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Lung genetics

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https://www.readbyqxmd.com/read/28212155/molecular-markers-in-lung-cancer-role-of-ebus
#1
Semra Bilaçeroğlu
PURPOSE OF REVIEW: As demonstrated by the recent therapeutic advances in nonsmall cell lung cancer (NSCLC), a personalized approach can considerably reduce its mortality. RECENT FINDINGS: Molecular tests identifying genetic mutations in NSCLC have led to a shift towards more effective and personalized therapies targeted to these alterations. Adequate tissue is required for diagnosing, subcharacterizing, and genotyping NSCLC by morphological, immunohistochemical, and molecular techniques...
February 16, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28211871/expression-level-is-a-key-determinant-of-e2f1-mediated-cell-fate
#2
Igor Shats, Michael Deng, Adam Davidovich, Carolyn Zhang, Jungeun S Kwon, Dinesh Manandhar, Raluca Gordân, Guang Yao, Lingchong You
The Rb/E2F network has a critical role in regulating cell cycle progression and cell fate decisions. It is dysfunctional in virtually all human cancers, because of genetic lesions that cause overexpression of activators, inactivation of repressors, or both. Paradoxically, the downstream target of this network, E2F1, is rarely strongly overexpressed in cancer. E2F1 can induce both proliferation and apoptosis but the factors governing these critical cell fate decisions remain unclear. Previous studies have focused on qualitative mechanisms such as differential cofactors, posttranslational modification or state of other signaling pathways as modifiers of the cell fate decisions downstream of E2F1 activation...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28211612/genetic-variants-in-the-plasminogen-activator-inhibitor-1-gene-are-associated-with-an-increased-risk-of-radiation-pneumonitis-in-lung-cancer-patients
#3
Bo Liu, Yang Tang, Minxiao Yi, Qingxu Liu, Huihua Xiong, Guangyuan Hu, Xianglin Yuan
Plasminogen activator inhibitor-1 (PAI-1) plays a crucial role in the process of lung injury, although its association with radiation pneumonitis (RP) is unclear. We hypothesized that genetic variants in PAI-1 may influence the risk of RP. In this study, 169 lung cancer patients were genotyped for six single-nucleotide polymorphisms in PAI-1 using the Sequenom MassARRAY system. The risk of RP was evaluated by Cox proportional hazards analyses. The cumulative RP probabilities by genotype were assessed using Kaplan-Meier analyses...
February 17, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28209717/autophagy-metabolism-and-cancer
#4
Jessie Yanxiang Guo, Eileen White
Macroautophagy (autophagy hereafter) is a process that collects cytoplasmic components, particularly mitochondria, and degrades them in lysosomes. In mammalian systems, basal autophagy levels are normally low but are profoundly stimulated by starvation and essential for survival. Cancer cells up-regulate autophagy and can be more autophagy-dependent than most normal tissues. Genetic deficiency in essential autophagy genes in tumors in many autochthonous mouse models for cancer reduces tumor growth. In K-ras(G12D)-driven non-small cell lung cancer (NSCLC) and other models, autophagy sustains metabolism and survival...
February 16, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28207789/carbapenem-resistance-and-pathogenicity-of-bovine-acinetobacter-indicus-like-isolates
#5
Peter Klotz, Stephan Göttig, Ursula Leidner, Torsten Semmler, Sandra Scheufen, Christa Ewers
The objective of this study was to characterize blaOXA-23 harbouring Acinetobacter indicus-like strains from cattle including genomic and phylogenetic analyses, antimicrobial susceptibility testing and evaluation of pathogenicity in vitro and in vivo. Nasal and rectal swabs (n = 45) from cattle in Germany were screened for carbapenem-non-susceptible Acinetobacter spp. Thereby, two carbapenem resistant Acinetobacter spp. from the nasal cavities of two calves could be isolated. MALDI-TOF mass spectrometry and 16S rDNA sequencing identified these isolates as A...
2017: PloS One
https://www.readbyqxmd.com/read/28206909/a-highly-pathogenic-avian-derived-influenza-virus-h5n1-with-2009-pandemic-h1n1-internal-genes-demonstrates-increased-replication-and-transmission-in-pigs
#6
Eugenio J Abente, Pravina Kitikoon, Kelly M Lager, Phillip C Gauger, Tavis K Anderson, Amy L Vincent
This study investigated the pathogenicity and transmissibility of a reverse-genetics-derived highly pathogenic avian influenza (HPAI) H5N1 lineage influenza A virus that was isolated from a human, A/Iraq/755/06. We also examined surface gene reassortant viruses composed of the haemagglutinin and neuraminidase from A/Iraq/755/06 and the internal genes of a 2009 pandemic H1N1 virus, A/New York/18/2009 (2Iraq/06 : 6NY/09 H5N1), and haemagglutinin and neuraminidase from A/New York/18/2009 with the internal genes of A/Iraq/755/06 (2NY/09 : 6Iraq/06 H1N1)...
January 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28205526/association-evidence-of-ccttt-repeat-polymorphism-in-the-inos-promoter-and-the-risk-of-atrial-fibrillation-in-taiwanese
#7
Lung-An Hsu, Yung-Hsin Yeh, Wei-Jan Chen, Chi-Tai Kuo, Feng-Chun Tsai, Yi-Hsin Chan, Chun-Li Wang, Chi-Jen Chang, Hsin-Yi Tsai
Inducible nitric oxide synthase (iNOS) plays an important role in the pathogenesis of atrial fibrillation (AF). The iNOS promoter has a CCTTT-repeat length polymorphism that can determine the level of gene transcription. This study enrolled 200 AF patients and 240 controls. The length of CCTTT-repeat polymorphism in the iNOS promoter region was examined by polymerase chain reactions, with the alleles with ≤11 repeats designated as S and alleles with ≥12 repeats designated as L alleles. AF patients carried significantly higher frequencies of the LL genotype than control subjects (40...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203297/therapeutic-approach-to-treating-patients-with-braf-mutant-lung-cancer-latest-evidence-and-clinical-implications
#8
REVIEW
Adrianus J de Langen, Egbert F Smit
Lung adenocarcinoma is known for its high rate of somatic mutations and genomic rearrangements. The identification of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements that sensitize tumors to specific drugs has changed the therapeutic approach and prognosis in these molecularly-defined subgroups. Several other key genetic alterations have been identified, of which BRAF mutations are found in 4% of non-small cell lung cancer (NSCLC) cases. Targeted drugs against BRAF and downstream MEK were recently approved for the treatment of BRAF-positive melanoma and have entered clinical evaluation in NSCLC...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28202524/scavenger-receptor-a1-prevents-metastasis-of-non-small-cell-lung-cancer-via-suppression-of-macrophage-serum-amyloid-a1
#9
Yan Zhang, Yongyue Wei, Bin Jiang, Lili Chen, Hui Bai, Xudong Zhu, Xiaoyu Li, Hanwen Zhang, Qing Yang, Junqing Ma, Yong Xu, Jingjing Ben, David C Christiani, Qi Chen
Mechanisms of crosstalk between tumor cells and tumor-associated macrophages (TAM) which drive metastasis are not fully understood. Scavenger receptor A1 (SR-A1) expressed primarily in macrophages has been associated with lung tumorigenesis. In this study, we used population genetics, transcriptomics and functional analyses to uncover how SR-A1 is involved in lung cancer and its prognosis. SR-A1 genetic variants were investigated for possible association with survival of advanced-stage NSCLC patients in the Harvard Lung Cancer Study cohort...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202516/modeling-the-genetic-regulation-of-cancer-metabolism-interplay-between-glycolysis-and-oxidative-phosphorylation
#10
Linglin Yu, Mingyang Lu, Dongya Jia, Jianpeng Ma, Eshel Ben-Jacob, Herbert Levine, Benny A Kaipparettu, Jose' N Onuchic
Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred to as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays a crucial role during cancer progression. Here we utilized a systems biology approach to decipher the regulatory principle of glycolysis and OXPHOS. Integrating information from literature, we constructed a regulatory network of genes and metabolites from which we extracted a core circuit containing HIF-1, AMPK, and ROS...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28200116/microrna-related-genetic-variants-in-iron-regulatory-genes-dietary-iron-intake-micrornas-and-lung-cancer-risk
#11
L Zhang, Y Ye, H Tu, M A Hildebrandt, L Zhao, J V Heymach, J A Roth, X Wu
No abstract text is available yet for this article.
February 13, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28199989/presence-of-cancer-associated-mutations-in-exhaled-breath-condensates-of-healthy-individuals-by-next-generation-sequencing
#12
Omar Youssef, Aija Knuuttila, Päivi Piirilä, Tom Böhling, Virinder Sarhadi, Sakari Knuutila
Exhaled breath condensate (EBC) is a non-invasive source that can be used for studying different genetic alterations occurring in lung tissue. However, the low yield of DNA available from EBC has hampered the more detailed mutation analysis by conventional methods. We applied the more sensitive amplicon-based next generation sequencing (NGS) to identify cancer related mutations in DNA isolated from EBC. In order to apply any method for the purpose of mutation screening in cancer patients, it is important to clarify the incidence of these mutations in healthy individuals...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28199899/role-of-outer-membrane-protein-t-in-pathogenicity-of-avian-pathogenic-escherichia-coli
#13
Hassan M A Hejair, Jiale Ma, Yingchu Zhu, Min Sun, Wenyang Dong, Yue Zhang, Zihao Pan, Wei Zhang, Huochun Yao
An outer membrane protein T (OmpT) could play a vital role in the pathogenesis of the neonatal meningitis Escherichia coli (NMEC) in human and animals. However, whether ompT plays a role in avian pathogenic E. coli (APEC) infection remains unclear. In this study we evaluated the potential of ompT in APEC pathogenesis. An ompT gene was deleted from APEC mutant strain (TW-XM) was constructed and characterized. The inactivation of ompT reduced significantly the adherence and invasion capabilities of APEC to mouse brain microvascular endothelial cell (BMEC) bEnd...
January 27, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28199742/genetic-analysis-and-clinicopathological-features-of-alk-rearranged-renal-cell-carcinoma-in-a-large-series-of-resected-chinese-renal-cell-carcinoma-patients-and-literature-review
#14
Wenjuan Yu, Yuewei Wang, Yanxia Jiang, Wei Zhang, Yujun Li
AIMS: Anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (RCC) is a rare subtype of RCC reported in recent years with 8 cases so far. The present study is focused on screening ALK-rearranged cases from a large cohort of RCCs in China to determine the frequency of ALK rearrangement and investigate the clinicopathological features and outcomes. METHODS AND RESULTS: Tissues from a total of 477 RCC patients in China were embedded into tissue microarrays for immunostaining...
February 15, 2017: Histopathology
https://www.readbyqxmd.com/read/28199134/genetic-control-of-fatty-acid-%C3%AE-oxidation-in-chronic-obstructive-pulmonary-disease
#15
Zhiqiang Jiang, Nelson H Knudsen, Gang Wang, Weiliang Qiu, Zun Zar Chi Naing, Yan Bai, Xingbin Ai, Chih-Hao Lee, Xiaobo Zhou
Bioenergetics homeostasis is important for cells to sustain normal functions and defend against injury. Genetics controls on bioenergetics homeostasis, especially lipid metabolism remain poorly understood in chronic obstructive pulmonary diseases (COPD), the third leading cause of death in the world. Additionally, biological function of most susceptible genes identified from genome-wide association studies (GWAS) in COPD remains unclear. Here, we aim to address 1) how fatty acid oxidation, specifically β-oxidation (FAO), a key lipid metabolism pathway that provides energy to cells, contributes to cigarette smoke (CS)-induced COPD; and 2) whether and how FAM13A (family with sequence similarity 13 member A), a well-replicated COPD GWAS gene, modulates FAO pathway...
February 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28199128/sox2-drives-bronchial-dysplasia-in-a-novel-organotypic-model-of-early-human-squamous-lung-cancer
#16
Lúcia L Correia, Jo-Anne Johnson, Peter McErlean, Julien Bauer, Hassan Farah, Doris M Rassl, Robert C Rintoul, Tariq Sethi, Paul Lavender, Emma L Rawlins, Trevor D Littlewood, Gerard I Evan, Frank M McCaughan
Rationale Improving the early detection and chemoprevention of lung cancer are key to improving outcomes. The pathobiology of early squamous lung cancer is poorly understood. We have shown that amplification of SOX2 is an early and consistent event in the pathogenesis of this disease but its functional oncogenic potential remains uncertain. We tested the impact of deregulated SOX2 expression in a novel organotypic system that recreates the molecular and microenvironmental context in which squamous carcinogenesis occurs...
February 15, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28198728/personalized-medicine-in-interstitial-lung-diseases
#17
Paolo Spagnolo, Justin M Oldham, Mark G Jones, Joyce S Lee
PURPOSE OF REVIEW: A number of recent studies have explored the possibility to apply personalized medicine to interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF), the most common and deadly of the idiopathic interstitial pneumonias. In our review, we summarize and discuss the most recent literature on personalized medicine in IPF as well as hypersensitivity pneumonitis and sarcoidosis, with emphasis on patient subgroups for which a personalized approach to disease prognostication and management may become a reality in the near future...
February 13, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28198450/identification-of-methylation-driven-differentially-expressed-stxbp6-as-a-novel-biomarker-in-lung-adenocarcinoma
#18
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/28197220/association-between-thyroid-cancer-and-epidermal-growth-factor-receptor-mutation-in-female-with-nonsmall-cell-lung-cancer
#19
Seo Yun Kim, Hye-Ryoun Kim, Cheol Hyeon Kim, Jae Soo Koh, Hee Jong Baek, Chang-Min Choi, Joon Seon Song, Jae Cheol Lee, Im Ii Na
BACKGROUND: The aim of this study was to investigate the association between epidermal growth factor receptor (EGFR) mutation and thyroid cancer in female patients with nonsmall-cell lung cancer (NSCLC). METHODS: In a retrospective study, we examined 835 female patients who were diagnosed with NSCLC and underwent an EGFR mutation test between June 2003 and August 2013. The associations of EGFR mutation with thyroid cancer and a family history of thyroid cancer were evaluated using logistic regression models...
January 2017: Annals of Thoracic Medicine
https://www.readbyqxmd.com/read/28196872/muc16-regulates-tspyl5-for-lung-cancer-cell-growth-and-chemoresistance-by-suppressing-p53
#20
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
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