Biomaterial Database

Mobilization of viable tumor cells into the circulation during radiation therapy. 2014

Olga A Martin, and Robin L Anderson, and Prudence A Russell, and R Ashley Cox, and Alesia Ivashkevich, and Agnieszka Swierczak, and Judy P Doherty, and Daphne H M Jacobs, and Jai Smith, and Shankar Siva, and Patricia E Daly, and David L Ball, and Roger F Martin, and Michael P MacManus

Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

OBJECTIVE To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. METHODS We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. RESULTS Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. CONCLUSIONS Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies.

UI	MeSH Term	Description	Entries
D008175	Lung Neoplasms	Tumors or cancer of the LUNG.	Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008856	Microscopy, Fluorescence	Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.	Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009360	Neoplastic Cells, Circulating	Exfoliate neoplastic cells circulating in the blood and associated with metastasizing tumors.	Circulating Neoplastic Cells,Embolic Tumor Cells,Embolism, Tumor,Neoplasm Circulating Cells,Tumor Cells, Embolic,Cells, Neoplasm Circulating,Circulating Cells, Neoplasm,Circulating Tumor Cells,Cell, Circulating Neoplastic,Cell, Circulating Tumor,Cell, Embolic Tumor,Cell, Neoplasm Circulating,Cells, Circulating Neoplastic,Cells, Circulating Tumor,Cells, Embolic Tumor,Circulating Neoplastic Cell,Circulating Tumor Cell,Embolic Tumor Cell,Embolisms, Tumor,Neoplasm Circulating Cell,Neoplastic Cell, Circulating,Tumor Cell, Circulating,Tumor Cell, Embolic,Tumor Cells, Circulating,Tumor Embolism,Tumor Embolisms
D002289	Carcinoma, Non-Small-Cell Lung	A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.	Carcinoma, Non-Small Cell Lung,Non-Small Cell Lung Cancer,Non-Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinoma,Nonsmall Cell Lung Cancer,Carcinoma, Non Small Cell Lung,Carcinomas, Non-Small-Cell Lung,Lung Carcinoma, Non-Small-Cell,Lung Carcinomas, Non-Small-Cell,Non Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinomas
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D006657	Histones	Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.	Histone,Histone H1,Histone H1(s),Histone H2a,Histone H2b,Histone H3,Histone H3.3,Histone H4,Histone H5,Histone H7
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368	Aged	A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available.	Elderly
D000369	Aged, 80 and over	Persons 80 years of age and older.	Oldest Old