シンポジウム 10

Clinicopathological factors associated withestablishment of gastric cancer PDXs andcell lines.
Patient-derived xenograft (PDX) models has been widely accepted as a suitable preclinicalmodel. However, the number of PDX models as well as cell-lines from gastric cancer (GC) are

Takeshi Kuwata
Department of Pathology and Clinical Laboratories
National Cancer Center Hospital East

[Awards or something, you can fill this part as you want]
2003

Uehar prize, Uehara Memorial Foundation「Research for Carcinogenic Signal by BCL11B」

limited. We ignited our project (DEF study) on May 2013 for establishing new gastric cancer(GC) PDX models and cell lines for accelerating the development of new therapeutics for GC.
Two hundred and fifty (250) patients, including 233 patients underwent gastrectomy in NationalCancer Center Hospital East (NCCHE) or National Cancer Center Hospital and 17 patients
received cell-free and concentrated ascites reinfusion therapy (CART) at NCCHE, were enrolled
For establishing PDX models, we subcutaneously engrafted 232 surgically resected gastric[References]1.

Kuwata T, et al. Cells (2019) 8: 585

2.

Kawazoe A, Kuwata T, et al. Gastric Cancer (2019) 22:69

cancer tissues into immune-deficient NOG mice and successfully established 35 gastric cancer
PDX models. PDX-establishment rate was 15.1%, and differentiated type adenocarcinomas (DAs)were more effectively established than poorly differentiated type adenocarcinomas (PDAs).
The histology of PDX resembled their primary tumors, and the concordance of histologicaldifferentiation grade between primary tumors and PDXs was significant.
Twenty-three (23) GC cell lines have been established from surgically resected primary or
subsequently transplanted PDX tissues. Another 2 GC lines were established by cultivating
primary GC tissues directly. Among 25 GC cell lines, 24 lines could develop subcutaneoustumors (CDXs) in SCID mice. In contrast to PDX, the concordance of histological differentiation
grade between primary tumors and CDXs was not significant. In addition, we have established
7 GC cell lines from ascites from 17 patients received CART, and six of them could develop
CDXs. All of the CDXs from CART cases showed PD histology.
As the results, we have established both PDX and Cell lines simultaneously from 21
patients, which allowed us to invest a direct histological comparison between primary, PDX,and CDX tumors. We will also discuss about lymphoproliferative lesions, most of which showed
proliferation of B cell with various cytological atypia, encountered during the PDX establishment
process.

Takeshi Kuwata, MD, PhD
Chief, National Cancer Center Research Institute
1991
1994
1994-95
1996-99
2000-01
2002-08
2008-16
2016-34

Graduate Gunma University School of Medicine
PhD from Tokyo Medical and Dental University
Post-doctoral research fellow, Mitsubishi-Kasei Institute of Life Sciences
Post-doctoral fellow, NICHD. National Institutes of Health USA
Lecturer, Department of Pathology, Kitasato University
Research associate, Department of Carcinogenesis, The Cancer InstituteSection Chief, Department of Pathology and Clinical Laboratories, NCC
Chief, Department of Pathology and Clinical Laboratories, NCC35