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1)  Sensitization of radiotherapy by hyperthermia combined with chemotherapeutic agents. To increase effects radiation can be sensitized with hyperthermia and/or chemotherapy. In the laboratory these sensitization effects are investigated. Especially agents that inhibit or interfere with DNA damage repair are a main topic. In ther study hyperthermia is also combined with small molecules like PARP1 inhibitors and/or chemotherapeutic agents e.g. cisplatin to sensitize radiation treatment.

2)Radiation sensitization effects of hyperthermia. Hyperthermia is one of the best sensitizers of radiotherapy. Hyperthermia treatment of cancer is increasing the temperature of the tumor up to 41- 43 C. Radiotherapy (ionizing radiation) induces DNA lesions. The most severe lesions are DNA double strand breaks (DSB). These DSB are repaired by two major repair pathways, Non-Homologous end-joining (NHEJ) and Homologous Recombination repair (HR). Hyperthermia treatment of 1 h at 42 C can inhibit the HR repair via a transient degradation of the BRCA2 protein which one of the major proteins of this pathway. In the laboratory we investigate the biological effects of hyperthermia in in vitro cell cultures. One of the the research topics is the study of the DNA damage repair pathway. DNA repair proteins that accumulate at the sites of the DSB are studied with fluorescently labelled antibodies and studied with the fluorescence microscope.

3) Development of tests to predict normal tissue damage after Radiotherapy and/or Hyperthermia. Normal tissue damage after radiotherapy is a major problem in the clinic. Therefore in the lab special markers are investigated that can predict late normal tissue damage. n.a.franken@amc.uva.nl