Digital Public Defence: Maria Mastrangelopoulou
MSc Maria Mastrangelopoulou at Institute of Clinical Medicine will be defending the thesis “A novel approach to inner cancer treatment through the activation of photosensitizers by protons.” for the degree of PhD (Philosophiae Doctor).
Photo: Christoffer Nordeng.
The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture – time and place
- First opponent: Senior Neurosurgeon Herwig Kostron, Private Clinic, Innsbruck
- Second opponent: Senior Scientist Ellen Bruzell, Nordic Institute of Dental Materials
- Third member and chair of the evaluation committee: Adjunct Professor Jørgen Wesche, University of Oslo
Chair of the Defence
Professor Lars Eide, Faculty of Medicine, University of Oslo
Reseacher, Project group leader Theodossis Athanassios Theodossiou, Oslo University Hospital
Brain cancers like glioblastoma multiforme (GBM) are practically incurable due to their location and infiltrative nature.
The current standard of care consists of surgery, followed by radiotherapy and chemotherapy. However, these therapies offer limited overall survival benefit with only 3% of patients living longer than five years after initial diagnosis, which delineates a high, unmet medical need.
The aim of the thesis was to fuse the strengths of photodynamic (PDT) and proton therapies into a new and radical hybrid anticancer treatment to overcome their limitations. We therefore proposed ‘protondynamic therapy’ (PrDT), where accelerated protons would be used to excite photosensitizers (PSs, light activated drugs) and elicit a ‘photodynamic-like’ effect to efficiently kill cancer cells in synergy with the proton radiotherapy. To validate our hypothesis, we mainly focused on two PSs; the naturally occurring PS cercosporin and the clinically established PS, PpIX, endogenously produced from 5-aminolevulinic acid (5-ALA).
We found cercosporin to be a potent singlet oxygen producer upon light activation, causing enhanced toxicity and a bioenergetic collapse to a panel of cancer cell lines upon application of PDT with light. Furthermore, we showed that cercosporin is a potent PS when applied to an intermediate complexity 3D culture system (cell spheroids).
We proposed and validated crucial and specific biomarkers, which can potentially predict the treatment outcome, while at the same time be used as therapeutic enhancers of 5-ALA-PDT or PrDT, especially for resistant cell lines.
We demonstrated for the first time that accelerated protons can activate PSs to emit their characteristic fluorescence and singlet oxygen in solutions and gels. We also provided proof of principle of the efficacy of ‘PrDT’ on GBM cell lines, laying the foundations of a novel treatment for enhanced tumour eradication based on accelerated protons, which can penetrate tissue much deeper than light.
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