Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells

类有机物 食管鳞状细胞癌 基底细胞 医学 肿瘤科 内科学 病理 生物 细胞生物学
作者
Takashi Kijima,Hiroshi Nakagawa,Masataka Shimonosono,Prasanna M. Chandramouleeswaran,Takeo Hara,Varun Sahu,Yuta Kasagi,Osamu Kikuchi,Koji Tanaka,Véronique Giroux,Amanda B. Muir,Kelly A. Whelan,Shinya Ohashi,Seiji Naganuma,Andres J. Klein‐Szanto,Yoshiaki Shinden,Ken Sasaki,Itaru Omoto,Yoshiaki Kita,Manabu Muto,Adam J. Bass,J. Alan Diehl,Gregory G. Ginsberg,Yuichiro� Doki,Masaki Mori,Yasuto Uchikado,Takaaki Arigami,Narayan G. Avadhani,Devraj Basu,Anil K. Rustgi,Shoji Natsugoe
出处
期刊:Cellular and molecular gastroenterology and hepatology [Elsevier BV]
卷期号:7 (1): 73-91 被引量:124
标识
DOI:10.1016/j.jcmgh.2018.09.003
摘要

Oropharyngeal and esophageal squamous cell carcinomas, especially the latter, are a lethal disease, featuring intratumoral cancer cell heterogeneity and therapy resistance. To facilitate cancer therapy in personalized medicine, three-dimensional (3D) organoids may be useful for functional characterization of cancer cells ex vivo. We investigated the feasibility and the utility of patient-derived 3D organoids of esophageal and oropharyngeal squamous cell carcinomas.We generated 3D organoids from paired biopsies representing tumors and adjacent normal mucosa from therapy-naïve patients and cell lines. We evaluated growth and structures of 3D organoids treated with 5-fluorouracil ex vivo.Tumor-derived 3D organoids were grown successfully from 15 out of 21 patients (71.4%) and passaged with recapitulation of the histopathology of the original tumors. Successful formation of tumor-derived 3D organoids was associated significantly with poor response to presurgical neoadjuvant chemotherapy or chemoradiation therapy in informative patients (P = 0.0357, progressive and stable diseases, n = 10 vs. partial response, n = 6). The 3D organoid formation capability and 5-fluorouracil resistance were accounted for by cancer cells with high CD44 expression and autophagy, respectively. Such cancer cells were found to be enriched in patient-derived 3D organoids surviving 5-fluorouracil treatment.The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
没有发布了新的文献求助10
刚刚
寒塘发布了新的文献求助30
刚刚
刚刚
1秒前
1秒前
1秒前
1秒前
DJN0717发布了新的文献求助10
2秒前
orixero应助科研鸭采纳,获得10
2秒前
2秒前
2秒前
3秒前
隐形曼青应助文安采纳,获得10
4秒前
4秒前
氢氧化钠发布了新的文献求助10
5秒前
忆枫发布了新的文献求助10
5秒前
上官若男应助爱笑笑采纳,获得10
5秒前
巫马夜安完成签到,获得积分10
5秒前
Han发布了新的文献求助10
5秒前
研友_LBKR9n发布了新的文献求助10
6秒前
小蘑菇应助iris采纳,获得10
6秒前
Cici发布了新的文献求助10
7秒前
nike完成签到,获得积分10
7秒前
ytshen3124完成签到,获得积分10
7秒前
Rustaring发布了新的文献求助30
7秒前
7秒前
7秒前
8秒前
hzx完成签到,获得积分10
8秒前
8秒前
Jessie完成签到,获得积分10
8秒前
9秒前
9秒前
super完成签到,获得积分10
9秒前
10秒前
田様应助程雯慧采纳,获得10
10秒前
无花果应助科研通管家采纳,获得10
10秒前
情怀应助科研通管家采纳,获得10
10秒前
酷波er应助科研通管家采纳,获得10
10秒前
10秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 360
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3970724
求助须知:如何正确求助?哪些是违规求助? 3515419
关于积分的说明 11178342
捐赠科研通 3250592
什么是DOI,文献DOI怎么找? 1795372
邀请新用户注册赠送积分活动 875802
科研通“疑难数据库(出版商)”最低求助积分说明 805181