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Lung Genome CT

Yoko Gunji-Niitsu, Toshio Kumasaka, Shigehiro Kitamura, Yoshito Hoshika, Takuo Hayashi, Hitoshi Tokuda, Riichiro Morita, Etsuko Kobayashi, Keiko Mitani, Mika Kikkawa, Kazuhisa Takahashi, Kuniaki Seyama
BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is a rare inherited autosomal genodermatosis and caused by germline mutation of the folliculin (FLCN) gene, a tumor suppressor gene of which protein product is involved in mechanistic target of rapamycin (mTOR) signaling pathway regulating cell growth and metabolism. Clinical manifestations in BHD syndrome is characterized by fibrofolliculomas of the skin, pulmonary cysts with or without spontaneous pneumothorax, and renal neoplasms. There has been no pulmonary neoplasm reported in BHD syndrome, although the condition is due to deleterious sequence variants in a tumor suppressor gene...
November 21, 2016: BMC Medical Genetics
Dragos Mihai Vasilescu, André B Phillion, Naoya Tanabe, Daisuke Kinose, David F Paige, Jacob J Kantrowitz, Gang Liu, Hanqiao Liu, Nick Fishbane, Stijn E Verleden, Bart M Vanaudenaerde, Marc E Lenburg, Christopher S Stevenson, Avrum Spira, Joel D Cooper, Tillie-Louise Hackett, James C Hogg
Micro Computed Tomography (CT) enables 3-dimensional (3D) imaging of complex soft tissue structures, but current protocols used to achieve this goal preclude cellular and molecular phenotyping of the tissue. Here we describe a radiolucent cryo stage that permits micro CT imaging of unfixed frozen human lung samples at a spatial resolution of 11 µm under conditions where the sample is maintained frozen at -30°C during imaging. The cryo stage was tested for thermal stability to maintain samples frozen up to 8 hours...
November 17, 2016: Journal of Applied Physiology
Junko Tanizaki, Eri Banno, Yosuke Togashi, Hidetoshi Hayashi, Kazuko Sakai, Masayuki Takeda, Hiroyasu Kaneda, Kazuto Nishio, Kazuhiko Nakagawa
Comprehensive genomic profiling for non-small cell lung cancer (NSCLC) is likely to identify more patients with rare genetic alterations including uncommon epidermal growth factor receptor gene (EGFR) mutations. It remains unclear how such patients should be treated, however. We here report a case of NSCLC positive for two uncommon mutations of EGFR and a KRAS mutation, including its treatment with the second-generation EGFR tyrosine kinase inhibitor (TKI) afatinib. Tumor specimen obtained by a NSCLC patient with no smoking history was analyzed by next-generation sequencing...
November 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Neema Jamshidi, Danshan Huang, Fereidoun G Abtin, Christopher T Loh, Stephen T Kee, Robert D Suh, Shota Yamamoto, Kingshuk Das, Sarah Dry, Scott Binder, Dieter R Enzmann, Michael D Kuo
Purpose To identify the variables and factors that affect the quantity and quality of nucleic acid yields from imaging-guided core needle biopsy. Materials and Methods This study was approved by the institutional review board and compliant with HIPAA. The authors prospectively obtained 232 biopsy specimens from 74 patients (177 ex vivo biopsy samples from surgically resected masses were obtained from 49 patients and 55 in vivo lung biopsy samples from computed tomographic [CT]-guided lung biopsies were obtained from 25 patients) and quantitatively measured DNA and RNA yields with respect to needle gauge, number of needle passes, and percentage of the needle core...
October 18, 2016: Radiology
Christopher Lee, Phillip L Guichet, Fereidoun Abtin
PURPOSE: This study aimed to assess the current practice patterns of radiologists performing percutaneous lung biopsies. MATERIALS AND METHODS: This cross-sectional study used a web-based survey sent to the Society of Thoracic Radiology membership from August to October 2015. Responses were collected anonymously, and results were tallied. RESULTS: A total of 244 Society of Thoracic Radiology members responded to the survey. One hundred thirty-seven radiologists regularly perform percutaneous lung biopsies, of whom 102 (74%) practice at an academic teaching hospital...
October 6, 2016: Journal of Thoracic Imaging
Eitan Halper-Stromberg, Michael H Cho, Carla Wilson, Dipti Nevrekar, James D Crapo, George Washko, Raúl San José Estépar, David A Lynch, Edwin K Silverman, Sonia Leach, Peter J Castaldi
RATIONALE: Automated analysis of computed tomographic (CT) lung images for epidemiologic nand genetic association studies is increasingly common, but little is known about the utility of visual versus semi-automated emphysema and airway assessments for genetic association studies. OBJECTIVES: Assess the relative utility of visual versus semi-automated emphysema and airway assessments for genetic association studies. METHODS: A standardized inspection protocol was used to visually assess chest CTs for 1540 non-Hispanic white subjects within the COPDGene Study for the presence and severity of radiographic features representing airway wall thickness and emphysema...
October 14, 2016: Annals of the American Thoracic Society
Adel Boueiz, Sharon M Lutz, Michael H Cho, Craig P Hersh, Russell P Bowler, George R Washko, Eitan Halper-Stromberg, Per Bakke, Amund Gulsvik, Nan M Laird, Terri H Beaty, Harvey O Coxson, James D Crapo, Edwin K Silverman, Peter J Castaldi, Dawn L DeMeo
RATIONALE: Emphysema has considerable variability in the severity and distribution of parenchymal destruction throughout the lungs. Upper lobe predominant emphysema has emerged as an important predictor of response to lung volume reduction surgery. Yet, aside from alpha-1 antitrypsin deficiency, the genetic determinants of emphysema distribution remain largely unknown. OBJECTIVES: To identify the genetic influences of emphysema distribution in non-alpha-1 antitrypsin deficient smokers...
September 26, 2016: American Journal of Respiratory and Critical Care Medicine
Avinash V Dharmadhikari, Jenny J Sun, Krzysztof Gogolewski, Brandi L Carofino, Vladimir Ustiyan, Misty Hill, Tadeusz Majewski, Przemyslaw Szafranski, Monica J Justice, Russell S Ray, Mary E Dickinson, Vladimir V Kalinichenko, Anna Gambin, Paweł Stankiewicz
FOXF1 heterozygous point mutations and genomic deletions have been reported in newborns with the neonatally lethal lung developmental disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV). However, no gain-of-function mutations in FOXF1 have been identified yet in any human disease conditions. To study the effects of FOXF1 overexpression in lung development, we generated a Foxf1 overexpression mouse model by knocking-in a Cre-inducible Foxf1 allele into the ROSA26 (R26) locus...
November 15, 2016: Biology Open
Zhongyuan Yin, Sisi Deng, Zhiwen Liang, Qiong Wang
This project aimed to set up a Beagle dog model of radiation-induced lung injury in order to supply fresh lung tissue samples in the different injury phases for gene and protein research. Three dogs received 18 Gy X-ray irradiation in one fraction, another three dogs received 8 Gy in each of three fractions at weekly intervals, and one control dog was not irradiated. Acute pneumonitis was observed during the first 3 months after radiation, and chronic lung fibrosis was found during the next 4-12 months in all the dogs exposed to radiation...
July 15, 2016: Journal of Radiation Research
Francesca Maria Carozzi, Simonetta Bisanzi
Lung cancer is the leading cause of cancer death worldwide and it would be essential to have effective tools to diagnose the disease in its early stages, to identify individuals at highest risk of developing the disease, and to set personalised therapies. The effectiveness of screening for lung cancer with low-dose CT (LDCT) in heavy smokers was demonstrated, in terms of reduction of cause-specific mortality, in recently published data by the study National Lung ScreeningTrial (NLST). In Europe, the introduction of LDCT as screening in individuals at risk is the object of a debate until the results of European randomized trials, expected in 2015-2016, are published...
January 2016: Epidemiologia e Prevenzione
Deborah A Hogan, Sven D Willger, Emily L Dolben, Thomas H Hampton, Bruce A Stanton, Hilary G Morrison, Mitchell L Sogin, Julianna Czum, Alix Ashare
Individuals with cystic fibrosis (CF) often acquire chronic lung infections that lead to irreversible damage. We sought to examine regional variation in the microbial communities in the lungs of individuals with mild-to-moderate CF lung disease, to examine the relationship between the local microbiota and local damage, and to determine the relationships between microbiota in samples taken directly from the lung and the microbiota in spontaneously expectorated sputum. In this initial study, nine stable, adult CF patients with an FEV1>50% underwent regional sampling of different lobes of the right lung by bronchoalveolar lavage (BAL) and protected brush (PB) sampling of mucus plugs...
2016: PloS One
Yalei Zhang, Mei Jiang, Qin Li, Wenhua Liang, Qihua He, Weiqing Chen, Jianxing He
INTRODUCTION: Recently, genome-wide association studies (GWAS) in Caucasian populations have identified an association between single nucleotide polymorphisms (SNPs) in the CHRNA5-A3-B4 nicotinic acetylcholine receptor subunit gene cluster on chromosome 15q25, lung cancer risk and smoking behaviors. However, these SNPs are rare in Asians, and there is currently no consensus on whether SNPs in CHRNA5-A3-B4 have a direct or indirect carcinogenic effect through smoking behaviors on lung cancer risk...
2016: PloS One
Simon Andreasen, Marta Persson, Katalin Kiss, Preben Homøe, Steffen Heegaard, Göran Stenman
A 69-year-old female with no previous medical history presented with a rapidly growing submandibular mass. Fine needle aspiration cytology suggested a small-cell carcinoma and PET-CT showed increased 18-FDG uptake in the submandibular mass as well as in a lung mass. Submandibular resection and selective neck dissection was performed and histopathologic examination revealed a combined large-cell neuroendocrine carcinoma (LCNEC) with a squamous component and without lymph node metastases. Resection of the lung tumor revealed a papillary adenocarcinoma that was morphologically distinctly different from the LCNEC...
April 2016: Oncology Reports
Zhi-Shuang Song, Yun Wu, Hong-Guo Zhao, Cai-Xia Liu, Hai-Yu Cai, Bao-Zhi Guo, Y A Xie, Hui-Rong Shi
Polymorphisms in microRNA (miR) genes and their target sites are a distinct classification of variation in the human genome, which are rapidly being identified and investigated in human cancer. A polymorphism in the miR-196a-2 locus has demonstrated significant associations with various types of cancer, including lung, breast, esophageal and gastric tumors. However, miR-196a-2 has not been fully explored in ovarian cancer, which shares similar biological characteristics with other types of cancer. Therefore, the present study aimed to elucidate the association between a single nucleotide polymorphism (SNP) in the mature sequence of miR-196a-2 (rs11614913, T/C) and the clinical features of 479 Chinese patients with epithelial ovarian cancer (EOC)...
January 2016: Oncology Letters
Jill E Kucab, Edwin P Zwart, Harry van Steeg, Mirjam Luijten, Heinz H Schmeiser, David H Phillips, Volker M Arlt
3-Nitrobenzanthrone (3-NBA) is a highly mutagenic compound and possible human carcinogen found in diesel exhaust. 3-NBA forms bulky DNA adducts following metabolic activation and induces predominantly G:CT:A transversions in a variety of experimental systems. Here we investigated the influence of nucleotide excision repair (NER) on 3-NBA-induced mutagenesis of the human tumour suppressor gene TP53 and the reporter gene lacZ. To this end we utilised Xpa -knockout (Xpa-Null) human TP53 knock-in (Hupki) embryo fibroblasts (HUFs)...
March 2016: DNA Repair
Md T Anam, Alokta Ishika, Md B Hossain, Jesmin
BACKGROUND: Hypoxia inducible factor 1-alpha (HIF1A) is a transcription factor that plays important role in regulating cascade of reactions. In this study, the effect of rs11549465 (1772 C/T) and rs11549467 (1790 G/A) polymorphisms of HIF1A gene and its association with cancers were investigated through meta-analysis. METHODS: Meta-analysis of genome wide association studies of HIF1A 1772 C/T polymorphism were conducted on 22 case-control studies of sample size 19024 and for 1790 G/A polymorphism 19 case-control studies were included with sample size 10654...
2015: Biomarker Research
Jian-Yue Jin, Feng-Ming Spring Kong
This chapter reviews and discusses approaches and strategies of personalized radiation therapy (PRT) for lung cancers at four different levels: (1) clinically established PRT based on a patient's histology, stage, tumor volume and tumor locations; (2) personalized adaptive radiation therapy (RT) based on image response during treatment; (3) PRT based on biomarkers; (4) personalized fractionation schedule. The current RT practice for lung cancer is partially individualized according to tumor histology, stage, size/location, and combination with use of systemic therapy...
2016: Advances in Experimental Medicine and Biology
Ferdouse Begum, Ingo Ruczinski, Shengchao Li, Edwin K Silverman, Michael H Cho, David A Lynch, Douglas Curran-Everett, James Crapo, Robert B Scharpf, Margaret M Parker, Jacqueline B Hetmanski, Terri H Beaty
Chronic obstructive pulmonary disease (COPD) is a progressive disease with both environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified multiple genomic regions influencing risk of COPD. To thoroughly investigate the genetic etiology of COPD, however, it is also important to explore the role of copy number variants (CNVs) because the presence of structural variants can alter gene expression and can be causal for some diseases. Here, we investigated effects of polymorphic CNVs on quantitative measures of pulmonary function and chest computed tomography (CT) phenotypes among subjects enrolled in COPDGene, a multisite study...
January 2016: Genetic Epidemiology
Wayne A Warner, Deborah J Wong, Fernando Palma-Diaz, Terry Y Shibuya, Jamil Momand
We describe the presentation, treatment, clinical outcome, and targeted genome analysis of a metastatic salivary acinic cell carcinoma (AciCC). A 71-year-old male presented with a 3 cm right tail of a parotid lesion, first detected as a nodule by the patient seven months earlier. He had a right total parotidectomy with cranial nerve VII resection, right facial nerve resection and grafting, resection of the right conchal cartilage, and right modified radical neck dissection. The primary tumor revealed AciCC with two distinct areas: a well-differentiated component with glandular architecture and a dedifferentiated component with infiltrative growth pattern associated with prominent stromal response, necrosis, perineural invasion, and cellular pleomorphism...
2015: Case Reports in Oncological Medicine
Nitasha Sehgal, Andrew J Fritz, Jaromira Vecerova, Hu Ding, Zihe Chen, Branislav Stojkovic, Sambit Bhattacharya, Jinhui Xu, Ronald Berezney
There is growing evidence that chromosome territories (CT) have a probabilistic non-random arrangement within the cell nucleus of mammalian cells including radial positioning and preferred patterns of interchromosomal interactions that are cell-type specific. While it is generally assumed that the three-dimensional (3D) arrangement of genes within the CT is linked to genomic regulation, the degree of non-random organization of individual CT remains unclear. As a first step to elucidating the global 3D organization (topology) of individual CT, we performed multi-color fluorescence in situ hybridization using six probes extending across each chromosome in human WI38 lung fibroblasts...
February 1, 2016: Human Molecular Genetics
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