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Title: Mechanisms of response to targeted irradiation in organotypic 3D skin cultures
Author: Acheva, Anna Rumenova
ISNI:       0000 0004 2740 8225
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2012
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Low linear energy transfer (LET) ionizing radiation as gamma and X-rays is widely used in the modem medicine for diagnostic and treatment purposes. Despite all the advantages that it gives for the early diagnosis and in the radiotherapy treatment of cancer, there are still unclear aspects about the mechanisms of the radiation effects in human tissue. Of particular interest is the detailed pathway which the directly irradiated cells use to communicate to their neighbours and its possible implications for radiotherapy applications. The aim of this project is to study the spatio-temporal signalling from irradiated to non- irradiated cells using in vitro 3D tissue models. For evaluation of radiation induced effects we used conventional 225 kVp X-ray and lead shielding to observe the effects in the non-targeted cells. Additionally we applied the novel 30 kVp micro collimator that could irradiate samples in wide 1-10 urn lines. The application of this targeted radiation source together with the shielding irradiation set up will cast light on the effects induced by localized radiation exposures and the signalling from the irradiated to non-irradiated cells using 3D organotypic skin as a model. Due to its fast cell turnover, the human epidermis is extremely sensitive to IR. This has a limiting effect on the radiotherapy as severe normal skin responses can delay treatment and even decline patients from radiotherapy. The current work is aiming to reveal the mechanisms of DNA damage, repair and their later consequences for the differentiation and development of inflammatory-like response in the irradiated and surrounding areas within the 3D organotypic skin model. We investigated use of inhibitors of pro-inflammatory pathways such as the transcription factor NF-KB and its downstream target COX-2, in order to reduce the signal transduction from the irradiated to non irradiared cells and to reduce the inflammatory responses in the surrounding normal tissue. Similar methods of control of the signal diffusion could be applied in the radiotherapy to reduce the inflammatory skin responses and decrease the range of the late side effects developing from the chronic inflammation that could further lead to ulceration and skin necrosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available