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dc.contributor.authorHou, Jian-Mei
dc.contributor.authorGreystoke, Alastair
dc.contributor.authorLancashire, Lee J
dc.contributor.authorCummings, Jeffrey
dc.contributor.authorWard, Timothy H
dc.contributor.authorBoard, Ruth E
dc.contributor.authorAmir, Eitan
dc.contributor.authorHughes, Sarah
dc.contributor.authorKrebs, Matthew G
dc.contributor.authorHughes, Andrew
dc.contributor.authorRanson, Malcolm R
dc.contributor.authorLorigan, Paul C
dc.contributor.authorDive, Caroline
dc.contributor.authorBlackhall, Fiona H
dc.date.accessioned2009-11-05T10:24:42Z
dc.date.available2009-11-05T10:24:42Z
dc.date.issued2009-08
dc.identifier.citationEvaluation of circulating tumor cells and serological cell death biomarkers in small cell lung cancer patients undergoing chemotherapy. 2009, 175 (2):808-16 Am. J. Pathol.en
dc.identifier.issn1525-2191
dc.identifier.pmid19628770
dc.identifier.doi10.2353/ajpath.2009.090078
dc.identifier.urihttp://hdl.handle.net/10541/85377
dc.description.abstractSerological cell death biomarkers and circulating tumor cells (CTCs) have potential uses as tools for pharmacodynamic blood-based assays and their subsequent application to early clinical trials. In this study, we evaluated both the expression and clinical significance of CTCs and serological cell death biomarkers in patients with small cell lung cancer. Blood samples from 88 patients were assayed using enzyme-linked immunosorbent assays for various cytokeratin 18 products (eg, M65, cell death, M30, and apoptosis) as well as nucleosomal DNA. CTCs (per 7.5 ml of blood) were quantified using Veridex CellSearch technology. Before therapeutic treatment, cell death biomarkers were elevated in patients compared with controls. CTCs were detected in 86% of patients; additionally, CD56 was detectable in CTCs, confirming their neoplastic origin. M30 levels correlated with the percentage of apoptotic CTCs. M30, M65, lactate dehydrogenase, and CTC number were prognostic for patient survival as determined by univariate analysis. Using multivariate analysis, both lactate dehydrogenase and M65 levels remained significant. CTC number fell following chemotherapy, whereas levels of serological cell death biomarkers peaked at 48 hours and fell by day 22, mirroring the tumor response. A 48-hour rise in nucleosomal DNA and M30 levels was associated with early response and severe toxicity, respectively. Our results provide a rationale to include the use of serological biomarkers and CTCs in early clinical trials of new agents for small cell lung cancer.
dc.language.isoenen
dc.subjectLung Canceren
dc.subjectCirculating Cancerous Cellsen
dc.subjectBiological Tumour Markersen
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshAntineoplastic Agents
dc.subject.meshApoptosis
dc.subject.meshClinical Trials as Topic
dc.subject.meshEnzyme-Linked Immunosorbent Assay
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshLung Neoplasms
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshNeoplastic Cells, Circulating
dc.subject.meshPrognosis
dc.subject.meshSerologic Tests
dc.subject.meshSmall Cell Lung Carcinoma
dc.subject.meshTreatment Outcome
dc.subject.meshTumor Markers, Biological
dc.titleEvaluation of circulating tumor cells and serological cell death biomarkers in small cell lung cancer patients undergoing chemotherapy.en
dc.typeArticleen
dc.contributor.departmentClinical and Experimental Pharmacology, Paterson Institute for Cancer Research, Wilmslow Road, Manchester, M20 4BX, UK.en
dc.identifier.journalThe American Journal of Pathologyen
html.description.abstractSerological cell death biomarkers and circulating tumor cells (CTCs) have potential uses as tools for pharmacodynamic blood-based assays and their subsequent application to early clinical trials. In this study, we evaluated both the expression and clinical significance of CTCs and serological cell death biomarkers in patients with small cell lung cancer. Blood samples from 88 patients were assayed using enzyme-linked immunosorbent assays for various cytokeratin 18 products (eg, M65, cell death, M30, and apoptosis) as well as nucleosomal DNA. CTCs (per 7.5 ml of blood) were quantified using Veridex CellSearch technology. Before therapeutic treatment, cell death biomarkers were elevated in patients compared with controls. CTCs were detected in 86% of patients; additionally, CD56 was detectable in CTCs, confirming their neoplastic origin. M30 levels correlated with the percentage of apoptotic CTCs. M30, M65, lactate dehydrogenase, and CTC number were prognostic for patient survival as determined by univariate analysis. Using multivariate analysis, both lactate dehydrogenase and M65 levels remained significant. CTC number fell following chemotherapy, whereas levels of serological cell death biomarkers peaked at 48 hours and fell by day 22, mirroring the tumor response. A 48-hour rise in nucleosomal DNA and M30 levels was associated with early response and severe toxicity, respectively. Our results provide a rationale to include the use of serological biomarkers and CTCs in early clinical trials of new agents for small cell lung cancer.


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