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外科的同所移植マウスを用いる
抗がん剤の薬効評価、受託サービス
Services of Efficacy Testing of AntiCancer
Drug by SOI mouse model
AntiCancer Japan Inc.
Tatushi Goto
May 8th, 2013 Biotech2013

AntiCancer Japan Inc.

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Business
Product sales‐ GFP/RFP-expressing cell lines（Wako Pure Chemical Industries Ltd.）‐ GFP-expressing nude mouse（Japan SLC Inc.）
Contract research using in vivo fluorescent imaging technology‐ Tumor imaging (SOI model, SC model, TVI model)‐ Drug distribution
Demonstration
Location〒567-0085
Saito Bioincubator 106, 7-7-15 Saitoasagi, Ibaraki,Osaka
URL: http://www.anticancerjapan.com/

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GFP/RFP-expressing cell lines

PC3-GFP

PC3-RFPHCT116-GFP

HT1080-Dual color

Now on sale !!
Wako Pure Chemical Industries
http://www.wako-chem.co.jp/siyaku/product/life/anti/index.htm
AntiCancer Japan
http://anticancerjapan.com/research/fluorescent_protein/index.html

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GFP-expressing nude mouse
RFP nude mouse

CFP nude mouse

Japan SLC
http://jslc.co.jp/
AntiCancer Japan
http://anticancerjapan.com/research/mousenude_protein/index.html

“Implantation of human tumor tissue into thecorresponding organ of mouse ”

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SOI model
SOI = Surgical Orthotopic Implantation
Prostate cancer Cell line：PC3-GFP① Cut subcutaneous tumor
into small pieces.

② Expose prostate.

③ Implant on prostateusing nylon suture.

④ Close a wound.

“Implantation of human tumor tissue into thecorresponding organ of mouse ”

SOI model
Prostate cancer Cell line：PC3-GFP
Day 0Day 7

Day 14

Day 24

Day 0Day 7

Day 14

Day 25SC

SOI
SOI model mouse shows tumor metastasis.

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“Implantation of human tumor tissue into thecorresponding organ of mouse ”

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SOI model
Breastcancer

No. of mice

No. of mice withPrimary tumor

No. of mice withlung metastasis

SOI886SC

770(Fu et al, Anticancer Res., 1993)

Colon cancer

Local tumor
growthSOI
Cell suspension

Metastasis
Regional
lymph node

Peritoneum

Liver

Lung

12 / 126 / 1210 / 129 / 126 / 123 / 120 / 120 / 120 / 120 / 12

(Furukawa et al, Jpn J. Surgery., 1993)

SOI model enhances metastatic ability of tumor.

“Implantation of human tumor tissue into thecorresponding organ of mouse ”

SOI model
Ovary

StomachColonVarious SOI models are available.

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“Implantation of human tumor tissue into thecorresponding organ of mouse ”

SOI model
Ovarian cancer Cell line：SKOV3-GFP
Day 14

Day 28

Day 42

Day 56

Day 56

GFP

Various SOI models are available.

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“Implantation of human tumor tissue into thecorresponding organ of mouse ”

SOI model
Stomach cancer Cell line：NUGC4-GFP
Day 13

Day 28

Day 42

Day 56

Day 60

GFP

Various SOI models are available.

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“Implantation of human tumor tissue into thecorresponding organ of mouse ”

SOI model
Colon cancer Cell line：HCT-116-GFP
Day 14

Day 22

Day 28

Day 41

Various SOI models are available.

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Evaluation of anticancer drug efficacy in SOI model
Colon cancer Cell line：HT29-GFP

AB

CDE

MEN4901/T-0128
Treatment
Inhibition
rate (%)

F

G

H

Irinotecan

1760 mg/kg,
single880 mg/kg,
q7d x 2880 mg/kg,
single

440 mg/kg,
q7d x 2440 mg/kg,
q4d x 480 mg/kg,
q4d x 440 mg/kg,
q4d x 4

Untreated

80.4

81.5

70.7

80.4

84.8

56.5

22.8

-(Ma et al, J. Surgical Res., 2011)

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Leukemia TVI model
Leukemia Cell line：U937-GFP
Day 10Day 21

Day 29Dorsalview

Ventralview

Bone metastases of leukemia were observed.

Cancer studies by fluorescent imaging
•

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Correlation between fluorescent area and tumor volume

Regression
95% confidence
r=0.89, p < 0.05

(Katz et al, J. Surgical Res., 2003)•

Detection of micro-metastasis

LiverLungCancer studies by fluorescent imaging•

Time course of angiogenesis(Yang et al, PNAS., 2001)•Vascular migration of cancer cellSkin flap

Migration

Extravasation* Movie* Movie15/21

AntiCancer’s SOI mouse model is….

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Growth and metastasis model of human cancer
Available model of various human cancers- Colon, Stomach, Pancreas, Breast, Ovary, Bladder, Prostate (TVI model are used in case of Lung cancer, Leukemia, Melanoma )Less invasive method

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Fluorescent imaging systems

NIPPON ROPER
Lumazone FL

UVP iBOX

INDEC Biosystems
FluorVivo100

OLYMPUS OV110

Our challenges for advanced imaging research

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1. Near infrared (NIR) probes for cancer•BTP derivatives
CHO(Zhang et al, Cancer Res., 2010)
HeLa

Pre-inj.

60 min20% O2

5% O2

Excitation: 575-675 nm
Emission : > 645 nm

Our challenges for advanced imaging research
2. Sensitivity improvement of fluorescent signal•

Usage of low fluorescent diet

Normal dietDay 0Day 2Day 4Day 7

NIR

NIR

NIR

NIR

Low-fluorescent diet * CE-2 (without alfalfa) (CLEA Japan Inc.)
Day 0Day 2Day 4Day 7NIR

NIR

NIR

NIR

Intrinsic NIR fluorescence decreased.

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Flow of contract researchContact

Discussion

Experiment

Report20/21

Anticancer Japan (info@anticancerjapan.com)
orWako Pure Chemical Industries (labchem-tec@wako-chem.co.jp)
Cell line : GFP/RFP cells (See our catalog), Custom-made GFP/RFP cells
Mouse : Nude mouse, Fluorescent nude mouse (GFP, RFP, CFP)
Model : SOI model, SC model, TVI model
Dosing : Intraperitoneal administration, Tail vein injection,
Oral administration
Imager : OV110(OLYMPUS), Lumazone FL(NIPPON ROPER)
iBOX (UVP), FluorVivo 100 (INDEC Biosystems)
Photo : Whole body, Necroscopy, cell observation

Within one month from end of the experiments

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Please visit to Wako pavilion in BIOtech 2013
and Anticancer Japan’s Saito lab.

Contact to AntiCancer Japan
Tel: 072-643-1048 / Fax: 072-646-8432 / Email: info@anticancerjapan.com
Contact to Wako Pure Chemical Industries
Tel: 0120-052-099 / Fax: 0120-052-806
Email: labchem-tec@wako-chem.co.jp