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A novel tumor spher...
A novel tumor spheroid model identifies selective enhancement of radiation by an inhibitor of oxidative phosphorylation
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- Karlsson, Henning (author)
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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- Senkowski, Wojciech (author)
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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- Fryknäs, Mårten (author)
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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- Mansoori, Sharmineh (author)
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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- Linder, Stig, 1954- (author)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten
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- Gullbo, Joachim (author)
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
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- Larsson, Rolf (author)
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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- Nygren, Peter (author)
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
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(creator_code:org_t)
- 2019-09-03
- 2019
- English.
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In: Oncotarget. - Orchard Park, NY United States : Impact Journals. - 1949-2553. ; 10:51, s. 5372-5382
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Abstract
Subject headings
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- There is a need for preclinical models that can enable identification of novel radiosensitizing drugs in clinically relevant high-throughput experiments. We used a new high-throughput compatible total cell kill spheroid assay to study the interaction between drugs and radiation in order to identify compounds with radiosensitizing activity. Experimental drugs were compared to known radiosensitizers and cytotoxic drugs clinically used in combination with radiotherapy. VLX600, a novel iron-chelating inhibitor of oxidative phosphorylation, potentiated the effect of radiation in tumor spheroids in a synergistic manner. This effect was specific to spheroids and not observed in monolayer cell cultures. In conclusion, the total cell kill spheroid assay is a feasible high-throughput method in the search for novel radiosensitizers. VLX600 shows encouraging characteristics for development as a novel radiosensitizer.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- high-throughput; hypoxia; radiosensitizer; spheroid; tumor model
Publication and Content Type
- ref (subject category)
- art (subject category)
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