Qualification of M30 and M65 ELISAs as surrogate biomarkers of cell death: long term antigen stability in cancer patient plasma

Cancer Chemotherapy and Pharmacology - Tập 60 - Trang 921-924 - 2007
J. Cummings1, M. Ranson2, F. Butt1, D. Moore1, C. Dive1
1Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, England
2Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, England

Tóm tắt

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. 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 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.

Tài liệu tham khảo

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