Research interest
Our group focuses on understanding cell and tumor responses to radiation, with the ultimate aim of predicting outcome and improving radiotherapy. Our work is divided between clinically related studies and mechanistic studies in the lab. In the clinic, we are studying factors affecting outcome after treatment involving radiotherapy, with or without cisplatin, including quantification of hypoxia (acute, chronic, intermediate), cisplatin-DNA adducts. We are also studying a variety of genetic factors known or suspected to affect response to radiation and platinum compounds. This includes expression profiling, exploiting our central microarray facility, and tissue microarrays. These studies are being carried out within several national and international clinical trials. In the lab, we focus on DNA repair. We have shown that inhibiting base excision repair using a dominant negative approach radiosensitizes human tumor cells and we are pursuing detailed mechanisms. This has led us into further investigations of lesion bypass DNA polymerases which can act as backup pathways for repair. They may also provide targets for increasing tumor cell radiosensitivity. Finally, we are investigating the link between cross-link repair and hypoxic radiosensitivity in human cells, an interesting and potentially clinically relevant finding so far described only in rodents.
Key publications
Vermeulen, C., Verwijs-Janssen, M., Cramers, P., Begg, A.C., Vens, C. (2007). Role for DNA polymerase beta in response to ionizing radiation. DNA Repair (Amst). 6(2):202-212.
Hoebers, F.J., Pluim, D., Verheij, M., Balm, A.J., Bartelink, H., Schellens, J.H., and Begg, A.C. (2006). Prediction of treatment outcome by cisplatin-DNA adduct formation in patients with stage III/IV head and neck squamous cell carcinoma, treated by concurrent cisplatin-radiation (RADPLAT). Int J Cancer. 119, 750-756.
Sprong, D., Janssen, H.L., Vens, C., and Begg, A.C. (2006). Resistance of hypoxic cells to ionizing radiation is influenced by homologous recombination status. Int J Radiat Oncol Biol Phys. 64, 562-572.
Janssen, H.L., Ljungkvist, A.S., Rijken, P.F., Sprong, D., Bussink, J., van der Kogel, A.J., Haustermans, K.M., and Begg, A.C. (2005). Thymidine analogues to assess microperfusion in human tumors. Int J Radiat Oncol Biol Phys. 62, 1169-1175.
Janssen, H.L., Haustermans, K.M., Balm, A.J., and Begg, A.C. (2005). Hypoxia in head and neck cancer: How much, how important? Head Neck 27, 622-638.
Neijenhuis, S., Begg, A.C., and Vens, C. (2005). Radiosensitization by a dominant negative to DNA polymerase beta is DNA polymerase beta-independent and XRCC1-dependent. Radiother. Oncol. ..
West, C.M., McKay, M.J., Holscher, T., Baumann, M., Stratford, I.J., Bristow, R.G., Iwakawa, M., Imai, T., Zingde, S.M., Anscher, M.S., Bourhis, J., Begg, A.C., Haustermans, K., Bentzen, S.M., and Hendry, J.H. (2005). Molecular markers predicting radiotherapy response: Report and recommendations from an International Atomic Energy Agency technical meeting. Int. J. Radiat. Oncol. Biol. Phys. 62, 1264-1273.
Begg, A.C. (2003). Is HIF-1alpha a good marker for tumor hypoxia? Int. J. Radiat. Oncol. Biol. Phys. 56, 917-919.
Begg, A., Sprong, D., Balm, A., and Coco Martin, J. (2002). Premature chromosome condensation and cell separation studies in biopsies from head and neck tumors for radiosensitivity prediction measurements. Radiother. Oncol. 62, 335.
Hofland, I., Ramakers, B., Begg, A.C., and Vens, C. (2002). Rapid fluorescence ratio assay for detecting changes in treatment sensitivity. Radiat. Res. 157, 734-739.
Vens, C., Dahmen-Mooren, E., Verwijs-Janssen, M., Begg, A.C. (2002). The role of DNA polymerase beta in determining sensitivity to ionizing radiation in human tumor cells. Nucleic Acids Res. 30, 2995-3004.
Begg, A.C., Hofland, I., Van de Pavert, I., Van der Schueren, B., Haustermans, K. (2000) The use of thymidine analogs to indicate vascular perfusion in murine tumors. Br. J. Cancer 83, 899-905.
Haustermans, K., Hofland, I., van de Pavert, I., Geboes, K., Varia, M., Raleigh, J., Begg, A.C. (2000). Diffusion Limited Hypoxia Estimated by Vascular Image analysis: Comparison with Pimonidazole Staining in Human Tumors. Radiother. Oncol. 55, 325-333.
Van de Vaart, P.J., Belderbos, J., De Jong, D., Sneeuw, K.C., Majoor, D., Bartelink, H., and Begg, A.C. (2000). DNA-adduct levels as a predictor of outcome for NSCLC patients receiving daily cisplatin and radiotherapy. Int. J. Cancer 89, 160-166.
Begg, A.C., Haustermans, K., Hart, A.A., Dische, S., Saunders, M., Zackrisson, B., Gustaffson, H., Coucke, P., Paschoud, N., Hoyer, M., Overgaard, J., Antognoni, P., Richetti, A., Bourhis, J., Bartelink, H., Horiot,J.C., Corvo, R., Giaretti, W., Awwad, H., Shouman, T., Jouffroy, T., Maciorowski, Z., Dobrowsky, W., Struikmans, H., and Wilson, G.D. (1999). The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis. Radiother. Oncol. 50, 13-23.
Coco Martin, J.M., Mooren, E, Ottenheim, C., Burrill, W., Nunez, M.I., Sprong, D., Bartelink, H., and Begg, A.C. (1999) Potential of radiation-induced chromosome aberrations to predict radiosensitivity in human tumour cells. Int. J. Radiat. Biol. 75,1161-1168.
More publications by Adrian Begg on PubMed
Biographic sketch
Adrian Begg carried out his PhD research at the University of London, firstly within Hammersmith Hospital and subsequently at the Cancer Research Campaign Gray Laboratory. He studied the cell kinetics of murine tumors in relation to their radiation response under the supervision of Jack Fowler. He then held a 3-year post-doctoral position at the University of California Medical Center, San Francisco, studying the interaction of cytotoxic drugs and radiation.
This was followed by a return to the Gray Laboratory as group head for a five year period where he pursued drug-radiation interactions, and began his translational research interests (applying radiobiological principals in clinical trials) under both Jack Fowler and subsequently Julie Denekamp. He then moved to the Netherlands Cancer Institute in 1984 with Fiona Stewart, where they set up a radiobiology group with the support of Harry Bartelink. Flow cytometry was coming of age and he was one of the first to apply IUdR antibodies for the measurement of cell proliferation in clinical tumor samples to predict tumor response. He became head of the Experimental Therapy division in 1990, and Professor of Molecular Radiobiology attached to Nijmegen University in 2002.
Co-workers
Conchita Vens, PhD Postdoctoral fellow
Christie Vermeulen, MSc Graduate student
Sari Neijenhuis, MSc Graduate student
Jimmy Pramana, MD, Graduate student
Monique de Jong, MD, Graduate student
Ben Floot, Technician
Ingrid Hofland, Technician
Manon Verwijs, Technician