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https://www.readbyqxmd.com/read/28919817/sirt1-gene-polymorphisms-and-risk-of-lung-cancer
#1
Yanbo Lv, Shuangyan Lin, Fang Peng
OBJECTIVE: Lung cancer, which is the leading cause of cancer death worldwide, is influenced by a wide variety of environmental and genetic risk factors. The silent information regulator 1 (SIRT1) gene is located on the long arm of chromosome 10 (10q21.3) and has been shown to play crucial roles in lung cancer development in previous studies. In this study, we determined whether variation in the SIRT1 gene is associated with lung cancer in Chinese population. METHODS: The case-control study comprised 246 controls and 257 non-small cell lung cancer patients, comprising 79 squamous cell carcinoma patients and 124 adenocarcinoma patients...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28918051/lrrk2-antisense-oligonucleotides-ameliorate-%C3%AE-synuclein-inclusion-formation-in-a-parkinson-s-disease-mouse-model
#2
Hien Tran Zhao, Neena John, Vedad Delic, Karli Ikeda-Lee, Aneeza Kim, Andreas Weihofen, Eric E Swayze, Holly B Kordasiewicz, Andrew B West, Laura A Volpicelli-Daley
No treatments exist to slow or halt Parkinson's disease (PD) progression; however, inhibition of leucine-rich repeat kinase 2 (LRRK2) activity represents one of the most promising therapeutic strategies. Genetic ablation and pharmacological LRRK2 inhibition have demonstrated promise in blocking α-synuclein (α-syn) pathology. However, LRRK2 kinase inhibitors may reduce LRRK2 activity in several tissues and induce systemic phenotypes in the kidney and lung that are undesirable. Here, we test whether antisense oligonucleotides (ASOs) provide an alternative therapeutic strategy, as they can be restricted to the CNS and provide a stable, long-lasting reduction of protein throughout the brain...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28915716/implementation-and-utilization-of-the-molecular-tumor-board-to-guide-precision-medicine
#3
REVIEW
Shuko Harada, Rebecca Arend, Qian Dai, Jessica A Levesque, Thomas S Winokur, Rongjun Guo, Martin J Heslin, Lisle Nabell, L Burt Nabors, Nita A Limdi, Kevin A Roth, Edward E Partridge, Gene P Siegal, Eddy S Yang
BACKGROUND: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine. MATERIALS AND METHODS: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915683/association-between-8q24-rs6983267-polymorphism-and-cancer-susceptibility-a-meta-analysis-involving-170-737-subjects
#4
Man Zhu, Xue Wen, Xuefang Liu, Yingchao Wang, Chunzi Liang, Jiancheng Tu
Published data on the association between 8q24 rs6983267 polymorphism and cancer risk are inconsistent. Thus, we conducted a meta-analysis to evaluate the relationship between rs6983267 polymorphism and cancer risk. We searched on PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) up to November 1, 2016 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of this association. We included 78 case-control studies with a total of 73,996 cases and 96,741 controls in this meta-analysis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915630/casp8-652-6n-insertion-deletion-polymorphism-and-overall-cancer-risk-evidence-from-49-studies
#5
Jiarong Cai, Qingjian Ye, Suling Luo, Ze Zhuang, Kui He, Zhen-Jian Zhuo, Xiaochun Wan, Juan Cheng
The CASP8 -652 6N insertion/deletion (I/D) polymorphism reduces expression of caspase 8. We conducted a meta-analysis to clarify the relationship between this polymorphism and cancer risk. Eligible articles were retrieved from PubMed, EMBASE, CNKI, and WANFANG databases through February 2017. A total of 33 articles with 49 studies, including 33,494 cases and 36,397 controls, were analyzed. We found that the CASP8 -652 6N ins/del polymorphism was associated with decreased overall cancer risk in five genetic models [DD vs...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915609/polymorphisms-of-pri-mir-219-1-are-associated-with-the-susceptibility-and-prognosis-of-non-small-cell-lung-cancer-in-a-northeast-chinese-population
#6
Chang Zheng, Xuelian Li, Lingzi Xia, Xue Fang, Xiaowei Quan, Zhihua Yin, Yuxia Zhao, Baosen Zhou
Occurrence and development of non-small cell lung cancer (NSCLC) is a complex process affected both by gene and environment. Single nucleotide polymorphisms (SNPs) in microRNAs' (miRNAs) biogenesis influenced the expression of mature miRNAs, further had an impact on risk of NSCLC. Our study focused on the correlation between rs213210, rs421446 or rs107822 polymorphisms in pri-miR-219-1 and susceptibility or prognosis of NSCLC in Chinese. A case-control study of 405 new-diagnosis patients and 405 controls was performed...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915575/hexokinase-2-promotes-tumor-growth-and-metastasis-by-regulating-lactate-production-in-pancreatic-cancer
#7
Marybeth Anderson, Raoud Marayati, Richard Moffitt, Jen Jen Yeh
Pancreatic ductal adenocarcinoma (PDAC) is a KRAS-driven cancer with a high incidence of metastasis and an overall poor prognosis. Previous work in a genetically engineered mouse model of PDAC showed glucose metabolism to be important for maintaining tumor growth. Multiple glycolytic enzymes, including hexokinase 2 (HK2), were upregulated in primary PDAC patient tumors, supporting a role for glycolysis in promoting human disease. HK2 was most highly expressed in PDAC metastases, suggesting a link between HK2 and aggressive tumor biology...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915364/nosocomial-multidrug-resistant-klebsiella-pneumoniae-strains-isolated-from-mexico-city-produce-robust-biofilms-on-abiotic-surfaces-but-not-on-human-lung-cells
#8
Martha Lorena Ostria-Hernandez, Karla Cecilia Juárez-de la Rosa, Patricia Arzate-Barbosa, Antonino Lara-Hernández, Fuminori Sakai, J Antonio Ibarra, Graciela Castro-Escarpulli, Jorge E Vidal
BACKGROUND: Klebsiella pneumoniae (Kpn) strains are a leading cause of hospital-acquired infections, including ventilator-associated pneumonia. Resistance to antibiotics, biofilm formation, and the production of certain fimbriae play an important role in the pathogenesis. AIM: We investigated the genetic relatedness, antibiotic resistance, virulence potential, and ability to form biofilms of Kpn strains isolated from hospital-acquired infections (n = 76). Strains were isolated at three major hospitals serving the largest metropolitan urban area in Mexico City, Mexico...
September 15, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28915221/metformin-exerts-beneficial-effects-in-hemorrhagic-shock-in-an-ampk%C3%AE-1-independent-manner
#9
Paul Kim, Giovanna Piraino, Michael O'Connor, Paul W Hake, Vivian Wolfe, Patrick Lahni, Basilia Zingarelli
Despite therapeutic advances in hemorrhagic shock, mortality from multiple organ failure remains high. AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Two catalytic subunits, α1 and α2, have been identified, with α1 subunit largely expressed in major organs. Here, we hypothesized that genetic deficiency of AMPKα1 worsens hemorrhage-induced multiple organ failure. We also investigated whether treatment with metformin, a clinically used drug for metabolic homeostasis, affords beneficial effects...
September 14, 2017: Shock
https://www.readbyqxmd.com/read/28914637/signal-transducer-and-activator-of-transcription-gain-of-function-primary-immunodeficiency-immunodysregulation-disorders
#10
Filippo Consonni, Laura Dotta, Francesca Todaro, Donatella Vairo, Raffaele Badolato
PURPOSE OF REVIEW: To describe primary immunodeficiencies caused by gain-of-function (GOF) mutations of signal transducer and activator of transcription (STAT) genes, a group of genetically determined disorders characterized by susceptibility to infections and, in many cases, autoimmune manifestations. RECENT FINDINGS: GOF mutations affecting STAT1 result in increased STAT tyrosine phosphorylation and secondarily increased response to STAT1-signaling cytokines, such as interferons...
September 13, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28914263/coexistent-genetic-alterations-involving-alk-ret-ros1-or-met-in-15-cases-of-lung-adenocarcinoma
#11
Zhenya Tang, Jianjun Zhang, Xinyan Lu, Wei Wang, Hui Chen, Melissa K Robinson, Joanne Cheng, Guilin Tang, L Jeffrey Medeiros
In lung cancer, targetable activating alterations in cancer genes, such as EGFR, ALK, RET, ROS1 and MET, are usually mutually exclusive. Rare lung cancer cases with coexistent alterations of EGFR and ALK or EGFR mutations with RET or ROS1 rearrangements have been reported. In this study, we report 15 patients (3 men and 12 women; 14 Caucasians and 1 African American) with ages ranging from 43 to 81 years (median 60 years) with lung adenocarcinoma in which coexistent alterations of two cancer-associated genes, including ALK, ROS1, or RET rearrangement or MET amplification were present...
September 15, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28912884/towards-translational-immunopet-mr-imaging-of-invasive-pulmonary-aspergillosis-the-humanised-monoclonal-antibody-jf5-detects-aspergillus-lung-infections-in-vivo
#12
Genna Davies, Anna-Maria Rolle, Andreas Maurer, Philipp R Spycher, Claudia Schillinger, Djamschid Solouk-Saran, Mike Hasenberg, Juliane Weski, Jesper Fonslet, Adrien Dubois, Frederic Boschetti, Franck Denat, Matthias Gunzer, Martin Eichner, Lauren S Ryder, Mikael Jensen, Roger Schibli, Bernd J Pichler, Stefan Wiehr, Christopher R Thornton
Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy or bone marrow transplant patients caused by the ubiquitous environmental fungus Aspergillus fumigatus. Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI) using a [(64)Cu]DOTA-labeled mouse monoclonal antibody (mAb), mJF5, specific to Aspergillus...
2017: Theranostics
https://www.readbyqxmd.com/read/28912510/the-th1-th17-balance-dictates-the-fibrosis-response-in-murine-radiation-induced-lung-disease
#13
Alexandra Paun, Marie-Eve Bergeron, Christina K Haston
Radiotherapy can result in lung diseases pneumonitis or fibrosis dependent on patient susceptibility. Herein we used inbred and genetically altered mice to investigate whether the tissue adaptive immune response to radiation injury influences the development of radiation-induced lung disease. Six inbred mouse strains were exposed to 18 Gy whole thorax irradiation and upon respiratory distress strains prone to pneumonitis with fibrosis presented an increased pulmonary frequency of Thelper (Th)17 cells which was not evident in strains prone solely to pneumonitis...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911086/large-scale-prospective-screening-of-egfr-mutations-in-the-blood-of-advanced-nsclc-patients-to-guide-treatment-decisions
#14
C Mayo-de-Las-Casas, N Jordana-Ariza, M Garzón-Ibañez, A Balada-Bel, J Bertrán-Alamillo, S Viteri-Ramírez, N Reguart, M A Muñoz-Quintana, P Lianes-Barragan, C Camps, E Jantús, J Remon-Massip, S Calabuig, D Aguiar, M L Gil, N Viñolas, A K Santos-Rodríguez, M Majem, B García-Peláez, S Villatoro, A Pérez-Rosado, J C Monasterio, E Ovalle, M J Catalán, R Campos, D Morales-Espinosa, A Martínez-Bueno, M González-Cao, X González, I Moya-Horno, A E Sosa, N Karachaliou, R Rosell, M A Molina-Vila
Background: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Patients and methods: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28910260/shining-new-light-on-newborn-screening-of-cystic-fibrosis-in-the-province-of-quebec
#15
Léticia Khendek
Newborn screening of cystic fibrosis, a severe genetic disease with high treatment burden, is offered in all of North America with the exception of the province of Quebec. This condition, when diagnosed on symptomatic presentation, is marked by chronic infections and progressive lung function decline leading to eventual respiratory failure. Patients continue to have a median age of survival notably below the Canadian average. Despite prevalence rates of cystic fibrosis almost three times the national average in certain regions of Quebec, the province still does not offer screening to its newborns...
September 14, 2017: Canadian Journal of Public Health. Revue Canadienne de Santé Publique
https://www.readbyqxmd.com/read/28906590/fgf19-genetic-amplification-as-a-potential-therapeutic-target-in-lung-squamous-cell-carcinomas
#16
Xiaochen Zhang, Mei Kong, Zhen Zhang, Suzhen Xu, Feifei Yan, Liyuan Wei, Jianying Zhou
BACKGROUND: Although FGF19 gene aberrations are associated with carcinogenesis and progression in human cancers, the roles of FGF19 genetic amplification and expression in Chinese patients with lung squamous cell carcinoma (LSCC) and FGF19 amplification as a potential therapeutic target for LSCC are not well understood. METHODS: Fluorescence in situ hybridization analysis and quantitative real-time-PCR was used to detect FGF19 genetic amplification and FGF19 messenger RNA expression in LSCC tumor and paired adjacent samples...
September 14, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28904888/routine-clinical-use-of-circulating-tumor-cells-for-diagnosis-of-mutations-and-chromosomal-rearrangements-in-non-small-cell-lung-cancer-ready-for-prime-time
#17
REVIEW
Emma Pailler, Vincent Faugeroux, Marianne Oulhen, Cyril Catelain, Françoise Farace
In non-small cell lung cancer (NSCLC), diagnosis of predictive biomarkers for targeted therapies is currently done in small tumor biopsies. However, tumor biopsies can be invasive, in some cases associated with risk, and tissue adequacy, both in terms of quantity and quality is often insufficient. The development of efficient and non-invasive methods to identify genetic alterations is a key challenge which circulating tumor cells (CTCs) have the potential to be exploited for. CTCs are extremely rare and phenotypically diverse, two characteristics that impose technical challenges and impact the success of robust molecular analysis...
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28904887/biology-and-clinical-significance-of-circulating-tumor-cell-subpopulations-in-lung-cancer
#18
REVIEW
Linda O'Flaherty, Harriet Wikman, Klaus Pantel
By identifying and tracking genetic changes in primary tumors and metastases, patients can be stratified for the most efficient therapeutic regimen by screening for known biomarkers. However, retrieving tissues biopsies is not always feasible due to tumor location or risk to patient. Therefore, a liquid biopsies approach offers an appealing solution to an otherwise invasive procedure. The rapid growth of the liquid biopsy field has been aided by improvements in the sensitivity and specificity of enrichment assays for isolating circulating tumor cells (CTCs) from normal surrounding blood cells...
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28904884/circulating-tumor-cells-and-cdx-models-as-a-tool-for-preclinical-drug-development
#19
REVIEW
Alice Lallo, Maximilian W Schenk, Kristopher K Frese, Fiona Blackhall, Caroline Dive
Lung cancers are the main cause of cancer-related deaths worldwide. Efforts placed to improve the survival of lung cancer patients and untangle the complexity of this disease, have resulted in the generation of hundreds of lung cancer cell lines and several genetically engineered mouse models (GEMMs). Although these research tools have extended our knowledge of lung cancer, improvement in the clinical care of lung cancer patients have been limited overall, with measured optimism regarding initial responses to targeted therapies in stratified subgroups of patients...
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28904861/a-modified-graft-versus-host-induced-model-for-systemic-sclerosis-with-pulmonary-fibrosis-in-rag2-deficient-mice
#20
Xue Yang, Chi Liu, Masayuki Fujino, Ji Yang, Xiao-Kang Li, Hejian Zou
Systemic sclerosis (SSc) is a connective tissue disease that results in fibrosis in multiple organs. Various animal models for this disease have been developed, both genetic and induced. One of the induced models, sclerodermatous graft-versus-host disease (scl-GvHD), exhibits the main characteristics of SSc, but involves lethal γ-irradiation of recipients. We sought to develop a modified scl-GvHD model. Spleen cells from B10.D2 donor mice were transplanted into immunodeficient Rag-2 recipients on the BALB/c genetic background...
September 2017: FEBS Open Bio
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