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https://read.qxmd.com/read/30785829/first-line-nivolumab-plus-ipilimumab-in-advanced-non-small-cell-lung-cancer-checkmate-568-outcomes-by-programmed-death-ligand-1-and-tumor-mutational-burden-as-biomarkers
#1
Neal Ready, Matthew D Hellmann, Mark M Awad, Gregory A Otterson, Martin Gutierrez, Justin F Gainor, Hossein Borghaei, Jacques Jolivet, Leora Horn, Mihaela Mates, Julie Brahmer, Ian Rabinowitz, Pavan S Reddy, Jason Chesney, James Orcutt, David R Spigel, Martin Reck, Kenneth John O'Byrne, Luis Paz-Ares, Wenhua Hu, Kim Zerba, Xuemei Li, Brian Lestini, William J Geese, Joseph D Szustakowski, George Green, Han Chang, Suresh S Ramalingam
PURPOSE: CheckMate 568 is an open-label phase II trial that evaluated the efficacy and safety of nivolumab plus low-dose ipilimumab as first-line treatment of advanced/metastatic non-small-cell lung cancer (NSCLC). We assessed the association of efficacy with programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB). PATIENTS AND METHODS: Two hundred eighty-eight patients with previously untreated, recurrent stage IIIB/IV NSCLC received nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks...
February 20, 2019: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://read.qxmd.com/read/30784913/integrated-analysis-of-the-prognostic-value-of-tp53-dependent-etoposide-induced-gene-24-in-non-small-cell-lung-cancer
#2
Maofeng Wang, Peipei Li, Rugen Wan, Xiyong Liu
BACKGROUND: Etoposide-induced gene 24 (EI24) is an induction target of TP53-mediated apoptosis in human cancer cells. The hypothesis of this study is that EI24 might be a prognostic biomarker of non-small cell lung carcinoma (NSCLC). MATERIAL AND METHODS: Fourteen gene expression NSCLC datasets with follow-up information (a total of 2582 accessible cases) were collected from Asia, Europe and North America. The Kaplan-Meier and Cox analyses were applied to evaluate the relation between EI24 and the outcomes of NSCLC...
February 18, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://read.qxmd.com/read/30783512/transforming-growth-factor-%C3%AE-induced-epithelial-to-mesenchymal-signature-predicts-metastasis-free-survival-in-non-small-cell-lung-cancer
#3
Edna Gordian, Eric A Welsh, Nicholas Gimbrone, Erin M Siegel, David Shibata, Ben C Creelan, William Douglas Cress, Steven A Eschrich, Eric B Haura, Teresita Muñoz-Antonia
Transforming growth factor beta (TGFβ) plays a key role in regulating epithelial-to-mesenchymal transition (EMT). A gene expression signature ( TGFβ-EMT ) associated with TGFβ-induced EMT activities was developed using human Non-Small Cell Lung Carcinoma (NSCLC) cells treated with TGFβ-1 and subjected to Affymetrix microarray analysis. The final 105-probeset TGFβ-EMT signature covers 77 genes, and a NanoString assay utilized a subset of 60 of these genes (TGFβ-EMTN signature). We found that the TGFβ-EMT and TGFβ-EMTN gene signatures predicted overall survival (OS) and metastasis-free survival (MFS)...
January 25, 2019: Oncotarget
https://read.qxmd.com/read/30779081/microrna-1205-promotes-cell-growth-by-targeting-apc2-in-lung-adenocarcinoma
#4
B Dai, D-L Kong, J Tian, T-W Liu, H Zhou, Z-F Wang
OBJECTIVE: An increasing amount of evidence indicates that microRNAs (miRNAs) can be potential diagnostic and prognostic markers for various cancers. In this study, a novel miRNA, miR-1205, was identified in lung adenocarcinoma (LUAD). PATIENTS AND METHODS: First, the expression of miR-1205 in tissues was determined and verified to be correlated with the prognosis of patients. Overexpression and knockdown in LUAD cells were chosen to evaluate the effect of miR-1205 on cell growth in vitro...
February 2019: European Review for Medical and Pharmacological Sciences
https://read.qxmd.com/read/30779079/circulating-microrna-array-mir-182-200b-and-205-for-the-early-diagnosis-and-poor-prognosis-predictor-of-non-small-cell-lung-cancer
#5
J-G Zou, L-F Ma, X Li, F-L Xu, X-Z Fei, Q Liu, Q-L Bai, Y-L Dong
OBJECTIVE: Non-small cell lung cancer (NSCLC) is the most common cause for cancer-related mortality worldwide. Currently, early detection of NSCLC is one of the main available strategies for improving its prognosis. Due to the lack of non-invasive and convenient tools, early diagnosis of NSCLC remains poor. Recently, it has been reported that circulating microRNAs (miRNAs) can be stably detected in serum. Meanwhile, they play a powerful role as biomarkers in various tumors. Therefore, the aim of this study was to detect the expression levels of serum miR-182, 200b and 205 in NSCLC patients, and to investigate their diagnostic and prognostic values...
February 2019: European Review for Medical and Pharmacological Sciences
https://read.qxmd.com/read/30778885/targeting-immune-checkpoints-in-lung-cancer-current-landscape-and-future-prospects
#6
REVIEW
Long Long, Chen Zhao, Muqimova Ozarina, Xianda Zhao, Jing Yang, Honglei Chen
Lung cancer is the most prevalent and deadly cancer worldwide. Immune checkpoint therapy, which targets regulatory pathways in T cells to boost anti-tumor immune response, has revolutionized lung cancer treatment paradigms. Inhibitors of the most established immune checkpoints such as programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) have been approved by the US Food and Drug Administration in the management of lung cancer. Despite the pronounced survival benefits that have been seen with immune checkpoint inhibitors, not all lung cancer patients respond to single-agent immunotherapy due to the complexity of the immune microenvironment and tumor resistance...
February 16, 2019: Clinical Drug Investigation
https://read.qxmd.com/read/30777100/challenges-and-potential-of-pd-1-pd-l1-checkpoint-blockade-immunotherapy-for-glioblastoma
#7
REVIEW
Xin Wang, Gaochao Guo, Hui Guan, Yang Yu, Jie Lu, Jinming Yu
PD-1/PD-L1 checkpoint blockades have achieved significant progress in several kinds of tumours. Pembrolizumab, which targets PD-1, has been approved as a first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with positive PD-L1 expression. However, PD-1/PD-L1 checkpoint blockades have not achieved breakthroughs in treating glioblastoma because glioblastoma has a low immunogenic response and an immunosuppressive microenvironment caused by the precise crosstalk between cytokines and immune cells...
February 18, 2019: Journal of Experimental & Clinical Cancer Research: CR
https://read.qxmd.com/read/30777071/a-two-circular-rna-signature-as-a-noninvasive-diagnostic-biomarker-for-lung-adenocarcinoma
#8
Xiao-Xia Liu, Yi-E Yang, Xiao Liu, Meng-Yu Zhang, Rui Li, Yun-Hong Yin, Yi-Qing Qu
BACKGROUND: Recently, circular RNAs (circRNAs) have been reported to be microRNA sponges and play essential roles in cancer development. This study aimed to evaluate whether circulating circRNAs could be used as diagnostic biomarkers for lung adenocarcinoma (LUAD). METHODS: The Gene Expression Omnibus (GEO) dataset was used to investigate differentially expressed circRNAs (DEcircRNAs) in paired LUAD tissues and adjacent nontumor tissues. The expression levels of the host genes were analyzed in The Cancer Genome Atlas (TCGA)-LUAD dataset, and the prognostic value was assessed using the Kaplan-Meier plotter...
February 18, 2019: Journal of Translational Medicine
https://read.qxmd.com/read/30776966/a-comparative-protein-analysis-of-lung-cancer-along-with-three-controls-using-a-multidimensional-proteomic-approach
#9
Mahwish Saleem, Syed K Raza, Syed G Musharraf
A multistep proteomics fractionation strategy was developed and validated for the discovery of proteomic biomarkers which could be used as potential diagnostic biomarkers for monitoring the progression of disease in smokers and COPD patients towards lung cancer.
January 2019: Experimental Biology and Medicine
https://read.qxmd.com/read/30775033/are-there-any-theranostic-biomarkers-in-small-cell-lung-carcinoma
#10
REVIEW
Federica Pezzuto, Francesco Fortarezza, Francesca Lunardi, Fiorella Calabrese
Small cell lung cancer (SCLC), an aggressive lung tumour with a poor prognosis, has a high load of somatic mutations, mainly induced by tobacco carcinogens given the strong association with smoking. Advances in genomic, epigenetic and proteomic profiling have significantly improved our understanding of the molecular and cellular biology of SCLC. Given the high mutational burden of SCLC the immune microenvironment is another exciting area under investigation even if it seems to be quite distinct from that of other solid tumours...
January 2019: Journal of Thoracic Disease
https://read.qxmd.com/read/30775031/update-on-emerging-biomarkers-in-lung-cancer
#11
REVIEW
Eric H Bernicker, Timothy Craig Allen, Phillip T Cagle
There has been considerable progress made in identifying oncogenic driver mutations in advanced lung cancer. The recognition that lung cancer is actually an umbrella classification that is comprised of multiple molecular subgroups has had a profound impact on how medical oncologists make treatment decisions. These mutations are clinically important as available targeted therapies can achieve significant responses and prolonged disease control. This review will summarize the current guidelines for biomarker testing and available therapeutic agents...
January 2019: Journal of Thoracic Disease
https://read.qxmd.com/read/30775030/current-views-on-tumor-mutational-burden-in-patients-with-non-small-cell-lung-cancer-treated-by-immune-checkpoint-inhibitors
#12
REVIEW
Léa Berland, Simon Heeke, Olivier Humbert, Adam Macocco, Elodie Long-Mira, Sandra Lassalle, Virginie Lespinet-Fabre, Salomé Lalvée, Olivier Bordone, Charlotte Cohen, Sylvie Leroy, Véronique Hofman, Paul Hofman, Marius Ilié
In the last few years, the treatment of patients with non-small cell lung cancer (NSCLC) has impressively benefitted from immunotherapy, in particular from the inhibition of immune checkpoints such as programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1). However, despite the significant survival benefit for some patients with advanced NSCLC, the objective response rates (ORRs) remain relatively low no more than 20-30% with a large proportion of patients demonstrating primary resistance...
January 2019: Journal of Thoracic Disease
https://read.qxmd.com/read/30775028/the-challenges-of-evaluating-predictive-biomarkers-using-small-biopsy-tissue-samples-and-liquid-biopsies-from-non-small-cell-lung-cancer-patients
#13
REVIEW
Paul Hofman
The list of theranostic biomarkers for the care of patients with advanced stage or metastatic non-small cell lung cancer has lengthened considerably these last few years. Moreover, the advances in therapeutics will certainly increase the number and complexity of these tests performed in laboratories in the near future. In addition, the methods for investigation of biomarkers that require access to biological tissue are less and less invasive with the consequential increase in the use of small-sized tissue biopsies and cytological and blood samples...
January 2019: Journal of Thoracic Disease
https://read.qxmd.com/read/30775024/mesenchymal-tumors-of-the-lung-diagnostic-pathology-molecular-pathogenesis-and-identified-biomarkers
#14
REVIEW
Hirotsugu Hashimoto, Yuta Tsugeno, Keisuke Sugita, Kentaro Inamura
Lung cancers are mainly composed of epithelial tumors such as carcinomas. Since mesenchymal tumors that arise in the lung are very rare, they have garnered little attention. The 2015 World Health Organization (WHO) classification of lung tumors has undergone revision, not only for carcinomas but also for mesenchymal tumors. The current version now includes PEComatous tumors, myoepithelial tumors, and pulmonary myxoid sarcomas with EWSR1-CREB1 translocation as new disease entities. To date, no review article has comprehensively summarized what is known about pulmonary mesenchymal tumors in accordance with the latest WHO classification...
January 2019: Journal of Thoracic Disease
https://read.qxmd.com/read/30775023/advance-of-theragnosis-biomarkers-in-lung-cancer-from-clinical-to-molecular-pathology-and-biology
#15
REVIEW
Christina Alidousty, Till Baar, Carina Heydt, Svenja Wagener-Ryczek, Anna Kron, Juergen Wolf, Reinhard Buettner, Anne Maria Schultheis
One distinct molecular subtype of non-small cell lung cancer (NSCLC) is defined by rearrangement of the anaplastic lymphoma kinase ( ALK ). The increasing knowledge over the last years has enabled the continuous improvement of ALK inhibitors; however, resistance in these patients remains a major concern. In this review, we summarize recent findings in ALK +-adenocarcinoma of the lung, highlighting the role of TP53 mutations in this specific cancer type and suggest new diagnostic strategies for the future, in order to improve patient's outcome...
January 2019: Journal of Thoracic Disease
https://read.qxmd.com/read/30775022/advances-in-theranostic-biomarkers-for-lung-cancer-from-clinical-to-molecular-pathology
#16
Paul Hofman
No abstract text is available yet for this article.
January 2019: Journal of Thoracic Disease
https://read.qxmd.com/read/30774384/hypertension-as-a-predictive-biomarker-in-patients-with-advanced-non-small-cell-lung-cancer-treated-with-apatinib
#17
Shen-Cun Fang, Wen Huang, Ying-Ming Zhang, Hai-Tao Zhang, Wei-Ping Xie
Background: Hypertension (HTN) is a common adverse event of the vascular endothelial growth factor pathway inhibitor apatinib. This study was conducted to evaluate the association of apatinib-induced HTN with clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC). Methods: We retrospectively analyzed 110 consecutive patients with advanced NSCLC who were treated with apatinib from August 2014 to January 2018. All patients were classified as normotensive or hypertensive based on blood pressure measurements after initiating therapy...
2019: OncoTargets and Therapy
https://read.qxmd.com/read/30772141/a-novel-approach-to-detect-programed-death-ligand-1-pd-l1-status-and-multiple-tumor-mutations-using-a-single-non-small-cell-lung-cancer-nsclc-bronchoscopy-specimen
#18
Amanda Vannitamby, Shona Hendry, Tanvi Makadia, Janine Danks, John Slavin, Louis Irving, Daniel Steinfort, Steven Bozinovski
Multiple biomarkers are under evaluation to guide the use of immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC), including programed death ligand 1 (PD-L1) tumor cell staining. We have developed a new approach that accurately quantifies PD-L1 status and identifies multiple mutations by using a single bronchoscopy specimen. A novel molecular marker was identified to detect the presence of malignant cells in radial endobronchial ultrasound bronchial brushings from NSCLC (n = 15) and benign (n = 13) nodules by quantitative real-time RT-PCR (RT-qPCR)...
February 8, 2019: Journal of Molecular Diagnostics: JMD
https://read.qxmd.com/read/30770789/plod3-suppression-exerts-an-anti-tumor-effect-on-human-lung-cancer-cells-by-modulating-the-pkc-delta-signaling-pathway
#19
Jeong-Hwa Baek, Hong Shik Yun, Gyoo Taik Kwon, Janet Lee, Ju-Young Kim, Yunhui Jo, Jae-Min Cho, Chang-Woo Lee, Jie-Young Song, Jiyeon Ahn, Jae-Sung Kim, Eun Ho Kim, Sang-Gu Hwang
Current lung cancer treatments are far from satisfactory; thus, finding novel treatment targets is crucial. We recently identified procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3), which is involved in fibrosis and tissue remodeling as a radioresistance-related protein in lung cancer cells; however, its mechanism is unclear. In this study, we designed human PLOD3-specific short interfering (si)RNAs and tested their effects on tumor growth inhibition in vitro and in vivo. PLOD3 knockdown overcame chemoresistance and decreased radioresistance by inducing caspase-3-dependent apoptosis in lung cancer cells...
February 15, 2019: Cell Death & Disease
https://read.qxmd.com/read/30764677/prognostic-value-of-rassf1a-methylation-status-in-non-small-cell-lung-cancer-nsclc-patients-a-meta-analysis-of-prospective-studies
#20
Hao Hu, Yuefei Zhou, Min Zhang, Rui Ding
Objective Ras association domain family 1A (RASSF1A) has been regarded as a biomarker predicting the prognosis of non-small cell lung cancer (NSCLC), but previous findings are inconsistent. This meta-analysis of prospective studies aimed to assess the value of RASSF1A methylation in predicting the prognosis of NSCLC patients. Methods Studies were searched in PubMed and Web of Science. The estimates of the effects and the corresponding 95% confidence intervals (95% CIs) were used for the analyses. The overall effects of RASSF1A methylation on overall survival (OS) were estimated, after which subgroup analysis based on regions was conducted...
February 15, 2019: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
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