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Osteosarcoma

儿科

关键词儿科 临床研究术语 恶性肿瘤

词汇介绍

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解析

osteosarcoma 英 /,ɒstɪəʊsɑː'kəʊmə/ 美 /,ɑstiosɑr'komə/

释    义   n. [肿瘤] 骨肉瘤

例    句   Osteosarcoma is one of the commonest primary malignant tumors of bone. It metastasizes fast, and has a high death rate. 骨肉瘤是原发于骨的肿瘤中最常见的一类恶性肿瘤,转移快,死亡率高。

概述

骨肉瘤是起源于间叶组织的恶性肿瘤,以能产生骨样组织的梭形基质细胞为特征。经典型骨肉瘤是原发于髓腔内的高度恶性肿瘤,肿瘤细胞产生骨样组织,可能是极少量。流行病学经典型骨肉瘤占所有骨肉瘤的80%,主要发生于儿童和青少年,中位发病年龄为 20 岁。常见发病部位是股骨远端和胫骨近端,首发症状常为疼痛及肿胀,最常见的转移方式是血行转移至肺脏。诊断影像学检查:(1)骨内始发骨破坏;(2)可破坏骨皮质;(3)可在骨外形成软组织肿块;(4)可伴有骨膜反应;(5)病变基质可为成骨、溶骨或混合;(6)病变局部

Ex vivo screen identifies CDK12 as a metastatic vulnerability in osteosarcoma复制标题

体外筛查将CDK12识别为骨肉瘤的转移易损性

发表时间:2019-10-01

影响因子:12.3

作者: Bayles Ian

期刊:J Clin Invest

Despite progress in intensification of therapy, outcomes for patients with metastatic osteosarcoma (OS) have not improved in thirty years. We developed a system that enabled preclinical screening of compounds against metastatic OS cells in the context of the native lung microenvironment. Using this strategy to screen a library of epigenetically targeted compounds, we identified inhibitors of CDK12 to be most effective, reducing OS cell outgrowth in the lung by more than 90% at submicromolar doses. We found that knockout of CDK12 in an in vivo model of lung metastasis significantly decreased the ability of OS to colonize the lung. CDK12 inhibition led to defects in transcription elongation in a gene length- and expression-dependent manner.

译文

尽管强化治疗取得了进展,但30年来转移性骨肉瘤(os)患者的预后并没有改善。我们开发了一个系统,能够在天然肺微环境的背景下,对针对转移性os细胞的化合物进行临床前筛选。利用这一策略筛选表观遗传靶向化合物库,我们确定cdk12抑制剂是最有效的,在亚微摩尔剂量下可将肺中os细胞的生长减少90%以上。我们发现在体内肺转移模型中cdk12的敲除显著降低os在肺中的定植能力。cdk12抑制以基因长度和表达依赖的方式导致转录延长缺陷。