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Title: Development of low temperature plasma as a novel focal therapy for prostate cancer
Author: Hirst, Adam
ISNI:       0000 0004 5990 1903
Awarding Body: University of York
Current Institution: University of York
Date of Award: 2016
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Cancer of the prostate is the most common male malignancy. Despite continual refinement, the treatment of localised prostate cancer remains unsatisfactory. Patients are often faced with the choice between invasive radical surgery and the risk of impotence, or radiological techniques with associated off-target toxicity and incomplete tumour ablation. Low temperature plasma (LTP) may present a completely new approach for the focal treatment of localised prostate cancer. LTPs create a rich source of reactive oxygen and nitrogen species, plus energetic photons, charged particles, and localised electric fields. Long-established radio- and chemo-therapies are known to exploit the ability of reactive species to induce cytopathic effects. The effects of LTP were first investigated in two commonly used prostate cell lines: BPH-1 and PC-3 cells. It was found that LTP treatment induced high levels of DNA damage, reduced cell viability and clonogenicity, and both apoptotic and necrotic cell death. The study then moved on to evaluate the effects of LTP in clinically relevant prostate models through the treatment of normal and cancer primary prostate cells derived directly from patient tissues. Whilst the immediate effects of LTP mirrored those found in cell lines, it was found that primary prostate cells do not undergo apoptosis; dying entirely via necrotic mechanisms. Evidence of an autophagic response was also observed following LTP treatment, and it was found that LTP showed no selectivity between normal and tumour cells. The treatment of three-dimensional aggregate and spheroid models was also evaluated, where it was found that the cytopathic effect of LTP occurred at the surface of treated spheres. Finally, the study concludes by speculating how LTP may compare with and overcome some of the issues encountered with current prostate cancer therapies, and outlines how focal LTP could be applied to patients in the clinic.
Supervisor: O'Connell, Deborah ; Maitland, Norman Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available