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建立上皮样肉瘤 PDCs 和 PDX 以评估药物敏感性。

Establishment of an epithelioid sarcoma PDCs and PDX to evaluate drug sensitivity.

机构信息

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.

Department of Gastrointestinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.

出版信息

Biochem Biophys Res Commun. 2022 Oct 15;625:140-146. doi: 10.1016/j.bbrc.2022.07.052. Epub 2022 Aug 6.

Abstract

Epithelioid sarcoma (ES) is a very rare mesenchymal malignancy. Its oncogenesis remains unknown, and few therapies are available for advanced patients. Improved therapies, such as combined therapies, are urgently needed for the treatment of advanced ES. To identify precision drugs for advanced ES patients, the sensitivity of the drugs must be screened and evaluated before they are used for treatment. In the present study, tumour tissue from an ES patient was subjected to NGS sequencing, cell culture and the construction of a PDX model. Using the early generations of tumour-derived cells, we performed a screen and found that the combined drugs ADM and trametinib exhibited coefficiency in tumour inhibition. This conclusion was further confirmed in experiments with later generations of cells and PDX models. Therefore, we suggest that early generations of tumour-derived cells be used to test the sensitivity of ES tumours to candidate drugs. Moreover, we speculate that trametinib may be combined with chemotherapy in ES patients to prolong the duration of the chemotherapeutic response.

摘要

上皮样肉瘤 (ES) 是一种非常罕见的间叶性恶性肿瘤。其致癌机制尚不清楚,晚期患者的治疗方法有限。为了治疗晚期 ES,迫切需要改进的治疗方法,如联合治疗。为了确定晚期 ES 患者的精准药物,在用于治疗之前,必须对药物的敏感性进行筛选和评估。在本研究中,对一名 ES 患者的肿瘤组织进行了 NGS 测序、细胞培养和 PDX 模型构建。使用早期的肿瘤衍生细胞进行筛选,我们发现 ADM 和 trametinib 联合药物在肿瘤抑制方面具有协同作用。这一结论在后续几代细胞和 PDX 模型的实验中得到了进一步证实。因此,我们建议使用早期的肿瘤衍生细胞来测试 ES 肿瘤对候选药物的敏感性。此外,我们推测 trametinib 可能与 ES 患者的化疗联合使用,以延长化疗反应的持续时间。

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