CANCEROLOGY AT UCL

2004
C A N C E R O L O G Y AT U C L
This booklet “Cancerology at UCL” has been implemented by the Research
Administration of the Université catholique de Louvain (UCL) under the
supervision of Professor Pierre Scalliet, President of the Cancer Center of the
academic hospital, Professor and Head of department of the Radiation
Oncology Unit of UCL.
Edited by D. Opfergelt (UCL ADRE) Dec. 2004
With the contribution of : O.Tirions, M. Plevoets, A. Distelmans, F. Kinard and N. Burteau
Cover : “Acute myeloblastic leukaemia” (Bone marrow aspirate stained by the May-Grünwald/Giemsa technique;
original magification : 460X)
Hematology unit, St Luc Hospital - Prof. Jean-Marie Scheiff
UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
Foreword
The main objective of this document is to catalyze the development of scientific research, to promote
synergies and to enrich the partnerships so as to develop the scientific assets an the industrial level and by
the way, improve the quality health care.
Besides the fact of being a public health problem of first order, cancer is a complex pathology which study requests
the collaboration of all the scientific disciplines. By essence, oncology is an “interdisciplinary” field because of the
interaction between specialists in the design and implementation of complex sequences of research and care : surgery,
drug, therapy, radiotherapy, rehabilitation, etc.
Many research projects performed at the Université catholique de Louvain and specially on its biomedical campus in
Brussels, are part of international networks.
This booklet presents the topics of interest, recent achievements and current developments of research teams
involved in cancerology. These topics are classified in nine categories, according to the main scientific or technological
approaches.
The last part gathers the different research centers and non profit associations established on the UCL campus and
devoted to cancer.
◗
PREVENTION AND EPIDEMIOLOGY
◗
MECHANISMS OF CANCER
◗
DIAGNOSTICS
◗
TREATMENT
◗
PSYCHO-ONCOLOGY
◗
RESEARCH CENTERS AND NON PROFIT ASSOCIATIONS
:
immunology - genetics
imaging
:
clinical studies
anti-cancer treatment
surgery
radiotherapy
3
UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
Content
A - PREVENTION AND EPIDEMIOLOGY
B.3 - Cytogenetic and molecular characterization
of T-cell proliferation in hypereosinophilic
patients.
23
A.1 - Risk assessment of carcinogenic
chemicals
9
CATHERINE E.T. SIBILLE
ALFRED BERNARD
B.4 - Identification of human tumor-specific
A.2 - Early detection and prevention of post
transplant lymphoproliferative diseases
antigens
11
THIERRY BOON, PIERRE VAN DER BRUGGEN, BENOÎT VAN DEN
EYNDE, PIERRE COULIE, ETIENNE DE PLAEN, BERNARD LETHE,
ALINE VAN PEL, CHRISTOPHE LURQUIN, FRANCIS BRASSEUR,
DANIÈLE GODELAINE
ETIENNE SOKAL, DOMINIQUE LATINNE, PATRICK GOUBAU, MONIQUE
BODEUS, BENOÎT KABAMBA MUKADI, YANNICK NIZET, FRANÇOISE SMETS
A.3 - Chemoprevention in liver cancer
25
13
B.5 - Analysis of the intracellular processing
YVES HORSMANS
of tumor antigens recognized by cytolytic
T lymphocytes
27
A.4 - Methodological support in epidemiology
and biostatistics applied to research in cancer
BENOÎT VAN DEN EYNDE
15
ANNIE ROBERT, RENÉ TONGLET
B.6 - Mechanisms of tumor resistance to the immune
system and development of a mouse model of
A.5 - Genetic profile of breast cancers : implication
in preventive and predictive medicine.
inducible melanoma
29
17
BENOÎT VAN DEN EYNDE
CATHERINE E.T.SIBILLE, MARTINE BERLIÈRE, CHRISTINE GALANT
B.7 - Aristolochic acid and ochratoxin A : etiological
factors of Balkan endemic nephropathy and
associated urothelial tumors
B - MECHANISMS OF CANCER
31
JEAN-PIERRE COSYNS
B.1 - Regulation of membrane trafficking and
motility by oncogenes
B.8 - AMP-activated protein kinase, a new potential
19
regulator of cytoskeleton organization : role in cell
PIERRE COURTOY
proliferation and/or differentiation.
B.2 - Mechanisms that regulate the migration of
brain cells in vitro and in vivo
LOUIS HUE, MARK RIDER
21
ANDRÉ M. GOFFINET
5
33
B.9 - Mammalian antioxidant enzymes
◗ DIAGNOSTICS
35
BERNARD KNOOPS, JEAN-PAUL DECLERCQ, JEAN-FRANÇOIS REES
D. IMAGING
B.10 - Mechanisms involved in apoptosis induced
by anticancerous drugs
D.1 - Rigid registration of PET, CT and
37
MR modalities for radiotherapy planning and
MARIE-PAULE MINGEOT-LECLERCQ
dense deformation field estimation for brain
intra-operative images registration
B.11 - Hox transcription factors and cancer
RENÉ REZSOHAZY
39
53
BENOÎT MACQ
D.2 - Functional magnetic resonance (NMR, EPR)
◗ DIAGNOSTICS
spectroscopy and imaging in tumors
55
BERNARD GALLEZ
C. IMMUNOLOGY – GENETICS
D.3 - Anatomic and functional imaging of liver
tumors
C.1 - Genetic analysis of brain tumours
41
BERNARD VAN BEERS
MIIKKA VIKKULA, CATHERINE GODFRAIND
57
C.2 - Characterization of malignant hemopathies
by molecular and flow cytometry
43
◗ TREATMENT
DOMINIQUE LATINNE, JEAN-LUC VAERMAN, VÉRONIQUE DENEYS
C.3 - Assays of tumor markers
E. CLINICAL STUDIES
45
MARIANNE PHILIPPE, PHILIPPE DE NAYER
E.1 - Academic clinical trials in medical
C.4 - Characterization of acute leukemias by gene
oncology
59
expression analysis : comparison of molecular and
JEAN-PASCAL MACHIELS, JEAN-FRANÇOIS BAURAIN
immunological approaches ; impact on diagnosis
and prognosis.
47
E.2 - Clinical studies in hematology
61
PASCALE SAUSSOY, DOMINIQUE LATINNE, AUGUSTIN FERRANT
AUGUSTIN FERRANT, LUCIENNE MICHAUX, ERIC VAN DEN NESTE
C.5 - Immunodiagnosis of paraneoplastic
neurological disorders
E.3 - Clinical studies in hematology :
49
Multiple myeloma, Hodgkin’s lymphoma
63
CHRISTIAN SINDIC
AUGUSTIN FERRANT, LUCIENNE MICHAUX, ERIC VAN DEN NESTE
C.6 - Development of new molecular based
diagnostic strategies in prostate cancer.
51
F. ANTI-CANCER TREATMENT
BERTRAND TOMBAL, JEAN LUC GALA
F.1 - Therapeutic vaccination of cancer patients
with tumor specific antigens
THIERRY BOON, MARIE MARCHAND, NICOLAS VAN BAREN
6
65
UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
◗ TREATMENT
F.2 - Isolation and structure determination of
active compounds from plants used in traditional
medicine to treat different forms of cancers.
Analysis of the mode of action.
G. SURGERY
67
JOËLLE QUETIN-LECLERCQ
G.1 - Cryopreservation of ovarian cortex removed
before chemotherapy allows the restoration of
F.3 - The tumor vascularity : bases for adjuvant
ovarian function after orthotopic
strategies to conventional anti-tumor treatments
and anti-angiogenic approaches.
autotransplantation
81
69
JACQUES DONNEZ, JEAN-LUC SQUIFFLET, PASCALE JADOUL,
CÉLINE PIRARD, CHRISTINE WYNS, DOMINIQUE DEMYLLE, MARIEMADELEINE DOLMANS, BELEN MARTINEZ-MADRID,
ANNE VAN LANGENDONCKT
OLIVIER FERON
F.4 - Phase II study of utilisation of a recombinant
chimeric protein in patients with recurrent
progressive glioblastoma
G.2 - Limb salvage in tumor surgery with massive
71
bone allografts
CHRISTIAN RAFTOPOULOS
83
CHRISTIAN DELLOYE, OLIVIER CORNU, XAVIER BANSE
F.5 - Cancer immunotherapy-clinical trials
73
JEAN-FRANÇOIS BAURAIN, JEAN-PASCAL MACHIELS
◗ TREATMENT
F.6 - Lung cancer - mesothelioma clinical research in diagnosis - active treatment supportive care
H. RADIOTHERAPY
75
DANIEL RODENSTEIN, PHILIPPE COLLARD, GIUSEPPE LIISTRO,
THIERRY PIETERS
H.1 - Biological dosimetry and radiobiological
calibration of clinical hadron beams
85
JOHN GUEULETTE
F.7 - Development of new calcium-based strategies
to induce apoptotic cell death in prostate cancer
cell lines.
H.2 - Radiobiology of light ions
ANDRÉ WAMBERSIE
BERTRAND TOMBAL, PHILIPPE GAILLY
F.8 - Breast cancer
87
77
H.3 - Molecular imaging for radiotherapy
89
79
VINCENT GRÉGOIRE
JACQUES DONNEZ, MARTINE BERLIERE, JEAN-LUC SQUIFFLET,
ISABELLE LECONTE, LATIFA FELLAH, CHRISTINE GALANT, CATHERINE
SIBILLE, BÉNÉDICTE BAYET
H.4 - Treatment planning of intensity modulated
radiotherapy (IMRT) for head and neck cancer :
optimization of the treatment technique
and validation by measurements and
Monte Carlo simulations
MILÀN TOMSEJ, NATHALIE DE PATOUL, STEFAAN VYNCKIER,
VINCENT GRÉGOIRE
7
91
I. PSYCHO-ONCOLOGY
J.8 - European Oncology Nursing
Society (EONS)
I.1 - Psycho-oncology - Physician patient
relationships - Communication skills training -
115
J.9 - The U.S. National Cancer Institute Liaison
Quality of life - Professionnal stress - Burnout
93
Office (NCI L.O.)
117
KEY WORDS INDEX
119
CHRISTINE REYNAERT, PIERRE SCALLIET, YVES LIBERT
I.2 - The question of meaning in front of cancer.
Biographical approach.
95
JEAN-LUC BRACKELAIRE, MICHEL LEGRAND, PATRICK DE NEUTER
I.3 - Coping styles, anxio-depression,
alexithymia and evolution of breast cancer
97
VINCENT JADOULLE
J. RESEARCH CENTERS & NON-PROFIT
ASSOCIATIONS
J.1 - Cancer Centre at UCL and Saint Luc
academic hospital
101
J.2 - The Brussels Branch of the Ludwig Institute
for Cancer Research (LICR)
103
J.3 - European Society for Therapeutic
Radiology and Oncology (ESTRO)
105
J.4 - Federation of European Cancer Societies
(FECS)
107
J.5 - European Organisation for Research and
Treatment of Cancer (EORTC)
109
J.6 - European society of surgical
oncology (ESSO)
111
J.7 - International Life Sciences Institute
(ILSI Europe)
113
8
UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
A 1
Risk assessment of carcinogenic chemicals
SENIOR SCIENTIST :
Alfred BERNARD
Research Field and Subjects
STAFF
Total : 5
The research team conducts a variety of studies in populations
exposed to toxic chemicals in the environment or the workplace.
The objectives of these studies include the evaluation of exposure, the identification of groups at risk, the derivation of safe
exposure levels or the validation of non invasive biomarkers of
exposure or early effects.
These studies are currently focused on food contaminants and
air pollutants.
KEY WORDS FOR R&D
air pollutants
biomarkers
dioxins
food contaminants
heavy metals
PCBs
risk assessment
Products and Services
SENIOR SCIENTIST
Alfred BERNARD
[email protected]
Tel. 32(0)2-764 39 34
Expertise in health risk assessment in incidents of food contamination or environmental pollution.
Biomonitoring of exposure.
WEB SITE
www.md.ucl.ac.be/toxi
Representative References
BERNARD A. Overview of epidemiological studies on the carcinogenicity of metals. In : Carcinogenicity of Inorganic Substances.
Risks from Occupational Exposure. Ed. J.H. Duffus. Royal Society of
Chemistry, Cambridge, UK., pp. 146 - 160, 1997.
BERNARD A., HERMANS C., BROECKAERT F., DEPOORTER G.,
DECOCK A., HOUINS G. Food contamination by PCBs and dioxins.
Nature 40, 231-232, 1999.
BERNARD A., BROECKAERT F., DEPOORTER G., DE COCK A.,
HERMANS C., SAEGERMAN C., HOUINS G. The Belgian
PCB/dioxin incident: analysis of the food chain contamination and
health risk evaluation. Environmental Research 88, 1-18, 2002.
Funding Sources
European Union
National Institute of Health, USA
Fonds national de la recherche scientifique (FNRS)
Brussels-Capital Region and Walloon Region
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
A 2
Early detection and prevention of post transplant
lymphoproliferative diseases
SENIOR SCIENTISTS :
Etienne SOKAL
Dominique LATINNE
Patrick GOUBAU
Monique BODEUS
Benoît KABAMBA MUKADI
Yannick NIZET
Françoise SMETS
re detected and quantified by counting the number of positive
spots of interferon gamma detected by ELISA.
Research Field and Subjects
Post Transplant Lymphoproliferative Disease (PTLD) is a common
complication following solid organ transplantation. PTLD is related to Epstein Barr Virus (EBV) infection. The virus is usually
transmitted during the transplant procedure, via the graft itself
or the blood products. The virus infects B lymphocytes and causes their clonal proliferation-immortalization. This clonal expansion is normally controlled by reactive T lymphocytes, but these
cells are inhibited by the immune suppression. PTLD can affect
all organs and causes massive lymphoproliferation with severe
complications which may cause patient’s death.
We have established that viral load > 20000 copies per ml and
anti-EBV T lymphocytes < 1/mm3 is at high risk of EBV development, while patients who have more than 1 anti-EBV T lymphocyte / mm3 do not develop PTLD, even in presence of high
viral load. This allows to better anticipate risk of PTLD, accordingly adapt immunosuppression, and restore appropriate
immunosuppression as soon as patient’s anti EBV cellular immunity appears, before onset of rejection.
Treatment includes arrest of immunosuppression, and possibly
anti- CD20 monoclonal antibodies. Chemotherapy is used only
in the true malignant forms, i.e. Burkitt or Hodgkin like syndromes. Arrest of immunosuppression may lead to graft rejection.
It is therefore important to have tools allowing to detect the
right moment to decrease and/or to restore the immunosuppression load.
Products and Services
EBV infection occurs usually in the first three months following
transplant. Detection by serology is impaired due to poor antibody response in these immunocompromized patients. We
have therefore set up detection of EBV primary infection by EBV
PCR and real time PCR to quantify viral load.
Main Equipment
Viral load is a risk factor for PTLD. Our team has demonstrated
that the risk of PTLD is not uniquely related to viral load, but
also to the lack of anti EBV CD8 specific cells. These cells are
currently detected by ELISPOT technique.
Representative References
Real time PCR for EBV
Elispot technique
Cell culture
Clinical management
TaqMan real time PCR
FACS
SOKAL E. M. and al. Epstein-Barr virus serology and EpsteinBarr virus-associated lymphoproliferative disorders in pediatric
liver transplant recipients. Transplantation X 56,1993, 1394-98.
SOKAL E. M. and al. Early signs and risk factors for the
increased incidence of Epstein Barr virus related post transplant
lymphoproliferative diseases in paediatric liver transplant recipients
treated with Tacrolimus. Transplantation X 64.10, 1997, 1438-42.
SMETS F. and al. Indications and results of chemotherapy in
children with posttransplant lymphoproliferative disease after
liver transplantation. Transplantation X 69.5, 2000, 982-84.
SMETS F. and al. Characteristics of Epstein-Barr virus primary
infection in pediatric liver transplant recipients. J. Hepatol. 32.1,
2000, 100-04.
Peripheral blood mononuclear cells of the patients are first cultured and infected by EBV in vitro, as soon as the transplant
indication is established.
Following transplant, and after appearance of primary EBV
infection (= first positive PCR), viral load is monitored by real
time PCR. ELISPOTS are then performed by detecting interferon
gamma release in vitro by the own patient’s T lymphocytes in
presence of his/her previously cultured B lymphocytes infected
by EBV. Presence of anti EBV specific T lymphocytes is therefo-
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11
SMETS F. and al. Characteristics of Epstein-Barr virus primary
infection in pediatric liver transplant recipients. Journal of
Hepatology 32, 2000, 100-04.
SMETS F. and al. Ratio between Epstein-Barr viral load and
virus specific T-cell response as a predictive marker of posttransplant lymphoproliferative disease. Hepatology Mosby 34.4
pt 2 of 2, 2001, 291A Abstract 745-291A.
SMETS F. and al. Ratio between Epstein-Barr viral load and
anti Epstein-Barr virus specific T-cell response as a predictive
marker of posttransplant lymphoproliferative disease.
Transplantation X 73.10, 2002, 1603-10.
STAFF
Total : 10
KEY WORDS FOR R&D
Epstein Barr Virus EBV
immunosuppression
pediatric transplantation
post transplant lymphoproliferative diseases
SENIOR SCIENTISTS
Etienne SOKAL
[email protected]
Tel. 32(0)2 764 13 87
Awards
Dominique LATINNE
[email protected]
Tel. 32(0)2 764 34 30
Award 2002 Glaxo SmithKline - infectious diseases
Patrick GOUBAU
[email protected]
Tel. 32(0)2 764 34 20
Funding Sources
Grant from Télévie, Fonds de la recherche scientifique médicale
Monique BODEUS
[email protected]
Tel. 32(0)2 764 34 20
Partnership
Benoît KABAMBA MUKADI
[email protected]
Tel. 32(0)2 764 34 21
Henogen
Yannick NIZET
[email protected]
Tel. 32(0)2 764 35 33
Françoise SMETS
[email protected]
Tel. 32(0)2 764 13 87
WEB SITES
www.pedi.ucl.ac.be
www.imex.ucl.ac.be
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
A 3
Chemoprevention in liver cancer
SENIOR SCIENTIST :
Yves HORSMANS
Research Field and Subjects
Representative References
The aim of the project is to assess the potential role of drugs in
the chemoprevention of primary liver cancer, namely hepatocellular carcinoma (HCC).
STÄRKEL P., HORSMANS Y., SEMPOUX Y., DE SAEGER C.,
WARY J., LAUSE P., MAITER D., LAMBOTTE L. After portal
branch ligation in rat, nuclear factor kB, interleukin 6, signal
transducers and activators of transcription 3, c-fos, c-myc, and
c-jun are similarly induced in the ligated and nonligated lobes.
Hepatology 29, 1999, 1463-1470.
STARKEL P., LAMBOTTE L., SEMPOUX C., DE SAEGER C.,
SALIEZ A., MAITER D., HORSMANS Y. After portal branch ligation in rat, cellular proliferation is associated with selective
induction of c-Ha-ras, p53, Cyclin E and Cdk2. Gut 49, 2001,
119-130.
PICARD Ch., STARKEL P., SEMPOUX Ch., SALIEZ A., LEBRUN
V. and HORSMANS Y. Molecular mechanisms of apoptosis in
the liver of rats after portal branch ligation with and without
retrorsine. Laboratory investigation, 2004, in press.
The two drugs that are studied are pioglitazone, a PPARgamma
agonist, which has shown interesting results in in vitro models;
and lanreotide, a somatostatine analogue, studied in vitro and
in vivo, as in human population. The effect of the drugs is analyzed in a sequential carcinogenic animal model. Focus is made
on the inhibitory effect on the apparition of early pre-neoplastic and neoplastic nodules in the rat liver, analysed by immunohistochemistry and western blot. Analysis of the proliferative
and apoptotic events is made by western blot and immunohistochemistry.
Preliminary results show that pioglitazone is efficient in the
reduction of the size of pre-neoplastic nodules in this model, on
the contrary to lanreotide, which decreases the size of the
nodules, though non significantly. The mechanisms of this
action are not fully understood at the present time, but preliminary data show differential alteration of proliferation and
apoptosis. Further analyses will be performed to determine the
effect of pioglitazone and lanreotide on the balance of proliferation and apoptosis in preneoplastic foci and surrounding liver
parenchyma.
Funding Sources
Proper funding
The effect of the two drugs will also be assessed in rats having
induced cirrhosis, to look at the preventive effect on neoplastic
nodules in an already pre-neoplastic organ. This study is
ongoing.
Main Equipment
Western Blot
Real-time PCR
Immunohistochemistry
Flow Cytometry
Laboratory animal handling and surgery
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13
STAFF
Total : 4
KEY WORDS FOR R&D
chemoprevention
gastroenterology, liver
liver tumors
SENIOR SCIENTIST
Yves HORSMANS
[email protected]
Tel. 32(0)2 764 28 20
WEB SITE
http://www.md.ucl.ac.be/gaen
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
A 4
Methodological support in epidemiology and biostatistics
applied to research in cancer
SENIOR SCIENTISTS :
Annie ROBERT
René TONGLET
“Progression-free survival” and “Time to progression” are
valuable alternative definitions of response to treatment, since
a recent harmonization of guidelines has been proposed to
assess the progression of cancer in solid tumors (RECIST
Therasse P. and al. J. Nat. Cancer Inst. 2000, 92:205).
Progression-free survival can be estimated using retrospective
analyses of phase III trials, in order to derive P0 and P1 values.
Such analysis has been done for soft tissue sarcomas (Van
Glabbeke and al. Eur. J. Cancer 2002, 38:543-549). We plan to
extend those analyses to other solid tumors such as lung cancers, bladder cancers, or breast cancers.
Efficiency and inefficiency estimations derived from such analyses
may be sensitive to loss-to-follow data, to left rather than right
censored data, or to variations in the cancer progression assessment. Sensitivity analyses will be conducted, together with the
consequences on size computations in designing phase II trials.
Research Field and Subjects
Epidemiology and biostatistics can be applied to cancer
research especially in the study of cancer incidence by products
or in the estimation of anticancer drugs efficiency.
Cancer incidence and mortality among cohorts
of pesticides producing workers, etc.
Epidemiological studies are conducted in order to assess if there
is an excess of cancer cases in current and ex-workers from a
plant and to identify workplace exposures which may explain
such a demonstrated excess.
Vital- and cancer status according to the ICD10 codes (international classification of diseases) are established for all workers, and
life table analyses are conducted, using the Belgian mortality and
the regional (Flanders, French community) registry of cancers.
Age- and sex standardised mortality (SMR) and incidence (SIR) ratios
are stratified by duration of employment, job title, time since first
employment, and time between the end of the job at the plant for
workers who left the plant. These occupational data are used as
latency- and intensity surrogates for testing the hypothesis of a relationship between occupational exposure and cancer development.
Products and Services
Methodological support on a contractual basis.
Main Equipment
Progression-free survival in solid tumors:
qualities of estimators of clinical efficiency
and inefficiency for designing Phase II trials.
Statistical and Epidemiological softwares: BMDP, The SAS System,
SPSS, Splus, EPIinfo, EPICURE.
Phase II trials play a key role in the development of new potential anticancer drugs because they are crucial in deciding whether or not proceeding to a phase III trial.
Phase II trials are conducted in order to assess the clinical efficiency (P1) or the clinical inefficiency (P0) of new treatments.
The number of patients enrolled in a phase II trial closely
depends on P0 and P1 values. An underestimation of P1 can
lead to rejection of an active treatment and an overestimation
of P0 can lead to keep a useless treatment. The classical definition of P0 and P1 is based on death rates because mortality is
an objective measure of response to therapy. Recent developments in anticancer agents are however oriented to antitumoral drugs, and consequently call for a new definition of early
response to therapy, taking into account a decrease in the size
of cancer lesions or a stabilization of disease.
Funding Sources
Industry
Occupational health services
Competitive research funds
Partnership
European Organization for Research and Treatment of Cancer
(EORTC).
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STAFF
Total : 6
KEY WORDS FOR R&D
applied statistics
clinical trials, drug evaluation
epidemiology
health- and medical statistics
occupational medicine, preventive medicine
pharmacotherapy
SENIOR SCIENTISTS
Annie ROBERT
[email protected]
Tel. 32 (0)2 764 33 21
René TONGLET
[email protected]
Tel. 32 (0)2 764 33 23
WEB SITE
http://rch.adre.ucl.ac.be/browse/list_alpha/EPID
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16
UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
A 5
Genetic profile of breast cancers : implication in preventive
and predictive medicine
SENIOR SCIENTISTS :
Catherine E.T. SIBILLE
Martine BERLIÈRE
Christine GALANT
the evaluation of early anticancer treatment response. In addition, the specific technological objectives are the generation
and the standardization of low-density DNA chips (expression
arrays).
Research Field and Subjects
In the western countries, breast cancer is the most frequent
female cancer. Its incidence is increasing and about 10 %
women will develop a breast carcinoma in their lifetime.
However, mortality does not progress proportionally, due to
advances in screening and treatment.
Since the cloning (discovery) of the BRCA1/BRCA2 genes (19941995) both predisposing to hereditary breast and /or ovarian cancers, we have developped in collaboration with the Psychological
Service a model of Oncogenetics clinics specially dedicated to the
predictive or symptomatic genetic diagnosis. Initially inspired
by the “good practices” in use for the predictive diagnosis of
Huntington disease, this clinic was soon afterwards individualized,
based on tumour screening and preventive treatment. The first
belgian BRCA1 and BRCA2 mutations were also obtained and
were found to be present in approximatively 7% of the breast cancer familial cases.
Main Equipment
DNA Sequencer, PCR blok Electrophoresis
Low density expression arrays
Products and Services
Clinical and fundamental research
Diagnostic and therapeutic development
Expertise in low density expression microarrays
Genetic counseling
Preventive Medicine
Psychology
Cancer Epidemiology
The first epidemiological trial in which our oncogenetics clinic was
involved was part of the “International BRCA1/2 Carrier Cohort
Study” (IBCCS). To illustrate the interest of evaluating environmental factors in this high risk population, this cohort has allowed
us to report recently about the increased sensitivity to low-dose
ionizing radiation in BRCA1/2 carriers.
In 2002, we initiated a second study funded by the CEE
and became part of the “BreastMed consortium”. This international study entitled “Genetic profile of breast cancers
in Mediterranean countries : implications in preventive and
predictive medicine” is conducted in collaboration with three
mediterranean countries and France. In the mediterranean
countries, breast cancer represents also an important public
health problem, but its prognosis is worse and it seems to express specific biological features. The BreastMed project aims at
comparing the genetic caracteristics of breast tumours in
Belgium and France, on one hand, in Morocco, Tunisia and
Lebanon, on the other hand. One of its important clinical objectives is to examine the contribution of environmental factors
different on both sides of the Mediterranean Sea, to the apparition of the disease in women exhibiting the same BRCA1/2
mutation. It should also allow a better tumour sub-classification
and the discovery of new prognosis markers, in particular for
Representative References
C. SIBILLE, A. JOOS DE TER BEERST, O. FROMENT, Y.
GILLEROT. Prise en charge des familles à risque génétique de
cancer: attitude en Belgique. Eurocancer, John Libbey, Eurotext,
Paris, 179-180, 1996.
C. SIBILLE, A. JOOS DE TER BEERST, O. FROMENT.
BRCA1/BRCA2 mutations in Belgian families with history of
breast/ovary cancer. Journal of European Cancer Prevention, 7
suppl. 1, 53-55, 1998.
C. SIBILLE, A. JOOS. D’une pierre, deux coups! A propos d’un
modèle de consultation en oncogénétique. Le Journal de
Cancer et Psychologie, December, 33, 1999.
Y.J. BIGNON, P. DESSENNE, C. SIBILLE, A. JOOS, A.
LEHMANN. L’impact psychique de la consultation d’oncogénétique sur l’entourage familial. Bulletin de la Société Française de
Psycho-Oncologie, 27: 10-12, 2000.
D. GOLDGAR, C. BONNARDEL, H. RENARD, O. YAQOUBI and
the IBCCS collaborators Group (belgian center participant C.
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17
Partnership
SIBILLE). The International BRCA1/2 Carrier Cohort Study : purpose, rationale, and study design. Breast Cancer Res., 2, 6 :
E010, 2000.
N. ANDRIEU, D. F. EASTON, J. CHANG-CLAUDE, M.A.
ROOKUS, R. BROHET, E. CARDIS, A. C. ANTONIOU, S. PEOCK,
C. NOGUES, F.E. VAN LEEUWEN, D. GOLDGAR and the IBCCS
collaborators group (belgian participant C. SIBILLE), EMBRACE,
GEO-HEBON, GENEPSO. Low-dose ionizing radiation significantly increases the risk of breast cancer among BRCA mutation
carriers in the IBCCS study (in press).
M. LACROIX, G. LECLERCQ, on behalf of BreastMed
Consortium (belgian center participant C. SIBILLE). The “portrait” of hereditary breast cancer. Breast cancer research and
treatment (in press).
W. MAHFOUTH, N. BOUAOUINA, Y.J. BIGNON, N.
UHRHAMMER, L. CHOUCHANE, and Breast Med. Consortium :
N. ZAMMATTEO, V. BERTHOLET, F. DE LONGUEVILLE, Y.J.
BIGNON, J. REMACLE, A. MEGARBANE, N. BEN JAAFAR, A.
SEFIANI, L. CHOUCHANE, A. BEN AMMAR-EL GAIED, G.
LECLERCQ, M. LACROIX, C. SIBILLE, V. VIDAL. BRCA1 germline
mutations in Tunisian families with hereditary breast cancer.
INCTR Annual Meeting, Cairo, 2004.
Breast Med. Consortium : N. ZAMMATTEO, V. BERTHOLET, F.
DE LONGUEVILLE, Y.J. BIGNON, J. REMACLE, A. MEGARBANE,
N. BEN JAAFAR, A. SEFIANI, L. CHOUCHANE, A. BEN AMMAREL GAIED, G. LECLERCQ, M. LACROIX, C. SIBILLE, V. VIDAL.
Gene expression profiling of breast tumors in european and
mediterranean countries. INCTR Annual Meeting, Cairo, 2004.
ULB, Institut Bordet, Bruxelles, Belgium.
FUNDP, Namur, Belgium.
Clermont-Ferrand university, France.
Mediterranean countries : Morocco, Tunisia, Lebanon.
IARC, Lyon, France.
STAFF
Total : 5
KEY WORDS FOR R&D
gynecology
medical genetics
molecular biology
pathology
SENIOR SCIENTISTS
Catherine E.T. SIBILLE
[email protected]
Tel. 32 (0)2 764 53 82
Martine BERLIÈRE
[email protected]
Tel. 32 (0)2 764 95 01
Christine GALANT
[email protected]
Tel. 32 (0)2 764 17 88
Patents
WEB SITES
The two spin-offs (Diagnogen, France and EAT-Eppendorff,
Namur, Belgium) associated with the CEE project, are in process
of patenting their “breast cancer” low density arrays.
http://www.cjp.fr/breastmed
http://rch.adre.ucl.ac.be/browse/list_alpha/GMED
http://rch.adre.ucl.ac.be/browse/list_alpha/ANPS
Funding Sources
Main source of funding : EEC
Fédération belge contre le cancer
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18
UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
B 1
Regulation of membrane trafficking and motility
by oncogenes
SENIOR SCIENTIST :
Pierre COURTOY
COURTOY, AND M.F. VAN DEN HOVE. The endocytic catalysts,
Rab5a and Rab7, are tandem regulators of thyroid hormone
production. Proc. Natl. Acad. Sci. USA 99, 8277-8282, 2002.
PLATEK A., METTLEN M., CAMBY I., KISS R., AMYERE M. and
COURTOY P.J. v-Src accelerates spontaneous motility via phosphoinositide 3-kinase, phospholipase C and phospholipase D,
but abrogates chemotaxis in Rat-1 and MDCK cells. J. Cell. Sci.
2004.
Research Field and Subjects
This research group addresses how the paradigmatic oncogenes, v-Src and K-Ras, subvert normal signal transduction pathways, resulting in altered plasma membrane dynamics. As endpoint, we focus on accelerated endocytosis and motility, two
properties directly linked to cellular invasion.
In these studies, thermosensitive v-Src mutants are amply used.
Key signalling molecular relays are identified and their hierarchy
is established using pharmacological inhibitors, dominant-positive and -negative constructs. Their localization is defined by
analytical subcellular fractionation combined with confocal
imaging of fixed and living cells.
Pierre Courtoy was awarded the “Francqui Chair” 2004 at
the Facultés Universitaires de Namur, Medical school, Belgium.
Products and Services
Funding Sources & Partnership
Awards
Fonds national de la recherche scientifique (FNRS)
Fondation pour la recherche scientifique médicale (FRSM)
Télévie
Molecular tracking in living and fixed cells
Cell motility
Main Equipments
Electron microscope
Confocal microscope
Life-cell imaging microscope
Ultracentrifuge
Microinjection
Representative References
A. VEITHEN, Ph. CUPERS, P. BAUDHUIN, AND P.J. COURTOY.
v-Src induces constitutive macropinocytosis in rat fibroblasts. J.
Cell. Sci. 109, 2005-2012, 1996.
M. AMYERE, B. PAYRASTRE, A. VEITHEN, P. VAN DER
SMISSEN, AND P.J. COURTOY. Constitutive macropinocytosis in
oncogene-transformed fibroblasts depends on permanent
combined activation of phosphoinositide 3-kinase and phospholipase C. Mol. Biol. Cell. 11, 3453-3467, 2000.
K. CROIZET-BERGER, C. DAUMERIE, M. COUVREUR, P.J.
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STAFF
Total : 12
KEY WORDS FOR R&D
cell biology
confocal microscopy
electron microscopy
endocytosis
fractionation
life-cell imaging
membrane
molecular biology
motility
proto(oncogenes)
SENIOR SCIENTIST
Pierre COURTOY
[email protected]
Tel. 32(0)2 764 75 69
WEB SITE
http://rch.adre.ucl.ac.be/browse/list_alpha/CELL
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20
UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
B 2
Mechanisms that regulate the migration of brain cells in
vitro and in vivo
SENIOR SCIENTIST :
André M. GOFFINET
Research Field and Subjects
Products and Services
This laboratory investigates the basic mechanisms that regulate
the migration of brain cells during normal and abnormal development.
Molecular biology
Immunohistochemistry
Histotypic culture of vibratome sections
Transgenic mouse techniques
Like other cells, brain cells migrate by leading extension, a step
that is mostly actin-dependent, followed by nucleokinesis,
which appears to depend on microtubules.
Main Equipment
Cell culture
Standard molecular biology
Standard histology
Transgenic mice
A new technique to study brain cell migration has been set up
and is widely used in order to define basic mechanisms.
Two projects are pursued in order to take advantage of that
new technology.
Representative References
First, we target candidate signal transduction pathways using
small molecular weight inhibitors, such as Iressa or Gleevec, in
order to define which pathways are implicated in brain cells
migration. This allowed us to identify a key role of Src family
kinases, atypical PKCs and a few others.
MEYER G., SCHAAPS J.P., MOREAU L., GOFFINET A.M. (2000)
Embryonic and early fetal development of the human neocortex. J. Neurosci., 20: 1858-1868.
BAR I., LAMBERT DE ROUVROIT C., GOFFINET A.M. (2000)
The evolution of cortical development: An hypothesis based on
the role of the reelin signaling pathway. Trends Neurosci., 23:
633-638.
HEVNER R.F., SHI L., HSUEH Y-P., SHENG M., SMIGA S.,
BULFONE A., GOFFINET A.M., RUBENSTEIN J.L.R. (2000) Tbr1
regulates differentiation of the preplate and layer 6. Neuron,
29: 353-366.
LAMBERT DE ROUVROIT C., GOFFINET A.M. (2001) Neuronal
migration. Mech. Dev. 105: 47-56.
JOSSIN Y., GOFFINET A.M. (2001) Reelin does not directly
influence axonal growth. J. Neurosci. 21, RC183: 1-4.
TISSIR F., DE BACKER O., GOFFINET A.M., LAMBERT DE
ROUVROIT C. (2002) Developmental expression profiles of Celsr
(Flamingo) genes in the mouse. Mech. Dev., 112: 157-160.
TISSIR F., BAR I., GOFFINET A.M., LAMBERT DE ROUVROIT C.
(2002) Expression of the ankyrin repeat domain protein 6 gene
(Ankrd6) during mouse brain development. Dev. Dyn. 224:
465-469.
BAR I., TISSIR F., LAMBERT DE ROUVROIT C., DE BACKER O.,
GOFFINET A.M. (2003) The Gene Encoding Disabled-1 (Dab1),
The second project is in collaboration with the National Cancer
Institute (NIH), which developed a diversity set of more than
2000 leading compounds that is currently under evaluation
using our in vitro system. Thus far, a first pass of this screening
has resulted in the identification of about 20 compounds that
remain to be better defined.
A second approach we pursue is to use transgenic mouse techniques in order to assess the role of some genes in brain cells
migration.
We are currently building a knock-in mouse in which the reporter gene EGFP and the recombinase Cre are targeted to the p73
locus, an oncogene of the p53 family that is important for
transcriptional regulation during brain development as well as
in some mechanisms of neoplastic growth. Using homologous
recombination in mouse ES cells, we have also inactivated a
new gene named Celsr3 that codes a protocadherin of the
Flamingo family implicated in epithelial planar cell polarity.
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the Intracellular Adaptor of the Reelin Pathway, Reveals
Unusual Complexity in Human and Mouse. J. Biol. Chem. 278:
5802-5812.
MEYER G., LAMBERT DE ROUVROIT C., GOFFINET A.M.,
WAHLE P. (2003) Dab1 mRNA and protein expression in developing human cortex. Eur. J. Neurosc. 17: 517-523.
JOSSIN Y., BAR I., IGNATOVA N., TISSIR F., LAMBERT DE
ROUVROIT C., GOFFINET A.M. (2003) The reelin signaling pathway : Some recent developments. Cereb. Cortex 13: 627-633.
TISSIR F., GOFFINET A.M. (2003) Reelin and brain development. Nat. Rev. Neurosci. 4: 496-505.
BOCK H.H., JOSSIN Y., LIU P., FORSTER E., MAY P., GOFFINET
A.M., HERZ J. (2003) PI3-Kinase interacts with the adaptor protein Dab1 in response to Reelin signaling and is required for
normal cortical lamination. J. Biol. Chem. 278 : 38772-9.
JOSSIN Y., OGAWA M., METIN C., TISSIR F., GOFFINET A.M.
(2003) Inhibition of SRC family kinases and non-classical protein
kinases C induces a reeler-like malformation of cortical plate
development. J. Neurosci. 23 : 9953-9.
JOSSIN Y., IGNATOVA N., HIESBERGER T., HERZ J., LAMBERT
DE ROUVROIT C., GOFFINET A.M. (2003) The central fragment
of Reelin, generated by proteolytic processing in vivo, is critical
to its function during cortical plate development. J. Neurosci.
24: 514-521.
IGNATOVA N., SINDIC C.J.M., GOFFINET A.M. (2004)
Characterization of the various forms of the Reelin protein in
the cerebrospinal fluid of normal subjects and in neurological
diseases. Neurobiol Dis.
TISSIR F., CHUAN-EN WANG; GOFFINET A.M. (2004)
Expression of the chemokine receptor Cxcr4 mRNA during
mouse brain development. Dev. Brain Res.
STAFF
Total : 8
KEY WORDS FOR R&D
cortical development
neuronal migration
reelin
slice culture
SENIOR SCIENTIST
André M. GOFFINET
[email protected]
Tel. 32 (0)2 764 73 86
WEB SITE
www.md.ucl.ac.be/dene
Funding Sources & Partnership
Fonds national de la recherche scientifique (FNRS), Belgium
Actions de recherche concertée (ARC), Belgium
Fondation Médicale Reine Elisabeth, Belgium
European Union
National Cancer Institute, USA
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
B 3
Cytogenetic and molecular characterization of T-cell
proliferation in hypereosinophilic patients
SENIOR SCIENTIST :
Catherine E.T. SIBILLE
Research Field and Subjects
Representative References
A study of regulatory pathways in lymphogenesis. Diagnostic
and prognostic implications
ROUFOSSE F., SCHANDENE L., SIBILLE C., KENNES B., EFIRA
A., COGAN E., GOLDMAN M. T-cell receptor-independent activation of clonal Th2 cells associated with chronic
hypereosinophilia. Blood, 1999, 94(3): 994-1002.
ROUFOSSE F., SCHANDENE L., SIBILLE C., WILLARD-GALLO
K., KENNES B., EFIRA A., GOLDMAN M., COGAN E. Clonal Th2
lymphocytes in patients with the idiopathic hypereosinophilic
syndrome. Br. J. Haematology, 2000, 109(3): 540-548.
LEROUX D., MUGNERET F., CALLANAN M., RADFORD-WEISS
I., DASTUGUE N., FEUILLARD J., LE MEE F., PLESSIS G.,
TALMANT P., GACHARD N., UETTWILLER F., PAGES M.P.,
MOZZICONACCI M-J., EDACHE V., SIBILLE C., AVET-LOISEAU
H., LAFAGE-POCHITALOFF M. CD4+, CD56+, DC2 acute
leukemia are characterized by recurrent clonal chromosomal
changes affecting major targets: a study of 21 cases by
the “Groupe Français de Cytogénétique Hématologique”.
Blood, 2002, 99 (11), 4154-415.
SIBILLE C., RAVOET M., ROUFOSSE F., SCHANDENE L.,
GOLDMAN M., WILLARD-GALLO K. 6q- is an early and persistant chromosomal aberration in 2 patients with hypereosinophilic syndrome leading to T-cell lymphoma. (submitted).
WILLARD-GALLO K., BADRAN B.M., RAVOET M., ROUFOSSE F.,
GOLDMAN M., BURNY A., SIBILLE C. Defect in gene transcription
potentially associated with the progression to T-cell lymphoma in
patients with hypereosinophilic syndrome (submitted).
In order to gain a better understanding of the mechanisms
involved in the transformation of the aberrant CD3–CD4+ Tcells in vivo, the HES (HyperEosinophilic Syndrome) patients
were tested for clonal chromosome aberrations and transcriptional gene expression profile.
For two patients, among different subclones, an early and
recurrent 6q interstitial deletion was found by using molecular
cytogenetics (Fluorescent In Situ Hybridization). Furthermore,
during the evolution in acute T-lymphoma of one patient, the
6q- clone was found overexpressed.
After FISH delimitation of the commonly deleted 6q segment, our
next goal was to identify the genes involved in this deletion and to
understand their interactions with the other genes located on
other chromosomes. This approach was made in collaboration by
using expression arrays (human A Affymetrix slides) in replicate.
We have found several candidate genes with tumour suppressive activity and we are presently confirming our results by
quantitative PCR (Taqman).
Our next experiments will focus on the other T-Lymphomas and
acute T-cell leukemias.
Funding Sources
Products and Services
Fonds national de la recherche scientifique (FNRS)
Télévie
Applied and fundamental research
Expertise in expression microarrays, molecular cytogenetics,
cytogenetics
Main Equipment
Fluorescent and light microscopes, CGH Metasystem analyser,
PCR blok
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STAFF
Total : 3
KEY WORDS FOR R&D
cytogenetics
hematology
molecular biology
SENIOR SCIENTIST
Catherine E.T. SIBILLE
[email protected]
Tel. 32(0)2 764 53 82 or 52 20
WEB SITE
http://rch.adre.ucl.ac.be/browse/list_alpha/GMED
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
B 4
Identification of human tumor-specific antigens
SENIOR SCIENTISTS :
Thierry BOON
Pierre VAN DER BRUGGEN
Benoît VAN DEN EYNDE
Pierre COULIE
Etienne DE PLAEN
Bernard LETHE
Aline VAN PEL
Christophe LURQUIN
Francis BRASSEUR
Danièle GODELAINE
Research Field and Subjects
Main Equipment
Most human tumors bear antigens that are recognized by cytolytic T lymphocytes (CTL) and that are strictly tumor-specific.
Stimulating the immune system against these antigens may
lead to a selective elimination of the cancer cells. The usefulness
of these tumor-specific antigens is presently evaluated in clinical trials involving the vaccination of cancer patients.
The genes coding for the tumor-specific antigens have been
identified by transfection and detection of the transfectants by
the CTLs. Several tumor-specific antigens are encoded by
human MAGE genes. Genes of this family are silent in most
healthy tissues (except male germ line and placental trophoblast cells), but are activated in tumors of different histological
types. Activation of the MAGE genes results from a demethylation of their promoter that correlates with genome-wide demethylation. Since a large number of epitopes encoded by MAGE
genes have now been identified, every cancer patient whose
tumor expresses a MAGE gene should have at least one HLA
molecule to present an epitope derived from a MAGE protein.
We have identified additional human gene families named,
BAGE, GAGE and LAGE that present the same pattern of
expression as MAGE genes. They also encode tumor-specific
antigens recognized by T lymphocytes.
To find new genes that present the same pattern of expression as the
MAGE genes, we recently applied subtraction of cDNA from a tumor
with cDNA from a panel of normal tissues. This approach applied to
a sarcoma cell line led to the identification of two new genes, SAGE
and HAGE that have a pattern of expression similar to MAGE genes.
They are potentially coding for antigens recognized by CTL.
The panel of tumor antigens that is now available may be used
in consecutive immunization. This could ensure a more effective rejection of tumor cells by reducing the risk of emergence of
antigen-loss variants.
Peptide synthesizer
Representative References
CHAUX P., VANTOMME V., STROOBANT V., THIELEMANS K.,
CORTHALS J., LUITEN R., EGGERMONT A.M., BOON T., VAN
DER BRUGGEN P. (1999) Identification of MAGE-3 epitopes
presented by HLA-DR molecules to CD4(+) T lymphocytes. J.
Exp. Med.;189:767-78.
HUANG L.Q., BRASSEUR F., SERRANO A., DE PLAEN E., VAN
DER BRUGGEN P., BOON T., VAN PEL A. (1999) Cytolytic T lymphocytes recognize an antigen encoded by MAGE-A10 on a
human melanoma. J. Immunol.; 162 : 6849-54.
DE SMET C., LURQUIN C., LETHE B., MARTELANGE V., BOON
T. (1999) DNA methylation is the primary silencing mechanism
for a set of germ line- and tumor-specific genes with a CpG-rich
promoter. Mol. Cell. Biol.;19:7327-35.
VAN DEN EYNDE B.J., GAUGLER B., PROBST-KEPPER M.,
MICHAUX L., DEVUYST O., LORGE F., WEYNANTS P., BOON T.
(1999) A new antigen recognized by cytolytic T lymphocytes on
a human kidney tumor results from reverse strand transcription.
J. Exp. Med.;190:1793-800.
LUCAS S., DE PLAEN E., AND BOON T. (2000) MAGE-B5,
MAGE-B6, MAGE-C2 and MAGE-C3 : four new members of
the MAGE family with tumor-specific expression. International
Journal of Cancer, 87 : 55-60.
MARTELANGE V., DE SMET C., DE PLAEN E., LURQUIN C.,
BOON T. (2000) Identification on a human sarcoma of two new
genes with tumor-specific expression. Cancer Res.; 60:3848-55.
VAN DEN EYNDE B.J., MOREL S. (2001) Differential processing of class-I-restricted epitopes by the standard proteasome
and the immunoproteasome. Curr. Opin. Immunol.;13:147-53.
SCHULTZ E.S., CHAPIRO J., LURQUIN C., CLAVEROL S.,
BURLET-SCHILTZ O., WARNIER G., RUSSO V., MOREL S., LEVY F.,
BOON T., VAN DEN EYNDE B.J., VAN DER BRUGGEN P. (2002)
The production of a new MAGE-3 peptide presented to cytolytic T lymphocytes by HLA-B40 requires the immunoproteasome.
J. Exp. Med.;195:391-9.
VAN DER BRUGGEN P., ZHANG Y., CHAUX P., STROOBANT V.,
Products and Services
Approaches to identify antigenic peptides recognized by
T lymphocytes.
Technique of cDNA subtraction.
Microarray.
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PANICHELLI C., SCHULTZ E.S., CHAPIRO J., VAN DEN EYNDE
B.J., BRASSEUR F., BOON T. (2002) Tumor-specific shared antigenic peptides recognized by human T cells. Immunol.
Rev.;188:51-64.
COULIE P.G., VAN DER BRUGGEN P. (2003) T-cell responses
of vaccinated cancer patients. Curr. Opin. Immunol.; 15:131-7.
LORIOT A., BOON T., DE SMET C. (2003) Five new human
cancer-germline genes identified among 12 genes expressed in
spermatogonia. Int. J. Cancer; 105: 371-6.
UYTTENHOVE C., PILOTTE L., THÉATE I., STROOBANT V.,
COLAU D., PARMENTIER N., BOON T. and VAN DEN EYNDE B.
(2003) Evidence for a tumoral resistance mechanism based on
tryptophan degradation by indoleamine 2,3-dioxygenase.
Nature Medicine, 9 : 1269-1274.
VIGNERON N., STROOBANT V., CHAPIRO J., OOMS A.,
DEGIOVANNI G., VAN DER BRUGGEN P., BOON T. and VAN DEN
EYNDE B. (2004) An antigenic peptide produced by peptide
splicing in the proteasome. Science, 304 : 587-590.
-
STAFF
Total: 79
KEY WORDS FOR R&D
antigenic peptide
cDNA subtraction
cytolytic T lymphocyte
epitope
immunotherapy
microarray
tumor
SENIOR SCIENTIST :
Thierry BOON
Thierry BOON
[email protected]
Tel. 32 (0)2 764 75 80
Patents
About 80 patents
Pierre VAN DER BRUGGEN
[email protected]
Tel.32 (0)2 764 74 31
Awards
Benoît VAN DEN EYNDE
[email protected]
Tel. 32 (0)2 764 75 72
T. Boon :
Prix Rik et Nel Wouters for cancer research, 1986
Prix De Vooght d’Immunologie, 1986
Cancer Research Institute, Award for Research in
Immunology, 1987
Dr Joseph Steiner Cancer prize, 1990
Prix Francqui, 1990
Prix Louis Jeantet, 1994
Rabbi Shai Shacknai Memorial Prize in Immunology and
Cancer Research, 1994
Prix Sandoz d’Immunologie, 1995
Prix Léopold Griffuel, 1999
Pierre COULIE
[email protected]
Tel. 32 (0)2 764 75 99
Etienne DE PLAEN
[email protected]
Tel. 32 (0)2 764 74 79
Bernard LETHE
[email protected]
Tel. 32 (0)2 764 74 76
Aline VAN PEL
[email protected]
Tel. 32 (0)2 764 74 83
Funding sources
Christophe LURQUIN
[email protected]
Tel. 32 (0)2 764 74 76
Ludwig Institute for Cancer Research;
FNRS
Francis BRASSEUR
[email protected]
Tel. 32 (0)2 764 74 56
Partnership
-
Mannheim, Germany (D. Schadendorf)
University Benjamin Franklin, Berlin, Germany (U. Keilholz)
Glaxosmithkline Biologicals, Rixensart, Belgium
Aventis Pasteur, Lyon, France
BruCells, Brussels, Belgium
Ludwig Institute for Cancer Research
ULB, Brussels, Belgium (Th. Velu, Fr. Uks)
VUB, Brussels, Belgium (B. Neyns)
KUL, Leuven, Belgium (M. Stas)
Institut Curie, Paris (T. Dorval, S. Piperno)
Institut Gustave-Roussy, Villejuif, France, (M.F. Avril, B. Escudier)
CHU de Nantes, France (B. Dreno)
Danièle GODELAINE
[email protected]
Tel. 32 (0)2 764 74 82
WEB SITES
www.licr.ucl.ac.be
www.gece.ucl.ac.be
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26
UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
B 5
Analysis of the intracellular processing of tumor antigens
recognized by cytolytic T lymphocytes
SENIOR SCIENTIST :
Benoît VAN DEN EYNDE
Main Equipment
Research Field and Subjects
Mass spectrometry
The central research theme of our group is the study of tumor
antigens recognized by T lymphocytes.
Representative References
Besides our continued efforts to identify additional antigens of
clinical interest for cancer immunotherapy, we mainly want to
address a number of fundamental or mechanistic issues that
have a direct impact on the utilization of such antigens as cancer vaccines in human patients.
S. MOREL, F. LÉVY, O. BURLET-SCHILTZ, F. BRASSEUR, M.
PROBST-KEPPER, A.-L. PEITREQUIN, B. MONSARRAT, R. Van
VELTHOVEN, J.-C. CEROTTINI, T. BOON, J.E. GAIRIN, AND B.J.
VAN DEN EYNDE. 2000. Processing of some antigens by the
standard proteasome but not by the immunoproteasome results
in poor presentation by dendritic cells. Immunity 12:107-117.
B.J. VAN DEN EYNDE AND S. MOREL. 2001. Differential processing of class-1-restricted epitopes by the standard proteasome and the immunoproteasome. Curr. Opin. Immunol.
13:147-153.
E.S. SCHULTZ, J. CHAPIRO, C. LURQUIN, S. CLAVEROL, O.
BURLET-SCHILTZ, G. WARNIER, V. RUSSO, S. MOREL, F. LEVY, T.
BOON, B.J. VAN DEN EYNDE, AND P. VAN DER BRUGGEN.
2002. The production of a new MAGE-3 peptide presented to
cytolytic T lymphocytes by HLA-B40 requires the immunoproteasome. J. Exp. Med. 195:391-399.
N. VIGNERON, V. STROOBANT, J. CHAPIRO, A. OOMS, G.
DEGIOVANNI, S. MOREL, P. VAN DER BRUGGEN, T. BOON, AND
B.J. VAN DEN EYNDE. 2004. An antigenic peptide produced by
peptide splicing in the proteasome. Science 304:587-590.
These antigens consist of peptides that are presented by MHC
class I molecules at the cell surface and derive from intracellular
proteins that are degraded by the proteasome. The intracellular
pathway leading from the protein to the peptide/MHC complex
is known as “antigen processing”.
We are currently studying the processing of several human
tumor antigens by the proteasome, and we are particularly
interested by the processing differences we have observed between the standard proteasome, which is present in most cells,
and the immunoproteasome which is found in some dendritic
cells and in cells exposed to interferon-gamma.
Such processing differences are important to consider in the
design of effective vaccination strategies, not only because they
condition the induction of the immune response per se, but also
because they represent a mechanism of tumor resistance to the
immune response, since tumors may change the proteasome type
they express and thereby escape the immune response.
Patents
A large portfolio of about 80 issued patents and patent applications on tumor antigens.
We are also studying a novel activity of the proteasome, which
we recently uncovered, and which allows the splicing of two
non-contiguous peptide fragments to produce an antigenic
peptide. The reaction occurs by transpeptidation within the
proteasome.
Awards
1998 : Prize of the “Fondation Clément Perdieus et Cécile Petit”
1998 : Annual prize of the “Fondation Maggy et Robert de Hovre”
1998 : Prize of the “Fondation Alexandre et Gaston Tytgat”
2001 : Prize of the 165th anniversary of the “Académie
Royale de Médecine de Belgique”
Products and Services
Mass spectrometry
Proteasome purification
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Funding Sources
STAFF
Total : 8
Ludwig Institute for Cancer Research
Institut de Pathologie cellulaire Christian de Duve (ICP)
Fonds national de la recherche scientifique (FNRS)
Télévie
Fédération Belge contre le Cancer
KEY WORDS FOR R&D
antigen processing
biochemistry
cancer vaccines
immunology
immunotherapy
proteasome
tumor antigens
Partnership
Dr. E. WARREN, Fred Hutchinson Cancer Institute, Seattle,
WA, USA.
Dr. K.-I. HANADA and Dr. P. ROBBINS, National Cancer
Institute, National Institutes of Health, Bethesda, MD, USA.
Dr. J.-E. GAIRIN, Institut de Pharmacologie et Biologie
Structurale, CNRS, Toulouse, France.
Dr. F. LEVY, Ludwig Institute for Cancer Research, Lausanne
Branch, Switzerland.
SENIOR SCIENTIST
Benoît VAN DEN EYNDE
[email protected]
Tel. 32(0)2 764 75 72
WEB SITE
www.licr.ucl.ac.be/tiap/tiap.html
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
B 6
Mechanisms of tumor resistance to the immune system and
development of a mouse model of inducible melanoma
SENIOR SCIENTIST :
Benoît VAN DEN EYNDE
Research Field and Subjects
Main Equipment
Crucial to the success of cancer immunotherapy is a precise
understanding of the interplay between growing tumors and
the anti-tumor immune response.
For example, tumors may develop a variety of mechanisms to
escape immune attack.
In that context, we have observed that a majority of tumor cells
express an enzyme called indoleamine 2,3-dioxygenase (IDO),
which rapidly degrades tryptophan, an essential amino acid
whose supply is mandatory for the activity of T lymphocytes.
Thus, by locally degrading tryptophan, tumor cells completely
inactivate T lymphocytes and thereby blunt the anti-tumor
immune response. We have also shown that this resistance
mechanism can be blocked by treating animals with 1-methyltryptophan, an inhibitor of IDO. These results suggest that the
efficacy of cancer immunotherapy could be improved by combining immunization strategies with a treatment aimed at inhibiting IDO. We are trying to develop novel inhibitors of IDO for
that purpose. We are also studying other mechanisms of tumoral immune resistance.
Laser-assisted microdissection and laser pressure catapulting
(P.A.L.M.®, Microlaser Technologies AG, Benried, Germany)
Representative References
UYTTENHOVE C., PILOTTE L., THÉATE I., STROOBANT V.,
COLAU D., PARMENTIER N., BOON T., VAN DEN EYNDE B.J.
Evidence for a tumoral immune resistance mechanism based on
tryptophan degradation by indoleamine 2,3-dioxygenase.
Nature Medicine 9 : 1269-1274, 2003.
Patents
A large portfolio of about 80 issued patents and patent applications on tumor antigens and their use for cancer therapy.
Funding Sources
In order to obtain meaningful information from mouse studies
with melanoma, we are also developing a new model of mice
that will develop melanomas upon local application of tamoxifen. The induction of melanomas is based on Cre-lox recombination and involves conditional activation of oncogene Ras and
inactivation tumor-suppressor gene INK4A. Tumors developing
slowly within a normal tissue are likely to represent the status
of human cancers much more closely than the transplanted
tumors currently used.
Such a model will be particularly useful to optimize strategies of
cancer immunotherapy, but will undoubtedly be also of great
interest in other contexts, such as the molecular definition of
the successive steps involved in carcinogenesis, local invasiveness and metastasis.
Ludwig Institute for Cancer Research
Institut de Pathologie cellulaire Christian de Duve (ICP)
Fonds national de la recherche scientifique (FNRS)
Télévie
Fédération Belge contre le Cancer
Partnership
The Netherlands Cancer Institute (NKI), Amsterdam, The
Netherlands.
Centre d’Immunologie INSERM-CNRS, Marseille-Luminy, Marseille
France.
Products and Services
Screening assay for the development of new IDO inhibitors
New mouse model of inducible melanomas
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STAFF
Total : 8
KEY WORDS FOR R&D
biochemistry
cancer vaccines
IDO inhibitors
immune escape
immunology
immunotherapy
inducible melanoma model
tumor antigens
SENIOR SCIENTIST
Benoît VAN DEN EYNDE
[email protected]
Tel. 32(0)2 764 75 72
WEB SITE
www.licr.ucl.ac.be/tiap/tiap.html
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
B 7
Aristolochic acid and ochratoxin A : etiological factors of
Balkan endemic nephropathy and associated urothelial tumors
SENIOR SCIENTIST :
Jean-Pierre COSYNS
Research Field and Subjects
Representative References
Balkan nephropathy (BN), a 50 years old chronic interstitial fibrosing
nephropathy of still unknown etiology, has been reported similar to
so-called Chinese herbs nephropathy (CHN).
The responsibility of aristolochic acid (AA) and ochratoxin A (OTA),
two nephrotoxic and carcinogenic substances respectively of herbal
and mycotic origin, has respectively been demonstrated and denied
in CHN. Exposure of BN patients to both alkaloids by the identification of specific tissular DNA adducts awaits further elucidation.
The hypothetical dAMP incorporation by polymerase at the site of
AA-adenine adducts may be assessed by the analysis of likely mutations in the tumour suppressor gene p53 of AA exposed patients.
COSYNS J.P., JADOUL M., SQUIFFLET J.P., DE PLAEN J.F.,
FERLUGA D., VAN YPERSELE DE STRIHOU C. Chinese herbs
nephropathy: a clue to Balkan endemic nephropathy ? Kidney
Int, F.I.: 5.0160, 1994, 45, 1680-1688.
COSYNS J.P., JADOUL M., SQUIFFLET J.P., VAN CANGH P.J.,
VAN YPERSELE DE STRIHOU C. Urothelial malignancy in
nephropathy due to Chinese herbs. Lancet, F.I.: 15.3970, 1994,
344, 188.
SCHMEISER H.H., BIELER C.A., WIESSLER M., VAN YPERSELE
DE STRIHOU C., COSYNS J.P. Detection of DNA adducts formed
by aristolochic acid in renal tissue from patients with Chinese
herbs nephropathy. Cancer Res, F.I.: 8.3180, 1996, 56, 20252028.
BIELER C.A., STIBOROVA M., WIESSLER M., COSYNS J.P., VAN
YPERSELE DE STRIHOU C. 32P -post-labelling analysis of DNA
adducts formed by aristolochic acid in tissues from patients
with Chinese herbs nephropathy. Carcinogenesis, F.I.: 5.4050,
1997, 18, 1063-1067
COSYNS J.P., GOEBBELS R.M., LIBERTON V., SCHMEISER H.H.,
BIELER C.A., BERNARD A.M. Chinese herbs nephropathy-associated slimming regimen induces tumours in the forestomach
but no interstitial nephropathy in rats. Arch. Toxicol., F.I.:
1.8520, 1998, 72, 738-743.
COSYNS J.P., JADOUL M., SQUIFFLET J.P., WESE F.X., VAN
YPERSELE DE STRIHOU C. Urothelial lesions in Chinese-herb
nephropathy. 1011-7. Am. J. Kidney Dis., F.I.: 3.6880, 1999, 33,
1011-1017.
GILLEROT G., JADOUL M., ARLT V.M., VAN YPERSELE DE
STRIHOU C., SCHMEISER H.H., BUT P.P., BIELER C.A., COSYNS
J.P. Aristolochic acid nephropathy in a Chinese patient: time to
abandon the term “Chinese herbs nephropathy”? Am. J. Kidney
Dis., F.I.: 3.6880, 2001, 38.
COSYNS J.P., DEHOUX J.P., GUIOT Y., GOEBBELS R.M., ROBERT
A., BERNARD A.M., VAN YPERSELE DE STRIHOU C. Chronic aristolochic acid toxicity in rabbits: a model of Chinese herbs
nephropathy ? Kidney Int., F.I.: 5.0160, 2001, 59, 2164-2173.
SOLEZ K., DAUGIRDAS J., GREGORY M.C., FROHNERT P.P.,
BHOWMIK D.M., JHA V., COSYNS J.P. Is “Chinese herbs
nephropathy” a prejudicial term ? Am. J. Kidney Dis., F.I.:
3.6880, 2001, 38, 1141-1142.
Several international collaborations were invaluable to achieve
these researches, in particular for :
the local selection of BN patients and pathologic samples
(University of Nis, and Clinical Center of Serbia, Belgrade, Serbia)
the evaluation of morphological aspects of BN (University of
Ljubljana, Slovenia)
the analysis of AA-DNA adducts by the 32P post-labelling
technique (University of Heidelberg, Germany)
the international collaborative works including validation of DNA
adduct detection by 32P post-labelling techniques and evaluations of
OTA exposure (Institut National Polytechnique de Toulouse, France)
the supervision of a thesis on the relationship between malignancy and the functional status of p53 and contribution to the
identification of mutations in the gene p53 (UCL, Bruxelles).
Products and Services
Detection of carcinogen-DNA adducts in human tissues using
the 32P post-labelling technique for diagnostic and research
purposes (Carcinogenesis 1994; 15:1187-92).
Main Equipment
Standard equipment of University Laboratory of Pathology
and Molecular Biology.
Standard facilities of University Medical and Surgical Clinic.
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COSYNS J.P. When is “aristolochic acid nephropathy” more
accurate than “Chinese herbs nephropathy”? Kidney Int., F.I.:
5.0160, 2002, 61, 1178.
ARLT V.M., FERLUGA D., STIBOROVA M., PFOHL-LESZKOWICZ
A., VUKELIC M., CEOVIC S., SCHMEISER H.H., COSYNS J.P. Is
aristolochic acid a risk factor for Balkan endemic nephropathyassociated urothelial cancer ? Int. J. Cancer, F.I.: 4.0560, 2002,
101, 500-502.
KANAAN N., COSYNS J.P., JADOUL M., GOFFIN E. The importance of a histology-based diagnosis of interstitial nephropathy
in two patients with renal insufficiency. Nephrol. Dial. Transplant.,
2003, 18, 440-442.
GILLEROT G., GOFFIN E., MOULIN P., ARLT V.M., PHILLIPS
D.H., COSYNS J.P., DEVUYST O. Aristolochic acid nephropathy
and the peritoneum: Functional, structural, and molecular studies. Kidney Int., F.I.: 5.0160, 2003, 64, 1883-92.
COSYNS J.P. Aristolochic acid and ‘Chinese herbs nephropathy’: a review of the evidence to date. Drug Safety, F.I.: 3.3160,
2003, 26, 33-48.
COSYNS J.P., VAN YPERSELE DE STRIHOU C. Chinese herbs and
other rare causes of interstitial nephropathy, Oxford Textbook of
Clinical Nephrology, edited by AM Davison, in press.
STEFANOVIC V., COSYNS J.P. Balkan Nephropathy, Oxford
Textbook of Clinical Nephrology, edited by AM Davison, in press.
STAFF
Total : 2
KEY WORDS FOR R&D
biomedical and agricultural sciences
environmental medicine
histopathology
medicine human pathology
molecular biology
molecular genetics
nephrology-urology
organic chemistry
pathology
pharmaceutical chemistry
prevention medicine
SENIOR SCIENTIST
Jean-Pierre COSYNS
[email protected]
Tel. 32 (0)2 764 17 21
WEB SITE
http://rch.adre.ucl.ac.be/browse/list_alpha/ANPS
Funding Sources
Télévie
Partnership
Prof. V. Stefanovic, V. Savic (University of Nis, Serbia) and J.
Nikolic (Clinical Center of Serbia, Belgrade, Serbia)
Prof. D. Ferluga (University of Ljubljana, Slovenia)
Prof. Schmeiser (University of Heidelberg, FRG)
Prof. Leszkowicz (Institut National Polytechnique de Toulouse,
France)
Prof. J.L. Gala (UCL, Bruxelles)
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
B 8
AMP-activated protein kinase, a new potential regulator of
cytoskeleton organization : role in cell proliferation and/or
differentiation
SENIOR SCIENTISTS :
Louis HUE
Mark RIDER
of elongation factor 2 and an inhibition of protein synthesis.
Current Biology, 2002, 12, 1419-1423.
HUE L., BEAULOYE C., MARSIN A.S., BERTRAND L., HORMAN
S., RIDER M. Insulin and ischemia stimulate glycolysis by acting
on the same targets through different and opposing signaling
pathways. J. Mol. Cell Cardiol., 2002, 34, 1091-1097.
HUE L., BEAULOYE C., BERTRAND L., HORMAN S., KRAUSE
U., MARSIN A.S., MEISSE D., VERTOMMEN D., RIDER M. New
targets of AMP-activated protein kinase. Biochem. Soc. Trans.,
2003, 31, 213-215.
HORMAN S., BEAULOYE C., VERTOMMEN D., VANOVERSCHELDE J.L., HUE L., RIDER M.H. Myocardial ischemia and
increased heart work modulate the phosphorylation state of
eukaryotic elongation factor-2. J. Biol. Chem., 2003, 278,
41970-6.
Research Field and Subjects
The AMP-activated protein kinase (AMPK) has recently received
much attention because of its important medical implications in
type II diabetes. We believe that other medical implications exist
because of our recent preliminary evidence for new substrates
of AMPK, such myosin light chain kinase involved notably in the
organization of actin cytoskeleton, the latter affecting cell
shape and from this, division. Indeed it is well-known that alterations in cell shape often accompany changes in cellular activities related not only to cell motility but also to differentiation
and/or division. The aim of our project is to evaluate the effect
of AMPK activation on cell motility and proliferation. This project relies on the implementation of technical approaches that
are at the forefront of molecular biology, biochemistry and cellular biology.
Funding Sources
Adenoviral vectors expressing dominant-negative or constitutively active AMPK are currently under construction in the laboratory. Techniques currently reffered to proteomics and
phosphoproteomics, aiming at identifying protein sequences
and phosphorylated peptides by mass spectrometry, represent a
technical achievement in the laboratory, as the measurement of
enzymatic activities. Finally, immunoblotting and immunocytochemistry techniques will allow us to investigate the phosphorylation states of proteins and their localization or organization
(for actin) in the cell.
Our laboratory is funded by Belgian (FRSM-Foundation for
Medical Scientific Research, IAP-Interuniversity Attraction Pole,
Télévie) and European (5th framework program) financial
supports.
Partnership
EU program FP6 “EXEGENESIS” Health benefits of exercise:
identification of genes and signalling pathways involved in
effects of exercise on insulin resistance, obesity and the metabolic syndrome.
Main Equipment
The laboratory contains the necessary equipment to develop
this project. A collaboration with cell biologists is foreseen in
order to achieve reliable measurements of cell motility.
Representative References
HORMAN S., BROWNE G.J., KRAUSE U., BEAULOYE C.,
McLEOD L.E., VERTOMMEN D., BERTRAND L., LAVOINNE A.,
HUE L., PROUD C.G., RIDER M.H. Activation of AMP-activated
protein kinase by anoxia is associated with the phosphorylation
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33
STAFF
Total : 5
KEY WORDS FOR R&D
AMP-activated protein kinase
biochemistry
cellular biology
cytology
cytoskeleton
differentiation
motility
myosin light chain kinase
proliferation
stress fibers
SENIOR SCIENTISTS
Louis HUE
[email protected]
Tel. 32 (0)2 764 74 85
Mark RIDER
[email protected]
Tel. 32 (0)2 764 74 86
WEB SITE
www.icp.ucl.ac.be/horm
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
B 9
Mammalian antioxidant enzymes
SENIOR SCIENTISTS :
Bernard KNOOPS
Jean-Paul DECLERCQ
Jean-François REES
Research Field and Subjects
Representative References
Oxidative stress is a major biological process involved in the development of a number of acute or chronic pathological situations
(inflammation, cancer, neurodegenerative diseases, atherosclerosis,
lung diseases, aging). Our research is focused on identification and
characterization of proteins that may play protective roles against
cell death caused by oxidative stress (apoptosis and necrosis). After
expression of these proteins in bacteria, in yeasts or in mammalian
cells, their protective antioxidant activity is tested in different in vitro
models such as animal and human cell lines exposed to oxidative or
pro-apoptotic compounds. The yeast Saccharomyces cerevisiae is
also used as model organism. Peroxide and peroxynitrite reductase
activities of recombinant proteins are measured. Tridimensional
structure is determined by X-ray crystallography.
B. KNOOPS, A. CLIPPE, K. ARSALANE, R. WATTIEZ, C. HERMANS, E. DUCONSEILLE, P. FALMAGNE and A. BERNARD
(1999) Cloning and characterization of AOEB166, a novel mammalian antioxidant enzyme of the peroxiredoxin family. J. Biol.
Chem. 274, 30451-30458.
J.-P. DECLERCQ, C. EVRARD, A. CLIPPE, D. VANDER STRICHT,
A. BERNARD and B. KNOOPS (2001) Crystal structure of human
peroxiredoxin 5, a novel type of mammalian peroxiredoxin at
1.5 A resolution. J. Mol. Biol. 311, 751-759.
M.X. WANG, A. WEI, J. YAN, A. CLIPPE, A. BERNARD, B.
KNOOPS and G.A. MURRELL (2001) Antioxidant enzyme
peroxiredoxin 5 is upregulated in degenerative human tendon.
Biochem. Biophys. Res. Commun., 284, 667-673.
N.T. NGUYEN-NHU and B. KNOOPS (2002) Alkyl hydroperoxide reductase 1 protects Saccharomyces cerevisiae against
metal ion toxicity and glutathione depletion. Toxicol. Letters.
135, 219-226.
M.X. WANG, A. WEI, J. YAN, A. TRICKETT, B. KNOOPS &
G.A.C. MURRELL (2002) Expression and regulation of peroxiredoxin 5 in human osteoarthitis. FEBS Letters. 531, 359-362.
F. PLAISANT, A. CLIPPE, D. VANDER STRICHT, B. KNOOPS & P.
GRESSENS (2003) Recombinant peroxiredoxin 5 protects
against excitotoxic brain lesions in newborn mice. Free Rad.
Biol. Med. 34, 862-872.
N.T. NGUYEN-NHU & B. KNOOPS (2003) Mitochondrial and
cytosolic expression of human peroxiredoxin 5 in
Saccharomyces cerevisiae protect yeast cells from oxidative
stress induced by paraquat. FEBS Letters. 534, 148-152.
G. LEYENS, I. DONNAY & B. KNOOPS (2003) Cloning of
bovine peroxiredoxins: gene expression in bovine tissues and
amino acid sequence comparison with rat, mouse and primate
peroxiredoxins. Comp. Biol. Phys., 136, 943-955.
I. BANMEYER, C. MARCHAND, C. VERHAEGHE, B. VUCIC, JF. REES & B. KNOOPS (2003) Overexpression of human peroxiredoxin 5 in subcellular compartments of Chinese hamster
ovary cells: effects on cytotoxicity and DNA damage caused by
peroxides. Free Rad. Biol. Med., 36, 65-77.
One of the proteins currently under investigation is a novel
mammalian thioredoxin peroxidase (PRDX5) which is a member
of the recently identified peroxiredoxin family of antioxidant
enzymes. We have solved crystal structure of PRDX5. Enzymatic
activities of PRDX5 as well as its physiological implication in cellular protection against oxidative stress are also explored using
E. coli recombinant proteins and cell transfection strategies. The
deletion of the gene homologous to human PRDX5 in
Saccharomyces cerevisiae has been performed and revealed the
importance of this protein in the defence against oxidative
stress but also against heavy metal toxicity.
Products and Services
Gene cloning
Recombinant proteins
Transfection of mammalian cell lines
Crystallography
Main Equipment
Cell culture equipment
Confocal and electron microscopy
Molecular biology equipment
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35
Patents
STAFF
Total : 16
B. KNOOPS, C. HERMANS, A. BERNARD, R. WATTIEZ & P. FALMAGNE (1999) Peroxisome-associated polypeptide, nucleotide
sequence encoding said polypeptide and their uses in the diagnosis and/or the treatment of lung injuries and diseases, and of
oxidative stress-related disorders. WO9909054.
J.-P. DECLERCQ, C. EVRARD, A. CLIPPE, D. VANDER STRICHT,
A. BERNARD & B. KNOOPS (2001) Crystal structure of PRDX5.
European Patent Application n° 01870016.1.
KEY WORDS FOR R&D
animal cell culture
antioxidant enzyme
crystallization
peroxidase activity
protein purification
recombinant protein
transfection vectors
tridimensional structure
Funding Sources
SENIOR SCIENTISTS
Bernard KNOOPS
[email protected]
Tel. 32(0)10 47 37 60
Fonds national de la recherche scientifique (FNRS)
Fonds de la recherche fondamentale collective - FRFC
Fonds pour la formation à la recherche dans l’industrie et
dans l’agriculture (FRIA)
Actions de recherche concertée (ARC)
Jean-Paul DECLERCQ
[email protected]
Tel. 32(0)10 47 29 24
Jean-François REES
[email protected]
Tel. 32(0)10 47 35 17
Partnership
Member of the Institut des Sciences de la Vie, Louvain-laNeuve, Belgium.
Prof. R. OUVRIER, New Children’s Hospital, Univ. Sydney,
Australia.
Prof. J.P. BRION, ULB, Belgium.
Dr. P. GRESSENS, INSERM, Paris, France.
Prof. G. MURRELL, St George Hospital Sydney, Australia.
Prof. L. POOLE, Wake Forest University School of Medicine, USA.
Prof. W.H. KOPPENOL, ETH, Zurich, Switzerland.
Prof. R.J. WANDER, University of Amsterdam,
The Netherlands.
Dr. R. WATTIEZ, UMH, Belgium.
WEB SITES
www.bani.ucl.ac.be
www.cstr.ucl.ac.be
www.isv.ucl.ac.be
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
B 10
Mechanisms involved in apoptosis induced by
anticancerous drugs
SENIOR SCIENTIST :
Marie-Paule MINGEOT-LECLERCQ
chondrial membranes, releasing cytochrome c and ensuing apoptosis.
Research Field and Subjects
The explosion of interest in apoptosis amongst cancer biologists
has been underpinned by the hope that an understanding of
cell death will enhance our knowledge of the mechanisms
involved in tumor drug resistance.
Two areas of fundamental importance are:
- the mechanism of the process of drug-induced apoptosis
- the modulation of cellular resistance to conventional agents,
which would derive from an understanding of the mechanisms
that allow cancer cells to evade apoptosis after drug-induced
damage.
The second aim of this study is to provide an understanding of
the apoptosis- induced by anthracyclines in resistant cells.
Especially, it is of great interest to study the mechanism involved in the increased accumulation of anthracyclines in the acidic organelles of a variety of drug-resistant cancer cells. This elevated accumulation may result from the action of transporters
that efflux the drug at the plasma membrane (or drive sequestration into organelles). Alternatively, the enhanced lysosometo-cytosol pH difference observed in resistant cell lines may
cause sequestration of anthracyclines in the organelles.
Most of the polychemotherapeutic strategies in haematological
oncology are based on the use of anthracyclines. Despite their
widespread use, the intracellular events leading to apoptotic
cell death are only partially understood.
The capacity of resistant- cells lines to compartmentalize anthracyclines away from intracellular target sites by accumulating them in
lysosomes could be taken as an advantage, allowing cancer cells
to enhance apoptosis after drug-induced damage.
Several organelles might initiate apoptosis by specific stress sensors and relay apoptosis-modulating signals to the rest of the
cell. Stress management intending to repair damaged structures probably involves an orchestrated response affecting several
organelles. During the last few years, lysosomal destabilization
with release of hydrolytic enzymes to the cytosol has been raised as an upstream event preceding apoptosis triggered by a
variety of different agonists.
The general aim of this work is to understand the molecular
mechanisms underlying apoptosis induced by anticancer drugs
in sensitive and resistant cells to overcome drug resistance and
to generate novel molecular targets.
Products and Services
Cellular models for the evaluation of the capacity of drugs to
induce apoptosis.
In vitro models (liposomes) for the evaluation of the capacity
of drugs to alter the membrane permeability.
We and others previously observed that lysosomotropic agents
(aminoglycoside antibiotics e.g.), which are concentrated inside
lysosomes by endocytosis and proton trapping, cause lysosomal
rupture and ensue apoptosis.
Main Equipment
The first aim of this study is to investigate the role of lysosomes in
apoptosis induced by anthracyclines. Due to their character of weak
bases, these drugs can partly accumulate in lysosomes by a mechanism of proton trapping. Therefore, if lysosomes are involved in
apoptosis induced by anthracyclines, we might study the involvement of a direct activation of pro-caspases by released lysosomal
proteases, especially cathepsins B, L, and D. Alternatively, cytoplasmic lysosomal enzymes might activate other cytosolic pro-enzymes,
or proteins of Bcl-2 family like Bid, or proteolytically attack mito-
Cell culture facilities.
General equipment for biochemical and molecular biology assays.
General equipment for preparing liposomes, binding experiments
and biophysical techniques (fluorimetry).
Microplate reader.
Fluorescence microscopy.
Equipment for assay of drugs by scintillation counting, HPLC.
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Representative References
SERVAIS H., VAN DER SMISSEN P., THIRION G., VAN DER
ESSEN G., VAN BAMBEKE F., TULKENS P.M. and MINGEOTLECLERCQ M.P. (2003). The antibiotic gentamicin induces
apoptosis in LLC-PK1: involvment of lysosomes and mitochondrial pathway. Kidney Intern. Submitted.
EL MOUEDDEN M., LAURENT G., MINGEOT-LECLERCQ M.P.
and TULKENS P.M. (2000) Apoptosis in renal proximal tubules
of rats treated with low doses of aminoglycosides. Antimicrob.
Agents Chemother., 44: 665-675.
EL MOUEDDEN M., LAURENT G., MINGEOT-LECLERCQ M.P.
and TULKENS P.M. (2000) Gentamicin-induced apoptosis in
renal cell lines and embryonic rat fibroblasts. Toxicol. Sciences,
56:229-239.
MINGEOT-LECLERCQ M.P., GALLET X., FLORE C., VAN BAMBEKE
F., PEUVOT J. and BRASSEUR R. (2001) Experimental and conformational analyses of interactions between butenafine and lipids.
Antimicrob. Agents Chemother., 45: 3347-3354.
MINGEOT-LECLERCQ M.P., LINS L., BENSLIMAN M., VAN
BAMBEKE F., VAN DER SMISSEN P., PEUVOT J., SCHANCK A.
and BRASSEUR R. (2002) Membrane destabilization induced by
beta-amyloid peptide 29-42: Importance of the amino-terminus. Chem. Phys. Lipids, 120: 57-74.
MINGEOT-LECLERCQ M.P., LINS L., BENSLIMAN M., THOMAS
A., VAN BAMBEKE F., PEUVOT J., SCHANCK A. and BRASSEUR
R. (2003) Piracetam inhibits the lipid-destabilising effect of the
amyloid peptide Abeta C-terminal fragment. Biochim. Biophys.
Acta, 1609: 28-38.
TYTECA D., SCHANCK A., DUFRENE Y. F., DELEU M., COURTOY
P.J., TULKENS P.M. and MINGEOT-LECLERCQ M.P. (2003) The
macrolide antibiotic azithromycin interacts with lipids and
affects membrane organization and fluidity: studies on
Langmuir-Blodgett monolayers, liposomes and J774
macrophages. J. Membr. Biol. 192: 203-215.
DOM G., SHAW-JACKSON C., MATIS C., BOUFFIOUX O.,
PICARD J.J., PROCHIANTZ A., MINGEOT-LECLERCQ M.P.,
BRASSEUR R. and REZSOHAZY R. (2003) Cellular uptake of
Antennapedia Penetratin peptides is a two-step process in
which phase transfer precedes a tryptophan-dependent
translocation. Nucleic Acids Res., 31: 556-561.
CHANTEUX H., PATERNOTTE I., MINGEOT-LECLERCQ M.P.,
BRASSEUR R., SONVEAUX E. and TULKENS P.M. (2003) Cell handling, membrane-binding properties, and membrane-penetration modeling approaches of pivampicillin and phthalimidomethylampicillin, two basic esters of ampicillin, in comparison
with chloroquine and azithromycin. Pharm. Res., 20: 624-631.
Funding Sources
UCL – FNRS – Télévie - Région wallonne
STAFF
Total: 23
KEY WORDS FOR R&D
anthracyclines
apoptosis
biophysics
lysosomes
membranes
molecular and cellular biology
molecular and cellular pharmacology
pharmaceutical sciences
resistance
tumor cells
SENIOR SCIENTIST
Marie-Paule MINGEOT-LECLERCQ
[email protected]
Tel. 32 (0)2 764 73 74
WEB SITE
http:// www.facm.ucl.ac.be
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
B 11
Hox transcription factors and cancer
SENIOR SCIENTIST :
René REZSOHAZY
Research Field and Subjects
In the context of a collaboration involving the clinic (Prof. G.
Cornu, Cliniques Universitaires St Luc), the Center for Human
Genetics (Prof. Ch. Verellen-Dumoulin) and our group, Hox
mutations have been identified in patients with lymphoid malignancy. Here again, our goal will be to determine the impact
of these mutations on the activity of the Hox proteins and to
evaluate to what extent they convert Hox genes into oncogenes.
The homeotic Hox genes code for important transcription factors that contribute to pattern the main body axis and the limbs
and to govern several steps of organogenesis during the
embryonic development of vertebrates. While these proteins
play critical roles during embryogenesis, accumulating data also
provides evidence that they fulfil important functions in modulating differentiation processes at adulthood. These genes are
for example involved in the commitment of cell fates in hematopoïesis or in the maturation of the mammary gland to support lactation.
Main Equipment
Regular cellular and molecular biology.
Our current research interests concern the mode of action of
this class of transcription factors.
What are their functional domains ? How do they specifically
achieve their roles? What are the target genes under their
control ? These are the questions we currently investigate.
Representative References
REMACLE S., SHAW-JACKSON C., MATIS C., LAMPE X., PICARD
J. and REZSOHAZY R. Changing homeodomain residues 2 and
3 of Hoxa1 alters its activity in a cell-type and enhancer dependent manner. 2002, Nucleic Acids Res., 30, 2663-2668.
DOM G., SHAW-JACKSON C., MATIS C., BOUFFIOUX O.,
PICARD J.J., PROCHIANTZ A., MINGEOT-LECLERCQ M.-P.,
BRASSEUR R. and REZSOHAZY R. Cellular uptake of
Antennapedia penetratin peptides is a two-step process in
which phase transfer precedes a tryptophan-dependent
translocation. 2003, Nucleic Acids Res., 31, 556-561.
LAMPE X., PICARD J.J. and REZSOHAZY R. The Hoxa2 enhancer
2 contains a critical Hoxa2 responsive regulatory element. 2004,
Bioch. Bioph. Res. Comm., 316, 898-902.
DIMAN N.Y.S.-G., CHAUVIER E., PACICO N., PICARD J.J. and
REZSOHAZY R. The proximal 2-kb of the Hoxa3 promoter
directs gene expression in distinct branchial compartments and
cranial ganglia. 2004, Dev. Brain Res., 150, 211-213.
REMACLE S., ABBAS L., DE BACKER O., PACICO N., GAVALAS
A., GOFFLOT F., PICARD J.J. and REZSOHAZY R. Loss-of-function but no gain-of-function caused by amino acid substitutions
in the hexapeptide of Hoxa1 in vivo. 2004, Mol. Cell Biol, in
press.
While most of our investigations to date were connected to the
developmental functions of these genes, we recently turned
towards the relationship between the activity of these proteins
and their involvement in differentiation or tumorigenesis.
A first approach is related to the Hoxa1 protein. Hoxa1 has
recently been associated with breast cancer development upon
increased expression of the human growth hormone. In vitro,
forced expression of Hoxa1 results in the oncogenic transformation of human mammary epithelial cells. We will use such in vitro
assays as a readout to identify new functional domains of
Hoxa1. This will allow to further unravel the Hoxa1 partners and
the pathways leading to the Hoxa1 associated tumorigenesis.
We generated recombinant mice in which the Hoxa1 gene has
been replaced by an allele coding for a Hoxa1 protein unable to
cooperate with Pbx, one of its key cofactors. In vitro data suggest that the partnership between Hoxa1 and Pbx is critical for
the oncogenic potential of Hoxa1. Our recombinant mice will
allow to validate this hypothesis. If the Hoxa1-Pbx interaction is
confirmed to be crucial for the Hoxa1 associated cancer development, the known interfaces between these proteins would
be considered as potential targets for antagonists design.
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Funding Sources
STAFF
Total 4
Fonds national de la recherche scientifique (FNRS)
Télévie
KEY WORDS FOR R&D
breast cancer
hox
lymphoid malignancy
transcription factors
Partnership
Prof. Ch. Verellen-Dumoulin, Center for Human genetics, UCL.
Prof. G. Cornu, Dept. Pediatric Hematology and Oncology,
Cliniques Universitaires St Luc, Belgium.
Prof. F. Rijli, IGBMC, Strasbourg, France.
Prof. M. Featherstone, Mc Gill University, Montreal, Canada.
SENIOR SCIENTIST
René REZSOHAZY
[email protected]
Tel. 32(0)10 47 37 06
WEB SITE
www.mige.ucl.ac.be
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
C 1
Genetic analysis of brain tumours
SENIOR SCIENTISTS :
Miikka VIKKULA
Catherine GODFRAIND
Research Field and Subjects
Funding Sources
Fonds national de la recherche scientifique (FNRS)
Télévie
Fonds Maisin
Fédération Belge contre le Cancer
We are interested in the genetic study of cerebral tumors (oligodendrogliomas and ependymal tumours) and of ocular melanoma.
Ours aims are :
to establish a correlation between molecular markers and
diagnosis, prognosis and therapeutic response;
to establish a correlation between (epi)genetic alterations and
tumourigenetic events.
Partnership
Collaborations with Prof. M.M. Rouchoux, CHU Lille, France
F. Scaravilli, Institute of Neurology, London, England
Prof. I. Salmon, Erasme, Brussels, Belgium
Products and Services
Development of genetic tests
STAFF
Total : 4
Main Equipment
KEY WORDS FOR R&D
Two institutional 8 capillaries sequencing units
One institutional whole genome analysis system for SNPs and
expression analysis (Affymetrix)
Two semi-automated analysis systems for human genome
linkage analysis (LICOR)
Array-CGH
DHPLC
brain tumor
CGH (comparative genomic hybridization)
DNA microarrays
ependymoma
LOH (loss of heterozygosity)
molecular genetics
ocular melanoma
oligodendroglioma
SENIOR SCIENTISTS
Representative References
Miikka VIKKULA
[email protected]
Tel : 32 (0)2 764 74 96
GODFRAIND C., ROUSSEAU E., RUCHOUX M.M., SCARAVILLI F., VIKKULA M. Tumour necrosis and microvascular proliferation are associated with 9p deletion and CDKN2A alterations in
1p/19q-deleted oligodendrogliomas. Neuropathology and
Applied Neurology, 2003, 29:462-471.
ROUSSEAU E., GODFRAIND C., RUCHOUX M.M., SCARAVILLI F., CHAPON F., VIKKULA M. Tumor necrosis and microvascular proliferation are associated with 9p deletion and CDKN2A,
CDKN2B and p14ARF are frequently and differentially methylated
in ependymal tumors. Neuropathology and Applied Neurology,
in press.
Catherine GODFRAIND
[email protected]
Tel : 32 (0)2 764 52 60
WEB SITES
www.icp.ucl.ac.be/vikkula
www.md.ucl.ac.be/vasc_anom
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
C 2
Characterization of malignant hemopathies by molecular
and flow cytometry
SENIOR SCIENTISTS :
Dominique LATINNE
Jean-Luc VAERMAN
Véronique DENEYS
Main Equipment
Research Field and Subjects
Genetic Analyser 310 Applied Biosystems
Sequence Detect System 7700
Acute leukemia are generally divided into myeloid (AML) and
lymphoid (ALL) leukemia. All diagnosis methods (cytology,
immunophenotyping and cytogenetics) are complementary;
none, on its own, is sufficient to allow precise diagnosis.
The aim of our project is triple :
We would like to know if the approach of quantitative Real
time PCR (RTQ-PCR) allows to obtain easily and simultaneously
quantitative expression profiles for multiple genes.
Specific lineage markers can be analysed by phenotypic (antigenic) or genotypic (RNA) expression. We would like to compare the expression, by flow cytometry and by RTQ-PCR, of a
panel of lineage or malignity specific genes.
We would like also to analyse the input of the analysis of
gene expression by Real time quantitative PCR in prognosis and
diagnosis of leukemia.
Representative References
SAUSSOY P., VAERMAN J.P., CORNU G., FERRANT A., LATINNE
D.L. Characterization of acute leukemias gene expression analysis: impact on diagnosis and prognosis. 8è Journée de Biologie
Clinique, 10 mai 2003, UCL. Abstract Acta Clinica Belgica.
SAUSSOY P., VAERMAN J.P., STRAEMANS N., CORNU G., FERRANT A., LATINNE D.L. Differential diagnosis between acute
myeloid leukemia, B-lineage acute lymphoid leukemia and T-lineage acute lymphoid leukemia using real time quantitative reverse
transcription-PCR. Accepted in Clinical Chemistry Dec. 20, 2003.
Up to now, we have analysed expression profiles of CD19,
CD79a, CD3e and myelo-peroxidase (MPO) in 72 leukemic
bone marrow samples at diagnosis. The expression level of
these genes has been expressed as delta CT. The analysis of the
co-expression of these genes allows to identify 3 patterns. The
first one shows a higher expression of CD3e and a lower one of
CD19, CD79a and MPO. The second one shows a higher
expression of MPO. The third one, a higher expression of CD19
and CD79a. These 3 patterns have a perfect correlation with T
ALL, AML and B ALL respectively.
Awards
Price of the best poster hematology section, 2003
Funding sources & Partnership
Fonds national de la recherche scientifique (FNRS)
Télévie
St Luc Hospital
Preliminary conclusion is that the analysis of lineage markers by
RTQ-PCR at diagnosis allows to differentiate AML, T ALL and B
ALL without specific blast selection and even if the blastic population is limited. In the future, we will extend this study to many
other genes in order to identify those of interest in diagnosis
and/or prognosis of acute leukemia.
Products and Services
Real time quantitative PCR
Gene sequencing
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STAFF
Total: 9
KEY WORDS FOR R&D
hematology
leukemia
molecular biology
realtime PCR
translocations
SENIOR SCIENTISTS
Dominique LATINNE
[email protected]
Tel. 32 (0) 2 764 31 45
Jean-Luc VAERMAN
[email protected]
Tel. 32 (0)2 764 31 75
Véronique DENEYS
[email protected]
Tel. 32 (0)2 764 17 31
WEB SITES
http://rch.adre.ucl.ac.be/browse/list_alpha/IMEX
http://rch.adre.ucl.ac.be/browse/list_alpha/SANG
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
C 3
Assays of tumor markers
SENIOR SCIENTISTS :
Marianne PHILIPPE
Philippe DE NAYER
Research Field and Subjects
STAFF
Total : 2
Assay of tumor markers in clinical settings and research.
KEY WORDS FOR R&D
clinical biology
clinical chemistry
clinical medicine
diagnosis
Products and Services
Immuno assay of tumor markers in gynecology, gastroenterology
neuroendocrinology and endocrinology.
SENIOR SCIENTISTS
Marianne PHILIPPE
[email protected]
Tel. 32 (0)2 764 17 35
Main Equipment
Immunochemistry automates
Philippe DE NAYER
[email protected]
Tel. 32 (0)2 764 25 63
Representative References
WEYNANTS P., BAUDHUIN M., MAJOIS F., MOENS D. and DE
NAYER Ph. Dosage sérique de la neurone spécifique énolase :
intérêt comme marqueur tumoral du cancer microcellulaire
bronchique. Acta Clin. Belgica, 44 (3) : 161-168, 1989.
VAN CANGH P.J., DE NAYER Ph., SAUVAGE Ph., TOMBAL B.,
ELSEN M., LORGE Fr., OPSOMER R. and WESE F.X. Free to total
prostate specific antigen (PSA) ratio is superior to total PSA in
differentiating benign prostate hypertrophy from prostate cancer. The Prostate, S7 : 30-34, 1996.
VAN CANGH P.J., DE NAYER Ph., DE VISSCHER L., SAUVAGE
Ph., TOMBAL B., LORGE F., WESE F.X., OPSOMER R.
Free to total PSA ratio improves the discrimination between
prostate cancer and benign hyperplasia in the diagnostic gray
zone of 1.8 to 10 ng/ml total PSA. Urology, 48S : 67-70, 1996.
ROELANTS V., DE NAYER Ph., BOUCKAERT A. and BECKERS C.
The predictive value of serum thyroglobulin in the follow-up of differentiated thyroid cancer. Eur. J. Nucl. Med., 24 : 722-727, 1997.
TOMBAL B., QUERTON M., DE NAYER Ph., SAUVAGE Ph.,
COSYNS J.P., FEYEARTS A., OPSOMER R., WESE F.X. and VAN
CANGH P.J. Free to total PSA ratio (ft PSA) does not improve
prediction of pathological stage and biochemical recurrence
after radical prostatectomy. J. Urology, 59 : 256-260, 2002.
WEB SITE
http://rch.adre.ucl.ac.be/browse/list_alpha/LBCM
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
C 4
Characterization of acute leukemias by gene expression
analysis : comparison of molecular and immunological
approaches; impact on diagnosis and prognosis.
SENIOR SCIENTISTS :
Pascale SAUSSOY
Dominique LATINNE
Augustin FERRANT
Research Field and Subjects
STAFF
Total : 6
The prognosis in acute myeloid leukemia depends on numerous
factors, including the white blood cell count, age, cytogenetics,
cell membrane immunological markers, and more recently
molecular markers. The aim is to improve the prognostic information using less but more specific genetic markers.
KEY WORDS FOR R&D
acute leukemia
clinical medicine
diagnosis
gene expression
hematology
immunophenotype
molecular biology
prognosis
Main Equipment
Sequencer, flow cytometry
SENIOR SCIENTISTS
Funding Sources
Pascale SAUSSOY
[email protected]
Tel. 32 (0)2 764 31 57
Fondation pour la recherche scientifique médicale (FRSM)
Télévie
Dominique LATINNE
[email protected]
Tel. 32 (0)2 764 31 45
Augustin FERRANT
[email protected]
Tel. 32 (0)2 764 18 80
WEB SITES
http://rch.adre.ucl.ac.be/browse/list_alpha/SANG
http://rch.adre.ucl.ac.be/browse/list_alpha/IMEX
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
C 5
Immunodiagnosis of paraneoplastic neurological disorders
SENIOR SCIENTIST :
Christian SINDIC
S., DEHAENE I., GOBIET Y., GOKA S., LALOUX P., MONTEYNE
PH., PEETERS A., PIERRE PH., GILLET S., VAN DEN BERGH P.Y.K.,
WINDHAUSEN K., LATERRE E.C. The anti-Hu syndrome : a clinical and immunological study of 7 cases. Acta Neurol. Belg.,
1996, 96 : 117-125.
DREESSEN J., JEANJEAN A.P., SINDIC C.J.M. Paraneoplastic
limbic encephalitis : diagnostic relevance of CSF analysis and
total body PET scanning. Acta Neurol. Belg., in press.
Research Field and Subjects
Paraneoplastic neurological disorders are devastating diseases
due to an autoimmune injury of the peripheral and/or the central nervous system triggered by the presence of an often occult
cancer, most frequently a small cell lung carcinoma, a gyneacological or a breast cancer, etc.
The neoplastic cells express an antigen also present on neural
cells, and the anti-tumoral immune reaction leads to an autoimmune attack of the nervous system. A rapid diagnosis permits the detection of the cancer, its treatment and an immunosuppressive therapy of the neurological disorder.
Funding Sources
Own resources (patronage)
Products and Services
STAFF
Total : 4
Detection of anti-neuronal nucleoproteins antibodies in the
serum and the CSF (ANNA-1 or anti-Hu, ANNA-2 or anti-Ri,
anti-Purkinje cell antibody or anti-Yo, anti-Myelin associated
Glycoprotein, anti-amphiphysine, anti-Ma1…).
KEY WORDS FOR R&D
autoimmunity
neurological diseases
onconeural antigens
paraneoplastic disorders
smal cell lung carcinoma
Main Equipment
ELISA
Western-Blot apparatus
Ultracentrifugation
SENIOR SCIENTIST
Christian SINDIC
[email protected]
Tel. 32 (02) 764 10 82
Representative References
WEB SITE
SINDIC C.J.M., BOUCQUEY D., BISTEAU M., LALOUX P.,
BRUCHER J.M., LATERRE E.C. Monoclonal IgM gammapathy
with anti-myelin associated glycoprotein (MAG) activity and
polyneuropathy. A study of three cases. Acta Neurol. Belg.,
1989, 89 : 331-345.
SINDIC C.J.M., ANDERSSON M., BOUCQUEY D., CHALON
M.P., BISTEAU M., BRUCHER J.M., LATERRE E.C. Anti-Purkinje
cells antibodies in two cases of paraneoplastic cerebellar
degeneration. Acta Neurol. Belg., 1993, 93 : 65-77.
PIERET F., SINDIC C.J.M., CHALON M.P., WARNY M., BOLYN
http://rch.adre.ucl.ac.be/browse/list_alpha/NCHM
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
C 6
Development of new molecular based diagnostic strategies
in prostate cancer
SENIOR SCIENTISTS :
Bertrand TOMBAL
Jean LUC GALA
cifically designed for prostate cancer prognostic and genetic
response to new biological agents.
Research Field and Subjects
Prostate cancer is the most frequent cancer in men aged more
than 55 years old. Despite important progress in early diagnostic and therapeutic procedures, there are still a lot of patients
who develop metastatic spread and require some form of systemic therapy.
The lab offers a direct connection with early human use (phase
I/II) trials and in vitro assays.
Main Equipment
It has become clear that in order to prevent metastatic spread,
it is required to combine hormonal therapy, chemotherapy and
new biological agents earlier in the course of the disease.
Such aggressive strategy requires identifying precisely patients
at risk of progression. Current staging procedures rely indeed
only on clinical, biological and pathological markers which
clearly lack specificity at the individual level.
Cell culture
Cloning and sequencing of gene products
DNA array technologies
Isolation of metastatic cells from human samples by positive
selection
Real-Time PCR
In the last few years, our group has developed and implemented molecular approaches to identify subjects at expression.
These were initially based on the ability to identify early metastatic spread by retrieving the RNA of prostatic cells circulating
freely in the blood of the patients.
Representative References
VAN CANGH P.J., DE NAYER P., SAUVAGE P., TOMBAL B.,
ELSEN M., LORGE F., OPSOMER R., WESE F.X. Free to total
Prostate-Specific Antigen (PSA) ratio is superior to Total-PSA in
differentiating Benign Prostate Hypertrophy from Prostate
Cancer. Prostate 7 (supl.), 30-34, 1996.
VAN CANGH P.J., DE NAYER P., DE VISSCHER L., SAUVAGE P.,
TOMBAL B., LORGE F., WESE F.X., OPSOMER R. Free to Total
prostate-specific antigen (PSA) ratio improves the discrimination between prostate cancer and benign prostatic hyperplasia
(BPH) in the diagnostic gray zone of 1.8 to 10 ng/ml total PSA.
Urology. 48 (6A Suppl.): 67-70, 1996.
GALA J-L., HEUTERSPREUTE M., HANON F., TOMBAL B., VAN
CANGH P., DE NAYER P., PHILIPPE M.: Illegitimate transcription
of the prostate specific antigen (PSA) and prostate-specific
membrane antigen (PSM) in blood cells: a genuine limitation for
the detection of prostate micrometastases. Clin. Chem. 44(3):
472-481, 1998.
GALA J.L., LORIC S., GUIOT Y., BRASSEUR F., HEUSTERSPREUTE
M., ESCHWÈGE P., HANON F., PHILIPPE M., DE NAYER P., VAN
CANGH P., TOMBAL B. Diagnostic and prognostic value of
Prostate Specific Membrane Antigen in Transitional Cell
Carcinoma of the Bladder. Clinical Cancer Research, 6: (10)
4049-4054, 2000.
Today with the development of modern DNA array technologies, circulating cells are not only identified but also retrieved
from the bone marrow of the patients and their molecular profile clearly identified.
These techniques are particularly useful to :
Identify certain molecular patterns suggesting a higher risk of
progression.
Apply molecular evaluation to new drugs by embedding
pharmacodynamic endpoints into early clinical trials.
Products and Services
The lab offers wide range of molecular diagnostic tools including standard and real-time PCR techniques, sequencing of
gene products.
In collaboration with EPPENDORF Array Technology, we are
implementing low cost low density DNA Array techniques spe-
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LARIBI A., BERTEAU P., GALA J.L., ESCHWÈGE P., BENOIT G.,
TOMBAL B., SCHMITT F., LORIC S. Blood-borne RT-PCR assay for
prostasin-specific transcript to identify circulating prostate cells
in cancer patient. Eur. Urol. 39 (1):65-71, 2001.
TOMBAL B., VAN CANGH P., LORIC S., GALA J.L. Prognostic
value of circulating prostate cells in patients with a rising PSA after
radical prostatectomy. The Prostate, 56(3), 163-170, 2003.
STAFF
Total : 9
KEY WORDS FOR R&D
DNA
DNA Array
molecular diagnostic
prostate cancer
RNA
tumor marker
Funding Sources
Fonds national de la recherche scientifique (FNRS)
Fondation pour la recherche scientifique médicale (FRSM)
Télévie
First Entreprise Région Wallonne
SENIOR SCIENTISTS
Bertrand TOMBAL
[email protected]
Tel. 32 (0)2 764 55 40
Jean LUC GALA
[email protected]
Tel. 32 (0)2 764 31 65
Partnership
Pr. Sylvain Loric, Biochemistry & Genetics Laboratory, Henri
Mondor AP-HP University Hospital, Creteil, France.
Dr Samuel Denmeade, Division of Experimental Therapeutic
Johns Hopkins Oncology Center, Baltimore, USA.
WEB SITES
http://www.fymu.ucl.ac.be
http://www.lbcm.ucl.ac.be
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
D 1
Rigid registration of PET, CT and MR modalities for
radiotherapy planning and dense deformation field
estimation for brain intra-operative images registration
SENIOR SCIENTIST :
Benoît MACQ
algorithms. The registration algorithm we developed is integrated in the Registration and Segmentation Toolkit
(http://www.itk.org) and is based on the optimization of the
Mutual Information metric.
Research Field and Subjects
The Communications and Remote Sensing Laboratory has
developed for ten years an activity in the field of medical images processing. We have undertaken a close collaboration with
the Oncology department (Pr. V. Gregoire and Dr. X. Geets). The
focus of our work has been the development of a visualization
platform called Medical Studio. Medical Studio includes facilites
for computer aided contouring of head and neck tumors; 3D
registration techniques to bring into alignment medical images
acquired with different modalities.
This software has been integrated in the Medical Studio visualization environment developed in our laboratory within the
Région Wallonne Mercator project.
The integrated modules contain facilities for the registration
and segmentation of medical images. The plug-in for registration in Medical Studio provides an automatic and a manual procedure. The use of the former increases considerably the variability of inter-operator exchanges. Through automatic registration it is now possible to obtain separately the same results
without consulting an expert. The fusion of the images can still
be improved by manual registration.
Two target applications have emerged : fast non-rigid registration algorithms to fuse pre-operative information (segmentations, planning) and intra-operative MRI images acquired
during neurosurgery and multi-modal registration of head and
neck images for radiotherapy planning.
The on levelset, growing treshold or watershed algorithms
based automatic segmentation is used for automatic contouring of tumors. The presence of manual segmentation utilities
permits high precision outlining. Due to these segmentation
tools 3D reconstruction and size estimation of the contaminated tissues has become possible. Any part of the tissues can be
highlighted by the use of differently contrasted masks, which
can be individually created and colored.
The intra-operative algorithm designed for brain intra-operative
and pre-operative images uses a Finite Element model of the
brain and fast segmentations algorithms. Surfaces (cortex, ventricles, tumor) are extracted in both modalities and correspondances are found using an active surface algorithm subject to a
linear elastic regularization. These surface displacements are
then propagated to the whole volume using a Finite Element
Model (FEM) of the brain. This model allows to employ different
material characteristics for different tissues.
Future developments will concern a medical aid module, destined to help to evaluate the effectiveness of a patient’s treatment by statistical analysis. These should be based on the size
estimation of the tumor and on different medical informations
introduced by the medical staff during the treatment. An other
part of the research is dedicated to intra-operative studies. For
these parts the software is still in experimental stage.
Furthermore, the solving of the FEM linear system has been
implemented for parallel architectures to meet computation
time requirements in the operating room. The same algorithm
has also been applied for intra-operative fusion of pre-operative 1.5T MRI images in 0.5T MRI images acquired during prostate biopsy. More recently, we have proposed a Mutual
Information based non-rigid registration technique to improve
the matching of internal structures inside the prostate.
Products and Services
Radiotherapic planning has been shown to be significantly
improved when different modalities are fused for a better delineation of the target volume. Therefore, we developed a collaboration with the UCL Department of Radiation Oncology to
test and validate Mutual Information based rigid registration
Rigid and Non-Rigid registration tools.
Visualization environment for 3D medical images (Medical
Studio).
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Main Equipment
Partnership
Within a short time, a public version of Medical Studio will
be downloadable from the www.medicalstudio.org website.
This software includes visualization, hand segmentations, rigid
registration plugins.
Oncology and Radiology departments (St-Luc Hospital), Brussels,
Belgium.
Multitel asbl, Mons, Belgium.
Brigham and Women’s Hospital, Surgical Planning Laboratory
and Computational Radiology Laboratory, Boston, USA.
Representative References
STAFF
A. BHARATHA, M. HIROSE, N. HATA, S. WARFIELD, M. FERRANT,
K. ZOU, E. SUAREZ-SANTANA, J. RUIZ-AZOLA, A. D’AMIO, R. CORMACK, F. JOLESZ, and C. TEMPANY. Evaluation of three-dimensional finite element-based deformable registration of pre- and intraoperative prostate imaging. Med. Phys., Dec. 2001, 28(12) : 255-60.
M. FERRANT, A. NABAVI, B. MACQ, R. KIKINIS & S. WARFIELD.
Serial registration of intra-operative MR images of the brain.
Medical Image Analysis, Vol. 6, December 2002, pp. 337-359.
A. DU BOIS D’AISCHE, M. DE CRAENE, B. MACQ, V. GREGOIRE. Fully Automatic rigid-body registration for multi-modal
head and neck images. Technical Report TELE, 2002.
M. DE CRAENE, A. DU BOIS D’AISCHE, B. MACQ, F. KIPFMUELLER, N. WEISENFELD, S. HAKER, S.K. WARFIELD. MultiModal Non-Rigid Registration using a Stochastic Gradient
Approximation. Accepted in International Symposium on
Biomedical Imaging, 2004.
M. FERRANT. Physics-based deformable modeling of volumes
and surfaces for medical image registration, segmentation and
visualization. Ph.D. Thesis, Communications and Remote
Sensing Laboratory, UCL.
Total : 10
KEY WORDS FOR R&D
diffusion tensor imaging processing
multi-modal registration
SENIOR SCIENTIST
Benoît MACQ
[email protected]
Tel. 32 (0)10 47 22 71
WEB SITES
http://www.medicalstudio.org
http://www.tele.ucl.ac.be
Awards
Informatics award, IBM Belgium.
Funding Sources
Mercator Project (Région Wallonne)
Fonds pour la formation à la recherche dans l’industrie et
dans l’agriculture (FRIA)
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
D 2
Functional magnetic resonance (NMR, EPR), spectroscopy
and imaging in tumors
SENIOR SCIENTIST :
Bernard GALLEZ
dient artefacts in BOLD contrast imaging of head and neck
tumors. Phys. Med. Biol. 47, 1819-1825, 2002.
B.F. JORDAN, V. GRÉGOIRE, R.J. DEMEURE, P. SONVEAUX, O.
FERON, J. O’HARA, V. VANHULLE, N. DELZENNE and B. GALLEZ.
Insulin increases the sensitivity of tumors to irradiation:
Involvement of an increase in tumor oxygenation mediated by
a nitric oxide dependent decrease of the tumor cells oxygen
consumption. Cancer Res. 62, 3555-3561, 2002.
C. BAUDELET AND B. GALLEZ. How Blood Oxygen Level
Dependent (BOLD) contrast is correlated to the oxygen partial pressure of oxygen in tumors? Magn. Reson. Med. 48, 980-986, 2002.
P. SONVEAUX, C. DESSY, A. BROUET, B. JORDAN, V. GRÉGOIRE,
B. GALLEZ, J.L. BALLIGAND and O. FERON. Modulation of the tumor
vasculature functionality by ionizing radiation accounts for tumor
radio-sensitization and promotes gene delivery. FASEB J. 16, 19791981, 2002.
B.F. JORDAN, N. BEGHEIN, M. AUBRY, V. GRÉGOIRE and B.
GALLEZ. Potentiation of radiation-induced regrowth delay by
isosorbide dinitrate in FSa II murine tumors. Int. J. Cancer
103,138-141, 2003.
B.F. JORDAN, P. SONVEAUX, O. FERON, V. GRÉGOIRE and B.
GALLEZ. Nitric oxide mediated increase in tumor blood flow and
oxygenation of tumors implanted in muscles stimulated by electric
pulses. Int. J. Radiat. Oncol. Biol. Phys. 55, 1066-1073, 2003.
C. BAUDELET and B. GALLEZ. A cluster analysis of fMRI times
series in tumors to study the heterogeneity of hemodynamic
response to treatments. Magn. Reson. Med. 49, 985-990, 2003.
M. ZDRAVKOVA, N. CROKART, F. TROMPIER, B. ASSELINEAU, E.
GAILLARD-LECANU, B. GALLEZ and R. DEBUYST. Retrospective
dosimetry after criticality accidents using low frequency EPR : a
study on whole human teeth irradiated in a mixed neutron and
gamma field. Radiat. Res. 160, 168-173, 2003.
P. MAHY, M. DE BAST, B. GALLEZ, J. GUEULETTE, C.J. KOCH, P.
SCALLIET, and V. GRÉGOIRE. In vivo co-localization of 2-nitroimidazole EF5 fluorescence intensity and electron paramagnetic resonance
oximetry in mouse tumors. Radiother. Oncol. 67, 53-61, 2003.
B.F. JORDAN, P. SONVEAUX, O. FERON, V. GRÉGOIRE, N.
BEGHEIN, C. DESSY and B. GALLEZ. Nitric oxide as radiosensitizer :
evidence for an intrinsic role additive to its effect on oxygen delivery
and consumption. Int. J. Cancer, 109, 768-773, 2004.
P. SONVEAUX, C. DESSY, P. MARTINIVE, X. HAVAUX, B.F. JORDAN,
B. GALLEZ, V. GRÉGOIRE, J.L. BALLIGAND and O. FERON. Endothelin-
Research Field and Subjects
The major theme of the research is to understand how the
tumor microenvironment influences the response to treatments. Two main areas of research are involved :
1. Development of sensors for monitoring the oxygen in tissues
by EPR.
Selection of paramagnetic materials possessing favourable features
for oximetry. Microencapsulation of oxygen sensors in biocompatible
films to improve their performance in vivo and their biocompatibility.
2. Applications of MR (EPR and NMR) to characterize the microenvironment in tumors and modulate the response to anti-cancer treatments.
Use of combination therapies against cancer (vasoactive agents
+ radiotherapy/antiangiogenesis + radiotherapy…) to improve
the response of tumors to treatments: characterization of pO2,
flow, oxygen consumption, permeability of vessels, nitric
oxide,… and correlation with the tumor growth.
Products and Services
EPR in vitro (free radicals, including spin trapping)
EPR in vivo in small animals
NMR imaging in small animals
Oxygen measurements
Flow measurements
Main Equipment
NMR spectrometer and imaging 4.7 Tesla for small animals
EPR spectrometer (9 GHz, X-Band) for in vitro experiments
EPR spectrometer (1 GHz, L-Band) for in vivo experiments
OxyLite (pO2 measurements by fluorescence quenching)
OxyFlo (laser-doppler)
Representative References
R.J. DEMEURE, B.F. JORDAN, Q.X. YANG, N. BEGHEIN, M.B.
SMITH, V. GRÉGOIRE and B. GALLEZ. Removal of local field gra-
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FNRS (FRSM, Télévie)
Fonds Joseph Maisin
Fonds spécial de recherche (Communauté Française)
1 is a critical mediator of myogenic tone in tumor arterioles : implications for cancer treatment. Cancer Res. 64, 3209-3214, 2004.
M. LAN, N. BEGHEIN, N. CHARLIER, and B. GALLEZ. Carbon
blacks as EPR sensors for localized measurements of tissue oxygenation. Magn. Reson. Med. 51, 1272-1278, 2004.
C. BAUDELET, R. ANSIAUX, B.F. JORDAN, X. HAVAUX, B.
MACQ and B. GALLEZ. Physiological noise in murine tumors
using T2* gradient echo imaging : a marker of tumor acute
hypoxia ? Phys. Med. Biol. 49, 3389-3411, 2004.
C. BAUDELET and B. GALLEZ. Effect of anesthesia on the signal
intensity in tumors using BOLD-MRI. Comparison with flow measurements by laser-doppler flowmetry and oxygen measurements by
luminescence probes. Magn. Reson. Imaging 22, 905-912, 2004.
B. GALLEZ, C. BAUDELET, B.F. JORDAN. Assessment of tumor
oxygenation by EPR oximetry: Principles and applications. NMR
Biomed. 17, 240-262, 2004
Partnership
Pharmacotherapy Unit and Radiobiology Unit, UCL, Brussels,
Belgium.
EPR Research Center, Dartmouth Medical School, USA.
Arizona Cancer Center, Tucson, USA.
STAFF
Total: 9
KEY WORDS FOR R&D
angiogenesis
biocompatibility
biomaterials
biomedical engineering
biophysics
biosensors
chemotherapy
EPR
free radicals
functional imaging
hemodynamics
imaging
MRI
nitric oxide
NMR
oxygen
pharmacology
radiotherapy
radiosensitivity
spectroscopy
spin trapping
tumor
Patents
Carbon blacks as EPR sensors for localized measurements of tissue oxygenation. US Patent, submitted 2003.
Awards
B. Gallez :
1995, Société Belge des Sciences Pharmaceutiques
1998, Fondation Universitaire- Alumni
Award Paul Van de Velde 2000 (Nouveaux outils diagnostiques
ou thérapeutiques)
Young Investigator Award, International EPR Society 2000
Award Léopold et Marthe Delsaux-Champy 2004 (Prévention,
traitement ou physiopathologie de maladies cardiovasculaires ou
cancéreuses)
B. Jordan :
Ishango francophone 2003.
SENIOR SCIENTIST
Bernard GALLEZ
[email protected]
Tel. 32(0)2 764 27 92
Funding sources
WEB SITE
http://www.md.ucl.ac.be/rema
NCI (National Cancer Institute, USA)
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
D 3
Anatomic and functional imaging of liver tumors
SENIOR SCIENTIST :
Bernard VAN BEERS
Software for the analysis of perfusion and diffusion images
Animal facilities
Research Field and Subjects
Our research in cancerology has been centred on the assessment of the value of non-specific and liver-specific contrast
agents to detect and characterize hepatic tumors by magnetic
resonance imaging.
These studies have been performed in humans with various primary and secondary liver tumors and in rats bearing chemically-induced or transplantable hepatocellular carcinomas.
We have shown that, depending on the specific contrast agent
used, several parameters such as the tumorous blood flow,
blood volume, interstitial volume, Kupffer cell activity, and
tumorous cellular differentiation determine the enhancement
pattern in magnetic resonance imaging.
Recently we have been interested in quantitative perfusion and
diffusion imaging of the liver.
We have developed and validated the use of a pharmacokinetic model to calculate the liver perfusion parameters from
contrast-enhanced magnetic resonance or computed tomographic images. Permeability changes of the hepatic sinusoids have
been demonstrated by using multiple contrast agents of different molecular weights.
These quantitative imaging methods are used to assess the perfusion and permeability abnormalities in liver tumors being
used to monitor the effects of various drugs, including inhibitors of angiogenesis.
Representative References
GRANDIN C., VAN BEERS B.E., ROBERT A., GIGOT J.F., GEUBEL
A., PRINGOT J. (1995) Benign hepatocellular tumors: MRI after
superparamagnetic iron oxide administration. J. Comput.
Assist. Tomogr. 19: 412-418.
GRANDIN C., VAN BEERS B.E., DEMEURE R., GOUDEMANT
J.F., MOTTET I., PRINGOT J. (1995) Comparison of gadoliniumDTPA and polylysine-gadolinium-DTPA-enhanced magnetic resonance imaging of hepatocarcinoma in the rat. Invest. Radiol.
30: 572-581.
VAN BEERS B., DAURES J.P., PRINGOT J., MATHIEU D., BRUEL
J.M. (1996) Detection of hepatic metastases: ferumoxidesenhanced MR imaging versus unenhanced MR imaging and CT
during arterial portography. Radiology 200: 785-792.
VAN BEERS B.E., GALLEZ B., PRINGOT J. (1997) Contrastenhanced MR imaging of the liver. Radiology 203: 297-306.
VAN BEERS B.E., LACROSSE M., JAMART J., GRANDIN C., GIGOT
J.F., HORSMANS Y., DEMEURE R., PRINGOT J. (1997) Detection and
segmental location of malignant hepatic tumors: comparison of ferumoxides-enhanced gradient-echo and T2-weighted spin-echo MR
imaging. Am. J. Roentgenol. 168: 713-717.
GRANDIN C.B., VAN BEERS B.E., PAUWELS S., DEMEURE R.,
JAMART J., PRINGOT J. (1997) Ferumoxides and Tc-99m sulfur
colloid: comparison of the tumor-to-liver uptake in focal nodular hyperplasia. J. Magn. Reson. Imaging, 7: 125-129.
VILGRAIN V., VAN BEERS B.E., FLEJOU J.F., BELGHITI J., DELOS
M., GAUTIER A.L., ZINS M., DENYS A., MENU Y. (1997)
Intrahepatic cholangiocarcinoma: MRI and pathologic correlation in 14 patients. J. Comput. Assist. Tomogr., 21: 59-65.
GOUDEMANT J.F., VAN BEERS B.E., DEMEURE R., GRANDIN
C., DELOS M., PRINGOT J. (1998) Comparison of unenhanced
and gadoxetate disodium-enhanced spin-echo magnetic resonance imaging for the detection of experimental hepatocellular
carcinoma in the rat. Invest. Radiol., 33: 80-84.
VAN BEERS B.E., MATERNE R., LACROSSE M., JAMART J.,
SMITH A.M., HORSMANS Y., GIGOT J.F., GILON R., PRINGOT J.
(1999) MR imaging of hypervascular liver tumors: timing opti-
Products and Services
MR imaging of liver tumors
Perfusion and diffusion weighted imaging of liver tumors
Assessment of specific contrast agents
Drug monitoring
Main Equipment
Three 1.5 Tesla MR scanners
3 Tesla MR scanner
Four multislices CT scanners
Image processing workstations
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57
mization during the arterial phase. J. Magn. Reson. Imaging, 9:
562-567.
MATERNE R., HORSMANS Y., JAMART J., SMITH A.M., GIGOT
J.F., VAN BEERS B.E. (2000) Gadolinium-enhanced arterialphase MR imaging of hypervascular liver tumors: comparison
between tailored and fixed scanning delays in the same
patients. J. Magn. Reson. Imaging, 11: 244-249.
MATERNE R., VAN BEERS B.E., SMITH A.M., LECONTE I.,
JAMART J., DEHOUX J.P., KEYEUX A., HORSMANS Y. (2000)
Non-invasive quantification of liver perfusion with dynamic
computed tomography and a dual-input one-compartmental
model. Clin. Sci. (Lond) 99: 517-525.
VAN BEERS B.E., SEMPOUX C., MATERNE R., DELOS M.,
SMITH A.M. (2001) Biodistribution of ultrasmall iron oxide particles in the rat liver. J. Magn. Reson. Imaging, 13: 594-599.
MATERNE R., SMITH A.M., PEETERS F., DEHOUX J.P., KEYEUX
A., HORSMANS Y., VAN BEERS B.E. (2002) Assessment of
hepatic perfusion parameters with dynamic MRI. Magn. Reson.
Med. 47: 135-142.
VAN BEERS B.E., MATERNE R., ANNET L., HERMOYE L.,
SEMPOUX C., PEETERS F., SMITH A.M., JAMART J., HORSMANS
Y. (2003) Capillarization of the sinusoids in liver fibrosis:
Noninvasive assessment with contrast-enhanced MRI in the rabbit. Magn. Reson. Med., 49: 692-699.
ANNET L., MATERNE R., DANSE E., JAMART J., HORSMANS Y.,
VAN BEERS B.E. (2003) Hepatic flow parameters measured with
MR imaging and Doppler sonography: correlations with degree of
cirrhosis and portal hypertension. Radiology , 229: 409-414.
STAFF
Total : 4
KEY WORDS FOR R&D
contrast agents
diffusion imaging
hepatocellular carcinoma
image processing
liver tumors
magnetic resonance imaging
medical imaging, radiology, tomography
perfusion imaging
SENIOR SCIENTISTS
Bernard VAN BEERS
[email protected]
Tel. 32(0)2 764 29 45
WEB SITE
http://www.md.ucl.ac.be/rdgn
Funding Sources
Fonds national de la recherche scientifique (FNRS)
Partnership
Division of imaging science and biomedical engineering,
University of Birmingham, Great Britain.
Laboratoire de recherche en imagerie, Inserm U 494, Faculté
de médecine Necker, Paris, France.
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
E 1
Academic clinical trials in medical oncology
SENIOR SCIENTISTS :
Jean-Pascal MACHIELS
Jean-François BAURAIN
BERLIÈRE M., GALANT C., MARQUES G., PIETTE P., DUCK L.,
FELLAH L., DONNEZ J. and MACHIELS J.P. LHRH agonists offer
very good protection against adverse gynaecological induced
by tamoxifen. Eur. J. Cancer, 2004, 40 : 1855-61.
DUCK L.; BAURAIN J.F. and MACHIELS J.P. Treatment of pulmonary angiosarcoma. Chest. 2004; 126(1):317-8
HENRY S., MACHIELS J.P., BAURAIN J.F. and DUCK L. Liver
insufficiency due to breast cancer metastases: fast biological
response with capecitabine. Acta Oncologica, 2004; 43(3):302.
DUCK L., SEMPOUX C., HONHON B., COSTER B., COCHE
J.C., CANON J.L., KERGER J., SCALLIET P., HUMBLET Y. and
MACHIELS J.P. A phase II study of preoperative oxaliplatin,
capecitabine, and external beam radiotherapy in patients with
locally advanced rectal adenocarcinoma. Proceedings of the
American Association of Clinical Oncology, 2004, Submitted.
MACHIELS J.P. and al. A phase II study of preoperative oxaliplatin, capecitabine, and external beam radiotherapy in patients
with locally advanced rectal adenocarcinoma. Journal of clinical
Oncology, 2004, Submitted.
MACHIELS J.P., MAZZEO F. and BERLIÈRE M. Neoadjuvant
chemotherapy versus primary surgery for advanced-stage ovarian cancer: the question remains opened. Gynecologic
Oncology, 2004, In Press. (I.F.2,1).
Research Field and Subjects
We have created a section able to design and conduct clinical
trials non-sponsored by pharmaceutical companies. These are
purely academic studies asking important questions for clinicians. Our section is taking care of designing, writing and coordinating (randomisation and monitoring) the protocols.
Topics:
Efficacy of neoadjuvant chemotherapy in ovarian cancer.
Efficacy of Gemcitabine in cholangiocarcinoma Preoperative radiochemotherapy in patients with locally advanced rectal cancer.
Chemotherapy in elderly patients with metastatic colorectal cancer.
A Belgian study to compare two chemotherapy regimens in
patients with hormone refractory prostate cancers.
Meta-analysis of efficacy of chemotherapy in metastatic
salivary gland tumors.
Main Equipment
Data managing unit
Randomisation programmes
Representative References
Awards
MAZZEO F., BERLIÈRE M., SQUIFFLET J., LONGUEVILLE J.,
BRICHARD J., D’HONDT V., HUMBLET Y., DONNEZ J. and
MACHIELS J.P. Neoadjuvant chemotherapy followed by surgery
and adjuvant chemotherapy in patients with advanced-stage
ovarian cancer. Proceedings of the American Association of
Clinical Oncology, 2002, 171b : abstr. 2501.
DUCK L., HUMBLET Y., GIGOT J.F., LONNEUX M., BAURAIN J.F.
and MACHIELS J.P. Gemcitabine in advanced cholangiocarcinoma:
a single-center retrospective study. Proceedings of the American
Association of Clinical Oncology, 2002, 125b : abst.2314.
MAZZEO F., BERLIÈRE M., KERGER J., SQUIFFLET J., D’HONDT
V., HUMBLET Y., DONNEZ J. and MACHIELS J.P. Neoadjuvant
chemotherapy followed by surgery and adjuvant chemotherapy
in patients with advanced-stage ovarian cancer. Gynecologic
Oncology, 2003; 90: 163-169.
J.-P. Machiels :
2002, AMGEN award, Belgian Society of Medical Oncology.
2000, Translational Research award; First prize, Johns Hopkins
Oncology Center, Baltimore, USA
Funding Sources
Various grants
Partnership
KUL, Profs Van Custem et Haustermans, Leuven, Belgium.
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STAFF
Total 4
KEY WORDS FOR R&D
academic studies
chemotherapy
clinical trial
radiotherapy
statistics
SENIOR SCIENTISTS
Jean-Pascal MACHIELS
[email protected]
Tel. 32 (0)2 764 54 57
Jean-François BAURAIN
[email protected]
Tel. 32 (0)2 764 54 72
WEB SITE
http://rch.adre.ucl.ac.be/browse/list_alpha/ONCO
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
E 2
Clinical studies in hematology
SENIOR SCIENTISTS :
Augustin FERRANT
Lucienne MICHAUX
Eric VAN DEN NESTE
Research Field and Subjects
with large B CD20+ cells (IPI age adjusted= 2-3).
LNH 03-6B : Randomized study comparing R-CHOP administered each 14 days and 21 days respectively. For the second
part, Darbepoietin alpha (ARANESP) vs symptomatic treatment
for anemia in patients with diffuse lymphoma with large B
CD20+ cells B in patients between 66-80 years.
Protocol 20031231 : darbepoetin alpha
A randomized, double blind, active-controlled study of darbepoetin alpha for the treatment of anemia in subjects with nonmyeloid malignancy receiving multicycle chemotherapy.
GRAALL2003
Multicentric protocol testing the feasibility of a therapeutic
approach in acute lymphoblastic leukemia in young adults.
Aim : collection of major prognostic factors on consolidation of
induction therapy and on the indication of an allograft in CR1.
HOVON Protocols
HOVON 42 : Randomized induction and post induction therapy in adult patients (<= 60 yrs of age) with acute myelocytic
leukemia (AML) or refractory anemia with excess of blasts
(RAEB, RAEB-t) with IPSS score ≥ 1.5.
The aim is
1. to evaluate, comparing 2 different doses of cytarabine
during induction I and II, the complete and partial remission
and the global survival.
2. to evaluate, by randomization, the therapeutic effect of a myeloablative chemotherapy with allograft in medium or high risk of
AML in comparison with an intensive post remission chemotherapy.
3. to estimate the value of a family- and nonrelated allograft
among patients with an AML.
HOVON 43 : Randomized induction and post induction therapy in older patients (>= 61 yrs of age).
The aim is to evaluate the effect of high dose daunomycin during
the first induction cure on survival without event, and to evaluate,
by randomization, the effect of the GO-treatment post-remission.
HOVON 51 : A dose-ranging phase I/II study of STI571
(Imatinib) in combination with Cytarabin in patients with first
chronic phase Chronic Myeloid Leukemia.
Objectives:
1. to evaluate the feasibility of a treatment combining STI571
and cytarabine
2. to determine the rate and duration of molecular, complete
hematological and complete cytogenetic remissions
3. to determine the time before progression and the global survival
AFR Protocols
AFR03 : Phase II study of Imatinib (GlivecTM) associated to
intensive consolidation chemotherapy in adults with ALL-Phi+
and/or BCR-ABL+ leukaemia in first complete remission.
Objective : evaluation of the combination Imatinib and chemotherapy, on day 45 : rate of molecular response.
AFR09 : Evaluation of Imatinib (GlivecTM) after induction treatment in ALL Phi+ patients over 55 years old.
Objective: improving the survival.
AUTO-LLC Protocol
Phase III randomized protocol comparing stem cell transplantation to a conventional treatment in stages B and C in 18-65
years-old-CLL patients.
LNH Protocols
Representative References
LNH 01-5B : Randomized study comparing ACVBP + Rituximab vs
CHOP + rituximab in patients between 60-65 years with diffuse
large cell B lymphoma.
LNH 03B : Randomized study comparing ACVBP vs ACVBP +
Rituximab in patients between 18-65 years with localized diffuse lymphoma with large B CD20+ cells.
LNH 03-3B : Randomized study comparing ACVBP + Rituximab
in patients between 18-59 years with high risk diffuse lymphoma
LOWENBERG B., VAN PUTTEN W.L., FERRANT A., OSSENKOPPELE G., VELLENGA E., VERDONCK L.F., GRATWOHL A.,
BOOGAERTS M.A. Peripheral blood progenitor cell transplantation as an alternative to autologous marrow transplantation in
the treatment of acute myeloid leukemia. Stem. Cells. 1997; 15
Suppl 1: 177-80, discussion 181.
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WENDUM D., SEBBAN C., GAULARD P., COIFFIER B., TILLY H.,
CAZALS D., BOEHN A., CASASNOVAS R.O., BOUABDALLAH R.,
JAUBERT J., FERRANT A., DIEBOLD J., DE MASCAREL A., GISSELBRECHT C. Follicular large-cell lymphoma treated with
intensive chemotherapy: an analysis of 89 cases included in the
LNH87 trial and comparison with the outcome of diffuse large
B-cell lymphoma. Groupe d’Etude des Lymphomes de l’Adulte.
J. Clin. Oncol., 1997 (4): 1654-63.
PENIKET A.J., RUIZ DE ELVIRA M.C., TAGHIPOUR G., CORDONNIER C., GLUCKMAN E., DE WITTE T., SANTINI G., BLAISE
D., GREINIX H., FERRANT A., CORNELISSEN J., SCHMITZ N.,
GOLDSTONE A.H. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher
procedure-related mortality rate than autologous transplantation. Bone Marrow Transplant., 2003 (8): 667-78.
VAN DEN NESTE E., SMAL C., CARDOEN S., DELACAUW A.,
FRANKARD J., FERRANT A., VAN DEN BERGHE G., BONTEMPS
F. Activation of deoxycytidine kinase by UV-C-irradiation in
chronic lymphocytic leukemia B-lymphocytes. BiochemPharmacol., 2003 Feb 15; 65(4): 573-80.
STAFF
Total : 3
KEY WORDS FOR R&D
AML
clinical medicine
diffuse lymphoma
hematology
hovon
Imatinib
phase I/II
randomization
stem cell transplantation
STI571
SENIOR SCIENTISTS
Augustin FERRANT
[email protected]
Tel. 32(0)2 764 18 80
Lucienne MICHAUX
[email protected]
Tel. 32(0)2 764 18 09
Eric VAN DEN NESTE
[email protected]
Tel. 32(0)2 764 18 75
Partnership
Multicentric, international studies
WEB SITES
http://rch.adre.ucl.ac.be/browse/list_alpha/SANG
http://rch.adre.ucl.ac.be/browse/list_alpha/GMED
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
E 3
Clinical studies in hematology :
Multiple myeloma, Hodgkin’s lymphoma
SENIOR SCIENTISTS :
Augustin FERRANT
Lucienne MICHAUX
Eric VAN DEN NESTE
Representatives References
Research Field and Subjects
Multiple myeloma
ROBIN V., LEBACQ J., MICHAUX L., FERRANT A. Hodgkin’s
disease and hypothermia : case report and review of the literature. Ann. Hematol., 2002 Feb; 81(2): 106-7.
VAN DEN NESTE E., LOUVIAUX I., MICHAUX J.L., DELANNOY
A., MICHAUX L., SONET A., BOSLY A., DOYEN C., MINEUR P.,
ANDRE M., STRAETMANS N., COCHE E., VENET C., DUPREZ T.,
FERRANT A. Phase I/II study of 2-chloro-2’-deoxyadenosine with
cyclophosphamide in patients with pretreated B cell chronic
lymphocytic leukemia and indolent non-Hodgkin’s lymphoma.
Leukemia. 2000 Jun; 14(6): 1136-42.
IFM 99-03 : Treatment of aggressive myeloma by familial allogeneic graft without myelo-ablation in patients lesser than 65
years old.
Objectives : study of the survival without progression, CR remission after six months, death rate related to allograft.
IFM 99-04 : Comparison of an intensive therapy with allograft
by melphalan 220mg/m2 and dexamethasone to melphalan
220mg/m2 + anti-IL6 antibodies and dexamethasone.
Objective : compare the CR rate between two intensive therapies.
Partnership
IFM 99-06 : Treatment of multiple myeloma in patients between
65 and 75 years old.
Objective: survival rate between the three series of patients in
the protocol.
Multicentric international studies
IFM 01-01 : Treatment of multiple myeloma in patients aged
more than 75 years old.
Objective : compare survival in patients with 12 cures of
Melphalan-Prednisone, Clodronate (dubble blind) arm A : placebo, arm B : Thalidomide.
CC-5013-MM-010 REVIMID : A multicenter, randomized, parallel-group, double-blind, placebo-controlled study of CC-5013
plus Dexamethasone versus Dexamethasone alone in previously treated subjects with multiple myeloma.
Hodgkin’s lymphoma
H9 : group favorable : Randomized prospective treatment trial
effect in sus-diaphragmatic stages I-II of Hodgkin’s disease.
Objective : to evalutate the effectiveness of standard 6 cycles
EBVP + IF 36 Gy versus the experimental 6 cycles EBVP + IF 20
Gy, to decrease the toxicity.
H 3-4 : Randomized prospective treatment trial in stage III-IV
Hodgkin’s disease : comparative evaluation of the effectiveness
and toxicity of two therapies : ABVD and BEACOPP.
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STAFF
Total : 3
KEY WORDS FOR R&D
allogenic graft
clinical medicine
hematology
Hodgkin
IFM
myeloma
SENIOR SCIENTISTS
Augustin FERRANT
[email protected]
Tel. 32 (0)2 764 18 80
Lucienne MICHAUX
[email protected]
Tel. 32 (0)2 764 18 09
Eric VAN DEN NESTE
[email protected]
Tel. 32 (0)2 764 18 75
WEB SITE
http://rch.adre.ucl.ac.be/browse/list_alpha/SANG
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
F 1
Therapeutic vaccination of cancer patients with tumor
specific antigens
SENIOR SCIENTISTS :
Thierry BOON
Marie MARCHAND
Nicolas VAN BAREN
Research Field and Subjects
Oncology, 2nd Edition. Eds: M. D. Abeloff, J.O. Armitage, A.S.
Lichter, J.E. Niederhuber. Churchill Livingstone, New York, 2000.
MARCHAND M., BRICHARD V., VAN BAREN N., and COULIE
P. Biological and clinical developments in melanoma vaccines.
Exp. Op. Biol. Trials 2001; 1 : 497-510.
COULIE P.G., KARANIKAS V., LURQUIN C., COLAU D.,
CONNEROTTE T., HANAGIRI T., VAN PEL A., LUCAS S., GODELAINE
D., LONCHAY C., MARCHAND M., VAN BAREN N., BOON T.
Cytolytic T-cell responses of cancer patients vaccinated with a
MAGE antigen. Immunological Reviews 2002; 188 : 33-42.
MARCHAND M., PUNT C.J., AAMDAL S., ESCUDIER B., KRUIT
W.H., KEILHOLZ U., HAKANSSON L., VAN BAREN N., HUMBLET Y.,
MULDERS P., AVRIL M.F., EGGERMONT A.M., SCHEIBENBOGEN C.,
UITERS J., WANDERS J., DELIRE M., BOON T., STOTER G.
Immunisation of metastatic cancer patients with MAGE-3 protein
combined with adjuvant SBAS-2: a clinical report. Eur. J. Cancer
2003; 39 : 70-7.
Tumor cells carry antigens such as MAGE antigens that are
absent from normal tissues, and that can be targeted by cytolytic T lymphocytes (CTL).
While it is possible to make such CTL recognize and kill autologous tumor cells in vitro, the precise way to induce an effective
CTL response against a MAGE antigen in cancer patients is not
known yet. In clinical vaccination trials, patients with a MAGE
expressing cancer, often melanoma, are treated repeatedly with
a MAGE vaccine.
These trials have two main objectives.
First, the effectiveness of various vaccination modalities can be
assessed by following the clinical evolution of the tumor, by
analyzing whether a specific CTL response to the vaccine antigen occurred, and by determining whether immunological and
clinical responses are correlated. Secondly, T lymphocytes and
tumor samples collected at different timepoints during vaccination can be analyzed in detail, which improves our understanding of what happens in patients who experience regression of
metastatic lesions, and which may explain why this does not
happen in the majority of patients with overall disease progression.
Patents
Patents covering clinical applications of the tumor-specific
antigens contained in our vaccines.
This knowledge can then be used to design new vaccination
modalities.
Funding sources
Ludwig Institute for cancer research
FB Assurances
Fédération belge contre le cancer
Representative References
MARCHAND M., VAN BAREN N., WEYNANTS P., BRICHARD
V., DRÉNO B., TESSIER M-H., RANKIN E., PARMIANI G., ARIENTI
F., HUMBLET Y., BOURLAND A., VANWIJCK R., LIÉNARD D.,
BEAUDUIN M., DIETRICH P-Y., RUSSO V., KERGER J., MASUCCI
G., JÄGER E., DE GREVE J., ATZPODIEN J., BRASSEUR F., COULIE
P.G., VAN DER BRUGGEN P., and BOON T. Tumor regressions
observed in patients with metastatic melanoma treated with an
antigenic peptide encoded by gene MAGE-3 and presented by
HLA-A1. Int. J. Cancer 1999; 80 : 219-230.
BOON T., COULIE P.G., VAN DER BRUGGEN P., VAN BAREN N.
Immunology of the cancer cell : T lymphocyte responses. In : Clinical
Partnership
Academic collaborations
UCL, Centre du cancer, Brussels, Belgium
ULB, Brussels, Belgium (Th. Velu)
VUB, Brussels, Belgium (B. Neyns)
KUL, Leuven (M. Stas)
Institut Curie, Paris (T. Dorval, S. Piperno)
Institut Gustave-Roussy, Villejuif, France, (M.F. Avril, B. Escudier)
CHU de Nantes, France (B. Dreno)
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Mannheim, Germany (D. Schadendorf)
University Benjamin Franklin, Berlin, Germany (U. Keilholz)
STAFF
Total: 8
Industrial collaborations
GlaxoSmithKline Biologicals, Rixensart, Belgium
Aventis Pasteur, Lyon, France
BruCELLS, Brussels, Belgium
KEY WORDS FOR R&D
cancer treatment
cytolytic T lymphocytes
immunology
immunotherapy
tumor antigens
International networks
EORTC : Melanoma Cooperative Group
SENIOR SCIENTISTS
Thierry BOON
[email protected]
Tel : 32 (0)2 764 7580
Marie MARCHAND
[email protected]
Tel : 32 (0)2 764 7533
Nicolas VAN BAREN
[email protected]
Tel : 32 (0)2 764 7533
WEB SITES
http://www.licr.ucl.ac.be/
http://www.icp.ucl.ac.be/ICP_en.html
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
F 2
Isolation and structure determination of active compounds
from plants used in traditional medicine to treat different
forms of cancers. Analysis of the mode of action.
SENIOR SCIENTIST :
Joëlle QUETIN-LECLERCQ
Research Field and Subjects
K. BONJEAN, M.C. DE PAUW-GILLET, M.P. DEFRESNE, P. COLSON,
C. HOUSSIER, L. DASSONNEVILLE, C. BAILLY, R. GREIMERS, C.
WRIGHT, J. QUETIN-LECLERCQ, M. TITS and L. ANGENOT. The
DNA intercalating alkaloid cryptolepine interferes with topoisomerase II and inhibits primarily DNA synthesis in B16 melanoma
cells. Biochemistry, 37, 1998, 5136-5146.
L. DASSONNEVILLE, K. BONJEAN, M.-CL. DE PAUW-GILLET, P.
COLSON, C. HOUSSIER, J. QUETIN-LECLERCQ, L. ANGENOT, C.
BAILLY. Stimulation of topoisomerase II-mediated DNA cleavage
by three DNA-intercalating plant alkaloids: cryptolepine, matadine and serpentine. Biochemistry, 38, 1999, 7719-7726.
S. BLOCK, C. STÉVIGNY, M.-C. DE PAUW-GILLET, E. DE
HOFFMANN, G. LLABRÈS, V. ADJAKIDJÉ, J. QUETIN-LECLERCQ.
Ent-Trachyloban-3ß-ol, a new cytotoxic diterpene from Croton
zambesicus. Planta Medica, 68, 2002, 647-649.
C. STÉVIGNY, S. BLOCK, M.-C. DE PAUW-GILLET, E. DE
HOFFMANN, G. LLABRÈS, V. ADJAKIDJE, J. QUETIN-LECLERCQ.
Cytotoxic aporphine alkaloids from Cassytha filiformis. Planta
Medica, 68, 2002, 1042-1044.
S. BLOCK, C. BACCELLI, B. TINANT, L. VAN MEERVELT, R.
ROZENBERG, J.-L. HABIB JIWAN, G. LLABRÈS, M.-C. DE PAUWGILLET, J. QUETIN-LECLERCQ Diterpenes from the leaves of
Croton zambesicus. Phytochemistry, 65, 2004, 1165-1171.
S. HOET, C. STÉVIGNY, S. BLOCK, F. OPPERDOES, P. COLSON,
B. BALDEYROU, A. LANSIAUX, C. BAILLY, J. QUETIN-LECLERCQ.
Alkaloids from Cassytha filiformis and related aporphines: antitrypanosomal activity, cytotoxicity, and interaction with DNA and
topoisomerases. Planta Medica, 70, 2004, 407-413.
Plants are a large reservoir of original molecules which may act
on new targets or possess new modes of action and can be
used as prototypes by chemists.
The aim of our studies is to isolate, by different preparative or
semi-preparative techniques (High speed Counter Current
Chromatography, MPLC…), cytotoxic and bio-active molecules
from plants selected on an ethnopharmacological basis.
Structures are determined by comparison with known compounds and spectroscopic methods (UV, IR, SM 1 or 2D, RMN).
The mode of action and cellular targets of the most interesting
compounds are analysed in collaboration with specialized
teams. Methods for quantification of these bioactive molecules
in extracts are also developed.
Products and Services
Analysis and quantification in complex extracts of natural
bioactive compounds.
Preparative purification techniques.
Main Equipment
High speed Counter Current, Chromatography (HSCCC)
Preparative MPLC, HPLC/UV, HPLC-DAD, HPLC-MS, GC-FID
GC-FTIR, GC-MS.
Funding Sources
Funds of Research of UCL
Fonds national de la recherche scientifique (FNRS)
Coopération universitaire au développement (CUD)
Representative References
J. QUETIN-LECLERCQ, B. BOUZAHZAH, A. PONS, R. GREIMERS,
L. ANGENOT, R. BASSLEER and H. BARBASON. Strychnopentamine,
a potential anticancer agent. Planta Med., 59, 1993, 59-62.
K. BONJEAN, M.-CL. DE PAUW-GILLET, J. QUETIN-LECLERCQ,
L. ANGENOT, R. BASSLEER. In vitro cytotoxic activities of two
potential anticancer drugs isolated from Strychnos :
strychnopentamine and usambarensine. Anticancer Research,
16, 1996, 1129-1138.
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STAFF
Total: 6
KEY WORDS FOR R&D
pharmaceutical sciences
pharmacognosy
separation techniques
structural chemistry
SENIOR SCIENTIST
Joëlle QUETIN-LECLERCQ
[email protected]
Tel. 32 (0)2 764 72 54
WEB SITE
http://www.md.ucl.ac.be/cham
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
F 3
The tumor vascularity : bases for adjuvant strategies to
conventional anti-tumor treatments and anti-angiogenic
approaches.
SENIOR SCIENTIST :
Olivier FERON
tumor permeability
tumor homing (stem cells and lymphocytes)
tumor angiogenesis
tumor endothelial cell resistance to treatments
Testing adjuvant strategies to chemo-, gene-, radio- and immunotherapy in dedicated animal models
Research Field and Subjects
Adjuvant therapy to anti-tumor treatments:
Identification of the determinants of the differential intrinsic
and induced reactivity/phenotype of tumor blood vasculature.
This goal is achieved through the microdissection of blood vessels (diameter between 80 and 300 µm) from mouse or human
tumors, followed
by the analysis of their vasoreactivity by videomicroscopy in
pressure and wire myographs. The effects of drugs and of
changes in pressure or shear stress are analysed. Similarly, the
changes in reactivity consecutive to treatments (anti-angiogenic, radiotherapy) are examined.
by DNA profiling and quantification of genes involved in vasomodulatory and adhesion processes; proteomics is applied in
second line.
Main Equipment
Pressure/ wire myographs and videomicroscopy setup
Cell culture equipment including 3-gas incubator (for hypoxia)
Molecular biology equipment including adenovirus technology
Immunoblotting equipment
Laser Doppler imaging
Tumor invasion chambers
Immunofluorescence microscopy
Authorized access to on-site FACS, DNA sequencer, real-time
PCR, EPR and NMR facilities
In vivo validation and exploitation of the differential reactivity of
blood vessels to increase the efficacy of anti-tumor treatments.
More particularly, these studies aim at identifying tumor-specific pathways leading to an increase in tumor pO2 (radiotherapy), drug/gene delivery (chemo- and gene therapy) and lymphocyte recruitment (immunotherapy).
Besides specific end-points related to these specific goals, the following parameters are measured: tumor blood flow (Laser Doppler
imager and needle probe), tumor oxygenation (EPR, histochemistry),
tumor vessel permeability (wick-in needle, Evans blue diffusion, histochemistry), tumor growth (caliper) and dissemination (histology).
Representative References
FERON O. and KELLY R.A. The Caveolar Paradox : suppressing,
inducing and terminating eNOS signaling. Circulation Research,
2001, 88, 129-131.
BROUET A., SONVEAUX P., DESSY C., BALLIGAND J.L. and FERON
O. Hsp90 ensures the transition from the early Ca2+-dependent
to the late phosphorylation-dependent activation of the
endothelial nitric oxide synthase (eNOS) in VEGF-exposed
endothelial cells. J. Biol. Chem., 2001, 276, 32663-9.
BROUET A., SONVEAUX P., DESSY C., MONIOTTE S., BALLIGAND
J.L. and FERON O. Hsp90 and caveolin are key targets for the
proangiogenic nitric oxide-mediated effects of statins. Circ.
Res., 2001, 89, 866-873.
JORDAN B.F., GREGOIRE V., DEMEURE R.J., SONVEAUX P.,
FERON O., O’HARA J., VANHULLE V.P., DELZENNE N., GALLEZ B.
Insulin increases the sensitivity of tumors to irradiation: involvement of an increase in tumor oxygenation mediated by a nitric
oxide dependant decrease of the tumor cells oxygen consumption. Cancer. Res., 2002, 62, 3555-3561.
SONVEAUX P., DESSY C., BROUET A., JORDAN B.F., GRÉGOIRE
Anti-angiogenic strategies:
Dissection of the biochemical VEGF/Akt/nitric oxide pathway to
identify new therapeutic targets to decrease tumor angiogenesis
or to reduce prosurvival advantages of tumor endothelial cells.
Identification of the determinants of endothelial progenitor cell
recruitment in tumors to develop strategies aiming to block stem
cell-derived angiogenesis.
Products and Services
Testing of drugs aiming to modulate
tumor blood flow
tumor oxygenation
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Fédération belge de recherche contre le cancer
Fonds J. Maisin
Fondation Fortis-Cancerology
V., GALLEZ B., BALLIGAND J.L. and FERON O. Modulation of
the tumor vasculature functionality by ionizing radiation
accounts for tumor radio-sensitization and promotes gene
delivery. FASEB J., 2002, 16, 1979-81.
VINCENT K.A., FERON O., KELLY R. A. Harnessing the Response
to Tissue Hypoxia: HIF-1a and Therapeutic Angiogenesis. Trends
Cardiovasc. Pharmacol., 2002, 12, 362-7.
JORDAN B.F., SONVEAUX P., FERON O., GRÉGOIRE V., BEGHEIN
N. and GALLEZ B. Nitric oxide-mediated increase in tumor blood
flow and oxygenation of tumors implanted in muscle stimulated by
electric pulses. Int. J. Rad. Oncol. Biol. Phys., 2003, 55, 1066-73.
SONVEAUX P., BROUET A., DESSY C., GRÉGOIRE V., BALLIGAND
J.L. and FERON O. Irradiation-induced angiogenesis through the
up-regulation of the NO pathway: implications for tumor radiotherapy. Cancer Res., 2003, 63, 1012-9.
SONVEAUX P., DESSY C., MARTINIVE P., JORDAN B., GALLEZ
B., GRÉGOIRE V., BALLIGAND J.L. and FERON O. Endothelin-1 is
a critical mediator of myogenic tone in tumor arterioles: implications for cancer treatment. Cancer Res., 2004, in press.
Partnership
UCL (Brussels) : Prof. B. Gallez, Laboratory of Biomedical Magnetic
Resonance; Prof. V. Grégoire, Laboratory of Radiobiology and
Radioprotection; Prof. JL. Gala, Unit of Medical Genetics; Prof. E.
Hermans, Unit of Pharmacology; Dr. JP Machiels, Unit of Medical
Oncology, Prof. O. Devuyst, Nephrology Division.
ULg (Liège) : Profs. A. Noël and J.M. Foidart, Laboratoire de
Biologie des Tumeurs et du Développement.
FUNDP (Namur) : Profs. C. Michiels and M. Raes, URBCBiochimie et Biologie Cellulaire.
Prof. P. Boekstegers and Dr. C. Kupatt, Ludwig-MaximiliansUniversitat, Internal Medicine University Klinikum Grosshadern
Munich, Germany.
Prof. R. Bianchi and Dr. R. Rezzani, Department of Biomedical
Sciences and Biotechnology, University of Brescia, Italy.
Prof. R.A. Kelly, Genzyme Corporation, Framingham, USA.
Patents
FERON O. and BALLIGAND J.L. Use of compound or pharmaceutical composition for the prevention and/or the treatment of
ischemic heart and cerebral diseases, tumour development and
for wound healing. PCT/EP00/07731 (filed in 2000).
DESSY C., SONVEAUX P. and FERON O. Evidence for an endothelin-1 mediated myogenic tone in tumor arterioles: implications for
cancer treatment. PCT/EP2004/004554 (filed in 2003).
STAFF
Total : 9
KEY WORDS FOR R&D
angiogenesis
blood flow
chemotherapy
gene therapy
hypoxia
immunotherapy
nitric oxide
radiotherapy
tumor vasculature
Awards
Société belge des Sciences Pharmaceutiques (1997)
Prix Galien (1999)
Prix de la Fondation Bekales (2000)
Prix Orbita (2001)
Prix MSD (2001)
SENIOR SCIENTIST
Olivier FERON
[email protected]
Tel. 32 (0)2 764 93 26
WEB SITE
Funding Sources
FNRS, FRSM, Télévie, FSR
http://www.mint.ucl.ac.be
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
F 4
Phase II study of utilisation of a recombinant chimeric protein
in patients with recurrent progressive glioblastoma
SENIOR SCIENTIST :
Christian RAFTOPOULOS
Research Field and Subjects
The aim of our research protocol is to evaluate the efficiency of
a recombinant chimeric protein composed of Transforming
Growth Factor (TGF) and a mutated form of the Pseudomonas
exotoxin termed PE-38 (TP-38) in those patients with recurrent
or progressive glioblastoma multiforme after resection and
radiation therapy.
The MRI must show one single target lesion with an area of
contrast enhancement of at least 1 cm in diameter. The Karnofsky
Performance Status must be > 60% and life expectancy of > 3
months.
The primary objective is to determine whether TP38 given at any of
two selected doses has sufficient activity to warrant further study.
The treatment will consist of a continous, intratumoral infusion
via a micro-infusion pump connection system with three catheters stereotacticly placed at investigator-determined areas.
A total of 38 evaluable patients will be recruited in at least
7 active open centers in several European countries. Patients
will be followed until death with evaluation of the percentage
of patients alive and progression free at 6 months.
RAND R.W., KREITMAN R.J., PATRONAS N. and al. Intratumoral
administration of recombinant circulary permuted interleukin4-Pseudomonas exotoxin in patients with high-grade glioma.
Clin. Cancer Res., 2000, 6 :2157-2165.
BASELGA J., PFISTER D., COOPER M.R. and al. Phase I studies of anti-epidermal growth factor receptor chimeric antibody
C225 alone and in combination with cisplatin. J. Clin. Oncol.,
2000, 18 :904-914.
FRANKEL A., KREITMAN R.J., SAUSVILLE E.A. Targeted toxins.
Clin. Cancer Res., 2000, 6/326-334.
KEPPLER-HAFKEMEYER A., KREITMAN R.J., PASTAN I. Apoptosis
induced by immunotoxins used in the treatment of hematologic malignancies. Int. J. Cancer, 2000, 87 :86-94.
KREITMAN R.J., WILSON W.H., WHITE J.D. and al. Phase I trial
of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in
patients with hematologic malignancies. J. Clin. Oncol., 2000,
18 :1622-1636.
ONDA M., WILLINGHAM M., WANG Q.C. and al. Inhibition
of TNF-alpha produced by Kuppfer cells protects against the
nonspecific liver toxicity of immunotoxin anti-Tac(Fv)-PE38
(LMB-2). J. Immunol. 2000, 165 :7150-7156.
Products and Services
Funding Sources & Partnership
IVAX Research, Inc.
Find a new treatment for patients suffering from progressive or
recurrent glioblastoma via in situ administration of TP38 by
minimal-invasive surgery.
Main Equipment
Pump connection system with 3 catheters surgically placed by
stereotactic technics.
Representative references
PAI-SCHERF L.H., VILLA J., PEARSON D. and al. Hepatotoxicity
in cancer patients receiving erb-38, a recombinant immunotoxin that targets the rebB2 receptor. Clin. Cancer Res., 1999,
5 :2311-2315.
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STAFF
Total : 4
KEY WORDS FOR R&D
cerebral tumor
histopathology
intratumoral infusion
neurology
neuropathology
neuroradiology
neurosurgery
recombinant chimeric protein, TP 38
recurrent multiforme glioblastoma
stereotaxy
surgery
surgical medicine
SENIOR SCIENTISTS
Christian RAFTOPOULOS
[email protected]
Tel. 32 (0)2 764 10 87
WEB SITE
http://www.chir.ucl.ac.be
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
F 5
Cancer immunotherapy - clinical trials
SENIOR SCIENTISTS :
Jean-François BAURAIN
Jean-Pascal MACHIELS
Research Field and Subjects
Representative References
Tumor cells carry antigenic peptides bound to surface HLA
molecules that can be recognized by T lymphocytes. An important category of tumor specific antigens includes those encoded by “cancer-germline genes” such as members of the
MAGE gene family. These antigens are not present on normal
tissues, but are frequently found on various types of tumors
such as melanoma, transitional bladder cancer, head and neck
squamous cell carcinoma, non-small cell lung cancer and esophageal cancer. Because of these characteristics, MAGE-type
antigens are particularly attractive targets for cancer immunotherapy.
M. MARCHAND, N. VAN BAREN, P. WEYNANTS, V.G. BRICHARD,
B. DRÉNO, M.-H. TESSIER, E. RANKIN, G. PARMIANI, F. ARIENTI, Y.
HUMBLET, A. BOURLOND, R. VANWIJK, D. LIÉNARD, M. BEAUDUIN,
P.-Y. DIETRICH, V. RUSSO, J. KERGER, G. MASUCCI, E. JÄGER, J. DE
GREVE, J. ATZPODIEN, F. BRASSEUR, P.G. COULIE, P. VAN DER
BRUGGEN, and T. BOON., 1999. Tumor regression observed in
patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int. J.
Cancer 80:219-230.
BRICHARD V., MACHIELS J.P., PIPERNO S. and DORVAL T. 2001.
Peptide–based immunization against tumor-specific antigen
NA17.A2 in HLA-A2 patients with metastatic cutaneous
melanoma. Proceedings of the American Association of Clinical
Oncology 272a : 1084.
BRICHARD V.G., DORVAL T., SALMON R.J., and MACHIELS
J.P. Peptide-based immunization against tumor specific antigen
NA17.A2 in HLA-A2 patients with metastatic cutaneous or ocular melanoma. Proceedings of the American Association of
Clinical Oncology 42: 699, 2001.
MACHIELS J.P., VAN BAREN N., and MARCHAND M., 2002.
Peptide-based cancer vaccines. Seminar in Oncology. 29: 494-502.
Another important category of tumor antigens comprises the
“melanoma differentiation antigens”, encoded by genes such
as tyrosinase, Melan-A and gp100, which are expressed exclusively by normal melanocytes and by melanoma cells.
Therapeutic vaccination with these antigens is only feasible in
melanoma patients, and carries an acceptable risk of inducing
autoimmune depigmentation diseases.
During the last years, we have acquired a great experience in
clinical vaccination trials with MAGE and with melanoma differentiation immunogens in patients with advanced cancer, with
a special focus on melanoma. Our group has studied immunization of patients with peptides, a recombinant protein and a
recombinant viral vector. We coordinate a large network of clinical centers participating in these clinical trials. Our common
research project combines this shared experience with the
rapidly evolving knowledge of cellular immunology to design
new vaccination modalities with improved clinical and immunological effectiveness.
Funding Sources
Fonds national de la recherche scientifique (FNRS)
Fédération Belge contre le Cancer
Main Equipment
Culture laboratory and molecular biology
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STAFF
Total : 4
KEY WORDS FOR R&D
clinical trial
immunology
tumor antigens
vaccination
SENIOR SCIENTISTS
Jean-François BAURAIN
[email protected]
Tel. 32 (0)2 764 54 72
Jean-Pascal MACHIELS
[email protected]
Tel. 32 (0)2 764 54 57
WEB SITE
http://rch.adre.ucl.ac.be/browse/list_alpha/ONCO
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
F 6
Lung cancer - mesothelioma - clinical research in diagnosis active treatment - supportive care
SENIOR SCIENTISTS :
Daniel RODENSTEIN
Philippe COLLARD
Giuseppe LIISTRO
Thierry PIETERS
Research Field and Subjects
Main Equipment
The pulmonology unit has participated for many years to randomized phase I, II, III or IV clinical trials in the treatment of lung
cancer or mesothelioma and in the diagnosis of lung cancer. Most
of studies are financially supported and/or conducted by pharmaceutical companies.
Modern endoscopic equipment for diagnostic and therapeutical approach of bronchial carcinoma and pleural diseases.
Modern computed radiological tomographic systems and nuclear
imaging technics (SPEC-PET).
18 in-hospitalisation beds for cancer management plus daycenter oncological beds.
Diagnostics
Project of detection of mutations of the Epidermal Growth
Factor Receptor in lung cancer.
Early detection of lung cancer by low-dose computed tomography (and FDG-PET).
Comparison of FDG-PET and transthoracic needle biopsy for
the diagnosis of lung cancer.
Use of a radiolabelled antibody to Annexin V for imaging of
chemotherapy-induced apoptosis in lung cancer.
The value of FDG-PET and endoscopic ultrasound-guided fineneedle aspiration to detect mediastinal lymph node involvement in lung cancer.
Treatment
Several clinical studies of chemotherapy combinations.
Studies with different Tyrosine Kinase Inhibitors (of EGFR and
VEGFR).
combination of an inhibitor of the CDK2/cyclin E complex with
chemotherapy.
Detection of malignant cells by intra-operative pleural lavage.
Detection of micro-metastasis in mediastinal lymph nodes
and bone marrow at the time of pulmonary resection.
Combination of a texaphyrin derivative and whole brain radiation therapy for cerebral metastasis of lung cancer.
In the future, the unit will develop studies in the early diagnosis (autofluorescence endoscopy) and local tumor therapy
(radiofrequence coagulation).
Funding Sources
External funds from pharmaceutical companies, FNRS (Fonds
National de la Recherche Scientifique).
Partnership
UCL multidisciplinary thoracic oncology group.
Numerous studies in collaboration with the pharmaceutical industry.
Collaboration with the Belgian Society of Pneumology (oncology and interventional endoscopy).
International interuniversity program in pneumology, including onco-pneumology.
Products and services
Opportunities for clinical research on about one hundred new
patients each year.
Facilities for data collection (oncology care coordinator fulltime available).
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STAFF
Total : 4
KEY WORDS FOR R&D
chemotherapy
cytology
diagnosis
histology
immunotherapy
internal medicine
lung cancer
molecular biology
pronostic factor of molecular markers
pulmonology
surgical medicine
treatment
SENIOR SCIENTISTS
Daniel RODENSTEIN
[email protected]
Tel. 32(0)2 764 28 86
Philippe COLLARD
[email protected]
Tel. 32(0)2 764 28 30
Giuseppe LIISTRO
[email protected]
Tel. 32(0)2 764 28 43
Thierry PIETERS
[email protected]
Tel. 32(0)2 764 28 33
WEB SITES
http://rch.adre.ucl.ac.be/browse/list_alpha/PNEU
http://pneu.ucl.ac.be
http://www.saintluc.be/english/index.html
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
F 7
Development of new calcium-based strategies to induce
apoptotic cell death in prostate cancer cell lines
SENIOR SCIENTISTS :
Bertrand TOMBAL
Philippe GAILLY
Research Field and Subjects
Main Equipment
Prostate cancer is the most frequent cancer in men aged more than
55 years old. Despite important progress in early diagnostic and therapeutic procedures, there are still a lot of patients who develop
metastatic spread and require some form of systemic therapy.
3 setups for imaging of living cells (including calcium measurement and GFP expression and trafficking studies)
patch-clamp equipment for early
wide range of urological cell lines for in vitro techniques
Prostate cancer is characterized by a very low proliferation rate and a
selective tropism to bone, which made it almost insensitive to modern
chemotherapeutical regimens. Progression and metastatic spread of
PCa result instead of a defect in the induction of apoptosis. Apoptosis
is a widespread, universal, cell suicide mechanism which helps multicellular organisms to control global cellular homeostasis.
Representative References
TOMBAL B., GAILLY P., VAN CANGH P.J., GILLIS J.M. Role of
intracellular calcium in the programmed cell death of prostatic
cancer cells. Acta Belgica Urologica 63(1), 1-5. 1995.
AU W.C., MOORE P.A., LAFLEUR D.W., TOMBAL B., PITTA P.
Characterization of the interferon regulatory factor-7 and its
potential role in the transcription activation of Interferon A
gene. A.J. Biol. Chem. 273(44), 29210-29217, 1998.
GAO J., TOMBAL B., ISAACS J.T. A Rapid In Situ Hybridization
Technique for Detecting Malignant Mouse Cell Contamination in
Human Xenograft Tissue from Nude Mice and In Vitro Cultures
from such Xenograft. The Prostate 39(1), 67-70, 1999.
DENMEADE S.R., LIN X.S., TOMBAL B., ISAACS J.T. Inhibition of
caspase activity does not prevent the signaling phase of apoptosis
in prostate cancer cells. The Prostate 39(4), 269-79, 1999.
CHRISTENSEN S.B., ANDERSEN A., KROMANN H., TREIMAN
M., TOMBAL B., DENMEADE S.R, and ISAACS J.T. Thapsigargin
Analogues for Targeting Programmed Death of AndrogenIndependent Prostatic Cancer Cells. Bioorg. Medicinal
Chemistry 7,1273-1280, 1999.
TOMBAL B., DENMEADE S.R., ISAACS J.T. Assessment and validation of a microinjection method for kinetic analysis of [Ca2+]i
in individual cells undergoing apoptosis. Cell Calcium. 25(1):1928, 1999.
TOMBAL B, WEERARATNA A.T., DENMEADE S.R. and al.
Thapsigargin induces a calmodulin/calcineurin-dependent
apoptotic cascade responsible for the death of prostatic cancer
cells. Prostate 43: (4) 303-317, 2000.
JACKISCH C., HAHM H.A., TOMBAL B., McCLOSKEY D.,
BUTASH K., DAVIDSON N.E., DENMEADE S.R. Delayed
Micromolar Elevation in Intracellular Calcium Precedes
Induction of Apoptosis in Thapsigargin-Treated Breast Cancer
Cells. Clin. Canc. Res. 6, 2844-2850, 2000.
The apoptotic potential can be initially restored in PCa cells by
lowering the circulating level of testosterone. Rapidly however,
PCa cells engage in a series of epigenetic and genetic mechanisms to overcome the apoptotic process and become hormone resistant (HRPCa).
In a previous work, we have demonstrated that this resistance
to apoptosis could be overcome by drugs that mobilize calcium
from the surrounding tissues and by disrupting growth factor
signaling pathways.
Our group is currently studying these pathways to test and
develop new agents targeted to inhibit growth of HRPCa. Our
major focuses are drugs modulating calcium entry and drugs
that block the spread of PCa to bone.
Products and Services
The lab has developed several original techniques to investigate apoptosis and ionic changes during apoptosis.
We have a particular competence in imaging technologies
using GFP/modified proteins in living and apoptotic cells.
The lab offers a direct connection with early human use (phase
I/II) trials and up-to-date pharmacogenomics and pharmacodynamic implementations.
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TOMBAL B., DENMEADE S.R, GILLIS J.M., ISAACS J.T. A supramicromolar elevation of intracellular free calcium ([Ca2+]i) is consistently required to induce the execution phase of apoptosis. Cell
Death and Differentiation, 9, 561-573 2002.
PIGOZZI D., TOMBAL B., DUCRET T., VACHER P., GAILLY PH.
Role of store-dependent influx of Ca2+ and efflux of K+ in apoptosis of CHO cells. Cell Calcium, In press.
STAFF
Total : 9
KEY WORDS FOR R&D
apoptosis
calcium
fluorescence
growth factors
prostate cancer
Funding Sources
SENIOR SCIENTISTS
Fonds national de la recherche scientifique (FNRS)
Fondation pour la recherche scientifique médicale (FRSM)
Télévie.
Pharmaceutical industry
Bertrand TOMBAL
[email protected]
Tel. 32 (0)2 764 55 40
Philippe GAILLY
[email protected]
Tel. 32 (0)2 764 55 42
Partnership
Dr Jean-Luc Gala, Laboratory of Applied Molecular Technologies,
Cliniques universitaires Saint Luc, Bruxelles, Belgium.
Dr Samuel Denmeade, Division of Experimental Therapeutic Johns
Hopkins Oncology Center, Baltimore, USA.
WEB SITE
http://rch.adre.ucl.ac.be/browse/list_alpha/FYMU
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
F 8
Breast cancer
SENIOR SCIENTISTS :
Jacques DONNEZ
Martine BERLIERE
Jean-Luc SQUIFFLET
Isabelle LECONTE
Latifa FELLAH
Christine GALANT
Catherine SIBILLE
Bénédicte BAYET
the same place, of different doctors involved in the various
aspects of breast cancer therapy (breast surgeon, oncologist,
radiotherapist, psychologist).
Since 1998, a specialist breast clinic has been under development at St Luc’s Hospital.
In those European countries where such breast centres already
exist, studies have shown that women have a much better
chance of being cured.
This concept implies the creation of different multidisciplinary subunits in all domains linked to breast cancer (diagnosis, molecular
biology, genetics, surgical treatment, techniques of radiotherapy,
chemotherapy, endocrine therapy and immunotherapy).
The purpose of this type of consultation is :
To acknowledge good clinical practices and promote its
development.
To ensure that a maximum number of women fully understand any proposed treatment options, including participation
in clinical trials.
To ensure quality supportive care during and after treatment.
To promote breast cancer research and its application to clinical practice.
To create meaningful partnerships between health professionals
and patient associations in the complex field of breast cancer
(diagnosis, treatment and research). To this end, we will invite
women from the “Vivre comme avant” association whom
patients will be able to meet after their multidisciplinary
consultation.
Evidence from scientific literature suggests that all phases of the
continuum of care have an important impact on breast cancer
outcome.
Quality of care is based on the results of well-designed randomized, controlled trials.
Here are some examples of trials in which our breast clinic is
currently involved :
Pathology : European project initiated by the EORTC, studying the genetic profile of breast tumors and their role as prognostic and predictive factors.
Adjuvant therapy : implication in different international clinical studies : chemotherapy trials investigating the place of taxanes in early breast cancer.
Endocrine therapy : partner in the TEAM trial which studies
the place and benefits of aromatase inactivators (aromasin,
exemestane) in the adjuvant treatment of breast cancer.
Academic study (neoadjuvant chemotherapy with taxanes and
Trastuzumab for locally advanced breast cancer). This study will
investigate the biology of the tumor and the changes in angiogenesis.
Immunotherapy :
Preventive trials such as IBIS II study.
Partnership
Bordet Institute, Brussels, Belgium (Professor M. Piccart).
French Federation of Cancer.
We are also engaged in research in the adjuvant setting (phase I
studies of immunotherapy and other studies of metastatic breast
cancer, studies coupling hormone therapy and antibodies).
In the coming months, we aim at conducting our own studies
on the treatment of advanced breast cancer.
We are developing a multidisciplinary approach to optimize the
different therapeutic aspects of breast cancer. This multidisciplinary consultation implies the presence, at the same time and in
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STAFF
WEB SITES
Total : 13
http://rch.adre.ucl.ac.be/browse/list_alpha/GYNE
http://rch.adre.ucl.ac.be/browse/list_alpha/GMED
http://rch.adre.ucl.ac.be/browse/list_alpha/ANPS
http://www.md.ucl.ac.be/rdgn
KEYWORDS
gynecology
medical psychology
multidisciplinary approach
particular pathology
SENIOR SCIENTISTS
Jacques DONNEZ
[email protected]
Tel. 32 (0)2 764 94 07 or 764 95 01
Martine BERLIERE
[email protected]
Tel. 32 (0)2 764 10 75
Jean-Luc SQUIFFLET
[email protected]
Tel. 32 (0)2 764 10 71
Isabelle LECONTE
[email protected]
Tel. 32 (0)2 764 29 34
Latifa FELLAH
[email protected]
Tel. 32 (0)2 764 29 13
Christine GALANT
[email protected]
Tel. 32 (0)2 764 17 88
Catherine SIBILLE
[email protected]
Tel. 32 (0)2 764 53 82
Bénédicte BAYET
[email protected]
Tel. 32 (0)2 764 14 07
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
G 1
Cryopreservation of ovarian cortex removed before chemotherapy allows the restoration of ovarian function after orthotopic
autotransplantation.
SENIOR SCIENTISTS :
Research Field and Subjects
Jacques DONNEZ
Jean-Luc SQUIFFLET
Pascale JADOUL
Céline PIRARD
Christine WYNS
Dominique DEMYLLE
Marie-Madeleine DOLMANS
Belen MARTINEZ-MADRID
Anne VAN LANGENDONCKT
Our results on whole ovary cryopreservation with a passive
cooling device showed, after thawing, a follicle viability rate of
75.9%. Intact and live vessels were also found in the medullar tissue. This is the first time that entire human ovaries have been
cryopreserved in liquid nitrogen using an accessible cryopreservation protocol and that follicle survival has been demonstrated.
We are also working on the optimization of follicle isolation
procedures. Different enzymatic digestion methods are tested,
as well as a new follicle recovery method based on Ficoll density gradient instead of filtration. Viability of isolated follicles is
tested by metabolic analysis of the follicles in culture with
microfluorometry, and their integrity is analysed by electron
microscopy and immunofluorescence. The isolated follicles are
grafted under the kidney capsule of immunosuppressed mice.
The vascularisation, viability and functionality of the grafted isolated follicles will be compared to those of grafted ovarian cortical strips. Grafting isolated follicles offers the advantage of circumventing the massive loss of follicles by ischaemia at early
stage of the grafting and excludes the theoretical reimplantation of malignant cells which cannot pass through the basal
membrane circumscribing the follicle.
Modern management of childhood malignancy is becoming increasingly effective. Aggressive chemotherapy and radiotherapy, as well
as bone marrow transplantation, can cure more than 90% of
patients. Unfortunately, the ovaries are very sensitive to cytotoxic
treatment, especially to alkylating agents and ionizing radiation,
resulting in the loss of both endocrine and reproductive functions.
In fact, it has been estimated that, by 2010, one in 250 people in
the adult population will actually be childhood cancer survivors.
The different options available to preserve fertility in young women
requiring chemo- and/or radiotherapy include cryopreservation of
oocytes, embryos or ovarian cortical tissue. For those patients who
require immediate chemotherapy, cryopreservation of ovarian tissue is a possible alternative. Laparoscopy allows simple retrieval of
ovarian tissue by either oophorectomy or multiple ovarian biopsies.
The aim is to reimplant tissue into the pelvic cavity (orthotopic site)
or a heterotopic site (like the forearm) once treatment is completed and the patient is disease-free.
We described, in June 2003, the first successful orthotopic
reimplantation of ovarian cortical tissue removed by laparoscopy from a woman with stage IV Hodgkin’s lymphoma before
she received chemotherapy.
For the first time, survival of primordial follicles was histologically demonstrated four months after reimplantation, and longterm restoration of ovarian function was proved by hormone
measurements, reappearance of regular menstrual bleeding
and vaginal echography. This is the first pregnancy after reimplantation of frozen ovarian cortical tissue in human. The baby
is born in september 2004.
Products and Services
Ovarian cryobanking
Experimental transplantation in nude mice and rats
Viability and apoptosis assays
Evaluation of neoangiogenesis
Main Equipment
Microscopy, morphometry and immunohistochemistry :
Orthoplan-Leitz microscope, 2 Axioscope Zeiss microscopes, 2
CCD 72E dag-MTI cameras, 2 Kontron image analysers, Leica
DMIL inverted microscope with fluorescence and camera,
Olympus fluorescence microscope.
Cellular culture : laminar flow hood, 2 CO2 incubators (Forma),
tissue chopper.
Cryopreservation : 2 Planer freezing apparatus, liquid nitrogen tanks, -85°C ultra low freezer Kryo 10 series III.
Biochemistry : electrophoresis and electrotransfer material, ELISA
plate analyser Model 550 (Biorad), UV/visible spectrophotometer (Biorad).
One major concern surrounding the use of ovarian tissue is the
potential risk that the frozen-thawed ovarian cortex might harbour malignant cells which could induce a recurrence of the disease after reimplantation. A recent study using a NOD/ SCID
xenograft model suggested that ovarian tissue transplantation
in Hodgkin’s disease was safe.
A significant follicular loss occurs with freezing, thawing and
grafting. Hypoxic damage to ovarian tissue could be reduced by
autografting a whole ovary after cryopreservation, or simply
isolated primordial follicles.
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Molecular biology : GeneAmp PCR System thermocycler 9600
Perkin-Elmer, agarose electrophoresis, transilluminator.
MARTINEZ-MADRID B., DOLMANS M.M., VAN EYCK A.S.,VAN
LANGENDONCKT A., DEFRERE S., DONNEZ J. Ficoll density gradient method for recovery of isolated human ovarian follicles.
Fertility Sterility, 2004, in press.
DONNEZ J., DOLMANS M.M., DEMYLLE D., JADOUL P., PIRARD
C., SQUIFFLET J., MARTINEZ-MADRID B., VAN LANGENDONCKT A.
Livebirth after orthotopic transplantation of cryopreserved ovarian
tissue. Lancet, 2004 Oct, 364.
Funding Sources
FNRS, FRSM, private grants.
Partnership
Inter-university project (Télévie) : Ulg, ULB, UCL.
Organizer of the first World Congress on Ovarian Cryopreservation and Ovarian Transplantation, June 2003.
UCL, Anatomo-Pathology Dept., Prof. Marbaix, Prof. Rahier,
Belgium.
VUB, Follicle Development Unit, Prof. Smitz, Brussels, Belgium.
University of Roma La Sapienza, Anatomo-Pathology Dept.,
Prof. Nottola, Italy.
STAFF
Total : 14
KEY WORDS FOR R&D
cancer
cryopreservation
follicles
ovary
Representative References
SENIOR SCIENTISTS
Jacques DONNEZ - Head of department
[email protected]
Tel. 32 (0)2 764 94 07 or 764 95 01
QU J., GODIN P.A., DONNEZ J. Expression of transforming growth
factor-, epidermal growth factor and epidermal growth factor
receptor in follicles of human ovarian tissue before and after cryopreservation. Fertil. Steril., 2000, 74 : 113-21.
DONNEZ J., QU J., DE HERTOGH O., NISOLLE M. Gonadal cryopreservation in the young patient with gynaecological malignancy. An
atlas of operative laparoscopy and hysteroscopy. Donnez J. and
Nisolle M. Eds, Parthenon Publishing, Carnforth, 2001, pp. 311-9.
DE HERTOGH O., QU J., NISOLLE M., DONNEZ J. Ovarian tissue
cryopreservation : technical aspects and existing alternatives. An
atlas of operative laparoscopy and hysteroscopy. Donnez J. and
Nisolle M. Eds, Parthenon Publishing, Carnforth, 2001, pp. 321-34.
JADOUL P., DONNEZ J. Conservative treatment may be beneficial
for young women with atypical endometrial hyperplasia or endometrial adenocarcinoma. Fertil Steril., 2003 Dec, 80(6) : 1315-24.
DONNEZ J., MUNSCHKE A., BERLIERE M., PIRARD C., JADOUL
P., SMETS M., SQUIFFLET J. Safety of conservative management
and fertility outcome in women with borderline tumors of the
ovary. Fertil Steril., 2003 May, 79(5) : 1216-21.
DOLMANS M.M., DEMYLLE D. Overview of the results of embryo
cryopreservation (D3, blastocysts); quality of embryos obtained
after an IVF attempt following one regimen of chemotherapy.
In: Program and Abstracts of the 1st World Congress on
Ovarian Cryopreservation & Ovarian Transplantation, Brussels,
June 27-28, 2003. Gunaïkeia, 2003, 8: 61, FA16.
MARTINEZ-MADRID B., DOLMANS M.M., VAN LANGENDONCKT
A., DEFRERE S., PIRARD C., DONNEZ J. Freezing entire human
ovaries with a passive cooling device. In: Program and Abstracts of
the 1st World Congress on Ovarian Cryopreservation & Ovarian
Transplantation, Brussels, June 27-28, 2003. Gunaïkeia, 2003, 8 :
159,O4.
DOLMANS M.M., MARTINEZ-MADRID B., VAN EYCK A.S.,VAN
LANGENDONCKT A., DEFRERE S., DONNEZ J. Apoptosis and viability in human ovarian tissue culture In: Program and Abstracts of
the 1st World Congress on Ovarian Cryopreservation & Ovarian
Transplantation, Brussels, June 27-28, 2003. Gunaïkeia, 2003, 8 :
162, O2.
Jean-Luc SQUIFFLET
[email protected]
Tel. 32 (0)2 764 10 71
Pascale JADOUL
[email protected]
Tel. 32 (0)2 764 95 02
Céline PIRARD
[email protected]
Tel. 32 (0)2 764 10 28
Christine WYNS
[email protected]
Tel. 32 (0)2 764 11 01
Dominique DEMYLLE
[email protected]
Tel : 32 (0)2 764 10 28
Marie-Madeleine DOLMANS
[email protected]
Tel. 32 (0)2 764 52 47
Belen MARTINEZ-MADRID
[email protected]
Tel. 32 (0)2 764 54 27
Anne VAN LANGENDONCKT
[email protected]
Tel. 32 (0)2 764 52 47
WEB SITES
http://www.gype.ucl.ac.be
http://rch.adre.ucl.ac.be/browse/list_alpha/
GYNE
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
G 2
Limb salvage in tumor surgery with massive bone allografts
SENIOR SCIENTISTS :
Christian DELLOYE
Olivier CORNU
Xavier BANSE
Research Field and Subjects
Products and Services
Study of massive allografts complications (fracture, infection,
non-union);
Bone allografts incorporation;
Treatment of non union or delayed union by autologous cell
therapy;
Osteo-induction by demineralised bone matrix.
The Tissue Bank is able to deliver massive bone allografts to
surgeons for skeletal reconstruction ([email protected]). The
Tissue Bank is applying the European standards and the
Belgian and French national regulations (see http://www.
eamst.org).
Research projects may cover all fields of interests from microbiological studies (in vitro testing of bacterial screening and
decontamination) to in vivo model of allografts incorporation
(Tibial critical defect in sheep). Mechanical and morphological
assessments of allograft reconstruction may be performed.
Among the different avenues to improve allograft incorporation and bone healing, autogenous cell augmentation represents an indirect approach. Stromal cells from the patient’s
bone marrow can be cultured and serve as a source of additional osteogenic cells. This attractive concept awaits further
in vivo research (rat nude model of osteoinduction) and clinical confirmation.
Bone allografts have a long history as a substitute for limb
reconstruction after tumor resection. They are commonly used
because they provide immediate structural support that can be
associated with a prosthesis or with osteosynthesis. Among
several advantages, their use allows anatomical reconstruction
of the skeletal defect, biological union to host bone through
callus formation, soft tissue adherence around the grafted bone
and the possibility of tendon reinsertion on its counterpart left
on the bone graft. Among possible disadvantages, there are the
risk, albeit remote, of disease transmission through the implant,
and a high rate of non union and fracture. These complications
are related to the non vitality of the bone graft.
Research projects are conducted to remote disadvantages of
bone allografts. Methods of bacterial screening and graft
decontamination are assessed by in vitro testing. Using the
graft as an antibiotic delivering system is also considered.
As a bone allograft serves primarily as an osseous spacer that
allows osteoconduction of host cells into its mass, biological
answer results in a progressive incorporation of the graft into
the host bone. Incorporation includes a series of events leading
to gradual replacement of the grafted bone by host bone
through a mechanism of osteoclastic resorption followed by
new bone deposition. This intricate process however is very
limited in time and space, leaving eventually a mass of dead
bone that has been poorly substituted by new bone.
Efforts are made to overcome this limited substitution through
improvement of the revascularisation and revitalisation of the
bone. The research is organised to explore the different avenues
available to achieve a better incorporation and avoiding a
mechanical failure.
Main Equipment
Bone morphological analysis
Cell culture facilities
Cleanroom facilities
Digitalisation table
Exact saw
Fluoroskan Ascent
Hip walking simulator
Leitz saw 1600
Microradiography (Bemtograph)
Microscopy
Microtome Leica
Multiscan RC200-240C
p-QCT, model XCT Research SA+® Stratec (RUMA)
Radiographic digitizer (Widar)
Tissue Bank
UTS model 100-1 (ERM)
Zwick model Z50/TH3A (ERM)
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Representative References
Partnership
BRESLER F., SIMON P., SCHMITT D., VERHELPEN M., DE GASPERI
M., DELLOYE C. Digital image analysis of bone allograft union in
sheep. Acta Orthop. Scand., 1998 Apr., 69(2):181-3.
DELLOYE C., DOCQUIER P.L., CORNU O., POILVACHE P., PETERS
M., WOITRIN B., ROMBOUTS J.J., DE NAYER P. Simple bone
cysts treated with aspiration and a single bone marrow injection. A preliminary report. Int. Orthop., 1998, 22(2):134-8.
DELLOYE C. Bone grafts using tissue engineering. Bull. Mem.
Acad. R. Med. Belg., 2001, 156(7-9):418-25.
DELLOYE C., SIMON P., NYSSEN-BEHETS C., BANSE X., BRESLER
F., SCHMITT D. Perforations of cortical bone allografts improve
their incorporation. Clin. Orthop., 2002 Mar., (396):240-7.
DOCQUIER P.L., DELLOYE C. Treatment of simple bone cysts
with aspiration and a single bone marrow injection. J. Pediatr.
Orthop., 2003, 23(6):766-73.
DELLOYE C., CORNU O. Incorporation of massive bone allografts: can we achieve better performance? Acta Orthop. Belg.,
2003 Apr., 69(2):104-11.
SCHECROUN N., DELLOYE C. Bone-like nodules formed by
human bone marrow stromal cells: comparative study and
characterization. Bone, 2003 Mar., 32(3):252-60.
DELLOYE C., CNOCKAERT N., CORNU O. Bone substitutes in
2003 : an overview. Acta Orthop. Belg., 2003, 69(1):1-8.
Royal Military School - Engineering (Prof Van Thomme), Bruxelles,
Belgium
Université de Strasbourg - Orthopaedic Department (Prof Simon),
Strasbourg, France.
Université de Nancy – Experimental Surgery (Prof Schmitt),
Nancy, France.
University of Bristol - Collagen Biochemistry Laboratory (Prof
Bailey), Bristol, UK.
University of Toronto – Phospho-calcic metabolism Lab (Prof
Grynpas), Toronto, Canada.
Institut Rizzoli (Prof Donati), Bologne, Italie.
Azienda Ospedaliera Careggi (Prof Capanna), Florence, Italie.
STAFF
Total : 20
KEY WORDS FOR R&D
allografts
anatomopathology
autologous cell therapy
bacteriology
biomechanic
bone induction
bone remodeling
delayed-union
fracture
infection
limb salvage
orthopaedic
surgery
transplantation
Awards
Dr
Dr
Dr
Dr
D. Dufrane BELACT - 2000
A. Bavadekar EFORT – Rhodos - 2001
D. Dufrane ESACT – Tylösand - 2001
P.L. Docquier – SORBCOT– 2004
SENIOR SCIENTISTS:
Christian DELLOYE
[email protected]
Tel. 32 (0)2 764 29 50
Funding Sources
Olivier CORNU
[email protected]
Tel. 32 (0)2 764 53 88
Télévie-FNRS
Salus Sanguinis fundation.
WEB SITE
http://rch.adre.ucl.ac.be/browse/list_alpha/
ORTO
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
H 1
Biological dosimetry and radiobiological calibration of
clinical hadron beams
SENIOR SCIENTIST :
John GUEULETTE
Research Field and Subjects
Representative References
Hadron beams (e.g. neutrons, protons heavy ions) are used in
advanced radiation therapy techniques. Due to their physical
characteristics (e.g. density of ionization or Linear Energy
Transfer, LET), these beams might exhibit a biological effectiveness (ratio of the biological effect to the dose) very different
from that of classical photon beams. From there, the necessity
of calibrating them, and determining the “gamma dose equivalents” allowing the radiation oncologist to refer to his clinical
experience with photons.
However, the Relative Biological Effectiveness (RBE) of a given
type of radiation is not constant but varies with different physical (e.g. energy of the beam) and biological (e.g. biological system, fractionation) factors.
Therefore, it was necessary to determine the physical and biological conditions relevant to the clinical applications and to
work out a specific experimental procedure for determining the
actual value of the dose weighting factors.
This procedure was applied to the radiobiological calibration of
most clinical hadron beams worldwide and is now called for as
the standard biological Quality Assurance (QA) procedure previous to the clinical implementation of new beams.
GUEULETTE J., BEAUDUIN M., GREGOIRE V., VYNCKIER S.,
DE COSTER B.M., OCTAVE-PRIGNOT M., WAMBERSIE A.,
STRIJKMANS K., DE SCHRIJVER A., EL-AKKAD S., BOHM L.,
SLABBERT J.P., MAUGHAN R., ONODA J., YUDELEV M., PORTER
A.T., POWERS W.E., SABATTIER R., BRETEAU N., COURDI A.,
BRASSART N., CHAUVEL P. RBE variation between fast neutron
beams as a function of energy. Intercomparison involving 7
neutrontherapy facilities. Bull. Cancer. Radiother., 1996, 83
Suppl:55s-63s.
GUEULETTE J., SLABBERT J.P., BOHM L., DE COSTER B.M.,
ROSIER J.F., OCTAVE-PRIGNOT M., RUIFROK A., SCHREUDER
A.N., WAMBERSIE A., SCALLIET P., JONES D.T. Proton RBE for
early intestinal tolerance in mice after fractionated irradiation.
Oncol., 2001 Nov., 61(2):177-84.
GUEULETTE J., BOHM L., SLABBERT J.P., DE COSTER B.M.,
RUTHERFOORD G.S., RUIFROK A., OCTAVE-PRIGNOT M., BINNS
P.J., SCHREUDER A.N., SYMONS J.E., SCALLIET P., JONES D.T.
Proton relative biological effectiveness (RBE) for survival in mice
after thoracic irradiation with fractionated doses. Int. J. Radiat.
Oncol. Biol. Phys., 2000 Jul 1, 47(4):1051-8.
YING H., SERHIR L., MAHY P., RENIERS B., GUEULETTE J.
Design of a cylindrical brachytherapy implant applicator for the
irradiation of an intestinal segment in mice. Radiat. Res., 2003
Jan, 159(1):123-7.
Products and Services
Radiobiological calibration and QA of clinical hadron beams.
Biological control of dynamic beam delivery systems (scanned
beams). Determination of irradiation protocols and design of
irradiation devices (e.g. animal holders) for the radiobiological
experimentation in extreme physical conditions (e.g. important
dose gradients, short distance from the source, continuous low
dose rate, etc.).
Awards
Radié Kotze Commemorative Lecture Medal : National
Accelerator Centre, Faure, Cape Town (South Africa), 1998.
Funding Sources
Main Equipment
Fonds de la Recherche Scientifique Médicale (FRSM)
International Atomic Energy Agency (IAEA)
Various occasional foreign grants
Linear accelerator (St-Luc hospital)
250 kV X-ray machine (faculty of Medicine)
Clinical neutron beam (cyclotron of Louvain-la-Neuve)
Biological laboratory and histology equipment
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Partnership
STAFF
Total : 4
FYNU, UCL, Louvain-la-Neuve, Belgium.
Radiotherapy Oncology Department, St-Luc hospital, Brussels,
Belgium.
Radiotherapy and Physics Departments of various foreign
Universities worldwide.
KEY WORDS FOR R&D
biological dosimetry
clinial hadron beams
radiation
radiobiological calibration
Relative Biological Effectiveness (RBE)
SENIOR SCIENTIST
John GUEULETTE
[email protected]
Tel. 32 (0)2 764 54 84
WEB SITE
www.md.ucl.ac.be/rbnt
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
H 2
Radiobiology of light ions
SENIOR SCIENTIST :
André WAMBERSIE
Research Field and Subjects
Representative References
Due to his large experience in non-conventional radiation therapy gained during clinical application of fast neutrons at the
cyclotron CYCLONE of Louvain-la-Neuve (1972-2001),
Professor A. Wambersie was selected as leader of the work package 4 of the the European Network for LIGht ion Hadron
Therapy (ENLIGHT).
A. BRAHME. Treatment optimization using physical and biological objective functions. In: Radiation Therapy Physics, Ed.:
Smith A, Berlin Springer (1995) pp 209-246.
U. AMALDI, B. LARSSON and Y. LEMOIGNE. Advances in
Hadrontherapy. Excerpta Medica, Elsevier Science, Amsterdam,
1997.
J. GUEULETTE, L. BÖHM, B.M. DE COSTER, A. WAMBERSIE
and al. RBE variation as a function of depth in the 200 MeV
proton beam produced at the NAC. Faure, Radiotherapy and
Oncology, 42, 303-309, 1997.
U. AMALDI. Conformal radiation therapy with hadron beams and
the programs of the TERA Foundation. Rays 23/3 (1998) 486-507.
U. AMALDI. Cancer therapy with particle accelerators. Nucl.
Phys. A654 (1999) 375c-399c.
H. ENGELS and A. WAMBERSIE. Cancer epidemiology and patient
recruitment for hadron therapy. Strahlentherapie und Onkologie,
175(II), 95-98, 1999.
A. BRAHME, R. LEWENSOHN, U. RINGBORG, U. AMALDI, F.
GERARDI, S. ROSSI. Design of a centre for biologically optimised light ion therapy in Stockholm. Nucl. Instr. Meth. Phys.
Res. 2001.
A. WAMBERSIE and R.GAHBAUER: Hadrons (protons,neutrons,
heavy ions) in radiation therapy: rationale, achievements and
expectations. Radiochimica Acta, 89, 245-253, 2001.
A. WAMBERSIE, H.G. MENZEL, R.A. GAHBAUER, D.T.L. JONES,
B.D. MICHAEL and H. PARETZKE. Biological weighting of absorbed
dose in radiation therapy. Radiation Protection Dosimetry, 99, 445452, 2002.
A. WAMBERSIE, J. GUEULETTE, D.T.L. JONES and R. GAHBAUER.
Ion-beam therapy: rationale, achievements and expectations,
in Charged particles and photon interactions with matter.
(Eds A. Mozumber and Y. Hatano), Marcel Dekker Inc., New York,
2003, 743-784.
V. GRÉGOIRE, R. PÖTTER and A. WAMBERSIE. General principles
for prescribing, recording and reporting a therapeutic irradiation.
Radiotherapy and Oncology, special issue, 2004, in press.
A. WAMBERSIE, R. GAHBAUER and G. MENZEL. RBE and weighting of absorbed dose in ion-beam therapy. Radiotherapy and
Oncology, Special issue, 2004, in press.
Insofar, as ion beams can provide a chance of cure to a subset
of patients with radio-resistant tumours, ENLIGHT aims at a
coordinated effort towards ion beam research in the EU.
Its main objective is :
1. to assess the respective strengths of each of the partners and
the advantages of the different approaches,
2. to evaluate the already developed technology in the light of
emerging new developments
3. to agree on the common development of still missing tools
and for approaching the industry. Last but certainly not least, a
common strategy for clinical validation and implementation will
be developed.
Expected results
Technological objectives
The aim is to have all the project groups responsible for the
various facilities work together and in close connection with the
European radiation oncologists so as to make the projects clinically effective, reduce their cost and increase their reliability. The
technological objectives are thus :
- to design and produce all technical systems (e.g. beam delivery system, patient positionning system, etc.) using all the available expertise so as to avoid work duplication and meet the
stringent criteria imposed by the clinical applications;
- to order jointly components to industry so as to reduce the
cost and have a better quality control during construction,
installation and running.
Scientific and Public Health objective
Through a European network coordinated by ESTRO, radiation
oncologists throughout Europe will develop a co-ordinated
action for the implementation of common treatment protocols
and clinical research.
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A. WAMBERSIE, J. HENDRY, J. GUEULETTE, R. GAHBAUER, R.
PÖTTER and V. GREGOIRE. Radiobiological rationale and patient
selection for high-LET radiation in cancer therapy. Radiotherapy
and Oncology, Special issue, 2004, in press.
STAFF
Total : 18
KEY WORDS FOR R&D
accelerator technology
beam
cancer therapy
carbon ion beams
DVH
epidemiology
high LET radiation
high LET radiobiology
ion beams
late tissue reactions
microdosimetry
radiation therapy
radiobiology
RBE
scanning beam
simulation
socio-economics
treatment planning
Patents
Results will be shared and published as open source information.
Funding Sources
European Commission, FP5, Quality of Life and Living Resources
Programme, Thematic Network.
Partnership
Facilities in different stages of development in several regional
centres in Europe provided the national research efforts.The
work is distributed over 6 task groups working in parallel over
a time frame of 3 years. 2 clinical groups will focus on
Epidemiology-Patient Selection and on the Design and Conduct
of Clinical Trials. The Network will bring together 87 scientists
from 9 different disciplines: radiation oncology, epidemiology,
nuclear medicine, basic physics, engineering, clinical physics,
radiobiology, computing and health economics.
SENIOR SCIENTIST
André WAMBERSIE
[email protected]
Tel. 32 (0)2 764 54 68
WEB SITE
http://www.estro.be
ESTRO: European Society for Therapeutic Radiology and
Oncology, Brussels, Belgium.
UCL, Radiobiology and radiation protection unit, Brussels,
Belgium.
CERN, European Organisation for Nuclear Research, Geneva,
Switzerland.
GSI, Gesellschaft für Scherionenforschung, Darmstadt, Germany.
DKTZ, German Cancer Research Center, Heidelberg, Germany.
TERA, Fondazione per Adroterapia Oncologica, c/o CERN,
Geneva, Switzerland.
Karolinska Institute, Stockholm, Sweden.
ETOILE, Université Claude Bernard, Lyon, France.
Med-AUSTRON, AKH, University Hospital, Vienna, Austria.
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
H 3
Molecular imaging for radiotherapy
SENIOR SCIENTIST :
Vincent GRÉGOIRE
Research Field and Subjects
Representative References
The aim of this project is to assess the value of functional imaging for tumor volume delineation and its impact on dose distribution in 3D-conformal radiotherapy for head & neck tumors.
J.F. DAISNE, M. SIBOMANA, A. BOL, T. DOUMONT, M.
LONNEUX and V. GRÉGOIRE. Tri-dimensional automatic segmentation of PET volumes based on measured source to background ratios: influence of reconstruction algorithms.
Radiother. Oncol., 69: 247-250, 2003.
J.F. DAISNE, M. SIBOMANA, A. BOL, G. COSNARD, M.
LONNEUX and V. GRÉGOIRE. Evaluation of a multimodality
image (CT, MRI and PET) coregistration procedure on phantom
and Head and Neck cancer patients: accuracy, reproducibility
and consistency. Radiother. Oncol. 69: 237-245, 2003.
X. GEETS, J.F. DAISNE, V. GREGOIRE, M. HAMOIR, M.
LONNEUX. Role of 11-C-methionine positron emission tomography for the delineation of the tumor volume in pharyngolaryngeal squamous cell carcinoma: comparison with FDG-PET
and CT. Radiother. Oncol. 71: 267-73, 2004.
J.F. DAISNE, T. DUPREZ, B. WEYNAND, M. LONNEUX, M.
HAMOIR, H. REYCHLER, V. GRÉGOIRE. Accuracy of CT scan,
MRI and FDG-PET in delineating the tumor volume in pharyngo-laryngeal squamous cell carcinomas treated by radiotherapy: validation with the macroscopic tumor specimen used as
reference. Radiology, 2004 (in press).
Positron Emission Tomography (PET) with various tracer of
metabolism, (FDG), proliferation (FLT, BFU), hypoxia (EF3),
magnetic resonance with perfusion and diffusion algorithms,
and CT-scan are compared. All functional images are co-registered on anatomic CT and MR images.
Patients are imaged before radiotherapy and during treatment
to assess the volume change. Validation of the various functional imaging modalities with anatomopathological examination
of tumor specimens is also foreseen in patients scheduled for
surgical treatment.
This project is conducted in collaboration with the former laboratory of Positron Emission Tomography (TOPO), presently merged in
a new entity Molecular Imaging and Experimental Radiotherapy
(IMRE), and the departments of head and neck surgery, oral and
maxillofacial surgery, nuclear medicine and radiology.
Products and Services
Patents
Development and design study of 1 mm resolution PET.
Are subject to the TRIPPS clauses in the Consortium Agreement.
Improved performance (speed-resolution) of PET-CT, MRSI and
other imaging modalities for RT.
Funding Sources
Methodologies, techniques, predictive assays and other tests, markers, radiolabeled inhibitors etc., for the optimisation and verification of biologically optimised intensity modulated radiotherapy.
Télévie
European Commission, FP6, Life Sciences, Major Diseases, Cancer
Belgian Federation against Cancer
Main Equipment
Partnership
Multi-modality imaging facilities.
Molecular biology research laboratory.
Radiotherapy simulation, planning treatment and verification
equipment and software.
Telecommunication laboratory, UCL, Prof. B. Macq.
Dept. of Radiation Oncology, KULeuven, Prof. K. Haustermans.
Dept. of Radiation Oncology, RUGent, Prof. W. De Neve.
BioCARE project, Karolinska Institute, Stockholm
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STAFF
Total : 20
KEY WORDS FOR R&D
head and neck tumor
hypoxia
metabolism
MRI
PET
proliferation
radiotherapy
tracers
SENIOR SCIENTIST
Vincent GRÉGOIRE
[email protected]
Tel. 32 (0)2 764 94 43
WEB SITES
http://www.md.ucl.ac.be/rbnt
http://www.md.ucl.ac.be/ccmf
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
H 4
Treatment planning of intensity modulated radiotherapy
(IMRT) for head and neck cancer : optimization of the
treatment technique and validation by measurements and
Monte Carlo simulations
SENIOR SCIENTISTS :
Milàn TOMSEJ
Nathalie DE PATOUL
Stefaan VYNCKIER
Vincent GREGOIRE
Furthermore, the verification of IMRT treatments could be done
with in vivo dosimetry. Actually, a reconstruction of dose distributions inside the patient from portal images acquired during the
treatment can be envisaged by Monte Carlo simulation as well.
Research Field and Subjects
Intensity Modulated Radiotherapy (IMRT) is a specific technique to
irradiate with high homogeneity tumor volumes whilst sparing
as much as possible the critical organs. This technique consists of
delivering a radiation dose by the means of photon beams with
non-uniform irradiation fields obtained by the superposition in
small beamlets. The different beam intensities are then the result
of a powerful mathematical optimization algorithm based on the
input of dosimetric constraints on critical organs and tumor volumes into the treatment planning system software.
In radiotherapy treatments of head and neck cancer, several
challenges exist in terms of irradiation optimization, such as for
instance the complex geometry of the patient outline, the complicated shape of target volumes located in proximity of critical
organs (parotid glands, spinal cord, etc) and obviously the
presence of heterogeneities in the head and neck region (bony
structures and very small air cavities).
Consequently, the implementation and the dosimetric validation of such irradiation technique (IMRT) for this pathology
have to be carried out.
Products and Services
Verification of complex and sophisticated treatments
Methodology to improve treatments for head and neck cancer
Main Equipment
Linear accelerator ELEKTA SLi25
Treatment planning systems HELAX-TMS (NUCLETRON), KONRAD (SIEMENS), PLATO ITP (NUCLETRON), ECLIPSE (VARIAN)
Monte Carlo code OTP (NUCLETRON)
Monte Carlo code BEAMnrc (NRC-CNRC)
Representative References
Mathematic algorithms for the dose calculation used by
modern treatment planning softwares are becoming limited in
terms of accuracy for the calculation of the dose distributions
of such complex and sophisticated irradiation technique.
Moreover, measurements made for the verification of these
treatments show uncertainties inherent to the limitations of the
current detectors applied to these extreme conditions.
G. KUHN. Towards IMRT treatments in head and neck tumors:
implementation of a new technique, preliminary dosimetric verification and first results. Thesis submitted for the degree of
European Master of Science, University of London, St
Bartholomey’s and the Royal London Hospital School of
Medicine and Dentistry London, (promotor: M. TOMSEJ), 2001.
M. TOMSEJ, V. GRÉGOIRE, S. VYNCKIER and P. SCALLIET. Sparing
parotids and increasing conformity in H&N treatments: development of a new conformal technique, description of a QA
program and first results. Radioth. and Oncol., 31, suppl.1,
pp.S45, 2001.
A. MARGOUM. Radiothérapie par faisceaux modulés en intensité
dans la région tête et cou : commissionnement et validation
dosimétrique. Thèse Physique médicale (promotor : M.
TOMSEJ), Janvier 2003.
M. TOMSEJ and al., Quality assurance program for intensity
modulated radiotherapy (IMRT) treatments of head and neck
carcinomas. Cancer/Radiothérapie 7, 2003, 172-178.
M. TOMSEJ and al., Recommandations pour un protocole
Therefore validation of IMRT requires the use of a very special calculation technique called “the Monte Carlo simulation”. This
consists in a numerical resolution of particle transport equations
in which it is possible to calculate energy losses into the body of
the patient and thus the deposited dose received by the patient.
Such technique is then able to consider the irradiation geometry
by a modelisation of the mechanical and physical characteristics
of the linear accelerator as well as the physical properties of the
patient (external geometry and different internal density structures). This theoretical solution can be considered as a first step validation of the treatment planning optimization.
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d’assurance de qualité de la radiothérapie conformationnelle
avec modulation d’intensité des cancers de la tête et du cou.
Cancer/Radiothérapie, 2004, in press.
NCS group, Monte-Carlo Treatment Planning, an introduction. Task group Monte Carlo treatment planning, in press.
STAFF
Total: 3
KEY WORDS FOR R&D
head and neck cancer
IMRT
Monte Carlo calculations
treatment planning
Patents
PIGG IMRT phantom (GORTEC), M. Tomsej & V. Marchesi
SENIOR SCIENTISTS
Milàn TOMSEJ
[email protected]
Tel. 32 (0)2 764 47 60 (61)
Awards
Nathalie DE PATOUL
[email protected]
Tel. 32 (0)2 764 47 60
Fondation Saint-Luc
Funding sources
Stefaan VYNCKIER
[email protected]
Tel. 32 (0)2 764 55 73
Fondation Saint-Luc
Vincent GREGOIRE
[email protected]
Tel. 32 (0)2 764 94 43
Partnership
GORTEC, Groupe Oncologie Radiothérapie Oncologie,
international scientific society
NCS (Nederlandse Commissie voor strahling dosimetrie),
international scientific society
NRC-CNRC, Research center
Nucletron, industrial company
Varian, industrial company
Siemens-MRC, industrial company
WEB SITE
www.md.ucl.ac.be/rbnt/pages/MTomsej.htm
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
I 1
Psycho-oncology - Physician-Patient relationships Communication skills training - Quality of life - Professionnal
stress - Burnout
SENIOR SCIENTISTS :
Christine REYNAERT
Pierre SCALLIET
Yves LIBERT
Research Field and Subjects
Partnership
Cancer diagnosis, treatment and follow-up provoke highly
emotional reactions and lead to various coping strategies
expressed by patients, their relatives and clinicians. The main
aim of psycho-oncology is to study these psychological and
behavioural reactions.
Université Libre de Bruxelles
Université de Liège
Representative References
In the last decades, a lot of attention has been devoted to the
study of patients’ and relatives’ ways of coping with cancer.
Predictors of these ways of coping and of their consequences in
terms of quality of life and sometimes in terms of life expectancy
have been described. Moreover, psychosocial interventions devoted to improve their adjustment to cancer have been developed.
REYNAERT CH., LIBERT Y., JANNE P., “Psychogenèse” du cancer : entre mythes, abus et réalité. Bull Cancer., 2000; 87 :655-64.
REYNAERT CH., LIBERT Y., JANNE P., “Psychogenèse” du cancer :
vers une piste psycho-neuro-endocrino-immunologique ? Ann.
Med. Psychol., 2001, 159, 273.
REYNAERT CH., LIBERT Y., JANNE P., ZDANOWICZ N. Comment
allez-vous, Docteur ? Le burn-out du médecin. Louvain Médical,
2001; 120 : 296-310.
LIBERT Y., CONRADT S., REYNAERT CH., JANNE P., TORDEURS
D., DELVAUX N., FONTAINE O., RAZAVI D. Améliorer les stratégies de communication des médecins en oncologie : état des
lieux et perspectives futures. Bull. Cancer. 2001; 88: 11671176.
JANNE P., TORDEURS D., MICHAUX G., GHISLAIN M.C., MAZY
S., DE WISPELAERE J.F., LIBERT Y., REYNAERT C. Le cancer du sein
et son approche psychologique : la famille, les autres, la chance
et… moi. Gynecol. Obstet. Fertil., 2001; 29 :28-33.
RAZAVI D., MERCKAERT I., MARCHAL S., LIBERT Y., CONRADT S.,
BONIVER J., ETIENNE A.M., FONTAINE O., JANNE P., KLASTERSKY J.,
REYNAERT CH., SCALLIET P., SLACHMUYLDER J.L., DELVAUX N.
How to optimise physicians’ communication skills in cancer care:
Results of a randomised study assessing the usefulness of post training consolidation workshops. Journal of Clinical Oncology, 2003;
16: 3141-3149.
LIBERT Y., JANNE P., RAZAVI D., MERCKAERT I., SCALLIET P.,
DELVAUX N., ETIENNE A.M., CONRADT S., KLASTERSKY J.,
BONIVER J., REYNAERT CH. Impact of medical specialist’s ocus
of control on communication skills in oncological interviews.
British Journal of Cancer, 2003, 88 : 2004-2005.
REYNAERT CH., LIBERT Y., JANNE P., ZDANOWICZ N. Le syndrome
d’épuisement du soignant ou burn-out syndrome. Approche cognitivo-comportementaliste. in Delbrouck M. (Ed.), Le burn-out du
soignant. Le syndrome d’épuisement professionnel, De Boeck &
Larcier, 2003; Bruxelles: 37-42.
Numerous studies have also focused on oncologists’ professional quality of life and on their ways of coping with professional
stress. These studies have highlighted numerous stress factors
associated with practice in oncology that could lead to burn
out. Among these factors, relationships with patients and the
feeling of being insufficiently trained in communication skills
have been widely underlined.
Consequently, specifically designed communication skills training
workshops have been developed and assessed. These research programs have highlighted that only training techniques such as roleplaying, case-discussion or feed-back could lead to significant changes in physicians’ behaviours. Previous studies have moreover suggested that the benefit of these workshops could be transient and
not observed in physicians’ everyday practice. However, no studies
have yet assessed the efficacy of post-training consolidation workshops following a basic training in communication skills.
The present project intended to explore the conditions of an optimal communication skills training program by assessing its effectiveness directly on changes in physicians’ communication skills as
well as on changes in their patients satisfaction with care.
Funding Sources
Fonds national de la recherche scientifique (FNRS) – Télévie
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REYNAERT CH., LIBERT Y., JANNE P., ZDANOWICZ N. Le stress
professionnel et les stratégies d’adaptation du soignant. in
Delbrouck M (Ed.), Le burn-out du soignant. Le syndrome
d’épuisement professionnel, De Boeck & Larcier, 2003;
Bruxelles: 121-128.
JANNE P., DARRAS E., TORDEURS D., REYNAERT CH.,
ZDANOVICZ N., LIBERT Y. Du “burn in” au “burn out” à propos
de la réponse du berger malheureux à la bergère ingrate. in
Delbrouck M (Ed.), Le burn-out du soignant. Le syndrome
d’épuisement professionnel, De Boeck & Larcier 2003;
Bruxelles: 121-128.
LIBERT Y., REYNAERT CH., RAZAVI D., MERCKAERT I., SCALLIET
P., DELVAUX N., ETIENNE A.M., CONRADT S., KLASTERSKY J.,
BONIVER J., JANNE P. Impact of medical specialist’s Locus of
Control on communication skills in three-person oncological interviews, 2004, submitted.
DELVAUX N., MERCKAERT I,. MARCHAL S., LIBERT Y., CONRADT
S., BONIVER J., ETIENNE A.M., FONTAINE O., JANNE P, KLASTERSKY
J., REYNAERT CH., SCALLIET P., SLACHMUYLDER J.L., RAZAVI D.
Impact of consolidation workshops on cancer specialists’ communication skills in three-person interviews: a randomised study,
2004, submitted.
CONRADT S., RAZAVI D., FONTAINE O., LIBERT Y., DUPUIS G.,
BONIVER J., MERCKAERT I., REYNAERT CH., JANNE P.,
SCALLIET P., KLASTERSKY J., DELVAUX N., ETIENNE A.M. The
impact of the specialist physician’s communication skills on the
cancer patient’s quality of life: A pilot study. Quality of life in
terms of goal attainment, 2004, submitted.
STAFF
Total : 3
KEY WORDS FOR R&D
applied psychology
clinical psychology
communication theory
emotion and cognition
emotion, stress and trauma
health psychology
human sciences
information and communication
interpersonal communication
medical psychology
palliative care
professional stress
psychology
psychosomatic
research methods in psychology
social cognition
SENIOR SCIENTISTS :
Christine REYNAERT
[email protected]
Tel. 32 (0)81 42 37 51
Pierre SCALLIET
[email protected]
Tel. 32 (0)2 764 37 63 or 47 26
Yves LIBERT
[email protected]
Te. 32(0)2 539 19 61
WEB SITES
http://www.md.ucl.ac.be/rbnt
http://rch.adre.ucl.ac.be/browse/list_alpha/PSME
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
I 2
The question of meaning in front of cancer
Biographical approach
SENIOR SCIENTISTS :
Jean-Luc BRACKELAIRE
Michel LEGRAND
Patrick DE NEUTER
Research Field and Subjects
STAFF
Total : 4
Questioning the place and the meaning of cancer within the
“story of life” of the subjects. Device of Biographical Approach
(+/- 10 interviews of 2 hours or 20 interviews of 1 hour).
KEY WORDS FOR R&D
biographical approach
clinical psychology
health psychology
meaning
medical psychology
psychosomatic
story of life
We investigate the possibility of the participation of a psychic
suffering (a relational impasse) on the development and evolution of cancer (in a multifactorial approach).
We question how the subjects, through the story of their life,
deploy one discourse which reveals their existential drama –
which is sometimes linked with cancer in the related story (evocation of one “psychological” origin of the disease).
SENIOR SCIENTISTS
Jean-Luc BRACKELAIRE
[email protected]
Tel. 32 (0)10 47 87 25
The research is about how to think this link beetween psychic
suffering and somatic disease (the psychosomatic questioning).
Michel LEGRAND
[email protected];
Tel. 32 (0)10 47 44 70
Products and Services
Patrick DE NEUTER
[email protected]
Tel. 32 (0)10 47 90 55
Psychological consultations specialized in “stories of life”
Representative References
WEB SITE
http://www.ucl.ac.be/cps/cpshistoiresdevie
PONCELET V. (2004). Un désespoir amoureux en attente de
se dire : récit de vie d’une femme en rémission d’un cancer
génital. Cliniques Méditérranéennes, 69, 159-174.
Funding Sources
Insitutional Funding
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
I 3
Coping styles, anxio-depression, alexithymia and evolution
of breast cancer
SENIOR SCIENTIST :
Vincent JADOULLE
Research Field and Subjects
STAFF
Total : 3
Study of the effect of psychological coping styles, depression
and alexithymia on the evolution of breast cancer.
KEY WORDS FOR R&D
alexithymia
breast cancer
coping styles
depression
health psychology
Study of the longitudinal evolution of psychological adaptation
to breast cancer.
Validation of the french version of a coping scale.
SENIOR SCIENTIST
Representative References
Vincent JADOULLE
[email protected]
Tel. 32 (0)2 764 21 65
JADOULLE V., OGEZ D., ROKBANI L. Le cancer, défaite du psychisme ? Bull. Cancer., 2004, 91: 249-256.
WEB SITE
http://www.saintluc.be/english/index.html
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
The Université catholique de Louvain (UCL) is located on two sites : Louvain-la-Neuve (pure and applied sciences and
human sciences) and Brussels (medical sciences).
The UCL-Brussels site extends on 52 ha and gathers university teaching, higher schools, an academic hospital and
research centers. The site is attended daily by more than 25.000 people.
At the education and research level, the site of UCL-Brussels, built around its Faculty of Medicine and the St Luc academic
hospital, associates multiple approaches around health : medicine, pharmacy, dentistry, public health, biomedical sciences...
Many research institutes of international reputation are also present on the site : the Institute of cellular pathology
(ICP) and the Ludwig Institute for cancer research (LICR), as well as an incubator where various research associations
are working in close relationship with the university and the hospital : EORTC, NCI, ESTRO, FECS, ESSO, ILSI, EONS.
www.ucl.ac.be
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
J 1
Cancer Center at UCL and Saint Luc academic hospital
Mission
Today, individual and isolated physicians no longer succeed in
mastering the entire spectrum of knowledge required to deliver
appropriate care in oncology.
Oncology has become an immense, multidisciplinary field.
Actually, “interdisciplinarity” is a better word since it emphasises the interaction between specialists in the design and implementation of complex sequences of care (surgery, drug therapy,
radiotherapy, rehabilitation, etc).
In the academic hospital of the UCL, a cancer centre was established in 1999, aiming at supporting the development of interdisciplinary oncology across the entire institution.
This transverse structure within the hospital is characterized by
an organization focused on organs and systems rather than on
individual specialities.
-
group
group
group
group
group
group
group
group
group
group
hematologic cancer
paediatric hemato-oncology
hepatobilio-pancreatic cancer
skin and ocular melanoma
oesophagus and stomach cancer
neurological cancerology
ophthalmologic cancerology
breast cancer and gynaecology
thoracic cancerology
urologic cancerology
The “treatment“division gathers the units of radiation oncology,
medical oncology (chemotherapy), palliative care and cancer
screening. These patients already have their treatment plan,
determined during a multidisciplinary meeting.
The “teaching and research“ division coordinates the efforts
in the field of teaching and research clinic, with the setting up
of a coordination of clinical trials.
Activities
Methodology
Cancer patients often present associated pathologies and may
therefore be diagnosed in departments or units where oncology is not necessarily the main activity. A hospital of cancer must
be able to treat the patient as a whole, resorting to consultants
in various oncologic and non-oncologic specialities. To formalize coordination between the departments and the specialists, a
cancer centre was created with three distinct divisions : orientation, treatment and research.
Oncology boards are meant to bring together the various cancer experts in the hospital, around individual patient cases, in
order to discuss the diagnosis, treatment and follow-up strategy that seems the most appropriate. The ultimate goal is to
bring homogeneity in the quality of care in oncology at the level
of the hospital.
The “orientation“ division consists of a series of groups that
bring together the various specialists involved in a particular type
of cancer. Each includes an organ specialist (gynaecologist,
ORL,...), a specialized surgeon, a medical oncologist, a radiation
oncologist, an imaging specialist, a pathologist and, according to
the cases, a geneticist and any other specialist concerned. 13
groups known as “groups of dialogue” are organized :
At regular intervals, depending on the type of cancer, the radiation
oncologist, medical and surgical oncologist, pathologist, specialist
in imaging, research nurse, psychologist meet to discuss the new
cancer cases, diagnosed since the previous board meeting. For frequent tumours, like lung cancer, weekly meetings are required.
Every individual case is discussed prior to any therapeutic intervention. The board makes proposals and a registry is maintained for recording the board decisions. Doctors are seating as
peers and the decisions are collegial.
- group cervico-maxillo-facial cancerology
- group tumours of the colon and rectum
- group endocrine and thyroid cancerology
It is the mission of each board to produce documented protocols for diagnosis, treatment and follow-up, the so-called gui-
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delines or SOR (standards, options, and recommendations), and
to enforce them in the routine practice.
The principles of operation are based on the collegial structure
in the decisions, the correct stadification of all the patients and
the recording of all the data in a computerized way. The treatments are applied according to the “guidelines“, strictly and
regularly confronted to the data of the literature; the doctors of
the clinic take part in many clinical studies on the level of
various national and international authorities of cancerologic
research (EORTC, GORTEC,…).
CONTACT PERSON
Prof. Pierre SCALLIET
Head of cancer centre
[email protected]
Tel. 32 (0)2 764 47 26
ADDRESS
Avenue Hippocrate, 10
1200 Brussels
WEB SITES
http://www.saintluc.be
Structure of operation :
- investigations necessary to allow a therapeutic decision
- standardized staging (TNM).
- protocols of treatment used in routine with their limits (age,
index of performance, etc). They must be based on the evidence
(french SOR, NCI, START...).
- research protocols with their eligibility criteria.
- recommendations in terms of monitoring (frequency, standard
examinations, patient contact or MT, etc.), including the decentralized monitoring.
- a multidisciplinary decision-making for each patient, either before or after surgical operation according to the anatomical site.
- therapeutic discussion of the attitude at the time of new
events in the oncological history of a patient.
- regular update of the protocols (staging and treatment).
- discussion of research protocols and assessment.
http://www.saintluc.be/hospitalisation/
dpts-serv/centre_cancer/index.html
http://www.saintluc.be/english/consultation/
specialite_eng.php
Partnership
EORTC
GELA (groupe d’études des lymphomes de l’adulte)
GORTEC (Groupe d'oncologie et radiothérapie des cancers
tête et cou)
SIOP (Société internationale d'oncologie pédiatrique)
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UCL
J 2
The Brussels Branch of the Ludwig Institute for Cancer
Research – LICR
Mission
The purpose of the Ludwig Institute for Cancer Research is to
conduct long-range research programmes directed to the ultimate goal of eradicating cancer.
The Brussels branch is active in the field of cancer immunology
and cancer genetics. Main orientations of the branch are the
study of tumor rejection antigens and that of cytokines.
Activities
Cancer is a major concern in human health. The prospects for
bringing cancer under control require linked innovative basic
and clinical research. In this view, Daniel K. Ludwig created in
1974 the Ludwig Institute for Cancer Research, an international
organization bringing together scientists and clinicians from
around the world. Ludwig investigators are active in many areas
of science, involving genetics, bioinformatics, immunology,
virology, cell biology and signal transduction.
Faithful to the organizing principles laid down by Mr Ludwig, the
Institute conducts its research through ten Branches, located in
seven countries. The Branch structure allows the Institute to interact with a number of different research and clinical environments.
Each Branch is focused on a research program defined by the
Branch Director in relation with the overall objectives of the
Institute. The Branches are established in association with
University Hospitals, to stimulate close collaborations between
research laboratories and the clinic. By organizing and controlling
its own clinical trials programs, the Institute has indeed created a
continuum that integrates laboratory and clinical research.
Branch staffs vary in size from 30 to over 70, and internationally
the Institute employs some 600 scientists, clinicians and support
personnel. The quality of the research is monitored on an
ongoing basis by the Institute’s Scientific Committee and by an
external peer review process.
The biological properties of any given cancer cell constantly
change, allowing tumors to spread and become more aggressive.
To overcome these obstacles, the Ludwig Institute has developed a broad-based discovery program that seeks to understand
the full complexity of cancer. Research is organized according to
the four major programmatic themes that define the Institute :
genetics, cell biology, cell signalling and immunology.
Research fields
Tumor immunology and antigen processing group :
www.licr.ucl.ac.be/tiap/tiap.html
Genes expressed in cancer and germline cells group :
www.licr.ucl.ac.be/gecgc/gecgc.html
Identification of human tumor antigens group :
www.licr.ucl.ac.be/ihta/ihta.html
Analysis of T cell responses of vaccinated cancer patients :
www.licr.ucl.ac.be/tcr/tcr.html
Therapeutic vaccination group :
www.licr.ucl.ac.be/tvac/tvac.html
Cytokines in immunity and inflammation group :
www.licr.ucl.ac.be/jcr/index.html
Signal transduction group : www.licr.ucl.ac.be/stg/stg.html
Partnership with UCL
In 1978 the Ludwig Institute for Cancer Research decided to
base its Belgian branch within the walls of UCL, at the Christian
de Duve Institute of Cellular Pathology (ICP). A happy collaboration between the two Institutions has been pursued since
that time. Even though the two Institutes are completely independent, the collaborations between the scientists of ICP and
the Ludwig Institute is extremely close and the sharing of
resources is considerable.
The Brussels Branch, under the leadership of Thierry Boon, specializes in cancer immunology and cancer genetics. The notion
that the immune system might be enlisted to rid the body of cancer draws on past work at the Branch which revealed that most
human tumors bear antigens that can be recognized by cytotoxic
T lymphocytes (CTLs). Some of these antigens are highly tumorspecific, others are expressed on certain normal cells. A number
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of antigens have been found on many different types of tumors,
suggesting that a therapeutic strategy targeting such antigens
could be used to treat a wide range of cancers. The Branch continues the search for tumor antigens, and evaluates their therapeutic potential in vaccine trials of cancer patients.
The Brussels Branch is also involved in research on the immunological functions of several cytokines, particularly IL-9 and IL-22,
which have been discovered at the branch. Signal transduction
by certain cytokine receptors is also under intense study.
STAFF
Total : 85
CONTACT PERSONS :
Prof. Thierry BOON
Director
[email protected]
Tel. 32 (0)2 764 75 80
Dario FLOREAN
Administrator
[email protected]
Tel. 32 (0)2 764 73 34
ADDRESS
Avenue Hippocrate, 74 (building 7459)
1200 Brussels
WEB SITES
http://www.licr.ucl.ac.be/
http://www.licr.ucl.ac.be/tiap/tiap.html
http://www.licr.ucl.ac.be/gecgc/gecgc.html
http://www.licr.ucl.ac.be/ihta/ihta.html
http://www.licr.ucl.ac.be/tcr/tcr.html
http://www.licr.ucl.ac.be/tvac/tvac.html
http://www.licr.ucl.ac.be/jcr/index.html
http://www.licr.ucl.ac.be/stg/stg.html
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J 3
European Society for Therapeutic Radiology and
Oncology – ESTRO
Mission
The European Society for Therapeutic Radiology and Oncology,
ESTRO, was founded in Milano in September 1980 as a Society
of individual members working in the field of radiotherapy and
oncology.
Its principal objectives are to :
Foster radiation oncology in all its aspects
Develop benchmarks, tools and methodologies for assuring
the quality of radiation oncology in Europe and stimulate their
implementation in clinical practice
Improve the standards of cancer treatment by enscribing radiation
oncology as a clinical specialty in the multidisciplinary approach
to cancer treatment
Promote international exchange of scientific information on
radiotherapy & oncology and related fields of science such as
radiophysics and radiobiology and stimulate research
Develop guidelines for education and best practice in radiation oncology and associated professions
Establish relationships and co-operation with international,
regional and national societies and bodies in the field of radiation
oncology.
ESTRO scientific meetings
Each year, ESTRO organises several scientific meetings, reviewing advances in radiotherapy and oncology and encouraging
a multidisciplinary approach to the treatment of cancer.
ESTRO education program
The society’s continuously evolving and expanding offer of
course modules is designed to assist national radiation oncology, medical physics and radiation technologists’ societies in the
provision of adequate teaching for the topics described as
mandatory in the European curricula developed by it. Gradually
also the offer in the field of continued professional development is being built up and broadened.
The ESTRO teaching courses play an important role in the
growing cohesiveness of the European radiation oncology community. By adding a European dimension to the education of
young professionals, mobility within Europe is both encouraged
and supported. The ESTRO Board also recognised the importance of exchange and transfer of expertise by committing
resources to the extremely successful Technology Transfer Grant
Programme for short visits to other departments which, in previous years, was funded by the European Commission
Partnership with UCL
Activities
ESTRO imbedded in its early years in the UZ KULeuven hospital environment, moved in 1997 to the UCL site to join other
cancer societies such as EORTC and FECS already established
there.
ESTRO’s core activities are articulated in its mission statement.
Besides activities for the exchange of scientific information and for
the education and training of radiotherapy professionals, as evidenced below, ESTRO has generated with support from various EU
programmes, a broad range of initiatives for the development of
guidelines and infrastructures for the surveillance of the quality in
RT, for drafting best practice guidelines and encouraging research
for the optimisation of radiation oncology.
Besides its geographical proximity to the UCL Faculty of
Medicine campus as a tenant in an UCL-owned building, ESTRO
became closely associated with its ”landlord” through the active involvement of department heads and other professionals of
the UCL radiation oncology department in ESTRO structures
and activities.
UCL experts have served or still function as members of ESTRO
scientific, website and education committees, are active as
members of the society’s international teaching faculty, coordinators or co-partners in ESTRO projects, co-editor of its journal
and other publications. Finally they served in the ESTRO Board
as secretary and executive administrator.
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STAFF
International Board : 15
Staff onsite : 12
CONTACT PERSON
Michel TAILLET
Executive Director
[email protected]
[email protected]
Tel. 32 (0)2 775 93 40
ADDRESS
ESTRO
Av. E. Mounierlaan 83
B-1200 Brussels
WEB SITE
http://www.estro.be
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
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J 4
Federation of European Cancer Societies – FECS
Mission
Promote and co-ordinate collaboration between European
societies active in the different fields of cancer research, prevention and treatment, with the ultimate goal of providing the
best possible treatment and care for all European cancer
patients.
Activities in the field of the EU Public health programmes to
raise awareness among public health authorities about disparities and unequal access to quality care across European regions
and to suggest ways to build on existing European strengths in
the field of oncology for improving research synergies and
public health strategies (implementation of medically significant
progress through an open but strictly co-ordinated network of
experts and centres of excellence across Europe).
Activities
Partnership with UCL
Promotion of continuing medical education (CME) through the
development of various CME activities (conferences, workshops) and acceptance of the FECS accreditation system of CME
in oncology (ACOE) throughout Europe and the USA for a
mutual recognition of CME credits.
Promotion of the implementation throughout Europe of a multidisciplinary approach in oncology through the establishment
of platforms for scientific exchanges such as ECCO, the
European Cancer Conference, the support of the development
of guidelines on quality cancer care and the setting up of standards for education and training in oncology.
The partnership of FECS with UCL is mainly through the membership of its member societies, some of which are also established onsite like ESTRO, ESSO, EONS or EORTC.
FECS workshops and Standing Committees welcome physicians
from the UCL and organisations established onsite to actively
contribute to the implementation of its mission and objectives.
In addition, their participation in conferences organised by the
Federation, in particular ECCO, the European Cancer
Conference, either as faculty members, speakers or participants
contribute to further develop interactions with UCL.
Support of special projects of European dimension and multidisciplinary nature, in collaboration with other organisations.
Communication with the authorities (European institutions),
health care providers, the public and patients’ organisations
through the provision of reliable information based on research
results and scientific data, the release of position statements on
specific cancer related issues in order to contribute to the
European legislation and policies, the development of proposals
to ensure the provision of sufficient support in Europe for oncology; the enhancement of the dialogue with national and international organisations and authorities.
Contribution to the drafting process of EU research framework
programmes and participation as co-ordinator or as partner in
multidisciplinary projects gathering organisations involved in
oncology.
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STAFF
Total onsite : 13
CONTACT PERSONS
Harry BARTELINK
President
[email protected]
Tel. 32 (0)2 775 29 31
Kathleen VANDENDAEL
Executive Director
[email protected]
Tel. 32 (0)2 775 29 31
Stuart BELL
Communication Manager
[email protected]
Tel. 32 (0)2 775 02 07
Kris VANTONGELEN
Conference and Programme Manager
[email protected]
Tel. 32 (0)2 775 02 06
Françoise VAN HEMELRYCK
Project Manager
[email protected]
Tel. 32 (0)2 775 02 03
ADDRESS
Avenue E. Mounier, 83
1200 Brussels
WEB SITE
http://www.fecs.be
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J 5
European Organisation for Research and Treatment of
Cancer – EORTC
Mission
Establishing new standards of cancer care with high-quality
research
Activities
The European Organisation for Research and Treatment of
Cancer (EORTC) is an international association under Belgian
law, created in 1962 by prominent European cancer specialists.
The aims of the EORTC are to promote, coordinate, analyze and
publish cancer research performed by multi-disciplinary groups of
clinicians and scientists in Europe. These research groups include
surgeons, radiotherapists, chemotherapists, pathologists, immunologists, basic researchers and numerous other specialists as well
as health care professionals. The ultimate goal of the EORTC is to
establish state-of-the-art cancer treatment to improve survival rate,
quality of life and quality of care for all patients with cancer.
The EORTC is primarily devoted to :
-Translational research and clinical studies, to evaluate new
anti-cancer agents including cytotoxic drugs but also innovative
agents as well as modalities such as vaccines, biological response modifiers and other novel treatments resulting from breakthrough discoveries in genomics etc...
- High-quality clinical research, to establish optimal therapeutic
strategies via large multi-center clinical studies in a multidisciplinary approach leading to state-of-the-art treatment and quality of cancer care.
The EORTC headquarters
The headquarters play a coordinating role in all activities and
deal with the scientific, legal and administrative issues related
to the EORTC. The Central Office, the Data Center, the
Education Office and the Cancer Communications Office are all
located in the EORTC headquarters, in Brussels.
Progress in the treatment of cancer requires high quality research
The EORTC is collaborating with the pharmaceutical industry to
decrease the time needed to develop new anti-cancer agents
and to minimize the delay between laboratory discoveries and
therapeutic benefit for patients.
After testing promising agents in the laboratory and on animals,
the next step is testing on humans; these clinical studies will determine whether or not a new anti-cancer agent will be registered,
i.e. approved by health authorities and then marketed.
The EORTC also promotes and funds translational research on
new compounds/concepts discovered in universities and private
research institutions. In this way, it facilitates the passage of
experimental discoveries into state-of-the-art treatment.
Evaluation of the best therapeutic approaches and development
of new standards of cancer care
EORTC clinical groups, are dealing with a specific type of cancer
(breast cancer, lung cancer, gastrointestinal cancer, genito-urinary
tract cancer, leukemia, soft tissue and bone sarcoma and others)
or therapeutic modality (radiation therapy, chronotherapy).
These groups conduct large clinical trials to quickly assess a sufficient
number of patients for the results to be statistically meaningful,
convincing and widely applicable and thereby to have maximum
impact on the quality of cancer care. These results are analyzed in a
scientific, objective and independent manner at the Data Center.
All studies are conducted according to national legal and ethical requirements as well as to the international Guidelines of
Good Clinical Practice.
All EORTC research projects and clinical studies are peer reviewed and have to be approved by the relevant committee including the protocol review committee.
The EORTC Data Center, a unique center of excellence in Europe
Overall, there are more than 6.500 new patients treated each
year according to EORTC protocols.
All research observations made by EORTC members are forwarded to the EORTC Data Center which comprises more than 100
staff members (14 nationalities) including medical doctors, statisticians, quality of life specialists, health economists, lawyers,
other scientific and administrative staff, computer specialists, as
well as research fellows and health care professionals.
The Data Center’s methodology (working procedures and
Standard Operating Procedures) to evaluate new anti-cancer
agents and to conduct clinical studies was filed at the Food and
Drug Administration in 1998. This greatly facilitates the submission of EORTC clinical data for drug registration in the USA.
The Data Center computerized clinical trials management system
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(VISTA) interfaces with the EORTC website. The central registration
and randomisation server (ORTA) allows clinicians to enroll their
patients into EORTC clinical studies 24 hours a day. E-forms is a
remote data entry system developed by the EORTC.
A permanent Independent Data Monitoring Committee reviews
the status of clinical trials and makes recommendations on safety
and efficacy leading to trial’s continuation, modification and/or discontinuation.
Quality control procedures are conducted by the Quality
Assurance Unit in collaboration with the Quality Assurance
Committee. The overall functioning of the groups is conducted
by the Scientific Audit Committee.
The activities of the EORTC Data Center are evaluated regularly by a committee of experts from the National Cancer Institute
(NCI) of the USA. These assessments have always been very
positive and the financial support allocated to the EORTC Data
Center by the NCI has been continuous since 1974.
Other sources of funding for the Data Center are the EORTC
Foundation, the Fondation Cancer, corporate sponsorship, private
donations and The National Lottery of Belgium. In addition, support is provided by the pharmaceutical industry (for clinical studies
on new anti-cancer agents performed in cooperation with the
EORTC) and occasionally by the European Commission (for specific research projects).
The EORTC has initiated an European tumour bank project to
improve and harmonise the histological review and the use of
telepathology, which will also facilitate translational research in
the context of EORTC trials, by providing rapid access to
tumour tissues and to clinical databases.
Publication of the results of EORTC research
Every year, the EORTC has hundreds of scientific articles published in prestigious international journals and over 250 scientific
communications are presented at international scientific meetings.
This wide dissemination of EORTC studies plays a crucial role in
assuring optimal treatment of all patients including for those
treated outside research oriented institutions.
Partnership with UCL
In 1972, the National Cancer Institute established its liaison office
adjacent to the EORTC headquarters on the UCL campus, in
Brussels.
Scientific collaborations with St Luc Hospital and Ludwig
Institute.
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CONTACT PERSON
Françoise MEUNIER
Director General
[email protected]
Tel. 32 (0)2 774 16 30
ADDRESS
“Strength through unity”
The EORTC is a unique research network which coordinates the
research of about 2000 European clinicians and scientists and
works in more than 300 university hospitals or affiliated institutions located in 32 countries.
There is a true need to promote participation of all partners in
clinical trials in Europe and worldwide. Therefore the EORTC is
also actively involved in intergroups studies. The Intergroup office deals with all logistic, legal and methodological issues to
enable inter-group collaboration.
Avenue Emmanuel Mounier 83, bte 11
1200 Brussels (Belgium)
WEBSITE
http://www.eortc.be
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
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UCL
J 6
European Society of Surgical Oncology – ESSO
Mission
STAFF
The mission of the European Society of Surgical Oncology,
founded in 1981, is to advance the art, science and practice of
surgery for the treatment of cancer.
Over 1000 members
Board composition : see web site
CONTACT PERSON
PILKIEWICZ Fabienne
Administrator
[email protected]
Tel. 32 (0)2 537 31 06
Activities
By arranging scientific conferences, professional exchanges and
seminars, ESSO endeavours to ensure that the highest possible
standard of surgical treatment is available to cancer patients
throughout Europe. It aims at fostering multi-disciplinary collaboration in the clinical management of cancer patients.
ESSO is increasingly involved in the training of surgeons concerned by cancer care throughout Europe and in promoting the
development of guidelines of good practice in cancer surgery.
ADDRESS
Avenue Emmanuel Mounier, 83
B 1200 Brussels
WEB SITE
http://www.esso-surgeonline.be
The Society also seeks to promote knowledge and education
about cancer care and to facilitate basic and clinical research in
oncology.
ESSO publishes the European Journal of Surgical Oncology
ten times a year and grants fellowships to facilitate international exchanges of surgeons specialising in oncology.
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J 7
International Life Sciences Institute – ILSI Europe
Mission
Partnership with UCL
To improve the well-being of the general public through the
pursuit of balanced science.
Scientific experts (including UCL staff) provide their expertise
to our working groups on an ad hoc basis.
Date of implantation on the UCL site : 1987.
ILSI Europe aisbl, European Branch of the International Life
Sciences Institute, is a non–profit, worldwide foundation that
promotes collaboration among industry, academia, governmental institutions and consumer groups and provides a neutral
forum for members of the scientific community to discuss and
resolve issues of common interest.
STAFF
Total onsite : 20
CONTACT PERSON
Activities
Most of our activities are in nutrition and food science, some
relate to oncology. One of the Institute´s Task Forces addresses
the risk assessment of genotoxic carcinogens in foods.
Background is that food may often be unavoidably contaminated with low levels of genotoxic carcinogens.
A theme group in the EC-sponsored PASSCLAIM project
(Process for the Assessment of Scientific Support for Claims on
Foods) also addresses diet-related cancer. Aims of this activity
are: to collate potentials types of health claims in this area, to
develop a list of criteria to justify these claims, and to assess the
suitability of available markers.
Nico van Belzen
Executive Director
[email protected]
Tel. 32 (0)2 771 00 14
ADDRESS
Avenue Mounier 83, 3rd Floor
1200 Brussels
WEB SITE
http://europe.ilsi.org
Acrylamide is a chemical that can be produced in starch-rich
foods that are prepared at high temperatures, such as crisps
and French fries. In animal studies acrylamide was shown to be
carcinogenic. ILSI Europe´s Acrylamide Task Force develops a
framework for the assessment of the risk for men of acrylamide in food.
Natural toxins addressed in one of the Task Forces include
potentially carcinogenic ones. Likewise, potentially carcinogenic
chemicals are among those targeted in the Task Force on Risk
Assessment of Chemicals and the FOSIE (Food Safety in Europe)
EC project.
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J 8
European Oncology Nursing Society – EONS
Mission
The mission of the European Oncology Nursing Society (EONS)
is to add value to the work of its individual members and societies in delivering care to patients with cancer. It aims to assist in
the promotion of developing healthy communities through
influencing, research and education.
Activities
EONS has developed a strategic plan which aims to establish a
solid foundation for the future serving to set direction and priorities for the organisation.
The goals set out in this strategy are related to :
Education
EONS will develop and implement, in collaboration with members,
post basic education and continuing education designed to improve knowledge and competence in agreed areas of cancer nursing.
In order to achieve this, EONS will act as a platform for multidisciplinary exchanges at both scientific and educational level; it
organises and develops educational events and will pursue the
work on accreditation.
EONS will also be active in the support and implementation of
guidelines, recommendations and in the development of the
framework of oncology nursing training programs.
Research
EONS will collaborate with member societies and key stakeholders to raise the profile of oncology nursing research in Europe.
It will have a facilitative role helping others to initiate research
through guidance with funding issues, mentoring, publication
and dissemination of results.
Influencing the political agenda
EONS will assist and support members to lobby for recognised
standards of oncology training / education, through recognition
of oncology nursing as a speciality within each membership
country.
EONS will provide current information to (inter)national professional representatives to raise the knowledge and awareness of
the contribution of cancer nurses in Europe.
Partnership with UCL
Partnership through the membership with FECS (Federation
of European Cancer Societies).
Communication
EONS, as the recognised representative of European oncology
nurses at the Federation of European Cancer Societies (FECS),
furthers and facilitates communication between EONS and its
membership, as well as the communication between the different member societies.
EONS strives to provide a unified voice for Member Societies, to
increase the visibility of Member Societies and support their
activities, to increase multidisciplinary exchanges at both clinical, scientific and educational level.
This through the EONS Newsletter and the scientific journal,
The European Journal of Oncology and our new website providing more information about EONS and its activities as well as
new opportunities of communication.
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STAFF
Onsite : 2
CONTACT PERSONS
Jan FOUBERT
President
[email protected]
Tel. 32 (0)476 39 61 48
Rudi BRIKÉ
Secretariat
Tel. 32 (0)2 779 99 23
ADDRESS
Avenue Mounier 83/8
B 1200 Brussels
WEB SITE
http://www.cancereurope.org/eons
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J 9
The U.S. National Cancer Institute Liaison Office – NCI L.O.
Mission
The US National Cancer Institute is the US Federal
Government’s principal agency for cancer research and training.
It coordinates the National Cancer Program, which conducts
and supports research, training, health information dissemination and other programs with respect to the cause, diagnosis,
prevention, and treatment of cancer.
The NCI Liaison Office was created in 1972 and was initially part
of NCI’s Division of Cancer Treatment & Diagnosis. It is now an
integral part of the Office of International Affairs. It facilitates
the interchange of information, ideas, experimental drugs, scientific expertise and scientists, and works in close collaboration
with the EORTC, the Cancer Research Campaign (CRUK), as
well as with other European cancer research institutes and
pharmaceutical/chemical industries, in areas of mutual interest
in preclinical and clinical cancer research. Recently, the collaboration has been extended to closer interactions with the
International Network for Cancer Research & Treatment, INCTR,
a unique organization dedicated to helping patients in developing countries, which is also located in Brussels and partially
supported by the NCI’s Office of International Affairs.
The NCI Liaison Office is the European hub for NCI’s TELESYNERGY® Medical Consultation WorkStation, which was
installed in March 2004. The Telesynergy Workstation allows
numerous research collaborators at greatly separated geographic sites to interact as if they were in the same room, viewing the same medical images. By integrating powerful telecommuniations technology into health care research and delivery,
telemedicine enables clinical researchers to simultaneously
communicate and view and manipulate data necessary for collaborations, including patient diagnosis and care, such as x-ray
films and pathology samples.
It acts as a link between NCI headquarters in Bethesda (USA)
and EORTC, CRUK, SENDO and other European cancer research
organizations and Institutes (i.e. the Mario Negri Institute in
Italy, the Max-Delbrück Zentrum in Germany) as well as the
European pharmaceutical/chemical industries.
For more than 25 years the Office has assisted with the international exchange of experimental drugs for preclinical and
clinical evaluation. A web-based submission process for new
potential anti-cancer compounds to be tested in NCI’s in-vitro
screen has been made available via the NCI Developmental
Therapeutics Program (DTP) website (http://dtp.nci.nih.gov),
and the NCI L.O. assists European suppliers with inquiries of all
kinds related to the submission and selection of their compounds.
The Office collects, submits and updates European cancer
research protocols for the International Cancer Information
Center (ICIC), NCI, for inclusion in NCI's clinical database
PDQ/CancerNet. The office actively seeks new European groups
with an interest to submit their research protocols to
PDQ/CancerNet, and assists them with the fullfilment of
requirements for exemption from further protocol review by the
NCI PDQ Editorial Board.
It coordinates the additional review of EORTC PhIII protocol outlines by selected NCI specialists.
Through the NCI Liaison Office, the NCI is represented on various European committees involved in new drug development,
as well as on the EORTC Board and Council and the CRUK PhI/II
clinical trials committee. It participates in European working
groups that disseminate cancer research and drug development
information throughout Europe, and is also an observer on the
European Drug Development Network (EDDN).
The office assists with the organization of joint NCI-European
meetings and symposia, and it coordinates the use of the
recently installed TELESYNERGY® MEDICAL WORKSTATION
Activities
The Office provides a European contact point for NCI and the
European cancer research community, and assists NCI staff in
matters related to European collaborations and cancer research
programs.
TELESYNERGY® MEDICAL WORKSTATION
Researchers of the National Cancer Institute and the Center for
Information Technology of the U.S. National Institutes of Health
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developed TELESYNERGY®, a telemedicine system with broadcast-quality multi-site teleconferencing capabilities that is also
capable of transmitting most types of diagnostic-quality medical images. By making the knowledge and experience of
oncology experts accessible regardless of where in the world
those experts are, TELESYNERGY® has the potential to dramatically accelerate cancer research and improve cancer care by
facilitating unique collaborations and connections.
STAFF
Note : The TELESYNERGY® Workstation is available to outside
collaborators for a very low cost. For further information please
feel free to contact the NCI Liaison Office.
ADDRESS
Onsite : 3
CONTACT PERSON
Susanne RADTKE
Programs Manager
[email protected]
[email protected]
Tel. 32 (0)2 772 22 17
Av. E. Mounier 83
B-1200 Brussels
WEB SITES
http://www.cancer.gov
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
AT
UCL
Key Words Index
academic studies
E1
breast cancer
accelerator technology
H2
calcium
B11, I3
F7
acute leukemia
C4
cancer therapy
H2
air pollutants
A1
cancer treatment
F1
alexithymia
I3
cancer vaccines
allogenic graft
E3
carbon ion beams
H2
allografts
G2
cDNA subtraction
B4
AML
E2
cell biology
B1
AMP-activated protein kinase
B8
cellular biology
B8
G2
cerebral tumor
F4
CGH (comparative genomic hybridization)
C1
anatomopathology
angiogenesis
animal cell culture
anthracyclines
D2, F3
B9
B10
B5, B6
chemoprevention
chemotherapy
A3
D2, E1, F3, F6
antigen processing
B5
clinial hadron beams
H1
antigenic peptide
B4
clinical biology
C3
antioxidant enzyme
B9
clinical chemistry
C3
B10, F7
clinical medicine
E2, C3, C4, E3
apoptosis
applied psychology
I1
clinical psychology
I1, I2
applied statistics
A4
clinical trials, drug evaluation
autoimmunity
C5
communication theory
autologous cell therapy
G2
confocal microscopy
B1
bacteriology
G2
contrast agents
D3
beam
H2
coping styles
biochemistry
biocompatibility
biographical approach
B5, B6, B8
D2
A4, E1, F5
I1
I3
cortical development
B2
cryopreservation
G1
B9
I2
crystallization
biological dosimetry
H1
cytogenetics
biomarkers
A1
cytology
B8, F6
biomaterials
D2
cytolytic T lymphocyte
B4, F1
biomechanic
G2
cytoskeleton
B8
biomedical and agricultural sciences
B7
delayed-union
G2
biomedical engineering
D2
depression
diagnosis
B3
I3
biophysics
D2, B10
biosensors
D2
differentiation
C3, C4, F6
B8
blood flow
F3
diffuse lymphoma
E2
bone induction
G2
diffusion imaging
D3
bone remodeling
G2
diffusion tensor imaging processing
D1
brain tumor
C1
dioxins
A1
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DNA
DNA (micro)arrays
C6
C1, C6
human sciences
hypoxia
I1
F3, H3
DVH
H2
IDO inhibitors
B6
electron microscopy
B1
IFM
E3
emotion (cognition stress and trauma)
I1
image processing
D3
endocytosis
B1
imaging, radiology, tomography
environmental medicine
B7
Imatinib
E2
ependymoma
C1
immune escape
B6
epidemiology
A4, H2
immunology
D2, D3
B5, B6, F1, F5
epitope
B4
immunophenotype
C4
EPR
D2
immunosuppression
A2
Epstein Barr Virus EBV
A2
immunotherapy
fluorescence
F7
IMRT
H4
follicles
G1
inducible melanoma model
B6
food contaminants
A1
infection
G2
fractionation
B1
information and communication
I1
fracture
G2
internal medicine
F6
free radicals
D2
interpersonal communication
I1
functional imaging
D2
intratumoral infusion
F4
gastroenterology, liver
A3
ion beams
H2
gene expression
C4
late tissue reactions
H2
gene therapy
F3
leukemia
C2
growth factors
F7
life-cell imaging
B1
B4, B5, B6, F1, F3, F6
gynecology
A5, F8
limb salvage
G2
head and neck cancer
H3, H4
liver tumors
A3, D3
health- and medical statistics
health psychology
heavy metals
hematology
A4
I1, I2, I3
A1
B3, C2, C4, E2, E3
LOH (loss of heterozygosity)
lung cancer
B11
lysosomes
B10
D2
magnetic resonance imaging
hepatocellular carcinoma
D3
meaning
high LET radiation
H2
medical genetics
high LET radiobiology
H2
medical psychology
histology
F6
medicine human pathology
B7, F4
F6
lymphoid malignancy
hemodynamics
histopathology
C1
membrane
D3
I2
A5
F8, I1, I2
B7
B1, B10
Hodgkin
E3
metabolism
H3
hovon
E2
microarray
B4
hox
B11
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UNIVERSITÉ CATHOLIQUE DE LOUVAIN - C A N C E R O L O G Y
microdosimetry
H2
molecular and cellular biology
molecular and cellular pharmacology
molecular biology
molecular genetics
Monte Carlo calculations
UCL
peroxidase activity
B9
B10
PET
H3
B10
pharmaceutical chemistry
A5, B1, B3, B7, C2, C4, F6
molecular diagnostic
AT
C6
B7, C1
H4
B7
pharmaceutical sciences
B10, F2
pharmacognosy
F2
pharmacology
D2
pharmacotherapy
A4
motility
B1, B8
phase I/II
E2
MRI
D2, H3
post transplant lymphoproliferative diseases
A2
B7
multidisciplinary approach
F8
prevention medicine
multi-modal registration
D1
professional stress
myeloma
E3
prognosis
myosin light chain kinase
B8
proliferation
nephrology-urology
B7
pronostic factor of molecular markers
neurological diseases
C5
prostate cancer
neurology
F4
proteasome
B5
neuronal migration
B2
protein purification
B9
neuropathology
F4
proto(oncogenes)
B1
neuroradiology
F4
psychology
neurosurgery
F4
psychosomatic
nitric oxide
D2, F3
I1
C4
B8, H3
F6
C6, F7
I1
I1, I2
pulmonology
F6
NMR
D2
radiation
H1
occupational medicine, preventive medicine
A4
radiation therapy
H2
ocular melanoma
C1
radiobiological calibration
H1
oligodendroglioma
C1
radiobiology
H2
onconeural antigens
C5
radiosensitivity
organic chemistry
B7
radiotherapy
orthopaedic
G2
randomization
E2
ovary
G1
RBE
H2
oxygen
D2
realtime PCR
C2
palliative care
paraneoplastic disorders
particular pathology
pathology
D2
D2, E1, F3, H3
recombinant chimeric protein TP38
F4
C5
recombinant protein
B9
F8
recurrent multiforme glioblastoma
F4
reelin
B2
H1
I1
A5, B7
PCBs
A1
Relative Biological Effectiveness (RBE)
pediatric transplantation
A2
research methods in psychology
perfusion imaging
D3
resistance
I1
B10
risk assessment
A1
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RNA
C6
scanning beam
H2
separation techniques
F2
simulation
H2
slice culture
B2
smal cell lung carcinoma
C5
social cognition
I1
socio-economics
H2
spectroscopy
D2
spin trapping
D2
statistics
E1
stem cell transplantation
E2
stereotaxy
F4
STI571
E2
story of life
I2
stress fibers
B8
structural chemistry
F2
surgery
F4, G2
surgical medicine
F4, F6
tracers
transcription factors
H3
B11
transfection vectors
B9
translocations
C2
transplantation
G2
treatment
F6
treatment planning
tridimensional structure
tumor
tumor antigens
tumor cells
H2, H4
B9
B4, D2
B5, B6, F1, F5
B10
tumor marker
C6
tumor vasculature
F3
vaccination
F5
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