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
Data are presented on pharmacodynamic (PD) method validation and preliminary clinical qualification of three PD biomarker assays. M65 Elisa, which quantitates different forms of circulating cytokeratin 18 (CK18) as putative surrogate markers of both apoptotic and nonapoptotic tumour cell death, was...
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| Veröffentlicht in: | British journal of cancer 2006-07, Vol.95 (1), p.42-48 |
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| creator | Cummings, J Ranson, M LaCasse, E Ganganagari, J R St-Jean, M Jayson, G Durkin, J Dive, C |
| description | Data are presented on pharmacodynamic (PD) method validation and preliminary clinical qualification of three PD biomarker assays. M65 Elisa, which quantitates different forms of circulating cytokeratin 18 (CK18) as putative surrogate markers of both apoptotic and nonapoptotic tumour cell death, was shown to be highly reproducible: calibration curve linearity
r
2
=0.996, mean accuracy >91% and mean precision |
| doi_str_mv | 10.1038/sj.bjc.6603220 |
| format | Article |
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r
2
=0.996, mean accuracy >91% and mean precision <3%,
n
=27. Employing recombinant (
r
) CK18 and caspase cleaved CK18 (CK18 Asp
396
neo-epitope) as external standards, kit to kit reproducibly was <6% (
n
=19). rCK18 was stable in plasma for 4 months at −20°C and −80°C, for 4 weeks at 4°C and had a half-life of 2.3 days at 37°C. Cytokeratin 18 Asp
396
NE, the M30 Apoptosense Elisa assay antigen, was stable in plasma for 6 months at −20°C and −80°C, for 3 months at 4°C, while its half-life at 37°C was 3.8 days. Within-day variations in endogenous plasma concentrations of the M30 and M65 antigens were assessed in two predose blood samples collected from a cohort of 15 ovarian cancer patients receiving carboplatin chemotherapy and were shown to be no greater than the variability associated with methods themselves. Between-day fluctuations in circulating levels of the M30 and M65 antigens and in XIAP mRNA levels measured in peripheral blood mononuclear cells by quantitative (q) RT–PCR were evaluated in two predose blood samples collected with a 5- to 7-day gap from 23 patients with advanced cancer enrolled in a phase I trial. The mean variation between the two pretreatment values ranged from 13 to 14 to 25%, respectively, for M65, M30 and qRT–PCR. These data suggest that the M30 and M65 Elisa's and qRT–PCR as PD biomarker assays have favourable performance characteristics for further investigation in clinical trials of anticancer agents which induce tumour apoptosis/necrosis or knockdown of the anti-apoptotic protein XIAP.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/sj.bjc.6603220</identifier><identifier>PMID: 16804528</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Apoptosis - drug effects ; Biological and medical sciences ; Biomarkers, Tumor - blood ; Biomedical and Life Sciences ; Biomedicine ; Calibration ; Cancer Research ; Drug Resistance ; Enzyme-Linked Immunosorbent Assay - methods ; Epidemiology ; Epitopes - blood ; Epitopes - immunology ; Female ; Humans ; Keratin-18 - blood ; Keratin-18 - immunology ; Leukocytes, Mononuclear - chemistry ; Leukocytes, Mononuclear - metabolism ; Medical sciences ; Molecular Medicine ; Oligonucleotides - pharmacokinetics ; Oncology ; Ovarian Neoplasms - blood ; Ovarian Neoplasms - drug therapy ; Peptide Fragments - blood ; Peptide Fragments - immunology ; Reagent Kits, Diagnostic - standards ; Reference Values ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - antagonists & inhibitors ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Sensitivity and Specificity ; Time Factors ; Translational Therapeutics ; Tumors ; X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors ; X-Linked Inhibitor of Apoptosis Protein - genetics</subject><ispartof>British journal of cancer, 2006-07, Vol.95 (1), p.42-48</ispartof><rights>The Author(s) 2006</rights><rights>2006 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jul 3, 2006</rights><rights>Copyright © 2006 Cancer Research UK 2006 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c570t-a07552d9404a072f5f3570789806c6ef4d08fcffcac2bf964369e0f9e34cefd23</citedby><cites>FETCH-LOGICAL-c570t-a07552d9404a072f5f3570789806c6ef4d08fcffcac2bf964369e0f9e34cefd23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360484/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360484/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,2727,27924,27925,41488,42557,51319,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17948147$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16804528$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cummings, J</creatorcontrib><creatorcontrib>Ranson, M</creatorcontrib><creatorcontrib>LaCasse, E</creatorcontrib><creatorcontrib>Ganganagari, J R</creatorcontrib><creatorcontrib>St-Jean, M</creatorcontrib><creatorcontrib>Jayson, G</creatorcontrib><creatorcontrib>Durkin, J</creatorcontrib><creatorcontrib>Dive, C</creatorcontrib><title>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</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Data are presented on pharmacodynamic (PD) method validation and preliminary clinical qualification of three PD biomarker assays. M65 Elisa, which quantitates different forms of circulating cytokeratin 18 (CK18) as putative surrogate markers of both apoptotic and nonapoptotic tumour cell death, was shown to be highly reproducible: calibration curve linearity
r
2
=0.996, mean accuracy >91% and mean precision <3%,
n
=27. Employing recombinant (
r
) CK18 and caspase cleaved CK18 (CK18 Asp
396
neo-epitope) as external standards, kit to kit reproducibly was <6% (
n
=19). rCK18 was stable in plasma for 4 months at −20°C and −80°C, for 4 weeks at 4°C and had a half-life of 2.3 days at 37°C. Cytokeratin 18 Asp
396
NE, the M30 Apoptosense Elisa assay antigen, was stable in plasma for 6 months at −20°C and −80°C, for 3 months at 4°C, while its half-life at 37°C was 3.8 days. Within-day variations in endogenous plasma concentrations of the M30 and M65 antigens were assessed in two predose blood samples collected from a cohort of 15 ovarian cancer patients receiving carboplatin chemotherapy and were shown to be no greater than the variability associated with methods themselves. Between-day fluctuations in circulating levels of the M30 and M65 antigens and in XIAP mRNA levels measured in peripheral blood mononuclear cells by quantitative (q) RT–PCR were evaluated in two predose blood samples collected with a 5- to 7-day gap from 23 patients with advanced cancer enrolled in a phase I trial. The mean variation between the two pretreatment values ranged from 13 to 14 to 25%, respectively, for M65, M30 and qRT–PCR. These data suggest that the M30 and M65 Elisa's and qRT–PCR as PD biomarker assays have favourable performance characteristics for further investigation in clinical trials of anticancer agents which induce tumour apoptosis/necrosis or knockdown of the anti-apoptotic protein XIAP.</description><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Calibration</subject><subject>Cancer Research</subject><subject>Drug Resistance</subject><subject>Enzyme-Linked Immunosorbent Assay - methods</subject><subject>Epidemiology</subject><subject>Epitopes - blood</subject><subject>Epitopes - immunology</subject><subject>Female</subject><subject>Humans</subject><subject>Keratin-18 - blood</subject><subject>Keratin-18 - immunology</subject><subject>Leukocytes, Mononuclear - chemistry</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Medical sciences</subject><subject>Molecular Medicine</subject><subject>Oligonucleotides - pharmacokinetics</subject><subject>Oncology</subject><subject>Ovarian Neoplasms - blood</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Peptide Fragments - blood</subject><subject>Peptide Fragments - immunology</subject><subject>Reagent Kits, Diagnostic - standards</subject><subject>Reference Values</subject><subject>Reproducibility of Results</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - antagonists & inhibitors</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Sensitivity and Specificity</subject><subject>Time Factors</subject><subject>Translational Therapeutics</subject><subject>Tumors</subject><subject>X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors</subject><subject>X-Linked Inhibitor of Apoptosis Protein - genetics</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kktv1DAUhSMEokNhyw5kVeK1yNRxHk42SKOqlEpFsACpu8jjXM94mtip7VTKT-XfcEOGDiDBKrHP8XdOnBtFzxO6TGhanvrdcr2Ty6KgKWP0QbRI8pTFScn4w2hBKeUxrRg9ip54v8NlRUv-ODpKipJmOSsX0fdPELa2IXei1Y0I2hoiTEN6B63utBFuJLcDakrLWbWK9FvhOiFtMxrRaUnW2nbC3YDzBLq-tSM0JFgCyBxEABK2QGSrDSJaAmpCyXECiSksaA_Go8N2vR0w--3q_CLNk7x4R4JwGwgzbqJcx4i5wbU2W73WwbqfmN72wXrtsbYNoA25vlx9eRo9UqL18Gz_PI6-fTj_evYxvvp8cXm2uoplzmmIBeV5zpoqoxm-MpWrFPd5WZW0kAWorKGlkkphZ7ZWVZGlRQVUVZBmElTD0uPo_czth3UHjQQTnGjr3mm8lLG2Qtd_KkZv6429q1la0KzMEPBmD3D2dgAf6k57CW0rDNjB1yXW4jmvpqjX_3UmVVZSxlM0nvxl3NnBGbwGTKU0YTmfcpezSTrrvQN13zmh9TRctd_VOFz1frjwwMvfv_Rg308TGl7tDcLjv1ZOGKn9wcexX5Jx9J3OPo-S2YA71Ptn9Iv5hBFhcHCP_KX_AA579v4</recordid><startdate>20060703</startdate><enddate>20060703</enddate><creator>Cummings, J</creator><creator>Ranson, M</creator><creator>LaCasse, E</creator><creator>Ganganagari, J R</creator><creator>St-Jean, M</creator><creator>Jayson, G</creator><creator>Durkin, J</creator><creator>Dive, C</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20060703</creationdate><title>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</title><author>Cummings, J ; Ranson, M ; LaCasse, E ; Ganganagari, J R ; St-Jean, M ; Jayson, G ; Durkin, J ; Dive, C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c570t-a07552d9404a072f5f3570789806c6ef4d08fcffcac2bf964369e0f9e34cefd23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - blood</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Calibration</topic><topic>Cancer Research</topic><topic>Drug Resistance</topic><topic>Enzyme-Linked Immunosorbent Assay - methods</topic><topic>Epidemiology</topic><topic>Epitopes - blood</topic><topic>Epitopes - immunology</topic><topic>Female</topic><topic>Humans</topic><topic>Keratin-18 - blood</topic><topic>Keratin-18 - immunology</topic><topic>Leukocytes, Mononuclear - chemistry</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Medical sciences</topic><topic>Molecular Medicine</topic><topic>Oligonucleotides - pharmacokinetics</topic><topic>Oncology</topic><topic>Ovarian Neoplasms - blood</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Peptide Fragments - blood</topic><topic>Peptide Fragments - immunology</topic><topic>Reagent Kits, Diagnostic - standards</topic><topic>Reference Values</topic><topic>Reproducibility of Results</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - antagonists & inhibitors</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Sensitivity and Specificity</topic><topic>Time Factors</topic><topic>Translational Therapeutics</topic><topic>Tumors</topic><topic>X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors</topic><topic>X-Linked Inhibitor of Apoptosis Protein - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cummings, J</creatorcontrib><creatorcontrib>Ranson, M</creatorcontrib><creatorcontrib>LaCasse, E</creatorcontrib><creatorcontrib>Ganganagari, J R</creatorcontrib><creatorcontrib>St-Jean, M</creatorcontrib><creatorcontrib>Jayson, G</creatorcontrib><creatorcontrib>Durkin, J</creatorcontrib><creatorcontrib>Dive, C</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cummings, J</au><au>Ranson, M</au><au>LaCasse, E</au><au>Ganganagari, J R</au><au>St-Jean, M</au><au>Jayson, G</au><au>Durkin, J</au><au>Dive, C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2006-07-03</date><risdate>2006</risdate><volume>95</volume><issue>1</issue><spage>42</spage><epage>48</epage><pages>42-48</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Data are presented on pharmacodynamic (PD) method validation and preliminary clinical qualification of three PD biomarker assays. M65 Elisa, which quantitates different forms of circulating cytokeratin 18 (CK18) as putative surrogate markers of both apoptotic and nonapoptotic tumour cell death, was shown to be highly reproducible: calibration curve linearity
r
2
=0.996, mean accuracy >91% and mean precision <3%,
n
=27. Employing recombinant (
r
) CK18 and caspase cleaved CK18 (CK18 Asp
396
neo-epitope) as external standards, kit to kit reproducibly was <6% (
n
=19). rCK18 was stable in plasma for 4 months at −20°C and −80°C, for 4 weeks at 4°C and had a half-life of 2.3 days at 37°C. Cytokeratin 18 Asp
396
NE, the M30 Apoptosense Elisa assay antigen, was stable in plasma for 6 months at −20°C and −80°C, for 3 months at 4°C, while its half-life at 37°C was 3.8 days. Within-day variations in endogenous plasma concentrations of the M30 and M65 antigens were assessed in two predose blood samples collected from a cohort of 15 ovarian cancer patients receiving carboplatin chemotherapy and were shown to be no greater than the variability associated with methods themselves. Between-day fluctuations in circulating levels of the M30 and M65 antigens and in XIAP mRNA levels measured in peripheral blood mononuclear cells by quantitative (q) RT–PCR were evaluated in two predose blood samples collected with a 5- to 7-day gap from 23 patients with advanced cancer enrolled in a phase I trial. The mean variation between the two pretreatment values ranged from 13 to 14 to 25%, respectively, for M65, M30 and qRT–PCR. These data suggest that the M30 and M65 Elisa's and qRT–PCR as PD biomarker assays have favourable performance characteristics for further investigation in clinical trials of anticancer agents which induce tumour apoptosis/necrosis or knockdown of the anti-apoptotic protein XIAP.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16804528</pmid><doi>10.1038/sj.bjc.6603220</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of cancer, 2006-07, Vol.95 (1), p.42-48 |
| issn | 0007-0920 1532-1827 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Nature Journals Online; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | Apoptosis - drug effects Biological and medical sciences Biomarkers, Tumor - blood Biomedical and Life Sciences Biomedicine Calibration Cancer Research Drug Resistance Enzyme-Linked Immunosorbent Assay - methods Epidemiology Epitopes - blood Epitopes - immunology Female Humans Keratin-18 - blood Keratin-18 - immunology Leukocytes, Mononuclear - chemistry Leukocytes, Mononuclear - metabolism Medical sciences Molecular Medicine Oligonucleotides - pharmacokinetics Oncology Ovarian Neoplasms - blood Ovarian Neoplasms - drug therapy Peptide Fragments - blood Peptide Fragments - immunology Reagent Kits, Diagnostic - standards Reference Values Reproducibility of Results Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - antagonists & inhibitors RNA, Messenger - genetics RNA, Messenger - metabolism Sensitivity and Specificity Time Factors Translational Therapeutics Tumors X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors X-Linked Inhibitor of Apoptosis Protein - genetics |
| title | 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 |
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