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Annual Report 2019

Central Animal Division

Toshio Imai, Mami Takahashi, Mie Naruse, Rikako Ishigamori, Angeline Teh Ping Ping, Ruri Nakanishi, Yurika Shiotani, Makiko Saitou, Momo Nakanishi, Yukino Machida, Noriyuki Kimura, Junichi Zukeyama, Hiroyuki Hayashida, Saori Kobayashi, Sakura Ueki, Ikuko Harada, Chitose Nishizawa, Takeru Sato

Introduction

 The important role of the Central Animal Division is health management of experimental animals and maintenance of animal experimentation facilities. The laboratory animal facility has been certified to be compatible with the “Basic policies for the conduct of animal experimentation in the Ministry of Health, Labour and Welfare” stipulated by the Ministry of Health, Labour and Welfare of Japan, based on an assessment by the Center for accreditation of Laboratory Animal Care and Use, Japan Health Sciences Foundation on March, 2020. Some researchers and technical staff also act in several support services, which are provided based on their biological skills, such as reproductive technologies for animal cleaning / embryo-sperm preservation, pathological analysis of mouse phenotypes, and establishment of expandable cells / xenograft transplantable models from clinical cancer tissues (PDX models).

The Team and What We Do

 Animal models are essential not only for basic cancer research but also for translational research (TR) fields. We willingly contribute to establish useful animal models including genetically engineered mice (GEM) for basic cancer research and PDX models for TR, and to analyze their molecular details.

Research activities

 As for PDX models, genetic and/or phenotypic changes during their passages and incubation in the mouse and characterizations of proliferative lesions that originated from human lymphocytes have been evaluated. Our members have established PDX models mainly from colorectal, pancreas and uterine endometrial cancers. Gene mutation/morphological characteristics of PDXs derived from colorectal cancers have not been shown to dramatically change by their passages. On the other hand, for PDX derived from endometrial cancers, the morphological or immunohistochemical characteristics have been demonstrated to gradually change by passages.

Education

 We contribute to organize the annual training sessions for researchers and technical experts on animal experiments. In addition, technical trainees are received for skill acquirement on animal experiments and rat tumor analysis.

Future prospects

 Research approaches using immune deficient/severely immune-deficient mice have become increasingly important over the past few years, and microbiological controls of the animal experimentation facility should become more strictly controlled. We will now review and revise the manual for hygiene management in the facility, and continue to keep researchers/technical staff informed about the rules.

List of papers published in 2019

Journal

1. Matsuura T, Maru Y, Izumiya M, Hoshi D, Kato S, Ochiai M, Hori M, Yamamoto S, Tatsuno K, Imai T, Aburatani H, Nakajima A, Hippo Y. Organoid-based ex vivo reconstitution of Kras-driven pancreatic ductal carcinogenesis. Carcinogenesis, 41:490-501, 2020

2. Oyama R, Kito F, Takahashi M, Hattori E, Noguchi R, Takai Y, Sakumoto M, Qiao Z, Toki S, Sugawara M, Tanzawa Y, Kobayashi E, Nakatani F, Iwata S, Yoshida A, Kawai A, Kondo T. Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors. Cancer Cell Int, 20:58, 2020

3. Yonemaru J, Takahashi M, Nara S, Ichikawa H, Ishigamori R, Imai T, Hiraoka N. A yolk sac tumor of the pancreas and derived xenograft model effectively responded to VIP chemotherapy. Pancreatology, 20:551-557, 2020

4. Masumura K, Yatagai F, Ochiai M, Nakagama H, Nohmi T. Effects of the scid mutation on X-ray-induced deletions in the brain and spleen of gpt delta mice. Genes Environ, 42:19, 2020

5. Machida Y, Sudo Y, Uchiya N, Imai T. Increased susceptibility to mammary carcinogenesis and an opposite trend in endometrium in Trp53 heterozygous knockout female mice by backcrossing the BALB/c strain onto the background C3H strain. J Toxicol Pathol, 32:197-203, 2019

6. Oyama R, Kito F, Takahashi M, Sakumoto M, Shiozawa K, Qiao Z, Noguchi R, Kubo T, Toki S, Nakatani F, Yoshida A, Kawai A, Kondo T. Establishment and characterization of a novel dedifferentiated chondrosarcoma cell line, NCC-dCS1-C1. Hum Cell, 32:202-213, 2019

7. Shiozawa K, Oyama R, Takahashi M, Kito F, Hattori E, Yoshida A, Kawai A, Ono M, Kondo T. Species-Specific Quantitative Proteomics Profiles of Sarcoma Patient-Derived Models Closely Reflect Their Primary Tumors. Proteomics Clin Appl, 13:e1900054, 2019