抄録
Biliary tract carcinomas (BTCs) are among the most aggressive malignancies and have a poor prognosis. Here, we successfully established organoid lines derived from intrahepatic cholangiocarcinoma, gallbladder cancer, and neuroendocrine carcinoma of the ampulla of Vater. These organoids derived from BTCs were cultured stably for >1 year and closely recapitulated the histopathology, gene expression, and genetic alterations evident in the primary tumors. Gene expression profiling of the organoids revealed that SOX2 could be a potential prognostic biomarker for patients with BTC. We screened a compound library consisting of drugs used clinically for their ability to suppress organoids derived from BTCs and found that the antifungal drugs amorolfine and fenticonazole significantly suppressed the growth of organoids derived from BTCs with minimal toxicity to normal biliary epithelial cells. Patient-derived organoids may be a powerful research tool for the clarification of molecular pathogenesis and the discovery of biomarkers and therapeutic drugs for refractory cancers.
| 元の言語 | English |
|---|---|
| ページ（範囲） | 1265-1276.e4 |
| ジャーナル | Cell Reports |
| 巻 | 27 |
| 発行部数 | 4 |
| DOI | |
| 出版物ステータス | Published - 2019 4 23 |
Fingerprint
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
これを引用
Establishment of Patient-Derived Organoids and Drug Screening for Biliary Tract Carcinoma. / Saito, Yoshimasa; Muramatsu, Toshihide; Kanai, Yae; Ojima, Hidenori; Sukeda, Aoi; Hiraoka, Nobuyoshi; Arai, Eri; Sugiyama, Yuko; Matsuzaki, Juntaro; Uchida, Ryoei; Yoshikawa, Nao; Furukawa, Ryo; Saito, Hidetsugu.
：: Cell Reports, 巻 27, 番号 4, 23.04.2019, p. 1265-1276.e4.研究成果: Article
}
TY - JOUR
T1 - Establishment of Patient-Derived Organoids and Drug Screening for Biliary Tract Carcinoma
AU - Saito, Yoshimasa
AU - Muramatsu, Toshihide
AU - Kanai, Yae
AU - Ojima, Hidenori
AU - Sukeda, Aoi
AU - Hiraoka, Nobuyoshi
AU - Arai, Eri
AU - Sugiyama, Yuko
AU - Matsuzaki, Juntaro
AU - Uchida, Ryoei
AU - Yoshikawa, Nao
AU - Furukawa, Ryo
AU - Saito, Hidetsugu
PY - 2019/4/23
Y1 - 2019/4/23
N2 - Biliary tract carcinomas (BTCs) are among the most aggressive malignancies and have a poor prognosis. Here, we successfully established organoid lines derived from intrahepatic cholangiocarcinoma, gallbladder cancer, and neuroendocrine carcinoma of the ampulla of Vater. These organoids derived from BTCs were cultured stably for >1 year and closely recapitulated the histopathology, gene expression, and genetic alterations evident in the primary tumors. Gene expression profiling of the organoids revealed that SOX2 could be a potential prognostic biomarker for patients with BTC. We screened a compound library consisting of drugs used clinically for their ability to suppress organoids derived from BTCs and found that the antifungal drugs amorolfine and fenticonazole significantly suppressed the growth of organoids derived from BTCs with minimal toxicity to normal biliary epithelial cells. Patient-derived organoids may be a powerful research tool for the clarification of molecular pathogenesis and the discovery of biomarkers and therapeutic drugs for refractory cancers.
AB - Biliary tract carcinomas (BTCs) are among the most aggressive malignancies and have a poor prognosis. Here, we successfully established organoid lines derived from intrahepatic cholangiocarcinoma, gallbladder cancer, and neuroendocrine carcinoma of the ampulla of Vater. These organoids derived from BTCs were cultured stably for >1 year and closely recapitulated the histopathology, gene expression, and genetic alterations evident in the primary tumors. Gene expression profiling of the organoids revealed that SOX2 could be a potential prognostic biomarker for patients with BTC. We screened a compound library consisting of drugs used clinically for their ability to suppress organoids derived from BTCs and found that the antifungal drugs amorolfine and fenticonazole significantly suppressed the growth of organoids derived from BTCs with minimal toxicity to normal biliary epithelial cells. Patient-derived organoids may be a powerful research tool for the clarification of molecular pathogenesis and the discovery of biomarkers and therapeutic drugs for refractory cancers.
KW - antifungal drug
KW - biliary tract carcinoma
KW - drug screening
KW - gallbladder cancer
KW - intrahepatic cholangiocarcinoma
KW - neuroendocrine carcinoma of the ampulla of Vater
KW - organoid culture
UR - http://www.scopus.com/inward/record.url?scp=85064155184&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064155184&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2019.03.088
DO - 10.1016/j.celrep.2019.03.088
M3 - Article
C2 - 31018139
AN - SCOPUS:85064155184
VL - 27
SP - 1265-1276.e4
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 4
ER -