Radiation response and cure rate of human colon adenocarcinoma spheroids of different size: the significance of hypoxia on tumor control modelling.

2.50
Hdl Handle:
http://hdl.handle.net/10541/85559
Title:
Radiation response and cure rate of human colon adenocarcinoma spheroids of different size: the significance of hypoxia on tumor control modelling.
Authors:
Buffa, Francesca M; West, Catharine M L; Byrne, Karen; Moore, James V; Nahum, Alan E
Abstract:
PURPOSE: To evaluate the adequacy of a Poisson tumor control probability (tcp) model and the impact of hypoxia on tumor cure. METHODS AND MATERIALS: A human colon adenocarcinoma cell line, WiDr, was grown as multicellular spheroids of different diameters. Measurements were made of cell survival and spheroid cure following 300-kV X-ray external beam irradiation in air and nitrogen. Cell survival data were fitted using a two-compartment and an oxygen diffusion model. Spheroid cure data were fitted using the tcp model. RESULTS: Hypoxia was seen only for spheroids greater than 500 microm in diameter. For small spheroids tcp estimates of radiosensitivity and clonogenic number showed excellent agreement with experimentally derived values. For large spheroids, although tcp estimates of radiosensitivity were comparable with measurements, estimates of the clonogenic number were considerably lower than the experimental count. Reoxygenation of large spheroids before irradiation resulted in the tcp estimates of the number of clonogenic cells agreeing with measured values. CONCLUSIONS: When hypoxia was absent, the tcp model accurately predicted cure from measured radiosensitivity and clonogen number. When hypoxia was present, the number of cells capable of regrowth in situ was considerably lower than the number of clonogenic cells that initially survived irradiation. As this counteracted the decreased radiosensitivity, hypoxia was less important for cure than predicted from cell survival assays. This finding suggests that chronic hypoxia may not limit directly the success of radiation therapy.
Affiliation:
Department of Physics, Institute of Cancer Research and Royal Marsden NHS Trust, London, England, United Kingdom. fbuffa@icr.ac.uk
Citation:
Radiation response and cure rate of human colon adenocarcinoma spheroids of different size: the significance of hypoxia on tumor control modelling. 2001, 49 (4):1109-18 Int. J. Radiat. Oncol. Biol. Phys.
Journal:
International Journal of Radiation Oncology, Biology, Physics
Issue Date:
15-Mar-2001
URI:
http://hdl.handle.net/10541/85559
PubMed ID:
11240253
Type:
Article
Language:
en
ISSN:
0360-3016
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBuffa, Francesca Men
dc.contributor.authorWest, Catharine M Len
dc.contributor.authorByrne, Karenen
dc.contributor.authorMoore, James Ven
dc.contributor.authorNahum, Alan Een
dc.date.accessioned2009-11-06T14:24:39Z-
dc.date.available2009-11-06T14:24:39Z-
dc.date.issued2001-03-15-
dc.identifier.citationRadiation response and cure rate of human colon adenocarcinoma spheroids of different size: the significance of hypoxia on tumor control modelling. 2001, 49 (4):1109-18 Int. J. Radiat. Oncol. Biol. Phys.en
dc.identifier.issn0360-3016-
dc.identifier.pmid11240253-
dc.identifier.urihttp://hdl.handle.net/10541/85559-
dc.description.abstractPURPOSE: To evaluate the adequacy of a Poisson tumor control probability (tcp) model and the impact of hypoxia on tumor cure. METHODS AND MATERIALS: A human colon adenocarcinoma cell line, WiDr, was grown as multicellular spheroids of different diameters. Measurements were made of cell survival and spheroid cure following 300-kV X-ray external beam irradiation in air and nitrogen. Cell survival data were fitted using a two-compartment and an oxygen diffusion model. Spheroid cure data were fitted using the tcp model. RESULTS: Hypoxia was seen only for spheroids greater than 500 microm in diameter. For small spheroids tcp estimates of radiosensitivity and clonogenic number showed excellent agreement with experimentally derived values. For large spheroids, although tcp estimates of radiosensitivity were comparable with measurements, estimates of the clonogenic number were considerably lower than the experimental count. Reoxygenation of large spheroids before irradiation resulted in the tcp estimates of the number of clonogenic cells agreeing with measured values. CONCLUSIONS: When hypoxia was absent, the tcp model accurately predicted cure from measured radiosensitivity and clonogen number. When hypoxia was present, the number of cells capable of regrowth in situ was considerably lower than the number of clonogenic cells that initially survived irradiation. As this counteracted the decreased radiosensitivity, hypoxia was less important for cure than predicted from cell survival assays. This finding suggests that chronic hypoxia may not limit directly the success of radiation therapy.en
dc.language.isoenen
dc.subjectColonic Canceren
dc.subjectCultured Tumour Cellsen
dc.subject.meshAdenocarcinoma-
dc.subject.meshAlgorithms-
dc.subject.meshCell Hypoxia-
dc.subject.meshCell Survival-
dc.subject.meshColonic Neoplasms-
dc.subject.meshHumans-
dc.subject.meshLinear Models-
dc.subject.meshOxygen-
dc.subject.meshPoisson Distribution-
dc.subject.meshRadiobiology-
dc.subject.meshSpheroids, Cellular-
dc.subject.meshTumor Cells, Cultured-
dc.titleRadiation response and cure rate of human colon adenocarcinoma spheroids of different size: the significance of hypoxia on tumor control modelling.en
dc.typeArticleen
dc.contributor.departmentDepartment of Physics, Institute of Cancer Research and Royal Marsden NHS Trust, London, England, United Kingdom. fbuffa@icr.ac.uken
dc.identifier.journalInternational Journal of Radiation Oncology, Biology, Physicsen
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