: X-Q
authors: XQ
authors: Zhang
authors: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Z
authors: Z
authors: Yang
authors: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: M F
authors: MF
authors: Munsell
authors: Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: C N P
authors: CN
authors: Dinney
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002793:Cholic Acids / Q000627:therapeutic use*; D004187:Disaccharides / Q000627:therapeutic use*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism* / Q000627:therapeutic use*; D053538:Keratin-18 / Q000652:urine*; D010446:Peptide Fragments / Q000652:urine; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000652:urine*
chemical_list: D002793:Cholic Acids; D004187:Disaccharides; D016898:Interferon-alpha; D053538:Keratin-18; C561463:M30 cytokeratin-18 peptide, human; C577325:M65 antigen, human; D010446:Peptide Fragments; C525256:Syn3 compound; D020169:Caspases