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Lung genetics

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https://www.readbyqxmd.com/read/27913639/modulation-of-apical-constriction-by-wnt-signaling-is-required-for-lung-epithelial-shape-transition
#1
Katsumi Fumoto, Hisako Takigawa-Imamura, Kenta Sumiyama, Tomoyuki Kaneiwa, Akira Kikuchi
In lung development the apically constricted columnar epithelium forms numerous buds during the pseudoglandular stage and subsequently changes the shape into flat or cuboidal pneumocytes that compose the air sacs during the canalicular and saccular (canalicular-saccular) stages, yet the impact of cell shapes on tissue morphogenesis remains unclear. The expression of Wnt components were decreased in the canalicular-saccular stages, and genetically constitutive activation of Wnt signaling impaired air sac formation by inducing apical constriction in the epithelium as seen in the pseudoglandular stage...
December 2, 2016: Development
https://www.readbyqxmd.com/read/27913437/surface-expression-of-tgf%C3%AE-docking-receptor-garp-promotes-oncogenesis-and-immune-tolerance-in-breast-cancer
#2
Alessandra Metelli, Bill X Wu, Caroline W Fugle, Saleh Rachidi, Shaoli Sun, Yongliang Zhang, Jennifer Wu, Stephen Tomlinson, Philip H Howe, Yi Yang, Elizabeth Garrett-Mayer, Bei Liu, Zihai Li
GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGFβ, which is expressed naturally by platelets and regulatory T cells (Treg). Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here, we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGFβ in the tumor microenvironment. We found that human breast, lung, and colon cancers expressed GARP aberrantly...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27913425/cd36-mediates-h2o2-induced-calcium-influx-in-lung-microvascular-endothelial-cells
#3
Karthik Suresh, Laura Servinsky, Jose Reyes, Clark Undem, Joel Zaldumbide, Otgonchimeg Rentsendorj, Sruti Modekurty, Jeffrey M Dodd-O, Alan L Scott, David B Pearse, Larissa A Shimoda
Elevated levels of reactive oxygen species (ROS) and intracellular Ca2+ play a key role in endothelial barrier dysfunction in acute lung injury (ALI). We previously showed that H2O2-induced increases in intracellular calcium concentrations ([Ca2+]i) in LMVECs involve the membrane Ca2+ channel, transient receptor potential vanilloid-4 (TRPV4), and that inhibiting this channel attenuated H2O2-induced barrier disruption in vitro. We also showed that phosphorylation of TRPV4 by the Src family kinase, Fyn, contributes to H2O2-induced Ca2+ influx in LMVEC...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27913191/the-shedding-derived-soluble-receptor-for-advanced-glycation-endproducts-sustains-inflammation-during-acute-pseudomonas-aeruginosa-lung-infection
#4
Antonella Antonelli, Stefania Di Maggio, Joanna Rejman, Francesca Sanvito, Alice Rossi, Alessandro Catucci, Andrea Gorzanelli, Alessandra Bragonzi, Marco E Bianchi, Angela Raucci
BACKGROUND: The membrane-bound isoform of the receptor for advanced glycation end products (FL-RAGE) is primarily expressed by alveolar epithelial cells and undergoes shedding by the protease ADAM10, giving rise to soluble cleaved RAGE (cRAGE). RAGE has been associated with the pathogenesis of several acute and chronic lung disorders. Whether the proteolysis of FL-RAGE is altered by a given inflammatory stimulus is unknown. Pseudomonas aeruginosa causes nosocomial infections in hospitalized patients and is the major pathogen associated with chronic lung diseases...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27912835/second-line-chemotherapy-and-beyond-for-non-small-cell-lung-cancer
#5
REVIEW
Greg Durm, Nasser Hanna
The landscape for the second- and third-line treatment of advanced non-small cell lung cancer has changed dramatically over the last two decades. Immunotherapeutic agents have become a preferred choice following progression on platinum-based first-line chemotherapy. However, there remains a role for cytotoxic chemotherapy and pemetrexed and docetaxel (with or without ramucirumab) are approved for single-agent use in the second-line setting. With the discovery of new genetic alterations and the development of novel targeted drugs, the treatment of advanced non-small cell lung cancer following progression on first-line therapy continues to become more complicated as new treatment algorithms evolve...
February 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/27911940/isoform-specific-effects-of-wild-type-ras-genes-on-carcinogen-induced-lung-tumorigenesis-in-mice
#6
Jamie D Weyandt, John M Carney, Elizabeth N Pavlisko, MengMeng Xu, Christopher M Counter
The gene KRAS is commonly mutated in lung cancer to encode a constitutively active and oncogenic protein that is well established to initiate and maintain lung tumorigenesis. However, the remaining wild-type KRAS protein, or the other family members HRAS and NRAS, can still be activated in the presence of oncogenic KRAS. Moreover, loss of any one of these three genes has been shown to increase the sensitivity of mice to the carcinogen urethane, which induces Kras mutation-positive early lung lesions. To determine the contribution of progressively disrupting Hras and Nras genes on urethane lung tumorigenesis, mice with different combinations of wild-type and null alleles of Hras and Nras were exposed with urethane and tumor burden was assessed...
2016: PloS One
https://www.readbyqxmd.com/read/27910778/mirsnps-of-mir1274-and-mir3202-genes-that-target-mecp2-and-dnmt3b-are-associated-with-lung-cancer-risk-a-study-conducted-on-massarray-genotyping
#7
Cansu Ozbayer, Irfan Degirmenci, Derya Ustuner, Guntulu Ak, Faruk Saydam, Ertugrul Colak, Hasan Veysi Gunes, Muzaffer Metintas
Genetic variants of miRNAs that target DNMTs and MBDs involved in DNA methylation were scanned with current databases, and 35 miRSNPs in 22 miRNA genes were identified. The aim of the study was to determine the association between these variants of miRNA genes and lung cancer (LC). DNA samples were isolated from blood samples and genotyped using a Sequenom MassARRAY System. An association between the rs188912830 gene variant of miR3202 that targets the MeCP2 protein and LC was indicated in both subtypes. The presence of the C-allele in patients with LC and its subtypes was significantly lower, and the absence of the C-allele was determined to increase the risk of LC by 7,429-times compared to the presence (p=0,010)...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27907224/single-versus-combination-intravenous-anti-pseudomonal-antibiotic-therapy-for-people-with-cystic-fibrosis
#8
REVIEW
Heather E Elphick, Alison Scott
BACKGROUND: Choice of antibiotic, and the use of single or combined therapy are controversial areas in the treatment of respiratory infection due to Pseudomonas aeruginosa in cystic fibrosis (CF). Advantages of combination therapy include wider range of modes of action, possible synergy and reduction of resistant organisms; advantages of monotherapy include lower cost, ease of administration and reduction of drug-related toxicity. Current evidence does not provide a clear answer and the use of intravenous antibiotic therapy in cystic fibrosis requires further evaluation...
December 1, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27906824/selection-of-patients-for-initial-clinical-trials-of-solid-organ-xenotransplantation
#9
David K C Cooper, Martin Wijkstrom, Sundaram Hariharan, Joshua L Chan, Avneesh Singh, Keith Horvath, Muhammad Mohiuddin, Arielle Cimeno, Rolf N Barth, John C LaMattina, Richard N Pierson
Several groups have reported extended survival of genetically-engineered pig organs in nonhuman primates, varying from almost 10 months for life-supporting kidney grafts and >2 years for nonlife-supporting heart grafts to less than 1 month for life-supporting liver and lung grafts. We have attempted to define groups of patients who may not have an option to wait for an allograft. These include kidney, heart, and lung candidates who are highly-allosensitized. In addition, some kidney candidates (who have previously lost at least 2 allografts from rapid recurrence of native kidney disease) have a high risk of further recurrence and will not be offered a repeat allotransplant...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27903671/sports-related-lung-injury-during-breath-hold-diving
#10
Tanja Mijacika, Zeljko Dujic
The number of people practising recreational breath-hold diving is constantly growing, thereby increasing the need for knowledge of the acute and chronic effects such a sport could have on the health of participants. Breath-hold diving is potentially dangerous, mainly because of associated extreme environmental factors such as increased hydrostatic pressure, hypoxia, hypercapnia, hypothermia and strenuous exercise.In this article we focus on the effects of breath-hold diving on pulmonary function. Respiratory symptoms have been reported in almost 25% of breath-hold divers after repetitive diving sessions...
December 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/27902695/text-mining-genotype-phenotype-relationships-from-biomedical-literature-for-database-curation-and-precision-medicine
#11
Ayush Singhal, Michael Simmons, Zhiyong Lu
The practice of precision medicine will ultimately require databases of genes and mutations for healthcare providers to reference in order to understand the clinical implications of each patient's genetic makeup. Although the highest quality databases require manual curation, text mining tools can facilitate the curation process, increasing accuracy, coverage, and productivity. However, to date there are no available text mining tools that offer high-accuracy performance for extracting such triplets from biomedical literature...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27902597/whole-exome-sequencing-of-independent-lung-adenocarcinoma-lung-squamous-cell-carcinoma-and-malignant-peritoneal-mesothelioma-a-case-report
#12
Irene Vanni, Simona Coco, Silvia Bonfiglio, Davide Cittaro, Carlo Genova, Federica Biello, Marco Mora, Valeria Rossella, Maria Giovanna Dal Bello, Anna Truini, Barbara Banelli, Dejan Lazarevic, Angela Alama, Erika Rijavec, Giulia Barletta, Francesco Grossi
The presence of multiple primary tumors (MPT) in a single patient has been identified with an increasing frequency. A critical issue is to establish if the second tumor represents an independent primary cancer or a metastasis. Therefore, the assessment of MPT clonal origin might help understand the disease behavior and improve the management/prognosis of the patient.Herein, we report a 73-year-old male smoker who developed 2 primary lung cancers (adenocarcinoma and squamous cell carcinoma) and a malignant peritoneal mesothelioma (PM)...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27902422/microbiota-dysbiosis-a-new-piece-in-the-understanding-of-carcinogenesis-puzzle
#13
Valeria García-Castillo, Enrique Sanhueza, Eileen McNerney, Sergio A Onate, Apolinaria García
Cancer is defined as an uncontrolled proliferation of malignant cells in a host and it is one of the main causes of death worldwide. Genetic and environmental factors play an important role in its development and the involvement of microbial communities has also recently been recognized. The close relationship that characterizes the colonization of human commensal communities involves health risks particularly when the homeostasis is disturbed. It has been hypothesized that this process may lead to cancer by modulating the inflammatory response of the host, by the production of carcinogenic metabolic products or by the production of toxins which disrupt the cell cycle...
October 21, 2016: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27901618/genome-wide-interaction-analysis-of-air-pollution-exposure-and-childhood-asthma-with-functional-follow-up
#14
Anna Gref, Simon Kebede Merid, Olena Gruzieva, Stéphane Ballereau, Allan Becker, Tom Bellander, Anna Bergström, Yohan Bossé, Matteo Bottai, Moira Chan-Yeung, Elaine Fuertes, Despo Ierodiakonou, Ruiwei Jiang, Stéphane Joly, Meaghan Jones, Michael S Kobor, Michal Korek, Anita L Kozyrskyj, Ashish Kumar, Nathanaël Lemonnier, Elaina MacIntyre, Camille Ménard, David Nickle, Ma'en Obeidat, Johann Pellet, Marie Standl, Annika Sääf, Cilla Söderhäll, Carla Mt Tiesler, Maarten van den Berge, Judith M Vonk, Hita Vora, Cheng-Jian Xu, Josep M Antó, Charles Auffray, Michael Brauer, Jean Bousquet, Bert Brunekreef, W James Gauderman, Joachim Heinrich, Juha Kere, Gerard H Koppelman, Dirkje Postma, Christopher Carlsten, Göran Pershagen, Erik Melén
RATIONALE: The evidence supporting an association between traffic-related air pollution exposure and incident childhood asthma is inconsistent, and may depend on genetic factors. OBJECTIVES: To identify gene-environment interaction effects on childhood asthma using genome-wide single nucleotide polymorphism (SNP) data and air pollution exposure. Identified loci were further analyzed at epigenetic and transcriptomic levels. METHODS: We used land use regression models to estimate individual air pollution exposure (represented by outdoor NO2 levels) at the birth address and performed a genome-wide interaction study for doctor's diagnosis of asthma up to 8 years in three European birth cohorts (n=1,534) with look-up for interaction in two separate North American cohorts, CHS and CAPPS/SAGE (n=1,602 and 186 subjects, respectively)...
November 30, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27900742/-precision-nursing-individual-based-knowledge-translation
#15
Li-Chi Chiang, Mei-Ling Yeh, Sui-Lung Su
U.S. President Obama announced a new era of precision medicine in the Precision Medicine Initiative (PMI). This initiative aims to accelerate the progress of personalized medicine in light of individual requirements for prevention and treatment in order to improve the state of individual and public health. The recent and dramatic development of large-scale biologic databases (such as the human genome sequence), powerful methods for characterizing patients (such as genomics, microbiome, diverse biomarkers, and even pharmacogenomics), and computational tools for analyzing big data are maximizing the potential benefits of precision medicine...
December 2016: Hu Li za Zhi the Journal of Nursing
https://www.readbyqxmd.com/read/27899532/long-term-management-for-ventilator-assisted-children-in-hong-kong-2-decades-experience
#16
Shuk-Kuen Chau, Ada Wing-Yan Yung, So-Lun Lee
BACKGROUND: The population of children receiving long-term mechanical ventilation is growing worldwide, but only limited data exist in Asian regions. The objective of the study was to review the management of these children in Hong Kong over the past 2 decades. METHODS: This was a retrospective cohort study. Hospital records from subjects receiving mechanical ventilation for >3 months were retrieved. Demographic characteristics and medical information of subjects (≤21 y old) under the care of the ventilator program at the Duchess of Kent Children's Hospital between 1997 and 2015 were reviewed...
November 29, 2016: Respiratory Care
https://www.readbyqxmd.com/read/27897011/a-spatiotemporal-model-to-simulate-chemotherapy-regimens-for-heterogeneous-bladder-cancer-metastases-to-the-lung
#17
Kimberly R Kanigel Winner, James C Costello
Tumors are composed of heterogeneous populations of cells. Somatic genetic aberrations are one form of heterogeneity that allows clonal cells to adapt to chemotherapeutic stress, thus providing a path for resistance to arise. In silico modeling of tumors provides a platform for rapid, quantitative experiments to inexpensively study how compositional heterogeneity contributes to drug resistance. Accordingly, we have built a spatiotemporal model of a lung metastasis originating from a primary bladder tumor, incorporating in vivo drug concentrations of first-line chemotherapy, resistance data from bladder cancer cell lines, vascular density of lung metastases, and gains in resistance in cells that survive chemotherapy...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27896964/integrative-analysis-for-lung-adenocarcinoma-predicts-morphological-features-associated-with-genetic-variations
#18
Chao Wang, Hai Su, Lin Yang, Kun Huang
Lung cancer is one of the most deadly cancers and lung adenocarcinoma (LUAD) is the most common histological type of lung cancer. However, LUAD is highly heterogeneous due to genetic difference as well as phenotypic differences such as cellular and tissue morphology. In this paper, we systematically examine the relationships between histological features and gene transcription. Specifically, we calculated 283 morphological features from histology images for 201 LUAD patients from TCGA project and identified the morphological feature with strong correlation with patient outcome...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27895891/gene-specific-sex-effects-on-eosinophil-infiltration-in-leishmaniasis
#19
Martina Slapničková, Valeriya Volkova, Marie Čepičková, Tatyana Kobets, Matyáš Šíma, Milena Svobodová, Peter Demant, Marie Lipoldová
BACKGROUND: Sex influences susceptibility to many infectious diseases, including some manifestations of leishmaniasis. The disease is caused by parasites that enter to the skin and can spread to the lymph nodes, spleen, liver, bone marrow, and sometimes lungs. Parasites induce host defenses including cell infiltration, leading to protective or ineffective inflammation. These responses are often influenced by host genotype and sex. We analyzed the role of sex in the impact of specific gene loci on eosinophil infiltration and its functional relevance...
2016: Biology of Sex Differences
https://www.readbyqxmd.com/read/27894259/genomic-signatures-of-mannheimia-haemolytica-that-associate-with-the-lungs-of-cattle-with-respiratory-disease-an-integrative-conjugative-element-and-antibiotic-resistance-genes
#20
Michael L Clawson, Robert W Murray, Michael T Sweeney, Michael D Apley, Keith D DeDonder, Sarah F Capik, Robert L Larson, Brian V Lubbers, Brad J White, Theodore S Kalbfleisch, Gennie Schuller, Aaron M Dickey, Gregory P Harhay, Michael P Heaton, Carol G Chitko-McKown, Dayna M Brichta-Harhay, James L Bono, Timothy P L Smith
BACKGROUND: Mannheimia haemolytica typically resides in cattle as a commensal member of the upper respiratory tract microbiome. However, some strains can invade their lungs and cause respiratory disease and death, including those with multi-drug resistance. A nucleotide polymorphism typing system was developed for M. haemolytica from the genome sequences of 1133 North American isolates, and used to identify genetic differences between isolates from the lungs and upper respiratory tract of cattle with and without clinical signs of respiratory disease...
November 29, 2016: BMC Genomics
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