Monitoring tumour cells in the peripheral blood of small cell lung cancer patients

Kularatne, Bihani; Lorigan, Paul; Browne, S; Suvarna, S K; Smith, Michelle; Lawry, J.

doi:10.1002/cyto.10071

Cited by 57 publications

(34 citation statements)

References 26 publications

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“…In the absence of tumor biopsies, CTCs hold great promise as a surrogate tissue. Although SCLC is often referred to as a neuroendocrine tumor, it is an epithelial tumor that co-expresses neural, endocrine, and epithelial markers 37 and so as we show, the latter can be exploited for detec- 38 A second preliminary study of lung cancer patients conducted using unvalidated manual technology and where just 13 patients had SCLC, found CTCs in a similar proportion of patients to that reported here but with smaller numbers than we observed. 39 To our knowledge this is the first report on CellSearch technology applied to patients with SCLC.…”

Section: Discussionsupporting

confidence: 74%

Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing Chemotherapy

Hou

Greystoke

Lancashire

et al. 2009

The American Journal of Pathology

213

186

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Serological 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 biomark- Small cell lung cancer (SCLC) is initially chemosensitive but invariably relapses with a chemoresistant phenotype.1 A number of molecularly targeted therapies have been evaluated attempting to improve outcome, but none have succeeded to date.2 Ideally, early clinical trials should incorporate validated pharmacodynamic biomarkers, conducted to good clinical laboratory practice, that demonstrate both proof of mechanism (drug hits target) and proof of concept (tumor responds to drug).3 Although possible, serial biopsies are rare in SCLC, and the tissue obtained often insufficient for extensive molecular profiling. Thus, there is a pressing need for blood-based biomarkers that report therapeutic response.Assays of drug-induced cell death are potential proof of concept biomarkers for multiple therapeutics. 4 The M30 Apoptosense and M65 assays (Peviva, Bromma, Sweden) detect cytokeratin (CK) 18, expressed in epithelial but not hematopoietic cells, and released into the blood following cytoskeletal disassembly and degradation during apoptotic and/or necrotic cell death. 5 The M30 antibody recognizes a caspase-cleaved neoepitope of CK18 that is only revealed during apoptosis, whereas the M65 assay detects full length and cleaved forms of CK18 reporting apoptosis and necrosis.6 Nucleosomal DNA (nDNA) results from cleavage of chromatin by apoptotic endonucleases into membrane bound DNA fragments that are phagocytosed by macrophages and sub-

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Section: Discussionsupporting

confidence: 74%

Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing Chemotherapy

Hou

Greystoke

Lancashire

et al. 2009

The American Journal of Pathology

213

186

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“…Kularatne et al utilised flow cytometry to detect CTCs in patients with SCLC in 2002 (21). Since this discovery both epitope dependent and epitope independent enrichment methods have detected an abundance of CTCs in SCLC patients, compared to other tumour types.…”

Section: Detection Of Circulating Tumour Cells (Ctcs) In Sclcmentioning

confidence: 99%

The clinical utility of circulating tumour cells in patients with small cell lung cancer

Foy

Fernández‐Gutiérrez

Faivre-Finn³

et al. 2017

Transl. Lung Cancer Res.

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Small cell lung cancer (SCLC) accounts for 15% of lung cancer diagnosed worldwide. It is aggressive and characterised by early metastatic spread with rapid development of chemo resistance such that less than 5% of patients diagnosed survive 5 years. Surgery is rarely performed and failure to identify new effective treatments has been attributed in a large part to lack of good quality tumour biopsies available for translational research. Liquid biopsies provide a minimally invasive alternative to traditional tumour biopsy.Circulating tumour cells (CTCs) are abundant in SCLC and can be enriched and isolated from a venous blood sample. In recent years progress has been made into the molecular characterisation of CTCs and their use to form tumour xenografts in mice for preclinical studies. This review will discuss the current status of the clinical utility of CTCs in patients with SCLC, highlighting their potential application to treatment decision making, drug development in clinical trials and preclinical testing.

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“…According to (14), when the QSR velocity U i varies insignificantly over the time ∆t so that U i (t i ) ≈ U i (t), the quasi-stationary regime ensues. Hence, we can formulate the sufficient condition for the QSR:…”

Section: Magnetic Particle Depositionmentioning

confidence: 99%

“…The biocompatibility and non-toxicity of magnetic colloids has led to their extensive use in the following: targeted drug delivery [1][2][3][4][5][6]; clinical diagnostics as contrast agents for magnetic resonance imaging [6][7][8][9][10]; tumor therapy by controlled hyperthermia [9][10][11][12]; cytological studies [13][14][15][16][17]; and in catheter embolization of blood vessels [18].…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling of magnetic field guided colloidal particle deposition with significant electric double layer interactions

Alfimov¹,

Shumova²,

Aryslanova³

et al. 2017

Nanosystems: Phys. Chem. Math.

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In this work, we propose a simple theoretical method for predicting the rate and localization of magnetic field guided particle deposition from aqueous colloids. This method accounts for the colloidal electric double layer interactions between particles and vessel walls. The obtained results suggest that the colloidal interactions can be used to increase the rate of particle deposition and improve its localization.

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Monitoring tumour cells in the peripheral blood of small cell lung cancer patients

Cited by 57 publications

References 26 publications

Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing Chemotherapy

Evaluation of Circulating Tumor Cells and Serological Cell Death Biomarkers in Small Cell Lung Cancer Patients Undergoing Chemotherapy

The clinical utility of circulating tumour cells in patients with small cell lung cancer

Mathematical modeling of magnetic field guided colloidal particle deposition with significant electric double layer interactions

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