Mechanisms of radiotherapy-induced vascular damage

Details

Radiotherapy is a common treatment for cancer, and is used in over 70% of breast cancer patients. However, radiotherapy is associated with longer term vascular damage including atherosclerosis development and fibrosis. Clinically, this can be observed in patients undergoing deep inferior epigastric perforator (DIEP) reconstruction following mastectomy and radiotherapy. In this procedure, skin, fat and blood vessels from the lower abdomen are used to create a reconstructed breast, with the blood vessels being intricately woven into the breast site to maintain reconstructed tissue viability. This includes perforator blood vessels, which are those that link the larger arteries and veins with the microvascular network in the skin. During surgery, the blood vessels in the irradiated tissue are seen to be more delicate than the blood vessels from the non-irradiated epigastric flap, with the layers of the blood vessels having a tendency to separate from each other with a fibrotic texture. The cellular and molecular causes of these clinical observations are unknown.

The clinical issue of post-radiotherapy vascular damage is poorly understood, with most studies using animal models or using in vitro radiation of isolated cells. In contrast, this project will use tissue from patients who have undergone radiotherapy prior to DIEP reconstruction to provide a comprehensive assessment of the effect of targeted radiotherapy on the vasculature of breast cancer patients. It will identify whether perforator smooth muscle cells can be used as a proxy for smooth muscle cell alterations in deeper macrovessels. It will use primary cell culture, molecular biology approaches (qPCR, siRNA) and immunoflurescent methods. Furthermore, the use of tissue from multiple patient donors will allow us to assess interpatient variability, which is important for translation of basic research findings into the clinic.

How to apply

Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account, select ‘Postgraduate Research’ as the course and then use the keywords ‘biomedical science’. Applicants should then specify the project title in the ‘Research Proposal’ section.

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