Liquid biopsies come of age: towards implementation of circulating tumour DNA

Improvements in genomic and molecular methods are expanding the range of potential applications for circulating tumour DNA (ctDNA), both in a research setting and as a ‘liquid biopsy’ for cancer management. Proof-of-principle studies have demonstrated the translational potential of ctDNA for prognostication, molecular profiling and monitoring. The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA. This is an opportune time to appraise potential approaches to ctDNA analysis, and to consider their applications in personalized oncology and in cancer research.We would like to acknowledge the support of The University of Cambridge, Cancer Research UK (grant numbers A11906, A20240, A15601) (to N.R., J.D.B.), the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement n. 337905 (to N.R.), the Cambridge Experimental Cancer Medicine Centre, and Hutchison Whampoa Limited (to N.R.), AstraZeneca (to R.B., S.P.), the Cambridge Experimental Cancer Medicine Centre (ECMC) (to R.B., S.P.), and NIHR Biomedical Research Centre (BRC) (to R.B., S.P.). J.G.C. acknowledges clinical fellowship support from SEOM

Using radiographs to analyze equivalent weakest transverse interface of fracture healing

目的地提取X线平片中包含的骨折愈合力学信息,为临床骨折愈合治疗过程定量判断愈合程度提供有效并且简便实用的方法.方法 12只家兔胫骨中部横断造成骨折模型,并穿针进行滑动固定.利用力传感器在胫骨中部体表从前向后横向手动加载.通过安装在滑动固定器上的微位移传感器测量断端活动位移.采用计算机数据采集系统记录加载力值P和滑动架滑动位移ΔL关系曲线.以K=P/ΔL值代表带滑动固定器兔胫骨整体等效抗弯刚性.每周测量1次.采用经过数字化改造的手提X线机每周拍摄正,侧位X线片;在delphi软件开发环境中编写图像处理和计算程序.在X线正,侧位片灰度分析基础上,沿胫骨轴向扫描计算寻找等效最弱截面并计算其等效抗弯截面惯性矩,得到定量的抗弯刚度和断裂强度判据.结果家兔骨折愈合拆架时间分布在29~41 d.在正侧位X线片上获得计算机模拟的等效最弱截面分界线,且得到其抗弯截面惯性矩.最弱抗弯截面惯性矩与最强抗弯截面惯性矩的比值随愈合时间逐渐升高.侧位片比值术后第1周为(0.31±0.17),第2周为(0.34±0.13),第3周为(0.43±0.20),第4周为(0.56±0.23).正位片位片比值术后第1周为(0.40±0.19),第2周为(0.47±0.16),第3周为(0.56±0.20),第4周为(0.66±0.11).家兔骨折胫骨在体抗弯刚性测试所得K值术前平均为(3.976±4.986)N.μm-1,术后第1周为(0.679±1.026)N.μm-1,术后第2周为(2.115±3.233)N.μm-1,术后第3周为(3.459±4.723)N.μm-1,术后第4周为(4.788±4.831)N.μm-1.从1~4周愈合过程,X线片计算得到的最弱抗弯截面惯性矩和最强抗弯截面惯性矩的比值与K值之间具有很好的相关性.结论外骨痂生长有较强规律性,并且在普通正侧位X线平片易于辨认.从骨折近端和远端分别生长的骨痂在愈合进程中逐渐合拢,最终弥合.本文所述方法较好地反映了实际读片感