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dc.contributor.advisorAfarinkia, Kamyar
dc.contributor.advisorVinader, Victoria
dc.contributor.authorBasheer, Haneen A.*
dc.date.accessioned2018-02-27T10:09:53Z
dc.date.available2018-02-27T10:09:53Z
dc.date.issued2017
dc.identifier.urihttp://hdl.handle.net/10454/15100
dc.description.abstractThe expression of CCR7 was evaluated in different cancer cell lines by using flow cytometry, western blot, Immunofluorescence and immunohistochemistry. We showed for the selected cell lines that the expression is maintained in cells grown as spheroids, and xenoplanted in mice. Furthermore, we showed the expression of CCR7 correlates with stage of the disease in patient derived head and neck cancer tissue. We also showed that expression of CCR7 in cancer cell lines correlates with migratory aptitude towards CCL21 in a scratch assay, Boyden chamber assay and spheroid invasion assay. We then showed that the expression of CCR7 is elevated under serum starvation and under hypoxia in cancer cell lines grown as monolayers and as spheroids; and that there is a correlation between hypoxia and CCR7 expression in spheroids, xenografted cells and clinical cancer tissue. However, we found that in cell line OSC-19, the increase in the expression of CCR7 did not correlate to increased migration. Our investigations following this observation showed that whilst hypoxia increases the expression of CCR7, it concurrently causes a decrease in reactive oxygen species (ROS) which strongly abrogates migratory aptitude in OSC-19, resulting in an overall loss of migration in OSC-19 cells. In addition, we characterised OSC-19 as a suitable model to evaluate small molecule CCR7 antagonists using a number of different assays. In particular, we showed that ICT13069 antagonised response of this cell line across a number of drivers of malignancy such as migration, invasion in 2D and 3D models.en
dc.description.sponsorshipZarqa Universityen_US
dc.language.isoenen_US
dc.rights<a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.eng
dc.subjectCancer; Chemokine receptor 7; CCR7; Therapeutic target; Pharmacologyen_US
dc.titlePharmacological characterization of chemokine receptor 7 (CCR7) as a potential therapeutic target in canceren_US
dc.type.qualificationleveldoctoralen_US
dc.publisher.institutionUniversity of Bradfordeng
dc.publisher.departmentInstitute of Cancer Therapeuticsen_US
dc.typeThesiseng
dc.type.qualificationnamePhDen_US
dc.date.awarded2017
dc.description.publicnotesThe full text was made available at the end of the embargo, 3rd December 2019en
refterms.dateFOA2020-06-09T11:40:48Z


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