Hypoxia.

We have extensively studied the issue poor oxygenation in (prostate) tumour. Analysis of patient specimens identified that immunostaining intensity for the two hypoxia markers HIF-1alpha and VEGF was significantly enhanced in 75% of malignant when compared to matched benign specimens. Presence of these high staining intensity regions was associated with raised PSA levels.

The lab has demonstrated that hypoxia affects the chemosensitivity and radiosensitivity of prostate cancer cells in vivo. We have furthermore studied the impact of hypoxia on the Notch pathway and identified the Notch-3 receptor as a potentially key hypoxic-responsive member of the Notch pathway in prostate tumorigenesis.

Radiation Resistance.

The lab has derived a new radiation-resistant 22Rv1 prostate cancer cell line. These cells were associated with increased clonogenic survival following radiation exposure that could be attributed to reduced susceptibility to DNA damage and increased DNA repair capacity. These cells furthermore demonstrated apoptosis resistance and increased invasion capacity.

The team investigated the impact of low doses of radiation on cell survival and identified the recognition of O6MeG Lesions and the DNA mismatch repair protein MSH2 as two mechanisms to the hyper-sensitivity observed at low doses.

Sex.

Sex is a fundamental biological variable that can get lost owing to the use of sex-neutral language (cells, animal, patient) and the practice of data pooling. Our lab has identified that sex is poorly considered as a biological variable in radiation therapy and bladder cancer preclinical and clinical studies. Ongoing work aims to examine the impact of sex on susceptibility to cancer cell destruction.