Research Interest
Late effects of radiotherapy
Radiobiology of normal tissues
Together with the group of Fiona Stewart (division of experimental therapy) we are investigating late vascular damage following radiotherapy, a side effect that long term can compromise health and survival. One project supported by the Dutch Cancer Society (NKB/KWF) studies the induction of atherosclerosis in murine and human studies. We have demonstrated an increased formation of “initial” (unstable) atherosclerotic plaques following irradiation, which are more prone to induce thombosis. Studies of therapeutic intervention strategies to combat these changes are underway. This work is in parallel with the projects of the department of Epidemiology on late cardiovascular and cerebrovascular effects of cancer treatments. The second project concerns micro-vascular damage and the development of telangiectasia in skin and mucous membranes. In vitro, in vivo, and clinical studies are helping to reveal the altered cytokine signaling pathways, particularly TGF-β / ALK and jagged / Notch signaling after irradiation. These pathways are involved in modulating endothelial cell migration and proliferation that leads to the development of abnormal micro-vasculature. The aim is to develop a tailored intervention strategy.
Radiation- induced breast cancer
Together with the departments of Epidemiology (prof.dr. Floor van Leeuwen) and molecular pathology (dr. Laura van ‘Veer) we have been involved in a series of projects to study the risks and causes of radiation-induced breast cancer. In particular gene- environment (radiation) interactions in patients treated with radiotherapy for Hodgkin’s lymphoma and a first breast cancer, specifically whether cancer susceptibility genes contribute to the development of radiation-induced breast cancer, and whether radiation-induced cancers are characterized by specific genomic alterations. A national case controlled cohort study (BReast cancer Induction followinG Hodgkin’s lymphoma Treatment, BRIGHT) is now underway including germ-line genetic analysis and data collection on clinical and life-style factors. Our studies also contribute to international collaborations in this field.
Clinical studies of breast cancer treatment
Nutritional studies and breast cancer
Together with the divisions of Psychosocial Research and Epidemiology, and Experimental therapy (Dr. Dorine Voskuil), we have performed studies on the effects of breast cancer treatments on weight gain, (a factor which can have a negative effect on prognosis) and also dietary intervention studies aimed at influencing the IGF (insulin-like growth factor) system. Strategies to help breast cancer patients attain and maintain an optimal body weight are currently under investigation.
Breast cancer clinical trials
EORTC 22051/10052 /MRC/ BIG/BOOG phase III SUPREMO clinical trial of the role of post mastectomy chest wall irradiation, is an international collaboration to define the role of radiotherapy in intermediate risk breast cancer patients and aims to improve long-term survival. (www.supremo-trial.com). Principle investigators for the EORTC: N.S. Russell and G.van Tienhoven (AMC, Amsterdam).
For the BIG 2-06 ALTTO study of lapatinib and trastuzumab in the adjuvant setting we are developing a radiotherapy sub-study to document and later analyse the interaction between these agents and radiotherapy on cardiac and lung function. Principle sub-study investigators: H. Westenberg (ARTI, Arnhem) and N. S. Russell.
Other trials of radiotherapy in breast cancer that are actively recruiting in our department are the Dutch “Young Boost trial” BOOG 2004-01 for patients under 50 years of age undergoing irradiation as part of breast conserving therapy, and the EORTC 10981-22023 AMAROS trial which investigates whether axillary irradiation can be applied as an alternative treatment to axillary nodal dissection for sentinel node positive breast cancer.
Further, the department of radiotherapy is actively implementing new radiotherapy techniques and incorporating developments resulting from clinical physical research in daily practice for breast cancer patients, including the use of a simultaneous integrated boost, intensity modulated radiotherapy and irradiation using a breath-hold technique to avoid cardiac exposure to radiation.
Key Publications
Russell N.S., Knaken H., Bruinvis I.A.D., Hart A.A.M., Begg A.C., Lebesque J.V. Quantification of patient to patient variation of skin erythema developing as a response to radiotherapy. Radiother. Oncol., 1994, 30:213-21
Russell N.S., Grummels A., Hart A.A.M., Smolders I.J.H., Borger J., Bartelink H., Begg A.C. Low predictive value of intrinsic fibroblast radiosensitivity for fibrosis development following radiotherapy for breast cancer. Int. J. Radiat. Biol. 1998, 6: 661-70.
Russell N.S., Lara P.C., Grummels A., Hart A.A.M., Coco-Martin J.M., Bartelink H., Begg A.C. In vitro differentiation characteristics of human skin fibroblasts: correlations with radiotherapy-induced breast fibrosis in patients. Int. J. Radiat. Biol. 2000, 76: 231-40
Broeks A. Russell N.S., Floore A.N., Urbanus J.H.M., Dahlers E.C.,van ‘t Veer M.B., Hagenbeek A., Noordijk E.M., Crommelin M.A., van Leeuwen F.E., van ‘t Veer L.J. Increased risk for breast cancer following irradiation for Hodgkin’s disease is not a result of ATM germline mutations. Int. J. Radiat. Biol. 2000, 76:693-98.
Broeks A, de Witte L, Nooijen A, Huseinovic A, Klijn JG, van Leeuwen FE, Russell NS, van't Veer LJ. Excess risk for contralateral breast cancer in CHEK2*1100delC germline mutation carriers. Breast Cancer Res Treat. 2004 Jan;83(1):91-3
Annegien Broeks, Linde M. Braaf, Angelina Huseinovic, Anke Nooije2, Jos Urbanus, Frans Hogervorst, Marjanka K. Schmidt, Jan G.M. Klijn, Nicola S. Russell, Flora E. Van Leeuwen and Laura J. Van ‘t Veer. Identification of women with an increased risk of developing radiation-induced secondary breast cancer: a case only study. Breast Cancer Res. 2007;9(2):R26.
van Leeuwen, F.E., Klokman W.J., Stovall M., Dahler E.C.,van ‘t Veer M.B., Noordijk E.M., Crommelin M.A., Aleman B.M.P., Broeks A., Gospodarowicz M., Travis, L., Russell, N.S. The roles of radiation dose, chemotherapy, and hormonal factors in breast cancer following Hodgkin’s disease. J. Natl. Cancer Inst 2003, 95:971-980
Kruse JJ, te Poele JA, Russell NS, Boersma LJ, Stewart FA.Microarray analysis to identify molecular mechanisms of radiation-inducedmicrovascular damage in normal tissues.Int J Radiat Oncol Biol Phys. 2004 Feb 1;58(2):420-6.
Stewart FA , Heeneman S, te Poele J, Kruse J, Russell NS, Gijbels M, Daemen M. Ionising radiation accelerates the development of atherosclerotic lesions in APOE-/- mice and predisposes to an inflammatory vulnerable plaque phenotype. Am J Pathol. 2006 Feb;168(2):649-58
Saske Hoving, Sylvia Heeneman, Marion J. Gijbels, Johannes A te Poele, Nicola S Russell, Mat J Daemen, Fiona A. Stewart. Single dose and fractionated irradiation promote initiation and progression of atherosclerosis and induce an inflammatory plaque phenotype in ApoE -/- mice. In press: International Journal of Radiotherapy Oncology Biology Physics.
D.W. Voskuil, A. Vrieling, C.M. Korse, J.H. Beijnen, J.M. Bonfrer, J. van Doorn, R. Kaas, N.S. Russell, E.J. Rutgers, F.E. van Leeuwen, L.J. van 't Veer & M.A. Rookus Effects of lycopene on the insulin-like growth factor (IGF) system in breast cancer survivors and women at high familial breast cancer risk; a randomized trial. In press International Journal of Cancer
J.J.C.M. Kruse, M. Scharpfenecker, D Sprong, N.S. Russell, P.ten Dijke, F.A. Stewart. Ionizing radiation shifts the PAI-1/ID-1 balance and activates Notch signaling in endothelial cells. In press International Journal of Radiation Oncology, Biology, Physics 2008
Biographical sketch
Nicola Russell graduated in Medicine from the University of Nottingham Medical School in 1983. She trained in Radiation Oncology at the Christie Hospital, Manchester, UK and the Netherlands Cancer Institute, receiving her board certification in 1993. A European Cancer Centre fellowship in 1993 enabled her to work in the laboratory of dr. Adrian Begg on variations in normal tissue radiation sensitivity. She was awarded a PhD in 2000 for her thesis entitled “Individual variation in normal tissue reactions to radiotherapy: correlations with radiobiological parameters”. Since 1993 she has been a staff Radiation Oncologist in the Division of Radiotherapy, specializing in breast cancer radiotherapy and continuing translational research particularly with the Divisions of Experimental Therapy and Psychosocial Research and Epidemiology.
Co-workers
Fiona Stewart, Academic staff (group leader Division of Experimental Therapy)
Saske Hoving, post-doc
Marion Scharpfenecker, post-doc
Hans te Poele, Technician
Ben Floot, Technician
Laura van’t Veer (group leader Division of Experimental Therapy)
Annegien Broeks, post-doc
Floor van Leeuwen, Academic staff (group leader Division of Psychosocial Research and Epidemiology)
Marieke De Bruin, Post-doc
Dorien Voskuil, Post doc
Berthe Aleman, academic staff
Paula Elkhuizen, academic staff
Babs Reichgelt, academic staff
Corine van Vliet Vroedindeweij, academic staff