Jacobs, D. (Daphne) (2012) Detection of circulating tumour cells in whole blood during the course of radiotherapy: relationship to tumour volume. thesis, Medicine.
Full text available on request.Abstract
Lung cancer is the most common cancer worldwide. Up to 80% of non-small-cell lung cancer (NSCLC) patients can benefit from radiotherapy (RT). Circulating Tumour Cells (CTCs) are useful prognostic and predictive biomarkers in several types of cancer. γ-H2AX is a sensitive biomarker for irradiation induced DNA double strand breaks and can identify CTCs that entered the circulation from the irradiated tumour. The role of tumour volume as a predictor for response after RT has been described for several cancers, but has not yet been linked to the presence of CTCs. We tested 2 hypotheses: 1) irradiated CTCs enter the bloodstream during a course of RT in NSCLC patients and can be identified by their γ-H2AX expression; 2) a larger irradiated tumour volume as estimated on the pre-treatment CT is associated with more CTCs during the course of RT in whole blood. Blood samples were obtained from 10 NSCLC patients before and during RT. The samples were enriched with Rosettesep® cocktail (Stemcell Technologies) to remove blood cells from CTCs. Enriched samples were stained with various combinations of antibodies (CD45, CK8/18, γ-H2AX) and sorted by FACS. Un-enriched samples were cytospun onto microscopy slides, stained, and analysed by microscopy. We detected elevations of γ-H2AX-positive cells of different types (tumour and non-tumour) after RT. In cytospin samples we recognized CTCs both by morphology and CK18 and γ-H2AX positivity. The amount of CTCs increased after the first fraction of RT. We have shown that CTCs are released from the primary tumour especially during the first fraction of RT. This finding provides a starting platform with many opportunities for useful future research. In this study we couldn’t determine any correlation between the presence of CTCs and tumour volume.
Item Type: | Thesis (Thesis) |
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Supervisor name: | Faculty supervisor: and Groen, Prof. dr. Harry J.M. |
Supervisor name: | External supervisor: and MacManus, Michael P. Assoc. Prof. and Department of Radiation Oncology and Laboratory of Molecular Radiation Biology and Peter MacCallum Cancer Centre and Melbourne, Australia |
Faculty: | Medical Sciences |
Date Deposited: | 25 Jun 2020 10:45 |
Last Modified: | 25 Jun 2020 10:45 |
URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/657 |
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