研究动态
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对于恶性骨肿瘤来说,进行一种基于三维培养的短期药物敏感性测试是可行的。

A short-term three dimensional culture-based drug sensitivity test is feasible for malignant bone tumors.

发表日期:2023 Sep 14
作者: Hiroaki Goto, Takashi Ohtsu, Mieko Ito, Maiko Sagisaka, Takuya Naruto, Jun-Ichi Nagai, Norihiko Kitagawa, Mio Tanaka, Masakatsu Yanagimachi, Yukihiko Hiroshima, Yohei Miyagi
来源: Cellular & Molecular Immunology

摘要:

通过使用两种由骨肉瘤细胞株(KCS8或KCS9)形成的异种移植(CDX)模型,评估了利用短期三维(3D)培养为基础的药物敏感性测试(DST)对手术切除的恶性骨肿瘤,包括骨肉瘤(OS)的可行性。在60种测试药物中,由细胞株在移植前获得的OS细胞中有23种(KCS8)或39种(KCS9)可能有效。而从CDX肿瘤分离的细胞中所选择的有效药物较少(19种:KCS8,26种:KCS9),尽管60种药物的药物敏感性在两种样本之间具有显著相关性。在样本中去除非肿瘤成分后,CDX肿瘤的药物敏感性没有显著改变。对于一个有OS的患者,经癌基因分析测试发现存在致病性PIK3CA突变,DST鉴定出mTOR和AKT抑制剂作为有效药物。在两个CDX和六个OS和Ewing肉瘤的临床样本中,DST确定蛋白酶体抑制剂(博来佐米,卡菲索米布)和CEP-701作为在常规情况下的潜在有效药物。这种利用三维细胞培养的体外药物测试方法对于手术切除的转移性恶性骨肿瘤的组织是可行的。©2023. 日本人类细胞学会独家许可的作者。
The feasibility of a short-term, three-dimensional (3D) culture-based drug sensitivity test (DST) for surgically resected malignant bone tumors, including osteosarcoma (OS), was evaluated utilizing two OS cell line (KCS8 or KCS9)-derived xenograft (CDX) models. Twenty-three (KCS8) or 39 (KCS9) of 60 tested drugs were likely effective in OS cells derived from a cell line before xenografting. Fewer drugs (19: KCS8, 26: KCS9) were selected as effective drugs in cells derived from a CDX tumor, although the drug sensitivities of 60 drugs significantly correlated between both types of samples. The drug sensitivity of a CDX tumor was not significantly altered after the depletion of non-tumorous components in the sample. In a surgically resected metastatic tumor obtained from a patient with OS, for whom a cancer genome profiling test detected a pathogenic PIK3CA mutation, DST identified mTOR and AKT inhibitors as effective drugs. Of two CDX and six clinical samples of OS and Ewing's sarcoma, DST identified proteasome inhibitors (bortezomib, carfilzomib) and CEP-701 as potentially effective drugs in common. This unique method of in vitro drug testing using 3D-cell cultures is feasible in surgically resected tissues of metastatic malignant bone tumors.© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.