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https://www.readbyqxmd.com/read/28214182/opportunistic-autoimmunity-secondary-to-cancer-immunotherapy-oasi-an-emerging-challenge
#1
M Kostine, L Chiche, E Lazaro, P Halfon, C Charpin, D Arniaud, F Retornaz, P Blanco, N Jourde-Chiche, C Richez, C Stavris
With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28213726/pd-1-and-pd-l1-antibodies-in-cancer-current-status-and-future-directions
#2
REVIEW
Arjun Vasant Balar, Jeffrey S Weber
Immunotherapy has moved to the center stage of cancer treatment with the recent success of trials in solid tumors with PD-1/PD-L1 axis blockade. Programmed death-1 or PD-1 is a checkpoint molecule on T cells that plays a vital role in limiting adaptive immune responses and preventing autoimmune and auto-inflammatory reactivity in the normal host. In cancer patients, PD-1 expression is very high on T cells in the tumor microenvironment, and PD-L1, its primary ligand, is variably expressed on tumor cells and antigen-presenting cells within tumors, providing a potent inhibitory influence within the tumor microenvironment...
February 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28212736/tap73-upregulates-il-1%C3%AE-in-cancer-cells-potential-biomarker-in-lung-and-breast-cancer
#3
Polina Vikhreva, Varvara Petrova, Tarik Gokbulut, Ilias Pestlikis, Mara Mancini, Nicola Di Daniele, Richard A Knight, Gerry Melino, Ivano Amelio
p73 is a transcription factor belonging to the p53 tumour suppressor family. p73(-/-) mice exhibit a range of phenotypes including neurological, reproductive and inflammatory defects. Although the role of p73 in the control of genomic stability explains part of these phenotypes, a clear mechanism of how p73 participates in the inflammatory response is still elusive. Interleukin-1β (IL-1β) has a crucial role in mediating the inflammatory response. Because of its high potency to induce inflammation, the activation and secretion of IL-1β is tightly regulated by large protein complexes, named inflammasomes...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#4
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211159/dda1-a-novel-oncogene-promotes-lung-cancer-progression-through-regulation-of-cell-cycle
#5
Lin Cheng, Qianmei Yang, Can Li, Lei Dai, Yang Yang, Qingnan Wang, Yu Ding, Junfeng Zhang, Lei Liu, Shuang Zhang, Ping Fan, Xun Hu, Rong Xiang, Dechao Yu, Yuquan Wei, Hongxin Deng
Lung cancer is globally widespread and associated with high morbidity and mortality. DDA1 (DET1 and DDB1 associated 1) was first discovered and registered in the GenBank database by our colleagues. DDA1, an evolutionarily conserved gene, might have significant functions. Recent reports have demonstrated that DDA1 is linked to the ubiquitin-proteasome pathway and facilitates the degradation of target proteins. However, the function of DDA1 in lung cancer was previously unknown. This study aimed to investigate whether DDA1 contributes to tumorigenesis and progression of lung cancer...
February 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28209906/first-evaluation-of-pet-based-human-biodistribution-and-dosimetry-of-18-f-faza-a-tracer-for-imaging-tumor-hypoxia
#6
Savi Annarita, Elena Incerti, Federico Fallanca, Valentino Bettinardi, Francesca Rossetti, Cristina Monterisi, Antonia Compierchio, Giampiero Negri, Piero Zannini, Luigi Gianolli, Maria Picchio
Fluorine-18 labelled fluoroazomycinarabinoside ((18)F-FAZA) is a positron emission tomography (PET) biomarker for non-invasive identification of regional tumor hypoxia. Aim of the present Phase I study was to firstly evaluate in non-small cell lung cancer patients the human biodistribution and dosimetry of (18)F-FAZA. Methods: Five patients awaiting surgical resection after histologically proven or radiologically suspected non-small cell lung cancer were prospectively enrolled for the study. The patients underwent a PET/computed tomography (CT) study after the injection of 371±32 MBq of (18)F-FAZA...
February 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28208308/ultrasensitive-surface-enhanced-raman-scattering-sensor-of-gaseous-aldehydes-as-biomarkers-of-lung-cancer-on-dendritic-ag-nanocrystals
#7
Zhen Zhang, Wei Yu, Jing Wang, Dan Luo, Xuezhi Qiao, Xiaoyun Qin, Tie Wang
Surface-enhanced Raman scattering (SERS) is expected as a technique that even theoretically detected chemicals at the single molecule level by surface plasmon phenomena of noble metal nanostructures. Insensitivity of detecting Raman weak-intensity molecules and low adsorptivity of gaseous molecules on solid substrates are two main factors hindering the application of SERS in gas detectors. In this manuscript, we demonstrated an operational SERS strategy to detect gaseous Raman weak-intensity aldehydes that have been considered as a biomarker of lung cancer for abnormal content was measured in volatile organic compounds (VOCs) of lung cancer patients...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28207525/plasma-levels-of-soluble-programmed-death-ligand-1-may-be-associated-with-overall-survival-in-nonsmall-cell-lung-cancer-patients-receiving-thoracic-radiotherapy
#8
Jing Zhao, Peng Zhang, Jianhua Wang, Qingsong Xi, Xueqi Zhao, Minghua Ji, Guangyuan Hu
Immune-checkpoint signaling plays an important role in immunosuppression of tumors. We aimed to investigate the association of soluble programmed death-ligand 1 (sPD-L1) level in plasma with overall survival (OS) in locally advanced or inoperable nonsmall-cell lung cancer (NSCLC) patients treated with thoracic radiotherapy (TRT). We used ELISA to evaluate the sPD-L1 levels at diagnosis and during TRT in 126 clinically inoperable NSCLC patients. OS rates were followed up and recorded. SPSS software and GraphPad Prism 5 were used for statistics...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28204826/pathway-deviation-based-biomarker-and-multi-effect-target-identification-in-asbestos-related-squamous-cell-carcinoma-of-the-lung
#9
Jiang Du, Lin Zhang
Asbestos-related lung carcinoma is one of the most devastating occupational cancers, and effective techniques for early diagnosis are still lacking. In the present study, a systematic approach was applied to detect a potential biomarker for asbestos-related lung cancer (ARLC); in particular asbestos-related squamous cell carcinoma (ARLC-SCC). Microarray data (GSE23822) were retrieved from the Gene Expression Omnibus database, including 26 ARLC-SCCs and 30 non-asbestos-related squamous cell lung carcinomas (NARLC-SCCs)...
February 6, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28203405/weighted-gene-co-expression-network-analysis-in-identification-of-metastasis-related-genes-of-lung-squamous-cell-carcinoma-based-on-the-cancer-genome-atlas-database
#10
Feng Tian, Jinlong Zhao, Xinlei Fan, Zhenxing Kang
BACKGROUND: Lung squamous cell carcinoma (lung SCC) is a common type of malignancy. Its pathogenesis mechanism of tumor development is unclear. The aim of this study was to identify key genes for diagnosis biomarkers in lung SCC metastasis. METHODS: We searched and downloaded mRNA expression data and clinical data from The Cancer Genome Atlas (TCGA) database to identify differences in mRNA expression of primary tumor tissues from lung SCC with and without metastasis...
January 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28202521/ex-vivo-explant-cultures-of-non-small-cell-lung-carcinoma-enable-evaluation-of-primary-tumor-responses-to-anticancer-therapy
#11
Ellie Karekla, Wen-Jing Liao, Barry Sharp, John Pugh, Helen Reid, John Pc Le Quesne, David Moore, Catrin A Pritchard, Marion MacFarlane, J Howard Pringle
To improve treatment outcomes in non-small cell lung cancer (NSCLC), preclinical models that can better predict individual patient response to novel therapies are urgently needed. Using freshly resected tumor tissue, we describe an optimized ex vivo explant culture model that enables concurrent evaluation of NSCLC response to therapy while maintaining the tumor microenvironment. We found that ~70% of primary NSCLC specimens were amenable to explant culture with tissue integrity intact for up to 72 hours after explant...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28200038/comprehensive-evaluation-of-published-gene-expression-prognostic-signatures-for-biomarker-based-lung-cancer-clinical-studies
#12
H Tang, S Wang, G Xiao, J Schiller, V Papadimitrakopoulou, J Minna, I I Wistuba, Y Xie
No abstract text is available yet for this article.
February 14, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28198463/overexpression-of-fam83h-as1-indicates-poor-patient-survival-and-knockdown-impairs-cell-proliferation-and-invasion-via-met-egfr-signaling-in-lung-cancer
#13
Jie Zhang, Shumei Feng, Wenmei Su, Shengbin Bai, Lei Xiao, Lihui Wang, Dafydd G Thomas, Jules Lin, Rishindra M Reddy, Philip W Carrott, William R Lynch, Andrew C Chang, David G Beer, You-Min Guo, Guoan Chen
Whole transcriptome analyses of next generation RNA sequencing (RNA-Seq) data from human cancer samples reveled thousands of uncharacterized non-coding RNAs including long non-coding RNA (lncRNA). Recent studies indicated that lncRNAs are emerging as crucial regulators in cancer processes and potentially useful as biomarkers for cancer diagnosis and prognosis. To delineate dysregulated lncRNAs in lung cancer, we analyzed RNA-Seq data from 461 lung adenocarcinomas (LUAD) and 156 normal lung tissues. FAM83H-AS1, one of the top dysregulated lncRNAs, was found to be overexpressed in tumors relative to normal lung and significantly associated with worse patient survival in LUAD...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198450/identification-of-methylation-driven-differentially-expressed-stxbp6-as-a-novel-biomarker-in-lung-adenocarcinoma
#14
Govinda Lenka, Mong-Hsun Tsai, Hsin-Chieh Lin, Jen-Hao Hsiao, Yi-Ching Lee, Tzu-Pin Lu, Jang-Ming Lee, Chung-Ping Hsu, Liang-Chuan Lai, Eric Y Chuang
DNA methylation is an essential epigenetic marker associated with the silencing of gene expression. Although various genome-wide studies revealed aberrantly methylated gene targets as molecular biomarkers for early detection, the survival rate of lung cancer patients is still poor. In order to identify methylation-driven biomarkers, genome-wide changes in DNA methylation and differential expression in 32 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined. This concurrent analysis identified 21 negatively correlated probes (r ≤ -0...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197929/epithelial-mesenchymal-transition-emt-and-non-small-cell-lung-cancer-nsclc-a-mutual-association-with-airway-disease
#15
Malik Quasir Mahmood, Chris Ward, Hans Konrad Muller, Sukhwinder Singh Sohal, Eugene Haydn Walters
NSCLC is a leading cause of morbidity and mortality worldwide. It includes adeno- and squamous cell carcinoma. In the background, COPD and smoking play a vital role in development of NSCLC. Local progression and metastasis of NSCLC has been associated with various mechanisms, but in particular by a process called epithelial mesenchymal transition (EMT), which is implicated in COPD pathogenesis. In this study, we have investigated whether expression of EGFR (activation marker) and S100A4, vimentin and N-cadherin (as EMT) is different both in central and leading edge of NSCLC and to what extent related to EMT activity of both small and large airways, stage and differentiation of NSCLC...
March 2017: Medical Oncology
https://www.readbyqxmd.com/read/28197634/sirt3-is-correlated-with-the-malignancy-of-non-small-cell-lung-cancer
#16
Yanlu Xiong, Mingxing Wang, Jinbo Zhao, Lei Wang, Xiaofei Li, Zhipei Zhang, Lintao Jia, Yong Han
The mitochondrial deacetylase SIRT3 plays a pivotal role in the initiation and the progression of certain cancers acting as an oncogene. However, in others it acts anti-oncogenically. Its conflicting action is possibly due to the different key proteins it modifies depending on the context of active intracellular signaling pathways in different cancers. SIRT3 is thus a novel target for preventing and treating cancer. In the present study, we explored the function of SIRT3 in non-small cell lung cancer (NSCLC) with the aim of elucidating the underlying mechanisms...
February 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28197383/analysis-of-the-prognostic-role-of-an-immune-checkpoint-score-in-resected-non-small-cell-lung-cancer-patients
#17
Marta Usó, Eloísa Jantus-Lewintre, Silvia Calabuig-Fariñas, Ana Blasco, Eva García Del Olmo, Ricardo Guijarro, Miguel Martorell, Carlos Camps, Rafael Sirera
Tumors develop mechanisms to recruit tolerogenic immune cells and to induce the expression of molecules that act as immune checkpoints. This regulation of the immune microenvironment favors immune tolerance to the neoplastic cells. In this study, we have investigated the prognostic role of immune-checkpoint expression markers in a cohort of resectable non-small cell lung cancer (NSCLC) patients. RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) (n = 178). RTqPCR was performed to analyze the relative expression of 20 immune-related genes that were normalized by the use of endogenous genes selected by GeNorm algorithm...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197362/prognostic-impact-of-the-expression-of-ncr1-and-ncr3-nk-cell-receptors-and-pd-l1-on-advanced-non-small-cell-lung-cancer
#18
Laetitia Fend, Sylvie Rusakiewicz, Julien Adam, Bérangère Bastien, Anne Caignard, Meriem Messaoudene, Christina Iribarren, Isabelle Cremer, Aurélien Marabelle, Christophe Borg, Michaela Semeraro, Luc Barraud, Jean-Marc Limacher, Alexander Eggermont, Guido Kroemer, Laurence Zitvogel
The putative contribution of natural killer (NK) cells to immunosurveillance in non-small cell lung cancer (NSCLC) has been an ongoing conundrum. Here, we used a readily standardizable quantitative real time polymerase chain reaction (qRT-PCR) to measure the expression of NK cell receptors in total peripheral blood mononuclear cells (PBMC) from healthy volunteers (HV), patients with gastrointestinal stromal tumors (GIST), neuroblastoma (NB), melanoma or NSCLC. We quantified NCR1 (which codes for NKp46) and NCR3 (which codes for NKp30), as well as that of three NCR3 splice variants (which give rise to immunostimulatory NKp30A and NKp30B, as well as to immunosuppressive NKp30C)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196872/muc16-regulates-tspyl5-for-lung-cancer-cell-growth-and-chemoresistance-by-suppressing-p53
#19
Imayavaramban Lakshmanan, Shireen Salfity, Parthasarathy Seshacharyulu, Satyanarayana Rachagani, Abigail Thomas, Srustidhar Das, Prabin D Majhi, Rama Krishna Nimmakayala, Raghupathy Vengoji, Subodh M Lele, Moorthy P Ponnusamy, Surinder K Batra, Apar Kishor Ganti
PURPOSE: MUC16, a tumor biomarker and cell surface associated mucin, is overexpressed in various cancers; however, its role in lung cancer pathogenesis is unknown. Here, we have explored the mechanistic role of MUC16 in lung cancer. EXPERIMENTAL DESIGN: To identify the functional role of MUC16, stable knockdown was carried in lung cancer cells with two different shRNAs. Clinical significance of MUC16 was evaluated in lung cancer patient's tissues using IHC. We have generated genetically engineered mouse model (KrasG12D; AdCre) to evaluate the preclinical significance of MUC16...
February 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28196386/-liquid-biopsy-detection-of-molecular-markers-for-treatment-decisions-in-lung-cancer
#20
W M Brückl, R M Wirtz, T Bertsch, J H Ficker, A Jung
Personalized, individualized, targeted therapy has successfully found entrance in the palliative treatment of lung cancer as they enable a personalized and individualized strategy going ahead with biomarker testing. Due to the crescending amount of predictive molecular and immunhistochemical analyses at different time points during therapy the need for more and actual tumor tissue increases; however these samples cannot always be obtained without major discomfort for the patients. Therefore, analyses from blood, the so called "liquid biopsy", is an alternative or additional method...
February 14, 2017: Pneumologie
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