dc.contributor.advisor |
Allshire, Ashley |
en |
dc.contributor.author |
Gebolys, Kinga |
|
dc.date.accessioned |
2015-08-13T14:07:03Z |
|
dc.date.issued |
2014 |
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dc.date.submitted |
2014 |
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dc.identifier.citation |
Gebolys, K. 2014. HIF-1alpha role in oxygen-dependent radio- and chemosensitivity. PhD Thesis, University College Cork. |
en |
dc.identifier.endpage |
234 |
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dc.identifier.uri |
http://hdl.handle.net/10468/1905 |
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dc.description.abstract |
Poor oxygenation (hypoxia) is a common characteristic of human solid tumours, and is associated with cell survival, metastasis and resistance to radio- and chemotherapies. Hypoxia-induced stabilisation of hypoxia-inducible factor-1α (HIF-1α) leads to changes in expression of various genes associated with growth, vascularisation and metabolism. However whether HIF-1α plays a causal role in promoting hypoxic resistance to antitumour therapies remains unclear. In this study we used pharmacological and genetic methods to investigate the HIF-1α contribution to radio- and chemoresistance in four cancer cell lines derived from cervical, breast, prostate and melanoma human tumours. Under normoxia or hypoxia (<0.2% or 0.5% oxygen) the cells were exposed to either a standard irradiation dose (6.2 Gy) or chemotherapeutic drug (cisplatin), and subsequent cell proliferation (after 7 days) was measured in terms of resazurin reduction. Oxygen-dependent radio- and chemosensitivity was evident in all wild type whereas it was reduced or abolished in HIF-1α (siRNA) knockdown cells. The effects of HIF-1α-modulating drugs (EDHB, CoCl2, deferoxamine to stabilise and R59949 to destabilise it) reflected both HIF-1α-dependent and independent mechanisms. Collectively the data show that HIF-1α played a causal role in our in vitro model of hypoxia-induced radioresistance whereas its contribution to oxygendependent sensitivity to cisplatin was less clear-cut. Although this behavior is likely to be conditioned by further biological and physical factors operating in vivo, it is consistent with the hypothesis that interventions directed at HIF-1α may improve the clinical effectiveness of tumour treatments. |
en |
dc.format.mimetype |
application/pdf |
en |
dc.language.iso |
en |
en |
dc.publisher |
University College Cork |
en |
dc.rights |
© 2014, Kinga Gebolys. |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-nd/3.0/ |
en |
dc.subject |
HIF-1alpha |
en |
dc.subject |
Cancer |
en |
dc.subject |
Hypoxia |
en |
dc.subject |
Oxygen-dependent radioresistance |
en |
dc.subject |
Oxygen-dependent chemoresistance |
en |
dc.title |
HIF-1alpha role in oxygen-dependent radio- and chemosensitivity |
en |
dc.type |
Doctoral thesis |
en |
dc.type.qualificationlevel |
Doctoral |
en |
dc.type.qualificationname |
PhD (Medicine and Health) |
en |
dc.internal.availability |
Full text available |
en |
dc.description.version |
Accepted Version |
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dc.contributor.funder |
Aid Cancer Treatment, Cork |
en |
dc.description.status |
Not peer reviewed |
en |
dc.internal.school |
Pharmacology and Therapeutics |
en |
dc.check.reason |
This thesis is due for publication or the author is actively seeking to publish this material |
en |
dc.check.opt-out |
Not applicable |
en |
dc.thesis.opt-out |
false |
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dc.check.chapterOfThesis |
3,4 |
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dc.check.embargoformat |
E-thesis on CORA only |
en |
ucc.workflow.supervisor |
a.allshire@ucc.ie |
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dc.internal.conferring |
Autumn Conferring 2014 |
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