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https://www.readbyqxmd.com/read/29790668/the-effects-of-aberrant-expression-of-lncrna-dgcr5-mir-873-5p-tusc3-in-lung-cancer-cell-progression
#1
Judong Luo, Hong Zhu, Hua Jiang, Yayun Cui, Mengjie Wang, Xinye Ni, Changsheng Ma
Lung cancer is the most common cause of cancer-related mortality worldwide, and nonsmall cell lung cancer (NSCLC) accounts for 80% of all pulmonary carcinomas. Recently, long noncoding RNAs (lncRNAs) have been paid attention for exploring treatment of various diseases. Upregulation of DiGeorge syndrome critical region gene 5 (DGCR5) predicts better lung squamous cell carcinoma prognosis; therefore, we explore the role of DGCR5 in lung cancer in our present study. Consecutive patients with LC were treated in our hospital between January 2015 and January 2016...
May 23, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29789542/rnf25-promotes-gefitinib-resistance-in-egfr-mutant-nsclc-cells-by-inducing-nf-%C3%AE%C2%BAb-mediated-erk-reactivation
#2
Jung Hee Cho, Yeon-Mi You, Young Il Yeom, Dong Chul Lee, Bo-Kyung Kim, Misun Won, Byoung Chul Cho, Minho Kang, Seulki Park, Suk-Jin Yang, Jang Seong Kim, Jung-Ae Kim, Kyung Chan Park
Non-small cell lung cancer (NSCLC) patients with EGFR mutations initially respond well to EGFR tyrosine kinase inhibitors (TKIs) but eventually exhibit acquired or innate resistance to the therapies typically due to gene mutations, such as EGFR T790M mutation or a second mutation in the downstream pathways of EGFR. Importantly, a significant portion of NSCLC patients shows TKI resistance without any known mechanisms, calling more comprehensive studies to reveal the underlying mechanisms. Here, we investigated a synthetic lethality with gefitinib using a genome-wide RNAi screen in TKI-resistant EGFR-mutant NSCLC cells, and identified RNF25 as a novel factor related to gefitinib resistance...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789295/integration-of-protein-phosphorylation-acetylation-and-methylation-data-sets-to-outline-lung-cancer-signaling-networks
#3
Mark Grimes, Benjamin Hall, Lauren Foltz, Tyler Levy, Klarisa Rikova, Jeremiah Gaiser, William Cook, Ekaterina Smirnova, Travis Wheeler, Neil R Clark, Alexander Lachmann, Bin Zhang, Peter Hornbeck, Avi Ma'ayan, Michael Comb
Protein posttranslational modifications (PTMs) have typically been studied independently, yet many proteins are modified by more than one PTM type, and cell signaling pathways somehow integrate this information. We coupled immunoprecipitation using PTM-specific antibodies with tandem mass tag (TMT) mass spectrometry to simultaneously examine phosphorylation, methylation, and acetylation in 45 lung cancer cell lines compared to normal lung tissue and to cell lines treated with anticancer drugs. This simultaneous, large-scale, integrative analysis of these PTMs using a cluster-filtered network (CFN) approach revealed that cell signaling pathways were outlined by clustering patterns in PTMs...
May 22, 2018: Science Signaling
https://www.readbyqxmd.com/read/29788985/establishment-of-lung-cancer-patient-derived-xenograft-models-and-primary-cell-lines-for-lung-cancer-study
#4
Yanan Jiang, Jimin Zhao, Yi Zhang, Ke Li, Tiepeng Li, Xinhuan Chen, Simin Zhao, Song Zhao, Kangdong Liu, Ziming Dong
BACKGROUND: The overall 5-year survival rate of lung cancer is about 15% even with therapeutic drugs like tyrosine kinase inhibitors. Ideal models are urgently needed for exploring mechanisms and finding new drugs. Patient-derived xenografts (PDX) models and primary cells are both used to screen therapeutic regimens for cancer. However, PDX models and primary cells from the same patient are difficult to establish. Their consistency to the original tumor tissue is not well studied. METHODS: 31 lung cancer patient tissues were procured to establish the lung cancer PDX models and primary cell lines...
May 22, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29788737/diagnosis-for-carcinoma-of-unknown-primary-site-with-the-aid-of-simple-pcr-tests-a-single-center-experience
#5
E Suspitsin, G Yanus, E Imyanitov
This study was aimed to incorporate PCR testing in the determination of organ/tissue origin for cancers of unknown primary site (CUP). We developed a PCR panel consisting of 7 expression markers (CDX2, CDH17, SPB, UGRP, MAM, LPB, TG) and 2 genes frequently mutated in cancer (KRAS and BRAF). The expression tests were intentionally interpreted in a non-quantitative way, i.e. classified tumors either as positive or negative expressors. While applying these tests to 135 cancers belonging to 8 common types of adenocarcinomas (AdCa), we observed that this panel was capable to clearly discriminate between gastrointestinal vs...
March 14, 2018: Neoplasma
https://www.readbyqxmd.com/read/29787863/validity-of-targeted-next-generation-sequencing-in-routine-care-for-identifying-clinically-relevant-molecular-profiles-in-non-small-cell-lung-cancer-results-of-a-2-year-experience-on-1-343-samples
#6
Antoine Legras, Marc Barritault, Anne Tallet, Elizabeth Fabre, Alice Guyard, Bastien Rance, William Digan, Nicolas Pecuchet, Etienne Giroux-Leprieur, Catherine Julie, Stéphane Jouveshomme, Véronique Duchatelle, Véronique Giraudet, Laure Gibault, Alain Cazier, Jean Pastre, Françoise LE Pimpec-Barthes, Pierre Laurent-Puig, Hélène Blons
Theranostic assays are based on single gene testing but the ability of next-generation sequencing (NGS) to interrogate numerous genetic alterations will progressively replace single gene assays. Although NGS was evaluated to screen for theranostic mutations, its usefulness in clinical practice on large series of samples remains to be demonstrated. NGS performance was assessed following guidelines. TaqMan probes and NGS were compared for their ability to detect EGFR and KRAS mutations and NGS mutation profiles were analyzed on a large series of NSCLC (n=1,343)...
May 19, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29786110/multi%C3%A2-layered-prevention-and-treatment-of-chronic-inflammation-organ-fibrosis-and-cancer-associated-with-canonical-wnt-%C3%AE-%C3%A2-catenin-signaling-activation-review
#7
Masaru Katoh
β‑catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E‑cadherin/CDH1, N‑cadherin/CDH2, VE‑cadherin/CDH5 and α‑catenins), transmembrane‑type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulators (BCL9, BCL9L, CREBBP/CBP, EP300/p300, FOXM1, MED12, SMARCA4/BRG1 and TCF/LEF). Gain‑of‑function CTTNB1 mutations are detected in bladder cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer and uterine cancer, whereas loss‑of‑function CTNNB1 mutations are also detected in human cancer...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29784736/targeted-therapy-for-patients-with-metastatic-non-small-cell-lung-cancer
#8
Karen L Reckamp
Molecular testing is recommended for initial diagnosis in patients with non-small cell lung cancer (NSCLC), according to the updated NCCN Guidelines, because targeted therapies are available that can improve patient outcomes. Targeted therapies are currently approved for EGFR mutations, ALK and ROS1 gene rearrangements, and BRAF mutations, with the list of emerging "actionable" targets growing. The 2018 NCCN Guidelines for NSCLC incorporate new therapies, including the EGFR tyrosine kinase inhibitor osimertinib and the ALK inhibitor alectinib, as first-line preferences...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784046/knockdown-of-annexin-a5-restores-gefitinib-sensitivity-by-promoting-g2-m-cell-cycle-arrest
#9
Jian Zhou, Meijia Chang, Jing Li, Tao Fang, Jie Hu, Chunxue Bai
BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, including gefitinib, are first-line drugs against advanced non-small cell lung cancer with activating EGFR mutations. However, the development of resistance to such drugs is a major clinical challenge. METHODS: The role of annexin A5 in resistance to EGFR tyrosine kinase inhibitors was investigated by qPCR and western blot of relevant molecules, by CCK8 and EdU assay of cell proliferation and viability, by annexin V/propidium iodide assay of apoptosis and cell cycle distribution, by JC-1 assay of mitochondrial integrity, and by xenograft assay of tumorigenicity...
May 21, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29781034/specific-inhibitor-of-notch%C3%A2-3-enhances-the-sensitivity-of-nsclc-cells-to-gemcitabine
#10
Bi-Dan Hu, Jia Guo, Yuan-Zi Ye, Ting Du, Chun-Song Cheng, Qian Jiang, Ruo-Nan Liu, Yan-Bei Zhang
Notch‑3 is a receptor of the Notch signaling pathway and plays an important role in regulating self‑renewal, differentiation and apoptosis in cancer cells. Overexpression of Notch‑3 has been proved to be associated with resistance to gemcitabine (GEM) and poor patient prognosis for various malignant tumors. In the present study, two non‑small cell lung cancer (NSCLC) cell lines, H1299 and A549, were induced with GEM for two months and then were treated with various concentrations of a Notch signaling blocker, N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (DAPT), with the goal of reducing expression of Notch intracellular domain 3 (NICD3)...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29780628/comprehensive-targeted-super-deep-next-generation-sequencing-enhances-differential-diagnosis-of-solitary-pulmonary-nodules
#11
Mingzhi Ye, Shiyong Li, Weizhe Huang, Chunli Wang, Liping Liu, Jun Liu, Jilong Liu, Hui Pan, Qiuhua Deng, Hailing Tang, Long Jiang, Weizhe Huang, Xi Chen, Di Shao, Zhiyu Peng, Renhua Wu, Jing Zhong, Zhe Wang, Xiaoping Zhang, Karsten Kristiansen, Jian Wang, Ye Yin, Mao Mao, Jianxing He, Wenhua Liang
Background: A non-invasive method to predict the malignancy of surgery-candidate solitary pulmonary nodules (SPN) is urgently needed. Methods: Super-depth next generation sequencing (NGS) of 35 paired tissues and plasma DNA was performed as an attempt to develop an early diagnosis approach. Results: Only ~6% of malignant nodule patients had driver mutations in the circulating tumour DNA (ctDNA) with >10,000-fold sequencing depth, and the concordance of mutation between tDNA and ctDNA was 3...
April 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29780256/the-utilization-of-next-generation-sequencing-to-detect-somatic-mutations-and-predict-clinical-prognosis-of-chinese-non-small-cell-lung-cancer-patients
#12
Liming Cao, Long Long, Min Li, Huaping Yang, Pengbo Deng, Xinru Mao, Jianxing Xiang, Bing Li, Tengfei Zhang, Chengping Hu
Purpose: The development of next-generation sequencing (NGS) has revolutionized the understanding of oncogenesis of multiple types of cancer, including non-small cell lung cancer (NSCLC). However, there has been some debate over the utility of NGS for predicting patient prognosis and determining molecular targeted therapy. Therefore, we sought to demonstrate the numerous applications of NGS in the prognostic predictions and treatment of NSCLC patients. Materials and methods: We performed NGS on either liquid or tissue tumor biopsies obtained from 53 NSCLC patients...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29778561/severe-xanthomatosis-in-heterozygous-familial-hypercholesterolemia
#13
Sumayah Aljenedil, Isabelle Ruel, Kevin Watters, Jacques Genest
BACKGROUND: Familial hypercholesterolemia is a genetic lipoprotein disorder characterized by elevated plasma low-density lipoprotein cholesterol level, (tendinous xanthomas, xanthelasmas, and premature arcus corneus) and early onset atherosclerotic cardiovascular disease. Familial hypercholesterolemia is caused by mutations in the low-density lipoprotein receptor, apolipoprotein B or proprotein convertase subtilisin/kexin type 9 genes. Rare mutations in low-density lipoprotein receptor adapter protein 1, APOE p...
April 3, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29777906/reduced-rar-%C3%AE-gene-expression-in-benzo-a-pyrene-induced-lung-cancer-mice-is-upregulated-by-dotap-lipo-atra-treatment
#14
S Viswanathan, V M Berlin Grace
Molecular targeted therapy for specific genes is an emerging research. Retinoic Acid Receptor (RAR-β) is a key tumor suppressor which is found to be lost drastically during much cancer progression. We hence, analyzed the expression level of RAR-β gene during B(a)P induced lung cancer development in mice and studied the lung cancer targeted action of All Trans Retinoic Acid (ATRA) in DOTAP liposomal formulation. The effect of its treatment on lung cancer was determined by histopathological analysis. RAR-β gene expression was assessed by RT-PCR and qPCR...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29777599/immense-random-colocalization-revealed-by-automated-high-content-image-cytometry-seriously-questions-fish-as-gold-standard-for-detecting-eml4-alk-fusion
#15
Gábor Smuk, Tamás Tornóczky, László Pajor, Ilse Chudoba, Béla Kajtár, Veronika Sárosi, Gábor Pajor
EML4-ALK gene fusion (inv2(p21p23)) of non-small cell lung cancer (NSCLC) predisposes to tyrosine kinase inhibitor treatment. One of the gold standard diagnostics is the dual color (DC) break-apart (BA) FISH technique, however, the unusual closeness of the involved genes has been suggested to raise likelihood of random co-localization (RCL) of signals. Although this is suspected to decrease sensitivity (often to as low as 40-70%), the exact level and effect of RCL has not been revealed thus far. Signal distances were analyzed to the 0...
May 19, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/29777315/the-mdm2-rs937283-a-g-variant-significantly-increases-the-risk-of-lung-and-gastric-cancer-in-chinese-population
#16
Bifeng Chen, Jieling Wang, Yucan Chen, Xiuli Gu, Xianhong Feng
BACKGROUND: Currently, the MDM2 promoter rs937283 A > G variant that is able to alter MDM2 gene expression has been widely studied to explore the association of MDM2 with cancer risk. In this report, we investigate the association of MDM2 rs937283 A > G variant with risk of lung cancer (LC) and gastric cancer (GC) in a Chinese population of Hubei province, which was followed by a meta-analysis. METHODS: The genotyping of rs937283 was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing...
May 18, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29776956/integrin-%C3%AE-3-inhibition-enhances-the-antitumor-activity-of-alk-inhibitor-in-alk-rearranged-nsclc
#17
Ka-Won Noh, Insuk Sohn, Ji-Young Song, Hyun-Tae Shin, Yu Jin Kim, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Se-Hoon Lee, Mi-Sook Lee, Yoon-La Choi
BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive cancers are sensitive to small molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication. PATIENTS AND METHODS: We screened ALK-rearranged non-small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence in situ hybridization, and then conducted multiplex gene expression analysis...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29776953/the-landscape-of-actionable-genomic-alterations-in-cell-free-circulating-tumor-dna-from-21-807-advanced-cancer-patients
#18
Oliver A Zill, Kimberly C Banks, Stephen R Fairclough, Stefanie Mortimer, James V Vowles, Reza Mokhtari, David R Gandara, Philip C Mack, Justin I Odegaard, Rebecca J Nagy, Arthur M Baca, Helmy Eltoukhy, Darya I Chudova, Richard B Lanman, AmirAli Talasaz
PURPOSE: Cell-free DNA (cfDNA) sequencing provides a non-invasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants. Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across >50 cancer types...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29775598/selective-cytotoxicity-of-the-nampt-inhibitor-fk866-toward-gastric-cancer-cells-with-markers-of-the-epithelial-mesenchymal-transition-due-to-loss-of-naprt
#19
Jooyoung Lee, Hyosil Kim, Jae Eun Lee, Su-Jin Shin, Sejin Oh, Sungjin Kwon, Hakhyun Kim, Yoon Young Choi, Michael A White, Soonmyung Paik, Jae-Ho Cheong, Hyun Seok Kim
BACKGROUND & AIMS: Markers of the epithelial-mesenchymal transition (EMT) in gastric tumor tissues are associated with poor outcomes of patients. We performed a screen to identify pharmacologic compounds that kill gastric cancer cells with EMT-associated gene expression patterns and investigate their mechanisms. METHODS: We identified 29 gastric cancer cell lines with gene expression signature previously associated with an EMT subtype, based on data from RNA sequence analyses, and confirmed their mesenchymal phenotypes of 7 lines (Hs746T, SNU1750, MKN1, SK4, SNU484, SNU668, and YCC11), based in invasive activity and protein markers...
May 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29775400/evaluating-the-cytotoxicity-of-tin-dioxide-nanofibers
#20
Ashley S Reynolds, Tanya H Pierre, Rebecca McCall, Ji Wu, Worlanyo E Gato
Tin dioxide nanofibers (SnDNFs) are small fibers that have many applications. Tin dioxide nanofibers can be used in cosmetics, solar cells, toxic gas release sensors, and air pollution control. To date there have been few studies on the cytotoxicity of SnDNFs. The goal of this research is to determine if electrospun SnDNFs are toxic in a lung cancer cell line (A549). Considering the nano-scale size of the fibers, they can easily be inhaled and enter the pulmonary system and cause toxic effects in the lung. Occupational exposure to SnDNFs has been linked to pulmonary disease, making the A549 cell line important in this study...
May 18, 2018: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
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