HISTORY
The National Children's Medical Research
Center (NCMRC) was established in October 1984 as an adjunct medical research
institute affiliated with National Children's Hospital. The National Children's
Hospital is a sole medical care center for the children in this country under
the auspices of the Ministry of Health and Welfare.
At its inception, four Departments and
eight laboratories were founded, i.e., Department of Pathology and
Pathophysiology, Department of Endocrinology and Metabolism, Department of
Congenital Abnormalities Research, and Department of Pediatric Ecology. At
the next year, in October 1985, two Departments and one Laboratory were
established in the Institute. They were Department of Immunology and Allergy,
Department of Infectious Disease, and Multidisciplinary Laboratories.
Furthermore, Department of Experimental
Surgery and Bioengineering in October 1986, and Department of Pediatric
Pharmacology in October 1987 were established. Thus, till to now the Institute
bears 8 departments and 16 laboratories.
In March 1996, Genox Research Institute
focusing on development of new medicine targeting allergic disease related novel
gene, was established as an annex to NCMRC.
INTRODUCTION
The primary mission of NCMRC is to
conduct and coordinate research projects in basic and applied medical sciences
aimed at the understanding of the causes of children's diseases, and also
developing new and better means of prophylaxis, diagnosis and treatments. The
affiliation with National Children's Hospital facilitates clinically oriented
research projects, as well as those in basic medical sciences, thereby providing
ideal research environments. The research activities of 32 official faculty
members and their associates encompass a wide range of molecular biology in
basic and clinical medical sciences, biomedical engineering, and psychology
reflecting recent development in technology and also the present and future
needs for the advanced care of sick children. In
the past much efforts have been devote to reduce an annual death rate of newborn
children, and hence Japan is now considered to be one of the most advanced
countries in the world in terms of the least rate of newborn child death.
Nevertheless, a cause death of the newborn children with congenital
abnormalities ranked as one of the highest and showed nearly 35 % of
the death. Therefore, based on the developmental aspects of the disease, more
synthetic research and clinical cares are required. Thus, we are focusing on an
overall goal to solve the various aspects of child development and its
abnormalities. Our research fields thus include molecular and cellular biology,
developmental biology, immunology, pharmacology, as well as social and medical
sciences.
Current acting members who engage in each
research project are 32, and the research projects of the center are funded by
the Department of Health and Welfare, Health Sciences Research Grant, and other
governmental funding agencies. It also includes many other foundations as well
as foreign agencies. A current annual budget of research grant is reaching
approximately 1,000,000,000 yen per year
including core grant of Organized Research Combination System with Encouragement
of Center of Excellence (COE) and NCMRC based Contract Research Grant funded by
the Department of Health and Welfare.
Inasmuch as the current social issues of
having fewer children are serious problems for future medical cares, a more
synthetic medical study including children as well as maternity and paternity is
required. As a leading medical center to cover a border and to solve related
medical issues, the center will be reborn as The National Medical Center for
Developmental Health Care with advanced and high technology in the year of 2001
after combined and reorganized by the National Children's Hospital and Ohkura
Hospital. (September 1 1999)
ORGANIZATION
Department of Pathology and Pathophysiology
Laboratory of
Pathology
Laboratory
of Pathophysiology
Department of Endocrinology and
Metabolism
Laboratory of Endocrinology
Laboratory of Metabolic Disorders
Department of Congenital Abnormalities
Research
Laboratory of Genetics and
Cytogenetics
Laboratory of Teratology
Department of Child Ecology
Laboratory of Environmental
Epidemiology
Laboratory of Interactive Development
Department of Allergy Research
Laboratory of
Immunology
Laboratory of
Allergy
Department of Infectious Diseases
Research
Laboratory of Bacteriology
Laboratory of Virology
Department of Experimental Surgery and
Bioengineering
Laboratory of Experimental Surgery
Laboratory of Bioengineering
Department of Pediatric Pharmacology
Laboratory of Toxicology
Division of Research Promotion
Genox Research, Inc.
Department of Pathology and Pathophysiology
Laboratory of Pathology
Main research subject is to analyze the
mechanism of growth and differentiation of blood cells and their malignant
counterparts, namely leukemias. Especially, foci are directed toward the signal
transduction of B-precursor cells and their malignancies, the mechanism of DNA
polyploidization in megakaryocyte maturation, and the effect of granulocyte
colony-stimulating factor in immune system. Analysis of organ dysfunction caused
by verotoxin producing bacteria is also conducted using renal tubular and
endothelial cells.
【Projects】
1. Molecular basis of hematopoiesis and its
dysregulation
1) Function of granulocyte
colony-stimulating factor
2) Megakaryocyte differentiation and
platelet production
3) Tyrosine phosphorylation in early
B-cells
4) Tyrosine phosphorylation in
allergy-related cells
5) Diagnosis of childhood hematopoietic
malignancies
2. Mechanism of organ failure induced by verotoxin (Shigatoxin)
1) Distribution of verotoxin binding
sites in human kidney
2) Mechanism of renal tubular cell
apoptosis
3) Mechanism of Burkitt's lymphoma cell
apoptosis
4) Cytotoxic activity of verotoxin
toward endothelial cells
5) Development of assay for early
detection of renal failure
3. Molecular mechanism of cell cycle regulation
Laboratory of Pathophysiology
Research from this laboratory, directly
related to the treatment of severely ill pediatric patients, has produced
results which are actually being put to use today. The complicated nature of
circulatory and respiratory physiology and pathology is being analyzed by using
the methods of applied physiology, without being limited to the molecular or
cellular microscopic level. The results are being put to use for the development
of artificial ventilators, devices to measure cardiopulmonary function,
artificial organs and even more effective methods of treatment involving
telemedicine.
【Projects】
Pathophysiology and treatment of critically ill
children
1. Optimal use of high frequency oscillatory ventilation
2. Etiology and strategy for lung injury prevention
3. Safe application of nitric oxide inhalation therapy
4. Heparin coated extra corporeal membrane oxygenation (ECMO)
5. Physiological effect of endoscopic surgery in children
6. Hepatorenal effect of volatile inhalational anesthetic agent, sevoflurane
7. Prevention of sudden infant death syndrome
8. Near infrared spectroscopy as an intracranial oxygen and hemodynamic monitor
in children
9. Development of pain management devices in pediatric patients
10 . Health telematics and home care pediatric patients
11. Organ transplantation in children and optimal method of transport
Department of Endocrinology and Metabolism
Main research projects of Endocrine Research
Laboratory are growth, which is the characteristics in children, and sexual
differentiation and maturation. We study on clinical oriented projects, such as
mechanism of growth, diagnosis and treatment of growth hormone deficiency,
establishment of treatment for non-growth hormone deficient short children,
classification and diagnosis of disorders of sex differentiation, treatment of
precocious puberty or hypogonadism. Molecular approach to endocrine and
metabolic disorders such as congenital adrenal hyperplasia, testotoxicosis, GH
deficiency Type 1A, Kallmann syndrome is investigated in cooperation with other
institutes.
【Projects】
1. Growth mechanism
1) Standardization of free IGF-1 and ALS
2) Study on 20K hGH
3) Computer-aided automatic measurement
of bone age
2. Clinical and basic approach to children with growth disturbance
1) Prediction of final height in short
children
2) Bone mineral density in endocrine
diseases
3) DNA analysis of GH or GH receptor
abnormality
4) DNA analysis in short stature
5) High dose GH treatment in children
with intrauterine growth retardation
6) Psychological approach to short
children
7) Treatment in children who enter
puberty at short stature
3. GH deficiency
1) Frequency of GH deficient children
2) Standardization of value measured by
GH kits
3) Biological assay for hGH
4. Clinical and basic study in obese children
1) Growth mechanism in obese children
2) Obese children and leptin
5. Study on sexual differentiation and sexual maturity
1) Treatment in children with central
precocious puberty with super-long acting analog
2) Social sex in children with abnormal
sexual differentiation
3) hCG-hMG treatment in male
hypogonadism
6. Molecular approach to endocrine diseases
1) Study on GHF receptor
2) Cloning of vitamin D hydroxylase and
clinical characteristics of vitamin D resistant richets
Laboratory of Metabolic Disorders
Study on physiological role of biotinidase,
which metabolites biotin is the main project of Metabolic Research Laboratory.
【Projects】
1. Study on physiological roles of biotin and
lipoic acid
1) Study on effects of biotin on
membrane-bound enzymes and/or receptors
2) Study on effects of biotin supply on
diabetes mellitus
3) Development of a method to determine
lipoic acid
2. Study on biotinidase and lipoamidase
1) Isolation and chemical
characterization of human serum biotinidase
2) Estimation of the origin (s) of serum
biotinidase
3) Isolation and chemical
characterization of human urine biotinidase
4) Isolation and chemical
characterization of human breast-milk biotinidase
5) Synthesis of novel substrates for
biotinidase and lipoamidase
6) Study on enzyme kinetics of
biotinidase and lipoamidase
7) Study on roles of glycosylation of
biotinidase and lipoamidase
8) Study on biotinidase and lipoamidase
in atopic dermatitis
9) Study on biotinidase and lipoamidase
in diabetes mellitus
3. Study on molecular basis of endocrine and metabolic diseases
1) Study on molecular basis of
congenital adrenal hypoplasia
2) Study on molecular basis of
congenital unresponsiveness to adrenocorticotropin
3) Study on molecular basis of congenital
adrenal hyperplasia
4) Study on molecular basis of apparent mineral corticoid
excess
5) Study on molecular basis of bone
diseases
6)Study on molecular basis of familial
male-limited gonadotropin independent precocious puberty
7) Study on molecular basis of
McCune-Albright syndrome
8) Study on molecular basis of isolated
growth hormone deficiency
Department of
Congenital Abnormalities Research
Laboratory of Genetics and Cytogenetics, and Laboratory of Teratology
We are studying on the structure and function
of the human genes using molecular and biochemical techniques to elucidate the
molecular mechanism in pathogenesis of hereditary diseases as well as childhood
tumors, and to apply the information to prevention and therapy. Our researches
include determination of the chromosomal location of an unidentified disease
gene (mapping), identification of responsible genes by positional cloning
strategies and/or by candidate gene approaches, and detection of mutations in
patients' genome. Our Department is proud to be a pioneer to identify causative
mutations and genes for three disorders: the amelogenin gene (AMG) for X-linked
amelogenesis imperfecta, trinucleotide repeat expansion for
dentatorubral-pallidoluysian atrophy (DRPLA), and a unique missense mutation of
PAX6 for isolated foveal hypoplasia.
Currently, our efforts to identify the
gene and novel mutations focus on a various types of congenital eye anomaly,
renal insufficiency and infantile jaundice. We are also analyzing molecular
mechanisms for the transcriptional control by WT1 and PAX6, and for apoptosis in
leukemia cells treated with chemotherapeutants as well as in cells expressing
expanded triplet repeats. We are also conducting basic researches with cultured
cells and model animals for gene therapy.
【Projects】
1. Molecular studies on genetic diseases and its
application to clinical medicine.
1) Identification of genes responsible for and involved in genetic diseases and
establishment of the genotype phenotype correlation.
2) DNA diagnosis for genetic diseases and improvement of its techniques.
3) DNA polymorphisms and mapping.
4) Human genome project.
5) Studies on molecular pathogenesis of triplet repeat disorders including
dentatorubral- pallidoluysian atrophy (DRPLA).
2. Molecular studies on oncogenes and tumor suppressor genes involved in
childhood tumors.
1) Identification of genes responsible for and involved in childhood tumors.
2) Functional analyses of the WT1 gene responsible for Wilm's tumor.
3. Molecular studies on expression regulation in mammalian cells.
1) Expression regulation of disease genes.
2) Expression regulation of pituitary hormone genes.
4. Molecular studies on apoptosis and its application to clinical medicine.
1) Apoptosis in the onset and remission of leukemia.
2) Apoptosis induced by extended polyglutamine tract.
5. Gene therapy
1) Vector systems introducing exogenous genes to hepatocytes.
2) Survival of allograft transplanted organs by suppression of the immune
reaction by the use of genes involved in apoptotic process.
3) Suppression of apoptosis in hepatocytes with the Bcl-2 expression.
Laboratory of Environmental Epidemiology
This division is aiming at investigation of
etiology and prevention of childhood disorders. The main tool of research is
epidemiologic approach with the use of computer. The major concern and ongoing
research topics include: multi-center clinical trial of childhood leukemia in
which a new treatment protocol is evaluated and new risk factors are sought for;
investigation of risk factors of childhood malignancy based on the tumor
registry of the National Children's Hospital; quantitative evaluation of family
history in the prevention of atherosclerotic disease from childhood; long-term
follow-up of low-birth-weight babies and evaluation of their physical and
psychological status; growth hormone administration and the relapse of brain
tumors and the development of leukemia; electromagneic waves and childhood
leukemia; genetic epidemiology of prenatal risk factors and of growth and
development of children.
【Projects】
1. Epidemiology of Childhood Diseases
1) Multi-center clinical trial of acute
lymphoblastic leukemia
2) Quantitative assessment of family
history of atherosclerotic diseases
3) Survival and risk factors of
childhood malignancy based on the inpatient registry
4) The role of aldose reductase in
complications of diabetes mellitus
5) Growth hormone administration and recurrence
of brain tumors
2. Genetic epidemiology
1) Genetic epidemiology of prenatal risk
factors, growth and development
3. Health promotion, psychology and other studies for children
1) Prevention of atherosclerotic
diseases from childhood
2) Psychological and social assessment
of short-statued children
3) Establishment of reference values for
pediatric laboratory tests
Laboratory of Interactive Development
Understanding the disorders and the diseases
of the developing children in the light of the host-environmental interaction is
our department's priority. Our special interest is focused on the development of
mucosal immunity of the infants and on the epidemiological study of the various
intractable diseases in a childhood. Using molecular and cell-biological
techniques as well as epidemiological analysis, the following studies are in
progress.
【Projects】
1. Nation-wide survey of childhood cancer and
chronic diseases
1) The Japan children's cancer registry
2) Genetical and epidemiological study
on childhood cancer and chronic diseases
3) The child abuse survey in pediatric clinics
in Japan
4) The registry for congenital diseases
in urban areas
2. Development and disorders of mucosal immunity in children
1) Role of the intestinal microflora in
mucosal immunity and oral tolerance
2) Pathogenic mechanism of the infection
by the enterohemorrhagic Escherichia coli
3) Influence of the proton pomp
inhibitors on mucosal immunity
3. Role of the host-environmental interactions in patients with intractable
diseases
1) Genetic factors that predispose
Japanese population to Kawasaki disease
2) Search for a pathogenic microbe in
patients with Kawasaki disease
4. Child health and development
1) Quality of life for chronically-ill
children
2) Effects of life environment on child
health and development
3) Effects of sociocultural factors on
child development
Department of Allergy Research
The refractory inflammatory diseases in
children are investigated here by various immunological methods. The main
projects include researches on roles of costimulatory molecules in the
carcinogenenesis, GVHD and autoimmune diseases, and how T cell activation by
superantigen influences pathodology of vasculitis. The bile duct diseases such
as biliary atresia and Allagile syndrome, are also studied from the genomic
(Jagged 1 gene) and viral (HCMV) aspects.
【Projects】
1. Analysis of lymphocyte functional molecules in
the immunological tolerance and the development of immune diseases.
1) Functional analysis for costimulatory
molecules involved in the development of immune diseases.
2) Development of a new therapeutic
approch for immuneintervention by manipulating costimulatory molecules.
3) Mechanisms of signal transduction
through T cell costimulatory molecules such as CD28 and CTLA-4.
2. Immunological analysis of the vasculitis induced by superantigen or
verotoxins.
1) Analysis for the mechanism of brain
and renal disturbance.
2) The role of YPM protein deribed from
Yersinia pseudotubercrosis in the development of vasculitis.
3. Analysis for pathogenesis of the bile duct and hepatic diseases.
1) Abnormalities of Jagged 1 gene and
the pathogenesis of the bile duct and hepatic diseases.
2) The correlation of cytomegarovirus
infection and the development of bile duct stresia.
Type I allergy is promoted by binding of IgE
antibodies that are produced by IL-4 stimulation to mast cells. The functional
roles of IL-4 and mast cells are recently found to vary depending on species,
i.e., between mouse and human. We have established the method of generating a
large amount of human mast cells in culture. Therefore, we are mainly
investigating the functional and genetic changes in activated human mast cells
and other inflammatory cells.
【Projects】
1. Studies on cells involved in allergic
inflammation.
1) Development of mast cells,
eosinophils and basophils.
2) Functional analyses of human mast
cells, basophils and eosinophils.
3) Cytokine production by epithelial
cells and fibroblasts.
2. Studies on environmental and food allergens.
1) Studies on environmental allergens.
2) Studies on food allergy.
3. Basic studies on atopic dermatitis.
1) Staphylococcal antigens.
2) Molecular analyses of intractable
atopic dermatitis.
4. Genes expressed in relation to pathological changes in atopic diseases.
Department of Infectious Diseases Research
Pathogenesis and host defense mechanisms of
intractable infectious diseases of children
Aims to clarify the molecular mechanisms
of bacterial infections toward the development of rapid diagnosis, prevention
and specific therapy. Current subjects are as follows: 1) Enterohemorrhagic
Escherichia coli O157:H7 infection including hemolytic uremic syndrome. 2)
Superantigen-mediated diseases such as Yersinia pseudotuberculosis infection
including Kawasaki Disease.
Host Defense Research Laboratory
Aims to clarify the defense mechanisms
against infection. Current subject is the molecular mechanisms of superoxide
anion produced by phagocytes. Chronic granulomatous disease is one of the
targeted illnesses.
【Projects】
1. Studies on the enterohemorrhagic Escherichia
coli O157 infection
1) Molecular mechanisms of the hemolytic
uremic syndrome (HUS)
2) Rapid diagnosis and specific
treatment of the enterohemorrhagic E. coli infec-tion.
(1) Clinical study of the Shiga
toxin-absorbing drug (Synsorb Pk)
(2) Development of a humanized
anti-Shiga toxin antibodies
(3) Development of rapid and simple
detection technique of fecal O157 antigen and Shiga toxins
2. Host-defense mechanisms by phagocytes
1) Studies on the NADPH oxidase system
responsible for anti-infectious activity of phagocytes
2) Structural and functional analysis of
the defective NADPH oxidase in chronic granulomatous disease (CGD)
Laboratory of Bacteriology
We have been working on the non-invasive
prenatal diagnosis using fetus' blood obtained in the peripheral blood of the
pregnant woman.
We have also been working on the
identification of the microbial species and toxic genes.
【Projects】
1. Non-invasive prenatal diagnosis using fetus'
blood in the peripheral blood of pregnant woman
2. Identification of microbial species and toxic genes
Our major interest focuses on molecular
mechanisms of childhood malignancies. In the case of childhood malignancies,
recent evidence suggests genetic background for each patient plays important
roles for disease susceptibility. Thus studies on the genetic control of DNA
repair, cell cycle and apoptosis in response to environmental stresses are being
conducted in our department.
【Projects】
1. Cell cycle and apoptosis regulation in tumor
development and cell differentiation.
1) Elucidation of novel a function of CDK
inhibitor p21 depending on its subcellular localization.
2) Cloning and functional analysis of a
novel molecule Kim-1, which is apparently involved in cell cycle regulation.
2. Molecular mechanisms for cancer development in cancer prone families.
1) Cancer susceptibility and cell cycle
and apoptosis dysregulation in Ataxia telangiectasia.
3. International collaborative work in molecular epidemiology and genetic
back-ground of infantile leukemia.
Department of Experimental Surgery and Bioengineering
For the radical therapy in pediatric patients with severe organ failure, we have been investigating the organ transplantation and the reconstruction of organ tissues in the field of experimental surgery, as well as the biomolecular immunoregulation after grafting and the development of substitute organs in the bioengineering field.
Laboratory of Experimental Surgery
For establishment of organ transplantation as
a radical therapy for congenital and acquired organ failure, following studies
are ongoing in this division: induction of recipient immunosuppression, analysis
of transplantation tolerance and microchimerism, finding of new genes related to
tolerance induction, and reconstruction of hepatocytes for the severe liver
failure.
【Projects】
1. Study for immunoregulation in the organ
transplantation
1) Immunoregulation by inducing
lymphocyte apoptosis and study of its biological mechanisms
2) Preclinical study of a novel
immunosuppressant FTY720 using canine model of kidney transplantation
3) Prevention of graft rejection and
induction of transplantation tolerance by pretransplant donor treatment
3. Fundamental study for the relationship between transplantation tolerance and
microchimerism following organ transplantation
4. Investigation of the genes related to transplantation tolerance
5. Study for reconstruction of the liver in patients with hepatic failure at an
end-stage
Laboratory of Bioengineering
The current aims in this division are to
perform the basic research for induction of immunosuppressive genes into grafted
organs, gene therapy and cell transplantation for metabolic organ disease, and
development of hybrid artificial liver.
【Projects】
1. Immunoreguration after organ transplantation and
radical treatment of metabolic disease by the therapy using gene-introduction
2. Study for developing an artificial hybrid liver
Department of Pediatric
Pharmacology
Laboratory of Toxicology
The Human Genome Project now hurtles toward
completion of the first finished human sequence (now scheduled for 2003). In the
near future, therefore, interest for biology would be predicted to be shifted
from structure of genome to function (Functional Genomics). Hence, we view that
future biological research should be based on the Genomic Information, and our
Department is focusing on studying the molecular mechanism of a variety of
multi-gene disorders and innovating novel therapeutics for them. More
specifically, we are now establishing a novel approach for Drug Discovery based
on the Genome information by using G-protein coupled receptor as a model.
"Dry Biology" (bioinformatics) and "Wet Biology" (molecular
biology and cell biology) would be integrated for the purpose.
【Projects】
1) Study on developmental alteration in
expression and function of G-protein coupled receptors
2) Molecular mechanism for change in
disease states
3) Structure-activity relationship of
drugs that act on G-protein coupled receptors 4)
Signal transduction, subcellular localization, physiological role and drug
action of G-protein coupled receptors
5) Drug discovery by using cloned
G-protein coupled receptors
6) Assessment of physiological role of
G-protein coupled receptors signaling by using gene-target animals
Division of Research Promotion
Research Administrations :
For the purpose of promoting research
activities in the National Children's Medical Research Center (NCMRC), the
Department of Research Promotion is corresponding to the administrations of
common facilities, equipments and research cooperations. In terms of common
facilities and equipments, the NCMRC has the Radioisotope Center, the
Experimental Animal Center, the Gene Engineering Center and common equipments.
These systems are usually under the control of individual committees composed of
NCMRC's stuffs. The promotion of research cooperations among institutes and/or
National Children's Hospital (NCH) is also performed by the Research Planning
Committee and the Joint Research Committee for NCH and NCMRC.
Research Activities:
Following researches are now undergoing.
The study of pharmacological action
mechanisms of a novel immunosuppressant FTY720.
The study of apoptosis inducing agents
and cancer research.
The research of chemical substance safety
tests for new born and fetal animals.
【Projects】
1. Research in control of immunological responses
Study of mechanisms on the bases of apoptotic induction in lymphocytes
2. Research in infantile carcinoma
Study of anti-cancer effect of apoptosis inducing agents
3. Research in developmental toxicities of chemical substances
Establishment of evaluation methods of toxic substances by means of rat
hepatocytes primary cultures
The mission of Genox Research Inc. is to
identify novel therapeutic targets for allergic diseases such as rhinitis,
bronchial asthma and atopic dermatitis in close collaboration with National
Children's Hospital.
We are studying T cells, eosinophils, and
monocytes isolated from peripheral blood of allergy patients. Genes expressed in
those cells are displayed by fluorescent differential display technology.
Comparison of the display patterns of the patient and control samples reveals
the genes preferentially up- or downregulated in patients. The level of
expression of these genes is also examined by quantitative PCR to determine the
relevance of a particular gene to allergy. Using these procedures, several
candidate genes have been identified thus far, and functional analysis of these
genes is now in progress.
Genox is also developing the Database
which integrates data on gene expression and the clinical features of allergy
patients. This database will be helpful in understanding the cross talk between
genes in the pathogenesis of allergy and in identifying new targets for drug
discovery.
【Project】
Project 1 Preparation and banking of research
materials from clinical samples
1) Isolation of peripheral blood
leukocytes from allergy patients and immortaliza-tion of B lymphocytes
2) Preparation of RNA from human
leukocyte samples
3) Preparation of cDNA libraries from
human leukocyte samples
Project 2 Allergic disease related gene
expression analysis
1) Gene expression analysis by
differential display methods
2) Sequencing of the expressed genes
3) cDNA cloning
4) Gene expression analysis by real time
quantitative RT-PCR and DNA microarray
5) Screening of associated genes by
yeast two hybrid systems
6) Analysis of gene function by
immunobiological studies
7) Functional study using in
vitro-differentiated mast cells and T cells
Project 3 Bioinformatics
1) Development of Genox database
managing materials and clinical and experi-mental information
2) Development of data mining systems
for gene expression analysis by linking experimental data and external data with
clinical information