Concurrent Driver Gene Mutations as Negative Predictive Factors in Epidermal Growth Factor Receptor-Positive Non-Small Cell Lung Cancer.


BACKGROUND:Tyrosine kinase inhibitors (TKIs) are clinically effective in non-small cell lung cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) oncogene mutations. Genetic factors, other than EGFR sensitive mutations, that allow prognosis of TKI treatment remain undefined. METHODS:We retrospectively screened 423 consecutive patients with advanced NSCLC and EGFR 19del or 21L858R mutations. A total of 71 patients whose progression-free survivals (PFS) were shorter than 6 months or longer than 24 months were included and stratified into separate groups. Genetic background discrepancy was analysed in the two groups using next generation sequencing (NGS). FINDINGS:Sensitive EGFR mutations of 19del or 21L858R were detected by NGS in all patients; the 21L858R mutation was the major type. The most frequent accompanying somatic mutations were TP53, RB1, MAP2K. ALK fusion, MET amplification, and BRAF V600E were found only in the short PFS group. Concurrent pretreament T790 M mutation was found in both groups, but was proportionally higher in the short PFS group. In the short PFS group, patients had significantly more driver gene mutations than in long PFS group (P = 0·018). The numbers of concomitant somatic mutations, EGFR pathway-related mutations, and tumor mutation burden (TMB) were not significantly different between the two groups. INTERPRETATION:Co-occuring driver gene mutations were negative predictive factors of TKI therapy in EGFR-mutated patients. This study highlights the importance of exploring co-occuring genomic alterations before initiation of EGFR-TKIs.






Chen M,Xu Y,Zhao J,Zhong W,Zhang L,Bi Y,Wang M




Has Abstract


2019-04-01 00:00:00










  • CRISPR/Cas9 - Mediated Precise Targeted Integration In Vivo Using a Double Cut Donor with Short Homology Arms.

    abstract::Precisely targeted genome editing is highly desired for clinical applications. However, the widely used homology-directed repair (HDR)-based genome editing strategies remain inefficient for certain in vivo applications. We here demonstrate a microhomology-mediated end-joining (MMEJ)-based strategy for precisely target...


    pub_type: 杂志文章


    authors: Yao X,Wang X,Liu J,Hu X,Shi L,Shen X,Ying W,Sun X,Wang X,Huang P,Yang H

    更新日期:2017-06-01 00:00:00

  • Structure-guided development of a high-affinity human Programmed Cell Death-1: Implications for tumor immunotherapy.

    abstract::Programmed Cell Death-1 (PD-1) is an inhibitory immune receptor, which plays critical roles in T cell co-inhibition and exhaustion upon binding to its ligands PD-L1 and PD-L2. We report the crystal structure of the human PD-1 ectodomain and the mapping of the PD-1 binding interface. Mutagenesis studies confirmed the c...


    pub_type: 杂志文章


    authors: Lázár-Molnár E,Scandiuzzi L,Basu I,Quinn T,Sylvestre E,Palmieri E,Ramagopal UA,Nathenson SG,Guha C,Almo SC

    更新日期:2017-03-01 00:00:00

  • Impact of the host environment on the antitubercular action of pyrazinamide.

    abstract::Pyrazinamide remains the only drug in the tuberculosis pharmacopeia to drastically shorten first-line therapy from nine to six months. Due to its unparalleled ability to sterilize non-replicating bacilli and reduce relapse rates, PZA is expected to be irreplaceable in future therapies against tuberculosis. While the m...


    pub_type: 杂志文章,评审


    authors: Lamont EA,Baughn AD

    更新日期:2019-11-01 00:00:00

  • Long non-coding RNA CDKN2B-AS1 contributes to atherosclerotic plaque formation by forming RNA-DNA triplex in the CDKN2B promoter.

    abstract:BACKGROUND:Atherosclerosis involves a slow process of plaque formation on the walls of arteries, and comprises a leading cause of cardiovascular disease. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of atherosclerosis. In this study, we aim to explore the possible involvement of lncRNA 'cycli...


    pub_type: 杂志文章


    authors: Ou M,Li X,Zhao S,Cui S,Tu J

    更新日期:2020-05-01 00:00:00

  • Traumatic Brain Injury and Alzheimer's Disease: The Cerebrovascular Link.

    abstract::Traumatic brain injury (TBI) and Alzheimer's disease (AD) are devastating neurological disorders, whose complex relationship is not completely understood. Cerebrovascular pathology, a key element in both conditions, could represent a mechanistic link between Aβ/tau deposition after TBI and the development of post conc...


    pub_type: 杂志文章,评审


    authors: Ramos-Cejudo J,Wisniewski T,Marmar C,Zetterberg H,Blennow K,de Leon MJ,Fossati S

    更新日期:2018-02-01 00:00:00

  • Vorinostat Renders the Replication-Competent Latent Reservoir of Human Immunodeficiency Virus (HIV) Vulnerable to Clearance by CD8 T Cells.

    abstract::Latently human immunodeficiency virus (HIV)-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR) induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen producti...


    pub_type: 杂志文章


    authors: Sung JA,Sholtis K,Kirchherr J,Kuruc JD,Gay CL,Nordstrom JL,Bollard CM,Archin NM,Margolis DM

    更新日期:2017-09-01 00:00:00

  • Splicing modulation as novel therapeutic strategy against diffuse malignant peritoneal mesothelioma.

    abstract:INTRODUCTION:Therapeutic options for diffuse malignant peritoneal mesothelioma (DMPM) are limited to surgery and locoregional chemotherapy. Despite improvements in survival rates, patients eventually succumb to disease progression. We investigated splicing deregulation both as molecular prognostic factor and potential ...


    pub_type: 杂志文章


    authors: Sciarrillo R,Wojtuszkiewicz A,El Hassouni B,Funel N,Gandellini P,Lagerweij T,Buonamici S,Blijlevens M,Zeeuw van der Laan EA,Zaffaroni N,Deraco M,Kusamura S,Würdinger T,Peters GJ,Molthoff CFM,Jansen G,Kaspers GJL,Cloos J

    更新日期:2019-01-01 00:00:00

  • MiR-765 functions as a tumour suppressor and eliminates lipids in clear cell renal cell carcinoma by downregulating PLP2.

    abstract:BACKGROUND:Lipid accumulation has been highlighted in cancer development and progression, but the exact mechanism remains unclear in renal cell carcinoma (RCC). MicroRNAs (miRNAs) have been confirmed to participate in the pathological processes of cancers, including tumour occurrence and inhibition. However, the role a...


    pub_type: 杂志文章


    authors: Xiao W,Wang C,Chen K,Wang T,Xing J,Zhang X,Wang X

    更新日期:2020-01-01 00:00:00

  • Contemporary update of overall prognosis and nomogram to predict individualized survival for Chinese patients with eyelid sebaceous carcinoma.

    abstract:BACKGROUND:The prognosis of Chinese patients with eyelid sebaceous carcinoma (SC) has not been updated for >3 decades. The prognostic predictors are multifactorial, and there is no validated prognostic model for eyelid SC. METHODS:This study included 238 consecutive patients with eyelid SC. All eligible patients were ...


    pub_type: 杂志文章


    authors: Zhou C,Shi Y,Chai P,Wu F,Xia W,He X,Shi Y,Huang H,Jia R,Fan X

    更新日期:2018-10-01 00:00:00

  • The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p.

    abstract:BACKGROUND:Non-small cell lung carcinomas (NSCLC) are prevalent, lethal cancers with especially grim prospects due to late-stage detection and chemoresistance. Circular RNAs (circRNAs) are non-coding RNAs that participate in tumor development. However, the role of circRNAs in NSCLC is not well known. This study investi...


    pub_type: 杂志文章


    authors: Wei S,Zheng Y,Jiang Y,Li X,Geng J,Shen Y,Li Q,Wang X,Zhao C,Chen Y,Qian Z,Zhou J,Li W

    更新日期:2019-06-01 00:00:00

  • Sphingomyelin synthase 1 enhances BCR signaling to promote lupus-like autoimmune response.

    abstract:BACKGROUND:Sphingomyelin synthase 1 (SMS1) has been reported to participate in hepatitis and atherosclerosis. However, its role in autoimmune response is not clear. This study investigates the possible involvement of SMS1 in B-cell activation and lupus-like autoimmunity. METHODS:SMS1 knockout lupus-like animal model a...


    pub_type: 杂志文章


    authors: Wang C,Ming B,Wu X,Wu T,Cai S,Hu P,Tang J,Tan Z,Liu C,Zhong J,Zheng F,Dong L

    更新日期:2019-07-01 00:00:00

  • Enriched Brain Omega-3 Polyunsaturated Fatty Acids Confer Neuroprotection against Microinfarction.

    abstract::Cerebral microinfarcts have significant effects on the development of geriatric neurological disorders, including vascular dementia and Alzheimer's disease. However, little is known about the pathophysiological mechanisms involved in the evolution of microinfarcts and potential treatment and prevention against these m...


    pub_type: 杂志文章


    authors: Luo C,Ren H,Yao X,Shi Z,Liang F,Kang JX,Wan JB,Pei Z,Su KP,Su H

    更新日期:2018-06-01 00:00:00

  • Endotype-phenotyping may predict a treatment response in progressive fibrosing interstitial lung disease.

    abstract:BACKGROUND:Some interstitial lung disease (ILD) patients develop a progressive fibrosing-ILD phenotype (PF-ILD), with similar persistent lung function decline suggesting common molecular pathways involved. Nintedanib, a tyrosine kinase inhibitor targeting the PDGF, FGF, VEGF and M-CSF pathways, has shown comparable eff...


    pub_type: 杂志文章


    authors: Hoffmann-Vold AM,Weigt SS,Saggar R,Palchevskiy V,Volkmann ER,Liang LL,Ross D,Ardehali A,Lynch JP 3rd,Belperio JA

    更新日期:2019-12-01 00:00:00

  • An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation.

    abstract:BACKGROUND:Sepsis involves aberrant immune responses to infection, but the exact nature of this immune dysfunction remains poorly defined. Bacterial endotoxins like lipopolysaccharide (LPS) are potent inducers of inflammation, which has been associated with the pathophysiology of sepsis, but repeated exposure can also ...


    pub_type: 杂志文章


    authors: Pena OM,Hancock DG,Lyle NH,Linder A,Russell JA,Xia J,Fjell CD,Boyd JH,Hancock RE

    更新日期:2014-11-01 00:00:00

  • Developed and validated a prognostic nomogram for recurrence-free survival after complete surgical resection of local primary gastrointestinal stromal tumors based on deep learning.

    abstract::This study aimed to develop and validate a prognostic nomogram for recurrence-free survival (RFS) after surgery in the absence of adjuvant therapy to guide the selection for adjuvant imatinib therapy based on Residual Neural Network (ResNet). The ResNet model was developed based on contrast-enhanced computed tomograph...


    pub_type: 杂志文章


    authors: Chen T,Liu S,Li Y,Feng X,Xiong W,Zhao X,Yang Y,Zhang C,Hu Y,Chen H,Lin T,Zhao M,Liu H,Yu J,Xu Y,Zhang Y,Li G

    更新日期:2019-01-01 00:00:00

  • A major role of TWEAK/Fn14 axis as a therapeutic target for post-angioplasty restenosis.

    abstract:BACKGROUND:Tumor necrosis factor-like weak inducer of apoptosis (Tnfsf12; TWEAK) and its receptor Fibroblast growth factor-inducible 14 (Tnfrsf12a; Fn14) participate in the inflammatory response associated with vascular remodeling. However, the functional effect of TWEAK on vascular smooth muscle cells (VSMCs) is not c...


    pub_type: 杂志文章


    authors: Méndez-Barbero N,Gutierrez-Muñoz C,Madrigal-Matute J,Mínguez P,Egido J,Michel JB,Martín-Ventura JL,Esteban V,Blanco-Colio LM

    更新日期:2019-08-01 00:00:00

  • Intra-tumour heterogeneity of diffuse large B-cell lymphoma involves the induction of diversified stroma-tumour interfaces.

    abstract:BACKGROUND:Intra-tumour heterogeneity in lymphoid malignancies encompasses selection of genetic events and epigenetic regulation of transcriptional programs. Clonal-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tis...


    pub_type: 杂志文章


    authors: Sangaletti S,Iannelli F,Zanardi F,Cancila V,Portararo P,Botti L,Vacca D,Chiodoni C,Di Napoli A,Valenti C,Rizzello C,Vegliante MC,Pisati F,Gulino A,Ponzoni M,Colombo MP,Tripodo C

    更新日期:2020-11-01 00:00:00

  • Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated Vasculitis.

    abstract:OBJECTIVE:The objective of our study is to investigate the Fc glycosylation profiles of both antigen-specific IgG targeted against proteinase 3 (PR3-ANCA) and total IgG as prognostic markers of relapse in patients with Granulomatosis with Polyangiitis (GPA). METHODS:Seventy-five patients with GPA and a PR3-ANCA rise d...


    pub_type: 杂志文章


    authors: Kemna MJ,Plomp R,van Paassen P,Koeleman CAM,Jansen BC,Damoiseaux JGMC,Cohen Tervaert JW,Wuhrer M

    更新日期:2017-03-01 00:00:00

  • Integrated epigenomic profiling reveals endogenous retrovirus reactivation in renal cell carcinoma.

    abstract:BACKGROUND:Transcriptional dysregulation drives cancer formation but the underlying mechanisms are still poorly understood. Renal cell carcinoma (RCC) is the most common malignant kidney tumor which canonically activates the hypoxia-inducible transcription factor (HIF) pathway. Despite intensive study, novel therapeuti...


    pub_type: 杂志文章


    authors: Siebenthall KT,Miller CP,Vierstra JD,Mathieu J,Tretiakova M,Reynolds A,Sandstrom R,Rynes E,Haugen E,Johnson A,Nelson J,Bates D,Diegel M,Dunn D,Frerker M,Buckley M,Kaul R,Zheng Y,Himmelfarb J,Ruohola-Baker H,Akiles

    更新日期:2019-03-01 00:00:00

  • An effective vaginal gel to deliver CRISPR/Cas9 system encapsulated in poly (β-amino ester) nanoparticles for vaginal gene therapy.

    abstract:BACKGROUND:Gene therapy has held promises for treating specific genetic diseases. However, the key to clinical application depends on effective gene delivery. METHODS:Using a large animal model, we developed two pharmaceutical formulations for gene delivery in the pigs' vagina, which were made up of poly (β-amino este...


    pub_type: 杂志文章


    authors: Niu G,Jin Z,Zhang C,He D,Gao X,Zou C,Zhang W,Ding J,Das BC,Severinov K,Hitzeroth II,Debata PR,Ma X,Tian X,Gao Q,Wu J,You Z,Tian R,Cui Z,Fan W,Xie W,Huang Z,Cao C,Xu W,Xie H,Xu H,Tang X,Wang Y,Yu Z

    更新日期:2020-08-01 00:00:00

  • Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults.

    abstract:BACKGROUND:T-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and...


    pub_type: 杂志文章


    authors: Coughlan L,Sridhar S,Payne R,Edmans M,Milicic A,Venkatraman N,Lugonja B,Clifton L,Qi C,Folegatti PM,Lawrie AM,Roberts R,de Graaf H,Sukhtankar P,Faust SN,Lewis DJM,Lambe T,Hill A,Gilbert SC

    更新日期:2018-03-01 00:00:00

  • Correcting a Fundamental Flaw in the Paradigm for Antimicrobial Susceptibility Testing.

    abstract::The emergence and prevalence of antibiotic-resistant bacteria are an increasing cause of death worldwide, resulting in a global 'call to action' to avoid receding into an era lacking effective antibiotics. Despite the urgency, the healthcare industry still relies on a single in vitro bioassay to determine antibiotic e...


    pub_type: 杂志文章


    authors: Ersoy SC,Heithoff DM,Barnes L 5th,Tripp GK,House JK,Marth JD,Smith JW,Mahan MJ

    更新日期:2017-06-01 00:00:00

  • MSBIS: A Multi-Step Biomedical Informatics Screening Approach for Identifying Medications that Mitigate the Risks of Metoclopramide-Induced Tardive Dyskinesia.

    abstract::In 2009 the U.S. Food and Drug Administration (FDA) placed a black box warning on metoclopramide (MCP) due to the increased risks and prevalence of tardive dyskinesia (TD). In this study, we developed a multi-step biomedical informatics screening (MSBIS) approach leveraging publicly available bioactivity and drug safe...


    pub_type: 杂志文章


    authors: Xu D,Ham AG,Tivis RD,Caylor ML,Tao A,Flynn ST,Economen PJ,Dang HK,Johnson RW,Culbertson VL

    更新日期:2017-12-01 00:00:00

  • Implementation and use of whole exome sequencing for metastatic solid cancer.

    abstract:BACKGROUND:Genomically-guided clinical trials are performed across different tumor types sharing genetic mutations, but trial organization remains complex. Here we address the feasibility and utility of routine somatic and constitutional exome analysis in metastatic cancer patients. METHODS:Exoma trial (NCT02840604) i...


    pub_type: 临床试验,杂志文章,多中心研究


    authors: Réda M,Richard C,Bertaut A,Niogret J,Collot T,Fumet JD,Blanc J,Truntzer C,Desmoulins I,Ladoire S,Hennequin A,Favier L,Bengrine L,Vincent J,Hervieu A,Dusserre JG,Lepage C,Foucher P,Borg C,Albuisson J,Arnould L,Na

    更新日期:2020-01-01 00:00:00

  • Gut microbiota from colorectal cancer patients enhances the progression of intestinal adenoma in Apcmin/+ mice.

    abstract:BACKGROUND:Accumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma. METHODS:The Apcmin/+ mice gavage with phosphate-buffere...


    pub_type: 杂志文章


    authors: Li L,Li X,Zhong W,Yang M,Xu M,Sun Y,Ma J,Liu T,Song X,Dong W,Liu X,Chen Y,Liu Y,Abla Z,Liu W,Wang B,Jiang K,Cao H

    更新日期:2019-10-01 00:00:00

  • Potent and Selective BACE-1 Peptide Inhibitors Lower Brain Aβ Levels Mediated by Brain Shuttle Transport.

    abstract::Therapeutic approaches to fight Alzheimer's disease include anti-Amyloidβ (Aβ) antibodies and secretase inhibitors. However, the blood-brain barrier (BBB) limits the brain exposure of biologics and the chemical space for small molecules to be BBB permeable. The Brain Shuttle (BS) technology is capable of shuttling lar...


    pub_type: 杂志文章


    authors: Ruderisch N,Schlatter D,Kuglstatter A,Guba W,Huber S,Cusulin C,Benz J,Rufer AC,Hoernschemeyer J,Schweitzer C,Bülau T,Gärtner A,Hoffmann E,Niewoehner J,Patsch C,Baumann K,Loetscher H,Kitas E,Freskgård PO

    更新日期:2017-10-01 00:00:00

  • The Effect of Mutations on Drug Sensitivity and Kinase Activity of Fibroblast Growth Factor Receptors: A Combined Experimental and Theoretical Study.

    abstract::Fibroblast growth factor receptors (FGFRs) are recognized therapeutic targets in cancer. We here describe insights underpinning the impact of mutations on FGFR1 and FGFR3 kinase activity and drug efficacy, using a combination of computational calculations and experimental approaches including cellular studies, X-ray c...


    pub_type: 杂志文章


    authors: Bunney TD,Wan S,Thiyagarajan N,Sutto L,Williams SV,Ashford P,Koss H,Knowles MA,Gervasio FL,Coveney PV,Katan M

    更新日期:2015-03-01 00:00:00

  • Plasma Circulating Extracellular RNAs in Left Ventricular Remodeling Post-Myocardial Infarction.

    abstract::Despite substantial declines in mortality following myocardial infarction (MI), subsequent left ventricular remodeling (LVRm) remains a significant long-term complication. Extracellular small non-coding RNAs (exRNAs) have been associated with cardiac inflammation and fibrosis and we hypothesized that they are associat...


    pub_type: 杂志文章,随机对照试验


    authors: Danielson KM,Shah R,Yeri A,Liu X,Camacho Garcia F,Silverman M,Tanriverdi K,Das A,Xiao C,Jerosch-Herold M,Heydari B,Abbasi S,Van Keuren-Jensen K,Freedman JE,Wang YE,Rosenzweig A,Kwong RY,Das S

    更新日期:2018-06-01 00:00:00

  • Nanoscale regulation of L-type calcium channels differentiates between ischemic and dilated cardiomyopathies.

    abstract:BACKGROUND:Subcellular localization and function of L-type calcium channels (LTCCs) play an important role in regulating contraction of cardiomyocytes. Understanding how this is affected by the disruption of transverse tubules during heart failure could lead to new insights into the disease. METHODS:Cardiomyocytes wer...


    pub_type: 杂志文章


    authors: Sanchez-Alonso JL,Loucks A,Schobesberger S,van Cromvoirt AM,Poulet C,Chowdhury RA,Trayanova N,Gorelik J

    更新日期:2020-07-01 00:00:00

  • Building the Evidence Base of Blood-Based Biomarkers for Early Detection of Cancer: A Rapid Systematic Mapping Review.

    abstract:BACKGROUND:The Early Cancer Detection Consortium is developing a blood-test to screen the general population for early identification of cancer, and has therefore conducted a systematic mapping review to identify blood-based biomarkers that could be used for early identification of cancer. METHODS:A mapping review wit...


    pub_type: 杂志文章,meta分析,评审


    authors: Uttley L,Whiteman BL,Woods HB,Harnan S,Philips ST,Cree IA,Early Cancer Detection Consortium.

    更新日期:2016-08-01 00:00:00