Abstract
Purpose
M30 and M65 ELISAs are proposed as surrogate biomarkers of tumour cell death in patients and are being applied increasingly in the pharmacodynamic (PD) evaluation of anticancer drugs during clinical trials. In the absence of such data, we have studied the long-term stability of the antigens of both assays in plasma of cancer patients stored at −80°C over 2 years.
Results
No evidence was detected of degradation in the M65 antigen. However, in a proportion of patients significant increases in levels of M30 antigen were detected
Conclusion
Plasma samples for M65 analysis can be stored at −80°C for 2 years; however, caution is recommended when considering long-term storage of samples for the M30 assay.
This is a preview of subscription content, log in via an institution to check access.
References
Ueno T, Toi M, Linder S (2005) Detection of epithelial cell death in the body by cytokeratin 18 measurement. Biomed Pharmacother 59(Suppl2):S359–S362
Leers MP, Kolgen W, Bjorklund V et al (1999) Immunocytochemical detection and mapping of a cytokeratin 18 neo-epitope exposed during early apoptosis. J Pathol 187:567–572
Kramer G, Erdal H, Mertens HJ et al (2004) Differentiation between cell death modes using measurements of different soluble forms of extracellular cytokeratin 18. Cancer Res 64:1751–1756
Schutte B, Henfling M, Kolgen W et al (2004) Keratin 8/18 breakdown and reorganization during apoptosis. Exp Cell Res 297:11–26
Cummings J, Ward TH, Lacasse E et al (2005) Validation of pharmacodynamic assays to evaluate the clinical efficacy of an antisense compound (AEG 35156) targeted to the X-linked inhibitor of apoptosis protein XIAP. Br J Cancer 92:532–538
Kramer G, Schwarz S, Hagg M et al (2006) Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles. Br J Cancer 94:1592–1598
Cummings J, Ranson M, Lacasse E et al (2006) Method validation and preliminary qualification of pharmacodynamic biomarkers employed to evaluate the clinical efficacy of an antisense compound (AEG35156) targeted to the X-linked inhibitor of apoptosis protein XIAP. Br J Cancer 95:42–48
Ranson M, Dive C, Ward TH et al (2005) A phase I trial of AEG35156 (XIAP antisense) administered as a 7-day continuous intravenous infusion in patients with advanced tumors. Clin Cancer Res 11:9116s, C9172
Anker P, Lyautey J, Lederrey C et al (2001) Circulating nucleic acids in plasma or serum. Clin Chim Acta 313:143–146
Rydlander L, Ziegler E, Bergman T et al (1996) Molecular characterization of a tissue-polypeptide-specific-antigen epitope and its relationship to human cytokeratin 18. Eur J Biochem 241:309–314
Ku NO, Liao J, Omary MB (1997) Apoptosis generates stable fragments of human type I keratins. J Biol Chem 272:33197–33203
Aho S (2004) Plakin proteins are coordinately cleaved during apoptosis but preferentially through the action of different caspases. Exp Dermatol 13:700–707
Holdenrieder S, Stieber P, Bodenmuller H et al (2001) Circulating nucleosomes in serum. Ann N Y Acad Sci 945:93–102
Holdenrieder S, Mueller S, Stieber P (2005) Stability of nucleosomal DNA fragments in serum. Clin Chem 51:1026–1029
Abid Hussein MN, Nieuwland R, Hau CM et al (2005) Cell-derived microparticles contain caspase 3 in vitro and in vivo. J Thromb Haemost 3:888–896
Deligezer U, Erten N, Akisik EE et al (2006) Circulating fragmented nucleosomal DNA and caspase-3 mRNA in patients with lymphoma and myeloma. Exp Mol Pathol 80:72–76
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cummings, J., Ranson, M., Butt, F. et al. Qualification of M30 and M65 ELISAs as surrogate biomarkers of cell death: long term antigen stability in cancer patient plasma. Cancer Chemother Pharmacol 60, 921–924 (2007). https://doi.org/10.1007/s00280-007-0437-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-007-0437-4