title: Establishment of patient-derived cancer xenografts in immunodeficient NOG mice.
abstract: Viable and stable human cancer cell lines and animal models combined with adequate clinical information are essential for future advances in cancer research and patient care. Conventional in vitro cancer cell lines are commonly available; however, they lack detailed information on the patient from which they originate, including disease phenotype and drug sensitivity. Patient-derived xenografts (PDX) with clinical information (so-called 'cancer xenopatients') are a promising advance that may accelerate the development of anticancer therapies. We established 61 PDX lines from 116 surgically removed tumor tissues inoculated subcutaneously into NOG mice (53% success rate). PDX lines were established from various types of epithelial tumors and also from sarcomas, including gastrointestinal stromal tumors and Ewing/PNET sarcomas. The metastatic tumors yielded PDX lines more effectively (65%) than the primary tumors (27%, P<0.001). In our PDX models, morphological characteristics, gene expression profiles, and genetic alteration patterns were all well preserved. In eight cases (7%), the transplantable xenografts for several generations were composed of large monotonous nonepithelial cells of human origin, revealed to be Epstein-Barr virus infection-associated lympho-proliferative lesions. Despite this, PDX linked with clinical information offer many advantages for preclinical studies investigating new anticancer drugs. The fast and efficient establishment of individual PDX may also contribute to future personalized anticancer therapies.
authors.affiliation: Central Institute for Experimental Animals, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Chijiwa
authors.affiliation: Central Institute for Experimental Animals, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Department of Pathology, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Noguchi
authors.affiliation: Department of Neurosurgery, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Neurosurgery, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Akimune
authors.initials: A
authors.lastname: Hayashi
authors.affiliation: Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Shiozawa
authors.affiliation: Department of Urology, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kishida
authors.affiliation: Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Morinaga
authors.affiliation: Department of Pathology, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokose
authors.affiliation: Department of Neurosurgery, Kawasaki Municipal Hospital, Shinkawa-tori, Kawasaki 210-0013, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Katayama
authors.affiliation: Department of Neurosurgery, Kawasaki Municipal Hospital, Shinkawa-tori, Kawasaki 210-0013, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Takenaka
authors.affiliation: Central Institute for Experimental Animals, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suemizu
authors.affiliation: Research Institute, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Roppei
authors.initials: R
authors.lastname: Yamada
authors.affiliation: Research Institute, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Research Institute, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohtsu
authors.affiliation: Research Institute, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
authors.affiliation: Research Institute, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.affiliation: Research Institute, Kanagawa Cancer Center, Nakao, Asahi-ku, Yokohama 241-8515, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.affiliation: Central Institute for Experimental Animals, Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009368:Neoplasm Transplantation / Q000379:methods*; D009369:Neoplasms / Q000473:pathology*; D057285:Precision Medicine; D014183:Transplantation, Heterologous / Q000379:methods*; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult