A
report from Leanne Fairley, Prous Science, Barcelona, SpainInternational Projects
China
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The First
Sino-European Workshop on Immunogenetics and Pathogenesis of Gastric Cancer
Xi'an, China 26-28 April 2001
Participants
of the workshop:
Europe
B. Appelmelk (Amsterdam, the Netherlands), H. Bazin and D. Latinne (Brussels,
Belgium), J. Crabtree (Leeds, UK), B. Crusius (Amsterdam, the Netherlands),
A. Lanas (Zaragoza, Spain), N. Muñoz (Lyon, France), D. Pantoflickova
(Lausanne, Switzerland), A.S. Peña (Amsterdam, the Netherlands), S. Shivananda
(Oegstgeest, the Netherlands), P. Sipponen (Espoo, Finland), J. Telford (Sienna,
Italy) and L.J. van Doorn (Delft, the Netherlands).
China
W.Y. Chan (Hong Kong), D. Fan (Xi'an), D. Fang (Chongqing), J. Hu (Xi'an), P.J.
Hu (Guangzhou), Y. Lu (Beijing), X. Ouyang (Chengdu), B. Pan (Xi'an), B.C.Y.
Wong (Hong Kong), K. Wu (Xi'an), S. Xiao (Shanghai), Y. Yuan (Shenyang), J.
Zhang (Guangzhou) and L. Zhang (Beijing).
European-Chinese research collaboration initiated at the First Sino-European Workshop on Immunogenetics and Pathogenesis of Gastric Cancer
A
report from Leanne Fairley, Prous Science, Barcelona, Spain
Top level scientists
from eight European countries and China gathered in the ancient Chinese capital
of Xi'an on April 26-28 to discuss collaboration on a modern approach to gastric
cancer prevention. Participants at the First Sino-European Workshop on Immunogenetics
and Pathogenesis of Gastric Cancer presented their most up-to-date research
results on topics ranging from epidemiology and immune mechanisms to Helicobacter
pylori and vaccine development. Researchers then formed groups with their Chinese
or European counterparts to plan future research endeavors which will benefit
Chinese and European populations alike. After 3 years of organization between
the Institute of Digestive Diseases of the Fourth Medical University in Xi'an,
China and the Laboratory of Gastrointestinal Immunogenetics of the Free University
Medical Center in Amsterdam the first workshop came into being under the joint
sponsorship of the Commission of the European Union, National Natural Science
Foundation of China and the Institute of Digestive Diseases, Xi'an, China. As
gastric cancer is the most prevalent malignant tumor in China, the workshop
was of special significance to the Chinese researchers and to the Chinese population
in general. Leanne Fairley from Prous Science was in Xi'an to cover the proceedings
and reinforce Prous Science's interest in the latest developments in Chinese
research.
During the workshop, presentations on the epidemiology of gastric cancer showed
that this disease is in fact common the world over: it is the second most common
cancer next to lung cancer and about 1 million new cases were diagnosed in 2000.
Three-quarters of the cases of gastric cancer occur in Asia, and approximately
80% of these cases are in China and Japan. Genetic factors and environmental
factors such as diet and H. pylori infection play a role in gastric carcinogenesis.
As a recognized cause of gastric cancer, H. pylori was the subject of various
presentations ranging from immunological studies, molecular analysis of strains
and pathogenesis to vaccine development. Specific areas of discussion included
bacterial-epithelial interactions in H. pylori infection, epidemiology in China,
global distribution of vacA and cagA genotypes, new evidence for host factors,
nonsteroidal antiinflammatory drugs and H. pylori as independent risk factor
for gastric cancer, new diagnostic techniques for H. pylori using serum levels
of pepsinogen I, and autoimmune processes in corpus atrophy.
Vaccine development using a variety of strategies against H. pylori was the
subject of an entire session of talks. Oral immunization with urease with Escherichia
coli heat labile enterotoxin was shown to be safe and immunogenic in humans
as a mucosal adjuvant. Results of a study using attenuated Salmonella typhimurium
as a vehicle for DNA-mediated immunization in mice were also presented. A final
presentation discussed an ongoing trial comparing strain variability in the
vacA and cagA gene sequences and disease expression between H. pylori infection
in Europe and China.
Researchers also discussed the role of IL1 family and tumor necrosis factor gene polymorphisms in gastric pathology and various immune mechanisms involved in gastric cancer such as down-regulation of NFkB, IL1, IL1RA, cyclooxygenase signaling, and identification of MGAg antibodies.
An interactive discussion followed each presentation and ideas and suggestions
were provided. According to specialty, the presenters were then assigned to
groups of four or five to make plans for joint research projects. A number of
international and Chinese observers were present, including representatives
from the European Commission, the World Health Organization and the Chinese
National Center for Biotechnology Development, and offered input on the financial
feasibility of such projects. With this in mind, plans to continue the scientific
and cultural collaboration at a Second Sino-European Workshop on Immunogenetics
and Pathogenesis of Gastric Cancer in Finland are underway.
The proceedings of the First Sino-European Workshop on Immunogenetics and Pathogenesis of Gastric Cancer will be published in Prous Science's Methods and Findings and also on the TTMed channel.
Participants
1. Laboratory of Gastrointestinal Immunogenetics, Medical Faculty Vrije Universiteit, Amsterdam, The Netherlands (Professor A.S. Peña, Head of the Laboratory of Gastrointestinal Immunogenetics of the Free University Amsterdam; Dr. S. Shivananda, Scientific Advisor & Honorary Professor of Medicine, Hubei Medical University Wuhan)
2.
Department of Gastroenterology, Second Affiliated Hospital, Hubei Medical University,
PR of China (Dr. Bing Xia, Department of Gastroenterology, Second Affiliated
Hospital of Hubei Medical University, Wuhan; Prof. Changsheng Deng, Head of
the Department of Gastroenterology, Second Affiliated Hospital of Hubei Medical
University, Wuhan)
Introduction
Inflammatory bowel disease (IBD) is a chronic, debilitating disease of the gut. It is a life-long disease and has no cure. Its etiology is unknown. Genetic as well as environmental factors are known to play an important role in the pathogenesis of this disease. So far, most studies in this field have been done in the laboratories and the populations of America, Europe and Israel. They have made an important contribution to our knowledge about disease causation. But the results remain inconclusive.
Understanding the genetic determinants of disease susceptibility in the Chinese population and a study of the influence of putative environmental factors such as smoking, the diet, and viral infection in the rapidly changing Chinese society may make an important contribution to the advancement of knowledge on the aetiology of this disease. This project provides a unique opportunity to conduct these studies in a population with a different genetic background and a different environment.
Since a disturbed immune response is involved in the development of this disease the Laboratory of Gastrointestinal Immunogenetics of the Vrije Universiteit Amsterdam is focused on immunogenetic studies for further understanding of the pathogenesis of this disease. Our plan is to set up a laboratory of immunogenetics and genetic epidemiology at the Second Affiliated Hospital of the Hubei Medical University in Wuhan that will enable the Chinese counterpart to collaborate with us in Amsterdam.
Aims
1. To perform
immunogenetic studies in Chinese patients with IBD (to investigate cytokine
gene polymorphisms)
2. To investigate
the production of cytokines and the autoantibody peri-nuclear anti-neutrophil
cytoplasmic antibodies (pANCA) in patients with IBD in China
Subjects
- Chinese
patients with ulcerative colitis and Crohn's disease
- Chinese patients
with infectious colitis, intestinal tuberculosis and other intestinal diseases
- Unrelated
healthy controls from the Chinese population from Hubei province
Methods
1.
A study of systemic and mucosal cytokine production in Chinese patients with
IBD and controls will be conducted in order to improve our understanding of
the factors influencing the disturbed immune response in IBD.
2. To
establish whether a genetic background determines this immune response cytokine
gene polymorphisms will be related to the production of these cytokines in case-control
studies of Chinese IBD patients.
3. A
high percentage of pANCA positive patients with ulcerative colitis has been
observed in Western countries. The frequency of pANCA in Chinese patients with
ulcerative colitis and other colitides and healthy controls will be established.
Report of a visit to the Peoples Republic of China
From
left to right :
Prof
General Su Bo, President of the 4th Military
Medical University Xi'an
J.B.A.
Crusius BSci Biol VU Amsterdam
Hon
Prof. S. Shivananda Wuhan and VU Hon Investigator
Dr.
H. van der Erve, DOS, VU
Prof.
Xia Bing Wuhan
From 31-07-1999 until 08-08-1999 a delegation from the Vrije Universiteit Amsterdam (VUA), consisting of Dr. S. Shivananda, Drs. J.B.A. Crusius, and Dr. H.J. van der Erve visited the Fourth Military Medical University (FMMU) in Xi'an also on behalf of Prof. A.S. Peña from the Laboratory of Immunogenetics of the Faculty of Medicine of the VUA.
Aim of the visit was to discuss with the partners of the Institute of Digestive Disease the possibilities for research cooperation in the field of Immunogenetics and Epidemiology of Helicobacter pylori (H. pylori), peptic ulcer & especially in gastric cancer and to investigate the possibility of a wider agreement of interest to both Institutes.
We met the President of the FMMU, Professor Su Bo. Information was exchanged about both universities and we made a tour through the new building of the university. We visited the research labs, teaching rooms, library, and computer instruction halls. The premises and facilities of FMMU were quite impressive. The university is expanding the use of computers in education and is quite interested in receiving a computer assisted learning Programme from the Medical Faculty of the VUA. Van der Erve will send a copy of the existing Programme as attached file by E-mail.
Professor Su Bo is very interested to have an agreement with the VUA in order to be able to start cooperation in more fields that might be interesting for both universities. If cooperation can come off the ground it will mainly play in a broad field of medical oriented topics. Dr. van der Erve promised to discuss in Amsterdam the possibilities for an agreement between both universities.
In a preparatory meeting with Prof. Fan Daiming and Prof. Pan Bo-Rong we discussed what route should be followed to try to formulate a good research proposal and how and where to apply for funding. We concluded that first a workshop should be held and that at the end of that workshop, based on the presentation of the state-of-the art of the topics of interest and the discussions, a research proposal will be formulated. For the workshop the VUA will approach the European Commission for funding.
During a meeting with a larger group of persons, Prof. Pan Bo-Rong, Prof. Fan Daiming, Prof. Bing Xia from Wuhan (who already has an established collaboration with the Laboratory of Immunogenetics of the VUA and is a PhD graduate from the VUA), Prof. Kaichun Wu, Dr. Jie Liu, we discussed the content and the organization of what will be called the First Sino-European Workshop on Immunogenetics and Epidemiology of Helicobacter pylori, Peptic Ulcer & Gastric Cancer. It will be hopefully be held in Xi'an in September 2000.
At the end of the meeting a Letter of Agreement was signed. Further we discussed a draft proposal for the workshop. VUA will prepare a new version of the proposal and will send it to Xi'an for consultation before it will be used for a grant application to the European Commission INCO-DEV Programme.
From left to
right :
Chinese Clinical
Investigator
Hon Prof. S.
Shivananda
Prof. Fan Daiming,
Prof. General
Su Bo
Dr, H. van
Erve
Prof. Bing
Xia
Report
of the visit of Elly Klinkenberg-Knol to San José, Costa Rica
11- 15 February 2001
foto: sidney vervuurt,
avc vu
Introduction
Since many years there is a co-operation between the University of Costa Rica,
San José, and the Vrije Universiteit Medical Center.
The main representatives in Costa Rica are Dr. Rafaela Sierra, epidemiologist
from the "Institute de investigaciones en Salud (INISA)" and Dr. Edgar
Izquierdo, gastroenterologist, University Hospital Calderón Guardia,
San José.
The main representative in the Netherlands is prof. dr. Salvador Peña,
gastroenterologist and head of the immunogenetic laboratory of the Vrije Universiteit
Medical Center.
The main common interest of this international contact is the relation between
Helicobacter pylori infection and gastric carcinoma.
Gastric Cancer
Cancer of the distal stomach is strongly associated with Helicobacter pylori
colonization. This bacterium causes chronic active inflammation of the gastric
mucosa in most of colonized subjects. In a considerable number of them, this
will eventually lead to a loss of gastric glands, and thus the establishment
of atrophic gastritis, which is associated with the development of intestinal
metaplasia and dysplasia. The presence of these consecutive disorders leads
to a 5-90 fold increased risk for cancer of the distal stomach. This sequence
explains the increased risk for gastric cancer in Hp infected subjects, as has
been shown in various cross-sectional and longitudinal studies. Factors that
influence the risks for atrophy and cancer in the presence of infection may
be related to the time that infection occurred and to characteristics of the
bacterial strain and the host.
Distal stomach cancer is the most frequently occurring malignant tumor in Costa
Rica and the mortality rate from this tumor is the highest for any type of cancer
in the world.
Proposal
It would be very challenging to study in Costa Rica the causal factors for gastric
carcinoma because of the high frequency of gastric cancer as well as Hp infection.
There are intracountry, regional differences in the incidence of gastric cancer,
even in this small country (comparable in size with the Netherlands) of 3.2
million inhabitants, although the prevalence of Hp infection does not differ
significantly. Therefore, it is very interesting to study other factors, like
characteristics of the bacterial strains and the host. Particularly genetic
factors and intraindividual differences in immunologic response to the Hp infection
are worthwhile to study. Why will one person develop only an acute gastritis
and the other chronic atrophy and carcinoma?
Available facilities
in Costa Rica
In San Jose, Costa Rica, Rafaela Sierra, has collected serum and gastric biopsies
from 502 Hp positive patients, who were referred for upper GI endoscopy. The
protocol includes:
An epidemiologic questionaire, endoscopy with 2 antrum and 2 corpus biopsies
for pathology and Hp determination, and serology for gastrin and pepsinogen
levels as well as genetic and immunologic study material.
Dutch contribution
Our, Dutch, share would be to perform the genetic and immunological studies
from the Costa Rica material and compare this with material from the Netherlands.
At the Vrije Universiteit Medical Center we have at our disposal gastric biopsies
from 365 reflux patients, treated with omeprazole for up to 11 years. We know
that 40% is Hp positive and also we know the degree of atrophic gastritis in
these patients.
It would be very interesting to study the possible genetic and immunological
factors, leading to atrophy and also look and the differences in the large group
from a "third world"country, like Costa Rica.
Visit Cosa
Rica
I visited Costa Rica for scientific reasons from 11-16 February 2001. In this
period I visited three GI departments of University Teaching Hospitals: the
Hospital Calderón Guardia, the Hospital Mexico and a private hospital:
Hospital Bíblica. Also I visited the private practice of a GI surgeon
originally from Japan and trained in Japan: Dr Wong. In Liberia, a regional
capital in the north of Costa Rica I visited the GI department of the local
regional hospital.
I was impressed with the scientific level of the doctors: within their financial
limitations the standards of investigations and treatment were quite comparable
with our situation.
Particularly the private endoscopic unit of Dr Wong was impressing. In my opinion
this unit would be very suitable for performing studies in GI patients, particularly
due to the outstanding data base capacities.
Next, I visited
Dr Rafaela Sierra at the INISA institute and we discussed the possibilities
for further cooperation between our universities.
Three conferences were scheduled: two in San Jose and one in Liberia. The subjects
of the lectures were: Gastro-oesophageal reflux disease; long-term efficacy
and safety of omeprazole; Hp infection and gastric cancer, and Hp causes accelerated
gastric atrophy in users of PPI's.
From the discussions after the lectures I have learned that reflux disease is
not a common encountered problem in Costa Rica. The main interest was the relation
between Hp and gastric cancer.
Brief conclusion
I would recommend a further cooperation between Costa Rica, particularly the
INISA institute, and the GI department of our university to study the causal
factors for the development of gastric atrophy and gastric cancer, particularly
in the field of genetics and immunology.
Amsterdam, March 2001
Hungary
 |
 |
| Andrea Nemetz |
The Regulation of Key Inflammatory Mediators in Inflammatory Bowel Disease, in collaboration with A. Nemetz MD (photo) of the Semmelweiss University in Budapest (Hungary), and T. Molnár MD PhD of the Szeged University in Budapest.
References :
1. Nemetz
A, Nosti-Escanilla MP, Molnar T, et al. IL1B gene polymorphisms influence
the course and severity of inflammatory bowel disease. Immunogenetics 1999;49(6):527-31.
2. Nemetz
A, Kope A, Molnar T, et al. Significant differences in the interleukin-1beta
and interleukin-1 receptor antagonist gene polymorphisms in a Hungarian population
with inflammatory bowel disease. Scand J Gastroenterol 1999;34(2):175-9.
3. Andrea Nemetz and Amado Salvador Pena, On the genetic contribution of osteoporosis and osteoporotic fractures Letter for Pekka Kannus, Mika Palvanen, Jaakko Kaprio, Jari Parkkari, and Markku Koskenvuo eBMJ, 23 Dec 1999; 319; 1334-1337. Electronic letters 1999 http://www.bmj.com/cgi/eletters/319/7221/1334#EL2
Ágota Kovács MD, PhD is a gastroenterologist of the Péterfy Hospital, in Budapest.
She is Director of the IBD outpatient clinic in Budapest.
She was secretary and founding member (1993) of the Hungarian Crohn Society of Hungary and in 1994 founding member of Hungarian Crohn Colitis Patients Association.
Dr. Kovács studied at the Budapest University and is specialist in Internal Medicine since 1966. She registered in 1988 as specialist in Gastroenterology. In 1961 studied at the Postgraduate School of Med. Dept. of Gastroenterology, specializing in IBD. In 1966 was at the Semmelweis Univ. Med. Clin. of Int. Med. assistant prof. In 1977 Univ. of Lund, Dept. of Tumorimmunology, research : development of of experimental colitis model in rats, six months 1978 obtained her PhD degree with the thesis on "Etiopathogenesis of ulcerative colitis"
Publications
Ulcus Pepticum, in collaboration with the Hospital Universitario de Zaragoza (Spain), Dr. A. Lanas.
Publications 2000-1998
1. Inarrea P, Esteva F, Cornudella R, Lanas A. Omeprazole does not interfere with the antiplatelet effect of low-dose aspirin in man. Scand J Gastroenterol 2000;35(3):242-6.
2. Arroyo MT, Lanas A, Sainz R. Prevention and healing of experimental indomethacin-induced gastric lesions: effects of ebrotidine, omeprazole and ranitidine. Eur J Gastroenterol Hepatol 2000;12(3):313-8.
3. Lanas A, Remacha B, Sainz R, Hirschowitz BI. Study of outcome after targeted intervention for peptic ulcer resistant to acid suppression therapy. Am J Gastroenterol 2000;95(2):513-9.
4. Lanas A. NSAID use and abuse in gastroenterology: refractory peptic ulcers. Acta Gastroenterol Belg 1999;62(4):418-20.
5. Santolaria S, Lanas A, Benito R, Perez-Aisa M, Montoro M, Sainz R. Helicobacter pylori infection is a protective factor for bleeding gastric ulcers but not for bleeding duodenal ulcers in NSAID users. Aliment Pharmacol Ther 1999;13(11):1511-8.
6. Lorente S, Lanas A, Aznar C, Jimenez E, Lozano R. [Recurrent digestive hemorrhage as a complication of an intraduodenal diverticulum]. Gastroenterol Hepatol 1999;22(6):282-5.
7. Lanas A. Non-steroidal anti-inflammatory drugs and gastrointestinal bleeding. Ital J Gastroenterol Hepatol 1999;31(Suppl 1):S37-42.
8. Lanas A, Hirschowitz BI. Toxicity of NSAIDs in the stomach and duodenum. Eur J Gastroenterol Hepatol 1999;11(4):375-81.
9. Jimenez P, Lanas A, Piazuelo E, Esteva F. Effects of extracellular pH on restitution and proliferation of rabbit oesophageal epithelial cells. Aliment Pharmacol Ther 1999;13(4):545-52.
10. Lanas A, Royo Y, Ortego J, Molina M, Sainz R. Experimental esophagitis induced by acid and pepsin in rabbits mimicking human reflux esophagitis. Gastroenterology 1999;116(1):97-107.
11. Sopena F, Lanas A, Sainz R. Esophageal motility and intraesophageal pH patterns in patients with esophagitis and chronic nonsteroidal anti-inflammatory drug use. J Clin Gastroenterol 1998;27(4):316-20.
12. Jimenez P, Lanas A, Piazuelo E, Esteva F. Effect of growth factors and prostaglandin E2 on restitution and proliferation of rabbit esophageal epithelial cells. Dig Dis Sci 1998;43(10):2309-16.
13. Hawkey CJ, Tulassay Z, Szczepanski L, van Rensburg CJ, Filipowicz-Sosnowska A, Lanas A, et al. Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study. Helicobacter Eradication for Lesion Prevention [see comments] [published erratum appears in Lancet 1998 Nov 14;352(9140):1634]. Lancet 1998;352(9133):1016-21.
14. Lanas A, Bajador E, Serrano P, Arroyo M, Fuentes J, Santolaria S. Effects of nitrate and prophylactic aspirin on upper gastrointestinal bleeding: a retrospective case-control study. J Int Med Res 1998;26(3):120-8.
15. Piazuelo E, Lanas A, Jimenez P, Garcia-Gonzalez A, Esteva F. In vitro wound repair by human gastric fibroblasts: implications for ulcer healing. Dig Dis Sci 1998;43(6):1230-40.
16. Hirschowitz BI, Lanas A. Intractable upper gastrointestinal ulceration due to aspirin in patients who have undergone surgery for peptic ulcer. Gastroenterology 1998;114(5):883-92.
17. Lanas Arbeloa A, Serrano Aullo MT. [Gastric lesion caused by NSAID and inflammation due to Helicobacter pylori. Is there potentiation or attenuation?]. Gastroenterol Hepatol 1998;21 Suppl 1:20-4.
18. Lanas
A, Garcia-Gonzalez A, Esteva F, Piazuelo E, Jimenez P, Morandeira JR. Collagen
secretion by human gastric and skin fibroblasts: implications for ulcer healing.
Eur Surg Res 1998;30(1):48-54.
IBD Unit 2003-2005
From Left to right: Carlos Taxonera, Sonia Izquierdo, Julio García Paredes, Professor Manuel Díaz-Rubio, Dulce Maria Cruz, Juan Luis Mendoza and Cristina Alba.
International IBD Unit 2001-2002
Hospital Clínico
Universitario San Carlos (HCSC) , Madrid, Spain
Department
of Digestive Diseases (head: Prof. M Díaz-Rubio)
Dr. J. García-Paredes, Dr M. Cruz-Santamaria, Dr. Juan Luis Mendoza
Inflammatory
Bowel Disease (IBD) VUmc and HCSC started with then collaboration between the
Laboratory of Immunogenetics and
Department of Digestive diseases (HCSC) 1999.
Dr. J.
García Paredes, Dr. G. López-Nava Breviere from the Department of Digestive Diseases,
Hospital
Clínico Universitario San Carlos (head: Prof. M Díaz-Rubio) and
Dr. E. Gómez de la Concha, Department of Immunology HCSC.
Dr. Gontrand López de Nava Breviere and Dr. J. García-Paredes
J. García-Paredes MD, PhD. Associate Professor and Consultant;
E-mail: jgparedes@bitmailer.net
| Mrs. Alicia Aparicio |
| Secretary |
Recent publications: