Urinary detection of lung cancer in mice via noninvasive pulmonary protease profiling.
Urinary detection of lung cancer in mice via noninvasive pulmonary protease profiling.
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DOI：
10.1126/scitranslmed.aaw0262
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发表时间：
2020-04-01
影响因子：
17.1
通讯作者：
Bhatia SN
中科院分区：
文献类型：
--
作者：
Kirkpatrick JD;Warren AD;Soleimany AP;Westcott PMK;Voog JC;Martin-Alonso C;Fleming HE;Tammela T;Jacks T;Bhatia SN
肺癌是癌症相关死亡的主要原因，并且患者最常见的是不可治愈的转移性疾病。国家指南建议用低剂量计算机断层扫描（LDCT）筛查高危患者，但这种方法有局限性，包括高假阳性率。基于活性的纳米传感器（ABN）检测体内失调的蛋白酶，并释放报告基因，以提供疾病活动的尿液读数。在这里，我们证明了ABN的翻译潜力，通过耦合ABN复用与肺内递送，以检测早期肺癌的免疫活性，基因工程小鼠模型（GEMM）。通过人和小鼠肺腺癌数据集的比较转录组学分析和用重组候选蛋白酶的体外切割测定来告知传感器的多路复用面板的设计。当用于Kras和Trp53突变型肺腺癌小鼠模型时，这种方法证实了金属蛋白酶在肺癌中的作用，并能够准确地早期检测疾病，灵敏度为92%，特异性为100%。
Lung cancer is the leading cause of cancer-related death and patients most commonly present with incurable metastatic disease. National guidelines recommend screening for high-risk patients with low-dose computed tomography (LDCT), but this approach has limitations including high false positive rates. Activity-based nanosensors (ABNs) detect dysregulated proteases in vivo and release a reporter to provide a urinary readout of disease activity. Here, we demonstrate the translational potential of ABNs by coupling ABN multiplexing with intrapulmonary delivery to detect early-stage lung cancer in an immunocompetent, genetically engineered mouse model (GEMM). The design of the multiplexed panel of sensors was informed by comparative transcriptomic analysis of human and mouse lung adenocarcinoma data sets and in vitro cleavage assays with recombinant candidate proteases. When employed in a Kras and Trp53 mutant lung adenocarcinoma mouse model, this approach confirmed the role of metalloproteases in lung cancer and enabled accurate early detection of disease, with 92% sensitivity and 100% specificity.
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DOI：
10.1056/nejmoa1312547
发表时间：
2014-11-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Black WC;Gareen IF;Soneji SS;Sicks JD;Keeler EB;Aberle DR;Naeim A;Church TR;Silvestri GA;Gorelick J;Gatsonis C;National Lung Screening Trial Research Team
通讯作者：
National Lung Screening Trial Research Team
影响因子：
11.1
作者：
Buss CG;Dudani JS;Akana RTK;Fleming HE;Bhatia SN
通讯作者：
Bhatia SN
DOI：
10.1152/ajplung.00061.2014
发表时间：
2015-07-01
影响因子：
4.9
作者：
Poroyko, Valeriy;Meng, Fanyong;Birukov, Konstantin G.
通讯作者：
Birukov, Konstantin G.
影响因子：
64.8
作者：
Maddalo, Danilo;Manchado, Eusebio;Concepcion, Carla P.;Bonetti, Ciro;Vidigal, Joana A.;Han, Yoon-Chi;Ogrodowski, Paul;Crippa, Alessandra;Rekhtman, Natasha;de Stanchina, Elisa;Lowe, Scott W.;Ventura, Andrea
通讯作者：
Ventura, Andrea
影响因子：
38.3
作者：
Loynachan, Colleen N.;Soleimany, Ava P.;Stevens, Molly M.
通讯作者：
Stevens, Molly M.