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Lung genetics

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https://www.readbyqxmd.com/read/29351449/personalized-medicine-in-cf-from-modulator-development-to-therapy-for-cystic-fibrosis-patients-with-rare-cftr-mutations
#1
Misak Harutyunyan, Yunjie Huang, Kyu-Shik Mun, Fanmuyi Yang, Kavisha Arora, Anjaparavanda P Naren
Cystic fibrosis (CF) is the most common life-shortening genetic disease affecting approximately 1 in 3500 of the Caucasian population. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. To date, over 2000 CFTR mutations have been identified and produce a wide range of phenotypes. The CFTR protein, a chloride channel, is normally expressed on epithelial cells lining the lung, gut, and exocrine glands. Mutations in CFTR have led to pleiotropic effects in CF patients and have resulted in early morbidity and mortality...
December 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351448/extracellular-oxidation-in-cystic-fibrosis-airway-epithelium-causes-enhanced-egfr-adam17-activity
#2
Marta Stolarczyk, Guido Veit, Andrea Schnur, Mieke Veltman, Gergely L Lukacs, Bob J Scholte
The EGFR/ADAM17 signaling pathway mediates the shedding of growth factors and secretion of cytokines, and is involved in chronic inflammation and tissue remodeling. Since these are hallmarks of cystic fibrosis (CF) lung disease, we hypothesized that CFTR deficiency enhances EGFR/ADAM17 activity in human bronchial epithelial cells. In CFBE41o- cells lacking functional CFTR (iCFTR-) cultured at air-liquid interface (ALI) we found enhanced ADAM17-mediated shedding of the EGFR ligand amphiregulin (AREG) compared to genetically identical cells with induced CFTR expression (iCFTR+)...
December 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29350941/immotile-active-matter-activity-from-death-and-reproduction
#3
Arben Kalziqi, David Yanni, Jacob Thomas, Siu Lung Ng, Skanda Vivek, Brian K Hammer, Peter J Yunker
Unlike equilibrium atomic solids, biofilms-soft solids composed of bacterial cells-do not experience significant thermal fluctuations at the constituent level. However, living cells stochastically reproduce and die, provoking a mechanical response. We investigate the mechanical consequences of cellular death and reproduction by measuring surface-height fluctuations of biofilms containing two mutually antagonistic strains of Vibrio cholerae that kill one another on contact via the type VI secretion system. While studies of active matter typically focus on activity via constituent mobility, here, activity is mediated by reproduction and death events in otherwise immobilized cells...
January 5, 2018: Physical Review Letters
https://www.readbyqxmd.com/read/29349535/mycobacterium-xenopi-genotype-associated-with-clinical-phenotype-in-lung-disease
#4
Takashi Hirama, Alex Marchand-Austin, Jennifer Ma, David C Alexander, Sarah K Brode, Theodore K Marras, Frances B Jamieson
Mycobacterium xenopi is responsible for pulmonary disease (PD) in Europe and Canada. Despite its high prevalence and increasing clinical importance, little is known about the genetic diversity of M. xenopi. Through a prospective study for M. xenopi strain type and the relation to clinical phenotype, 39 patients with M. xenopi PD were analyzed. Our study demonstrated that sequence type (ST) 5 was dominant in Ontario among 15 distinct STs and caused PD in people even without underlying lung disease, whereas disease due to non-ST5 was found almost exclusively in patients with underlying lung disease...
January 18, 2018: Lung
https://www.readbyqxmd.com/read/29348862/digital-gene-expression-analysis-in-mice-lung-with-coinfection-of-influenza-and-streptococcus-pneumoniae
#5
Jun Luo, Linlin Zhou, Hongren Wang, Zhen Qin, Li Xiang, Jie Zhu, Xiaojun Huang, Yuan Yang, Wanyi Li, Baoning Wang, Mingyuan Li
Influenza A virus (IAV) and Streptococcus pneumoniae (SP) are two major upper respiratory tract pathogens that can also cause infection in polarized bronchial epithelial cells to exacerbate disease in coinfected individuals which may result in significant morbidity. However, the underlying molecular mechanism is poorly understood. Here, we employed BALB/c ByJ mice inflected with SP, IAV, IAV followed by SP (IAV+SP) and PBS (Control) as models to survey the global gene expression using digital gene expression (DGE) profiling...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348685/overexpression-of-adhesion-molecules-and-barrier-molecules-is-associated-with-differential-infiltration-of-immune-cells-in-non-small-cell-lung-cancer
#6
Young Kwang Chae, Wooyoung M Choi, William H Bae, Jonathan Anker, Andrew A Davis, Sarita Agte, Wade T Iams, Marcelo Cruz, Maria Matsangou, Francis J Giles
Immunotherapy is emerging as a promising option for lung cancer treatment. Various endothelial adhesion molecules, such as integrin and selectin, as well as various cellular barrier molecules such as desmosome and tight junctions, regulate T-cell infiltration in the tumor microenvironment. However, little is known regarding how these molecules affect immune cells in patients with lung cancer. We demonstrated for the first time that overexpression of endothelial adhesion molecules and cellular barrier molecule genes was linked to differential infiltration of particular immune cells in non-small cell lung cancer...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29346604/unique-genetic-profiles-from-cerebrospinal-fluid-cell-free-dna-in-leptomeningeal-metastases-of-egfr-mutant-non-small-cell-lung-cancer-a-new-medium-of-liquid-biopsy
#7
Y S Li, B Y Jiang, J J Yang, X C Zhang, Z Zhang, J Y Ye, W Z Zhong, H Y Tu, H J Chen, Z Wang, C R Xu, B C Wang, H J Du, S Chuai, H Han-Zhang, J Su, Q Zhou, X N Yang, W B Guo, H H Yan, Y H Liu, L X Yan, B Huang, M M Zheng, Y L Wu
Background: Leptomeningeal metastases (LM) are more frequent in non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM. Patients and methods: Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled...
January 15, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29346418/the-relationship-of-lung-function-with-ambient-temperature
#8
Joseph M Collaco, Lawrence J Appel, John McGready, Garry R Cutting
BACKGROUND: Lung function is complex trait with both genetic and environmental factors contributing to variation. It is unknown how geographic factors such as climate affect population respiratory health. OBJECTIVE: To determine whether ambient air temperature is associated with lung function (FEV1) in the general population. DESIGN/SETTING: Associations between spirometry data from two National Health and Nutrition Examination Survey (NHANES) periods representative of the U...
2018: PloS One
https://www.readbyqxmd.com/read/29345518/bacterial-pathogenesis-and-interleukin-17-interconnecting-mechanisms-of-immune-regulation-host-genetics-and-microbial-virulence-that-influence-severity-of-infection
#9
Michelle N Chamoun, Antje Blumenthal, Matthew J Sullivan, Mark A Schembri, Glen C Ulett
Interleukin-17 (IL-17) is a pro-inflammatory cytokine involved in the control of many different disorders, including autoimmune, oncogenic, and diverse infectious diseases. In the context of infectious diseases, IL-17 protects the host against various classes of microorganisms but, intriguingly, can also exacerbate the severity of some infections. The regulation of IL-17 expression stems, in part, from the activity of Interleukin-23 (IL-23), which drives the maturation of different classes of IL-17-producing cells that can alter the course of infection...
January 18, 2018: Critical Reviews in Microbiology
https://www.readbyqxmd.com/read/29345411/ethnicity-socioeconomic-status-and-the-severity-and-course-of-non-cystic-fibrosis-bronchiectasis
#10
Sally de Boer, Christopher A Lewis, Wendy Fergusson, Kevin Ellyett, Margaret L Wilsher
Background and aims This study evaluated whether there are ethnic factors which affect the severity and progression of bronchiectasis in our adult multi-ethnic population in Auckland, New Zealand. METHODS: Clinical records were reviewed from patients attending the outpatient facilities of our institution between 2007 and 2010. Data collected included demographics, clinical features, smoking status, self-reported ethnicity, socioeconomic status (NZDep), pulmonary function and sputum microbiology...
January 18, 2018: Internal Medicine Journal
https://www.readbyqxmd.com/read/29345197/neonatal-hyperoxia-depletes-pulmonary-vein-cardiomyocytes-in-adult-mice-via-mitochondrial-oxidation
#11
Min Yee, Ethan David Cohen, William Domm, George A Porter, Andrew N McDavid, Michael A O'Reilly
Supplemental oxygen given to preterm infants has been associated with permanently altering postnatal lung development. Now that these individuals are reaching adulthood, there is growing concern that early-life oxygen exposure may also promote cardiovascular disease through poorly understood mechanisms. We previously reported that adult mice exposed to 100% oxygen between postnatal days 0-4 develop pulmonary hypertension defined pathologically by capillary rarefaction, dilation of arterioles and veins, cardiac failure, and a reduced lifespan...
January 18, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29344953/established-emerging-and-elusive-molecular-targets-in-the-treatment-of-lung-cancer
#12
REVIEW
Jean-Nicolas Gallant, Christine M Lovly
Although histological subtype still underlies tumor classification and treatment, the recognition that lung cancer is, largely, a genetic disease has prompted a push to reconfigure cancer taxonomies according to molecular criteria. In this review, we discuss established (e.g. EGFR, ALK, ROS1, PD-1/PD-L1), emerging (e.g. MET, RET, NTRK), and elusive (e.g. TP53, KRAS, MYC) molecular targets in the treatment of lung cancer. We synthesize a large and rapidly growing body of literature regarding the discovery and therapeutic inhibition of these targets in lung cancer...
January 17, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29344803/toxoplasma-gondii-prevalence-and-characterization-of-new-genotypes-in-free-range-chickens-from-south-brazil
#13
Fernando Emmanuel Gonçalves Vieira, João Pedro Sasse, Ana Flávia Minutti, Ana Carolina Miura, Luiz Daniel de Barros, Sergio Tosi Cardim, Thais Agostinho Martins, Mércia de Seixas, Milton Issashi Yamamura, Chunlei Su, João Luis Garcia
Toxoplasma gondii is an intracellular parasite that can infect all warm-blooded animals including humans. Recent studies showed that T. gondii strains from South America are genetically diverse. The present work aimed to determine T. gondii prevalence in free-ranging chicken in northwest Parana state in Brazil by two serological tests, to isolate the parasites from seropositive chickens and to genotype the isolates. Antibodies to T. gondii in 386 serum samples from 24 farms were investigated by immunofluorescence antibody assay (IFA) and modified agglutination test (MAT)...
January 18, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29344123/ex-vivo-model-of-non-small-cell-lung-cancer-using-mouse-lung-epithelial-cells
#14
Taku Sato, Mami Morita, Ryota Tanaka, Yui Inoue, Miyuki Nomura, Yoshimi Sakamoto, Koh Miura, Shigemi Ito, Ikuro Sato, Nobuyuki Tanaka, Jiro Abe, Satomi Takahashi, Masaaki Kawai, Masami Sato, Yoshitaka Hippo, Hiroshi Shima, Yoshinori Okada, Nobuhiro Tanuma
Lung cancer is the most common cause of cancer mortality, however, efficient methods to culture, expand and transform lung epithelial (LE) cells have not been established. In the present study, an efficient ex vivo method was applied to recapitulate lung carcinogenesis using mouse LE cells. A Matrigel-assisted three-dimensional culture was used to isolate and selectively expand LE cells from mouse lungs. Purified LE cells were passaged and expanded for at least 2 to 3 months while maintaining epidermal growth factor-dependence...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343688/wee1-inhibitor-mk1775-sensitizes-kras-mutated-nsclc-cells-to-sorafenib
#15
Elisa Caiola, Roberta Frapolli, Michele Tomanelli, Rossana Valerio, Alice Iezzi, Marina C Garassino, Massimo Broggini, Mirko Marabese
Non-Small-Cell Lung Cancer (NSCLC) is a poorly chemosensitive tumor and targeted therapies are only used for about 15% of patients where a specific driving and druggable lesion is observed (EGFR, ALK, ROS). KRAS is one of the most frequently mutated genes in NSCLC and patients harboring these mutations do not benefit from specific treatments. Sorafenib, a multi-target tyrosine kinase inhibitor, was proposed as a potentially active drug in KRAS-mutated NSCLC patients, but clinical trials results were not conclusive...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343557/dicer1-and-associated-conditions-%C3%A2-identification-of-at-risk-individuals-and-recommended-surveillance-strategies
#16
Kris Ann P Schultz, Gretchen M Williams, Junne Kamihara, Douglas R Stewart, Anne K Harris, Andrew J Bauer, Joyce Turner, Rachana Shah, Katherine Schneider, Kami Wolfe Schneider, Ann Garrity Carr, Laura A Harney, Shari Baldinger, A Lindsay Frazier, Daniel Orbach, Dominik T Schneider, David Malkin, Louis P Dehner, Yoav H Messinger, Ashley Hill
Pathogenic germline DICER1 variants cause a hereditary cancer predisposition syndrome with a variety of manifestations. In addition to conferring increased cancer risks for pleuropulmonary blastoma (PPB) and ovarian sex cord-stromal tumors, particularly Sertoli-Leydig cell tumor, individuals with pathogenic germline DICER1 variants may also develop lung cysts, cystic nephroma, renal sarcoma and Wilms tumor, nodular hyperplasia of the thyroid, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, genitourinary embryonal rhabdomyosarcoma and brain tumors including pineoblastoma and pituitary blastoma...
January 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29343556/rasa1-nf1-mutant-lung-cancer-racing-to-the-clinic
#17
Shunsuke Kitajima, David A Barbie
Although mutation of NF1 has been described in non-small cell lung cancer (NSCLC), co-mutation with RASA1, another Ras-GTPase activating protein (RasGAP), defines a novel genetically defined subclass of NSCLC. RASA1/NF1 mutant cell lines are highly sensitive to MEK inhibitors, warranting clinical evaluation of MAPK inhibition in this subclass of patients.
January 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29343520/evidence-for-the-isg15-specific-deubiquitinase-usp18-as-an-antineoplastic-target
#18
REVIEW
Lisa Maria Mustachio, Yun Lu, Masanori Kawakami, Jason Roszik, Sarah J Freemantle, Xi Liu, Ethan Dmitrovsky
Ubiquitination and ubiquitin-like posttranslational modifications (PTM) regulate activity and stability of oncoproteins and tumor suppressors. This implicates PTMs as antineoplastic targets. One way to alter PTMs is to inhibit activity of deubiquitinases (DUB) that remove ubiquitin or ubiquitin-like proteins from substrate proteins. Roles of DUBs in carcinogenesis have been intensively studied, yet few inhibitors exist. Prior work provides a basis for the ubiquitin-specific protease 18 (USP18) as an antineoplastic target...
January 17, 2018: Cancer Research
https://www.readbyqxmd.com/read/29343426/environmental-mycobacterium-avium-subsp-hominissuis-have-a-higher-probability-to-act-as-a-recipient-in-conjugation-than-clinical-strains
#19
Salma A Shoulah, Anna M Oschmann, Abdelfattah Selim, Torsten Semmler, Carsten Schwarz, Elisabeth Kamal, Faysal Hamouda, Elsayed Galila, Wilbert Bitter, Astrid Lewin
Mycobacterium avium subsp. hominissuis (MAH) is a widespread opportunistic pathogen that can be isolated from environment (dust, soil and water) and patients with lung or lymphnode infection. In our previous research we revealed the pronounced genetic diversity in MAH by identifying eight different types of a newly described genomic island. In order to identify mechanisms of such horizontal gene transfer we now analyzed the ability of 47 MAH isolates to inherit the conjugative plasmid pRAW from M. marinum. A higher percentage of environmental isolates (22...
January 14, 2018: Plasmid
https://www.readbyqxmd.com/read/29341459/multicenter-study-of-diagnostic-procedures-genetic-aberration-analysis-and-first-line-treatment-of-lung-cancer-in-jiangsu-province-china
#20
YangBo Hu, Huan Hu, LiYun Miao, Xin Zhao, Wei Gu, Wei Heng, ZiLi Meng, Jian Feng, Yi You, XingXiang Xu, Rong Hu, HaiQuan Li, Jie Zhao, XiaoLi Zhu, MeiQi Shi, Li Shen, XiuWei Zhang, XiaoWei Yin, Hang Ma, MinHua Shi, Yong Yu, Hong Lv, LiMing Cai, GaoHua Feng, YeQing Zhang, Feng Wu, TangFeng Lv, Yong Song
BACKGROUND: Jiangsu Province, China, is highly developed economically and culturally, and has a high prevalence of lung cancer. We aimed to evaluate the diagnostic procedures, genetic aberration analysis status, and first-line treatment models of lung cancer in Jiangsu Province. METHODS: Lung cancer patients diagnosed in 2016 at 22 tertiary care hospitals were evaluated. Demographic characteristics, tumor histology, staging, family history of lung cancer, auxiliary examinations, genetic testing, and first-line treatment were collected on discharge...
January 17, 2018: Thoracic Cancer
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