Annual Report 1988 THE NETHERLANDS CANCER INSTITUTE CANCER RESEARCH LABORATORY AND CANCER HOSPIT AL

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2 Annual Report 1988 THE NETHERLANDS CANCER INSTITUTE CANCER RESEARCH LABORATORY AND CANCER HOSPIT AL Copyright: Antoni van Leeuwenhoek Huis PIesmanlaan CX Amsterdam The Netherlands Phone (09) Telex Fax

3 INTERNATIONAL SCIENTIFIC ADVISORY BOARD Jon J. van Rood, Professor ofimmuno-hematology, Leiden, president Joseph R. Bertino, American Cancer Society Professor of Medicine and Pharmacology, New Haven, USA George Klein, Professor of Tumor Biology, Stockholm, Sweden Hilary Koprowski, Professor Director ofthe Wistar Institute, Philadelphia, USA Susumu Tonegawa, M.I.T., Center ofcancer Research, Cambridge, Mass., USA I. Bernard Weinstein, Professor of Medicine and Environmental Sciences, New Vork, USA Charles Weissmann, Professor of Molecular Biology, Zürich, Switzerland NA TIONAL SCIENTIFIC ADVISORY BOARD D. Bootsma, Professor ofcell Biology and Genetics, Rotterdam A.J. van der Eb, Professor of Fundamental Tumor Virology, Leiden V.P. Eijsvoogel, Professor ofimmunology, Amsterdam C.A.M. Haanen, Professor of Internal Medicine, Nijmegen W.GJ. Hol, Professor of Molecular Biology, Groningen S.W.J. Lamberts, Professor ofinternal Medicine, Rotterdam (since ) H.L. Langevoort, Professor of Histology and Embryology, Amsterdam C.J.L.M. Meijer, Professor ofpathological Anatomy, Amsterdam J. Oldhoff, Professor of General Surgery, Groningen J.J. van Rood, Professor ofimmuno-hematology, Leiden P.G. Smelik, Professor of Pharmacology, Amsterdam (till ) T.D. Stahlie, Professor ofpediatrics, Amsterdam (retired) J. Spaander, Bilthoven (deceased) O. Vos, Professor of Cell Biology, Histology and Microscopical Anatomy, Rotterdam 2

4 PATRON H.M. THE QUEEN BOARD OF DIRECTORS P. Borst, research director P. Emmelot, deputy research director S.G.Th. Hulst, clinical director A. Roest, financial director J.G. McVie, clinical research associate director LABORATORY RESEARCH COORDINA TOR L. den Engelse BOARD OF GOVERNORS E.H. van der Beugel, president I J.D. Hooglandt, president 2 T.D. Stahlie, vice-president P. den Tex, secretary C.T.C. Heyning, treasurer A.C. van den Blink J.E.G. de Boer H.P.M. van der Drift M.L. Frohn-de Winter R. Hazelhoff P. G. Hoorweg P. Siderius J.H.M. Temmink G.N.J. Tytgat G.Z. de Vos3 LADIES COMMITTEE M.C. Sickinge-van Eeghen, president D.G. von Kospoth-Teipe, secretary A.L. Meijer-Kortebos, treasurer Until November 16, 1988 From November 16, 1988 Deceased 3

5 RESEARCH DIVISIONS Cell bi%gy E. Roos, head J.G. Collard e.a. Feitkamp Chemica/ carcinogenesis E. Kriek, head P. Emmelot L. den Engelse R. Plasterk E. Scherer J.G. Westra Cellu/ar biochemistry H.L. Ploegh, head WJ. van Blitterswijk W.M. Mooienaar A. Tulp L.N. Vernie Immun%gy CJ.M. Melief, head J. Borst W.S. Bont e.g. Figdor A. Hekman Ph. Rümke e.j.m. Vennegoor F.A. Vyth-Dreese Mo/ecu/ar bi%gy R. Nusse, head P. Borst J. Calafat A.P.M. Jongsma H.V. Westerhoff Tumor bi%gy R.J.A.M. Michalides, head J.H. Daams A.A. van der Gugten Ph.e. Hageman J. Hilkens D.lvanyi M. Sluyser A.A. Verstraeten Mo/ecu/ar genetics A.J.M. Berns, head P. Demant R. van Nie M. Oudshoorn-Snoek M.A. van der Valk Experimental therapy W.J. Nooijen, he ad H. Bartelink A.C. Begg e. Benckhuijsen J.V. Lebesque J.G. McVie L.M.F. Moonen S. Rodenhuis L.A. Smets F.A. Stewart Laboratory anima/ department R.G.M. ten Berg, head Biophysics department GJ.F. Blommestijn, acting head E.L.L. Sonnhammer Radiation physics B.J. Mijnheer, head H. Bartelink R.W. de Boer J. Borger LA.D. Bruinvis L.G.H. Dewit A.A.M. Hart J.V. Lebesque H. Meertens L.M.F. Moonen HOSPIT AL DIVISIONS (research funding: 14.3 persons) Anesthesia M. Hellendoorn-Smit, head e. Blackburn J. Overweg-van Kints H. Vis Surgery J.A. van Dongen, head E. Gortzak B.B.R. Kroon F.A.N. Zoetmulder vacancy Gynaec%gy E.J. Aartsen vacancy Interna/ medicine R. Somers, head W.W. ten Bokkel Huinink P.F. Bruning E. Engelsman S.P. Israëls J.G. McVie S. Rodenhuis vacancy Nuclear medicine C.A. Hoefnagel R.A. Valdes Olmos E.N. T. Head and Neck Surgery FJ.M. Hilgers P.F. Schouwenburg Clinica/ chemistry W.J. Nooijen, head J.M.G. Bonfrer 4

6 Pa th ology Psychiatry WJ. Mooi, head L.M. Gualthérie van Weezei C.E. Albus-Lutter J.F.M. Delemarre CONSULT ANT ST AFF P. van Heerde Dermatology W. Misdorp N. Neering J.L. Peterse K. Weijer Pediatrics P.A. Voûte Radiotherapy H. Bartelink, head Pharmacy J.A. Bangert, head L.J.H. Beijnen G. Baris, R.W. de Boer Plastic surgery J. Borger R.B. Bergman LA.D. Bruinvis P.L.M. Lichtveld B.N.F.M. van Bunningen J.M.V. Burgers Bateriology L.G.H. Dewit W. Pauw A.A.M. Hart R.B. Keus Neurology J.V. Lebesque W. Boogerd E.A.H. Masselink J.J. van der Sande H. Meertens L.M.F. Moonen Neurosurgery B.J. Mijnheer B. Matricali C.C.E. Schaake-Koning Z.D. Goedhart Röntgen-diagnostics Orthopedie surgery R. Steinmetz, head J.W. van der Eijken P. Cohen M.W. Fidler R. Kröger F. de Leeuw Opthalmology L. Koornneeff Dental surgery S. Gonggrijp Rehabilitation A.P. Timmers E.L.D. Angenot Gastroenterology B.G. Taal F.C.A. den Hartog Jager HEADS OF GENERAL SERVICES Central cancer library S. Bakker Pulmonology Custodian research laboratory N. van Zandwijk R.P. van Hoeven Urology Housekeeping services S. Horenbias R. Schellens Scientific administration Financial administration O.B. Dalesio, head J.K. Koppenol H. Franklin F.E. van Leeuwen Medical administration S. Max-Kregar EJ. Schouten, deputy Hospital pastors Audio visual service C. van Beek J.M. Lomecky P. G. Kousemaker Personnel department Patient counsellor J.P. Strikwerda M. Keessen Technical service Psychosocial service T.C.M. Wilmering F.S.A.M. van Dam N.K. Aaronson Radiation protection E.L. Dekker P. de Lange 5

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8 Contents Introduction 9 75th Anniversary 15 Cell Biology Chemical Carcinogenesis Cellular Biochemistry 39 IV Immunology 49 V Molecular Biology 61 VI Tumor Biology 71 VII Molecular Genetics 81 VIII Experimental Therapy 91 IX Radiotherapy 103 X Clinical Oncology 113 Laboratory Animal Department 157 Biophysics Department 161 Education in Oncology 165 Cancer Hospital 177 Meetings (Abstracts) 181 Publications 225 Author index 267 Projects 279 Personnel-project index 287 7

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10 INTRODUCTION 1988 was an eventful year for the Netherlands Cancer Institute (NKl). We celebrated our 75th anniversary with a one-day Symposium attended by over 1000 scientists and culminating in asession honored by the presence of our patron, H.M. The Queen ofthe Netherlands, and many other distinguished guests. A full report of this event follows this introduction. After 18 years of imaginative and productive leadership, the chairman of our board of governors, Prof.E. van der Beugel, resigned. We are grateful to him for his unfailing support of our endeavors, his advice and his effective interventions at critical moments in our existence. We are most fortunate to have found a worthy successor in Mr J. Hooglandt, former president of the board of directors of Hoogovens Ltd. Our desperate financial situation eased somewhat. With the help of parliament we succeeded in reducing government cutbacks and the remaining deficit was covered with the proceeds of a unique NKI bond issue. Research continued to flourish, resulting in several important breakthroughs and a high influx of talented, highly motivated young research workers, increasing the pressure on space. Fifteen years af ter opening the new hospital and ten years after the laboratory wing became operational, space is again a major problem. Ifthe NKI wants to retain its national and international position in the face of a rapid increase in both cancer incidence and cancer research, a considerable increase in floor space (and budget) will need to be realized in the coming years. Research highlights Important advances we re registered in all ten research divisions. I can only mention a few here: Roos and coworkers in the Division of Cell Biology have isolated mutant lymphoma celllines, deficient in the production of the adhesion protein LF A-I. These mutants have largely lost the ability to invade tissues in vi/ra or metastasize in vivo. Application of the 'wet cleaving' method, developed in the NKI by Brands, Feltkamp and Roos and associates (Division I), to 'adhesion plaques' (structures that hold cells together and that disappear af ter oncogenic transformation) has shown th at current models of this structure are incorrect. Kriek, Westra and Van Leeuwen and their associates in the Division of Chemical Carcinogenesis (Division Il) have completed an analysis of DNA adducts in white blood cells of coke-oven workers. A highly significant correlation was found between adduct levels and exposure to polycyclic hydrocarbons. A technical breakthrough in the synthesis of reactive intermediates ofheterocyclic aromatic am in es has greatly facilitated the study ofthe interaction of these amines with DNA. The Division of Celluiar Biochemistry (Division lil) welcomed Dr Wouter Mooienaar, who is continuing his basic studies on signal transduction initiated at the Hubrecht Laboratory in Utrecht. Kast and Melief in the Division of Immunology (Division IV) used the elegant adenovirus tumor model to demonstrate highly specific and efficient tumor therapy in mice with a combination of Cytotoxic T-Iymphocytes and Interleukin-2. Several other tumor model systems analysed in this division provide the basis for new clinical trials in man. The isolation of monoclonal antibodies directed against the gamma-delta T-cell receptor by J. Borst and coworkers, should open the way to define the function of the intriguing sub-set of lymphocytes carrying this receptor. Van de Vijver and Nusse ofthe Division of Molecular Biology (Division V), in collaboration with Peterse and Mooi of the Pathology Department, demonstrated that the neu oncogene is very frequently overexpressed in the comedotype of ductal carcinoma in situ. This group also found that neu overexpression is oflimited prognostic value in stage Il breast cancer, in contrast to reports of other investigators. The article in The New England Journal of Medicine reporting these results, led to substantial coverage in the American popular press. In the Division of Tumor Biology (Division VI), K. Mooienaar and Michalides and their associates discovered th at a group of monoclonal antibodies which preferentially recognize human small-celllung cancer cells, actually reacts with the surf ace adhesion protein N-CAM. This protein is present in high concentrations on human neuroendocrine tumors. Sonnenberg and coworkers discovered a new cellular adhesion complex on platelets, VLA-6, and showed that this complex functions as aspecific laminin receptor. In the Division of Molecular Genetics (Division VII) Berns and coworkers demonstrated that tumor induction by Murine Leukaemia Viruses is markedly accelerated in transgenic mice carrying activated oncogenes in their genome. This is proving an excellent system to uncover oncogenes that act synergistically with the transgene in oncogenesis (eg. pim-l with either c-myc or N-myc). It should also be mentioned that the work by Krimpenfort and Berns on the expression oft-cell receptor (TCR) genes in transgenic mice has paved the way for spectacular advances in our understanding of the shaping of the T-cell repertoire. The identification oftcr enhancer element 5 kbp downstream of the TCRB-chain gene made it possible to express the TCRB-chain gene at high levels in transgenic mice. This allowed unequivocal identification of positive and negative selection 9

11 mechanisms of T cells during their passage through the thymus by H. von Boehmer, Basel Institute of Immunology. In the Division of Experimental Therapy (Division VIII) Loesberg and Smets discovered that meta-iodobenzylguanidine (MIBG), used in the radioiodinated form against neuroblastomas, is a specific inhibitor of mono-adp-ribosylation, the first specific inhibitor of this process known. This may all ow a better analysis of the function of th is intriguing process. Against expectation, Los and McVie found that carboplatin penetrated less efficiently into intraperitoneal tumor nodules than the parent compound cisplatin. The results obtained with this mouse model may explain the disappointing outcome of a clinical trial in our clinic with intraperitoneal carboplatin. Rodenhuis and coworkers have shown that K-ras oncogene activation occurs in one third ofthe adenocarcinomas ofthe lung, but not in other lung tumor types. The K-ras mutations appear to be associated with a smoking history, but this requires validation in a larger group of patients. A major highlight in the Radiotherapy Department (Division IX) was the introduction in the clinic ofthe new digital image detection system for determining patient position during radiotherapy. This novel system was developed by Van Herk and Meertens and their associates in the NKI and it has already received an awanj for its originality and evident clinical relevance. It is also gratifying to see that the dosimetry comparisons carried out by Mijnheer and coworkers in 21 radiotherapy institutes in The Netherlands showed only minimal deviations from calculated dose, in contrast to a comparable study in Great Britain. The major clinical result ofthe year has been in the field ofbreast cancer conservation. The EORTC trial, of which we are a major participant has been closed and the first analysis ofthe data ofthe trial which compares breast conservation for early breast cancer with mastectomy has shown no difference in local recurrence between the two arms and no difference in survival. There is a clear advantage in quality oflife and patient satisfaction for the group ofwomen who retained their breast. Out of 1200 patients treated in our Institute with breast conservation, and a follow up to 10 years, the local recurrence rate is only 2%. This is one ofthe lowest figures reported in the literature and it is of particular significance because it comes from such a large study. Also in the Division of Oncology (Division X) Rodenhuis and Dalesio (in collaboration with K. Mars of Twente University) developed a new and innovative computer supported scheme for matching new patients in the clinic and out-patient clinic with the available clinical trial. This trial matching programma allows the busy clinician to be informed by the touch of a button, which trials are currently open for a particular patient. In the laboratory side ofthe Institute the rejuvenated Biophysics department installed the first part ofthe NKI Ethernet, the counterpart ofthe hospital Wangnet automation system. This brief list of research highlights is necessarily incomplete and somewhat arbitrary. The pages that follow present a more balanced and complete overview of our accomplishments (and frustrations) in Major changes in organization and personnel No major changes we re made in the organisation of the research divisions. Our attempts to find astrong tumor biologist or cytogeneticist to fill the vacancy that arose in the Division of Tumor Biology by the departure ofdr J. Hilgers at the end of 1987 have th us far been unsuccessful. As the research programme in the Tumor Biology Division is rather diverse and has many connections with work of other divisions, four new interdivisional working groups are created: - Acellular adhesion group in which divisions I and IV also participate, headed by Dr E. Roos. - A clinical application of monoclonal antibodies group with divisions IV and X, headed by Dr C. Melief. - An immunopathology group with the department of Pathology, headed by Dr W.J. Mooi. - A molecular biology group in which all molecular biologists of the NKI who are not part of divisions V and VII participate. This group is headed by Dr A.J.M. Berns and Dr R. Nusse. These inter-divisional groups should not only provide scientific support to the Division of Tumor Biology in a period oftransition and increase the inter-divisional contacts, but also lead to a more effectively coordinated effort in areas like cell adhesion or application of monoclonal antibodies, in which the NKI has the knowhow and the people to make a major contribution. Considerable time was also spent in 1988 in discussing the structure of our clinical research and redefining priorities within this research. In line with a general trend in clinical research in The Netherlands we shall start to make a clear distinction between clinicians mainly involved in patient care and clinicians who spend a substantial part of their time on clinical research. By restructuring the present, rather unwieldy division of clinical oncology, we hope to create smaller and more effective research groups. The implementation ofthese plans will start in For the quality control of our research programme we rely on elaborate internal review procedures and the incidental help of members of our advisory boards and other external experts. We have organized mini-reviews of specific projects in association with vi sits of members of our International Scientific Advisory Board to the Institute. In 1988, for instance, we saw Charles Weissmann and Susumu Tonegawa within one week in March and they provided us with stimulating ideas and sound advise. In the past year we have started to complement these internal reviews with more formal site vi sits by external reviewers. Radiotherapy-associated research was assessed at the end of 1987 (outside reviewers were Prof. Michael Peckham, London, and Prof. Emmanuel Van der Schueren, Louvain), psycho-social research in 1988 by Prof. J erome Cohen, Los Angeles, and Prof. J ohn Ware, Boston). Both reviews have been stimulating and helpful to the investigators reviewed and they have helped the directors in assessing the relative merits of competing research programs. Hence, the frequency of these reviews will be increased in the coming years. Nearly all major changes in research personnel in 1988 occurred in the clinical organization. The urologist Tom Boon, the surgeon Peter de Graaf and the gynaecologist Peter Heintz went to the University of 10

12 Utrecht (the last as professor). In their place we welcomed Dr S. Horenbias as our new urologist, as gynaecologist Dr Th. Helmerhorst, and we are still looking for a top surgeon. Our trusted immunologist and renowned melanoma expert, Prof. Philip Rümke retired in April Philip built up the basic immunology division that contains now one of the most important and productive research programmes in the Institute. He made important contributions to basic immunology and clinical oncology and with one foot in the lab and one in the clinic, he was one of the few clinicians contributing to both worlds. As clinical research coordinator in the period and as head of the Division of Oncology he was a stimulating, knowledgeable and gentle leader. It is fortunate th at he will continue his research in our Institute as honorary staff member. He is succeeded by Dr Elaine Rankin, currently senior lecturer in oncology in Glasgow, who was the driving force behind some of our early clinical trials with monoclonal antibodies a few years ago. The expansion of the radiotherapy department allowed the addition of another young radiotherapist to our staff, Jacques Borger. Herbert Marcuse retired as the head of N uclear Medicine and was succeeded by Ce es Hoefnagel. We welcome Dr P.A. Valdes Olmos as our second medical specialist in nuclear medicine. After leading the Pathology department for almost 17 years, Jan Delemarre decided to step down in 1988 in favor ofwolter Mooi. Fortunately, Jan will continue his work in our Institute in the coming years allowing us and all his Dutch colleagues to draw on his large expertise in oncopathology. Finally Mr O.G.H. Lie, the trusted librarian ofthe National Cancer Library, situated in the NKl, retired in For nearly 30 years he has been areliabie and helpful source of information for anybody in the cancer field. We welcome Suzanne Bakker, trained both as a biochemist and a librarian, as his successor. Changes in Board of Governors and Advisory Boards The succession of the chairman of our board of governors was al ready mentioned in the opening paragraph ofthis report. We also lost in 1988 Mr George de Vos who died after a protracted illness. Over many years, we have profited from his extensive knowledge of hospital management and labor relations and we shall miss his valuable, down-to-earth advice. Our National Scientific Advisory Board underwent several changes in 1988: Prof. P.G. Smelik resigned, whereas Dr J. Spaander died after a long illness. Prof. Smelik has been very helpful in our board during the period th at we still had an active endocrinology division. In Dr Spaander we lost one of the oldest members of the board. As a former director ofthe National Institute of Health, Spaander was one of the most talented and experienced research managers in The Netherlands and we have of ten profited from his advice. We remain grateful to both Smelik and Spaander for their contributions to our Institute. Wim Hol, a protein structural chemist, joined the board, underlining the importance that protein structure is gaining in immunology, in the study of oncogene products and other areas of cancer research. A new wing for the Radiotherapy Department After 10 years of planning, we finally obtained government permission to build an extension to our overcrowded Radiotherapy Department. Building was started in 1987 and in November 1988, we celebrated the festive opening ofthe expanded department. The extension adds 2350m 2 floor space and two new linear accelerators and also contains adequate office space for the staff. The excellent working conditions in the renewed Radiotherapy Department are in marked contrast to the situation elsewhere in the hospital part ofthe Institute. As patient care intensified and research expanded, occupation density was pushed to the limit. The research workers in epidemiology and psycho-social oncology were transferred to barracks (called Office Center) next to the laboratory wing ofthe Institute. Plans for expansion ofthe hospital are held up by a general freeze on hospital building in the Amsterdam area. We are considering various options to break this unfortunate deadlock. The laboratory wing has also seen the last bit of usabie space occupied, however, and it is becoming clear that imaginative actions will be required to create space for further growth. Financial problems (and some solutions) As 1987 ended, our financial situation looked grim indeed. We had failed to find compensation for a f 2.3 million cutback in government subsidy and a drastic reduction in staff seemed inevitable. In 1988 the tide turned. First, sound arguments (and persistent lobbying) led parliament to reduce the subsidy cutback from f2.3 to f 1.3 million. Then a financial wizard came up with an imaginative plan for a f 275 million zero-coupon premium bond issue, yielding a net profit for the NKl of sufficient magnitude to cover the remaining hole in the budget. The Queen Wilhelmina Fund (KWF), the Dutch Cancer Foundation, generously took care ofthe remaining deficit that we had accumulated in the years Although it is gratifying to finally see the budget balanced, it remains unsatisfactory to direct research in a rapidly expanding field with a basic budget that has remained essentially unchanged for 8 years now. Although we have succeeded in increasing our share of competitive project grants, such grants do not have an overhead component in the Dutch situation and we have reached the limit ofwhat our infrastructure can carry. If the Institute wants to retain its leading position, we must find ways to break out of this financial shell. National and International activities Besides their research and clinical activities, staff members ofthe Netherlands Cancer Institute participated in a large number of important functions in internationalorganizations such as AACI, CIBA, EMBO, EORTC, ICRU, MRC, OECI, WHO. Staffmembers also served on boards of organizations such as the EORTC co-operative groups, International Association for Breast Cancer Research, Nederlandse Commissie voor Stralingsdosimetrie, American Association for Psychological Oncology, European Society for 11

13 Therapeutic Oncology, the WHO Quality of Life Group, the International Academy ofpathology, etc. Others served as editors of scientific books or served on editorial boards ofjournals such as Journal of Molecular and Cellular Immunology, Cell, Leukemia Research, Clinical and Experimental Metastasis, European Journal ofimmunology, Netherlands Cancer Journal, Journalof Psychosocial Oncology, Human Immunology, Biochimica et Biophysica Acta, Chemico Biological Interactions, Breast Cancer Research and Treatment, Cancer Chemotherapy and Pharmacology, Cancer Immunology and Immunotherapy, Molecular and Biochemical Parasitology, Nucleic Acids Research, Radiotherapy and Oncology. Staff members were also active in organizing national and international oncology meetings, workshops and congresses, and participated in the teachings ofthe European School ofoncology, the ESTRO teaching Course on Quality Assurance of Equipment for External Beam Therapy. Clinical specialists from the hospital gave oncologic advice to doctors in 23 hospitals in the Amsterdam area and other parts of Holland. Outlook As the NKI enters the last quarter ofits first century, prospects are good, but there is no reason for complacency. Our insight in the nature of cancer is increasing every day and the NKI is at the cutting edge of this rapidly ádvancing frontier. Lagging behind is the translation of these advances into improved diagnosis and treatment of cancer. This is not an easy task. We now know th at only a very few genetic changes suffice to convert a normal cell into a cancer cello Hence, a cancer cell is more than 99.99% normal and the task of detecting and exploiting the minute differences in which the tumor cell differs from its normal counterpart, is indeed a formidable one. We intend to strengthen our clinical research progr~m in the coming years to bring our contributions in that area to the same level as those in basic research. We are fortunate to have the support of so many capable people in the endeavor: our governing board and scientific advisory boards, and organizations and many individuals providing support. We are grateful to all ofthem and hope th at this Annual Report presents a perspective ofthe future making th is support worthwhile. Piet Borst, Director of Research Honors Drs Marcel van Herk received the first prize ofthe ESTRO-Varian Clinical Research Award 1988 for a paper entitled 'A matrix ionisation chamber imaging device for on-line patient set up verification during radiotherapy' and this on account ofthe originality of the project and its evident clinical relevance and applications related to optimizing radiotherapy Budgets (x 10 6 HFL) 1. Annual program grants a. Department of health: - structural incidental b. Cancer Foundation KWF - structural incidental Large equipment and special facilities Project grants Deficit 5. Yield bond issue * * Estimate 12

14 Prof E. van der Beugel resigned as chairman of the Board after 18 years and was succeeded by J. Hooglandt. The extension of NKI's department of Radiotherapy was ojjicially opened in November by Th. StraathoJ, director ofthe planning division ofthe ministry ofpublic Health by cutting the knot. 13

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16 75th ANNIVERSARY The Netherlands Cancer Institute ( ) can look back with satisfaction on the celebration ofits 75th anniversary, which was held this year during the third week of April. The celebration started on Tuesday the 19th, with a modest but special meeting, at which the director ofthe Netherlands Postal Services presented a stamp, commemorating the occasion. The stamp, beautifully designed by Kees Ruyter, shows the shoulder part of a healthy body, thus picturing a part of the anatomy with special importance for the diagnosis of cancer. Following this meeting, the chairman ofthe board, Prof. E.H. van der Beugel, opened the exhibition 'Cancer in Perspective', which gives to a general public an overview of the state of the art in prevention, diagnostics and treatment of cancer. This exhibition currently makes a tour of several hospitals and cancer centers. Friday, Apri122nd was the day ofthe scientific symposium and official celebration, which took place in the RAl Congress Center in Amsterdam. For an audience of about 1300 oncologists and other scientists, the symposium offered insights in the latest developments in cancer research and treatment. The NKI was fortunate to find six excellent speakers: H.E. Varrnus (University ofcalifornia), R.A. Weinberg (Cambridge, USA), W.F. Bodmer (ICRF, London), J. Mendelsohn (Sloan-Kettering, New Vork), J.D. Minna (Bethesda, USA) and M. Tubiana (Villejuif, France). In the afternoon, the official celebration followed in the presence of H.M. Queen Beatrix and many other prominent guests. After chairman E. H. van der Beugel had opened the proceedings, poet and biologist Leo V roman presented a playfullecture in which he compared cancer growth to biological and mathematical phenomena. Amsterdam's mayor, Ed. van Thijn, symbolically handed over the anniversary gift, a hostel facility for patients and their relatives, to clinical director S.G.Th. Hulst. Thanks to the Netherlands Cancer Foundation and donations of many supporters, the NKI will be able to realize this facility in the very near future. Finally, NKI's director of research, P. Borst, explained in didactic terms the state of the art in cancer research for a general public. After the meeting, the approximately 1000 guests boarded canal boats which took them to the Rijksmuseum, where areception took place among Rembrandts, Vermeers and other masterpieces of Dutch pictorial art. The reception was offered by the city of Amsterdam and the Dutch government. On Saturday, April 23rd, almost 5000 interested people made use of the occasion to make or renew their aquaintance with the work of the NKI at the open-doorsday. 32 hospital and research divisions presented their work and gave a wealth of information on cancer treatment and research to the general public. The common effort of so many workers created a special atmosphere ofunity. On Saturday night a party was held for the employees of the NKI. Two workers who had dedicated themselves for many years to the institute, Philip Rümke and Piet van Westen, received royal decorations. Throughout the year, several other activities took place in the context ofthe jubilee, such as scientific meetings on gynaecological oncology, the treatment of the elderly and the breast conserving procedure as well as a symposium on steroid receptors and growth factors. The NKI 75th anniversary received good attention from the general and scientific press. Special editions appeared ofthe European Joumal ofsurgical Oncology, the European Joumal of Radiotherapy, and Het Nederlands Tijdschrift voor Geneeskunde, filled with contributions by the scientific and medical staff of the NKI. Tijdschrift Kanker published an article on the history of the NKI, by Prof. J.A. van Dongen. The November 1988 edition ofcancer Research shows the institute on its cover. The NKI has experienced the celebration as an inspirational event which has strengthened the ties with the national and international scientific and medical community as well as among workers ofthe Institute. Maarten de Haas secretary to the Board of Directors 15

17 Drs A W van Ommeren presented on behalf of the Netherlands Postal Services the commemorative stamp to the chairman Prof van der Beugel. H.M. Queen Beatrix was guided by Prof van Dongen through the exhibition in the RAl Congress Center. Amsterdam's mayor Van Thijn (right) symbolically handed over the anniversary gift to clinical director Hulst. Listening to Prof van der Beugel's opening speech:f!.t.r. undersecretary ofstatefor Public Health, Dees, H.M. The Queen, Prof Borst, Van Thijn and Vroman. 16

18 For one day visitors could walkfreely through the operation room and be informed by NKi's staf! about diagnostic and therapeutic means and methods. Prof Rümke (middle) and Van Westen received royal decorations. Andfina/ly, Saturday night's party for NKi's employees. 17

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20 I Division of Cell Biology Head: E. Roos, Ph.D. Permanent academic staff: J.G. Collard, Ph.D., C.A. Feltkamp, Ph.D. Other academic staff: R.Brands, Ph.D.I, G. Habets, M.Sc. l, E.e. Homan M.Sc. I,2, G. La Rivière, M.Sc. l, F.F. Roossien, Ph.D.I Permanent technical staff: R. van der Kammen, I.V. van de Pavert, M. Pijnenburg Other technical staf[: A. de Boerl,2, D. de Rijkl, C.A. Schipperi, W.H.M. Scholtes l Students and trainee technicians: A. de Boer3,4, P. van de Berk3,4, A. Gilles 5,6, C.N. van der Maas7,8, NJ.H. Raat8,9, G. Stoopen5,8, J. Viëtor8,9, R.VogelsIO,ll, A.H.M. Wijnakkerl2,13 Notes I Funding: The Netherlands Cancer Foundation (KWF). 2 From July, School of Technicians, Delft. 4 Until June, School of Technicians, Etten-Leur. 6 Until May, School oftechnicians, Alkmaar. From September, University of Amsterdam. 10 Agricultural University, Wageningen. II Until March, University of Utrecht. 13 From October,