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Raltitrexed as a synergistic hyperthermia chemotherapy drug screened in patient-derived colorectal cancer organoids

查看全文 作　　者：Lisi [1]Zeng;Quanxing [2]Liao;Haoran [3,4]Zhao;Shengwei [3,4,5]Jiang;Xianzi [6]Yang;Hongsheng [2]Tang;Qingjun [2]He;Xiansheng [2]Yang;Shuxian [2]Fang;Jinfu [2]He;Weiwen [7]Cui;Laiqiang [3,4,5]Huang;Shaohua [3,4]Ma;Shuzhong [2]Cui 高影响力作者 机构地区：[1]Institute of Oncology,Affiliated Cancer Hospital and Institute of Guangzhou Medical University,Guangzhou 510095,China;[2]Department of Abdominal Surgery,Affiliated Cancer Hospital and Institute of Guangzhou Medical University,Guangzhou 510095,China;[3]Institute of Biopharmaceutical and Health Engineering,Shenzhen International Graduate School,Tsinghua University,Shenzhen 518055,China;[4]Tsinghua-Berkeley Shenzhen Institute(TBSI),Tsinghua University,Shenzhen 518055,China;[5]Shenzhen Key Laboratory of Gene and Antibody Therapy,Tsinghua University,Shenzhen 518055,China;[6]Department of Medical Oncology,Affiliated Cancer Hospital and Institute of Guangzhou Medical University,Guangzhou 510095,China;[7]Department of Bioengineering,University of California,Berkeley 94720,USA高影响力机构 出　　处：《Cancer Biology & Medicine》索引2021年第18卷第3期,共13页高影响力期刊 基　　金：supported by grants from the National Natural Science Foundation of China(Grant Nos.81972918 and 61971255);Shenzhen Science and Technology Innovation Committee(Grant No.KQJSCX20180327143623167);NANJING CHIA TAI TIANQING Company,Foundation for Young Innovative Talents in Education of Guangdong(Grant No.2017KQNCX161);Natural Science Foundation of Guangdong Province(Grant No.2018A030310249);Key Clinical Technique of Guangzhou(Grant No.2019ZD16)。 摘　　要：Objective:Organoids have recently been used as in vitro models to screen chemotherapy drugs in combination with hyperthermia treatment in colorectal cancer.Our research aimed to establish a library of patient-derived colorectal cancer organoids to evaluate synergism between chemotherapy drugs and hyperthermia;validate an index of the hyperthermia chemotherapy sensitization enhancement ratio(HCSER)to identify the chemotherapeutics most enhanced by hyperthermia;and recommend chemotherapy drugs for hyperthermic intraperitoneal treatment.Methods:Organoids were grown from cells extracted from colorectal cancer patient samples or colorectal cancer cell lines.Cells from both sources were encapsulated in 3 D Matrigel droplets,which were formulated in microfluidics and phase-transferred into identical cell-laden Matrigel microspheres.The microspheres were seeded in 96-well plates,with each well containing a single microsphere that developed into an organoid after 7 days.The organoids were used to evaluate the efficacy of chemotherapy drugs at both 37℃ as a control and 43℃ for 90 min to examine hyperthermia synergism.Cell viability was counted with 10%CCK8.Results:We successfully established a library of colorectal cancer organoids from 22 patient parental tumors.We examined the hyperthermia synergism of 7 commonly used hyperthermic intraperitoneal chemotherapy drugs.In 11 of the 22 patient organoids,raltitrexed had significant hyperthermia synergism,which was indexed as the highest HCSER score within each patient group.Conclusions:Our results primarily demonstrated the use of patient-derived colorectal cancer organoids as in vitro models to evaluate hyperthermia synergistic chemotherapeutics.We found that hyperthermia enhanced the effect of raltitrexed the most among the common anti-colorectal cancer drugs. 关 键 词：Colorectal cancer ORGANOIDS hyperthermia chemotherapy sensitization enhancement ratio RALTITREXED
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