ImmunoTox Letter
The 23th Annual Meeting of JSIT 2016
June,2016(Japanese Society of Immunotoxicology)

September 5-7,2016

The 5th Japanese Society of(9/5 Lecture open to the public, 9/6-7 Annual Meeting)

Immunotoxicology Award(The 2016 JSIT Award)

Kitakyushu International Conference Center
3-9-30 Asano, Kokurakita-ku, Kitakyushu-shi,

Effects of genetic polymorphisms on

Fukuoka 802-0001

anti-cancer drug-induced myelotoxicity

URL： http://convention-a.jp/en/Jun-ichi Sawada
President:
Pharmaceuticals and Medical Devices Agency
Prof. Yasuo Morimoto,
University of Occupational and Environmental Health,Individual or ethnic differences in drug responsivenessJapan.
are wellknown.

The genetic

polymorphisms

ofInstitute of Industrial Ecological Sciencesdrug-responsive molecules, including metabolic enzymes
Department of Occupational Pneumology
detoxifying

drugs, have been extensively studied.

At theNational Institute of Health Sciences, we had surveyed
Office:genetic

polymorphisms

responsible

for theadverse

reactions induced by several anti-cancer drugs.

In thisUniversity of Occupational and Environmental Health,Japan.
presentation, I would like to talk about the two genes,
Institute of Industrial Ecological SciencesUGT1A1 and CDA for irinotecan and gemcitabine
Department of Occupational Pneumology]toxicities, respectively, and recent trends in this field.
Phone: +81-93-691-7466
Irinotecan is a prodrug generating SN-38, an active
Fax: +81-93-691-4284
anti-cancer metabolite. SN-38 is further metabolized into
Deadline for abstract submission: June 24(Fri), 2016an inactive metabolite, SN38G, glucuronidated SN-38, by
The theme for this Meeting:
the UDP-glucuronosyl transferase, UGT1A1.

“Immunotoxicology practiced in society”

Patients having defective UGT1A1 genotypes may exhibit
strong adverse reactions following administration ofirinotecan.

《 Outline of Meeting 》

We have shown that the diplotypes, *28/*28,*6/*28, *6/*6, are causative genotypes responsible forSpecial lecture:
severe adverse reactions including leukopenia.

Thus, for
Victor J. Johnson, Ph.D.

the first time, we showed that *6, in addition to *28 was an（Grants & Contracts PI / Study Director.

important factor in irinotecan-induced leukopenia in
Burleson Research Technologies, Inc.）
Japanese patients.

No.1（13） 13

ImmunoTox Letter
Currently,

reportsonalarge

number ofdrug

Educational lecture:
response-relatedgenetic

polymorphisms

havebeen

Dr. Kazuyoshi Saito
accumulating.

When efficacy or safety of a drug is largely(University of Occupational and Environmental
affected by genetic polymorphisms, development of aHealth, Japan.)so-called companion diagnostics is necessary for theDr. Kazuhiro Yatera
prediction of such effects.

For searching biomarkers to be(University of Occupational and Environmental
used for companion diagnostic devices, new technologies
Health, Japan.)including whole genom or epi-genome analysis are
Dr. Minoru Satoavailable.

It is desirable that true “precision medicine”(University of Occupational and Environmental
using good biomarkers are achieved.
Health, Japan.)Symposium:

The 5th Japanese Society of“Effect of ultra fine and fine particle on the lung

Immunotoxicology Prize for Encouragement

and its social practice”
Dr. Kenji Mizuguchi
Dr. Yasumitsu Nishimura

An Immunotoxic Perspective Regarding

Dr. Etsushi Kuroda

the Impact of Environmental Pollutants

Dr. Hiroto Izumi

On Allergic Diseases and Lifestyle Diseases

WorkshopRie Yanagisawa

Oral / Poster Presentation

Center for Health and Environmental Risk Research,Awards ceremony

Molecular Pathology Section

Social gathering September 6(Tue)Over the past few decades, environmental factors havecaused an increase in allergic diseases and lifestyle diseases.
Fetuses, infants, children, and patients are considered
Gemcitabine is a still important drug for treatment ofpancreatic cancer.

particularly vulnerable to environmental factors. This

Gemcitabine (dFdC) is also a prodrug,

study investigates the effects of exposure to environmental

activated by phosphorylation (into dFdCDP and dFdCTP).

pollutants in allergic diseases and lifestyle diseases, such as

Gemcitabine is metabolized into an inactive compoundobesity.

dFdU by cytidine deaminase (CDA).

We have found thatFirst, we examined whether exposure to components of

the haplotype *3 of the CDA gene with the amino acid

dieselsubstitutionforrespiratory diseases, such as allergic airway inflammation

gemcitabine-mediated toxicity. Especially, the homozygotes

and lipopolysaccharide (LPS)-induced acute lung injury inof *3 showed life-threatening severe reactions.

mice. Our findings revealed that DEP components

Ala70Thrisresponsible

exhaustparticles(DEP)

aggravatesdiversely affect a variety of respiratory diseases.

No.1（14） 14

certainImmunoTox Letter
Words fromNew councilors

Second, we established a model of mite allergen–induced
atopic dermatitis-like skin lesion using NC/Nga mice andshowed that diethylhexyl phthalate (DEHP) aggravates
atopicdermatitis-likeskinlesions

atGreeting to becoming a new councilorambient

concentrations. In addition, we found that maternal

Eiko Koike

exposure to DEHP in the lactation period can accelerate

National Institute for Environmental Studies

atopic dermatitis-like skin lesions in male mouse offspring,First of all, I would like to express my sincere

possibly via Th2-dominant responses.
Next, we also focused the effects of exposure toenvironmental pollutants on the development of obesity.

appreciation to the Board of Directors of Japanese Societyof Immunotoxicology for accepting me as a councilor.
Environmental pollutants are thought to be critical

Imbalance between caloric intake and expenditure isconsidered a key reason for the present obesity epidemic.
However, emerging evidence exists demonstrating that
exposure to environmental pollutants is also an importantcontributor. Therefore, we investigated whether exposure
tohexabromocyclododecane

flame-retardant,contributes(HBCD),
totheanadditive

initiation

andprogression of obesity and related metabolic dysfunction inmice fed a normal diet (ND) or a high-fat diet (HFD). This
study

demonstrates

thatenhanced

weightgain,hyperglycemia, hyperinsulinemia, hepatic steatosis, andmacrophage accumulation in adipose tissue occur in micefed HBCD-treated HFD diet but not in mice fed
HBCD-treated ND diet. These results suggest that HBCD
may be associated with metabolic dysfunction via
interactions with the diet.

problems for the increase in modern disease such as allergy
and lifestyle-related diseases. I have investigated the effects
of pollutants existingin theindoor and outdoor

environment on respiratory system and immune system.
Currently, I have been focusing on chemicals in consumer
products, such as phthalates ubiquitously used asplasticizers and brominated flame retardants. I am doing
research about these chemical-mediated disruptions of theimmune cell function which contribute to the exacerbationof

chronic

inflammationsuchasallergy

andlifestyle-related diseases. I am also concerned with thecross talk between cell-cell and cell-matrix adhesion toelucidate the molecular mechanisms in the aggravation ofchronic inflammation induced by chemicals.
I will try to do my best to contribute to development ofJapanese Society of Immunotoxicology. I will greatly
appreciate helpful advice and support from JSIT members.

No.1（15） 15

ImmunoTox Letter
I will vigorously endeavor to contribute to theWords fromNew councilors

development of the JSIT, and wish to express in advance
my appreciation to you for your ongoing support andGreetings on the occasion of becoming aencouragement.

new councilor member
Akihiko Hisatomi
Drug Safety Reach Labs., Drug Discovery Research,Astellas Pharma Inc.
I am Akihiko Hisatomi. I am a researcher at the Drug
Safety Reach Labs. of Astellas Pharma Inc. I have taken
office as a councilor of the Japanese Society ofImmunotoxicology. I would like to express my heartfelt
gratitude to the doctors and senior who recommended andaccepted me as to this prestigious position.
Allow me to tell you a little about myself. After
graduating from Kyushu University with a masters degree,
I started my career at Fujisawa Pharmaceutical Co. Ltd.,
which is now known as Astellas Pharma Inc. I have long
worked in safety research and in the evaluation of many
drug candidate substances.
My first work in immunotoxicology was in a study
entitled“Collaborativeimmunotoxicology

study

evaluation

toestablish

procedures

forpharmaceuticals” under the auspices of the Japan
Pharmaceutical Manufacturers Association. At the 7th
annual meeting of the JSIT, I was able to present theresults for one substance in that study. Since then, I haveworked on this field of research. Currently, I also work as astudy director in immunotoxicity studies and in general
toxicity studies.
Recently, I have developed an interest in the predictionof drug-induced interstitial pneumonia in the non-clinicalfield. Since drug-induced interstitial pneumonia is a serious
adverse event in clinical settings, however, it is now
difficult to detect potential risks of this pneumonia in
non-clinical studies.

No.1（16） 16