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A.L. Oei PhD

Positions
Other Academic Staff, Research Associate
Main activities
Research
Specialisation
Hyperthermia and radiobiology
Focus of research

1)  Enhancing radiotherapy or chemotherapy with DNA repair inhibiting agents, such as hyperthermia and PARP1-inhibitors. In the laboratory these sensitization effects are investigated and potential new treatment combinations are tested, both in cell lines and animal experiments. Hyperthermia is a local treatment, in which the tumour is heated up to 41- 43 C for approximately one hour. As a cancer treatment, hyperthermia should always be combined with either radiotherapy of chemotherapy; as a single therapy, hyperthermia is not effective in treating cancer. This is due to the fact that both radiotherapy (ionizing radiation) and chemotherapy induce 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 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. 

2) In our laboratory we also study the effects of hyperthermia (in combination treatments) on tumours infected with the human papillomavirus (HPV). From clinical studies it is known that hyperthermia is very effective on cervical cancers, of which almost all tumours are infected with HPV. In our laboratory we found that hyperthermia can disrupt the interaction between the HPV-protein E6 and tumor suppressor protein p53, which causes activite p53 resulting in more cell kill. More recently, we investigated the effects of combination treatments of radiotherapy or chemotherapy with hyperthermia and immune checkpoint inhibitors on the effectiveness on the primary tumour growth and on distant metastases (in animal models).  

3) Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is used to treat peritoneal metastases of colon cancer. In our laboratory we are focussing on developming personalized HIPEC treatment. This involves thorough investigations of different hyperthermia temperatures and durations, and various chemotherapeutic agents on multiple cell lines and mouse models.

4) 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.

Key publications
  • Oei Arlene L., van Leeuwen Caspar M., ten Cate Rosemarie, Rodermond Hans M., Buist Marrije R., Stalpers Lukas J. A., Crezee Johannes, Kok H. Petra, Medema Jan Paul, Franken Nicolaas A. P. Hyperthermia Selectively Targets Human Papillomavirus in Cervical Tumors via p53-Dependent Apoptosis Cancer research 2015;75 (23):5120-5129 [PubMed]
  • Oei Arlene L., Korangath Preethi, Mulka Kathleen, Helenius Mikko, Coulter Jonathan B., Stewart Jacqueline, Velarde Esteban, Crezee Johannes, Simons Brian, Stalpers Lukas J. A., Kok H. Petra, Gabrielson Kathleen, Franken Nicolaas A. P., Ivkov Robert Enhancing the abscopal effect of radiation and immune checkpoint inhibitor therapies with magnetic nanoparticle hyperthermia in a model of metastatic breast cancer International journal of hyperthermia 2019;36:47-63 [PubMed]
  • Oei Arlene L., Vriend Lianne E. M., Crezee Johannes, Franken Nicolaas A. P., Krawczyk Przemek M. Effects of hyperthermia on DNA repair pathways: one treatment to inhibit them all Radiation oncology (London, England) 2015;10:165 [PubMed]
  • Oei Arlene L., van Leeuwen Caspar M., Ahire Vidhula R., Rodermond Hans M., ten Cate Rosemarie, Westermann Anneke M., Stalpers Lukas J. A., Crezee Johannes, Kok H. Petra, Krawczyk Przemek M., Kanaar Roland, Franken Nicolaas A. P. Enhancing synthetic lethality of PARP-inhibitor and cisplatin in BRCA-proficient tumour cells with hyperthermia Oncotarget 2017;8 (17):28116-28124 [PubMed]
  • Oei A. L., Kok H. P., Oei S. B., Horsman M. R., Stalpers L. J. A., Franken N. A. P., Crezee J. Molecular and biological rationale of hyperthermia as radio- and chemosensitizer Advanced drug delivery reviews 2020 [PubMed]
All Publications
Research programmes

N.A.P. Franken PhD (Combined ionizing radiation and hyperthermia treatment to improve cancer therapy)