Multifarious Roles of Intrinsic Disorder in Proteins Illustrate Its Broad Impact on Plant Biology

PubMed Central

Sun, Xiaolin; Rikkerink, Erik H.A.; Jones, William T.; Uversky, Vladimir N.

2013-01-01

Intrinsically disordered proteins (IDPs) are highly abundant in eukaryotic proteomes. Plant IDPs play critical roles in plant biology and often act as integrators of signals from multiple plant regulatory and environmental inputs. Binding promiscuity and plasticity allow IDPs to interact with multiple partners in protein interaction networks and provide important functional advantages in molecular recognition through transient protein–protein interactions. Short interaction-prone segments within IDPs, termed molecular recognition features, represent potential binding sites that can undergo disorder-to-order transition upon binding to their partners. In this review, we summarize the evidence for the importance of IDPs in plant biology and evaluate the functions associated with intrinsic disorder in five different types of plant protein families experimentally confirmed as IDPs. Functional studies of these proteins illustrate the broad impact of disorder on many areas of plant biology, including abiotic stress, transcriptional regulation, light perception, and development. Based on the roles of disorder in the protein–protein interactions, we propose various modes of action for plant IDPs that may provide insight for future experimental approaches aimed at understanding the molecular basis of protein function within important plant pathways. PMID:23362206

Molecular biological analysis in a patient with multiple lung adenocarcinomas.

PubMed

Wakayama, Tomoshige; Hirata, Hirokuni; Suka, Shunsuke; Sato, Kozo; Tatewaki, Masamitsu; Souma, Ryosuke; Satoh, Hideyuki; Tamura, Motohiko; Matsumura, Yuji; Imada, Hiroki; Sugiyama, Kumiya; Arima, Masafumi; Kurasawa, Kazuhiro; Fukuda, Takeshi; Fukushima, Yasutsugu

2018-05-01

The utility of molecular biological analysis in lung adenocarcinoma has been demonstrated. Herein we report a rare case presenting as multiple lung adenocarcinomas with four different EGFR gene mutations detected in three lung tumors. After opacification was detected by routine chest X-ray, the patient, a 64-year-old woman, underwent chest computed tomography which revealed a right lung segment S4 ground-glass nodule (GGN). Follow-up computed tomography revealed a 42 mm GGN nodule with a 26 mm nodule (S6) and a 20 mm GGN (S10). Histopathology of resected specimens from the right middle and lower lobes revealed all three nodules were adenocarcinomas. Four EGFR mutations were detected; no three tumors had the same mutations. Molecular biological analysis is a promising tool for the diagnosis of primary tumors in patients with multiple lung carcinomas of the same histotype, enabling appropriate treatment. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Complicating Whiteness: Identifications of Veteran White Teachers in Multicultural Settings

ERIC Educational Resources Information Center

Miele, Anthony

2013-01-01

A scrupulous search of whiteness literatures in relation to multicultural education reveals a preponderance of scholarship noting White privilege and race evasiveness. Given contrasting scholarship arguing White identity as complicated, multifarious, and bound to social and historical context, concurrent with a dearth of scholarship that examines…

Anti-food allergic activity of sulfated polysaccharide from gracilaria lemaneiformis is dependent on immunosuppression and inhibition of p38 mapk

USDA-ARS?s Scientific Manuscript database

Polysaccharides from marine sources offer diverse therapeutic functions due to their multifarious biological nature. Polysaccharide from Gracilaria lemaneiformis possesses various bioactive functions, but its anti-allergic activity remains incompletely defined. Objective: This study aimed to extract...

An Essay in Culture, Society, Education and Vocational Training

ERIC Educational Resources Information Center

Cully, John H.

2007-01-01

In many developing countries it is apparent that there are multifarious impediments associated with, and acting upon, educational development and the complexity of diverse socio-cultural landscapes. Indeed, numerous perspectives tend to be overlooked or possibly not even taken under consideration when it comes to the transmission of salient…

The Challenges of Defining and Measuring Student Engagement in Science

ERIC Educational Resources Information Center

Sinatra, Gale M.; Heddy, Benjamin C.; Lombardi, Doug

2015-01-01

Engagement is one of the hottest research topics in the field of educational psychology. Research shows that multifarious benefits occur when students are engaged in their own learning, including increased motivation and achievement. However, there is little agreement on a concrete definition and effective measurement of engagement. This special…

Treating Dyslexic and Dyscalculic Students

ERIC Educational Resources Information Center

Kumar, S. Praveen; Raja, B. William Dharma

2009-01-01

This article focusses on the specific learning disabilities found in schools such as Dyslexia and Dyscalculia, the influence of dyslexia on dyscalculia and the need to adopt certain strategies that help cope with this problem. Learners with multifarious language-related or arithmetic-related disabilities are found in most schools. These children…

EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk

PubMed Central

Wilson, Ian M.; Vucic, Emily A.; Enfield, Katey S.S.; Thu, Kelsie L.; Zhang, Yu-An; Chari, Raj; Lockwood, William W.; Radulovich, Niki; Starczynowski, Daniel T.; Banáth, Judit P.; Zhang, May; Pusic, Andrea; Fuller, Megan; Lonergan, Kim M.; Rowbotham, David; Yee, John; English, John C.; Buys, Timon P.H.; Selamat, Suhaida A.; Laird-Offringa, Ite A.; Liu, Pengyuan; Anderson, Marshall; You, Ming; Tsao, Ming-Sound; Brown, Carolyn J.; Bennewith, Kevin L.; MacAulay, Calum E.; Karsan, Aly; Gazdar, Adi F.; Lam, Stephen; Lam, Wan L.

2015-01-01

In an effort to identify novel biallelically inactivated tumor suppressor genes (TSG) in sporadic invasive and pre-invasive non-small cell lung cancer (NSCLC) genomes, we applied a comprehensive integrated multi-‘omics approach to investigate patient matched, paired NSCLC tumor and non-malignant parenchymal tissues. By surveying lung tumor genomes for genes concomitantly inactivated within individual tumors by multiple mechanisms, and by the frequency of disruption in tumors across multiple cohorts, we have identified a putative lung cancer TSG, Eyes Absent 4 (EYA4). EYA4 is frequently and concomitantly deleted, hypermethylated and underexpressed in multiple independent lung tumor data sets, in both major NSCLC subtypes, and in the earliest stages of lung cancer. We find not only that decreased EYA4 expression is associated with poor survival in sporadic lung cancers, but EYA4 SNPs are associated with increased familial cancer risk, consistent with EYA4’s proximity to the previously reported lung cancer susceptibility locus on 6q. Functionally, we find that EYA4 displays TSG-like properties with a role in modulating apoptosis and DNA repair. Cross examination of EYA4 expression across multiple tumor types suggests a cell type-specific tumorigenic role for EYA4, consistent with a tumor suppressor function in cancers of epithelial origin. This work shows a clear role for EYA4 as a putative TSG in NSCLC. PMID:24096489

Rhetoric, Literacy, and Social Change in Post-Mao China

ERIC Educational Resources Information Center

Wexler, Steven

2009-01-01

State, citizen, and corporate readings of a multifarious "Chineseness" fundamentally shape the space where East and West clash in post-Mao China. This dialectic represents a citizen's working-through a crisis of agency and a nation's negotiation of its role within a global economy. Given that China's subaltern literacies operate within…

Effects of urban development on ant communities: implications for ecosystem services and management

Treesearch

M.P. Sanford; Patricia N. Manley; Dennis D. Murphy

2009-01-01

Research that connects the effects of urbanization on biodiversity and ecosystem services is lacking. Ants perform multifarious ecological functions that stabilize ecosystems and contribute to a number of ecosystem services. We studied responses of ant communities to urbanization in the Lake Tahoe basin by sampling sites along a gradient...

Service-Learning in Supply Chain Management: Benefits, Challenges and Best Practices

ERIC Educational Resources Information Center

Schoenherr, Tobias

2015-01-01

Service-learning (SL) is a pedagogical approach in which students are assigned a course-related project in a not-for-profit organization, and are tasked to apply course content to execute the project. While the benefits are multifarious, only recently have supply chain management (SCM) courses adapted this innovative teaching methodology. The…

Targeting Extracellular Histones with Novel RNA Biodrugs for the Treatment of Acute Lung Injury

DTIC Science & Technology

2017-10-01

inactivate) circulating histones and prevent the morbidity and mortality associated with multiple organ dysfunction/ acute respiratory distress syndrome ...patients. 15. SUBJECT TERMS Acute lung injury (ALI), acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome , extracellular...are acute lung injury (ALI) from smoke/chlorine gas inhalation, burns, radiation , influenza and severe infection. Only recently have investigators

PPAR-γ in innate and adaptive lung immunity.

PubMed

Nobs, Samuel Philip; Kopf, Manfred

2018-05-16

The transcription factor PPAR-γ (peroxisome proliferator-activated receptor-γ) is a key regulator of lung immunity exhibiting multiple cell type specific roles in controlling development and function of the lung immune system. It is strictly required for the generation of alveolar macrophages by controlling differentiation of fetal lung monocyte precursors. Furthermore, it plays an important role in lung allergic inflammation by licensing lung dendritic cell t helper 2 (Th2) priming capacity as well as acting as a master transcription factor for pathogenic Th2 cells. Due to this plethora of functions and its involvement in multiple pulmonary diseases including asthma and pulmonary alveolar proteinosis, understanding the role of PPAR-γ in lung immunity is an important subject of ongoing research. ©2018 Society for Leukocyte Biology.

Successful intelligence: finding a balance.

PubMed

Sternberg

1999-11-01

Human intelligence has long been on the borderline between a scientific and a quasi-scientific field within the scope of psychological science. This is partially because its study and measurement have been particularly susceptible to socio-political agendas, but also because empirical tests of theories of intelligence have too often ranged from inadequate to nonexistent. In this article it is argued that two extremes have prevailed in the study of intelligence. At one extreme are general-ability (g) theorists, who have collected large amounts of data to test the theory of general intelligence, but often using restricted ranges of participants, materials or situational contexts. They also show a tendency to limit their methods of data analysis (e.g. to exploratory factor analysis). At another extreme are theorists arguing for new, multiple intelligences, whose theories have been subjected to few or no empirical tests. I argue that a middle ground is needed that recognizes the multifarious nature of intelligence and of people's conceptions of it, but that also is subjected to rigorous empirical tests.

Leaf economics and hydraulic traits are decoupled in five species-rich tropical-subtropical forests.

PubMed

Li, Le; McCormack, M Luke; Ma, Chengen; Kong, Deliang; Zhang, Qian; Chen, Xiaoyong; Zeng, Hui; Niinemets, Ülo; Guo, Dali

2015-09-01

Leaf economics and hydraulic traits are critical to leaf photosynthesis, yet it is debated whether these two sets of traits vary in a fully coordinated manner or there is room for independent variation. Here, we tested the relationship between leaf economics traits, including leaf nitrogen concentration and leaf dry mass per area, and leaf hydraulic traits including stomatal density and vein density in five tropical-subtropical forests. Surprisingly, these two suites of traits were statistically decoupled. This decoupling suggests that independent trait dimensions exist within a leaf, with leaf economics dimension corresponding to light capture and tissue longevity, and the hydraulic dimension to water-use and leaf temperature maintenance. Clearly, leaf economics and hydraulic traits can vary independently, thus allowing for more possible plant trait combinations. Compared with a single trait dimension, multiple trait dimensions may better enable species adaptations to multifarious niche dimensions, promote diverse plant strategies and facilitate species coexistence. © 2015 John Wiley & Sons Ltd/CNRS.

Constructivisms and Relativisms: A Shopper`s Guide

NASA Astrophysics Data System (ADS)

Bickhard, Mark H.

Diverse forms of constructivism can be found in the literature today. They exhibit a commonality regarding certain classical positions that they oppose - a unity in their negative identities - but a sometimes wild multiplicity and incompatibility regarding the positive proposals that they put forward. In particular, some constructivisms propose an epistemological idealism, with a concomitant relativism, while others are explicitly opposed to such positions, and move in multifarious different directions. This is a potentially confusing situation, and has resulted in some critics branding all constructivisms with the charge of relativism, and throwing out the baby with the bath water. In addition, since the epistemological foundations of even non-relativist constructivisms are not as familiar as the classical positions, there is a risk of mis-interpretation of constructivisms and their consequences, even by some who endorse them, not to mention those who criticize. Because I urge that some version of constructivism is an epistemological necessity, this situation strikes me as seriously unfortunate for philosophy, and potentially dangerous for the practice of education.

Mathematical supply-chain modelling: Product analysis of cost and time

NASA Astrophysics Data System (ADS)

Easters, D. J.

2014-03-01

Establishing a mathematical supply-chain model is a proposition that has received attention due to its inherent benefits of evolving global supply-chain efficiencies. This paper discusses the prevailing relationships found within apparel supply-chain environments, and contemplates the complex issues indicated for constituting a mathematical model. Principal results identified within the data suggest, that the multifarious nature of global supply-chain activities require a degree of simplification in order to fully dilate the necessary factors which affect, each sub-section of the chain. Subsequently, the research findings allowed the division of supply-chain components into sub-sections, which amassed a coherent method of product development activity. Concurrently, the supply-chain model was found to allow systematic mathematical formulae analysis, of cost and time, within the multiple contexts of each subsection encountered. The paper indicates the supply-chain model structure, the mathematics, and considers how product analysis of cost and time can improve the comprehension of product lifecycle management.

How the zebra got its stripes: a problem with too many solutions

PubMed Central

Larison, Brenda; Harrigan, Ryan J.; Thomassen, Henri A.; Rubenstein, Daniel I.; Chan-Golston, Alec M.; Li, Elizabeth; Smith, Thomas B.

2015-01-01

The adaptive significance of zebra stripes has thus far eluded understanding. Many explanations have been suggested, including social cohesion, thermoregulation, predation evasion and avoidance of biting flies. Identifying the associations between phenotypic and environmental factors is essential for testing these hypotheses and substantiating existing experimental evidence. Plains zebra striping pattern varies regionally, from heavy black and white striping over the entire body in some areas to reduced stripe coverage with thinner and lighter stripes in others. We examined how well 29 environmental variables predict the variation in stripe characteristics of plains zebra across their range in Africa. In contrast to recent findings, we found no evidence that striping may have evolved to escape predators or avoid biting flies. Instead, we found that temperature successfully predicts a substantial amount of the stripe pattern variation observed in plains zebra. As this association between striping and temperature may be indicative of multiple biological processes, we suggest that the selective agents driving zebra striping are probably multifarious and complex. PMID:26064590

Genetic susceptibility to lung cancer—light at the end of the tunnel?

PubMed Central

Christiani, David C.

2013-01-01

Lung cancer is one of the most common and deadliest cancers in the world. The major socio-environmental risk factor involved in the development of lung cancer is cigarette smoking. Additionally, there are multiple genetic factors, which may also play a role in lung cancer risk. Early work focused on the presence of relatively prevalent but low-penetrance alterations in candidate genes leading to increased risk of lung cancer. Development of new technologies such as genomic profiling and genome-wide association studies has been helpful in the detection of new genetic variants likely involved in lung cancer risk. In this review, we discuss the role of multiple genetic variants and review their putative role in the risk of lung cancer. Identifying genetic biomarkers and patterns of genetic risk may be useful in the earlier detection and treatment of lung cancer patients. PMID:23349013

Brain abscess mimicking lung cancer metastases; a case report.

PubMed

Asano, Michiko; Fujimoto, Nobukazu; Fuchimoto, Yasuko; Ono, Katsuichiro; Ozaki, Shinji; Kimura, Fumiaki; Kishimoto, Takumi

2013-01-01

A 76-year-old woman came to us because of staggering, fever, dysarthria, and appetite loss. Magnetic resonance imaging (MRI) of the brain revealed multiple masses with surrounding edema. Chest X-ray and computed tomography demonstrated a mass-like lesion in the left lung and left pleural effusion. Lung cancer and multiple brain metastases were suspected. However, the brain lesions demonstrated a high intensity through diffusion-weighted MRI. The finding was an important key to differentiate brain abscesses from lung cancer metastases. Copyright © 2013 Elsevier Inc. All rights reserved.

Validation of the Lung Subtyping Panel in Multiple Fresh-Frozen and Formalin-Fixed, Paraffin-Embedded Lung Tumor Gene Expression Data Sets.

PubMed

Faruki, Hawazin; Mayhew, Gregory M; Fan, Cheng; Wilkerson, Matthew D; Parker, Scott; Kam-Morgan, Lauren; Eisenberg, Marcia; Horten, Bruce; Hayes, D Neil; Perou, Charles M; Lai-Goldman, Myla

2016-06-01

Context .- A histologic classification of lung cancer subtypes is essential in guiding therapeutic management. Objective .- To complement morphology-based classification of lung tumors, a previously developed lung subtyping panel (LSP) of 57 genes was tested using multiple public fresh-frozen gene-expression data sets and a prospectively collected set of formalin-fixed, paraffin-embedded lung tumor samples. Design .- The LSP gene-expression signature was evaluated in multiple lung cancer gene-expression data sets totaling 2177 patients collected from 4 platforms: Illumina RNAseq (San Diego, California), Agilent (Santa Clara, California) and Affymetrix (Santa Clara) microarrays, and quantitative reverse transcription-polymerase chain reaction. Gene centroids were calculated for each of 3 genomic-defined subtypes: adenocarcinoma, squamous cell carcinoma, and neuroendocrine, the latter of which encompassed both small cell carcinoma and carcinoid. Classification by LSP into 3 subtypes was evaluated in both fresh-frozen and formalin-fixed, paraffin-embedded tumor samples, and agreement with the original morphology-based diagnosis was determined. Results .- The LSP-based classifications demonstrated overall agreement with the original clinical diagnosis ranging from 78% (251 of 322) to 91% (492 of 538 and 869 of 951) in the fresh-frozen public data sets and 84% (65 of 77) in the formalin-fixed, paraffin-embedded data set. The LSP performance was independent of tissue-preservation method and gene-expression platform. Secondary, blinded pathology review of formalin-fixed, paraffin-embedded samples demonstrated concordance of 82% (63 of 77) with the original morphology diagnosis. Conclusions .- The LSP gene-expression signature is a reproducible and objective method for classifying lung tumors and demonstrates good concordance with morphology-based classification across multiple data sets. The LSP panel can supplement morphologic assessment of lung cancers, particularly when classification by standard methods is challenging.

Intensity and Passion: On Musical Experience, Layers of Meaning, and Stages

ERIC Educational Resources Information Center

Varkøy, Øivind; Westby, Inger Anne

2014-01-01

In this article, the authors link the discussion of differing musical experiences to Frede V. Nielsen's exploration of music as a multifarious universe of meaning, which, in encounter with the listener's receptive consciousness, presents different layers of musical meaning. The focal point of the article is that which Nielsen refers to…

Defining a New 21st Century Skill-Computational Thinking: Concepts and Trends

ERIC Educational Resources Information Center

Haseski, Halil Ibrahim; Ilic, Ulas; Tugtekin, Ufuk

2018-01-01

Computational Thinking is a skill that guides the 21th century individual in the problems experienced during daily life and it has an ever-increasing significance. Multifarious definitions were attempted to explain the concept of Computational Thinking. However, it was determined that there was no consensus on this matter in the literature and…

From Face-to-Face to Paired Oral Proficiency Interviews: The Nut Is yet to Be Cracked

ERIC Educational Resources Information Center

Birjandi, Parviz; Bagherkazemi, Marzieh

2011-01-01

The pressing need for English oral communication skills in multifarious contexts today is compelling impetus behind the large number of studies done on oral proficiency interviewing. Moreover, given the recently articulated concerns with the fairness and social dimension of such interviews, parallel concerns have been raised as to how most fairly…

Educational Change in Scotland: Policy, Context and Biography

ERIC Educational Resources Information Center

Priestley, M.; Miller, K.

2012-01-01

The poor success rate of policy for curriculum change has been widely noted in the educational change literature. Part of the problem lies in the complexity of schools, as policy-makers have proven unable to micro-manage the multifarious range of factors that impact upon the implementation of policy. This article draws upon empirical data from a…

Facilities Offered by the University of Ibadan (Nigeria) Distance Learning Centre towards Learners' Academic Goal--An Evaluation

ERIC Educational Resources Information Center

Adegbile, J. A.; Oyekanmi, J. O.

2011-01-01

Distance learners in the University of Ibadan, Nigeria unlike other distance learners of different parts of the world are faced with various educational, social and psychological problems associated with the code of distance learning. The facilities offered by the University of Ibadan distance learning centre towards the users' multifarious needs…

Every Reader a Reviewer: The Online Book Conversation

ERIC Educational Resources Information Center

Hoffert, Barbara

2010-01-01

Over the last 15 years, the book review landscape has changed seismically. Reviewing is no longer centralized, with a few big voices leading the way, but fractured among numerous multifarious voices found mostly on the web. In turn, readers aren't playing the captive audience any more. Undone by economics, many traditional print sources have been…

Highly sensitive detection of multiple tumor markers for lung cancer using gold nanoparticle probes and microarrays.

PubMed

Gao, Wanlei; Wang, Wentao; Yao, Shihua; Wu, Shan; Zhang, Honglian; Zhang, Jishen; Jing, Fengxiang; Mao, Hongju; Jin, Qinghui; Cong, Hui; Jia, Chunping; Zhang, Guojun; Zhao, Jianlong

2017-03-15

Assay of multiple serum tumor markers such as carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (CYFRA21-1), and neuron specific enolase (NSE), is important for the early diagnosis of lung cancer. Dickkopf-1 (DKK1), a novel serological and histochemical biomarker, was recently reported to be preferentially expressed in lung cancer. Four target proteins were sandwiched by capture antibodies attached to microarrays and detection antibodies carried on modified gold nanoparticles. Optical signals generated by the sandwich structures were amplified by gold deposition with HAuCl 4 and H 2 O 2 , and were observable by microscopy or the naked eye. The four tumor markers were subsequently measured in 106 lung cancer patients and 42 healthy persons. The assay was capable of detecting multiple biomarkers in serum sample at concentration of <1 ng mL -1 in 1 h. Combined detection of the four tumor markers highly improved the sensitivity (to 87.74%) for diagnosis of lung cancer compared with sensitivity of single markers. A rapid, highly sensitive co-detection method for multiple biomarkers based on gold nanoparticles and microarrays was developed. In clinical use, it would be expected to improve the early diagnosis of lung cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel approach to analyzing lung cancer mortality disparities: Using the exposome and a graph-theoretical toolchain

PubMed Central

Juarez, Paul D; Hood, Darryl B; Rogers, Gary L; Baktash, Suzanne H; Saxton, Arnold M; Matthews-Juarez, Patricia; Im, Wansoo; Cifuentes, Myriam Patricia; Phillips, Charles A; Lichtveld, Maureen Y; Langston, Michael A

2017-01-01

Objectives The aim is to identify exposures associated with lung cancer mortality and mortality disparities by race and gender using an exposome database coupled to a graph theoretical toolchain. Methods Graph theoretical algorithms were employed to extract paracliques from correlation graphs using associations between 2162 environmental exposures and lung cancer mortality rates in 2067 counties, with clique doubling applied to compute an absolute threshold of significance. Factor analysis and multiple linear regressions then were used to analyze differences in exposures associated with lung cancer mortality and mortality disparities by race and gender. Results While cigarette consumption was highly correlated with rates of lung cancer mortality for both white men and women, previously unidentified novel exposures were more closely associated with lung cancer mortality and mortality disparities for blacks, particularly black women. Conclusions Exposures beyond smoking moderate lung cancer mortality and mortality disparities by race and gender. Policy Implications An exposome approach and database coupled with scalable combinatorial analytics provides a powerful new approach for analyzing relationships between multiple environmental exposures, pathways and health outcomes. An assessment of multiple exposures is needed to appropriately translate research findings into environmental public health practice and policy. PMID:29152601

[Meta-analysis for correlation between multiple lung lobe lesions and prognostic influence on acquired pneumonia in hospitalized elderly patients].

PubMed

Huang, Wenjie; Feng, Wei; Li, Yang; Chen, Yu

2014-11-01

To explore the correlation regarding the prognostic influence between multiple lung lobe lesions and acquired pneumonia in hospitalized elderly patients by a Meta-analysis. We collected all studies which investigated the correlation regarding the prognostic effect between multiple lung lobe lesions and acquired pneumonia by searching China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, Chinese Biological Medical Literature Database, PubMed, and EMBase in accordance with the inclusion and exclusion criteria. Th e retrieval limit time of searches was from databases establishment to July 2014. Th e Meta-analysis was performed by using RevMan5.2 soft ware. We calculated the odds ratio (OR) and 95% confidence interval (95% CI) by using heterogeneous tests. Publication bias was assessed by Egger's test and funnel plot, and the sensitivity was analyzed. Ten studies involving 1 836 patients were finally included, with 487 cases (the dead group) and 1 349 controls (the survival group). The Meta-analysis demonstrated that multiple lung lobe lesions was highly correlated with the prognosis for the aged acquired pneumonia (OR=3.22, 95% CI 1.84 to 5.63). Multiple lung lobe lesions increase the risk of death in the prognosis of the aged patients with acquired pneumonia.

Interplay between the lung microbiome and lung cancer.

PubMed

Mao, Qixing; Jiang, Feng; Yin, Rong; Wang, Jie; Xia, Wenjie; Dong, Gaochao; Ma, Weidong; Yang, Yao; Xu, Lin; Hu, Jianzhong

2018-02-28

The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer. Some recent studies have shown that certain microbes and microbiota dysbiosis are correlated with development of lung cancer. In this mini-review, we briefly summarize current research findings describing the relationship between the lung microbiome and lung cancer. We further discuss the potential mechanisms through which the lung microbiome may play a role in lung carcinogenesis and impact lung cancer treatment. A better knowledge of the interplay between the lung microbiome and lung cancer may promote the development of innovative strategies for early prevention and personalized treatment in lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Estimation of lung tumor position from multiple anatomical features on 4D-CT using multiple regression analysis.

PubMed

Ono, Tomohiro; Nakamura, Mitsuhiro; Hirose, Yoshinori; Kitsuda, Kenji; Ono, Yuka; Ishigaki, Takashi; Hiraoka, Masahiro

2017-09-01

To estimate the lung tumor position from multiple anatomical features on four-dimensional computed tomography (4D-CT) data sets using single regression analysis (SRA) and multiple regression analysis (MRA) approach and evaluate an impact of the approach on internal target volume (ITV) for stereotactic body radiotherapy (SBRT) of the lung. Eleven consecutive lung cancer patients (12 cases) underwent 4D-CT scanning. The three-dimensional (3D) lung tumor motion exceeded 5 mm. The 3D tumor position and anatomical features, including lung volume, diaphragm, abdominal wall, and chest wall positions, were measured on 4D-CT images. The tumor position was estimated by SRA using each anatomical feature and MRA using all anatomical features. The difference between the actual and estimated tumor positions was defined as the root-mean-square error (RMSE). A standard partial regression coefficient for the MRA was evaluated. The 3D lung tumor position showed a high correlation with the lung volume (R = 0.92 ± 0.10). Additionally, ITVs derived from SRA and MRA approaches were compared with ITV derived from contouring gross tumor volumes on all 10 phases of the 4D-CT (conventional ITV). The RMSE of the SRA was within 3.7 mm in all directions. Also, the RMSE of the MRA was within 1.6 mm in all directions. The standard partial regression coefficient for the lung volume was the largest and had the most influence on the estimated tumor position. Compared with conventional ITV, average percentage decrease of ITV were 31.9% and 38.3% using SRA and MRA approaches, respectively. The estimation accuracy of lung tumor position was improved by the MRA approach, which provided smaller ITV than conventional ITV. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Inflammatory responses to neutral fat and fatty acids in multiple organs in a rat model of fat embolism syndrome.

PubMed

Takada, Meri; Chiba, Shoetsu; Nagai, Tomonori; Takeshita, Hiroshi; Kanno, Sanae; Ikawa, Toru; Sakamoto, Kana; Sagi, Morihisa; Ichiba, Kazue; Mukai, Toshiji

2015-09-01

Fat embolism syndrome (FES) is a common complication of long bone fractures. FES is rare but with significant morbidity and occasional fatalities. Studies of animal models of FES are numerous; however, few studies compare inflammatory reactions in multiple organs. The present study investigated the effect of neutral fat and fatty acids, which cause changes in multiple organs and induce FES. Using rats we evaluated the ratio of lung-to-body weight and conducted histological analyses and quantitative analysis of inflammatory cytokine mRNAs in the lungs following intravenous administration of neutral fat or fatty acids. Neutral fat increased the ratio of lung-to-body weight, and neutral fat formed emboli in lung capillaries. The levels of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in the lungs increased after injection of neutral fat and oleic acid. Analysis of the histologic changes revealed that the highest numbers of fat droplets, occluding the capillaries of the lungs, kidney, heart, and brain formed 12h after the injection of neutral fat and fat droplets gradually diminished 48h later. Fat droplets were not detected in any organs after the injection of oleic acid. IL-1β and TNF-α levels in the lungs were elevated 9-24h after the injection of neutral fat, although IL-6 levels peaked at 6h. After injection of oleic acid, peak levels of IL-1β, IL-6, and TNF-α were detected at 6h, and IL-6 again increased in all organs and plasma at 15h. Neutral fat, but not fatty acids, formed emboli in the capillaries of multiple organs. These findings suggest that neutral fat increased inflammatory cytokine levels by forming emboli in organ capillaries, particularly in the lungs, while oleic acid augmented inflammatory cytokine levels by stimulating endothelial cells of multiple organs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Porcupine quill migration in the thoracic cavity of a German shorthaired pointer.

PubMed

Guevara, Jose L; Holmes, Elaine S; Reetz, Jennifer; Holt, David E

2015-01-01

A 7 yr old German shorthaired pointer presented with progressive respiratory distress and lethargy. Two weeks prior to presentation, the dog had porcupine quills removed from the left forepaw, muzzle, and sternal area. At the time of presentation, the dog had bounding pulses and friction rubs in the right dorsal lung field. Harsh lung sounds and decreased lung sounds were ausculted in multiple lung fields. Radiographs revealed a pneumothorax and rounding of the cardiac silhouette suggestive of pericardial effusion. Computed tomographic imaging was performed and revealed multiple porcupine quills in the thoracic cavity. Surgery was performed and quills were found in multiple lung lobes and the heart. Following surgery the dog remained hypotensive. A post-operative echocardiogram revealed multiple curvilinear soft-tissue opacities in the heart. Given the grave prognosis the dog was subsequently euthanized and a postmortem examination was performed. A single porcupine quill was discovered in the left atrium above the mitral valve annulus. The quill extended across the aortic root, impinging on the coronary artery below the level of the aortic valve. To the authors' knowledge, this is the first known report of porcupine quill migration through the heart.

A Harvard Attorney Whose Job Is Advising Undocumented Students in the Age of Trump

ERIC Educational Resources Information Center

Corral, Jason

2018-01-01

As an immigration attorney for the past 14 years in both private practice and legal services, the author feels confident in saying there is not a "single" kind of immigrant or one kind of immigration story. There are multifarious individuals and families of diverse global origin bearing a cornucopia of ideas, perspectives, hopes and…

Quantitative determination of a-Arbutin, ß-Arbutin, Kojic acid, nicotinamide, hydroquinone, resorcinol, 4-methoxyphenol, 4-ethoxyphenol and ascorbic acid from skin whitening Products by HPLC-UV

USDA-ARS?s Scientific Manuscript database

Development of an analytical method for the simultaneous determination of multifarious skin whitening agents will provide an efficient tool to analyze skin whitening cosmetics. An HPLC-UV method was developed for quantitative analysis of six commonly used whitening agents, a-arbutin, ß-arbutin, koji...

"I'm Just a Numbers Person": The Complexity, Nature and Effects of the Quantification of Education

ERIC Educational Resources Information Center

Hardy, Ian

2015-01-01

This paper draws upon the sociology of numbers, particularly work by Theodore Porter, to reveal the multifarious ways in which numbers actively constitute practices in schools. Drawing upon a case study of one low-performing school in a low-performing region in the state of Queensland, Australia, and theorising into the sociology of numbers, the…

Language Testing: An Overview and Language Testing in Educational Institutions of Bangladesh

ERIC Educational Resources Information Center

Hossain, Md. Mahroof; Ahmed, Md. Kawser

2015-01-01

Test is procedures for measuring ability, knowledge or performance. Testing can be defined as a method of assessment and improvement of the students. Language testing in any point is an extremely multifarious task that ought to be based on method as well as exercise. The results of assessments are used for one or more purposes. So they have an…

A model for treating avian aspergillosis: serum and lung tissue kinetics for Japanese quail (Coturnix japonica) following single and multiple aerosol exposures of a nanoparticulate itraconazole suspension.

PubMed

Rundfeldt, Chris; Wyska, Elżbieta; Steckel, Hartwig; Witkowski, Andrzej; Jeżewska-Witkowska, Grażyna; Wlaź, Piotr

2013-11-01

Aspergillosis is frequently reported in parrots, falcons and other birds held in captivity. Inhalation is the main route of infection for Aspergillus fumigatus, resulting in both acute and chronic disease conditions. Itraconazole (ITRA) is an antifungal commonly used in birds, but administration requires repeated oral dosing and the safety margin is narrow. We describe lung tissue and serum pharmacokinetics of a nanoparticulate ITRA suspension administered to Japanese quail by aerosol exposure. Aerosolized ITRA (1 and 10% suspension) administered over 30 min did not induce adverse clinical reactions in quail upon single or 5-day repeated doses. High lung concentrations, well above the inhibitory levels for A. fumigatus, of 4.14 ± 0.19 μg/g and 27.5 ± 4.58 μg/g (mean ± SEM, n = 3), were achieved following single-dose inhalation of 1% and 10% suspension, respectively. Upon multiple dose administration of 10% suspension, mean lung concentrations reached 104.9 ± 10.1 μg/g. Drug clearance from the lungs was slow with terminal half-lives of 19.7 h and 35.8 h following inhalation of 1% and 10% suspension, respectively. Data suggest that lung clearance is solubility driven. Lung concentrations of hydroxy-itraconazole reached 1-2% of the ITRA lung tissue concentration indicating metabolism in lung tissue. Steady, but low, serum concentrations of ITRA could be measured after multiple dose administration, reaching less than 0.1% of the lung tissue concentration. This formulation may represent a novel, easy to administer treatment modality for fungal lung infection, preventing high systemic exposure. It may also be useful as metaphylaxis to prevent the outbreak of aspergillosis in colonized animals.

Recurrence of lung adenocarcinoma after an interval of 15 years revealed by demonstration of the same type of EML4-ALK fusion gene.

PubMed

Tsukamoto, Yoshitane; Kanamori, Kiyonobu; Watanabe, Takahiro; Mikami, Koji; Ieki, Ryuji; Nakano, Takashi; Kajimoto, Kazuyoshi; Hirota, Seiichi

2014-12-01

We carried out an experiment on a 58-year-old man with multiple left lung tumors and swelling of multiple lymph nodes. For clinical staging and therapeutic purposes, bronchoalveolar lavage (BAL) cytology and lung biopsy were performed. The biopsy specimen revealed the left lower lung mass to be immunohistochemically ALK (anaplastic lymphoma kinase)-positive adenocarcinoma. Using the BAL specimen from the left lower lung, EML4 (echinoderm microtubule-associated protein-like 4)-ALK variant 1 fusion gene was detected by reverse transcription-polymerase chain reaction (RT-PCR). His past history showed that he had undergone an operation for lung adenocarcinoma of the right lower lobe 15 years before, and the pathological specimen at that time revealed that the lung adenocarcinoma with pleural invasion and single metastasis of mediastinal lymph node showed a mucinous cribriform pattern and/or signet-ring cell pattern. The typical histology led us to examine the ALK rearrangement in the primary lung cancer and mediastinal metastatic tumor. Immunohistochemistry (IHC) for ALK was positive, and ALK break apart fluorescence in situ hybridization (FISH) showed a positive result. Moreover, RT-PCR using formalin-fixed, paraffin-embedded tissue from the right lung cancer also demonstrated EML4-ALK variant 1 fusion gene. Although there is a possibility that the left lung cancer is de novo one with multiple metastases, detection of the same fusion gene of the very rare EML4-ALK variant 1 in both tumors suggests that the left cancer is a recurrence of the right lung cancer after an interval of 15 years. Copyright © 2014 Elsevier GmbH. All rights reserved.

Development of Multiple Primary Cancers in Lung Cancer Patients: Appalachian Versus Non-Appalachian Populations of Kentucky.

PubMed

Pravosud, Vira; Huang, Bin; Tucker, Thomas; Vanderford, Nathan L

2017-12-01

The aim of this study was to investigate whether patients with lung cancer in Appalachian Kentucky are more likely to develop multiple primary cancers than patients in non-Appalachian Kentucky. Additional analyses were conducted to identify other factors that may be associated with an increased hazard of developing multiple primary cancers in patients with lung cancer. The data for this retrospective, population-based cohort study of 26,456 primary lung cancer patients were drawn from the Kentucky Cancer Registry. For inclusion in the study, patients must have been diagnosed between January 1, 2000 and December 31, 2013 and they must either have continually resided in Appalachian Kentucky or continually resided in non-Appalachian Kentucky. Cases were excluded if the patient was diagnosed as having additional primary cancers within 3 months of the initial diagnosis of primary lung cancer. The medical records for each case were examined to determine whether the patient was subsequently diagnosed as having additional primary cancers. The Cox proportional hazards model was then used to assess whether there was an association between the region in which the patients live and the likelihood of developing multiple primary cancers. Time to event was considered as the time from diagnosis to either death or development of a second primary cancer. The results presented here indicate that the risk of developing multiple primary cancers is the same for patients with lung cancer throughout Kentucky (hazard ratio [HR] 1.002, P = 0.9713). We found no evidence for a greater hazard in patients from Appalachia; however, additional analyses revealed several high-risk groups. Male patients and older patients had a significantly greater hazard of developing multiple primary cancers (HR 1.169, P = 0.012 and 1.015, P = 0.0001, respectively). In addition, patients who underwent surgery and those who were diagnosed initially as having an earlier stage of cancer also were more likely to develop multiple primary cancers (HR 1.446, P = 0.0003 and 0.684, P = 0.0015, respectively). This is a negative study. Patients with primary lung cancer living in Appalachian Kentucky are not at a greater risk of developing multiple primary cancers than those residing in non-Appalachian Kentucky. High-risk groups identified in this study are male patients and older patients. The increased hazard seen in patients who underwent surgery or those who were diagnosed as having earlier stages of lung cancer are likely an artifact of these patients living longer and, therefore, having more time to develop additional primary cancers.

Treatment with a neutralising anti-rat interleukin-17 antibody after multiple-trauma reduces lung inflammation.

PubMed

Dai, Heling; Xu, Li; Tang, Yu; Liu, Zhi; Sun, Tiansheng

2015-08-01

It has been well recognised that a deficit of numbers and function of CD4(+)CD25(+)Foxp3(+) cells (Treg) is attributed to the development of autoimmune diseases and inflammatory diseases; additionally, IL-17-producing cells (Th17) have a pro-inflammatory role. The balance between Th17 and Treg may be essential for maintaining immune homeostasis and has long been thought as one of the important factors in the development/prevention of autoimmune diseases and inflammatory diseases. In our previous research, we explored that cytokines (IL-17) and the balance of Treg/Th17 had a significant relevance with tissue (lung) inflammation and injury in acute-phase after multiple-trauma. To more verify whether an imbalance of Treg/Th17 is characteristic of rats suffering from multiple trauma. Using IL-17 monoclonal antibody (IL-17mAb)-treated multiple-trauma rat, we tested the pathogenic role of IL-17 in the development of multiple-trauma. Rat models were treated respectively with IL-17mAb or rat IgG 2A isotype control or phosphate-buffered solution after model was established. Normal rats only received anaesthesia and cannulation were taken as sham. Rats in each group were killed respectively at the end of 1h, 4h, 8h after injection. Collected serum and lung samples for assessment dynamically of MPO, IL-17, IL-6, and TGF-β-mRNA, and cytokine (IL-17, IL-6, TGF-β) and lung tissue for pulmonary histological analysis. Neutralisation of IL-17 with anti-IL-17 can decrease serum IL-17 level and the IL-17-mRNA transcript level in lung, and ameliorate tissue inflammatory, defer disease course. Our data suggest that IL-17 is crucially involved in the pathogenesis of multiple-trauma in rat, IL-17 inhibition might ameliorate the lung inflammation in acute-phase after multiple-trauma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Salivary duct carcinoma treated with cetuximab-based targeted therapy: A case report.

PubMed

Kawahara, Kenta; Hiraki, Akimitsu; Yoshida, Ryoji; Arita, Hidetaka; Matsuoka, Yuichiro; Yamashita, Toshio; Koga, Kan-Ichi; Nagata, Masashi; Hirosue, Akiyuki; Fukuma, Daiki; Nakayama, Hideki

2017-06-01

Salivary duct carcinoma is a highly aggressive disease with a poor prognosis. Surgical resection is currently the only curative treatment, as there is no effective systemic therapy for this malignancy. Recently, trastuzumab has been shown to exhibit therapeutic efficacy in the treatment of salivary duct carcinoma; similarly, molecularly targeted agents, such as cetuximab, are expected to be useful for salivary duct carcinoma treatment. We herein describe the case of a 56-year-old man diagnosed with salivary duct carcinoma in the left submandibular region, with ipsilateral multiple metastases to the neck lymph nodes. Radical resection of the tumor and submandibular gland with neck dissection were performed. One month after radical surgery, computed tomography (CT) scans indicated metastasis in the lower lobe of the left lung. CT-guided transthoracic fine-needle aspiration biopsy revealed a single metastasis and lung metastasectomy was immediately performed. The tumor cells of the primary lesion and those of the lung metastasis were immunohistochemically positive for epidermal growth factor receptor. One month later, multiple right lung metastases appeared, and the patient was treated with cisplatin/5-fluorouracil (5-FU) chemotherapy plus cetuximab, achieving a complete radiographic response. However, multiple lung metastases developed during adjuvant weekly cetuximab monotherapy. Subsequently, treatment with S-1 and weekly cetuximab was initiated, and the multiple lung metastases have been maintained as stable disease for 5 months. To the best of our knowledge, this is the first report of cetuximab use for the treatment of salivary duct carcinoma. Although cisplatin/5-FU chemotherapy plus cetuximab was efficacious in treating the lung metastasis, cetuximab monotherapy was insufficient for controlling tumor growth.

Deflation-activated receptors, not classical inflation-activated receptors, mediate the Hering-Breuer deflation reflex.

PubMed

Yu, Jerry

2016-11-01

Many airway sensory units respond to both lung inflation and deflation. Whether those responses to opposite stimuli come from one sensor (one-sensor theory) or more than one sensor (multiple-sensor theory) is debatable. One-sensor theory is commonly presumed in the literature. This article proposes a multiple-sensor theory in which a sensory unit contains different sensors for sensing different forces. Two major types of mechanical sensors operate in the lung: inflation- and deflation-activated receptors (DARs). Inflation-activated sensors can be further divided into slowly adapting receptors (SARs) and rapidly adapting receptors (RARs). Many SAR and RAR units also respond to lung deflation because they contain DARs. Pure DARs, which respond to lung deflation only, are rare in large animals but are easily identified in small animals. Lung deflation-induced reflex effects previously attributed to RARs should be assigned to DARs (including pure DARs and DARs associated with SARs and RARs) if the multiple-sensor theory is accepted. Thus, based on the information, it is proposed that activation of DARs can attenuate lung deflation, shorten expiratory time, increase respiratory rate, evoke inspiration, and cause airway secretion and dyspnea.

Characterization of the Lung Parenchyma Using Ultrasound Multiple Scattering.

PubMed

Mohanty, Kaustav; Blackwell, John; Egan, Thomas; Muller, Marie

2017-05-01

The purpose of the study described here was to showcase the application of ultrasound to quantitative characterization of the micro-architecture of the lung parenchyma to predict the extent of pulmonary edema. The lung parenchyma is a highly complex and diffusive medium for which ultrasound techniques have remained qualitative. The approach presented here is based on ultrasound multiple scattering and exploits the complexity of ultrasound propagation in the lung structure. The experimental setup consisted of a linear transducer array with an 8-MHz central frequency placed in contact with the lung surface. The diffusion constant D and transport mean free path L* of the lung parenchyma were estimated by separating the incoherent and coherent intensities in the near field and measuring the growth of the incoherent diffusive halo over time. Significant differences were observed between the L* values obtained in healthy and edematous rat lungs in vivo. In the control rat lung, L* was found to be 332 μm (±48.8 μm), whereas in the edematous lung, it was 1040 μm (±90 μm). The reproducibility of the measurements of L* and D was tested in vivo and in phantoms made of melamine sponge with varying air volume fractions. Two-dimensional finite difference time domain numerical simulations were carried out on rabbit lung histology images with varying degrees of lung collapse. Significant correlations were observed between air volume fraction and L* in simulation (r = -0.9542, p < 0.0117) and sponge phantom (r = -0.9932, p < 0.0068) experiments. Ex vivo measurements of a rat lung in which edema was simulated by adding phosphate-buffered saline revealed a linear relationship between the fluid volume fraction and L*. These results illustrate the potential of methods based on ultrasound multiple scattering for the quantitative characterization of the lung parenchyma. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Identification of NPM and DDX5 as Therapeutic Targets in TSC

DTIC Science & Technology

2017-12-01

Individuals with TSC develop benign tumors in multiple organs, including the retina, skin, lung, kidney and brain. The identification of valid targets in TSC...individuals. Individuals with TSC develop benign tumors in multiple organs, including the retina, skin, lung, kidney and brain. However, these lesions can

Assessing the feasibility of a web-based registry for multiple orphan lung diseases: the Australasian Registry Network for Orphan Lung Disease (ARNOLD) experience.

PubMed

Casamento, K; Laverty, A; Wilsher, M; Twiss, J; Gabbay, E; Glaspole, I; Jaffe, A

2016-04-18

We investigated the feasibility of using an online registry to provide prevalence data for multiple orphan lung diseases in Australia and New Zealand. A web-based registry, The Australasian Registry Network of Orphan Lung Diseases (ARNOLD) was developed based on the existing British Paediatric Orphan Lung Disease Registry. All adult and paediatric respiratory physicians who were members of the Thoracic Society of Australia and New Zealand in Australia and New Zealand were sent regular emails between July 2009 and June 2014 requesting information on patients they had seen with any of 30 rare lung diseases. Prevalence rates were calculated using population statistics. Emails were sent to 649 Australian respiratory physicians and 65 in New Zealand. 231 (32.4%) physicians responded to emails a total of 1554 times (average 7.6 responses per physician). Prevalence rates of 30 rare lung diseases are reported. A multi-disease rare lung disease registry was implemented in the Australian and New Zealand health care settings that provided prevalence data on orphan lung diseases in this region but was limited by under reporting.

Cystic lung disease in birt-hogg-dubé syndrome: a case series of three patients.

PubMed

Kilincer, Abidin; Ariyurek, Orhan Macit; Karabulut, Nevzat

2014-06-01

Birt-Hogg-Dubé syndrome is characterized by clinical manifestations such as hamartomas of the skin, renal tumors and lung cysts with spontaneous pneumothoraces. Patients with Birt-Hogg-Dubé syndrome may present with only multiple lung cysts. We report the chest computerized tomography (CT) features of three patients with Birt-Hogg-Dubé syndrome. Each patient had multiple lung cysts of various sizes according to chest CT evaluation, most of which were located in lower lobes and related to pleura. The identification of unique characteristics in the chest CT of patients with Birt-Hogg-Dubé syndrome may provide an efficient mechanism for diagnosis.

Different EGFR gene mutations in two patients with synchronous multiple lung cancers: A case report

PubMed Central

Sakai, Hiroki; Kimura, Hiroyuki; Tsuda, Masataka; Wakiyama, Yoichi; Miyazawa, Tomoyuki; Marushima, Hideki; Kojima, Koji; Hoshikawa, Masahiro; Takagi, Masayuki; Nakamura, Haruhiko

2017-01-01

Routine clinical and pathological evaluations to determine the relationship between different lesions are often not completely conclusive. Interestingly, detailed genetic analysis of tumor samples may provide important additional information and identify second primary lung cancers. In the present study, we report cases of two synchronous lung adenocarcinomas composed of two distinct pathological subtypes with different EGFR gene mutations: a homozygous deletion in exon 19 of the papillary adenocarcinoma subtype and a point mutation of L858R in exon 21 of the tubular adenocarcinoma. The present report highlights the clinical importance of molecular cancer biomarkers to guide management decisions in cases involving multiple lung tumors. PMID:29090842

Lung tumor promotion by chromium-containing welding particulate matter in a mouse model.

PubMed

Zeidler-Erdely, Patti C; Meighan, Terence G; Erdely, Aaron; Battelli, Lori A; Kashon, Michael L; Keane, Michael; Antonini, James M

2013-09-05

Epidemiology suggests that occupational exposure to welding particulate matter (PM) may increase lung cancer risk. However, animal studies are lacking to conclusively link welding with an increased risk. PM derived from stainless steel (SS) welding contains carcinogenic metals such as hexavalent chromium and nickel. We hypothesized that welding PM may act as a tumor promoter and increase lung tumor multiplicity in vivo. Therefore, the capacity of chromium-containing gas metal arc (GMA)-SS welding PM to promote lung tumors was evaluated using a two-stage (initiation-promotion) model in lung tumor susceptible A/J mice. Male mice (n = 28-30/group) were treated either with the initiator 3-methylcholanthrene (MCA;10 μg/g; IP) or vehicle (corn oil) followed by 5 weekly pharyngeal aspirations of GMA-SS (340 or 680 μg/exposure) or PBS. Lung tumors were enumerated at 30 weeks post-initiation. MCA initiation followed by GMA-SS welding PM exposure promoted tumor multiplicity in both the low (12.1 ± 1.5 tumors/mouse) and high (14.0 ± 1.8 tumors/mouse) exposure groups significantly above MCA/sham (4.77 ± 0.7 tumors/mouse; p = 0.0001). Multiplicity was also highly significant (p < 0.004) across all individual lung regions of GMA-SS-exposed mice. No exposure effects were found in the corn oil groups at 30 weeks. Histopathology confirmed the gross findings and revealed increased inflammation and a greater number of malignant lesions in the MCA/welding PM-exposed groups. GMA-SS welding PM acts as a lung tumor promoter in vivo. Thus, this study provides animal evidence to support the epidemiological data that show welders have an increased lung cancer risk.

Lung tumor promotion by chromium-containing welding particulate matter in a mouse model

PubMed Central

2013-01-01

Background Epidemiology suggests that occupational exposure to welding particulate matter (PM) may increase lung cancer risk. However, animal studies are lacking to conclusively link welding with an increased risk. PM derived from stainless steel (SS) welding contains carcinogenic metals such as hexavalent chromium and nickel. We hypothesized that welding PM may act as a tumor promoter and increase lung tumor multiplicity in vivo. Therefore, the capacity of chromium-containing gas metal arc (GMA)-SS welding PM to promote lung tumors was evaluated using a two-stage (initiation-promotion) model in lung tumor susceptible A/J mice. Methods Male mice (n = 28-30/group) were treated either with the initiator 3-methylcholanthrene (MCA;10 μg/g; IP) or vehicle (corn oil) followed by 5 weekly pharyngeal aspirations of GMA-SS (340 or 680 μg/exposure) or PBS. Lung tumors were enumerated at 30 weeks post-initiation. Results MCA initiation followed by GMA-SS welding PM exposure promoted tumor multiplicity in both the low (12.1 ± 1.5 tumors/mouse) and high (14.0 ± 1.8 tumors/mouse) exposure groups significantly above MCA/sham (4.77 ± 0.7 tumors/mouse; p = 0.0001). Multiplicity was also highly significant (p < 0.004) across all individual lung regions of GMA-SS-exposed mice. No exposure effects were found in the corn oil groups at 30 weeks. Histopathology confirmed the gross findings and revealed increased inflammation and a greater number of malignant lesions in the MCA/welding PM-exposed groups. Conclusions GMA-SS welding PM acts as a lung tumor promoter in vivo. Thus, this study provides animal evidence to support the epidemiological data that show welders have an increased lung cancer risk. PMID:24107379

Increased expression of connective tissue growth factor (CTGF) in multiple organs after exposure of non-human primates (NHP) to lethal doses of radiation

PubMed Central

Zhang, Pei; Cui, Wanchang; Hankey, Kim G.; Gibbs, Allison M.; Smith, Cassandra P.; Taylor-Howell, Cheryl; Kearney, Sean R.; MacVittie, Thomas J.

2015-01-01

Exposure to sufficiently high doses of ionizing radiation is known to cause fibrosis in many different organs and tissues. Connective tissue growth factor (CTGF/CCN2), a member of the CCN family of matricellular proteins, plays an important role in the development of fibrosis in multiple organs. The aim of the present study was to quantify the gene and protein expression of CTGF in a variety of organs from non-human primates (NHP) that were previously exposed to potentially lethal doses of radiation. Tissues from non-irradiated NHP, and NHP exposed to whole thoracic lung irradiation (WTLI) or partial-body irradiation with 5% bone marrow sparing (PBI/BM5) were examined by real-time quantitative reverse transcription PCR, western blot, and immunohistochemistry. Expression of CTGF was elevated in the lung tissues of NHP exposed to WTLI relative to the lung tissues of the non-irradiated NHP. Increased expression of CTGF was also observed in multiple organs from NHP exposed to PBI/BM5 compared to non-irradiated NHP; these included the lung, kidney, spleen, thymus and liver. These irradiated organs also exhibited histological evidence of increased collagen deposition compared to the control tissues. There was significant correlation of CTGF expression with collagen deposition in the lung and spleen of NHP exposed to PBI/BM5. Significant correlations were observed between spleen and multiple organs on CTGF expression and collagen deposition respectively, suggesting possible crosstalk between spleen and other organs. Our data suggest that CTGF levels are increased in multiple organs after radiation exposure and that inflammatory cell infiltration may contribute to the elevated levels of CTGF in multiple organs. PMID:26425899

Beta-cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice

USDA-ARS?s Scientific Manuscript database

Nicotine, a large constituent of cigarette smoke, is associated with an increased risk of lung cancer, but the data supporting this relationship are inconsistent. Here, we found that nicotine treatment not only induced emphysema but also increased both lung tumor multiplicity and volume in 4-nitrosa...

Sticks and Stones: The Multifarious Effects of Body-Based Harassment on Young Girls' Healthy Lifestyle Choices

ERIC Educational Resources Information Center

Holman, Margery J.; Johnson, Jay; Lucier, Mary-Kaye

2013-01-01

The purpose of this study was to investigate the perceptions of girls and boys about the effects that body-based harassment would have on girls' eating habits and engagement in physical activity. Five scenarios were read to focus groups comprised of 12- to 14-year-old students in grades 7 and 8. Each scenario represented behaviours that fall…

Multifarious selection through environmental change: acidity and predator-mediated adaptive divergence in the moor frog (Rana arvalis)

PubMed Central

Egea-Serrano, Andrés; Hangartner, Sandra; Laurila, Anssi; Räsänen, Katja

2014-01-01

Environmental change can simultaneously cause abiotic stress and alter biological communities, yet adaptation of natural populations to co-changing environmental factors is poorly understood. We studied adaptation to acid and predator stress in six moor frog (Rana arvalis) populations along an acidification gradient, where abundance of invertebrate predators increases with increasing acidity of R. arvalis breeding ponds. First, we quantified divergence among the populations in anti-predator traits (behaviour and morphology) at different rearing conditions in the laboratory (factorial combinations of acid or neutral pH and the presence or the absence of a caged predator). Second, we evaluated relative fitness (survival) of the populations by exposing tadpoles from the different rearing conditions to predation by free-ranging dragonfly larvae. We found that morphological defences (relative tail depth) as well as survival of tadpoles under predation increased with increasing pond acidity (under most experimental conditions). Tail depth and larval size mediated survival differences among populations, but the contribution of trait divergence to survival was strongly dependent on prior rearing conditions. Our results indicate that R. arvalis populations are adapted to the elevated predator pressure in acidified ponds and emphasize the importance of multifarious selection via both direct (here: pH) and indirect (here: predators) environmental changes. PMID:24552840

Multifarious selection through environmental change: acidity and predator-mediated adaptive divergence in the moor frog (Rana arvalis).

PubMed

Egea-Serrano, Andrés; Hangartner, Sandra; Laurila, Anssi; Räsänen, Katja

2014-04-07

Environmental change can simultaneously cause abiotic stress and alter biological communities, yet adaptation of natural populations to co-changing environmental factors is poorly understood. We studied adaptation to acid and predator stress in six moor frog (Rana arvalis) populations along an acidification gradient, where abundance of invertebrate predators increases with increasing acidity of R. arvalis breeding ponds. First, we quantified divergence among the populations in anti-predator traits (behaviour and morphology) at different rearing conditions in the laboratory (factorial combinations of acid or neutral pH and the presence or the absence of a caged predator). Second, we evaluated relative fitness (survival) of the populations by exposing tadpoles from the different rearing conditions to predation by free-ranging dragonfly larvae. We found that morphological defences (relative tail depth) as well as survival of tadpoles under predation increased with increasing pond acidity (under most experimental conditions). Tail depth and larval size mediated survival differences among populations, but the contribution of trait divergence to survival was strongly dependent on prior rearing conditions. Our results indicate that R. arvalis populations are adapted to the elevated predator pressure in acidified ponds and emphasize the importance of multifarious selection via both direct (here: pH) and indirect (here: predators) environmental changes.

The Rho Kinases: Critical Mediators of Multiple Profibrotic Processes and Rational Targets for New Therapies for Pulmonary Fibrosis

PubMed Central

Knipe, Rachel S.; Tager, Andrew M.

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung scarring, short median survival, and limited therapeutic options, creating great need for new pharmacologic therapies. IPF is thought to result from repetitive environmental injury to the lung epithelium, in the context of aberrant host wound healing responses. Tissue responses to injury fundamentally involve reorganization of the actin cytoskeleton of participating cells, including epithelial cells, fibroblasts, endothelial cells, and macrophages. Actin filament assembly and actomyosin contraction are directed by the Rho-associated coiled-coil forming protein kinase (ROCK) family of serine/threonine kinases (ROCK1 and ROCK2). As would therefore be expected, lung ROCK activation has been demonstrated in humans with IPF and in animal models of this disease. ROCK inhibitors can prevent fibrosis in these models, and more importantly, induce the regression of already established fibrosis. Here we review ROCK structure and function, upstream activators and downstream targets of ROCKs in pulmonary fibrosis, contributions of ROCKs to profibrotic cellular responses to lung injury, ROCK inhibitors and their efficacy in animal models of pulmonary fibrosis, and potential toxicities of ROCK inhibitors in humans, as well as involvement of ROCKs in fibrosis in other organs. As we discuss, ROCK activation is required for multiple profibrotic responses, in the lung and multiple other organs, suggesting ROCK participation in fundamental pathways that contribute to the pathogenesis of a broad array of fibrotic diseases. Multiple lines of evidence therefore indicate that ROCK inhibition has great potential to be a powerful therapeutic tool in the treatment of fibrosis, both in the lung and beyond. PMID:25395505

State-of-the-art MS technology applications in lung disease.

PubMed

Végvári, Ákos; Döme, Balázs

2011-12-01

Two frontline MS technologies, which have recently gained much attention, are discussed within the scope of this review. Besides a brief summary on the contemporary state of lung cancer and chronic obstructive pulmonary disease, the principles of multiple reaction monitoring and matrix assisted laser desorption ionization (MALDI) MS imaging are presented. A comprehensive overview of quantitative mass spectrometry applications is provided, covering multiple reaction monitoring assay developments for analysis of proteins (biomarkers) and low-molecular-weight compounds (drugs) with a special focus on the disease areas of lung cancer and chronic obstructive pulmonary disease. The MALDI-MS imaging applications are discussed similarly, providing references to studies conducted on lung tissues in order to localize drug compounds and protein biomarkers.

[A case of lung abscess during chemotherapy for testicular tumor].

PubMed

Hayashi, Yujiro; Miyago, Naoki; Takeda, Ken; Yamaguchi, Yuichiro; Nakayama, Masashi; Arai, Yasuyuki; Kakimoto, Ken-ichi; Nishimura, Kazuo

2014-05-01

32-year-old man was seen in a clinic because of prolonged cough and slight-fever. Chest X-ray showed multiple pulmonary nodules, and multiple lung and mediastinal lymph node metastases from right testicular tumor was suspected by positron emission tomography/CT (PET/CT) scan. He was diagnosed with right testicular germ cell tumor (embryonal carcinoma + seminoma, pT2N1M1b), and classified into the intermediate risk group according to International Germ Cell Cancer Collaborative Group. He underwent 4 cycles of chemotherapy with bleomycin, etoposide and cisplatin (BEP therapy). During BEP therapy, sputum with foul odor appeared and chest CT scan revealed lung abscess with a necrotic lesion of metastatic tumor. The lung abscess was treated successfully with antibiotics.

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities

PubMed Central

Hammitt, Laura L.; Murdoch, David R.; O’Brien, Katherine L.; Scott, J. Anthony G.

2017-01-01

Abstract Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. PMID:28575369

A squamous cell lung carcinoma with abscess-like distant metastasis.

PubMed

Dursunoğlu, Neşe; Başer, Sevin; Evyapan, Fatma; Kiter, Göksel; Ozkurt, Sibel; Polat, Bahattin; Karabulut, Nevzat

2007-01-01

This is a metastatic spread of squamous cell lung carcinoma to lungs, liver, lymph node, bone and subcutanous region as multiple abscess-like lesions. A fifty-five years old man admitted to the out-patient clinic with fever, cough, hemopthysis, night sweats, chest pain, abdominal pain and weight loss. In a short period of time abcess like lesions developed in his lungs, liver, lymph node, bone and subcutanous region. Though the clinical presentation is suggestive for an infectious condition, no success to antimicrobial treatment and negative results of microbiological studies have arised a need to further investigations. Histopathological studies of the abscess wall ultimately gave the definitive diagnosis as metastatic squamous cell carcinoma. We believe that case report is interesting because of the uncommon metastatic lesions masquerading the abscesses and also wide-spread multiple distant invasions of a squamous cell lung carcinoma in a short time period.

Molecular Testing in Multiple Synchronous Lung Adenocarcinomas: Case Report and Literature Review.

PubMed

Rafael, Oana C; Lazzaro, Richard; Hasanovic, Adnan

2016-02-01

Discovery of driver mutations in pulmonary adenocarcinoma has revolutionized the field of thoracic oncology with major impact on therapy and diagnosis. Testing for EGFR, ALK, and KRAS mutations has become part of everyday practice. We report a case with multiple synchronous primary pulmonary adenocarcinomas in a 72-year-old female with previous history of smoking. The patient presented with cough and bilateral lung ground glass opacities. A positron emission tomography/computed tomography scan showed no activity in mediastinal lymph nodes. She underwent a left upper lobe biopsy and a right upper lobe wedge resection. Pathology revealed 4 morphologically distinct adenocarcinoma foci, suggestive of synchronous primary lung tumors. Molecular testing demonstrated no mutation in the left tumor. Three different driver mutations were present in the right lung tumors: KRAS codon 12 G12D and G12V and EGFR exon 21 L858R mutation, confirming the initial histologic impression. Subsequently, left upper lobe lobectomy showed 3 additional foci of adenocarcinoma with different morphologies, suggestive of synchronous primaries as well. No additional molecular testing was performed. Synchronous pulmonary adenocarcinomas are not uncommon; however, 4 or more synchronous tumors are rare. Distinguishing multiple primary tumors from intrapulmonary metastases is a common problem in thoracic oncology with major implications for staging, prognosis, and treatment. Lung adenocarcinoma subclassification based on predominant and coexisting histologic patterns can greatly facilitate differentiation between intrapulmonary metastases and multiple synchronous tumors. Use of molecular profiling is recommended since it further increases confidence in the diagnostic workup of multiple pulmonary adenocarcinomas and helps guiding therapy. © The Author(s) 2015.

Blood and lung microRNAs as biomarkers of pulmonary tumorigenesis in cigarette smoke-exposed mice

PubMed Central

Izzotti, Alberto; Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Longobardi, Mariagrazia; Pulliero, Alessandra; Geretto, Marta; Micale, Rosanna T.; La Maestra, Sebastiano; Miller, Mark Steven; Steele, Vernon E.; De Flora, Silvio

2016-01-01

Cigarette smoke (CS) is known to dysregulate microRNA expression profiles in the lungs of mice, rats, and humans, thereby modulating several pathways involved in lung carcinogenesis and other CS-related diseases. We designed a study aimed at evaluating (a) the expression of 1135 microRNAs in the lung of Swiss H mice exposed to mainstream CS during the first 4 months of life and thereafter kept in filtered air for an additional 3.5 months, (b) the relationship between lung microRNA profiles and histopathological alterations in the lung, (c) intergender differences in microRNA expression, and (d) the comparison with microRNA profiles in blood serum. CS caused multiple histopathological alterations in the lung, which were almost absent in sham-exposed mice. An extensive microRNA dysregulation was detected in the lung of CS-exposed mice. Modulation of microRNA profiles was specifically related to the histopathological picture, no effect being detected in lung fragments with non-neoplastic lung diseases (emphysema or alveolar epithelial hyperplasia), whereas a close association occurred with the presence and multiplicity of preneoplastic lesions (microadenomas) and benign lung tumors (adenomas). Three microRNAs regulating estrogen and HER2-dependent mechanisms were modulated in the lung of adenoma-bearing female mice. Blood microRNAs were also modulated in mice affected by early neoplastic lesions. However, there was a poor association between lung microRNAs and circulating microRNAs, which can be ascribed to an impaired release of mature microRNAs from the damaged lung. Studies in progress are evaluating the feasibility of analyzing blood microRNAs as a molecular tool for lung cancer secondary prevention. PMID:27713172

ABERRANT PROMOTER METHYLATION OF MULTIPLE GENES IN SPUTUM FROM INDIVIDUALS EXPOSED TO SMOKY COAL EMISSIONS

EPA Science Inventory

Aberrant methylation in the promoter region of cancer-related genes leads to gene transcriptional inactivation and plays an integral role in lung tumorigenesis. Recent studies demonstrated that promoter methylation was detected not only in lung tumors from patients with lung canc...

β-cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice.

PubMed

Iskandar, Anita R; Liu, Chun; Smith, Donald E; Hu, Kang-Quan; Choi, Sang-Woon; Ausman, Lynne M; Wang, Xiang-Dong

2013-04-01

Nicotine, a large constituent of cigarette smoke, is associated with an increased risk of lung cancer, but the data supporting this relationship are inconsistent. Here, we found that nicotine treatment not only induced emphysema but also increased both lung tumor multiplicity and volume in 4-nitrosamino-1-(3-pyridyl)-1-butanone (NNK)-initiated lung cancer in A/J mice. This tumor-promoting effect of nicotine was accompanied by significant reductions in survival probability and lung Sirtuin 1 (SIRT1) expression, which has been proposed as a tumor suppressor. The decreased level of SIRT1 was associated with increased levels of AKT phosphorylation and interleukin (il)-6 mRNA but decreased tumor suppressor p53 and retinoic acid receptor (RAR)-β mRNA levels in the lungs. Using this mouse model, we then determined whether β-cryptoxanthin (BCX), a xanthophyll that is strongly associated with a reduced risk of lung cancer in several cohort studies, can inhibit nicotine-induced emphysema and lung tumorigenesis. We found that BCX supplementation at two different doses was associated with reductions of the nicotine-promoted lung tumor multiplicity and volume, as well as emphysema in mice treated with both NNK and nicotine. Moreover, BCX supplementation restored the nicotine-suppressed expression of lung SIRT1, p53, and RAR-β to that of the control group, increased survival probability, and decreased the levels of lung il-6 mRNA and phosphorylation of AKT. The present study indicates that BCX is a preventive agent against emphysema and lung cancer with SIRT1 as a potential target. In addition, our study establishes a relevant animal lung cancer model for studying tumor growth within emphysematous microenvironments.

[The controversy regarding the cause of death of Wolfgang Amadeus Mozart (28 January 1756-5 May 1791)].

PubMed

Ludewig, R

1991-09-01

All since two hundred years closely contested hypotheses about the causes of Wolfgang Amadeus Mozart's death are to be verified and to be made credible by the same "original sources" in spite of considerable contrasts. In the present study it is tried to indicate the reasons for the multifariousness of the opinions and to represent Mozart's death as the consequence of a multifactorial process.

Population balance modeling: current status and future prospects.

PubMed

Ramkrishna, Doraiswami; Singh, Meenesh R

2014-01-01

Population balance modeling is undergoing phenomenal growth in its applications, and this growth is accompanied by multifarious reviews. This review aims to fortify the model's fundamental base, as well as point to a variety of new applications, including modeling of crystal morphology, cell growth and differentiation, gene regulatory processes, and transfer of drug resistance. This is accomplished by presenting the many faces of population balance equations that arise in the foregoing applications.

Mathematical Modeling and Optimization Studies on Development of Fuel Cells for Multifarious Applications

DTIC Science & Technology

2010-05-12

multicomponent steady-state model for liquid -feed solid polymer electrolyte DBFCs. These fuel cells use sodium borohydride (NaBH4) in alkaline media...layers, diffusion layers and the polymer electrolyte membrane for a liquid feed DBFC. Diffusion of reactants within and between the pores is accounted...projected for futuristic portable applications. In this project we developed a three- dimensional, multicomponent steady-state model for liquid -feed solid

New simple radiological criteria proposed for multiple primary lung cancers.

PubMed

Matsunaga, Takeshi; Suzuki, Kenji; Takamochi, Kazuya; Oh, Shiaki

2017-11-01

Controversies remain as to the differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IM) in lung cancers. We have investigated the clinical criteria for MPLC and here propose a set of new and simple criteria from the stand point of prognosis. A retrospective study was conducted on 588 consecutive patients with resected lung cancer of clinical Stage IA between 2009 and 2012. Multiple lung cancers (MLCs) were observed in 103 (17.5%) of the 588 patients. All main and other tumors were divided into solid tumor (ST) and non-solid tumor (non-ST). We defined Group A as MLCs having at least one non-ST and Group B as all tumors being ST. Cox's proportional hazard model was used for the multivariate analyses to investigate the preoperative prognostic factors. We divided the MLCs into MPLC and IM based on the preoperative prognostic factors, and survival was estimated by the Kaplan-Meier method. A multivariate analysis with Cox's proportional hazards model revealed that Group A independently predicted good overall survival (HR = 0.165, 95% CI: 0.041-0.672).Differences in the 3- and 5-year overall survivals between Groups A and B were statistically significant (96.3%/92.2% vs. 70.0%/60.0%, Pvalue = 0.0002). We suggest that Group A, defined as the presence of at least one tumor with a ground glass opacity component and clinical N0, should be excluded from the conventional concept of multiple lung cancers based on the criteria of Martini and Melamed as it has a very good prognosis. This group would be considered to be radiological MPLC. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Maternal inflammation modulates infant immune response patterns to viral lung challenge in a murine model.

PubMed

Gleditsch, Dorothy D; Shornick, Laurie P; Van Steenwinckel, Juliette; Gressens, Pierre; Weisert, Ryan P; Koenig, Joyce M

2014-07-01

Chorioamnionitis, an inflammatory gestational disorder, commonly precedes preterm delivery. Preterm infants may be at particular risk for inflammation-related morbidity related to infection, although the pathogenic mechanisms are unclear. We hypothesized that maternal inflammation modulates immune programming to drive postnatal inflammatory processes. We used a novel combined murine model to treat late gestation dams with low-dose lipopolysaccharide (LPS) and to secondarily challenge exposed neonates or weanlings with Sendai virus (SeV) lung infection. Multiple organs were analyzed to characterize age-specific postnatal immune and inflammatory responses. Maternal LPS treatment enhanced innate immune populations in the lungs, livers, and/or spleens of exposed neonates or weanlings. Secondary lung SeV infection variably affected neutrophil, macrophage, and dendritic cell proportions in multiple organs of exposed pups. Neonatal lung infection induced brain interleukin (IL)-4 expression, although this response was muted in LPS-exposed pups. Adaptive immune cells, including lung, lymph node, and thymic lymphocytes and lung CD4 cells expressing FoxP3, interferon (IFN)-γ, or IL-17, were variably prominent in LPS-exposed pups. Maternal inflammation modifies postnatal immunity and augments systemic inflammatory responses to viral lung infection in an age-specific manner. We speculate that inflammatory modulation of the developing immune system contributes to chronic morbidity and mortality in preterm infants.

Pneumothorax caused by cystic and nodular lung metastases from a malignant uterine perivascular epithelioid cell tumor (PEComa).

PubMed

Okamoto, Shouichi; Komura, Moegi; Terao, Yasuhisa; Kurisaki-Arakawa, Aiko; Hayashi, Takuo; Saito, Tsuyoshi; Togo, Shinsaku; Shiokawa, Akira; Mitani, Keiko; Kobayashi, Etsuko; Kumasaka, Toshio; Takahashi, Kazuhisa; Seyama, Kuniaki

2017-01-01

Perivascular epithelioid cell tumors (PEComas) are mesenchymal neoplasms with immunoreactivity for both melanocytic and smooth muscle markers. PEComas occur at multiple sites, and malignant PEComas can undergo metastasis, recurrence and aggressive clinical courses. Although the lung is a common metastatic site of PEComas, they usually appear as multiple nodules but rarely become cystic or cavitary. Here, we describe a female patient whose lungs manifested multiple cystic, cavity-like and nodular metastases 3 years after the resection of uterine tumors tentatively diagnosed as epithelioid smooth muscle tumors with uncertain malignant potential. This patient's subsequent pneumothorax necessitated video-assisted thoracoscopic surgery, and examination of her resected lung specimens eventually led to correcting the diagnosis, i.e., to a PEComa harboring tuberous sclerosis complex 1 ( TSC1 ) loss-of-heterozygosity that originated in the uterus and then metastasized to the lungs. The administration of a gonadotropin-releasing hormone analogue later stabilized her clinical course. To the best of our knowledge, the present case is the first in the literature that associates PEComas with a TSC1 abnormality. Additionally, the pulmonary manifestations, including imaging appearance and pneumothorax, somewhat resembled those of lymphangioleiomyomatosis, a representative disease belonging to the PEComa family. Although PEComas are rare, clinicians, radiologists and pathologists should become aware of this disease entity, especially in the combined clinical setting of multiple cystic, cavity-like, nodular lesions on computed tomography of the chest and a past history of the tumor in the female reproductive system.

Deviations from Haber’s Law for Multiple Measures of Acute Lung Injury in Chlorine-Exposed Mice

PubMed Central

Hoyle, Gary W.; Chang, Weiyuan; Chen, Jing; Schlueter, Connie F.; Rando, Roy J.

2010-01-01

Chlorine gas is considered a chemical threat agent that can cause acute lung injury. Studies in the early 20th century on war gases led Haber to postulate that the dose of an inhaled chemical expressed as the product of gas concentration and exposure time leads to a constant toxicological effect (Haber’s Law). In the present work, mice were exposed to a constant dose of chlorine (100 ppm-h) delivered using different combinations of concentration and time (800 ppm/7.5 min, 400 ppm/15 min, 200 ppm/30 min, and 100 ppm/60 min). Significant effects of exposure protocol on survival evaluated 6 h after exposure were observed, ranging from 0% for the 7.5-min exposure to 100% for the 30- and 60-min exposures. Multiple parameters indicative of lung injury were examined to determine if any aspects of lung injury were differentially affected by the exposure protocols. Most parameters (pulmonary edema, neutrophil influx, and levels of protein, immunoglobulin M, and the chemokine KC [Cxcl1] in lavage fluid) indicated that lung injury was most pronounced for the 15-min exposure and least for the 60-min exposure. In contrast, changes in pulmonary function at baseline and in response to inhaled methacholine were similar following the three exposure regimens. The results indicate that the extent of lung injury following chlorine inhalation depends not only on total dose but also on the specifics of exposure concentration and time, and they suggest that evaluation of countermeasures against chlorine-induced lung injury should be performed using multiple types of exposure scenarios. PMID:20819911

Cryptogenic organizing pneumonia masquerading as lung carcinoma: A case report and review of the literature

PubMed Central

Huo, Ji-Ping; Liu, Cui; Jin, Bei-Bei; Duan, Feng-Xia; Mei, Sheng-Hui; Li, Xin-Gang; Zhao, Zhi-Gang

2018-01-01

Cryptogenic organizing pneumonia (COP) is a rare pulmonary disorder of unknown etiology. COP with hemoptysis as the primary presenting symptom has rarely been reported. The present study reported a case of COP that resembled lung carcinoma with hemoptysis as the only clinical symptom. The patient recovered well following thoracoscope surgery. A literature review of 119 COP cases between 1995 and 2015 was presented. Cough, fever and dyspnea were the most common clinical manifestations. The most common imaging manifestations were multiple or single consolidation, lung nodules, migratory sign, reversed halo sign, and multiple ground-glass opacity. A total of 3 cases exhibited COP accompanied by lung cancer. Glucocorticoids were effective for the majority of cases and invasive surgeries were implemented in most cases. The majority of cases recovered or relieved, and the prognosis of COP was relatively good. COP was easily confused with lung tumor and it is necessary to make differential diagnosis between COP and lung cancer. Invasive surgery should be avoided when possible to avoid or reduce patient trauma. PMID:29399056

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate and colorectal cancer reveals novel pleiotropic associations

PubMed Central

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fred; Schildkraut, Joellen; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Olama, Ali Amin Al; Berndt, Sonja I; Giovannucci, Edward; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter; Goode, Ellen L.; Permuth, Jennifer; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; dos-Santos-Silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Wang, Zhaoming; Whittemore, Alice S.; Yang, Xiaohong R.; Zheng, Wei; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N.; Stefansson, Kari; Sulem, Patrick; Chen, Y. Ann; Tyrer, Jonathan P.; Christiani, David C.; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma’en; Nickle, David; Timens, Wim; Freedman, Matthew L.; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J.; Gong, Jian; Peters, Ulrike; Gruber, Stephen B.; Amos, Christopher I.; Sellers, Thomas A.; Easton, Douglas F.; Hunter, David J.; Haiman, Christopher A.; Henderson, Brian E.; Hung, Rayjean J.

2016-01-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-staged approach to conduct genome-wide association studies for lung, ovary, breast, prostate and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. PMID:27197191

Multiple exposures to swine barn air induce lung inflammation and airway hyper-responsiveness

PubMed Central

Charavaryamath, Chandrashekhar; Janardhan, Kyathanahalli S; Townsend, Hugh G; Willson, Philip; Singh, Baljit

2005-01-01

Background Swine farmers repeatedly exposed to the barn air suffer from respiratory diseases. However the mechanisms of lung dysfunction following repeated exposures to the barn air are still largely unknown. Therefore, we tested a hypothesis in a rat model that multiple interrupted exposures to the barn air will cause chronic lung inflammation and decline in lung function. Methods Rats were exposed either to swine barn (8 hours/day for either one or five or 20 days) or ambient air. After the exposure periods, airway hyper-responsiveness (AHR) to methacholine (Mch) was measured and rats were euthanized to collect bronchoalveolar lavage fluid (BALF), blood and lung tissues. Barn air was sampled to determine endotoxin levels and microbial load. Results The air in the barn used in this study had a very high concentration of endotoxin (15361.75 ± 7712.16 EU/m3). Rats exposed to barn air for one and five days showed increase in AHR compared to the 20-day exposed and controls. Lungs from the exposed groups were inflamed as indicated by recruitment of neutrophils in all three exposed groups and eosinophils and an increase in numbers of airway epithelial goblet cells in 5- and 20-day exposure groups. Rats exposed to the barn air for one day or 20 days had more total leukocytes in the BALF and 20-day exposed rats had more airway epithelial goblet cells compared to the controls and those subjected to 1 and 5 exposures (P < 0.05). Bronchus-associated lymphoid tissue (BALT) in the lungs of rats exposed for 20 days contained germinal centers and mitotic cells suggesting activation. There were no differences in the airway smooth muscle cell volume or septal macrophage recruitment among the groups. Conclusion We conclude that multiple exposures to endotoxin-containing swine barn air induce AHR, increase in mucus-containing airway epithelial cells and lung inflammation. The data also show that prolonged multiple exposures may also induce adaptation in AHR response in the exposed subjects. PMID:15932644

[A case of fat embolism syndrome associated with pathological femoral fracture caused by metastatic adenocarcinoma of the lung].

PubMed

Sato, Takashi; Soejima, Kenzo; Nakayama, Sohei; Satomi, Ryosuke; Sayama, Koichi; Asano, Koichiro

2010-10-01

A 76-year-old woman with multiple bone metastases from lung adenocarcinoma was admitted due to a pathological femoral fracture. On the night after admission, her consciousness deteriorated rapidly and she developed progressive respiratory failure. Computed tomography of the chest revealed diffuse ground glass opacities in both lungs, and magnetic resonance imaging of the brain showed multiple acute infarctions. Her condition improved after several days of supportive treatment with oxygen, corticosteroids and diuretics. Fat embolism syndrome should be considered as a differential diagnosis if consciousness disturbance and respiratory failure occur in patients with metastatic bone carcinoma and pathological long bone fractures.

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities.

PubMed

Feikin, Daniel R; Hammitt, Laura L; Murdoch, David R; O'Brien, Katherine L; Scott, J Anthony G

2017-06-15

Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Method and apparatus for measuring lung density by Compton backscattering

DOEpatents

Loo, Billy W.; Goulding, Frederick S.

1991-01-01

The density of the lung of a patient suffering from pulmonary edema is monitored by irradiating the lung by a single collimated beam of monochromatic photons and measuring the energies of photons Compton backscattered from the lung by a single high-resolution, high-purity germanium detector. A compact system geometry and a unique data extraction scheme are utilized to monimize systematic errors due to the presence of the chestwall and multiple scattering.

Lung Entrapment between the Pectus Bar and Chest Wall after Pectus Surgery: An Incidental Finding during Video-Assisted Thoracoscopic Surgery

PubMed Central

Kim, Kyung Soo; Hyun, Kwanyong; Kim, Do Yeon; Choi, Kukbin; Choi, Hahng Joon; Park, Hyung Joo

2015-01-01

We report a case of an entrapped lung after the pectus bar repair of a pectus deformity. The entrapped lung was found incidentally during video-assisted thoracoscopic surgery (VATS) for pneumothorax. Based on VATS exploration, multiple bullae seemed to be the cause of the pneumothorax, but the entrapped lung was suspected to have been a cause of the air leakage. PMID:26509135

Separation of left and right lungs using 3D information of sequential CT images and a guided dynamic programming algorithm

PubMed Central

Park, Sang Cheol; Leader, Joseph Ken; Tan, Jun; Lee, Guee Sang; Kim, Soo Hyung; Na, In Seop; Zheng, Bin

2011-01-01

Objective this article presents a new computerized scheme that aims to accurately and robustly separate left and right lungs on CT examinations. Methods we developed and tested a method to separate the left and right lungs using sequential CT information and a guided dynamic programming algorithm using adaptively and automatically selected start point and end point with especially severe and multiple connections. Results the scheme successfully identified and separated all 827 connections on the total 4034 CT images in an independent testing dataset of CT examinations. The proposed scheme separated multiple connections regardless of their locations, and the guided dynamic programming algorithm reduced the computation time to approximately 4.6% in comparison with the traditional dynamic programming and avoided the permeation of the separation boundary into normal lung tissue. Conclusions The proposed method is able to robustly and accurately disconnect all connections between left and right lungs and the guided dynamic programming algorithm is able to remove redundant processing. PMID:21412104

Separation of left and right lungs using 3-dimensional information of sequential computed tomography images and a guided dynamic programming algorithm.

PubMed

Park, Sang Cheol; Leader, Joseph Ken; Tan, Jun; Lee, Guee Sang; Kim, Soo Hyung; Na, In Seop; Zheng, Bin

2011-01-01

This article presents a new computerized scheme that aims to accurately and robustly separate left and right lungs on computed tomography (CT) examinations. We developed and tested a method to separate the left and right lungs using sequential CT information and a guided dynamic programming algorithm using adaptively and automatically selected start point and end point with especially severe and multiple connections. The scheme successfully identified and separated all 827 connections on the total 4034 CT images in an independent testing data set of CT examinations. The proposed scheme separated multiple connections regardless of their locations, and the guided dynamic programming algorithm reduced the computation time to approximately 4.6% in comparison with the traditional dynamic programming and avoided the permeation of the separation boundary into normal lung tissue. The proposed method is able to robustly and accurately disconnect all connections between left and right lungs, and the guided dynamic programming algorithm is able to remove redundant processing.

Multiple-Breath Washout Outcomes Are Sensitive to Inflammation and Infection in Children with Cystic Fibrosis.

PubMed

Ramsey, Kathryn A; Foong, Rachel E; Grdosic, Jasmine; Harper, Alana; Skoric, Billy; Clem, Charles; Davis, Miriam; Turkovic, Lidija; Stick, Stephen M; Davis, Stephanie D; Ranganathan, Sarath C; Hall, Graham L

2017-09-01

The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. The lung clearance index is increased in the presence of lower respiratory tract inflammation and infection in infants with cystic fibrosis; however, the associations during the preschool years are unknown. We assessed the ability of the lung clearance index to detect the presence and extent of lower respiratory tract inflammation and infection in preschool children with cystic fibrosis. Ventilation distribution outcomes were assessed at 82 visits with 58 children with cystic fibrosis and at 38 visits with 31 healthy children aged 3-6 years. Children with cystic fibrosis also underwent bronchoalveolar lavage fluid collection for detection of lower respiratory tract inflammation and infection. Associations between multiple-breath washout indices and the presence and extent of airway inflammation and infection were assessed using linear mixed effects models. Lung clearance index was elevated in children with cystic fibrosis (mean [SD], 8.00 [1.45]) compared with healthy control subjects (6.67 [0.56]). In cystic fibrosis, the lung clearance index was elevated in individuals with lower respiratory tract infections (difference compared with uninfected [95% confidence interval], 0.62 [0.06, 1.18]) and correlated with the extent of airway inflammation. These data suggest that the lung clearance index may be a useful surveillance tool for monitoring the presence and extent of lower airway inflammation and infection in preschool children with cystic fibrosis.

Estimation of regional lung expansion via 3D image registration

NASA Astrophysics Data System (ADS)

Pan, Yan; Kumar, Dinesh; Hoffman, Eric A.; Christensen, Gary E.; McLennan, Geoffrey; Song, Joo Hyun; Ross, Alan; Simon, Brett A.; Reinhardt, Joseph M.

2005-04-01

A method is described to estimate regional lung expansion and related biomechanical parameters using multiple CT images of the lungs, acquired at different inflation levels. In this study, the lungs of two sheep were imaged utilizing a multi-detector row CT at different lung inflations in the prone and supine positions. Using the lung surfaces and the airway branch points for guidance, a 3D inverse consistent image registration procedure was used to match different lung volumes at each orientation. The registration was validated using a set of implanted metal markers. After registration, the Jacobian of the deformation field was computed to express regional expansion or contraction. The regional lung expansion at different pressures and different orientations are compared.

Beta-cryptoxanthin reduced lung tumor multiplicity and inhibited lung cancer cell motility by downregulating nicotinic acetylcholine receptor alpha7 signaling

USDA-ARS?s Scientific Manuscript database

Despite the consistent association between a higher intake of the provitamin A carotenoid beta-cryptoxanthin (BCX) and a lower risk of lung cancer among smokers, potential mechanisms supporting BCX as a chemopreventive agent are needed. We first examined the effects of BCX on 4-[methyl nitrosamino]-...

Preparing the Future--Women, Literacy and Development. The Impact of Female Literacy on Human Development and the Participation of Literate Women in Change. ActionAid Development Report No. 4.

ERIC Educational Resources Information Center

Bown, Lalage

The outcomes of 43 project case studies and a country case study (Nepal) were examined to identify the impact of adult women's literacy. A look at women's situation in developing countries showed that women had multifarious roles, long working hours, and less access to education than males. The case studies revealed the following social effects of…

Evaluation of multifarious plant growth promoting traits, antagonistic potential and phylogenetic affiliation of rhizobacteria associated with commercial tea plants grown in Darjeeling, India.

PubMed

Dutta, Jintu; Thakur, Debajit

2017-01-01

Plant growth promoting rhizobacteria (PGPR) are studied in different agricultural crops but the interaction of PGPR of tea crop is not yet studied well. In the present study, the indigenous tea rhizobacteria were isolated from seven tea estates of Darjeeling located in West Bengal, India. A total of 150 rhizobacterial isolates were screened for antagonistic activity against six different fungal pathogens i.e. Nigrospora sphaerica (KJ767520), Pestalotiopsis theae (ITCC 6599), Curvularia eragostidis (ITCC 6429), Glomerella cingulata (MTCC 2033), Rhizoctonia Solani (MTCC 4633) and Fusarium oxysporum (MTCC 284), out of which 48 isolates were antagonist to at least one fungal pathogen used. These 48 isolates exhibited multifarious antifungal properties like the production of siderophore, chitinase, protease and cellulase and also plant growth promoting (PGP) traits like IAA production, phosphate solubilization, ammonia and ACC deaminase production. Amplified ribosomal DNA restriction analysis (ARDRA) and BOX-PCR analysis based genotyping clustered the isolates into different groups. Finally, four isolates were selected for plant growth promotion study in two tea commercial cultivars TV-1 and Teenali-17 in nursery conditions. The plant growth promotion study showed that the inoculation of consortia of these four PGPR isolates significantly increased the growth of tea plant in nursery conditions. Thus this study underlines the commercial potential of these selected PGPR isolates for sustainable tea cultivation.

Absence of multiplicative interactions between occupational lung carcinogens and tobacco smoking: a systematic review involving asbestos, crystalline silica and diesel engine exhaust emissions.

PubMed

El Zoghbi, Mohamad; Salameh, Pascale; Stücker, Isabelle; Brochard, Patrick; Delva, Fleur; Lacourt, Aude

2017-02-02

Tobacco smoking is the main cause of lung cancer, but it is not the sole causal factor. Significant proportions of workers are smokers and exposed to occupational lung carcinogens. This study aims to systematically review the statistical interaction between occupational lung carcinogens and tobacco smoking, in particular asbestos, crystalline silica and diesel engine exhaust emissions. Articles were identified using Scopus, PubMed, and Web of Science, and were limited to those published in English or French, without limitation of time. The reference list of selected studies was reviewed to identify other relevant papers. One reviewer selected the articles based on the inclusion and exclusion criteria. Two reviewers checked the eligibility of articles to be included in the systematic review. Data were extracted by one reviewer and revised by two other reviewers. Cohorts and case-control studies were analyzed separately. The risk of bias was evaluated for each study based on the outcome. The results of the interaction between the tobacco smoking and each carcinogen was evaluated and reported separately. Fifteen original studies were included for asbestos-smoking interaction, seven for silica-smoking interaction and two for diesel-smoking interaction. The results suggested the absence of multiplicative interaction between the three occupational lung carcinogens and smoking. There is no enough evidence from the literature to conclude for the additive interaction. We believe there is a limited risk of publication bias as several studies reporting negative results were published. There are no multiplicative interactions between tobacco smoking and occupational lung carcinogens, in particular asbestos, crystalline silica and diesel engine exhaust emissions. Even though, specific programs should be developed and promoted to reduce concomitantly the exposure to occupational lung carcinogens and tobacco smoking.

Chronic Nicotine Consumption does not Influence 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Induced Lung Tumorigenesis

PubMed Central

Murphy, Sharon E.; von Weymarn, Linda B.; Schutten, Melissa M.; Kassie, Fekadu; Modiano, Jaime F.

2011-01-01

Nicotine replacement therapy (NRT) is often used to maintain smoking cessation. However, concerns exist about the safety of long term NRT use in ex-smokers and its concurrent use in smokers. In this study, we determined the effect of nicotine administration on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumors in A/J mice. Female mice were administered a single dose of NNK (10 μmol) and 0.44 μmol/ml nicotine in the drinking water. Nicotine was administered 2 weeks prior to NNK, 44 weeks after NNK, throughout the experiment, or without NNK treatment. The average weekly consumption of nicotine-containing water was 15 ± 3 mls/mouse, resulting in an estimated daily nicotine dose of 0.9 μmol (0.15 mg) per mouse. Nicotine administration alone for 46 weeks did not increase lung tumor multiplicity (0.32 ± 0.1 tumor/mouse versus 0.53 ± 0.1 tumors/mouse). Lung tumor multiplicity in NNK-treated mice was 18.4 ± 4.5 and was not different than for mice consuming nicotine before or after NNK administration, 21.9 ± 5.3 and 20.0 ± 5.4 tumors per mouse, respectively. Lung tumor multiplicity in animals consuming nicotine both before and after NNK administration was 20.4 ± 5.4. Tumor size and progression of adenomas to carcinomas was also not affected by nicotine consumption. In addition, nicotine consumption had no effect on the level of O6-methylguanine in the lung of NNK-treated mice. These negative findings in a commonly used model of human lung carcinogenesis should lead us to question the interpretation of the many in vitro studies that find nicotine stimulates cancer cell growth. PMID:22027684

Method and apparatus for measuring lung density by Compton backscattering

DOEpatents

Loo, B.W.; Goulding, F.S.

1988-03-11

The density of the lung of a patient suffering from pulmonary edema is monitored by irradiating the lung by a single collimated beam of monochromatic photons and measuring the energies of photons compton back-scattered from the lung by a single high-resolution, high-purity germanium detector. A compact system geometry and a unique data extraction scheme are utilized to minimize systematic errors due to the presence of the chestwall and multiple scattering. 11 figs., 1 tab.

Genomic profiling of multiple sequentially acquired tumor metastatic sites from an “exceptional responder” lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response. | Center for Cancer Research

Cancer.gov

Biswas et al. describe an “exceptional responder” lung adenocarcinoma patient who survived with metastatic lung adenocarcinoma for 7 years while undergoing single or combination ERBB2-directed therapies. Whole-genome, whole-exome, and high-coverage ion-torrent targeted sequencing were used to demonstrate extreme genomic heterogeneity between the lung and lymph node metastatic

Mutations of the Birt–Hogg–Dubé gene in patients with multiple lung cysts and recurrent pneumothorax

PubMed Central

Gunji, Yoko; Akiyoshi, Taeko; Sato, Teruhiko; Kurihara, Masatoshi; Tominaga, Shigeru; Takahashi, Kazuhisa; Seyama, Kuniaki

2007-01-01

Rationale Birt–Hogg–Dubé (BHD) syndrome, a rare inherited autosomal genodermatosis first recognised in 1977, is characterised by fibrofolliculomas of the skin, an increased risk of renal tumours and multiple lung cysts with spontaneous pneumothorax. The BHD gene, a tumour suppressor gene located at chromosome 17p11.2, has recently been shown to be defective. Recent genetic studies revealed that clinical pictures of the disease may be variable and may not always present the full expression of the phenotypes. Objectives We hypothesised that mutations of the BHD gene are responsible for patients who have multiple lung cysts of which the underlying causes have not yet been elucidated. Methods We studied eight patients with lung cysts, without skin and renal disease; seven of these patients have a history of spontaneous pneumothorax and five have a family history of pneumothorax. The BHD gene was examined using PCR, denaturing high‐performance liquid chromatography and direct sequencing. Main results We found that five of the eight patients had a BHD germline mutation. All mutations were unique and four of them were novel, including three different deletions or insertions detected in exons 6, 12 and 13, respectively and one splice acceptor site mutation in intron 5 resulting in an in‐frame deletion of exon 6. Conclusions We found that germline mutations of the BHD gene are involved in some patients with multiple lung cysts and pneumothorax. Pulmonologists should be aware that BHD syndrome can occur as an isolated phenotype with pulmonary involvement. PMID:17496196

Tumor growth affects the metabonomic phenotypes of multiple mouse non-involved organs in an A549 lung cancer xenograft model.

PubMed

Xu, Shan; Tian, Yuan; Hu, Yili; Zhang, Nijia; Hu, Sheng; Song, Dandan; Wu, Zhengshun; Wang, Yulan; Cui, Yanfang; Tang, Huiru

2016-06-22

The effects of tumorigenesis and tumor growth on the non-involved organs remain poorly understood although many research efforts have already been made for understanding the metabolic phenotypes of various tumors. To better the situation, we systematically analyzed the metabolic phenotypes of multiple non-involved mouse organ tissues (heart, liver, spleen, lung and kidney) in an A549 lung cancer xenograft model at two different tumor-growth stages using the NMR-based metabonomics approaches. We found that tumor growth caused significant metabonomic changes in multiple non-involved organ tissues involving numerous metabolic pathways, including glycolysis, TCA cycle and metabolisms of amino acids, fatty acids, choline and nucleic acids. Amongst these, the common effects are enhanced glycolysis and nucleoside/nucleotide metabolisms. These findings provided essential biochemistry information about the effects of tumor growth on the non-involved organs.

Histopathology of lung disease in the connective tissue diseases.

PubMed

Vivero, Marina; Padera, Robert F

2015-05-01

The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. Copyright © 2015 Elsevier Inc. All rights reserved.

Stereological assessment of mouse lung parenchyma via nondestructive, multiscale micro-CT imaging validated by light microscopic histology

PubMed Central

Vasilescu, Dragoş M.; Klinge, Christine; Knudsen, Lars; Yin, Leilei; Wang, Ge; Weibel, Ewald R.; Ochs, Matthias

2013-01-01

Quantitative assessment of the lung microstructure using standard stereological methods such as volume fractions of tissue, alveolar surface area, or number of alveoli, are essential for understanding the state of normal and diseased lung. These measures are traditionally obtained from histological sections of the lung tissue, a process that ultimately destroys the three-dimensional (3-D) anatomy of the tissue. In comparison, a novel X-ray-based imaging method that allows nondestructive sectioning and imaging of fixed lungs at multiple resolutions can overcome this limitation. Scanning of the whole lung at high resolution and subsequent regional sampling at ultrahigh resolution without physically dissecting the organ allows the application of design-based stereology for assessment of the whole lung structure. Here we validate multiple stereological estimates performed on micro–computed tomography (μCT) images by comparing them with those obtained via conventional histology on the same mouse lungs. We explore and discuss the potentials and limitations of the two approaches. Histological examination offers higher resolution and the qualitative differentiation of tissues by staining, but ultimately loses 3-D tissue relationships, whereas μCT allows for the integration of morphometric data with the spatial complexity of lung structure. However, μCT has limited resolution satisfactory for the sterological estimates presented in this study but not for differentiation of tissues. We conclude that introducing stereological methods in μCT studies adds value by providing quantitative information on internal structures while not curtailing more complex approaches to the study of lung architecture in the context of physiological or pathological studies. PMID:23264542

Intersections of lung progenitor cells, lung disease and lung cancer.

PubMed

Kim, Carla F

2017-06-30

The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

The SARS coronavirus nucleocapsid protein--forms and functions.

PubMed

Chang, Chung-ke; Hou, Ming-Hon; Chang, Chi-Fon; Hsiao, Chwan-Deng; Huang, Tai-huang

2014-03-01

The nucleocapsid phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV N protein) packages the viral genome into a helical ribonucleocapsid (RNP) and plays a fundamental role during viral self-assembly. It is a protein with multifarious activities. In this article we will review our current understanding of the N protein structure and its interaction with nucleic acid. Highlights of the progresses include uncovering the modular organization, determining the structures of the structural domains, realizing the roles of protein disorder in protein-protein and protein-nucleic acid interactions, and visualizing the ribonucleoprotein (RNP) structure inside the virions. It was also demonstrated that N-protein binds to nucleic acid at multiple sites with a coupled-allostery manner. We propose a SARS-CoV RNP model that conforms to existing data and bears resemblance to the existing RNP structures of RNA viruses. The model highlights the critical role of modular organization and intrinsic disorder of the N protein in the formation and functions of the dynamic RNP capsid in RNA viruses. This paper forms part of a symposium in Antiviral Research on "From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses." Copyright © 2014 Elsevier B.V. All rights reserved.

Applications of RNA Indexes for Precision Oncology in Breast Cancer.

PubMed

Ma, Liming; Liang, Zirui; Zhou, Hui; Qu, Lianghu

2018-05-09

Precision oncology aims to offer the most appropriate treatments to cancer patients mainly based on their individual genetic information. Genomics has provided numerous valuable data on driver mutations and risk loci; however, it remains a formidable challenge to transform these data into therapeutic agents. Transcriptomics describes the multifarious expression patterns of both mRNAs and non-coding RNAs (ncRNAs), which facilitates the deciphering of genomic codes. In this review, we take breast cancer as an example to demonstrate the applications of these rich RNA resources in precision medicine exploration. These include the use of mRNA profiles in triple-negative breast cancer (TNBC) subtyping to inform corresponding candidate targeted therapies; current advancements and achievements of high-throughput RNA interference (RNAi) screening technologies in breast cancer; and microRNAs as functional signatures for defining cell identities and regulating the biological activities of breast cancer cells. We summarize the benefits of transcriptomic analyses in breast cancer management and propose that unscrambling the core signaling networks of cancer may be an important task of multiple-omic data integration for precision oncology. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Multifarious anchovy and sardine regimes in the Humboldt Current System during the last 150 years.

PubMed

Salvatteci, Renato; Field, David; Gutiérrez, Dimitri; Baumgartner, Tim; Ferreira, Vicente; Ortlieb, Luc; Sifeddine, Abdel; Grados, Daniel; Bertrand, Arnaud

2018-03-01

The Humboldt Current System (HCS) has the highest production of forage fish in the world, although it is highly variable and the future of the primary component, anchovy, is uncertain in the context of global warming. Paradigms based on late 20th century observations suggest that large-scale forcing controls decadal-scale fluctuations of anchovy and sardine across different boundary currents of the Pacific. We develop records of anchovy and sardine fluctuations since 1860 AD using fish scales from multiple sites containing laminated sediments and compare them with Pacific basin-scale and regional indices of ocean climate variability. Our records reveal two main anchovy and sardine phases with a timescale that is not consistent with previously proposed periodicities. Rather, the regime shifts in the HCS are related to 3D habitat changes driven by changes in upwelling intensity from both regional and large-scale forcing. Moreover, we show that a long-term increase in coastal upwelling translates via a bottom-up mechanism to top predators suggesting that the warming climate, at least up to the start of the 21st century, was favorable for fishery productivity in the HCS. © 2017 John Wiley & Sons Ltd.

Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations.

PubMed

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D; Eeles, Rosalind A; Chatterjee, Nilanjan; Schumacher, Fredrick R; Schildkraut, Joellen M; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Amin Al Olama, Ali; Berndt, Sonja I; Giovannucci, Edward L; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J; Stevens, Victoria L; Wiklund, Fredrik; Willett, Walter C; Goode, Ellen L; Permuth, Jennifer B; Risch, Harvey A; Reid, Brett M; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T; Chang-Claude, Jenny; Hudson, Thomas J; Kocarnik, Jonathan K; Newcomb, Polly A; Schoen, Robert E; Slattery, Martha L; White, Emily; Adank, Muriel A; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; Dos-Santos-Silva, Isabel; Eliassen, A Heather; Figueroa, Jonine D; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A; Nevanlinna, Heli; Peeters, Petra H; Peto, Julian; Prentice, Ross L; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F; Schmutzler, Rita K; Southey, Melissa C; Tamimi, Rulla; Travis, Ruth C; Turnbull, Clare; Uitterlinden, Andre G; Wang, Zhaoming; Whittemore, Alice S; Yang, Xiaohong R; Zheng, Wei; Buchanan, Daniel D; Casey, Graham; Conti, David V; Edlund, Christopher K; Gallinger, Steven; Haile, Robert W; Jenkins, Mark; Le Marchand, Loïc; Li, Li; Lindor, Noralene M; Schmit, Stephanie L; Thibodeau, Stephen N; Woods, Michael O; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N; Stefansson, Kari; Sulem, Patrick; Chen, Y Ann; Tyrer, Jonathan P; Christiani, David C; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma'en; Nickle, David; Timens, Wim; Freedman, Matthew L; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J; Gong, Jian; Peters, Ulrike; Gruber, Stephen B; Amos, Christopher I; Sellers, Thomas A; Easton, Douglas F; Hunter, David J; Haiman, Christopher A; Henderson, Brian E; Hung, Rayjean J

2016-09-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103-14. ©2016 AACR. ©2016 American Association for Cancer Research.

Lung function and exhaled nitric oxide in healthy unsedated African infants

PubMed Central

Gray, Diane; Willemse, Lauren; Visagie, Ane; Smith, Emilee; Czövek, Dorottya; Sly, Peter D; Hantos, Zoltán; Hall, Graham L; Zar, Heather J

2015-01-01

Background and objective Population-appropriate lung function reference data are essential to accurately identify respiratory disease and measure response to interventions. There are currently no reference data in African infants. The aim was to describe normal lung function in healthy African infants. Methods Lung function was performed on healthy South African infants enrolled in a birth cohort study, the Drakenstein child health study. Infants were excluded if they were born preterm or had a history of neonatal respiratory distress or prior respiratory tract infection. Measurements, made during natural sleep, included the forced oscillation technique, tidal breathing, exhaled nitric oxide and multiple breath washout measures. Results Three hundred sixty-three infants were tested. Acceptable and repeatable measurements were obtained in 356 (98%) and 352 (97%) infants for tidal breathing analysis and exhaled nitric oxide outcomes, 345 (95%) infants for multiple breath washout and 293 of the 333 (88%) infants for the forced oscillation technique. Age, sex and weight-for-age z score were significantly associated with lung function measures. Conclusions This study provides reference data for unsedated infant lung function in African infants and highlights the importance of using population-specific data. PMID:26134556

The lung may play a role in the pathogenesis of rheumatoid arthritis

PubMed Central

Demoruelle, M Kristen; Solomon, Joshua J; Fischer, Aryeh; Deane, Kevin D

2015-01-01

Multiple studies have identified strong associations between the lung and rheumatoid arthritis (RA). Such studies identify a high prevalence of lung disease, both airways and parenchymal disease, in subjects with clinically classifiable RA. It has been suggested that lung disease in RA results from targeting of the lung from circulating autoimmunity or other factors such as medications. However, findings that lung disease, specifically inflammatory airways disease, and lung generation of autoimmunity can be present before the onset of joint symptoms suggest that immune reactions in the lung may be involved in the initial development of RA-related autoimmunity. Herein we review these issues in detail, as well as outline a potential research agenda to understand the natural history of lung involvement in RA and its relation to the overall pathogenesis of RA. PMID:26089988

Inhaled gene therapy in lung cancer: proof-of-concept for nano-oncology and nanobiotechnology in the management of lung cancer.

PubMed

Zarogoulidis, Paul; Darwiche, Kaid; Hohenforst-Schmidt, Wolfgang; Huang, Haidong; Li, Qiang; Freitag, Lutz; Zarogoulidis, Konstantinos

2013-08-01

Lung cancer still remains one of the leading causes of death among cancer patients. Although novel targeted therapies have been established in everyday treatment practice, and conventional platinum-based doublets have demonstrated effective results regarding overall and progression-free survival, we have still failed to achieve long-term survival. Therefore, several strategies of applying locoregional therapy are under investigation. Aerosol chemotherapy is already under investigation and, taking this a step further, aerosol gene therapies with multiple delivery systems are being developed. Several efforts have demonstrated its efficiency and effectiveness, but there are still multiple factors that have to be considered and combined to achieve an overall more effective multifunctional treatment. In the current review, we present data regarding aerosol delivery systems, transporters, carriers, vectors, genes, toxicity, efficiency, specificity, lung microenvironment and delivery gene therapy systems. Finally, we present current studies and future perspectives.

Lung lobar collapse as the first manifestation of pulmonary epithelioid haemangioendothelioma diagnosed with fibreoptic bronchoscopy.

PubMed

Abdalla, Ahmed; Seedahmed, Elfateh; Bachuwa, Ghassan; Congdon, Douglas

2016-10-24

Pulmonary epithelioid haemangioendothelioma (PEH) is a rare tumour of endothelial origin that usually occurs in the lung and liver. It usually presents as bilateral multiple nodular lesions. We report a middle-aged woman with a unique presentation of PEH with lung lobar collapse. The diagnosis was made with fibreoptic bronchoscopy rather than video-assisted thoracoscopy. Clinicians and pathologists should be aware of rare conditions that can present as lung lobar collapse. 2016 BMJ Publishing Group Ltd.

Two Cases of Chloromethylisothiazolinone and Methylisothiazolinone-associated Toxic Lung Injury

PubMed Central

2018-01-01

Previous animal studies have not conclusively determined the association between exposure to humidifier disinfectants (HDs) containing 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT) and/or 2-methyl-4-isothiazolin-3-one (MIT) and development of HD-associated lung injuries. Nonetheless, patients exposed to HDs containing only CMIT and/or MIT showed clinically similar lung injuries to those exposed to HDs containing polyhexamethylene guanidine (PHMG) or oligo (2-[2-ethoxy]ethoxyethyl) guanidinium chloride (PGH). Here, we report twin sisters with lung injuries associated with exposure to CMIT/MIT-containing HDs. At 6 months of age, a younger twin sister presented with the 3-day history of cough, sputum, and respiratory difficulty. Chest radiography revealed multiple patchy consolidation and ground-glass opacities with pneumothorax and pneumomediastinum. Thoracostomy was performed due to pneumothorax at admission and she was discharged at 11 days of hospitalization. At 5 years of age, multiple tiny nodules and faint centrilobular ground-glass opacities were observed with the small pneumatocele. The elder sister visited a tertiary hospital due to dyspnea at 12 months of age. Chest radiography showed consolidation, pneumomediastinum, and pulmonary interstitial emphysema. There was no response to the administration of immunosuppressant drugs and antifibrotic agents. At 5 years of age, chest CT revealed ground-glass opacity and multiple tiny centrilobular ground-glass opacities nodules in both lungs with exercise intolerance. PMID:29651817

Two Cases of Chloromethylisothiazolinone and Methylisothiazolinone-associated Toxic Lung Injury.

PubMed

Lee, Eun; Son, Seung Kook; Yoon, Jisun; Cho, Hyun Ju; Yang, Song I; Jung, Sungsu; Do, Kyung Hyun; Cho, Young Ah; Lee, So Yeon; Park, Dong Uk; Hong, Soo Jong

2018-04-16

Previous animal studies have not conclusively determined the association between exposure to humidifier disinfectants (HDs) containing 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT) and/or 2-methyl-4-isothiazolin-3-one (MIT) and development of HD-associated lung injuries. Nonetheless, patients exposed to HDs containing only CMIT and/or MIT showed clinically similar lung injuries to those exposed to HDs containing polyhexamethylene guanidine (PHMG) or oligo (2-[2-ethoxy]ethoxyethyl) guanidinium chloride (PGH). Here, we report twin sisters with lung injuries associated with exposure to CMIT/MIT-containing HDs. At 6 months of age, a younger twin sister presented with the 3-day history of cough, sputum, and respiratory difficulty. Chest radiography revealed multiple patchy consolidation and ground-glass opacities with pneumothorax and pneumomediastinum. Thoracostomy was performed due to pneumothorax at admission and she was discharged at 11 days of hospitalization. At 5 years of age, multiple tiny nodules and faint centrilobular ground-glass opacities were observed with the small pneumatocele. The elder sister visited a tertiary hospital due to dyspnea at 12 months of age. Chest radiography showed consolidation, pneumomediastinum, and pulmonary interstitial emphysema. There was no response to the administration of immunosuppressant drugs and antifibrotic agents. At 5 years of age, chest CT revealed ground-glass opacity and multiple tiny centrilobular ground-glass opacities nodules in both lungs with exercise intolerance. © 2018 The Korean Academy of Medical Sciences.

Examine How Botswana Defense Force in Concurrence with Other Instruments of National Power, Promote Botwana’s National Interests in a Multifarious International Security Environment Regionally

DTIC Science & Technology

2016-06-10

national objectives that will be pursued through the implementation of the NSS. It is now prudent to focus arguments on the NDS. Formulating the...interests through foreign policy development ) in the region and abroad. 83 The fundamental purpose of Botswana’s NSS is principally based on a...notion. This will also be shown in subsequent arguments when discussing the Foreign Policy; Formulation and Implementation Model . But it is equally

Thermophilic and alkaliphilic Actinobacteria: biology and potential applications

PubMed Central

Shivlata, L.; Satyanarayana, Tulasi

2015-01-01

Microbes belonging to the phylum Actinobacteria are prolific sources of antibiotics, clinically useful bioactive compounds and industrially important enzymes. The focus of the current review is on the diversity and potential applications of thermophilic and alkaliphilic actinobacteria, which are highly diverse in their taxonomy and morphology with a variety of adaptations for surviving and thriving in hostile environments. The specific metabolic pathways in these actinobacteria are activated for elaborating pharmaceutically, agriculturally, and biotechnologically relevant biomolecules/bioactive compounds, which find multifarious applications. PMID:26441937

TU-F-CAMPUS-J-01: Dosimetric Effects of HU Changes During the Course of Proton Therapy for Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teng, C; Yin, L; Ainsley, C

2015-06-15

Purpose: To characterize the changes in Hounsfield unit (HU) in lung radiotherapy with proton beams during the course of treatment and to study the effect on the proton plan dose distribution. Methods: Twenty consecutive patients with non-small cell lung cancer treated with proton radiotherapy who underwent multiple CT scans including the planning CT and weekly verification CTs were studied. HU histograms were computed for irradiated lung volumes in beam paths for all scans using the same treatment plan. Histograms for un-irradiated lung volume were used as control to characterize inter-scan variations. HU statistics were calculated for both irradiated and un-irradiatedmore » lung volumes for each patient scan. Further, multiple CT scans based on the same planning CT were generated by replacing the HU of the lung based on the verification CT scans HU values. Using the same beam arrangement, we created plans for each of the altered CT scans to study the dosimetric effect using the dose volume histogram. Results: Lung HU decreased for irradiated lung volume during the course of radiotherapy. The magnitude of this change increased with total irradiation dose. On average, HU changed by −53.8 in the irradiated volume. This change resulted in less than 0.5mm of beam overshoot in tissue for every 1cm beam traversed in the irradiated lung. The dose modification is about +3% for the lung, and less than +1% for the primary tumor. Conclusion: HU of the lung decrease throughout the course of radiation therapy. This change results in a beam overshoot (e.g. 3mm for 6cm of lung traversed) and causes a small dose modification in the overall plan. However, this overshoot does not affect the quality of plans since the margins used in planning, based on proton range uncertainty, are greater. HU needs to change by 150 units before re-planning is warranted.« less

Possible familial case of Birt-Hogg-Dubé syndrome complicated with lung cancer: A possible link between these two disease entities.

PubMed

Nishida, Chinatsu; Yatera, Kazuhiro; Yamasaki, Kei; Torii, Ryo; Kawanami, Yukiko; Kawanami, Toshinori; Ishimoto, Hiroshi; Shibuya, Ryo; Takenaka, Masaru; Yamada, Sohusuke; Kasai, Takahiko; Tanaka, Fumihiro; Mukae, Hiroshi

2015-07-01

A 65-year-old Japanese woman was introduced to our hospital for an examination of multiple pulmonary cystic lesions and a pulmonary nodule in the left lower lobe. She had a smoking history of 25 pack-years, and her two younger brothers had suffered from pneumothorax; one of them additionally had lung cancer with pulmonary multiple cystic lesions. A surgical biopsy specimen obtained from her left lower lobe revealed adenocarcinoma surrounded by a single epithelial layer that was covered with collagen fibers. The pathological features were compatible with the findings of the cystic lesions in the patients with Birt-Hogg-Dubé syndrome (BHDS). A diagnosis of BHDS was eventually made according to the detection of a folliculin gene mutation. This is the first report of a possible familial case of BHDS complicated with primary lung cancer. We herein reviewed the previously reported cases of BHDS with lung cancer and other tumors and discussed a potential mechanism of tumorigenesis and carcinogenesis in the lung in the patients with BHDS. Copyright © 2015 Elsevier Ltd. All rights reserved.

Polyp measurement with CT colonography: multiple-reader, multiple-workstation comparison.

PubMed

Young, Brett M; Fletcher, J G; Paulsen, Scott R; Booya, Fargol; Johnson, C Daniel; Johnson, Kristina T; Melton, Zackary; Rodysill, Drew; Mandrekar, Jay

2007-01-01

The risk of invasive colorectal cancer in colorectal polyps correlates with lesion size. Our purpose was to define the most accurate methods for measuring polyp size at CT colonography (CTC) using three models of workstations and multiple observers. Six reviewers measured 24 unique polyps of known size (5, 7, 10, and 12 mm), shape (sessile, flat, and pedunculated), and location (straight or curved bowel segment) using CTC data sets obtained at two doses (5 mAs and 65 mAs) and a previously described colonic phantom model. Reviewers measured the largest diameter of polyps on three proprietary workstations. Each polyp was measured with lung and soft-tissue windows on axial, 2D multiplanar reconstruction (MPR), and 3D images. There were significant differences among measurements obtained at various settings within each workstation (p < 0.0001). Measurements on 2D images were more accurate with lung window than with soft-tissue window settings (p < 0.0001). For the 65-mAs data set, the most accurate measurements were obtained in analysis of axial images with lung window, 2D MPR images with lung window, and 3D tissue cube images for Wizard, Advantage, and Vitrea workstations, respectively, without significant differences in accuracy among techniques (0.11 < p < 0.59). The mean absolute error values for these optimal settings were 0.48 mm, 0.61 mm, and 0.76 mm, respectively, for the three workstations. Within the ultralow-dose 5-mAs data set the best methods for Wizard, Advantage, and Vitrea were axial with lung window, 2D MPR with lung window, and 2D MPR with lung window, respectively. Use of nearly all measurement methods, except for the Vitrea 3D tissue cube and the Wizard 2D MPR with lung window, resulted in undermeasurement of the true size of the polyps. Use of CTC computer workstations facilitates accurate polyp measurement. For routine CTC examinations, polyps should be measured with lung window settings on 2D axial or MPR images (Wizard and Advantage) or 3D images (Vitrea). When these optimal methods are used, these three commercial workstations do not differ significantly in acquisition of accurate polyp measurements at routine dose settings.

Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood

PubMed Central

Harris, Donald G.; Quinn, Kevin J.; French, Beth M.; Schwartz, Evan; Kang, Elizabeth; Dahi, Siamak; Phelps, Carol J.; Ayares, David L.; Burdorf, Lars; Azimzadeh, Agnes M.; Pierson, Richard N.

2014-01-01

Background Genetically modified pigs are a promising potential source of lung xenografts. Ex-vivo xenoperfusion is an effective platform for testing the effect of new modifications, but typical experiments are limited by testing of a single genetic intervention and small sample sizes. The purpose of this study was to analyze the individual and aggregate effects of donor genetic modifications on porcine lung xenograft survival and injury in an extensive pig lung xenoperfusion series. Methods Data from 157 porcine lung xenoperfusion experiments using otherwise unmodified heparinized human blood were aggregated as either continuous or dichotomous variables. Lungs were wild type in 17 perfusions (11% of the study group), while 31 lungs (20% of the study group) had 1 genetic modification, 40 lungs (39%) had 2, and 47 lungs (30%) had 3 or more modifications. The primary endpoint was functional lung survival to 4 hours of perfusion. Secondary analyses evaluated previously identified markers associated with known lung xenograft injury mechanisms. In addition to comparison among all xenografts grouped by survival status, a subgroup analysis was performed of lungs incorporating the GalTKO.hCD46 genotype. Results Each increase in the number of genetic modifications was associated with additional prolongation of lung xenograft survival. Lungs that exhibited survival to 4 hours generally had reduced platelet activation and thrombin generation. GalTKO and the expression of hCD46, HO-1, hCD55 or hEPCR were associated with improved survival. hTBM, HLA-E, and hCD39 were associated with no significant effect on the primary outcome. Conclusion This meta-analysis of an extensive lung xenotransplantation series demonstrates that increasing the number of genetic modifications targeting known xenogeneic lung injury mechanisms is associated with incremental improvements in lung survival. While more detailed mechanistic studies are needed to explore the relationship between gene expression and pathway-specific injury, and explore why some genes apparently exhibit neutral (hTBM, HLA-E) or inconclusive (CD39) effects, GalTKO, hCD46, HO-1, hCD55, and hEPCR modifications were associated with significant lung xenograft protection. This analysis supports the hypothesis that multiple genetic modifications targeting different known mechanisms of xenograft injury will be required to optimize lung xenograft survival. PMID:25470239

Differential diagnosis and cancer staging of a unique case with multiple nodules in the lung - lung adenocarcinoma, metastasis of colon adenocarcinoma, and colon adenocarcinoma metastasizing to lung adenocarcinoma.

PubMed

Bai, Yun; Qiu, Jianxing; Shang, Xueqian; Liu, Ping; Zhang, Ying; Wang, Ying; Xiong, Yan; Li, Ting

2015-05-01

Lung cancer is the most common cancer in the world. Despite this, there have been few cases of simultaneous primary and metastatic cancers in the lung reported, let alone coexisting with tumor-to-tumor metastasis. Herein, we describe an extremely unusual case. A 61-year-old man with a history of colon adenocarcinoma was revealed as having three nodules in the lung 11 months after colectomy. The nodule in the left upper lobe was primary lung adenocarcinoma, the larger one in the right upper lobe was a metastasis of colon adenocarcinoma, and the smaller one in the right upper lobe was colon adenocarcinoma metastasizing to lung adenocarcinoma. Our paper focused on the differential diagnosis and cancer staging of this unique case, and discussed the uncommon phenomenon of the lung acting as a recipient in tumor-to-tumor metastasis.

Radiofrequency Ablation Using a Multiple-Electrode Switching System for Lung Tumors with 2.0-5.0-cm Maximum Diameter: Phase II Clinical Study.

PubMed

Kodama, Hiroshi; Yamakado, Koichiro; Hasegawa, Takaaki; Fujimori, Masashi; Yamanaka, Takashi; Takaki, Haruyuki; Uraki, Junji; Nakatsuka, Atsuhiro; Sakuma, Hajime

2015-12-01

To prospectively evaluate the safety and effectiveness of radiofrequency ablation (RFA) by using a multiple-electrode switching system to treat 2.0-5.0-cm lung tumors. The institutional review board approved this prospective phase II study. Written informed consent was obtained from all patients. Between September 2009 and July 2011, RFA using two or three radiofrequency (RF) electrodes and a multiple-electrode switching system was performed for malignant lung tumors with a maximum tumor diameter of 2.0-5.0 cm in nonsurgical candidates. The primary endpoint was safety, as evaluated using the Common Terminology Criteria for Adverse Events. Patients were observed for at least 1 year. Local tumor progression and overall survival were analyzed with the Kaplan-Meier method. Thirty-three patients (26 men, seven women; mean age, 70.5 years ± 10.0; age range, 46-87 years) with 35 lung tumors with a mean maximum diameter of 3.0 cm ± 0.7 (standard deviation; range, 2.0-4.4 cm) underwent treatment in 35 sessions. No procedure-related death or grade 4 adverse events (AEs) occurred. Grade 3 AEs occurred in four patients (12%), with pleural effusion requiring chest tube placement in two patients, pneumothorax requiring pleural adhesion in one patient, and pulmonary hemorrhage requiring pulmonary artery coil embolization in one patient. Grade 2 AEs were detected in 13 patients (39%). The 1-year local tumor progression and overall survival rates were 12.7% (95% confidence interval [CI]: 1.0, 25.5) and 81.2% (95% CI: 67.6, 94.8). RFA with a multiple-electrode switching system may be a safe therapeutic option with which to treat 2.0-5.0-cm lung cancer tumors.

Lung and stomach cancer associations with groundwater radon in North Carolina, USA

PubMed Central

Messier, Kyle P; Serre, Marc L

2017-01-01

Abstract Background: The risk of indoor air radon for lung cancer is well studied, but the risks of groundwater radon for both lung and stomach cancer are much less studied, and with mixed results. Methods: Geomasked and geocoded stomach and lung cancer cases in North Carolina from 1999 to 2009 were obtained from the North Carolina Central Cancer Registry. Models for the association with groundwater radon and multiple confounders were implemented at two scales: (i) an ecological model estimating cancer incidence rates at the census tract level; and (ii) a case-only logistic model estimating the odds that individual cancer cases are members of local cancer clusters. Results: For the lung cancer incidence rate model, groundwater radon is associated with an incidence rate ratio of 1.03 [95% confidence interval (CI) = 1.01, 1.06] for every 100 Bq/l increase in census tract averaged concentration. For the cluster membership models, groundwater radon exposure results in an odds ratio for lung cancer of 1.13 (95% CI = 1.04, 1.23) and for stomach cancer of 1.24 (95% CI = 1.03, 1.49), which means groundwater radon, after controlling for multiple confounders and spatial auto-correlation, increases the odds that lung and stomach cancer cases are members of their respective cancer clusters. Conclusion: Our study provides epidemiological evidence of a positive association between groundwater radon exposure and lung cancer incidence rates. The cluster membership model results find groundwater radon increases the odds that both lung and stomach cancer cases occur within their respective cancer clusters. The results corroborate previous biokinetic and mortality studies that groundwater radon is associated with increased risk for lung and stomach cancer. PMID:27639278

Lung and stomach cancer associations with groundwater radon in North Carolina, USA.

PubMed

Messier, Kyle P; Serre, Marc L

2017-04-01

The risk of indoor air radon for lung cancer is well studied, but the risks of groundwater radon for both lung and stomach cancer are much less studied, and with mixed results. Geomasked and geocoded stomach and lung cancer cases in North Carolina from 1999 to 2009 were obtained from the North Carolina Central Cancer Registry. Models for the association with groundwater radon and multiple confounders were implemented at two scales: (i) an ecological model estimating cancer incidence rates at the census tract level; and (ii) a case-only logistic model estimating the odds that individual cancer cases are members of local cancer clusters. For the lung cancer incidence rate model, groundwater radon is associated with an incidence rate ratio of 1.03 [95% confidence interval (CI) = 1.01, 1.06] for every 100 Bq/l increase in census tract averaged concentration. For the cluster membership models, groundwater radon exposure results in an odds ratio for lung cancer of 1.13 (95% CI = 1.04, 1.23) and for stomach cancer of 1.24 (95% CI = 1.03, 1.49), which means groundwater radon, after controlling for multiple confounders and spatial auto-correlation, increases the odds that lung and stomach cancer cases are members of their respective cancer clusters. Our study provides epidemiological evidence of a positive association between groundwater radon exposure and lung cancer incidence rates. The cluster membership model results find groundwater radon increases the odds that both lung and stomach cancer cases occur within their respective cancer clusters. The results corroborate previous biokinetic and mortality studies that groundwater radon is associated with increased risk for lung and stomach cancer. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

[Liver and lung metastases of colorectal cancer. Long-term survival and prognostic factors].

PubMed

Sponholz, S; Bölükbas, S; Schirren, M; Oguzhan, S; Kudelin, N; Schirren, J

2016-02-01

The resection of liver and lung metastases from colorectal cancer has not yet been completely investigated. The aim of this study was to investigate the overall survival and prognostic factors for patients with liver and lung metastases from colorectal cancer. A retrospective review of a prospective database of 52 patients with liver and lung metastases from colorectal cancer, undergoing metastasectomy with curative intent from 1999-2009 at a single institution was carried out. The mean overall survival (OS) was 64 months. For synchronous liver and lung metastases the mean overall survival was 63 months (5-year survival 54 %) and for metachronous liver and lung metastases 74 months (5-year survival 58 %, p = 0.451). A poor prognostic outcome was observed in cases of localization of the primary tumor in the rectum (OS 81 vs. 38 months, p = 0.004), with multiple lung metastases (≥ 2 metastases, OS 74 vs. 59 months, p = 0.032) and with disease progression after premetastasectomy chemotherapy (OS 74 vs. 63 vs. 15 months, p < 0.001). No influence on overall survival was detected for bilateral lung metastases, thoracic lymph node metastases, disease recurrence and disease-free interval < 36 months. Metastasectomy for liver and lung metastases of colorectal cancer is associated with a good overall survival in selected cases. Patients with liver and lung metastases should not be routinely excluded from metastasectomy and patients with thoracic lymph node metastases should also not be routinely excluded. Negative prognostic factors for survival are localization of the tumor in the rectum, multiple metastases and disease progression after premetastasectomy chemotherapy. Patients with disease progression after premetastasectomy chemotherapy should be excluded from metastasectomy.

Influence of experimental rat model of multiple organ dysfunction on cefepime and amikacin pharmacokinetics.

PubMed Central

Mimoz, O; Jacolot, A; Padoin, C; Quillard, J; Tod, M; Louchahi, K; Samii, K; Petitjean, O

1996-01-01

We adapted an experimental model of multiple organ dysfunction to study the alterations it induces in the pharmacology of cefepime and amikacin. The half-lives of both antibiotics were significantly prolonged because of nonsignificant enhancement of the volume of distribution and reduced renal elimination. In the presence of multiple organ dysfunction, the concentration of each antibiotic in the lungs, compared with that in the lungs of healthy controls, was significantly decreased, despite similar concentrations in plasma, indicating that the application of a standard antibiotic concentration in plasma could lead to underdosage in tissues during the initial days of therapy. PMID:8851623

[Hemopleuritis in closed thoracic injuries and multiple trauma].

PubMed

Kabanov, A N; Astafurov, V N; Blokh, E R

1991-09-01

In examination of 817 patients with closed chest injury and multiple trauma 57% of them were found to have obvious or latent hemopleuritis. According to the character of the primary damage and the developing pathophysiological changes, 3 forms of hemopleuritis were revealed: cardiac, pulmonary, and abdominal. A single complex of symptoms forms finally: pulmonary hypertension, venous stasis in the lungs, right-ventricular cardiac insufficiency. As a result, venous blood escapes through the lymph nodes, mainly those of the right lung, and together with the lymph flows in the dilated lymph vessels of the lungs into the pleural cavity. The differential-diagnostic signs of each form of hemopleuritis are pointed out, the prognostic criteria of their development are revealed, and the pathogenetically substantiated therapy is determined.

Quantitative Proteomic Profiling the Molecular Signatures of Annexin A5 in Lung Squamous Carcinoma Cells.

PubMed

Sun, Bing; Bai, Yuxin; Zhang, Liyuan; Gong, Linlin; Qi, Xiaoyu; Li, Huizhen; Wang, Faming; Chi, Xinming; Jiang, Yulin; Shao, Shujuan

Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target. We used a stable isotope dimethyl labeling based quantitative proteomic method to identify differentially expressed proteins in NSCLC cell lines after ANXA5 transfection. Out of 314 proteins, we identified 26 and 44 proteins that were down- and up-regulated upon ANXA5 modulation, respectively. The IPA analysis revealed that glycolysis and gluconeogenesis were the predominant pathways modulated by ANXA5. Multiple central nodes, namely HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP and KRT6A appeared to occupy regulatory nodes in the protein-protein networks upon ANXA5 modulation. Taken together, ANXA5 appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of ANXA5 as a potential target in lung cancer. This study might provide a new insight into the mechanism of ANXA5 in lung cancer.

Lung Cancer Screening with Low-Dose Computed Tomography for Primary Care Providers

PubMed Central

Richards, Thomas B.; White, Mary C.; Caraballo, Ralph S.

2015-01-01

This review provides an update on lung cancer screening with low-dose computed tomography (LDCT) and its implications for primary care providers. One of the unique features of lung cancer screening is the potential complexity in patient management if an LDCT scan reveals a small pulmonary nodule. Additional tests, consultation with multiple specialists, and follow-up evaluations may be needed to evaluate whether lung cancer is present. Primary care providers should know the resources available in their communities for lung cancer screening with LDCT and smoking cessation, and the key points to be addressed in informed and shared decision-making discussions with patients. PMID:24830610

Pain management in lung cancer.

PubMed

Nurwidya, Fariz; Syahruddin, Elisna; Yunus, Faisal

2016-01-01

Lung cancer is the leading cause of cancer-related mortality worldwide. Not only burdened by the limited overall survival, lung cancer patient also suffer from various symptoms, such as pain, that implicated in the quality of life. Cancer pain is a complicated and transiently dynamic symptom that results from multiple mechanisms. This review will describe the pathophysiology of cancer pain and general approach in managing a patient with lung cancer pain. The use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and adjuvant analgesia, as part of the pharmacology therapy along with interventional strategy, will also be discussed.

Lung cancer induced in hamsters by low doses of alpha radiation from polonium-210.

PubMed

Little, J B; Kennedy, A R; McGandy, R B

1975-05-16

Lung cancers have been induced in 9 to 53 percent of hamsters given multiple intratracheal instillations of polonium-210 in amounts yielding lifetime exposures of 15 to 300 rads to the lungs. Cigarette smokers have previously been estimated to receive 20 rads to areas of the bronchial epithelium from deposited polonium-210. This finding thus supports the hypothesis that alpha radiation resulting from the polonium-210 or lead-210 present in cigarette smoke may be a significant causative factor in human lung cancer.

Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection

PubMed Central

Cantone, Martina; Santos, Guido; Wentker, Pia; Lai, Xin; Vera, Julio

2017-01-01

Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection. This failure can result in systemic spreading of pathogens or overwhelming immune response followed by a systemic inflammatory response. Mathematical modeling is a promising tool to dissect the complexity underlying pathogenesis of bacterial lung infection at the molecular, cellular and tissue levels, and also at the interfaces among levels. In this article, we introduce mathematical and computational modeling frameworks that can be used for investigating molecular and cellular mechanisms underlying bacterial lung infection. Then, we compile and discuss published results on the modeling of regulatory pathways and cell populations relevant for lung infection and inflammation. Finally, we discuss how to make use of this multiplicity of modeling approaches to open new avenues in the search of the molecular and cellular mechanisms underlying bacterial infection in the lung. PMID:28912729

Multiplicity of Mathematical Modeling Strategies to Search for Molecular and Cellular Insights into Bacteria Lung Infection.

PubMed

Cantone, Martina; Santos, Guido; Wentker, Pia; Lai, Xin; Vera, Julio

2017-01-01

Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection. This failure can result in systemic spreading of pathogens or overwhelming immune response followed by a systemic inflammatory response. Mathematical modeling is a promising tool to dissect the complexity underlying pathogenesis of bacterial lung infection at the molecular, cellular and tissue levels, and also at the interfaces among levels. In this article, we introduce mathematical and computational modeling frameworks that can be used for investigating molecular and cellular mechanisms underlying bacterial lung infection. Then, we compile and discuss published results on the modeling of regulatory pathways and cell populations relevant for lung infection and inflammation. Finally, we discuss how to make use of this multiplicity of modeling approaches to open new avenues in the search of the molecular and cellular mechanisms underlying bacterial infection in the lung.

Association between the Type of Workplace and Lung Function in Copper Miners

PubMed Central

Gruszczyński, Leszek; Wojakowska, Anna; Ścieszka, Marek; Turczyn, Barbara; Schmidt, Edward

2016-01-01

The aim of the analysis was to retrospectively assess changes in lung function in copper miners depending on the type of workplace. In the groups of 225 operators, 188 welders, and 475 representatives of other jobs, spirometry was performed at the start of employment and subsequently after 10, 20, and 25 years of work. Spirometry Longitudinal Data Analysis software was used to estimate changes in group means for FEV1 and FVC. Multiple linear regression analysis was used to assess an association between workplace and lung function. Lung function assessed on the basis of calculation of longitudinal FEV1 (FVC) decline was similar in all studied groups. However, multiple linear regression model used in cross-sectional analysis revealed an association between workplace and lung function. In the group of welders, FEF75 was lower in comparison to operators and other miners as early as after 10 years of work. Simultaneously, in smoking welders, the FEV1/FVC ratio was lower than in nonsmokers (p < 0,05). The interactions between type of workplace and smoking (p < 0,05) in their effect on FVC, FEV1, PEF, and FEF50 were shown. Among underground working copper miners, the group of smoking welders is especially threatened by impairment of lung ventilatory function. PMID:27274987

Bronchoscopy with endobronchial ultrasound guided transbronchial needle aspiration vs. transthoracic needle aspiration in lung cancer diagnosis and staging.

PubMed

Munoz, Mark L; Lechtzin, Noah; Li, Qing Kay; Wang, KoPen; Yarmus, Lonny B; Lee, Hans J; Feller-Kopman, David J

2017-07-01

In evaluating patients with suspected lung cancer, it is important to not only obtain a tissue diagnosis, but also to obtain enough tissue for both histologic and molecular analysis in order to appropriately stage the patient with a safe and efficient strategy. The diagnostic approach may often be dependent on local resources and practice patterns rather than current guidelines. We Describe lung cancer staging at two large academic medical centers to identify the impact different procedural approaches have on patient outcomes. We conducted a retrospective cohort study of all patients undergoing a lung cancer diagnostic evaluation at two multidisciplinary centers during a 1-year period. Identifying complication rates and the need for multiple biopsies as our primary outcomes, we developed a multivariate regression model to determine features associated with complications and need for multiple biopsies. Of 830 patients, 285 patients were diagnosed with lung cancers during the study period. Those staged at the institution without an endobronchial ultrasound (EBUS) program were more likely to require multiple biopsies (OR 3.62, 95% CI: 1.71-7.67, P=0.001) and suffer complications associated with the diagnostic procedure (OR 10.2, 95% CI: 3.08-33.58, P<0.001). Initial staging with transthoracic needle aspiration (TTNA) and conventional bronchoscopy were associated with greater need for subsequent biopsies (OR 8.05 and 14.00, 95% CI: 3.43-18.87 and 5.17-37.86, respectively) and higher complication rates (OR 37.75 and 7.20, 95% CI: 10.33-137.96 and 1.36-37.98, respectively). Lung cancer evaluation at centers with a dedicated EBUS program results in fewer biopsies and complications than at multidisciplinary counterparts without an EBUS program.

Repeated exposures to roadside particulate matter extracts suppresses pulmonary defense mechanisms, resulting in lipid and protein oxidative damage.

PubMed

Pardo, Michal; Porat, Ziv; Rudich, Assaf; Schauer, James J; Rudich, Yinon

2016-03-01

Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM. Copyright © 2015 Elsevier Ltd. All rights reserved.

The lung mycobiome in the next-generation sequencing era

PubMed Central

Tipton, Laura; Ghedin, Elodie; Morris, Alison

2017-01-01

ABSTRACT The fungi that reside in the human lungs represent an understudied, but medically relevant comm-unity. From the few studies published on the lung mycobiome, we find that there are fungi in both the healthy and diseased respiratory tract, that these fungi vary widely between individuals, and that there is a trend toward lower fungal diversity among individuals with disease. This review discusses the few studies of the lung mycobiome and details the challenges that accompany lung mycobiome studies. These challenges include sample collection and processing, sequence amplification and processing, and a history of multiple names for species. Some challenges may never be solved, but others can be solved with more data and additional studies of the lung mycobiome. PMID:27687858

Right Ventricular Dysfunction in Chronic Lung Disease

PubMed Central

Kolb, Todd M.; Hassoun, Paul M.

2012-01-01

Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, except during acute exacerbations of chronic lung disease or when multiple co-morbidities are present. Treatment is targeted at correcting hypoxia and improving pulmonary gas exchange and mechanics. There are presently no convincing data to support the use of pulmonary hypertension-specific therapies in patients with right ventricular dysfunction secondary to chronic lung disease. PMID:22548815

Effects of antenatal multiple micronutrient supplementation on lung function in mid-childhood: follow-up of a double-blind randomised controlled trial in Nepal

PubMed Central

Devakumar, D; Stocks, J; Ayres, JG; Kirkby, J; Yadav, SK; Saville, NM; Devereux, G; Wells, JCK; Manandhar, DS; Costello, A; Osrin, D

2015-01-01

A randomised trial of prenatal multiple micronutrient supplementation in Nepalese women increased birthweight and weight at two years of age in offspring, compared with those born to mothers who only received iron and folic acid supplements. Further follow-up of this cohort provided an opportunity to investigate the effect of antenatal multiple micronutrients on subsequent lung function, by measuring spirometry at 7-9 years of age in children born in the trial. 841 children (80% of the cohort) were seen at mean (SD) 8.5 (0.4) years. Technically successful spirometry results were obtained in 793 children (94.3%), 50% of whom had been randomised to micronutrient supplementation. Background characteristics, including anthropometry, were similar in the two allocation groups. Lung function was also similar, mean (95%CI) difference in z-scores (supplementation – control) being −0.08 (−0.19, 0.04) for FEV1; −0.05 (−0.17, 0.06) for FVC and −0.04 (−0.15, 0.07) for FEV1/FVC. Compared with healthy White children, FEV1 and FVC in the ‘healthy’ Nepalese children were ~1 z-score (~13%) lower, with no difference in FEV1/FVC. We conclude that, compared with routine iron and folic acid, multiple micronutrient supplementation during pregnancy has no effect on spirometric lung function in Nepalese children at 8.5 years of age. PMID:25700386

SU-F-R-20: Image Texture Features Correlate with Time to Local Failure in Lung SBRT Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrews, M; Abazeed, M; Woody, N

Purpose: To explore possible correlation between CT image-based texture and histogram features and time-to-local-failure in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT).Methods and Materials: From an IRB-approved lung SBRT registry for patients treated between 2009–2013 we selected 48 (20 male, 28 female) patients with local failure. Median patient age was 72.3±10.3 years. Mean time to local failure was 15 ± 7.1 months. Physician-contoured gross tumor volumes (GTV) on the planning CT images were processed and 3D gray-level co-occurrence matrix (GLCM) based texture and histogram features were calculated in Matlab. Data were exported tomore » R and a multiple linear regression model was used to examine the relationship between texture features and time-to-local-failure. Results: Multiple linear regression revealed that entropy (p=0.0233, multiple R2=0.60) from GLCM-based texture analysis and the standard deviation (p=0.0194, multiple R2=0.60) from the histogram-based features were statistically significantly correlated with the time-to-local-failure. Conclusion: Image-based texture analysis can be used to predict certain aspects of treatment outcomes of NSCLC patients treated with SBRT. We found entropy and standard deviation calculated for the GTV on the CT images displayed a statistically significant correlation with and time-to-local-failure in lung SBRT patients.« less

Lung Cancer Cell Lines as Tools for Biomedical Discovery and Research

PubMed Central

Girard, Luc; Lockwood, William W.; Lam, Wan L.; Minna, John D.

2010-01-01

Lung cancer cell lines have made a substantial contribution to lung cancer translational research and biomedical discovery. A systematic approach to initiating and characterizing cell lines from small cell and non–small cell lung carcinomas has led to the current collection of more than 200 lung cancer cell lines, a number that exceeds those for other common epithelial cancers combined. The ready availability and widespread dissemination of the lines to investigators worldwide have resulted in more than 9000 citations, including multiple examples of important biomedical discoveries. The high (but not perfect) genomic similarities between lung cancer cell lines and the lung tumor type from which they were derived provide evidence of the relevance of their use. However, major problems including misidentification or cell line contamination remain. Ongoing studies and new approaches are expected to reveal the full potential of the lung cancer cell line panel. PMID:20679594

Measurement of lung volumes from supine portable chest radiographs.

PubMed

Ries, A L; Clausen, J L; Friedman, P J

1979-12-01

Lung volumes in supine nonambulatory patients are physiological parameters often difficult to measure with current techniques (plethysmograph, gas dilution). Existing radiographic methods for measuring lung volumes require standard upright chest radiographs. Accordingly, in 31 normal supine adults, we determined helium-dilution functional residual and total lung capacities and measured planimetric lung field areas (LFA) from corresponding portable anteroposterior and lateral radiographs. Low radiation dose methods, which delivered less than 10% of that from standard portable X-ray technique, were utilized. Correlation between lung volume and radiographic LFA was highly significant (r = 0.96, SEE = 10.6%). Multiple-step regressions using height and chest diameter correction factors reduced variance, but weight and radiographic magnification factors did not. In 17 additional subjects studied for validation, the regression equations accurately predicted radiographic lung volume. Thus, this technique can provide accurate and rapid measurement of lung volume in studies involving supine patients.

Outcomes of stereotactic body radiotherapy (SBRT) treatment of multiple synchronous and recurrent lung nodules.

PubMed

Owen, Dawn; Olivier, Kenneth R; Mayo, Charles S; Miller, Robert C; Nelson, Kathryn; Bauer, Heather; Brown, Paul D; Park, Sean S; Ma, Daniel J; Garces, Yolanda I

2015-02-18

Stereotactic body radiotherapy (SBRT) is evolving into a standard of care for unresectable lung nodules. Local control has been shown to be in excess of 90% at 3 years. However, some patients present with synchronous lung nodules in the ipsilateral or contralateral lobe or metasynchronous disease. In these cases, patients may receive multiple courses of lung SBRT or a single course for synchronous nodules. The toxicity of such treatment is currently unknown. Between 2006 and 2012, 63 subjects with 128 metasynchronous and synchronous lung nodules were treated at the Mayo Clinic with SBRT. Demographic patient data and dosimetric data regarding SBRT treatments were collected. Acute toxicity (defined as toxicity < 90 days) and late toxicity (defined as toxicity > = 90 days) were reported and graded as per standardized CTCAE 4.0 criteria. Local control, progression free survival and overall survival were also described. The median age of patients treated was 73 years. Sixty five percent were primary or recurrent lung cancers with the remainder metastatic lung nodules of varying histologies. Of 63 patients, 18 had prior high dose external beam radiation to the mediastinum or chest. Dose and fractionation varied but the most common prescriptions were 48 Gy/4 fractions, 54 Gy/3 fractions, and 50 Gy/5 fractions. Only 6 patients demonstrated local recurrence. With a median follow up of 12.6 months, median SBRT specific overall survival and progression free survival were 35.7 months and 10.7 months respectively. Fifty one percent (32/63 patients) experienced acute toxicity, predominantly grade 1 and 2 fatigue. One patient developed acute grade 3 radiation pneumonitis at 75 days. Forty six percent (29/63 patients) developed late effects. Most were grade 1 dyspnea. There was one patient with grade 5 pneumonitis. Multiple courses of SBRT and SBRT delivery after external beam radiotherapy appear to be feasible and safe. Most toxicity was grade 1 and 2 but the risk was approximately 50% for both acute and late effects.

MEASUREMENTS OF AIR POLLUTANT BIOMARKERS WITH EXHALED BREATH TECHNIQUES

EPA Science Inventory

Use of exhaled breath condensate (EBC) has appeal as a noninvasive surrogate sample for lung-derived fluid. Additionally, EBC can be collected multiple times over the course of a study, unlike many other lung sampling techniques which can be performed fewer times. However validat...

Proteomic analysis of lung tissue by DIGE

USDA-ARS?s Scientific Manuscript database

Lungs perform an essential physiological function, mediated by a complex series of events that involve the coordination of multiple cell types to support not only gaseous exchange, but homeostasis and protection from infection. Guinea pigs are an important animal disease model for a number of infect...

Aerosolized 3-bromopyruvate inhibits lung tumorigenesis without causing liver toxicity.

PubMed

Zhang, Qi; Pan, Jing; North, Paula E; Yang, Shoua; Lubet, Ronald A; Wang, Yian; You, Ming

2012-05-01

3-Bromopyruvate, an alkylating agent and a well-known inhibitor of energy metabolism, has been proposed as a specific anticancer agent. However, the chemopreventive effect of 3-bromopyruvate in lung tumorigenesis has not been tested. In this study, we investigated the chemopreventive activity of 3-bromopyruvate in a mouse lung tumor model. Benzo(a)pyrene was used to induce lung tumors, and 3-bromopyruvate was administered by oral gavage to female A/J mice. We found that 3-bromopyruvate significantly decreased tumor multiplicity and tumor load by 58% and 83%, respectively, at a dose of 20 mg/kg body weight by gavage. Due to the known liver toxicity of 3-bromopyruvate in animal models given large doses of 3-bromopyruvate, confirmed in this study, we decided to test the chemopreventive activity of aerosolized 3-bromopyruvate in the same lung tumor model. As expected, aerosolized 3-bromopyruvate similarly significantly decreased tumor multiplicity and tumor load by 49% and 80%, respectively, at a dose of 10 mg/mL by inhalation. Interestingly, the efficacy of aerosolized 3-bromopyruvate did not accompany any liver toxicity indicating that it is a safer route of administering this compound. Treatment with 3-bromopyruvate increased immunohistochemical staining for cleaved caspase-3, suggesting that the lung tumor inhibitory effects of 3-bromopyruvate were through induction of apoptosis. 3-Bromopyruvate also dissociated hexokinase II from mitochondria, reduced hexokinase activity, and blocked energy metabolism in cancer cells, finally triggered cancer cell death and induced apoptosis through caspase-3, and PARP in human lung cancer cell line. The ability of 3-bromopyruvate to inhibit mouse lung tumorigenesis, in part through induction of apoptosis, merits further investigation of this compound as a chemopreventive agent for human lung cancer.

Epigenetics in non-small cell lung cancer: from basics to therapeutics.

PubMed

Ansari, Junaid; Shackelford, Rodney E; El-Osta, Hazem

2016-04-01

Lung cancer remains the number one cause of cancer-related deaths worldwide with 221,200 estimated new cases and 158,040 estimated deaths in 2015. Approximately 80% of cases are non-small cell lung cancer (NSCLC). The diagnosis is usually made at an advanced stage where the prognosis is poor and therapeutic options are limited. The evolution of lung cancer is a multistep process involving genetic, epigenetic, and environmental factor interactions that result in the dysregulation of key oncogenes and tumor suppressor genes, culminating in activation of cancer-related signaling pathways. The past decade has witnessed the discovery of multiple molecular aberrations that drive lung cancer growth, among which are epidermal growth factor receptor (EGFR) mutations and translocations involving the anaplastic lymphoma kinase (ALK) gene. This has translated into therapeutic agent developments that target these molecular alterations. The absence of targetable mutations in 50% of NSCLC cases and targeted therapy resistance development underscores the importance for developing alternative therapeutic strategies for treating lung cancer. Among these strategies, pharmacologic modulation of the epigenome has been used to treat lung cancer. Epigenetics approaches may circumvent the problem of tumor heterogeneity by affecting the expression of multiple tumor suppression genes (TSGs), halting tumor growth and survival. Moreover, it may be effective for tumors that are not driven by currently recognized druggable mutations. This review summarizes the molecular pathology of lung cancer epigenetic aberrations and discusses current efforts to target the epigenome with different pharmacological approaches. Our main focus will be on hypomethylating agents, histone deacetylase (HDAC) inhibitors, microRNA modulations, and the role of novel epigenetic biomarkers. Last, we will address the challenges that face this old-new strategy in treating lung cancer.

Postoperative Management of Multiple Primary Cancers Associated with Non-small Cell Lung Cancer.

PubMed

Shoji, Fumihiro; Yamazaki, Koji; Miura, Naoko; Katsura, Masakazu; Oku, Yuka; Takeo, Sadanori; Maehara, Yoshihiko

2018-06-01

Modern treatment for primary cancers has improved survival. Therefore, increased numbers of patients with multiple primary cancers (MPC) associated with lung cancer may be expected. The aim of the present study was to report MPC associated with lung cancer and discuss patients' characteristics and postoperative management. Overall, 973 consecutive patients who underwent surgery for non-small cell lung cancer (NSCLC) were retrospectively studied. NSCLC with MPC was observed in 148 patients (15.2%). MPC comprised 24 synchronous (2.5%) and 124 metachronous (12.7%) diseases. Of the 124 metachronous patients, NSCLC was detected before cancers were detected in other organs (lung cancer first (LCF)) in 25 (20.2%) patients and subsequently in other organs after treatment (other organs, primary cancer-first (OCF)) in 99 (79.8%) patients. MPC was significantly associated with advanced age (p<0.0001) and chronic obstructive pulmonary disease (COPD) (p=0.0040). The leading sites of MPC in patients with synchronous tumors and those with OCF were the digestive organs. In contrast, the leading site of MPC in patients with LCF was the lung. In the latter, at least two primary lung cancers were detected within 5 years as well as 5 years after surgery for the treatment of the first detected lung cancer, while primary cancers of other organs were detected within 5 years. Advanced age and COPD may represent a high-risk of MPCs. Therefore, we recommend careful follow-up to detect MPC in the lung as well as the digestive organs beyond 5 years after treatment of the first cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Sudden multiple fractures in a patient with sarcoidosis in multiple organs.

PubMed

Sada, Mitsuru; Saraya, Takeshi; Ishii, Haruyuki; Goto, Hajime

2014-04-07

A 30-year-old man who incidentally fractured his right olecranon and other multiple phalanges was admitted to our hospital. He had a 2-year history of uveitis and bilateral hilar lymphadenopathy (BHL), and pulmonary sarcoidosis was diagnosed from transbronchial lung biopsy. Right elbow arthrodesis was performed, and biopsied specimens showed non-caseating epithelioid cell granuloma, suggesting osseous sarcoidosis. He was discharged uneventfully without further treatment, but BHL had progressed with the appearance of lung parenchymal lesions 3 months later. At that time, involvement of other organs was also noted on Gallium-67 scintigraphy, showing accumulations in BHL, axillary and inguinal lymph nodes, enlarged liver and spleen and subcutaneous areas. After initiation of steroid therapy, multiple organ involvement improved, and no further bone involvement has been recognised to date. Osseous sarcoidosis complicated by bone fracture is an extremely rare presentation, but should be considered in patients with sarcoidosis, especially when multiple organs are involved.

β-Cryptoxanthin Reduced Lung Tumor Multiplicity and Inhibited Lung Cancer Cell Motility by Downregulating Nicotinic Acetylcholine Receptor α7 Signaling.

PubMed

Iskandar, Anita R; Miao, Benchun; Li, Xinli; Hu, Kang-Quan; Liu, Chun; Wang, Xiang-Dong

2016-11-01

Despite the consistent association between a higher intake of the provitamin A carotenoid β-cryptoxanthin (BCX) and a lower risk of lung cancer among smokers, potential mechanisms supporting BCX as a chemopreventive agent are needed. We first examined the effects of BCX on 4-[methyl nitrosamino]-1-[3-pyridyl]-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. BCX supplementation was given daily to the mice starting 2 weeks prior to the injection of NNK and continued 16 weeks after NNK injection. BCX supplementation resulted in a dose-dependent increase of BCX concentration in both serum and lungs of the mice without a significant alteration of vitamin A (retinol and retinyl palmitate) concentration. BCX significantly reduced the multiplicity of the NNK-induced lung tumor by 52% to 63% compared with the NNK-treated mice without BCX supplementation. The protective effect of BCX in the lungs was associated with reductions of both mRNA and protein of the homopentameric neuronal nicotinic acetylcholine receptor α7 (α7-nAChR), which has been implicated in lung tumorigenesis. We then conducted an in vitro cell culture study and found that BCX treatment suppressed α7-nAChR expression and inhibited the migration and invasion of α7-nAChR-positive lung cancer cells but not in cells lacking α7-nAChR. The activities of BCX were significantly attenuated by activators of α7-nAChR/PI3K signaling or by overexpression of constitutively active PI3K. Collectively, the results suggest that BCX inhibits lung tumorigenesis and cancer cell motility through the downregulation of α7-nAChR/PI3K signaling, independent of its provitamin A activity. Therefore, BCX can be used as a chemopreventive agent or a chemotherapeutic compound against lung cancer. Cancer Prev Res; 9(11); 875-86. ©2016 AACR. ©2016 American Association for Cancer Research.

Bone Marrow Mesenchymal Stem Cells Suppress Acute Lung Injury Induced by Lipopolysaccharide Through Inhibiting the TLR2, 4/NF-κB Pathway in Rats with Multiple Trauma.

PubMed

Li, Dequan; Pan, Xuebo; Zhao, Jing; Chi, Chuang; Wu, Guangyu; Wang, Yuanyuan; Liao, Shiyao; Wang, Cong; Ma, Jihong; Pan, Jingye

2016-06-01

Multiple trauma normally leads to acute lung injury (ALI) and other multiple organ dysfunction syndrome (MODS). Finding effective treatments for ALI remains a medical as well as socioeconomic challenge. Several studies show that bone marrow mesenchymal stem cells (BMSCs) have the potent anti-inflammation activity and transfusion of BMSCs can effectively inhibit inflammatory and autoimmune diseases. In this study, we investigated the TLR2, 4/NF-κB signaling pathway to determine the therapeutic value of BMSCs on lipopolysaccharide (LPS)-induced ALI. To investigate the immunosuppression effects of BMSCs, rats subjected to multiple trauma were administrated with LPS to induce ALI and then treated with BMSCs. The histology of the lung was examined. Serum levels of the pro-inflammatory factors TNFα, interleukin (IL)-6, and IL-1β, as well as anti-inflammatory factor IL-10 were measured at 3, 6, 12, and 24 h after the treatment. Moreover, expressions of TLR2 and TLR4 at the mRNA and protein levels, as well as phosphorylation of p65 in the lungs, were assessed at these time points. We found that BMSCs reduced inflammatory injury, inhibited LPS-induced upregulation of TLR2 and TLR4 expression at the mRNA and protein levels, and compromised p65 phosphorylation. In addition, infusion of BMSCs also downregulated the abundance of pro-inflammatory TNFα, IL-6, and IL-1β and upregulated the abundance of anti-inflammatory IL-10 levels in the serum. Our results suggest that BMSCs suppress the inflammatory reactions through inhibition of the TLR2, 4 mediated NF-κB signal pathway, which hints that BMSCs can potentially be used to treat ALI in multiple trauma.

Mitochondrial DNA Damage Initiates Acute Lung Injury and Multi-Organ System Failure Evoked in Rats by Intra-Tracheal Pseudomonas Aeruginosa.

PubMed

Lee, Yann-Leei; Obiako, Boniface; Gorodnya, Olena M; Ruchko, Mykhaylo V; Kuck, Jamie L; Pastukh, Viktor M; Wilson, Glenn L; Simmons, Jon D; Gillespie, Mark N

2017-07-01

Although studies in rat cultured pulmonary artery endothelial cells, perfused lungs, and intact mice support the concept that oxidative mitochondrial (mt) DNA damage triggers acute lung injury (ALI), it has not yet been determined whether enhanced mtDNA repair forestalls development of ALI and its progression to multiple organ system failure (MOSF). Accordingly, here we examined the effect of a fusion protein construct targeting the DNA glycosylase, Ogg1, to mitochondria in a rat model intra-tracheal Pseudomonas aeruginosa (strain 103; PA103)-induced ALI and MOSF. Relative to controls, animals given PA103 displayed increases in lung vascular filtration coefficient accompanied by transient lung tissue oxidative mtDNA damage and variable changes in mtDNA copy number without evidence of nuclear DNA damage. The approximate 40% of animals surviving 24 h after bacterial administration exhibited multiple organ dysfunction, manifest as increased serum and tissue-specific indices of kidney and liver failure, along with depressed heart rate and blood pressure. While administration of mt-targeted Ogg1 to control animals was innocuous, the active fusion protein, but not a DNA repair-deficient mutant, prevented bacteria-induced increases in lung tissue oxidative mtDNA damage, failed to alter mtDNA copy number, and attenuated lung endothelial barrier degradation. These changes were associated with suppression of liver, kidney, and cardiovascular dysfunction and with decreased 24 h mortality. Collectively, the present findings indicate that oxidative mtDNA damage to lung tissue initiates PA103-induced ALI and MOSF in rats.

Urothelial bladder cancer with cavitary lung metastases

PubMed Central

Kurian, Anil; Lee, Jason; Born, Abraham

2011-01-01

Transitional cell carcinoma (TCC) of the bladder tends to remain superficial; however, in 5% to 20% of cases, it progresses to muscle invasion and, more rarely, can metastasize. TCC of the bladder primarily spreads via regional lymphatics. The most common sites of distant metastases of TCC are the liver, lung, mediastinum and bone. Long-term survival of patients with metastatic bladder cancer is rare. Patterns of pulmonary metastasis include multiple nodules, a solitary mass or interstitial micronodule. When multiple nodules are present, they are round and well-circumscribed, without calcification or cavitation. An unusual case of rapidly metastatic TCC to the lung causing large cavitary masses and nodules is presented. Imaging performed after the patient began chemotherapy revealed widespread necrosis of the metastatic cavitary masses causing moderate volume hemoptysis. PMID:21766082

Squamous Cell Cancer of The Lung with Synchronous Renal Cell Carcinoma

PubMed Central

Ateş, İhsan; Yazıcı, Ozan; Ateş, Hale; Yazılıtaş, Doğan; Özcan, Ayşe Naz; Ağaçkıran, Yetkin; Zengin, Nurullah

2016-01-01

Coexistence of two or more primary cancers is a relatively rare case. Not with standing that the coexistence of multiple primary cancers is often discussed in the literature, there is a small number of publications concerning the coexistence of squamous cell lung carcinoma and renal cancer. In this case report, detection of both squamous cell lung carcinoma and primary renal cancer in one male patient is going to be discussed. PMID:29404140

Lung cancer signature biomarkers: tissue specific semantic similarity based clustering of digital differential display (DDD) data.

PubMed

Srivastava, Mousami; Khurana, Pankaj; Sugadev, Ragumani

2012-11-02

The tissue-specific Unigene Sets derived from more than one million expressed sequence tags (ESTs) in the NCBI, GenBank database offers a platform for identifying significantly and differentially expressed tissue-specific genes by in-silico methods. Digital differential display (DDD) rapidly creates transcription profiles based on EST comparisons and numerically calculates, as a fraction of the pool of ESTs, the relative sequence abundance of known and novel genes. However, the process of identifying the most likely tissue for a specific disease in which to search for candidate genes from the pool of differentially expressed genes remains difficult. Therefore, we have used 'Gene Ontology semantic similarity score' to measure the GO similarity between gene products of lung tissue-specific candidate genes from control (normal) and disease (cancer) sets. This semantic similarity score matrix based on hierarchical clustering represents in the form of a dendrogram. The dendrogram cluster stability was assessed by multiple bootstrapping. Multiple bootstrapping also computes a p-value for each cluster and corrects the bias of the bootstrap probability. Subsequent hierarchical clustering by the multiple bootstrapping method (α = 0.95) identified seven clusters. The comparative, as well as subtractive, approach revealed a set of 38 biomarkers comprising four distinct lung cancer signature biomarker clusters (panel 1-4). Further gene enrichment analysis of the four panels revealed that each panel represents a set of lung cancer linked metastasis diagnostic biomarkers (panel 1), chemotherapy/drug resistance biomarkers (panel 2), hypoxia regulated biomarkers (panel 3) and lung extra cellular matrix biomarkers (panel 4). Expression analysis reveals that hypoxia induced lung cancer related biomarkers (panel 3), HIF and its modulating proteins (TGM2, CSNK1A1, CTNNA1, NAMPT/Visfatin, TNFRSF1A, ETS1, SRC-1, FN1, APLP2, DMBT1/SAG, AIB1 and AZIN1) are significantly down regulated. All down regulated genes in this panel were highly up regulated in most other types of cancers. These panels of proteins may represent signature biomarkers for lung cancer and will aid in lung cancer diagnosis and disease monitoring as well as in the prediction of responses to therapeutics.

Effect of Ergothioneine on Acute Lung Injury and Inflammation in Cytokine Insufflated Rats

PubMed Central

Repine, John E.; Elkins, Nancy D.

2012-01-01

Objective The Acute Respiratory Distress Syndrome (ARDS), the most severe form of Acute Lung Injury (ALI), is a highly-fatal, diffuse non-cardiogenic edematous lung disorder. The pathogenesis of ARDS is unknown but lung inflammation and lung oxidative stress are likely contributing factors. Since no specific pharmacologic intervention exists for ARDS, our objective was to determine the effect of treatment with ergothioneine---a safe agent with multiple anti-inflammatory and antioxidant properties on the development of lung injury and inflammation in rats insufflated with cytokines found in lung lavages of ARDS patients. Method Sprague-Dawley rats (3-10/group) were given 15 mg/kg or 150 mg/kg L-ergothioneine intravenously 1 hour before or 18 hours after cytokine (IL-1 and IFNγ) insufflation. Lung injury (lavage LDH levels) and lung inflammation (lavage neutrophil numbers) were measured 24 hours after cytokine insufflation. Results Ergothioneine pre- and post- treatment generally decreased lung injury and lung inflammation in cytokine insufflated rats. Conclusion Ergothioneine should be considered for additional testing as a potential therapy for treating and preventing ARDS. PMID:22197759

Treatment of acute lung injury by targeting MG53-mediated cell membrane repair

PubMed Central

Lieber, Gissela; Nishi, Miyuki; Yan, Rosalie; Wang, Zhen; Yao, Yonggang; Li, Yu; Whitson, Bryan A.; Duann, Pu; Li, Haichang; Zhou, Xinyu; Zhu, Hua; Takeshima, Hiroshi; Hunter, John C.; McLeod, Robbie L.; Weisleder, Noah; Zeng, Chunyu; Ma, Jianjie

2014-01-01

Injury to lung epithelial cells has a role in multiple lung diseases. We previously identified mitsugumin 53 (MG53) as a component of the cell membrane repair machinery in striated muscle cells. Here we show that MG53 also has a physiological role in the lung and may be used as a treatment in animal models of acute lung injury. Mice lacking MG53 show increased susceptibility to ischemia-reperfusion and over-ventilation induced injury to the lung when compared with wild type mice. Extracellular application of recombinant human MG53 (rhMG53) protein protects cultured lung epithelial cells against anoxia/reoxygenation-induced injuries. Intravenous delivery or inhalation of rhMG53 reduces symptoms in rodent models of acute lung injury and emphysema. Repetitive administration of rhMG53 improves pulmonary structure associated with chronic lung injury in mice. Our data indicate a physiological function for MG53 in the lung and suggest that targeting membrane repair may be an effective means for treatment or prevention of lung diseases. PMID:25034454

Genomic profiling of multiple sequentially acquired tumor metastatic sites from an “exceptional responder” lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response

PubMed Central

Biswas, Romi; Gao, Shaojian; Cultraro, Constance M.; Maity, Tapan K.; Venugopalan, Abhilash; Abdullaev, Zied; Shaytan, Alexey K.; Carter, Corey A.; Thomas, Anish; Rajan, Arun; Song, Young; Pitts, Stephanie; Chen, Kevin; Bass, Sara; Boland, Joseph; Hanada, Ken-Ichi; Chen, Jinqiu; Meltzer, Paul S.; Panchenko, Anna R.; Yang, James C.; Pack, Svetlana; Giaccone, Giuseppe; Schrump, David S.; Khan, Javed; Guha, Udayan

2016-01-01

We used next-generation sequencing to identify somatic alterations in multiple metastatic sites from an “exceptional responder” lung adenocarcinoma patient during his 7-yr course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ∼1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies showed increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy because of L869R mutation and increased migration because of ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a subclone metastasized early from the primary site and evolved independently in lymph nodes. PMID:27900369

Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies

ClinicalTrials.gov

2018-04-30

Hematological Neoplasms; Non-Hodgkin's Lymphoma; Hodgkin's Lymphoma; Lymphoma; Multiple Myeloma; Acute Myeloid Leukemia; Leukemia; Myelodysplastic Syndromes; Neoplasms; Melanoma; Breast Cancer; Metastatic Breast Cancer; Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Renal Cell Carcinoma; Glioblastoma Multiforme; Osteosarcoma; Sarcoma; Thyroid Cancer; Genitourinary

Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium

ClinicalTrials.gov

2016-02-18

Breast Cancer; Hypercalcemia of Malignancy; Colon Cancer; Endocrine Cancer; Head and Neck Cancer; Kidney Cancer; Lung Cancer; Lymphoma; Metastatic Cancer; Multiple Myeloma; Parathyroid Neoplasms; Renal Cancer; Thyroid Cancer; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Non-Small Cell Lung Cancer

Ex vivo Live Imaging of Lung Metastasis and Their Microenvironment

PubMed Central

Maynard, Carrie; Plaks, Vicki

2016-01-01

Metastasis is a major cause for cancer-related morbidity and mortality. Metastasis is a multistep process and due to its complexity, the exact cellular and molecular processes that govern metastatic dissemination and growth are still elusive. Live imaging allows visualization of the dynamic and spatial interactions of cells and their microenvironment. Solid tumors commonly metastasize to the lungs. However, the anatomical location of the lungs poses a challenge to intravital imaging. This protocol provides a relatively simple and quick method for ex vivo live imaging of the dynamic interactions between tumor cells and their surrounding stroma within lung metastasis. Using this method, the motility of cancer cells as well as interactions between cancer cells and stromal cells in their microenvironment can be visualized in real time for several hours. By using transgenic fluorescent reporter mice, a fluorescent cell line, injectable fluorescently labeled molecules and/or antibodies, multiple components of the lung microenvironment can be visualized, such as blood vessels and immune cells. To image the different cell types, a spinning disk confocal microscope that allows long-term continuous imaging with rapid, four-color image acquisition has been used. Time-lapse movies compiled from images collected over multiple positions and focal planes show interactions between live metastatic and immune cells for at least 4 hr. This technique can be further used to test chemotherapy or targeted therapy. Moreover, this method could be adapted for the study of other lung-related pathologies that may affect the lung microenvironment. PMID:26862704

[Pulmonary cystic disease may be a rare complication to recurrent respiratory human papilloma virus infection].

PubMed

Laurberg, Peter Thaysen; Weinreich, Ulla M Øller

2014-12-08

A 19-year-old woman with a history of juvenile laryngeal papillomatosis (JLP), treated since childhood with multiple resections, was admitted with symptoms of pneumonia. A chest X-ray and CAT-scan revealed multiple lung cysts and a bronchoalveolar lavage detected human papilloma virus 11. The patient responded well to antibiotics. A body plethysmography showed small lung volumes and low diffusion capacity for carbon monoxide, but normal volume diffusion capacity divided by alveolar volume. Pulmonary cystic disease should be considered when patients with JLP have symptoms of pneumonia.

Imaging in lung transplants: Checklist for the radiologist.

PubMed

Madan, Rachna; Chansakul, Thanissara; Goldberg, Hilary J

2014-10-01

Post lung transplant complications can have overlapping clinical and imaging features, and hence, the time point at which they occur is a key distinguisher. Complications of lung transplantation may occur along a continuum in the immediate or longer postoperative period, including surgical and mechanical problems due to size mismatch and vascular as well as airway anastomotic complication, injuries from ischemia and reperfusion, acute and chronic rejection, pulmonary infections, and post-transplantation lymphoproliferative disorder. Life expectancy after lung transplantation has been limited primarily by chronic rejection and infection. Multiple detector computed tomography (MDCT) is critical for evaluation and early diagnosis of complications to enable selection of effective therapy and decrease morbidity and mortality among lung transplant recipients.

High-performing LiMgxCuyCo₁-x-yO₂ cathode material for lithium rechargeable batteries.

PubMed

Nithya, Chandrasekaran; Thirunakaran, Ramasamy; Sivashanmugam, Arumugam; Gopukumar, Sukumaran

2012-08-01

Sustainable power requirements of multifarious portable electronic applications demand the development of high energy and high power density cathode materials for lithium ion batteries. This paper reports a method for rapid synthesis of a cobalt based layered cathode material doped with mixed dopants Cu and Mg. The cathode material exhibits ordered layered structure and delivers discharge capacity of ∼200 mA h g(-1) at 0.2C rate with high capacity retention of 88% over the investigated 100 cycles.

Epidemiology’s 350th Anniversary: 1662–2012

PubMed Central

Morabia, Alfredo

2013-01-01

Between 1600 and 1700, sudden, profound, and multifarious changes occurred in philosophy, science, medicine, politics, and society. In an extremely convulsed century, these profound and convergent upheavals produced the equivalent of a cultural big bang, which opened a new domain of knowledge acquisition based on population thinking and group comparisons. In 1662, when John Graunt applied—for the first time—the new approach to the analysis of causes of death in London, he gave epidemiology a singular date of birth. This was exactly 350 years ago. PMID:23377087

[Effects of granulocyte-macrophage colony stimulating factor on nuclear factor-KappaB activation in multiple organs of hemorrhage-induced acute lung injury in mice].

PubMed

Wang, Qian; Song, Yong; Shi, Yi

2007-05-01

To investigate the effects of nuclear factor-KappaB (NF-KappaB) activation in multiple organs of hemorrhage-induced acute lung injury (ALI) by the specific granulocyte-macrophage colony stimulating factor (GM-CSF)-neutralizing antibody (22E9) and dexamethasone (DEX) in mice. Twenty male C57BL/6 mice were used to reproduce a model of hemorrhagic shock by cardiac puncture. Before cardiac puncture, mice in different groups were transnasally administered with phosphate buffered solution (PBS, PCG group), PBS plus 1 microg 22E9 (HS1 group), PBS plus 10 microg 22E9 (HS10 group) and PBS plus 20 microg DEX (DEX group), respectively. In negative control group (NCG group) received cardiac puncture without shock followed by transnasal administration with PBS without shock. Lungs, hearts, livers and kidneys tissues of mice were harvested at 4 hours after hemorrhagic shock. The activities of NF-KappaB in different organs was determined by electrophoretic mobility shift assay (EMSA). The tumor necrosis factor-alpha (TNF-alpha) in lung and heart were determined by enzyme-linked immunosorbent assay (ELISA). 22E9 in both low or high doses could significantly inhibit NF-KappaB activities in lung, heart and liver, and elevated NF-KappaB activity in kidney compared with those of PCG group (all P<0.05). The effect of 22E9 was much better in HS1 group than in HS10 group (all P<0.05). DEX significantly strengthened NF-KappaB activity in kidney (P<0.05) and didn't significantly inhibit NF-KappaB activities in heart and liver compared with those of PCG group. 22E9 significantly inhibited TNF-alpha in lung and heart, while DEX significantly inhibited TNF-alpha in heart (all P<0.05). 22E9 can inhibit the NF-KappaB activation and inflammatory reaction in multiple organs after hemorrhage-induced ALI and reduce injury in multiple organs, while DEX has no significant effect.

& Source apportionment of particulate matter in the United States and associations with lung inflammatory Markers

EPA Science Inventory

Size-fractionated particulate matter (PM) samples were collected from six U.S. cities and chemically analyzed as part of the Multiple Air Pollutant Study. Particles were administered to cultured lung cells and the production of three different proinflammatory markers was measured...

Metabolomics reveals the formation of aldehydes and iminium in gefitinib metabolism

USDA-ARS?s Scientific Manuscript database

Gefitinib (GEF), an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is widely used for the treatment of cancers, particularly non-small cell lung cancer. However, its clinical use is limited by multiple adverse effects associated with GEF, such as liver and lung injuries, sever...

Targeting Extracellular Histones with Novel RNA Bio drugs for the Treatment of Acute Lung Injury

DTIC Science & Technology

2017-10-01

organ involved in MODS is the lung (referred to as acute respiratory distress syndrome or ARDS). Trauma, smoke inhalation, burns, radiation , severe...and mortality associated with multiple organ dysfunction/ acute respiratory distress syndrome (MODS/ARDS) and ALI that can be easily delivered in combat...MODS, the risk of death is 40%. The most common organ involved in MODS is the lungs (referred to as acute respiratory distress syndrome or ARDS

[A case report: an EML4-ALK positive lung adenocarcinoma diagnosed 
with lymphoma previously].

PubMed

Liu, Li; Heng, Wei

2015-02-01

In recent years, with the deepening of the research of molecular biology, targeted therapy has become one of the trend of lung cancer treatment. The individualized treatment of lung cancer is attached great importance at present. Echinoderm microtubule associated protein like 4 anaplastic lymphoma kinase (EML4-ALK) as a new biological marker is a hot topic in the field of lung cancer treatment. Meanwhile, with the improvement of anticancer treatment and survival, the incidence of multiple primary carcinomas (MPC) has become increasingly. But the report that malignant lymphoma complicated with lung adenocarcinoma harboring EML4-ALK fusion gene in one individual is rare. Here, we report an EML4-ALK positive non-small cell lung cancer (NSCLC) in a patient previously diagnosed with T cell lymphoma and review literature on metachronous lung cancer complicating with lymphoma.

Prognostic effect of liver metastasis in lung cancer patients with distant metastasis.

PubMed

Ren, Yijiu; Dai, Chenyang; Zheng, Hui; Zhou, Fangyu; She, Yunlang; Jiang, Gening; Fei, Ke; Yang, Ping; Xie, Dong; Chen, Chang

2016-08-16

Because the need of clinical prognostic evaluation by specific metastatic organ, we aim to analyze the prognostic factors in lung cancer patients with M1b disease with Surveillance Epidemiology and End-Results database (SEER). This retrospective study evaluated lung cancer patients of adenocarcinoma (AD), squamous cell carcinoma (SQCC), and small cell lung cancer (SCLC) selected from SEER. We provided the prognostic correlates of overall survival (OS) and lung cancer-specific survival (LCSS) in this population. 23,679 eligible patients were included. Bone was the most common metastatic site in AD (63.1%) and SQCC (61.1%), while liver was the most prevalent site (61.9%) in SCLC. Single site metastasis was significantly associated with better outcome compared to multiple sites metastases in all patients. Among patients with single site metastasis, OS and LCSS were longer for AD and SCLC if involving brain or bone, with median survival time of 5 to 7 months, comparing to 3 months if invloving liver (all p-values < 0.001). Similarly, among patients with multiple metastases, better outcomes were observed in AD patients (4 vs 3 months; OS and LCSS, p < 0.001) and SCLC patients (6 vs 4 months; OS, p = 0.017; LCSS, p = 0.023) without liver metastasis compared to those with liver metastasis. In conclusion, we estimated multiple survival outcomes by histology of primary tumor and sites of metastasis. Liver metastasis is found to be the worst prognostic factor for AD and SCLC patients with distant metastasis. More in-depth research is warranted to identify patients who are prone to develop distance metastasis, especially to liver.

The microdistribution of α-active nuclides in the human lung

NASA Astrophysics Data System (ADS)

Henshaw, D. L.; Fews, A. P.

1984-06-01

Elsewhere (refs. [4,5]) the authors have discussed new and elaborate techniques for alpha-particle autoradiography using the nuclear track detector CR-39. These techniques are at present being applied in a major study of the microdistribution of alpha-active nuclides in the human lung. Whole lungs with trachea are obtained at autopsy. Case histories representing a wide spectrum of lung burden are sought but that from the general population serves as a baseline from which all abnormal levels may be compared. The lungs are dissected, loaded against CR-39 and stored deep frozen for 3-20 months. Subsequent analysis of the autoradiograph reveals: (i) The microdistribution of activity. This includes for example the pattern of deposition around the tracheal bifurcation and across the tracheal wall for both the total activity and separately that due to 222Rn + daughter nuclei and, the distribution of single and multiple decays from single points over the storage period of the autoradiograph. The information enables the frequency of single and multiple hits to sensitive cells in the lung to be calculated. This is an important step in estimating the frequency of radiation induced mutations. (ii) The absolute abundance of alpha-active nuclides present at each site. This quantity is determined at particular locations in lung such as bifurcations in the major airways, in corresponding positions on the posterior aspect of the trachea and bronchus and parenchymal lung for each of the five lobes and in the lymph nodes. The information is obtained in normal lung over a wide span of age. This overall information may be used to study the deposition, retention and clearance patterns of different alpha-emitting elements with associated differences in size and physical and chemical nature. These studies in normal lung may provide new information on the mechanism at work in lung for the clearance of particulate matter. They may also be used to predict the behaviour of inhaled alpha-particulate matter in lung and perform microdosimetric calculations. This information may be applied to cases of occupational exposure to alpha-emitting particles such as plutonium.

Whole lung morphometry with 3D multiple b-value hyperpolarized gas MRI and compressed sensing.

PubMed

Chan, Ho-Fung; Stewart, Neil J; Parra-Robles, Juan; Collier, Guilhem J; Wild, Jim M

2017-05-01

To demonstrate three-dimensional (3D) multiple b-value diffusion-weighted (DW) MRI of hyperpolarized 3 He gas for whole lung morphometry with compressed sensing (CS). A fully-sampled, two b-value, 3D hyperpolarized 3 He DW-MRI dataset was acquired from the lungs of a healthy volunteer and retrospectively undersampled in the k y and k z phase-encoding directions for CS simulations. Optimal k-space undersampling patterns were determined by minimizing the mean absolute error between reconstructed and fully-sampled 3 He apparent diffusion coefficient (ADC) maps. Prospective three-fold, undersampled, 3D multiple b-value 3 He DW-MRI datasets were acquired from five healthy volunteers and one chronic obstructive pulmonary disease (COPD) patient, and the mean values of maps of ADC and mean alveolar dimension (Lm D ) were validated against two-dimensional (2D) and 3D fully-sampled 3 He DW-MRI experiments. Reconstructed undersampled datasets showed no visual artifacts and good preservation of the main image features and quantitative information. A good agreement between fully-sampled and prospective undersampled datasets was found, with a mean difference of +3.4% and +5.1% observed in mean global ADC and Lm D values, respectively. These differences were within the standard deviation range and consistent with values reported from healthy and COPD lungs. Accelerated CS acquisition has facilitated 3D multiple b-value 3 He DW-MRI scans in a single breath-hold, enabling whole lung morphometry mapping. Magn Reson Med 77:1916-1925, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Progenitors of Secondary Crest Myofibroblasts are Developmentally Committed in Early Lung Mesoderm

PubMed Central

Li, Changgong; Li, Min; Li, Sha; Xing, Yiming; Yang, Chang-Yo; Li, Aimin; Borok, Zea; De Langhe, Stijn; Minoo, Parviz

2015-01-01

Development of the mammalian lung is predicated on cross-communications between two highly interactive tissues, the endodermally-derived epithelium and the mesodermally-derived pulmonary mesenchyme. While much attention has been paid the lung epithelium, the pulmonary mesenchyme, partly due to lack of specific tractable markers remains under-investigated. The lung mesenchyme is derived from the lateral plate mesoderm and is the principal recipient of Hedgehog (Hh) signaling, a morphogenetic network that regulates multiple aspects of embryonic development. Using the Hh-responsive Gli1-creERT2 mouse line, we identified the mesodermal targets of Hh signaling at various time points during embryonic and postnatal lung development. Cell lineage analysis showed these cells serve as progenitors to contribute to multiple lineages of mesodermally-derived differentiated cell types that include parenchymal or interstitial myofibroblasts, parabronchial and perivascular smooth muscle as well as rare populations of cells within the mesothelium. Most importantly, Gli1-creERT2 identified the progenitors of secondary crest myofibroblasts, a hitherto intractable cell type that plays a key role in alveolar formation, a vital process about which little is currently known. Transcriptome analysis of Hh-targeted progenitor cells transitioning from the pseudoglandular to the saccular phase of lung development revealed important modulations of key signaling pathways. Amongst these, there was significant down-regulation of canonical WNT signaling. Ectopic stabilization of β-Catenin via inactivation of Apc by Gli1-creERT2 expanded the Hh-targeted progenitor pools, which caused the formation of fibroblastic masses within the lung parenchyma. The Gli1-creERT2 mouse line represents a novel tool in the analysis of mesenchymal cell biology and alveolar formation during lung development. PMID:25448080

Risk Factors for Lung Cancer in Iowa Women: Implications for Prevention

PubMed Central

Neuberger, John S.; Mahnken, Jonathan D.; Mayo, Matthew S.; Field, R. William

2007-01-01

Background Multiple risk factors possibly associated with lung cancer were examined as part of a large-scale residential radon case-control study conducted in Iowa between 1994 and 1997. We were particularly interested in stratifying risk factors by smoking status. Relatively little risk factor information is available for Midwestern rural women. Methods Four hundred thirteen female lung cancer cases and 614 controls aged 40-84, who were residents of their current home for at least 20 years, were included. Risk factors examined included cigarette smoking, passive smoking, occupation, chemical exposure, previous lung disease, family history of cancer, and urban residence. Multiple logistic regression analysis was conducted after adjusting for age, education, and cumulative radon exposure. Results As expected, active cigarette smoking was the major risk factor for lung cancer. While cessation of smoking was significantly associated with a reduced risk for lung cancer, the risk remained significantly elevated for 25 years. Among all cases, asbestos exposure was a significant risk. Among ex-smokers, pack-year history predominated as the major risk. Among never smokers, a family history of kidney or bladder cancer were significant risk factors (OR= 7.34, 95% CI = 1.91 - 28.18; and 5.02, 95% CI = 1.64-15.39, respectively), as was a history of previous lung disease (OR=2.28, 95% CI=1.24-4.18) and asbestos exposure. No statistically significant increase in lung cancer risk was found for occupation or urban residence. Conclusions Smoking prevention activities are urgently needed in rural areas of the United States. Relatives of individuals with smoking-related cancers are potentially at increased risk. Genetic risk factors should be more fully investigated in never smokers. PMID:16581199

Choroidal metastasis from early rectal cancer: Case report and literature review

PubMed Central

Tei, Mitsuyoshi; Wakasugi, Masaki; Akamatsu, Hiroki

2014-01-01

INTRODUCTION Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer. PRESENTATION OF CASE A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases. The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye, and continues to receive systemic chemotherapy for multiple lung metastases. DISCUSSION Current literatures have few recommendations regarding the appropriate treatment of choroidal metastasis from colorectal cancer, but an aggressive multi-disciplinary approach may be effective in local regression. CONCLUSION This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer. PMID:25460493

Choroidal metastasis from early rectal cancer: Case report and literature review.

PubMed

Tei, Mitsuyoshi; Wakasugi, Masaki; Akamatsu, Hiroki

2014-01-01

Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer. A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases. The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye, and continues to receive systemic chemotherapy for multiple lung metastases. Current literatures have few recommendations regarding the appropriate treatment of choroidal metastasis from colorectal cancer, but an aggressive multi-disciplinary approach may be effective in local regression. This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mapping cardiogenic oscillations using synchrotron-based phase contrast CT imaging

NASA Astrophysics Data System (ADS)

Thurgood, Jordan; Dubsky, Stephen; Siu, Karen K. W.; Wallace, Megan; Siew, Melissa; Hooper, Stuart; Fouras, Andreas

2012-10-01

In many animals, including humans, the lungs encase the majority of the heart thus the motion of each organ affects the other. The effects of the motion of the heart on the lungs potentially provides information with regards to both lung and heart health. We present a novel technique that is capable of measuring the effect of the heart on the surrounding lung tissue through the use of advanced synchrotron imaging techniques and recently developed X-ray velocimetry methods. This technique generates 2D frequency response maps of the lung tissue motion at multiple projection angles from projection X-ray images. These frequency response maps are subsequently used to generate 3D reconstructions of the lung tissue exhibiting motion at the frequency of ventilation and the lung tissue exhibiting motion at the frequency of the heart. This technique has a combined spatial and temporal resolution sufficient to observe the dynamic and complex 3D nature of lung-heart interactions.

EGFR-mutant Non-small Cell Lung Cancer Accompanied by Transient Asymptomatic Pulmonary Opacities Successfully Treated with "Stop-And-Go" Osimertinib.

PubMed

Kobayashi, Keigo; Naoki, Katsuhiko; Kuroda, Aoi; Yasuda, Hiroyuki; Kawada, Ichiro; Soejima, Kenzo; Betsuyaku, Tomoko

2018-04-01

A 69-year-old man with post-operative recurrence of lung adenocarcinoma was treated with multiple chemotherapies, including epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. A second biopsy revealed an EGFR T790M mutation. As 10th-line chemotherapy, osimertinib was initiated. After 24 weeks, chest computed tomography (CT) revealed asymptomatic ground-glass opacities in both lobes. After four weeks of osimertinib discontinuation, imaging revealed rapid lung cancer progression. Osimertinib was resumed. After 11 weeks, CT revealed decreased lung nodules with no exacerbation of interstitial lung disease. We describe a patient who experienced transient asymptomatic pulmonary opacities during treatment with osimertinib, which was successfully managed by a "stop-and-go" approach.

Small Nodules Localization on CT Images of Lungs

NASA Astrophysics Data System (ADS)

Snezhko, E. V.; Kharuzhyk, S. A.; Tuzikov, A. V.; Kovalev, V. A.

2017-05-01

According to the World Health Organization (WHO) lung cancer remains the leading cause of death of men among all malignant tumors [1, 2]. One of the reasons of such a statistics is the fact that the lung cancer is hardly diagnosed on the yearly stages when it is almost asymptomatic. The purpose of this paper is to present a Computer-Aided Diagnosis (CAD) software developed for assistance of early detection of nodules in CT lung images including solitary pulmonary nodules (SPN) as well as multiple nodules. The efficiency of nodule localization was intended to be as high as the level of the best practice. The software developed supports several functions including lungs segmentation, selection of nodule candidates and nodule candidates filtering.

Pollutional haze as a potential cause of lung cancer.

PubMed

Shi, Xuefei; Liu, Hongbing; Song, Yong

2015-10-01

Along with fast economic growth over the past few decades, the world is faced with cumulatively serious environmental pollution and now is paying increased attention to pollutional haze. In the last few years, multiple epidemiological studies and animal models have provided compelling evidences that inhalation of pollutional haze could be linked to several adverse health effects. Since the respiratory tract is the crucial passageway of entry of pollutional haze, the lung is the main affected organ. Therefore, here, we reviewed some of the important information around long-term exposure to pollutional haze and lung cancer, as well as highlight important roles of pollutional haze in human lung carcinogenesis, providing evidence for pollutional haze acting as another risk factor for lung cancer.

NOX2 protects against progressive lung injury and multiple organ dysfunction syndrome.

PubMed

Whitmore, Laura C; Goss, Kelli L; Newell, Elizabeth A; Hilkin, Brieanna M; Hook, Jessica S; Moreland, Jessica G

2014-07-01

Systemic inflammatory response syndrome (SIRS) is a common clinical condition in patients in intensive care units that can lead to complications, including multiple organ dysfunction syndrome (MODS). MODS carries a high mortality rate, and it is unclear why some patients resolve SIRS, whereas others develop MODS. Although oxidant stress has been implicated in the development of MODS, several recent studies have demonstrated a requirement for NADPH oxidase 2 (NOX2)-derived oxidants in limiting inflammation. We recently demonstrated that NOX2 protects against lung injury and mortality in a murine model of SIRS. In the present study, we investigated the role of NOX2-derived oxidants in the progression from SIRS to MODS. Using a murine model of sterile systemic inflammation, we observed significantly greater illness and subacute mortality in gp91(phox-/y) (NOX2-deficient) mice compared with wild-type mice. Cellular analysis revealed continued neutrophil recruitment to the peritoneum and lungs of the NOX2-deficient mice and altered activation states of both neutrophils and macrophages. Histological examination showed multiple organ pathology indicative of MODS in the NOX2-deficient mice, and several inflammatory cytokines were elevated in lungs of the NOX2-deficient mice. Overall, these data suggest that NOX2 function protects against the development of MODS and is required for normal resolution of systemic inflammation. Copyright © 2014 the American Physiological Society.

Dynamics of multiple resistance mechanisms in plasma DNA during EGFR-targeted therapies in non-small cell lung cancer.

PubMed

Tsui, Dana Wai Yi; Murtaza, Muhammed; Wong, Alvin Seng Cheong; Rueda, Oscar M; Smith, Christopher G; Chandrananda, Dineika; Soo, Ross A; Lim, Hong Liang; Goh, Boon Cher; Caldas, Carlos; Forshew, Tim; Gale, Davina; Liu, Wei; Morris, James; Marass, Francesco; Eisen, Tim; Chin, Tan Min; Rosenfeld, Nitzan

2018-06-01

Tumour heterogeneity leads to the development of multiple resistance mechanisms during targeted therapies. Identifying the dominant driver(s) is critical for treatment decision. We studied the relative dynamics of multiple oncogenic drivers in longitudinal plasma of 50 EGFR -mutant non-small-cell lung cancer patients receiving gefitinib and hydroxychloroquine. We performed digital PCR and targeted sequencing on samples from all patients and shallow whole-genome sequencing on samples from three patients who underwent histological transformation to small-cell lung cancer. In 43 patients with known EGFR mutations from tumour, we identified them accurately in plasma of 41 patients (95%, 41/43). We also found additional mutations, including EGFR T790M (31/50, 62%), TP53 (23/50, 46%), PIK3CA (7/50, 14%) and PTEN (4/50, 8%). Patients with both TP53 and EGFR mutations before treatment had worse overall survival than those with only EGFR Patients who progressed without T790M had worse PFS during TKI continuation and developed alternative alterations, including small-cell lung cancer-associated copy number changes and TP53 mutations, that tracked subsequent treatment responses. Longitudinal plasma analysis can help identify dominant resistance mechanisms, including non-druggable genetic information that may guide clinical management. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

A 26-year-old man with dyspnea and chest pain.

PubMed

Mittal, Saurabh; Jain, Akanksha; Arava, Sudheer; Hadda, Vijay; Mohan, Anant; Guleria, Randeep; Madan, Karan

2017-01-01

A 26-year-old smoker male presented with a history of sudden onset dyspnea and right-sided chest pain. Chest radiograph revealed large right-sided pneumothorax which was managed with tube thoracostomy. High-resolution computed tomography thorax revealed multiple lung cysts, and for a definite diagnosis, a video-assisted thoracoscopic surgery-guided lung biopsy was performed followed by pleurodesis. This clinicopathologic conference discusses the clinical and radiological differential diagnoses, utility of lung biopsy, and management options for patients with such a clinical presentation.

A 26-year-old man with dyspnea and chest pain

PubMed Central

Mittal, Saurabh; Jain, Akanksha; Arava, Sudheer; Hadda, Vijay; Mohan, Anant; Guleria, Randeep; Madan, Karan

2017-01-01

A 26-year-old smoker male presented with a history of sudden onset dyspnea and right-sided chest pain. Chest radiograph revealed large right-sided pneumothorax which was managed with tube thoracostomy. High-resolution computed tomography thorax revealed multiple lung cysts, and for a definite diagnosis, a video-assisted thoracoscopic surgery-guided lung biopsy was performed followed by pleurodesis. This clinicopathologic conference discusses the clinical and radiological differential diagnoses, utility of lung biopsy, and management options for patients with such a clinical presentation. PMID:29099006

A novel miRNA-mediated STOP sign in lung cancer: miR-340 inhibits the proliferation of lung cancer cells through p27KIP1

PubMed Central

Fernandez, Serena; Risolino, Maurizio; Verde, Pasquale

2015-01-01

Oncosuppressor miRNAs inhibit cancer cell proliferation by targeting key components of the cell cycle machinery. In our recent report we showed that miR-340 is a novel tumor suppressor in non-small cell lung cancer. miR-340 inhibits neoplastic cell proliferation and induces p27KIP1 by targeting multiple translational and post-translational regulators of this cyclin-dependent kinase inhibitor. PMID:27308439

Fibrogenic Lung Injury Induces Non-Cell-Autonomous Fibroblast Invasion.

PubMed

Ahluwalia, Neil; Grasberger, Paula E; Mugo, Brian M; Feghali-Bostwick, Carol; Pardo, Annie; Selman, Moisés; Lagares, David; Tager, Andrew M

2016-06-01

Pathologic accumulation of fibroblasts in pulmonary fibrosis appears to depend on their invasion through basement membranes and extracellular matrices. Fibroblasts from the fibrotic lungs of patients with idiopathic pulmonary fibrosis (IPF) have been demonstrated to acquire a phenotype characterized by increased cell-autonomous invasion. Here, we investigated whether fibroblast invasion is further stimulated by soluble mediators induced by lung injury. We found that bronchoalveolar lavage fluids from bleomycin-challenged mice or patients with IPF contain mediators that dramatically increase the matrix invasion of primary lung fibroblasts. Further characterization of this non-cell-autonomous fibroblast invasion suggested that the mediators driving this process are produced locally after lung injury and are preferentially produced by fibrogenic (e.g., bleomycin-induced) rather than nonfibrogenic (e.g., LPS-induced) lung injury. Comparison of invasion and migration induced by a series of fibroblast-active mediators indicated that these two forms of fibroblast movement are directed by distinct sets of stimuli. Finally, knockdown of multiple different membrane receptors, including platelet-derived growth factor receptor-β, lysophosphatidic acid 1, epidermal growth factor receptor, and fibroblast growth factor receptor 2, mitigated the non-cell-autonomous fibroblast invasion induced by bronchoalveolar lavage from bleomycin-injured mice, suggesting that multiple different mediators drive fibroblast invasion in pulmonary fibrosis. The magnitude of this mediator-driven fibroblast invasion suggests that its inhibition could be a novel therapeutic strategy for pulmonary fibrosis. Further elaboration of the molecular mechanisms that drive non-cell-autonomous fibroblast invasion consequently may provide a rich set of novel drug targets for the treatment of IPF and other fibrotic lung diseases.

Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity.

PubMed

Botelho, Danielle J; Leo, Bey Fen; Massa, Christopher B; Sarkar, Srijata; Tetley, Terry D; Chung, Kian Fan; Chen, Shu; Ryan, Mary P; Porter, Alexandra E; Zhang, Junfeng; Schwander, Stephan K; Gow, Andrew J

2016-01-01

Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 μg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered.

Cerebral Metastases of Lung Cancer Mimicking Multiple Ischaemic Lesions - A Case Report and Review of Literature.

PubMed

Zacharzewska-Gondek, Anna; Maksymowicz, Hanna; Szymczyk, Małgorzata; Sąsiadek, Marek; Bladowska, Joanna

2017-01-01

Restricted diffusion that is found on magnetic resonance diffusion-weighted imaging (DWI) typically indicates acute ischaemic stroke. However, restricted diffusion can also occur in other diseases, like metastatic brain tumours, which we describe in this case report. A 57-year-old male, with a diagnosis of small-cell cancer of the right lung (microcellular anaplastic carcinoma), was admitted with focal neurological symptoms. Initial brain MRI revealed multiple, disseminated lesions that were hyperintense on T2-weighted images and did not enhance after contrast administration; notably, some lesions manifested restricted diffusion on DWI images. Based on these findings, disseminated ischaemic lesions were diagnosed. On follow-up MRI that was performed after 2 weeks, we observed enlargement of the lesions; there were multiple, disseminated, sharply outlined, contrast-enhancing, oval foci with persistent restriction of diffusion. We diagnosed the lesions as disseminated brain metastases due to lung cancer. To our knowledge, this is the first description of a patient with brain metastases that were characterised by restricted diffusion and no contrast enhancement. Multiple, disseminated brain lesions, that are characterised by restricted diffusion on DWI, typically indicate acute or hyperacute ischemic infarcts; however, they can also be due to hypercellular metastases, even if no contrast enhancement is observed. This latter possibility should be considered particularly in patients with cancer.

A General Approach to the Evaluation of Ventilation-Perfusion Ratios in Normal and Abnormal Lungs

ERIC Educational Resources Information Center

Wagner, Peter D.

1977-01-01

Outlines methods for manipulating multiple gas data so as to gain the greatest amount of insight into the properties of ventilation-perfusion distributions. Refers to data corresponding to normal and abnormal lungs. Uses a two-dimensional framework with the respiratory gases of oxygen and carbon dioxide. (CS)

Promotion of Lung Health: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

PubMed Central

Budinger, G. R. Scott; Escobar, Gabriel J.; Hansel, Nadia N.; Hanson, Corrine K.; Huffnagle, Gary B.; Buist, A. Sonia

2014-01-01

Lung-related research primarily focuses on the etiology and management of diseases. In recent years, interest in primary prevention has grown. However, primary prevention also includes “health promotion” (actions in a population that keep an individual healthy). We encourage more research on population-based (public health) strategies that could not only maximize lung health but also mitigate “normal” age-related declines—not only for spirometry but across multiple measures of lung health. In developing a successful strategy, a “life course” approach is important. Unfortunately, we are unable to achieve the full benefit of this approach until we have better measures of lung health and an improved understanding of the normal trajectory, both over an individual’s life span and possibly across generations. We discuss key questions in lung health promotion, with an emphasis on the upper (healthier) end of the distribution of lung functioning and resiliency and briefly summarize the few interventions that have been studied to date. We conclude with suggestions regarding the most promising future research for this important, but largely neglected, area of lung research. PMID:24754821

Sequential resection of lung metastasis following partial hepatectomy for colorectal cancer.

PubMed

Ike, H; Shimada, H; Togo, S; Yamaguchi, S; Ichikawa, Y; Tanaka, K

2002-09-01

Multiple organ metastases from colorectal carcinoma may be considered incurable, but long survival after both liver and lung resection for metastases has been reported. A retrospective analysis of 48 patients who underwent lung resection for metastatic colorectal cancer between 1992 and 1999 was undertaken. Twenty-seven patients had lung metastasis alone, 15 had previous partial hepatectomy, and six had previous resection of local or lymph node recurrence. The relationship of clinical variables to survival was assessed. Survival was calculated from the time of first pulmonary resection. Five-year survival rates after resection of lung metastasis were 73 per cent in patients without preceding recurrence, 50 per cent following previous partial hepatectomy and zero after resection of previous local recurrence. Independent prognostic variables that significantly affected survival after thoracotomy were primary tumour histology and type of preceding recurrence. There was no significant difference in survival after lung resection between patients who had sequential liver and lung resection versus those who had lung resection alone. Sequential lung resection after partial hepatectomy for metastatic colorectal cancer may lead to long-term survival.

Molecular Typing of Lung Adenocarcinoma on Cytological Samples Using a Multigene Next Generation Sequencing Panel

PubMed Central

Fassan, Matteo; Rachiglio, Anna Maria; Cappellesso, Rocco; Antonello, Davide; Amato, Eliana; Mafficini, Andrea; Lambiase, Matilde; Esposito, Claudia; Bria, Emilio; Simonato, Francesca; Scardoni, Maria; Turri, Giona; Chilosi, Marco; Tortora, Giampaolo; Fassina, Ambrogio; Normanno, Nicola

2013-01-01

Identification of driver mutations in lung adenocarcinoma has led to development of targeted agents that are already approved for clinical use or are in clinical trials. Therefore, the number of biomarkers that will be needed to assess is expected to rapidly increase. This calls for the implementation of methods probing the mutational status of multiple genes for inoperable cases, for which limited cytological or bioptic material is available. Cytology specimens from 38 lung adenocarcinomas were subjected to the simultaneous assessment of 504 mutational hotspots of 22 lung cancer-associated genes using 10 nanograms of DNA and Ion Torrent PGM next-generation sequencing. Thirty-six cases were successfully sequenced (95%). In 24/36 cases (67%) at least one mutated gene was observed, including EGFR, KRAS, PIK3CA, BRAF, TP53, PTEN, MET, SMAD4, FGFR3, STK11, MAP2K1. EGFR and KRAS mutations, respectively found in 6/36 (16%) and 10/36 (28%) cases, were mutually exclusive. Nine samples (25%) showed concurrent alterations in different genes. The next-generation sequencing test used is superior to current standard methodologies, as it interrogates multiple genes and requires limited amounts of DNA. Its applicability to routine cytology samples might allow a significant increase in the fraction of lung cancer patients eligible for personalized therapy. PMID:24236184

The clinical utility of lung clearance index in early cystic fibrosis lung disease is not impacted by the number of multiple-breath washout trials

PubMed Central

Foong, Rachel E.; Harper, Alana J.; King, Louise; Turkovic, Lidija; Davis, Miriam; Clem, Charles C.; Davis, Stephanie D.; Ranganathan, Sarath; Hall, Graham L.

2018-01-01

The lung clearance index (LCI) from the multiple-breath washout (MBW) test is a promising surveillance tool for pre-school children with cystic fibrosis (CF). Current guidelines for MBW testing recommend that three acceptable trials are required. However, success rates to achieve these criteria are low in children aged <7 years and feasibility may improve with modified pre-school criteria that accepts tests with two acceptable trials. This study aimed to determine if relationships between LCI and clinical outcomes of CF lung disease differ when only two acceptable MBW trials are assessed. Healthy children and children with CF aged 3–6 years were recruited for MBW testing. Children with CF also underwent bronchoalveolar lavage fluid collection and a chest computed tomography scan. MBW feasibility increased from 46% to 75% when tests with two trials were deemed acceptable compared with tests where three acceptable trials were required. Relationships between MBW outcomes and markers of pulmonary inflammation, infection and structural lung disease were not different between tests with three acceptable trials compared with tests with two acceptable trials. This study indicates that pre-school MBW data from two acceptable trials may provide sufficient information on ventilation distribution if three acceptable trials are not possible. PMID:29707562

Advances in combination therapy of lung cancer: Rationales, delivery technologies and dosage regimens.

PubMed

Wu, Lan; Leng, Donglei; Cun, Dongmei; Foged, Camilla; Yang, Mingshi

2017-08-28

Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy using different pharmaceuticals has been proven highly effective due to the ability to affect multiple cellular pathways involved in the disease progression. However, the currently used drug combination designs are primarily based on empirical clinical studies, and little attention has been given to dosage regimens, i.e. how administration routes, onsets, and durations of the combinations influence the therapeutic outcome. This is partly because combination therapy is challenged by distinct physicochemical properties and in vivo pharmacokinetics/pharmacodynamics of the individual pharmaceuticals, including small molecule drugs and biopharmaceuticals, which make the optimization of dosing and administration schedule challenging. This article reviews the recent advances in the design and development of combinations of pharmaceuticals for the treatment of lung cancer. Focus is primarily on rationales for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Arsenic, tobacco smoke, and occupation: associations of multiple agents with lung and bladder cancer.

PubMed

Ferreccio, Catterina; Yuan, Yan; Calle, Jacqueline; Benítez, Hugo; Parra, Roxana L; Acevedo, Johanna; Smith, Allan H; Liaw, Jane; Steinmaus, Craig

2013-11-01

Millions of people worldwide are exposed to arsenic in drinking water, and many are likely coexposed to other agents that could substantially increase their risks of arsenic-related cancer. We performed a case-control study of multiple chemical exposures in 538 lung and bladder cancer cases and 640 controls in northern Chile, an area with formerly high drinking water arsenic concentrations. Detailed information was collected on lifetime arsenic exposure, smoking, secondhand smoke, and other known or suspected carcinogens, including asbestos, silica, and wood dust. Very high lung and bladder cancer odds ratios (ORs), and evidence of greater than additive effects, were seen in people exposed to arsenic concentrations >335 µg/L and who were tobacco smokers (OR = 16, 95% confidence interval = 6.5-40 for lung cancer; and OR = 23 [8.2-66] for bladder cancer; Rothman Synergy Indices = 4.0 [1.7-9.4] and 2.0 [0.92-4.5], respectively). Evidence of greater than additive effects were also seen in people coexposed to arsenic and secondhand tobacco smoke and several other known or suspected carcinogens, including asbestos, silica, and wood dust. These findings suggest that people coexposed to arsenic and other known or suspected carcinogens have very high risks of lung or bladder cancer.

Genetically engineered humanized anti-ganglioside GM2 antibody against multiple organ metastasis produced by GM2-expressing small-cell lung cancer cells.

PubMed

Yamada, Tadaaki; Bando, Hideaki; Takeuchi, Shinji; Kita, Kenji; Li, Qi; Wang, Wei; Akinaga, Shiro; Nishioka, Yasuhiko; Sone, Saburo; Yano, Seiji

2011-12-01

Small-cell lung cancer (SCLC) grows rapidly and metastasizes to multiple organs. We examined the antimetastatic effects of the humanized anti-ganglioside GM2 (GM2) antibodies, BIW-8962 and KM8927, compared with the chimeric antibody KM966, in a SCID mouse model of multiple organ metastases induced by GM2-expressing SCLC cells. BIW-8962 and KM8927 induced higher antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity than KM966 against the GM2-expressing SCLC cell line SBC-3 in vitro. These humanized antibodies inhibited the production of multiple organ metastases, increased the number of apoptotic cells, and prolonged the survival of the SCID mice. Histological analyses using clinical specimens showed that SCLC cells expressed GM2. These findings suggest that humanized anti-GM2 antibodies could be therapeutically useful for controlling multiple organ metastases of GM2-expressing SCLC. © 2011 Japanese Cancer Association.

WE-G-204-07: Automated Characterization of Perceptual Quality of Clinical Chest Radiographs: Improvements in Lung, Spine, and Hardware Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wells, J; Zhang, L; Samei, E

Purpose: To develop and validate more robust methods for automated lung, spine, and hardware detection in AP/PA chest images. This work is part of a continuing effort to automatically characterize the perceptual image quality of clinical radiographs. [Y. Lin et al. Med. Phys. 39, 7019–7031 (2012)] Methods: Our previous implementation of lung/spine identification was applicable to only one vendor. A more generalized routine was devised based on three primary components: lung boundary detection, fuzzy c-means (FCM) clustering, and a clinically-derived lung pixel probability map. Boundary detection was used to constrain the lung segmentations. FCM clustering produced grayscale- and neighborhood-based pixelmore » classification probabilities which are weighted by the clinically-derived probability maps to generate a final lung segmentation. Lung centerlines were set along the left-right lung midpoints. Spine centerlines were estimated as a weighted average of body contour, lateral lung contour, and intensity-based centerline estimates. Centerline estimation was tested on 900 clinical AP/PA chest radiographs which included inpatient/outpatient, upright/bedside, men/women, and adult/pediatric images from multiple imaging systems. Our previous implementation further did not account for the presence of medical hardware (pacemakers, wires, implants, staples, stents, etc.) potentially biasing image quality analysis. A hardware detection algorithm was developed using a gradient-based thresholding method. The training and testing paradigm used a set of 48 images from which 1920 51×51 pixel{sup 2} ROIs with and 1920 ROIs without hardware were manually selected. Results: Acceptable lung centerlines were generated in 98.7% of radiographs while spine centerlines were acceptable in 99.1% of radiographs. Following threshold optimization, the hardware detection software yielded average true positive and true negative rates of 92.7% and 96.9%, respectively. Conclusion: Updated segmentation and centerline estimation methods in addition to new gradient-based hardware detection software provide improved data integrity control and error-checking for automated clinical chest image quality characterization across multiple radiography systems.« less

SU-F-T-312: Identifying Distinct Radiation Therapy Plan Classes Through Multi-Dimensional Analysis of Plan Complexity Metrics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Desai, V; Labby, Z; Culberson, W

Purpose: To determine whether body site-specific treatment plans form unique “plan class” clusters in a multi-dimensional analysis of plan complexity metrics such that a single beam quality correction determined for a representative plan could be universally applied within the “plan class”, thereby increasing the dosimetric accuracy of a detector’s response within a subset of similarly modulated nonstandard deliveries. Methods: We collected 95 clinical volumetric modulated arc therapy (VMAT) plans from four body sites (brain, lung, prostate, and spine). The lung data was further subdivided into SBRT and non-SBRT data for a total of five plan classes. For each control pointmore » in each plan, a variety of aperture-based complexity metrics were calculated and stored as unique characteristics of each patient plan. A multiple comparison of means analysis was performed such that every plan class was compared to every other plan class for every complexity metric in order to determine which groups could be considered different from one another. Statistical significance was assessed after correcting for multiple hypothesis testing. Results: Six out of a possible 10 pairwise plan class comparisons were uniquely distinguished based on at least nine out of 14 of the proposed metrics (Brain/Lung, Brain/SBRT lung, Lung/Prostate, Lung/SBRT Lung, Lung/Spine, Prostate/SBRT Lung). Eight out of 14 of the complexity metrics could distinguish at least six out of the possible 10 pairwise plan class comparisons. Conclusion: Aperture-based complexity metrics could prove to be useful tools to quantitatively describe a distinct class of treatment plans. Certain plan-averaged complexity metrics could be considered unique characteristics of a particular plan. A new approach to generating plan-class specific reference (pcsr) fields could be established through a targeted preservation of select complexity metrics or a clustering algorithm that identifies plans exhibiting similar modulation characteristics. Measurements and simulations will better elucidate potential plan-class specific dosimetry correction factors.« less

Skin metastases from lung cancer: a case report.

PubMed

Pajaziti, Laura; Hapçiu, Syzana Rexhepi; Dobruna, Shkendije; Hoxha, Naim; Kurshumliu, Fisnik; Pajaziti, Artina

2015-04-11

Lung cancer is one of the most frequent malignancies, with high mortality rates. It can metastasize in almost all organs, but more often invades hilar nodes, liver, adrenal glands, bones and brain. There are various data on the incidence of lung cancer metastases in the skin. In 1-12% of patients with lung cancer are developed skin metastases. Metastases in the skin may be the first sign of lung cancer. Forty-five years old Albanian male, smoker, was admitted to our department with multiple nodules localized in the skin of the head, neck, back and chest. The nodules measuring 5-15 millimeters in greatest dimension were round and skin-colored, with telangiectasias, firm and tender. They appeared in an eruptive form about two weeks before being admitted at our hospital. In addition, the patient exhibited signs of weight loss, anorexia and fatigue. Excisional biopsy was performed to one of the lesions. Histopathology confirmed metastatic nature of the lesion namely, malignant tumor of neuroendocrine phenotype consistent with small-cell carcinoma. Chest X-ray and computed tomography revealed an expansive process in the 7(th) segment of the left lung, left hilar and mediastinal lymphadenopathy and a suspicious initial secondary deposit in the left adrenal gland. The patient was referred to the department of oncology for further treatment. After the third cycle of chemotherapy, the magnetic resonance imaging revealed brain metastases. The patient passed away four months after the diagnosis of lung cancer first presented with skin metastases. Metastases in skin may be the first sign of lung cancer. Although rare appearing, we should raise suspicion in cases of atypical lesions in the skin not only of the smokers, but also of the non-smokers. Skin metastases from small-cell lung carcinoma are a poor prognostic indicator. The appearance of multiple skin metastases with other internal metastases shorten the survival time.

The impact of emphysema on dosimetric parameters for stereotactic body radiotherapy of the lung

PubMed Central

Ochiai, Satoru; Nomoto, Yoshihito; Yamashita, Yasufumi; Inoue, Tomoki; Murashima, Shuuichi; Hasegawa, Daisuke; Kurita, Yoshie; Watanabe, Yui; Toyomasu, Yutaka; Kawamura, Tomoko; Takada, Akinori; Noriko; Kobayashi, Shigeki; Sakuma, Hajime

2016-01-01

The purpose of this study was to evaluate the impact of emphysematous changes in lung on dosimetric parameters in stereotactic body radiation therapy (SBRT) for lung tumor. A total of 72 treatment plans were reviewed, and dosimetric factors [including homogeneity index (HI) and conformity index (CI)] were evaluated. Emphysematous changes in lung were observed in 43 patients (60%). Patients were divided into three groups according to the severity of emphysema: no emphysema (n = 29), mild emphysema (n = 22) and moderate to severe emphysema groups (n = 21). The HI (P < 0.001) and the CI (P = 0.029) were significantly different in accordance with the severity of emphysema in one-way analysis of variance (ANOVA). The HI value was significantly higher in the moderate to severe emphysema group compared with in the no emphysema (Tukey, P < 0.001) and mild emphysema groups (P = 0.002). The CI value was significantly higher in the moderate to severe emphysema group compared with in the no emphysema group (P = 0.044). In multiple linear regression analysis, the severity of emphysema (P < 0.001) and the mean material density of the lung within the PTV (P < 0.001) were significant factors for HI, and the mean density of the lung within the PTV (P = 0.005) was the only significant factor for CI. The mean density of the lung within the PTV was significantly different in accordance with the severity of emphysema (one-way ANOVA, P = 0.008) and the severity of emphysema (P < 0.001) was one of the significant factors for the density of the lung within the PTV in multiple linear regression analysis. Our results suggest that emphysematous changes in the lung significantly impact on several dosimetric parameters in SBRT, and they should be carefully evaluated before treatment planning. PMID:27380802

Gene-by-environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma.

PubMed

Bunyavanich, S; Boyce, J A; Raby, B A; Weiss, S T

2012-02-01

Distinct receptors likely exist for leukotriene (LT)E(4), a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for LTE(4)-induced airways inflammation, and P2Y12 antagonism attenuates house dust mite-induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied. To test for association between variants in the P2Y12 gene (P2RY12) and lung function in human subjects with asthma, and to examine for gene-by-environment interaction with house dust mite exposure. Nineteen single nucleotide polymorphisms (SNPs) in P2RY12 were genotyped in 422 children with asthma and their parents (n = 1266). Using family based methods, we tested for associations between these SNPs and five lung function measures. We performed haplotype association analyses and tested for gene-by-environment interactions using house dust mite exposure. We used the false discovery rate to account for multiple comparisons. Five SNPs in P2RY12 were associated with multiple lung function measures (P-values 0.006–0.025). Haplotypes in P2RY12 were also associated with lung function (P-values 0.0055–0.046). House dust mite exposure modulated associations between P2RY12 and lung function, with minor allele homozygotes exposed to house dust mite demonstrating worse lung function than those unexposed (significant interaction P-values 0.0028–0.040). The P2RY12 variants were associated with lung function in a large family-based asthma cohort. House dust mite exposure caused significant gene-by-environment effects. Our findings add the first human evidence to experimental data supporting a role for P2Y12 in lung function. P2Y12 could represent a novel target for asthma treatment.

Increased Procurement of Thoracic Donor Organs After Thyroid Hormone Therapy.

PubMed

Novitzky, Dimitri; Mi, Zhibao; Collins, Joseph F; Cooper, David K C

2015-01-01

Hormonal therapy to the brain-dead organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), antidiuretic hormone, corticosteroids, or insulin. There has been a controversy on whether thyroid hormone enables more organs to be procured. Data on 63,593 donors of hearts and lungs (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in all donors (study 1), and in 40,124 details of all 4 hormones were recorded (study 2). In this cohort, group A (23,022) received T3/T4 and group B (17,102) no T3/T4. Univariate analyses and multiple regressions were performed. Posttransplant graft and recipient survival at 1 and 12 months were compared. In study 1, 30,962 donors received T3/T4, with 36.59% providing a heart and 20.05% providing 1 or both lungs. Of the 32,631 donors who did not receive T3/T4, only 29.62% provided a heart and 14.61% provided lungs, an increase of 6.97% hearts and 5.44% lungs from T3/T4-treated donors (both P < 0.0001). In study 2, 34.99% of group A provided a heart and 20.99% provided lungs. In group B only 25.76% provided a heart and 15.09% provided lungs, an increase of 9.23% (hearts) and 5.90% (lungs), respectively, in group A (both P < 0.0001). The results of multiple regression analyses indicated a beneficial effect of T3/T4 on heart (P < 0.0001) and lung (P < 0.0001) procurement independent of other factors. T3/T4 therapy to the donor was associated with either improved posttransplant graft and recipient survival or no difference in survival. T3/T4 therapy results in more transplantable hearts and lungs, with no detriment to posttransplant graft or recipient survival. Copyright © 2015 Elsevier Inc. All rights reserved.

Epithelial-mesenchymal transition is associated with a distinct tumor microenvironment including elevation of inflammatory signals and multiple immune checkpoints in lung adenocarcinoma

PubMed Central

Lou, Yanyan; Diao, Lixia; Cuentas, Edwin Roger Parra; Denning, Warren L.; Chen, Limo; Fan, Youhong; Byers, Lauren A.; Wang, Jing; Papadimitrakopoulou, Vassiliki; Behrens, Carmen; Rodriguez, Jaime Canales; Hwu, Patrick; Wistuba, Ignacio I.; Heymach, John V.; Gibbons, Don L.

2016-01-01

Purpose Promising results in the treatment of NSCLC have been seen with agents targeting immune checkpoints, such as PD-1 or PD-L1. However, only a select group of patients respond to these interventions. The identification of biomarkers that predict clinical benefit to immune checkpoint blockade is critical to successful clinical translation of these agents. Methods We conducted an integrated analysis of three independent large datasets, including The Cancer Genome Atlas (TCGA) of lung adenocarcinoma and two datasets from MD Anderson Cancer Center, Profiling of Resistance patterns and Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax (named PROSPECT) and Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (named BATTLE-1). Comprehensive analysis of mRNA gene expression, reverse phase protein array (RPPA), immunohistochemistry and correlation with clinical data were performed. Results Epithelial-mesenchymal transition (EMT) is highly associated with an inflammatory tumor microenvironment in lung adenocarcinoma, independent of tumor mutational burden. We found immune activation co-existent with elevation of multiple targetable immune checkpoint molecules, including PD-L1, PD-L2, PD-1, TIM-3, B7-H3, BTLA and CTLA-4, along with increases in tumor infiltration by CD4+Foxp3+ regulatory T cells in lung adenocarcinomas that displayed an EMT phenotype. Furthermore, we identify B7-H3 as a prognostic marker for NSCLC. Conclusions The strong association between EMT status and an inflammatory tumor microenvironment with elevation of multiple targetable immune checkpoint molecules warrants further investigation of using EMT as a predictive biomarker for immune checkpoint blockade agents and other immunotherapies in NSCLC and possibly a broad range of other cancers. PMID:26851185

Two Cases of Tuberous Sclerosis Complex Suggestive of Complicating Multifocal Micronodular Pneumocyte Hyperplasia: A Case Report.

PubMed

Nishida, Chinatsu; Yatera, Kazuhiro; Kido, Takashi; Noguchi, Shingo; Akata, Kentaro; Hanaka, Minako; Yamasaki, Kei; Hoshino, Teppei; Shimono, Masayuki; Ishimoto, Hiroshi; Sakamoto, Noriho; Mukae, Hiroshi

Multifocal micronodular pneumocyte hyperplasia (MMPH) is pathologically characterized by multifocal nodular hyperplasia of type Ⅱ pneumocyte-like cells. MMPH is usually complicated with tuberous sclerosis complex (TSC). MMPH patients tend to be asymptomatic or only slightly symptomatic. MMPH tends to progress slowly and needs no treatment. We herein describe two cases of MMPH with its characteristic radiological features and clinical manifestations of TSC. Case 1: a 20-year-old female with definitive TSC in infancy. Chest CT at the age of 18 revealed multiple nodular opacities and ground-glass attenuations in a scattered and random distribution in the bilateral lungs. Case 2: a 44-year-old female with probable TSC at 36 years of age. Chest CT at the age of 43 showed random areas of small ground-glass attenuations, predominantly in the upper lung fields. Case 1 and Case 2 have had no respiratory symptoms or radiographic changes in the recent two years and four years, respectively. Although pathological examinations of the lung were not performed because consent for surgical lung biospies was unobtainable, we considered that these pulmonary manifestations were most likely MMPH with TSC because of these characteristic radiographical findings of multiple nodular opacities and ground-glass attenuations of 10 mm or less in size and their scattered distribution, and because there have been no abnormal laboratory data or changes in their chest radiological findings for years. Neither patient is under treatment for pulmonary lesions. Although MMPH is a rare disease, multiple nodules and ground-glass attenuations on lung imaging findings should be considered as pulmonary manifestations in patients with TSC.

In Vivo Evaluation of Lung Microwave Ablation in a Porcine Tumor Mimic Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Planche, Olivier, E-mail: oli.hrp@gmail.com; Teriitehau, Christophe; Boudabous, Sana

2013-02-15

To evaluate the microwave ablation of created tumor mimics in the lung of a large animal model (pigs), with examination of the ablative synergy of multiple antennas. Fifty-six tumor-mimic models of various sizes were created in 15 pigs by using barium-enriched minced collected thigh muscle injected into the lung of the same animal. Tumors were ablated under fluoroscopic guidance by single-antenna and multiple-antenna microwaves. Thirty-five tumor models were treated in 11 pigs with a single antenna at 75 W for 15 min, with 15 measuring 20 mm in diameter, 10 measuring 30 mm, and 10 measuring 40 mm. Mean circularitymore » of the single-antenna ablation zones measured 0.64 {+-} 0.12, with a diameter of 35.7 {+-} 8.7 mm along the axis of the antenna and 32.7 {+-} 12.8 mm perpendicular to the feeding point. Multiple-antenna delivery of 75 W for 15 min caused intraprocedural death of 2 animals; modified protocol to 60 W for 10 min resulted in an ablation zone with a diameter of 43.0 {+-} 7.7 along the axis of the antenna and 54.8 {+-} 8.5 mm perpendicular to the feeding point; circularity was 0.70 {+-} 0.10. A single microwave antenna can create ablation zones large enough to cover lung tumor mimic models of {<=}4 cm with no heat sink effect from vessels of {<=}6 mm. Synergic use of 3 antennas allows ablation of larger volumes than single-antenna or radiofrequency ablation, but great caution must be taken when 3 antennas are used simultaneously in the lung in clinical practice.« less

Bayesian modelling of lung function data from multiple-breath washout tests.

PubMed

Mahar, Robert K; Carlin, John B; Ranganathan, Sarath; Ponsonby, Anne-Louise; Vuillermin, Peter; Vukcevic, Damjan

2018-05-30

Paediatric respiratory researchers have widely adopted the multiple-breath washout (MBW) test because it allows assessment of lung function in unsedated infants and is well suited to longitudinal studies of lung development and disease. However, a substantial proportion of MBW tests in infants fail current acceptability criteria. We hypothesised that a model-based approach to analysing the data, in place of traditional simple empirical summaries, would enable more efficient use of these tests. We therefore developed a novel statistical model for infant MBW data and applied it to 1197 tests from 432 individuals from a large birth cohort study. We focus on Bayesian estimation of the lung clearance index, the most commonly used summary of lung function from MBW tests. Our results show that the model provides an excellent fit to the data and shed further light on statistical properties of the standard empirical approach. Furthermore, the modelling approach enables the lung clearance index to be estimated by using tests with different degrees of completeness, something not possible with the standard approach. Our model therefore allows previously unused data to be used rather than discarded, as well as routine use of shorter tests without significant loss of precision. Beyond our specific application, our work illustrates a number of important aspects of Bayesian modelling in practice, such as the importance of hierarchical specifications to account for repeated measurements and the value of model checking via posterior predictive distributions. Copyright © 2018 John Wiley & Sons, Ltd.

Animal Models of Fibrotic Lung Disease

PubMed Central

Lawson, William E.; Oury, Tim D.; Sisson, Thomas H.; Raghavendran, Krishnan; Hogaboam, Cory M.

2013-01-01

Interstitial lung fibrosis can develop as a consequence of occupational or medical exposure, as a result of genetic defects, and after trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can develop in an idiopathic manner. The pathogenesis of each form of lung fibrosis remains poorly understood. They each result in a progressive loss of lung function with increasing dyspnea, and most forms ultimately result in mortality. To better understand the pathogenesis of lung fibrotic disorders, multiple animal models have been developed. This review summarizes the common and emerging models of lung fibrosis to highlight their usefulness in understanding the cell–cell and soluble mediator interactions that drive fibrotic responses. Recent advances have allowed for the development of models to study targeted injuries of Type II alveolar epithelial cells, fibroblastic autonomous effects, and targeted genetic defects. Repetitive dosing in some models has more closely mimicked the pathology of human fibrotic lung disease. We also have a much better understanding of the fact that the aged lung has increased susceptibility to fibrosis. Each of the models reviewed in this report offers a powerful tool for studying some aspect of fibrotic lung disease. PMID:23526222

Lung abscess following bronchoscopy due to multidrug-resistant Capnocytophaga sputigena adjacent to lung cancer with high PD-L1 expression.

PubMed

Migiyama, Yohei; Anai, Moriyasu; Kashiwabara, Kosuke; Tomita, Yusuke; Saeki, Sho; Nakamura, Kazuyoshi; Okamoto, Shinichiro; Ichiyasu, Hidenori; Fujii, Kazuhiko; Kohrogi, Hirotsugu

2018-04-24

Lung abscess following flexible bronchoscopy is a rare and sometimes fatal iatrogenic complication. Here, we report the first case of a lung abscess caused by multidrug-resistant Capnocytophaga sputigena following bronchoscopy. A 67-year-old man underwent bronchoscopy to evaluate a lung mass. Seven days after transbronchial lung biopsy, he presented with an abscess formation in a lung mass. Empirical antibiotic therapy, including with garenoxacin, ampicillin/sulbactam, clindamycin and cefepime, was ineffective. Percutaneous needle aspiration of lung abscess yielded C. sputigena resistant to multiple antibiotics but remained susceptible to carbapenem. He was successfully treated by the combination therapy with surgery and with approximately 6 weeks of intravenous carbapenem. Finally he was diagnosed with a lung abscess with adenocarcinoma expressing high levels of programmed cell death ligand 1. The emergence of multidrug-resistant Capnocytophaga species is a serious concern for effective antimicrobial therapy. Clinicians should consider multidrug-resistant C. sputigena as a causative pathogen of lung abscess when it is refractory to antimicrobial treatment. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Target of obstructive sleep apnea syndrome merge lung cancer: based on big data platform.

PubMed

Li, Lifeng; Lu, Jingli; Xue, Wenhua; Wang, Liping; Zhai, Yunkai; Fan, Zhirui; Wu, Ge; Fan, Feifei; Li, Jieyao; Zhang, Chaoqi; Zhang, Yi; Zhao, Jie

2017-03-28

Based on our hospital database, the incidence of lung cancer diagnoses was similar in obstructive sleep apnea Syndrome (OSAS) and hospital general population; among individual with a diagnosis of lung cancer, the presence of OSAS was associated with an increased risk for mortality. In the gene expression and network-level information, we revealed significant alterations of molecules related to HIF1 and metabolic pathways in the hypoxic-conditioned lung cancer cells. We also observed that GBE1 and HK2 are downstream of HIF1 pathway important in hypoxia-conditioned lung cancer cell. Furthermore, we used publicly available datasets to validate that the late-stage lung adenocarcinoma patients showed higher expression HK2 and GBE1 than early-stage ones. In terms of prognostic features, a survival analysis revealed that the high GBE1 and HK2 expression group exhibited poorer survival in lung adenocarcinoma patients. By analyzing and integrating multiple datasets, we identify molecular convergence between hypoxia and lung cancer that reflects their clinical profiles and reveals molecular pathways involved in hypoxic-induced lung cancer progression. In conclusion, we show that OSAS severity appears to increase the risk of lung cancer mortality.

Multiple myeloma associated with acquired cutis laxa.

PubMed

Cho, S Y; Maguire, R F

1980-08-01

Acquired cutis laxa is a rare disorder characterized by diffuse laxity of the skin and loss of connective tissue support with involvement of the lungs, gastrointestinal tract, pelvic organs, and aorta. The case report presented herein describes a forty-six year old woman with multiple myeloma and cutis laxa. Her history included several severe allergic reactions and the gradual development of lax skin, loss of connective tissue support throughout the body, and emphysema. At autopsy, multiple myeloma, diffuse laxity of the skin, and panacinar emphysema were found. The amount of elastic fiber in the skin, lungs, and aorta was decreased and showed abnormal fragmentation. Results of direct immunofluorescence study demonstrated IgG bound to dermal elastic fibers. Speculation regarding an immunologic etiology of the elastic tissue abnormality is presented herein.

EGFR-mutant Non-small Cell Lung Cancer Accompanied by Transient Asymptomatic Pulmonary Opacities Successfully Treated with “Stop-And-Go” Osimertinib

PubMed Central

Kobayashi, Keigo; Naoki, Katsuhiko; Kuroda, Aoi; Yasuda, Hiroyuki; Kawada, Ichiro; Soejima, Kenzo; Betsuyaku, Tomoko

2017-01-01

A 69-year-old man with post-operative recurrence of lung adenocarcinoma was treated with multiple chemotherapies, including epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. A second biopsy revealed an EGFR T790M mutation. As 10th-line chemotherapy, osimertinib was initiated. After 24 weeks, chest computed tomography (CT) revealed asymptomatic ground-glass opacities in both lobes. After four weeks of osimertinib discontinuation, imaging revealed rapid lung cancer progression. Osimertinib was resumed. After 11 weeks, CT revealed decreased lung nodules with no exacerbation of interstitial lung disease. We describe a patient who experienced transient asymptomatic pulmonary opacities during treatment with osimertinib, which was successfully managed by a “stop-and-go” approach. PMID:29269665

Relaxation and Guided Imagery: A School-Based Intervention for Children with Asthma.

ERIC Educational Resources Information Center

Peck, Heather L.; Bray, Melissa A.; Kehle, Thomas J.

2003-01-01

This investigation analyzed the effect of relaxation and guided imagery on lung function and anxiety by employing a multiple baseline design across four middle school students with asthma. With the introduction of the intervention, it was found that lung function improved and anxiety decreased in all students. (Contains 63 references, 1 table, and…

[Medical history impressions of Karl Marx 1983].

PubMed

Kaiser, W

1983-12-15

Excerpts of his London era first published on the occasion of the Karl Marx testimonials of 1983 gave rise to extend the memory of the fundamental achievements of Karl Marx to medico-historical aspects. In this case Karl Marx paid special attention to the working and living conditions of the working class and an analysis of his adequate statements and records shows multifarious details which give a research basis also for the history of medicine. Marx and Engels had friendly contacts with several physicians who shared the opinions of the two classics: their way of life is shown in the most important points.

A post-Bertalanffy Systemics Healthcare Competitive Framework Proposal.

PubMed

Fiorini, Rodolfo A; Santacroce, Giulia F

2014-01-01

Health Information community can take advantage of a new evolutive categorization cybernetic framework. A systemic concept of principles organizing nature is proposed. It can be used as a multiscaling reference framework to develop successful and competitive antifragile system and new HRO information management strategies in advanced healthcare organization (HO) and high reliability organization (HRO) conveniently. Expected impacts are multifarious and quite articulated at different system scale level: major one is that, for the first time, Biomedical Engineering ideal system categorization levels can be matched exactly to practical system modeling interaction styles, with no paradigmatic operational ambiguity and information loss.

Challenges and Strategies for Breeding Resistance in Capsicum annuum to the Multifarious Pathogen, Phytophthora capsici

PubMed Central

Barchenger, Derek W.; Lamour, Kurt H.; Bosland, Paul W.

2018-01-01

Phytophthora capsici is the most devastating pathogen for chile pepper production worldwide and current management strategies are not effective. The population structure of the pathogen is highly variable and few sources of widely applicable host resistance have been identified. Recent genomic advancements in the host and the pathogen provide important insights into the difficulties reported by epidemiological and physiological studies published over the past century. This review highlights important challenges unique to this complex pathosystem and suggests strategies for resistance breeding to help limit losses associated with P. capsici. PMID:29868083

Research and Application of Marine Microbial Enzymes: Status and Prospects

PubMed Central

Zhang, Chen; Kim, Se-Kwon

2010-01-01

Over billions of years, the ocean has been regarded as the origin of life on Earth. The ocean includes the largest range of habitats, hosting the most life-forms. Competition amongst microorganisms for space and nutrients in the marine environment is a powerful selective force, which has led to evolution. The evolution prompted the marine microorganisms to generate multifarious enzyme systems to adapt to the complicated marine environments. Therefore, marine microbial enzymes can offer novel biocatalysts with extraordinary properties. This review deals with the research and development work investigating the occurrence and bioprocessing of marine microbial enzymes. PMID:20631875

Lung cancer: biology and treatment options

PubMed Central

Hassan, Omer; Yang, Yi-Wei; Buchanan, Petra

2015-01-01

Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLC) and non-small cell lung carcinomas (NSCLC). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation. PMID:26297204

Silica-induced Chronic Inflammation Promotes Lung Carcinogenesis in the Context of an Immunosuppressive Microenvironment12

PubMed Central

Freire, Javier; Ajona, Daniel; de Biurrun, Gabriel; Agorreta, Jackeline; Segura, Victor; Guruceaga, Elizabeth; Bleau, Anne-Marie; Pio, Ruben; Blanco, David; Montuenga, Luis M

2013-01-01

The association between inflammation and lung tumor development has been clearly demonstrated. However, little is known concerning the molecular events preceding the development of lung cancer. In this study, we characterize a chemically induced lung cancer mouse model in which lung cancer developed in the presence of silicotic chronic inflammation. Silica-induced lung inflammation increased the incidence and multiplicity of lung cancer in mice treated with N-nitrosodimethylamine, a carcinogen found in tobacco smoke. Histologic and molecular analysis revealed that concomitant chronic inflammation contributed to lung tumorigenesis through induction of preneoplastic changes in lung epithelial cells. In addition, silica-mediated inflammation generated an immunosuppressive microenvironment in which we observed increased expression of programmed cell death protein 1 (PD-1), transforming growth factor-β1, monocyte chemotactic protein 1 (MCP-1), lymphocyte-activation gene 3 (LAG3), and forkhead box P3 (FOXP3), as well as the presence of regulatory T cells. Finally, the K-RAS mutational profile of the tumors changed from Q61R to G12D mutations in the inflammatory milieu. In summary, we describe some of the early molecular changes associated to lung carcinogenesis in a chronic inflammatory microenvironment and provide novel information concerning the mechanisms underlying the formation and the fate of preneoplastic lesions in the silicotic lung. PMID:23908592

Long intergenic non-protein coding RNA 319 aggravates lung adenocarcinoma carcinogenesis by modulating miR-450b-5p/EZH2.

PubMed

Zhang, Zeng-Wang; Chen, Jia-Jun; Xia, Shi-Hui; Zhao, Hua; Yang, Jun-Bo; Zhang, Hao; He, Bin; Jiao, Jun; Zhan, Bo-Tao; Sun, Cheng-Cao

2018-04-15

Growing evidence shows that long non-coding RNAs (lncRNAs) have been wildly verified to modulate multiple tumorigenesis, especially lung adenocarcinoma. In present study, we aim to investigate the role of lncRNA LINC00319 in the lung adenocarcinoma carcinogenesis. We observed that increased expression of LINC00319 in lung adenocarcinoma tissues and cells in comparison to their corresponding controls. Moreover, the aberrant overexpression of LINC00319 indicated the poor prognosis of lung adenocarcinoma patients. Silence of LINC00319 was able to repress lung adenocarcinoma cell growth in vitro. Rescue assay was performed to further confirm that LINC00319 contributed to lung adenocarcinoma progression by regulating miR-450b-5p/EZH2 signal pathway. Taken together, our study discovered the oncogenic role of LINC00319 in clinical specimens and cellular experiments, showing the potential LINC00319/miR-450b-5p/EZH2 pathway. This results and findings provide a novel insight for lung adenocarcinoma tumorigenesis. Copyright © 2018. Published by Elsevier B.V.

Lung tumor production and tissue metal distribution after exposure to manual metal ARC-stainless steel welding fume in A/J and C57BL/6J mice.

PubMed

Zeidler-Erdely, Patti C; Battelli, Lori A; Salmen-Muniz, Rebecca; Li, Zheng; Erdely, Aaron; Kashon, Michael L; Simeonova, Petia P; Antonini, James M

2011-01-01

Stainless steel welding produces fumes that contain carcinogenic metals. Therefore, welders may be at risk for the development of lung cancer, but animal data are inadequate in this regard. Our main objective was to examine lung tumor production and histopathological alterations in lung-tumor-susceptible (A/J) and -resistant C57BL/6J (B6) mice exposed to manual metal arc-stainless steel (MMA-SS) welding fume. Male mice were exposed to vehicle or MMA-SS welding fume (20 mg/kg) by pharyngeal aspiration once per month for 4 mo. At 78 wk postexposure, gross tumor counts and histopathological changes were assessed and metal analysis was done on extrapulmonary tissue (aorta, heart, kidney, and liver). At 78 wk postexposure, gross lung tumor multiplicity and incidence were unremarkable in mice exposed to MMA-SS welding fume. Histopathology revealed that only the exposed A/J mice contained minimal amounts of MMA-SS welding fume in the lung and statistically increased lymphoid infiltrates and alveolar macrophages. A significant increase in tumor multiplicity in the A/J strain was observed at 78 wk. Metal analysis of extrapulmonary tissue showed that only the MMA-SS-exposed A/J mice had elevated levels of Cr, Cu, Mn, and Zn in kidney and Cr in liver. In conclusion, this study further supports that MMA-SS welding fume does not produce a significant tumorigenic response in an animal model, but may induce a chronic lung immune response. In addition, long-term extrapulmonary tissue alterations in metals in the susceptible A/J mouse suggest that the adverse effects of this fume might be cumulative.

Raw garlic consumption as a protective factor for lung cancer, a population-based case-control study in a Chinese population

PubMed Central

Jin, Zi-Yi; Wu, Ming; Han, Ren-Qiang; Zhang, Xiao-Feng; Wang, Xu-Shan; Liu, Ai-Ming; Zhou, Jin-Yi; Lu, Qing-Yi; Zhang, Zuo-Feng; Zhao, Jin-Kou

2013-01-01

Protective effect of garlic on the development of cancer has been reported in vitro and in vivo experimental studies, however, few human epidemiological studies have evaluated the relationship. A population-based case-control study has been conducted in a Chinese population from 2003 to 2010, with the aim to explore the association between raw garlic consumption and lung cancer. Epidemiological data were collected by face-to-face interviews using a standard questionnaire among 1,424 lung cancer cases and 4,543 healthy controls. Unconditional logistic regression was employed to estimate adjusted odds ratios (OR) and their 95% confidence intervals (CIs), and to evaluate ratio of odds ratios (ROR) for multiplicative interactions between raw garlic consumption and other risk factors. After adjusting for potential confounding factors, raw garlic consumption of ≥ 2 times per week is inversely associated with lung cancer (OR = 0.56, 95% CI = 0.44-0.72) with a monotonic dose-response relationship (p for trend <0.001). Furthermore, strong interactions at either additive and/or multiplicative scales were observed between raw garlic consumption and tobacco smoking (Synergy Index (SI) = 0.70, 95% CI = 0.57-0.85; and ROR = 0.78, 95% CI = 0.67-0.90), as well as high-temperature cooking oil fume (ROR = 0.77, 95% CI = 0.59-1.00). In conclusion, protective association between intake of raw garlic and lung cancer has been observed with a dose-response pattern, suggesting that garlic may potentially serve as a chemopreventive agent for lung cancer. Effective components in garlic in lung cancer chemoprevention warrant further in-depth investigation. PMID:23658367

A Case of Transient Pulmonary Interstitial Lesions in Aquaporin-4-positive Neuromyelitis Optica Spectrum Disorder.

PubMed

Asato, Yuko; Kamitani, Toshiaki; Ootsuka, Kuniyuki; Kuramochi, Mizuki; Nakanishi, Kozo; Shimada, Tetsuya; Takahashi, Toshiyuki; Misu, Tatsuro; Aoki, Masashi; Fujihara, Kazuo; Kawabata, Yoshinori

2018-05-18

We herein report the case of a 76-year old man with aquaporin-4-Immunoglobulin-G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD), in whom transient interstitial pulmonary lesions developed at the early stage of the disease. Chest X-ray showed multiple infiltrative shadows in both upper lung fields, and computed tomography revealed abnormal shadows distributed randomly in the lungs. Surgical lung biopsy showed features of unclassifiable interstitial pneumonia, characterized by various types of air-space organization, which resulted in obscure lung structure. This is the first report to describe the pathological findings of interstitial pneumonia, which may represent a rare extra-central nervous system complication of NMOSD.

LungMAP: The Molecular Atlas of Lung Development Program

PubMed Central

Ardini-Poleske, Maryanne E.; Ansong, Charles; Carson, James P.; Corley, Richard A.; Deutsch, Gail H.; Hagood, James S.; Kaminski, Naftali; Mariani, Thomas J.; Potter, Steven S.; Pryhuber, Gloria S.; Warburton, David; Whitsett, Jeffrey A.; Palmer, Scott M.; Ambalavanan, Namasivayam

2017-01-01

The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic cross talk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis, and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have a significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. A consortium of four research centers, a data coordinating center, and a human tissue repository provides high-quality molecular data of developing human and mouse lungs. LungMAP includes mouse and human data for cross correlation of developmental processes across species. LungMAP is generating foundational data and analysis, creating a web portal for presentation of results and public sharing of data sets, establishing a repository of young human lung tissues obtained through organ donor organizations, and developing a comprehensive lung ontology that incorporates the latest findings of the consortium. The LungMAP website (www.lungmap.net) currently contains more than 6,000 high-resolution lung images and transcriptomic, proteomic, and lipidomic human and mouse data and provides scientific information to stimulate interest in research careers for young audiences. This paper presents a brief description of research conducted by the consortium, database, and portal development and upcoming features that will enhance the LungMAP experience for a community of users. PMID:28798251

Effects of vascular flow and PEEP in a multiple hit model of lung injury in isolated perfused rabbit lungs.

PubMed

Piacentini, Enrique; López-Aguilar, Josefina; García-Martín, Carolina; Villagrá, Ana; Saenz-Valiente, Alicia; Murias, Gastón; Fernández-Segoviano, Pilar; Hotchkiss, John R; Blanch, Lluis

2008-07-01

High vascular flow aggravates lung damage in animal models of ventilator-induced lung injury. Positive end-expiratory pressure (PEEP) can attenuate ventilator-induced lung injury, but its continued effectiveness in the setting of antecedent lung injury is unclear. The objective of the present study was to evaluate whether the application of PEEP diminishes lung injury induced by concurrent high vascular flow and high alveolar pressures in normal lungs and in a preinjury lung model. Two series of experiments were performed. Fifteen sets of isolated rabbit lungs were randomized into three groups (n = 5): low vascular flow/low PEEP; high vascular flow/low PEEP, and high vascular flow/high PEEP. Subsequently, the same protocol was applied in an additional 15 sets of isolated rabbit lungs in which oleic acid was added to the vascular perfusate to produce mild to moderate lung injury. All lungs were ventilated with peak airway pressure of 30 cm H2O for 30 minutes. Outcome measures included frequency of gross structural failure, pulmonary hemorrhage, edema formation, changes in static compliance, pulmonary vascular resistance, and pulmonary ultrafiltration coefficient. In the context of high vascular flow, application of a moderate level of PEEP reduced pulmonary rupture, edema formation, and lung hemorrhage. The protective effects of PEEP were not observed in lungs concurrently injured with oleic acid. Under these experimental conditions, PEEP attenuates lung injury in the setting of high vascular flow. The protective effect of PEEP is lost in a two-hit model of lung injury.

Endothelial cells are not required for specification of respiratory progenitors

PubMed Central

Havrilak, Jamie A.; Melton, Kristin R.; Shannon, John M.

2017-01-01

Crosstalk between mesenchymal and epithelial cells influences organogenesis in multiple tissues, such as lung, pancreas, liver, and the nervous system. Lung mesenchyme comprises multiple cell types, however, and precise identification of the mesenchymal cell type(s) that drives early events in lung development remains unknown. Endothelial cells have been shown to be required for some aspects of lung epithelial patterning, lung stem cell differentiation, and regeneration after injury. Furthermore, endothelial cells are involved in early liver and pancreas development. From these observations we hypothesized that endothelial cells might also be required for early specification of the respiratory field and subsequent lung bud initiation. We first blocked VEGF signaling in E8.5 cultured foreguts with small molecule VEGFR inhibitors and found that lung specification and bud formation were unaltered. However, when we examined E9.5 mouse embryos carrying a mutation in the VEGFR Flk-1, which do not develop endothelial cells, we found that respiratory progenitor specification was impeded. Because the E9.5 embryos were substantially smaller than control littermates, suggesting the possibility of developmental delay, we isolated and cultured foreguts from mutant and control embryos on E8.5, when no size differences were apparent. We found that both specification of the respiratory field and lung bud formation occurred in mutant and control explants. These observations were unaffected by the presence or absence of serum. We also observed that hepatic specification and initiation occurred in the absence of endothelial cells, and that expansion of the liver epithelium in culture did not differ between mutant and control explants. Consistent with previously published results, we also found that pancreatic buds were not maintained in cultured foreguts when endothelial cells were absent. Our observations support the conclusion that endothelial cells are not required for early specification of lung progenitors and bud initiation, and that the diminished lung specification seen in E9.5 Flk−/− embryos is likely due to developmental delay resulting from the insufficient delivery of oxygen, nutrients, and other factors in the absence of a vasculature. PMID:28501476

Prolactin-dependent modulation of organogenesis in the vertebrate: Recent discoveries in zebrafish.

PubMed

Nguyen, Nhu; Stellwag, Edmund J; Zhu, Yong

2008-11-01

The scientific literature is replete with evidence of the multifarious functions of the prolactin (PRL)/growth hormone (GH) superfamily in adult vertebrates. However, little information is available on the roles of PRL and related hormones prior to the adult stage of development. A limited number of studies suggest that GH functions to stimulate glucose transport and protein synthesis in mouse blastocytes and may be involved during mammalian embryogenesis. In contrast, the evidence for a role of PRL during vertebrate embryogenesis is limited and controversial. Genes encoding GH/PRL hormones and their respective receptors are actively transcribed and translated in various animal models at different time points, particularly during tissue remodeling. We have addressed the potential function of GH/PRL hormones during embryonic development in zebrafish by the temporary inhibition of in vivo PRL translation. This treatment caused multiple morphological defects consistent with a role of PRL in embryonic-stage organogenesis. The affected organs and tissues are known targets of PRL activity in fish and homologous structures in mammalian species. Traditionally, the GH/PRL hormones are viewed as classical endocrine hormones, mediating functions through the circulatory system. More recent evidence points to cytokine-like actions of these hormones through either an autocrine or a paracrine mechanism. In some situations they could mimic actions of developmentally regulated genes as suggested by experiments in multiple organisms. In this review, we present similarities and disparities between zebrafish and mammalian models in relation to PRL and PRLR activity. We conclude that the zebrafish could serve as a suitable alternative to the rodent model to study PRL functions in development, especially in relation to organogenesis.

Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis.

PubMed

Solanki, Hitendra S; Advani, Jayshree; Khan, Aafaque Ahmad; Radhakrishnan, Aneesha; Sahasrabuddhe, Nandini A; Pinto, Sneha M; Chang, Xiaofei; Prasad, Thottethodi Subrahmanya Keshava; Mathur, Premendu Prakash; Sidransky, David; Gowda, Harsha; Chatterjee, Aditi

2017-08-01

Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke. Using high resolution Orbitrap Velos mass spectrometer, we identified the hyperphosphorylation of 493 sites, which corresponds to 341 proteins and 195 hypophosphorylated sites, mapping to 142 proteins upon smoke exposure (2.0-fold change). We report differential phosphorylation of multiple kinases, including PAK6, EPHA4, LYN, mitogen-activated protein kinase, and phosphatases, including TMEM55B, PTPN14, TIGAR, among others, in response to chronic cigarette smoke exposure. Bioinformatics analysis revealed that the molecules differentially phosphorylated upon chronic exposure of cigarette smoke are associated with PI3K/AKT/mTOR and CDC42-PAK signaling pathways. These signaling networks are involved in multiple cellular processes, including cell polarity, cytoskeletal remodeling, cellular migration, protein synthesis, autophagy, and apoptosis. The present study contributes to emerging proteomics insights on cigarette smoke mediated global signaling in lung cells, which in turn may aid in development of precision medicine therapeutics and postgenomics biomarkers.

Hyperpolarized Xenon-129 Gas-Exchange Imaging of Lung Microstructure: First Case Studies in Subjects with Obstructive Lung Disease

PubMed Central

Dregely, Isabel; Mugler, John P.; Ruset, Iulian C.; Altes, Talissa A.; Mata, Jaime F.; Miller, G. Wilson; Ketel, Jeffrey; Ketel, Steve; Distelbrink, Jan; Hersman, F.W.; Ruppert, Kai

2011-01-01

Purpose To develop and test a method to non-invasively assess the functional lung microstructure. Materials and Methods The Multiple exchange time Xenon polarization Transfer Contrast technique (MXTC) encodes xenon gas-exchange contrast at multiple delay times permitting two lung-function parameters to be derived: 1) MXTC-F, the long exchange-time depolarization value, which is proportional to the tissue to alveolar-volume ratio and 2) MXTC-S, the square root of the xenon exchange-time constant, which characterizes thickness and composition of alveolar septa. Three healthy volunteers, one asthmatic and two COPD (GOLD stage I and II) subjects were imaged with MXTC MRI. In a subset of subjects, hyperpolarized xenon-129 ADC MRI and CT imaging were also performed. Results The MXTC-S parameter was found to be elevated in subjects with lung disease (p-value = 0.018). In the MXTC-F parameter map it was feasible to identify regional loss of functional tissue in a COPD patient. Further, the MXTC-F map showed excellent regional correlation with CT and ADC (ρ ≥ 0.90) in one COPD subject. Conclusion The functional tissue-density parameter MXTC-F showed regional agreement with other imaging techniques. The newly developed parameter MXTC-S, which characterizes the functional thickness of alveolar septa, has potential as a novel biomarker for regional parenchymal inflammation or thickening. PMID:21509861

Endoscopic fluorescent diagnostics and PDT of early malignancies of lung and esophagus

NASA Astrophysics Data System (ADS)

Sokolov, Victor V.; Chissov, Valery I.; Trakhtenberg, A. K.; Mamontov, A. S.; Frank, George A.; Filonenko, E. V.; Telegina, L. V.; Gladunov, V. K.; Belous, T. A.; Aristarkhova, E. I.; Zharkova, Natalia N.; Smirnov, V. V.; Kozlov, Dmitrij N.

1996-01-01

In this paper the results of fluorescence diagnostics and photodynamic therapy of early stage malignancies of lung (17 patients) and esophagus (8 patients) are presented. 13 patients had multiple primary tumors. As photosensitizers the new drugs Photoheme and Photosense were used. Complete remission was obtained in 92%. The patients are followed up without relapses to 2,5 years.

Quantitative evaluation of local pulmonary distribution of TiO2 in rats following single or multiple intratracheal administrations of TiO2 nanoparticles using X-ray fluorescence microscopy.

PubMed

Zhang, Guihua; Shinohara, Naohide; Kano, Hirokazu; Senoh, Hideki; Suzuki, Masaaki; Sasaki, Takeshi; Fukushima, Shoji; Gamo, Masashi

2016-10-01

Uneven pulmonary nanoparticle (NP) distribution has been described when using single-dose intratracheal administration tests. Multiple-dose intratracheal administrations with small quantities of NPs are expected to improve the unevenness of each dose. The differences in local pulmonary NP distribution (called microdistribution) between single- and multiple-dose administrations may cause differential pulmonary responses; however, this has not been evaluated. Here, we quantitatively evaluated the pulmonary microdistribution (per mesh: 100 μm × 100 μm) of TiO2 in lung sections from rats following one, two, three, or four doses of TiO2 NPs at a same total dosage of 10 mg kg(-1) using X-ray fluorescence microscopy. The results indicate that: (i) multiple-dose administrations show lower variations in TiO2 content (ng mesh(-1) ) for sections of each lobe; (ii) TiO2 appears to be deposited more in the right caudal and accessory lobes located downstream of the administration direction of NP suspensions, and less so in the right middle lobes, irrespective of the number of doses; (iii) there are not prominent differences in the pattern of pulmonary TiO2 microdistribution between rats following single and multiple doses of TiO2 NPs. Additionally, the estimation of pulmonary TiO2 deposition for multiple-dose administrations imply that every dose of TiO2 would be randomly deposited only in part of the fixed 30-50% of lung areas. The evidence suggests that multiple-dose administrations do not offer remarkable advantages over single-dose administration on the pulmonary NP microdistribution, although multiple-dose administrations may reduce variations in the TiO2 content for each lung lobe. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

VEGF (Vascular Endothelial Growth Factor) and Fibrotic Lung Disease.

PubMed

Barratt, Shaney L; Flower, Victoria A; Pauling, John D; Millar, Ann B

2018-04-24

Interstitial lung disease (ILD) encompasses a group of heterogeneous diseases characterised by varying degrees of aberrant inflammation and fibrosis of the lung parenchyma. This may occur in isolation, such as in idiopathic pulmonary fibrosis (IPF) or as part of a wider disease process affecting multiple organs, such as in systemic sclerosis. Anti-Vascular Endothelial Growth Factor (anti-VEGF) therapy is one component of an existing broad-spectrum therapeutic option in IPF (nintedanib) and may become part of the emerging therapeutic strategy for other ILDs in the future. This article describes our current understanding of VEGF biology in normal lung homeostasis and how changes in its bioavailability may contribute the pathogenesis of ILD. The complexity of VEGF biology is particularly highlighted with an emphasis on the potential non-vascular, non-angiogenic roles for VEGF in the lung, in both health and disease.

Evaluation of Neonatal Lung Volume Growth by Pulmonary Magnetic Resonance Imaging in Patients with Congenital Diaphragmatic Hernia.

PubMed

Schopper, Melissa A; Walkup, Laura L; Tkach, Jean A; Higano, Nara S; Lim, Foong Yen; Haberman, Beth; Woods, Jason C; Kingma, Paul S

2017-09-01

To evaluate postnatal lung volume in infants with congenital diaphragmatic hernia (CDH) and determine if a compensatory increase in lung volume occurs during the postnatal period. Using a novel pulmonary magnetic resonance imaging method for imaging neonatal lungs, the postnatal lung volumes in infants with CDH were determined and compared with prenatal lung volumes obtained via late gestation magnetic resonance imaging. Infants with left-sided CDH (2 mild, 9 moderate, and 1 severe) were evaluated. The total lung volume increased in all infants, with the contralateral lung increasing faster than the ipsilateral lung (mean ± SD: 4.9 ± 3.0 mL/week vs 3.4 ± 2.1 mL/week, P = .005). In contrast to prenatal studies, the volume of lungs of infants with more severe CDH grew faster than the lungs of infants with more mild CDH (Spearman's ρ=-0.086, P = .01). Although the contralateral lung volume grew faster in both mild and moderate groups, the majority of total lung volume growth in moderate CDH came from increased volume of the ipsilateral lung (42% of total lung volume increase in the moderate group vs 32% of total lung volume increase in the mild group, P = .09). Analysis of multiple clinical variables suggests that increased weight gain was associated with increased compensatory ipsilateral lung volume growth (ρ = 0.57, P = .05). These results suggest a potential for postnatal catch-up growth in infants with pulmonary hypoplasia and suggest that weight gain may increase the volume growth of the more severely affected lung. Copyright © 2017 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maneckjee, R.; Minna, J.D.

Using specific radioactively-labeled ligands, the authors find that lung cancer cell lines of diverse histologic types express multiple, high-affinity membrane receptors for {mu}, {delta}, and {kappa} opioid agonists and for nicotine and {alpha}-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas {mu}, {delta}, and {kappa} opioid agonists at low concentrations inhibited lung cancer growth in vitro. They also found that lung cancer cells expressed various combinations of immunoreactive opioid peptidesmore » ({beta}-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, they tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a tumor suppressor system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer.« less

Contribution of radon and radon daughters to respiratory cancer.

PubMed Central

Harley, N; Samet, J M; Cross, F T; Hess, T; Muller, J; Thomas, D

1986-01-01

This article reviews studies on the contribution of radon and radon daughters to respiratory cancer and proposes recommendations for further research, particularly a national radon survey. The steady-state outdoor radon concentration averages 200 pCi/m3, and indoor levels are about 4 times higher. The primary source of radon in homes is the underlying soil; entry depends on multiple variables and reduced ventilation for energy conservation increases indoor radon levels. Occupational exposures are expressed in units of radon daughter potential energy concentration or working level (WL). Cumulative exposure is the product of the working level and the time exposed. The unit for cumulative exposure is the working level month (WLM). The occupational standard for radon exposure is 4 WLM/year, and 2 WLM/year has been suggested as a guideline for remedial action in homes. Epidemiologic studies show that miners with cumulative radon daughter exposures somewhat below 100 WLM have excess lung cancer mortality. Some 3% to 8% of miners studied have developed lung cancer attributable to radon daughters. All of the underground mining studies show an increased risk of lung cancer with radon daughter exposure. All cell types of lung cancer increased with radon exposure. If radon and smoking act in a multiplicative manner, then the risk for smokers could be 10 times that for nonsmokers. The potential risk of lung cancer appears to be between 1 and 2 per 10,000/WLM, which yields a significant number of lung cancers as some 220 million persons in the United States are exposed on average to 10 to 20 WLM/lifetime. PMID:3830103

Gingerol Reverses the Cancer-Promoting Effect of Capsaicin by Increased TRPV1 Level in a Urethane-Induced Lung Carcinogenic Model.

PubMed

Geng, Shengnan; Zheng, Yaqiu; Meng, Mingjing; Guo, Zhenzhen; Cao, Ning; Ma, Xiaofang; Du, Zhenhua; Li, Jiahuan; Duan, Yongjian; Du, Gangjun

2016-08-10

Both gingerol and capsaicin are agonists of TRPV1, which can negatively control tumor progression. This study observed the long-term effects of oral administration of 6-gingerol alone or in combination with capsaicin for 20 weeks in a urethane-induced lung carcinogenic model. We showed that lung carcinoma incidence and multiplicity were 70% and 21.2 ± 3.6, respectively, in the control versus 100% and 35.6 ± 5.2 in the capsaicin group (P < 0.01) and 50% and 10.8 ± 3.1 in the 6-gingerol group (P < 0.01). The combination of 6-gingerol and capsaicin reversed the cancer-promoting effect of capsaicin (carcinoma incidence of 100% versus 20% and multiplicity of 35.6 ± 5.2 versus 4.7 ± 2.3; P < 0.001). The cancer-promoting effect of capsaicin was due to increased epidermal growth-factor receptor (EGFR) level by decreased transient receptor potential vanilloid type-1 (TRPV1) level (P < 0.01) . The capsaicin-decreased EGFR level subsequently reduced levels of nuclear factor-κB (NF-κB) and cyclin D1 that favored enhanced lung epithelial proliferation and epithelial-mesenchymal transition (EMT) during lung carcinogenesis (P < 0.01). In contrast, 6-gingerol promoted TRPV1 level and drastically decreased the levels of EGFR, NF-κB, and cyclin D1 that favored reduced lung epithelial proliferation and EMT (P < 0.01). This study provides valuable information for the long-term consumption of chili-pepper-rich diets to decrease the risk of cancer development.

Moonlighting microtubule-associated proteins: regulatory functions by day and pathological functions at night.

PubMed

Oláh, J; Tőkési, N; Lehotzky, A; Orosz, F; Ovádi, J

2013-11-01

The sensing, integrating, and coordinating features of the eukaryotic cells are achieved by the complex ultrastructural arrays and multifarious functions of the cytoskeletal network. Cytoskeleton comprises fibrous protein networks of microtubules, actin, and intermediate filaments. These filamentous polymer structures are highly dynamic and undergo constant and rapid reorganization during cellular processes. The microtubular system plays a crucial role in the brain, as it is involved in an enormous number of cellular events including cell differentiation and pathological inclusion formation. These multifarious functions of microtubules can be achieved by their decoration with proteins/enzymes that exert specific effects on the dynamics and organization of the cytoskeleton and mediate distinct functions due to their moonlighting features. This mini-review focuses on two aspects of the microtubule cytoskeleton. On the one hand, we describe the heteroassociation of tubulin/microtubules with metabolic enzymes, which in addition to their catalytic activities stabilize microtubule structures via their cross-linking functions. On the other hand, we focus on the recently identified moonlighting tubulin polymerization promoting protein, TPPP/p25. TPPP/p25 is a microtubule-associated protein and it displays distinct physiological or pathological (aberrant) functions; thus it is a prototype of Neomorphic Moonlighting Proteins. The expression of TPPP/p25 is finely controlled in the human brain; this protein is indispensable for the development of projections of oligodendrocytes that are responsible for the ensheathment of axons. The nonphysiological, higher or lower TPPP/p25 level leads to distinct CNS diseases. Mechanisms contributing to the control of microtubule stability and dynamics by metabolic enzymes and TPPP/p25 will be discussed. Copyright © 2013 Wiley Periodicals, Inc.

Molecular diversity and multifarious plant growth promoting attributes of Bacilli associated with wheat (Triticum aestivum L.) rhizosphere from six diverse agro-ecological zones of India.

PubMed

Verma, Priyanka; Yadav, Ajar Nath; Khannam, Kazy Sufia; Kumar, Sanjay; Saxena, Anil Kumar; Suman, Archna

2016-01-01

The diversity of culturable Bacilli was investigated in six wheat cultivating agro-ecological zones of India viz: northern hills, north western plains, north eastern plains, central, peninsular, and southern hills. These agro-ecological regions are based on the climatic conditions such as pH, salinity, drought, and temperature. A total of 395 Bacilli were isolated by heat enrichment and different growth media. Amplified ribosomal DNA restriction analysis using three restriction enzymes AluI, MspI, and HaeIII led to the clustering of these isolates into 19-27 clusters in the different zones at >70% similarity index, adding up to 137 groups. Phylogenetic analysis based on 16S rRNA gene sequencing led to the identification of 55 distinct Bacilli that could be grouped in five families, Bacillaceae (68%), Paenibacillaceae (15%), Planococcaceae (8%), Staphylococcaceae (7%), and Bacillales incertae sedis (2%), which included eight genera namely Bacillus, Exiguobacterium, Lysinibacillus, Paenibacillus, Planococcus, Planomicrobium, Sporosarcina, and Staphylococcus. All 395 isolated Bacilli were screened for their plant growth promoting attributes, which included direct-plant growth promoting (solubilization of phosphorus, potassium, and zinc; production of phytohormones; 1-aminocyclopropane-1-carboxylate deaminase activity and nitrogen fixation), and indirect-plant growth promotion (antagonistic, production of lytic enzymes, siderophore, hydrogen cyanide, and ammonia). To our knowledge, this is the first report for the presence of Bacillus endophyticus, Paenibacillus xylanexedens, Planococcus citreus, Planomicrobium okeanokoites, Sporosarcina sp., and Staphylococcus succinus in wheat rhizosphere and exhibit multifunctional PGP attributes. These niche-specific and multifarious PGP Bacilli may serve as inoculants for crops growing in respective climatic conditions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A hybrid approach for fusing 4D-MRI temporal information with 3D-CT for the study of lung and lung tumor motion.

PubMed

Yang, Y X; Teo, S-K; Van Reeth, E; Tan, C H; Tham, I W K; Poh, C L

2015-08-01

Accurate visualization of lung motion is important in many clinical applications, such as radiotherapy of lung cancer. Advancement in imaging modalities [e.g., computed tomography (CT) and MRI] has allowed dynamic imaging of lung and lung tumor motion. However, each imaging modality has its advantages and disadvantages. The study presented in this paper aims at generating synthetic 4D-CT dataset for lung cancer patients by combining both continuous three-dimensional (3D) motion captured by 4D-MRI and the high spatial resolution captured by CT using the authors' proposed approach. A novel hybrid approach based on deformable image registration (DIR) and finite element method simulation was developed to fuse a static 3D-CT volume (acquired under breath-hold) and the 3D motion information extracted from 4D-MRI dataset, creating a synthetic 4D-CT dataset. The study focuses on imaging of lung and lung tumor. Comparing the synthetic 4D-CT dataset with the acquired 4D-CT dataset of six lung cancer patients based on 420 landmarks, accurate results (average error <2 mm) were achieved using the authors' proposed approach. Their hybrid approach achieved a 40% error reduction (based on landmarks assessment) over using only DIR techniques. The synthetic 4D-CT dataset generated has high spatial resolution, has excellent lung details, and is able to show movement of lung and lung tumor over multiple breathing cycles.

LungMAP: The Molecular Atlas of Lung Development Program.

PubMed

Ardini-Poleske, Maryanne E; Clark, Robert F; Ansong, Charles; Carson, James P; Corley, Richard A; Deutsch, Gail H; Hagood, James S; Kaminski, Naftali; Mariani, Thomas J; Potter, Steven S; Pryhuber, Gloria S; Warburton, David; Whitsett, Jeffrey A; Palmer, Scott M; Ambalavanan, Namasivayam

2017-11-01

The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic cross talk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis, and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have a significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. A consortium of four research centers, a data coordinating center, and a human tissue repository provides high-quality molecular data of developing human and mouse lungs. LungMAP includes mouse and human data for cross correlation of developmental processes across species. LungMAP is generating foundational data and analysis, creating a web portal for presentation of results and public sharing of data sets, establishing a repository of young human lung tissues obtained through organ donor organizations, and developing a comprehensive lung ontology that incorporates the latest findings of the consortium. The LungMAP website (www.lungmap.net) currently contains more than 6,000 high-resolution lung images and transcriptomic, proteomic, and lipidomic human and mouse data and provides scientific information to stimulate interest in research careers for young audiences. This paper presents a brief description of research conducted by the consortium, database, and portal development and upcoming features that will enhance the LungMAP experience for a community of users. Copyright © 2017 the American Physiological Society.

GLI pathogenesis-related 1 functions as a tumor-suppressor in lung cancer.

PubMed

Sheng, Xiumei; Bowen, Nathan; Wang, Zhengxin

2016-03-18

GLI pathogenesis-related 1 (GLIPR1) was originally identified in glioblastomas and its expression was also found to be down-regulated in prostate cancer. Functional studies revealed both growth suppression and proapoptotic activities for GLIPR1 in multiple cancer cell lines. GLIPR1's role in lung cancer has not been investigated. Protein arginine methyltransferase 5 (PRMT5) is a protein arginine methyltransferase and forms a stoichiometric complex with the WD repeat domain 77 (WDR77) protein. Both PRMT5 and WDR77 are essential for growth of lung epithelial and cancer cells. But additional gene products that interact genetically or biochemichally with PRMT5 and WDR77 in the control of lung cancer cell growth are not characterized. DNA microarray and immunostaining were used to detect GLIPR1 expression during lung development and lung tumorigenesis. GLIPR1 expression was also analyzed in the TCGA lung cancer cohort. The consequence of GLIPR1 on growth of lung cancer cells in the tissue culture and lung tumor xenografts in the nude mice was observed. We found that GLIPR1 expression is negatively associated with PRMT5/WDR77. GLIPR1 is absent in growing epithelial cells at the early stages of mouse lung development and highly expressed in the adult lung. Expression of GLIPR1 was down-regulated during lung tumorigenesis and its expression suppressed growth of lung cancer cells in the tissue culture and lung tumor xenografts in mice. GLIPR1 regulates lung cancer growth through the V-Erb-B avian erythroblastic leukemia viral oncogene homolog 3 (ErbB3). This study reveals a novel pathway that PRMT5/WDR77 regulates GLIPR1 expression to control lung cancer cell growth and GLIPR1 as a potential therapeutic agent for lung cancer.

Sarcoidosis and multiple myeloma: Concurrent presentation of an unusual association

PubMed Central

Nair, Vidya; Prajapat, Deepak; Talwar, Deepak

2016-01-01

Literature on concurrent association of sarcoidosis with lymphoproliferative malignancies other than lymphoma e.g. multiple myeloma is meager. The rarity of the situation prompted us to report this patient who was a 51-year-old woman with a 2-years history of breathlessness, cough with expectoration, chest pain and backache. Initial evaluation revealed mild anemia, increased alkaline phosphatase with chest skiagram showing both lower zone non homogenous opacities with calcified hilar lymph nodes. CECT chest showed mediastinal with bilateral hilar lymphadenopathy, parenchymal fibrosis, traction bronchiectasis, ground glass opacities, septal and peribronchovascular thickening affecting mid and lower lung zones bilaterally. MRI Dorsolumbar spine was suggestive of marrow infiltrative disorder. EBUS FNA of intrathoracic nodes, EBB and TBLB confirmed sarcoidosis. PET CT revealed hyper metabolic activity in lung, multiple lymph nodes and lytic bone lesions. Serum protein electrophoresis and immunofixation revealed a monoclonal paraprotein, immunoglobulin IgG kappa type. Bone marrow biopsy revealed an increase in plasma cells (15%), but no granulomas. Diagnosis of Indolent or multiple myeloma with sarcoidosis was established. 12 cases of sarcoidosis and multiple myeloma have been reported in literature, and mostly preceding the onset of multiple myeloma by many years, in our case both were diagnosed concurrently. PMID:26933313

Cross sectional study on lung function of coke oven workers: a lung function surveillance system from 1978 to 1990

PubMed Central

Wu, J; Kreis, I; Griffiths, D; Darling, C

2002-01-01

Aims: To determine the association between lung function of coke oven workers and exposure to coke oven emissions. Methods: Lung function data and detailed work histories for workers in recovery coke ovens of a steelworks were extracted from a lung function surveillance system. Multiple regressions were employed to determine significant predictors for lung function indices. The first sets of lung function tests for 613 new starters were pooled to assess the selection bias. The last sets of lung function tests for 834 subjects with one or more year of coke oven history were pooled to assess determinants of lung function. Results: Selection bias associated with the recruitment process was not observed among the exposure groups. For subjects with a history of one or more years of coke oven work, each year of working in the most exposed "operation" position was associated with reductions in FEV1 of around 9 ml (p = 0.006, 95% CI: 3 ml to 16 ml) and in FVC of around 12 ml (p = 0.002, 95% CI: 4 ml to 19 ml). Negative effects of smoking on lung function were also observed. Conclusions: Exposure to coke oven emissions was found to be associated with lower FEV1 and FVC. Effects of work exposure on lung function are similar to those found in other studies. PMID:12468747

Oral kanglaite injection (KLTI) attenuates the lung cancer-promoting effect of high-fat diet (HFD)-induced obesity.

PubMed

Cao, Ning; Ma, Xiaofang; Guo, Zhenzhen; Zheng, Yaqiu; Geng, Shengnan; Meng, Mingjing; Du, Zhenhua; Lin, Haihong; Duan, Yongjian; Du, Gangjun

2016-09-20

Obesity is a risk factor for cancer and cancer-related mortality, however, its role in lung cancer progression remains controversial. This study aimed to assess whether high-fat diet (HFD)-induced obesity promotes lung cancer progression and whether the promotion can be decreased by Kanglaite injection (KLTI). In vivo, HFD-induced overweight or obesity increases the lung carcinoma incidence and multiplicity in a urethane-induced lung carcinogenic model and cancer-related mortality in a LLC allograft model by increasing oxidative stress and cellular signaling molecules including JAK, STAT3, Akt, mTOR, NF-κB and cyclin D1. These changes resulted in increases in vascular disruption and the lung water content, thereby promoting lung epithelial proliferation and the epithelial-mesenchymal transition (EMT) during carcinogenesis. Chronic KLTI treatment substantially prevented the weight gain resulting from HFD consumption, thereby reversing the metabolic dysfunction-related physiological changes and reducing susceptibility to lung carcinogenesis. In vitro, KLTI significantly suppressed the proliferation and induced apoptosis and differentiation in 3T3-L1 preadipocyte cells and attenuated endothelial cell permeability in HUVECs. Our study indicates that there is a potential relationship between obesity and lung cancer. This is the first study to show that obesity can directly accelerate carcinogen-induced lung cancer progression and that KLTI can decrease the lung cancer-promoting effect of HFD-induced obesity.

Contextual convolutional neural networks for lung nodule classification using Gaussian-weighted average image patches

NASA Astrophysics Data System (ADS)

Lee, Haeil; Lee, Hansang; Park, Minseok; Kim, Junmo

2017-03-01

Lung cancer is the most common cause of cancer-related death. To diagnose lung cancers in early stages, numerous studies and approaches have been developed for cancer screening with computed tomography (CT) imaging. In recent years, convolutional neural networks (CNN) have become one of the most common and reliable techniques in computer aided detection (CADe) and diagnosis (CADx) by achieving state-of-the-art-level performances for various tasks. In this study, we propose a CNN classification system for false positive reduction of initially detected lung nodule candidates. First, image patches of lung nodule candidates are extracted from CT scans to train a CNN classifier. To reflect the volumetric contextual information of lung nodules to 2D image patch, we propose a weighted average image patch (WAIP) generation by averaging multiple slice images of lung nodule candidates. Moreover, to emphasize central slices of lung nodules, slice images are locally weighted according to Gaussian distribution and averaged to generate the 2D WAIP. With these extracted patches, 2D CNN is trained to achieve the classification of WAIPs of lung nodule candidates into positive and negative labels. We used LUNA 2016 public challenge database to validate the performance of our approach for false positive reduction in lung CT nodule classification. Experiments show our approach improves the classification accuracy of lung nodules compared to the baseline 2D CNN with patches from single slice image.

Disseminated Skeletal Muscle and Cardiac Metastasis from Squamous Cell Carcinoma of the Lung Detected with FDG and FLT PET/CT.

PubMed

Jain, Tarun Kumar; Rayamajhi, Sampanna Jung; Basher, Rajender Kumar; Gupta, Dheeraj; Maturu, Venkata Nagarjuna; Mittal, Bhagwant Rai

2016-09-01

Lung cancer is one of the leading cancers all over the world. Positron emission tomography (PET) using 18F fluorodeoxyglucose (18F FDG) is useful for staging of the disease and decide the appropriate management. 3'-deoxy-3'-18 F-fluorothymidine (18F FLT) is a tracer being extensively evaluated currently and is said to represent tumor proliferation. Common sites of metastases from lung cancer include adrenal glands, bone, and brain. Muscle metastasis and cardiac metastasis are uncommon findings. We report a case of squamous cell carcinoma of the lung with metastases to multiple skeletal muscles and myocardium detected with both FDG and FLT PET/computed tomography (CT).

Disseminated Skeletal Muscle and Cardiac Metastasis from Squamous Cell Carcinoma of the Lung Detected with FDG and FLT PET/CT

PubMed Central

Jain, Tarun Kumar; Rayamajhi, Sampanna Jung; Basher, Rajender Kumar; Gupta, Dheeraj; Maturu, Venkata Nagarjuna; Mittal, Bhagwant Rai

2016-01-01

Lung cancer is one of the leading cancers all over the world. Positron emission tomography (PET) using 18F fluorodeoxyglucose (18F FDG) is useful for staging of the disease and decide the appropriate management. 3’-deoxy-3’-18 F-fluorothymidine (18F FLT) is a tracer being extensively evaluated currently and is said to represent tumor proliferation. Common sites of metastases from lung cancer include adrenal glands, bone, and brain. Muscle metastasis and cardiac metastasis are uncommon findings. We report a case of squamous cell carcinoma of the lung with metastases to multiple skeletal muscles and myocardium detected with both FDG and FLT PET/computed tomography (CT). PMID:27651747

Direct Measurement of Lung Motion Using Hyperpolarized Helium-3 MR Tagging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai Jing; Miller, G. Wilson; Altes, Talissa A.

2007-07-01

Purpose: To measure lung motion between end-inhalation and end-exhalation using a hyperpolarized helium-3 (HP {sup 3}He) magnetic resonance (MR) tagging technique. Methods and Materials: Three healthy volunteers underwent MR tagging studies after inhalation of 1 L HP {sup 3}He gas diluted with nitrogen. Multiple-slice two-dimensional and volumetric three-dimensional MR tagged images of the lungs were obtained at end-inhalation and end-exhalation, and displacement vector maps were computed. Results: The grids of tag lines in the HP {sup 3}He MR images were well defined at end-inhalation and remained evident at end-exhalation. Displacement vector maps clearly demonstrated the regional lung motion and deformationmore » that occurred during exhalation. Discontinuity and differences in motion pattern between two adjacent lung lobes were readily resolved. Conclusions: Hyperpolarized helium-3 MR tagging technique can be used for direct in vivo measurement of respiratory lung motion on a regional basis. This technique may lend new insights into the regional pulmonary biomechanics and thus provide valuable information for the deformable registration of lung.« less

Diagnosis by Volatile Organic Compounds in Exhaled Breath from Lung Cancer Patients Using Support Vector Machine Algorithm

PubMed Central

Sakumura, Yuichi; Koyama, Yutaro; Tokutake, Hiroaki; Hida, Toyoaki; Sato, Kazuo; Itoh, Toshio; Akamatsu, Takafumi; Shin, Woosuck

2017-01-01

Monitoring exhaled breath is a very attractive, noninvasive screening technique for early diagnosis of diseases, especially lung cancer. However, the technique provides insufficient accuracy because the exhaled air has many crucial volatile organic compounds (VOCs) at very low concentrations (ppb level). We analyzed the breath exhaled by lung cancer patients and healthy subjects (controls) using gas chromatography/mass spectrometry (GC/MS), and performed a subsequent statistical analysis to diagnose lung cancer based on the combination of multiple lung cancer-related VOCs. We detected 68 VOCs as marker species using GC/MS analysis. We reduced the number of VOCs and used support vector machine (SVM) algorithm to classify the samples. We observed that a combination of five VOCs (CHN, methanol, CH3CN, isoprene, 1-propanol) is sufficient for 89.0% screening accuracy, and hence, it can be used for the design and development of a desktop GC-sensor analysis system for lung cancer. PMID:28165388

Dynamic MRI of Grid-Tagged Hyperpolarized Helium-3 for the Assessment of Lung Motion During Breathing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai Jing; Sheng Ke; Benedict, Stanley H.

2009-09-01

Purpose: To develop a dynamic magnetic resonance imaging (MRI) tagging technique using hyperpolarized helium-3 (HP He-3) to track lung motion. Methods and Materials: An accelerated non-Cartesian k-space trajectory was used to gain acquisition speed, at the cost of introducing image artifacts, providing a viable strategy for obtaining whole-lung coverage with adequate temporal resolution. Multiple-slice two-dimensional dynamic images of the lung were obtained in three healthy subjects after inhaling He-3 gas polarized to 35%-40%. Displacement, strain, and ventilation maps were computed from the observed motion of the grid peaks. Results: Both temporal and spatial variations of pulmonary mechanics were observed inmore » normal subjects, including shear motion between different lobes of the same lung. Conclusion: These initial results suggest that dynamic imaging of grid-tagged hyperpolarized magnetization may potentially be a powerful tool for observing and quantifying pulmonary biomechanics on a regional basis and for assessing, validating, and improving lung deformable image registration algorithms.« less

Diagnosis by Volatile Organic Compounds in Exhaled Breath from Lung Cancer Patients Using Support Vector Machine Algorithm.

PubMed

Sakumura, Yuichi; Koyama, Yutaro; Tokutake, Hiroaki; Hida, Toyoaki; Sato, Kazuo; Itoh, Toshio; Akamatsu, Takafumi; Shin, Woosuck

2017-02-04

Monitoring exhaled breath is a very attractive, noninvasive screening technique for early diagnosis of diseases, especially lung cancer. However, the technique provides insufficient accuracy because the exhaled air has many crucial volatile organic compounds (VOCs) at very low concentrations (ppb level). We analyzed the breath exhaled by lung cancer patients and healthy subjects (controls) using gas chromatography/mass spectrometry (GC/MS), and performed a subsequent statistical analysis to diagnose lung cancer based on the combination of multiple lung cancer-related VOCs. We detected 68 VOCs as marker species using GC/MS analysis. We reduced the number of VOCs and used support vector machine (SVM) algorithm to classify the samples. We observed that a combination of five VOCs (CHN, methanol, CH₃CN, isoprene, 1-propanol) is sufficient for 89.0% screening accuracy, and hence, it can be used for the design and development of a desktop GC-sensor analysis system for lung cancer.

Computational Modeling of Airway and Pulmonary Vascular Structure and Function: Development of a “Lung Physiome”

PubMed Central

Tawhai, M. H.; Clark, A. R.; Donovan, G. M.; Burrowes, K. S.

2011-01-01

Computational models of lung structure and function necessarily span multiple spatial and temporal scales, i.e., dynamic molecular interactions give rise to whole organ function, and the link between these scales cannot be fully understood if only molecular or organ-level function is considered. Here, we review progress in constructing multiscale finite element models of lung structure and function that are aimed at providing a computational framework for bridging the spatial scales from molecular to whole organ. These include structural models of the intact lung, embedded models of the pulmonary airways that couple to model lung tissue, and models of the pulmonary vasculature that account for distinct structural differences at the extra- and intra-acinar levels. Biophysically based functional models for tissue deformation, pulmonary blood flow, and airway bronchoconstriction are also described. The development of these advanced multiscale models has led to a better understanding of complex physiological mechanisms that govern regional lung perfusion and emergent heterogeneity during bronchoconstriction. PMID:22011236

Fine mapping in TERT-CLPTM1L region identified three independent lung cancer susceptibility signals: a large-scale multi-ethnic population study.

PubMed

Li, Zhihua; Fan, Jingyi; Li, Ni; Zhu, Meng; Zhang, Jiahui; Wang, Yuzhuo; Geng, Liguo; Cheng, Yang; Ma, Hongxia; Jin, Guangfu; Dai, Juncheng; Hu, Zhibin; Shen, Hongbing

2018-05-29

Genome-wide association studies (GWAS) and fine mapping studies have identified multiple lung cancer susceptibility variants in TERT-CLPTM1L region. However, it is still unclear about the relationship between these risk variants and the independent lung cancer risk signals in this region. Therefore, we evaluated the independent susceptibility signals for lung cancer and explored the potential functional variants in this region. Sequential conditional analysis was used to detect the independent susceptibility loci based on four lung cancer GWAS datasets with 12,843 lung cases and 12,639 controls. Comprehensively functional annotations were performed for each independent signal. Three independent susceptibility signals were identified in multi-ethnic population. For the first signal, rs2736100 showed the most significant association with lung cancer risk (C > A, OR = 0.82, 95%CI: 0.79-0.85, P = 1.98 × 10 -25 ). Rs36019446 was the top-ranked site (A > G, OR = 0.88, 95%CI: 0.84-0.92, P = 1.74 × 10 -9 ) in the second signal. For the third signal, rs326048 was the leading SNP (A > G, OR = 0.91, 95%CI: 0.87-0.95, P = 1.38 × 10 -5 ). The following subgroup analysis found the same three loci among Asian population. Further, we compared the difference between various subgroup populations. Functional annotations revealed that rs2736100, rs27996 (r 2  = 0.85 with rs36019446) and rs326049 (r 2  = 0.73 with rs326048) could be potential functional variants in these three risk signals, respectively. In conclusion, although multiple variants have been found associated with lung cancer risk in TERT-CLPTM1L region, our findings indicated that there are three independent lung cancer susceptibility signals in this region. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Multiple tuberculous nodules with metachronous changes: a case report

PubMed Central

2013-01-01

Background Spontaneous regression of lesions occurs in non-infectious benign diseases, such as sarcoidosis, as well as in infectious diseases, such as tuberculosis. Lung cancer and malignant lymphoma, on the other hand, rarely follow a similar course. We report a rare case of lung tuberculosis that presented with multiple nodules with metachronous changes in size. Case presentation We describe the case of a 50-year-old immunocompetent Japanese man with pulmonary tuberculosis in the form of multifocal nodules. He came to our hospital because of a chest X-ray abnormality. During the course of observation, some nodules reduced while others enlarged in size. Two years after the first visit, fever and pleural effusion appeared. The sputum examination turned out to be positive for tuberculosis. A course of anti-tubercular agents resolved the pleural effusion and multifocal nodules. Conclusion Differences in the manner of granuloma formation suggest that the local immune response can be different even in the same lung field. PMID:23937966

Surgical lung biopsy to diagnose Behcet's vasculitis with adult respiratory distress syndrome.

PubMed

Vydyula, Ravikanth; Allred, Charles; Huartado, Mariana; Mina, Bushra

2014-10-01

A 34-year-old female presented with fever and abdominal pain. Past medical history includes Crohn's and Behcet's disease. Examination revealed multiple skin ulcerations, oral aphthae, and bilateral coarse rales. She developed respiratory distress with diffuse bilateral alveolar infiltrates on chest radiograph requiring intubation. PaO2/FiO2 ratio was 132. The chest computed tomography revealed extensive nodular and patchy ground-glass opacities. Bronchoalveolar lavage demonstrated a predominance of neutrophils. Methylprednisolone 60 mg every 6 h and broad-spectrum antimicrobials were initiated. No infectious etiologies were identified. Surgical lung biopsy demonstrated diffuse alveolar damage (DAD) mixed with lymphocytic and necrotizing vasculitis with multiple small infarcts and thrombi consistent with Behcet's vasculitis. As she improved, steroids were tapered and discharged home on oral cyclophosphamide. Pulmonary involvement in Behcet's is unusual and commonly manifests as pulmonary artery aneurysms, thrombosis, infarction, and hemorrhage. Lung biopsy findings demonstrating DAD are consistent with the clinical diagnosis of adult respiratory distress syndrome. The additional findings of necrotizing vasculitis and infarcts may have led to DAD.

Anti-Aspergillus Activities of the Respiratory Epithelium in Health and Disease.

PubMed

Bertuzzi, Margherita; Hayes, Gemma E; Icheoku, Uju J; van Rhijn, Norman; Denning, David W; Osherov, Nir; Bignell, Elaine M

2018-01-08

Respiratory epithelia fulfil multiple roles beyond that of gaseous exchange, also acting as primary custodians of lung sterility and inflammatory homeostasis. Inhaled fungal spores pose a continual antigenic, and potentially pathogenic, challenge to lung integrity against which the human respiratory mucosa has developed various tolerance and defence strategies. However, respiratory disease and immune dysfunction frequently render the human lung susceptible to fungal diseases, the most common of which are the aspergilloses, a group of syndromes caused by inhaled spores of Aspergillus fumigatus . Inhaled Aspergillus spores enter into a multiplicity of interactions with respiratory epithelia, the mechanistic bases of which are only just becoming recognized as important drivers of disease, as well as possible therapeutic targets. In this mini-review we examine current understanding of Aspergillus -epithelial interactions and, based upon the very latest developments in the field, we explore two apparently opposing schools of thought which view epithelial uptake of Aspergillus spores as either a curative or disease-exacerbating event.

Historical review of lung counting efficiencies for low energy photon emitters

DOE PAGES

Jeffers, Karen L.; Hickman, David P.

2014-03-01

This publication reviews the measured efficiency and variability over time of a high purity planar germanium in vivo lung count system for multiple photon energies using increasingly thick overlays with the Lawrence Livermore Torso Phantom. Furthermore, the measured variations in efficiency are compared with the current requirement for in vivo bioassay performance as defined by the American National Standards Institute Standard.

Turpentine oil inhalation leading to lung necrosis and empyema in a toddler.

PubMed

Khan, Awais J; Akhtar, Raja P; Faruqui, Zia S

2006-05-01

Household poisons can cause serious damage to the health of children. Turpentine oil, used chiefly as a solvent in paints, varnishes, and waxes; is often placed within easy reach of children during polishing or painting work. It is capable of causing serious toxicity, whether ingested or inhaled. Pulmonary aspiration can lead to lung parenchymal damage and turpentine-associated pneumonia. We report a case of exploratory ingestion and inhalation of turpentine oil in an 18-month-old boy, leading to extensive lung parenchymal damage, formation of multiple abscess cavities, and necrosis treated with decortication and segmental resection.

Pulmonary Actinomycosis Imitating Lung Cancer on (18)F-FDG PET/CT: A Case Report and Literature Review.

PubMed

Qiu, Lin; Lan, Lianjun; Feng, Yue; Huang, Zhanwen; Chen, Yue

2015-01-01

Here we report a case of 41-year-old man with a soft tissue density mass at right upper lung and palpable abscesses at right upper backside and right wrist. (18)F-fluorodeoxyglucose positron emission tomography/computed tomography demonstrated a 7.8 × 5.0 cm mass with soft-tissue density in the upper lobe of the right lung with high metabolic activity. The infiltrative mass extended to adjacent chest wall soft tissue. Final diagnosis of pulmonary actinomycosis with multiple abscesses was made. The patient responded well to antibiotics treatment.

“Pulmonary Effects of Maternal Smoking on the Fetus and Child: Effects on Lung Development, Respiratory Morbidities, and Life Long Lung Health”

PubMed Central

McEvoy, Cindy T.; Spindel, Eliot R.

2016-01-01

Summary Maternal smoking during pregnancy is the largest preventable cause of abnormal in-utero lung development. Despite well known risks, rates of smoking during pregnancy have only slightly decreased over the last ten years, with rates varying from 5-40% worldwide resulting in tens of millions of fetal exposures. Despite multiple approaches to smoking cessation about 50% of smokers will continue to smoke during pregnancy. Maternal genotype plays an important role in the likelihood of continued smoking during pregnancy and the degree to which maternal smoking will affect the fetus. The primary effects of maternal smoking on offspring lung function and health are decreases in forced expiratory flows, decreased passive respiratory compliance, increased hospitalization for respiratory infections, and an increased prevalence of childhood wheeze and asthma. Nicotine appears to be the responsible component of tobacco smoke that affects lung development, and some of the effects of maternal smoking on lung development can be prevented by supplemental vitamin C. Because nicotine is the key agent for affecting lung development, e-cigarette usage during pregnancy is likely to be as dangerous to fetal lung development as is maternal smoking. PMID:27639458

Chemically-induced Mouse Lung Tumors: Applications to ...

EPA Pesticide Factsheets

A state-of-the-science workshop on chemically-induced mouse lung tumors was conducted by U.S. Environmental Protection Agency to better understand the mouse lung tumor data’s role in human health assessments. Three environmental chemicals - naphthalene, styrene, and ethylbenzene were chosen for the analysis due to the commonality of mouse lung tumors in all three chemicals. The goals of the workshop were to: identify the evidence, from multiple scientific disciplines, regarding formation of chemically-induced lung tumors in mice; discuss analysis and interpretation of the evidence; discuss how such evidence informs human health assessments; and identify commonalities, linkages, or differences between the evidence from various disciplines and across the chemicals. Evidence informing the association between occupational exposure to styrene, ethylbenzene, or naphthalene and lung cancer; comparative biology of mouse lung tumors, associated pathologic effects, issues related to tissue and species concordance; mode of action analysis and biological mechanisms including pharmacokinetics and pharmacodynamics; and evidence from cellular, genetic and molecular toxicity was discussed. In summary, although consensus was not sought, the panelists agreed that available mouse lung tumor data should be considered for human health risk evaluation on an individual chemical basis. Key data gaps were identified that would assist in further understanding the mechanism and relevan

CD22 antigen is broadly expressed on lung cancer cells and is a target for antibody-based therapy.

PubMed

Tuscano, Joseph M; Kato, Jason; Pearson, David; Xiong, Chengyi; Newell, Laura; Ma, Yunpeng; Gandara, David R; O'Donnell, Robert T

2012-11-01

Most patients with lung cancer still die from their disease, necessitating additional options to improve treatment. Here, we provide evidence for targeting CD22, a cell adhesion protein known to influence B-cell survival that we found is also widely expressed in lung cancer cells. In characterizing the antitumor activity of an established anti-CD22 monoclonal antibody (mAb), HB22.7, we showed CD22 expression by multiple approaches in various lung cancer subtypes, including 7 of 8 cell lines and a panel of primary patient specimens. HB22.7 displayed in vitro and in vivo cytotoxicity against CD22-positive human lung cancer cells and tumor xenografts. In a model of metastatic lung cancer, HB22.7 inhibited the development of pulmonary metastasis and extended overall survival. The finding that CD22 is expressed on lung cancer cells is significant in revealing a heretofore unknown mechanism of tumorigenesis and metastasis. Our work suggests that anti-CD22 mAbs may be useful for targeted therapy of lung cancer, a malignancy that has few tumor-specific targets. ©2012 AACR.

Increasing physical activity and exercise in lung cancer: reviewing safety, benefits, and application.

PubMed

Bade, Brett C; Thomas, D David; Scott, JoAnn B; Silvestri, Gerard A

2015-06-01

Lung cancer continues to be a difficult disease frequently diagnosed in late stages with a high mortality and symptom burden. In part because of frequent lung comorbidity, even lung cancer survivors often remain symptomatic and functionally limited. Though targeted therapy continues to increase treatment options for advanced-stage disease, symptom burden remains high with few therapeutic options. In the last several decades, exercise and physical activity have arisen as therapeutic options for obstructive lung disease and lung cancer. To date, exercise has been shown to reduce symptoms, increase exercise tolerance, improve quality of life, and potentially reduce length of stay and postoperative complications. Multiple small trials have been performed in perioperative non-small-cell lung cancer patients, although fewer studies are available for patients with advanced-stage disease. Despite the increased interest in this subject over the last few years, a validated exercise regimen has not been established for perioperative or advanced-stage disease. Clinicians underutilize exercise and pulmonary rehabilitation as a therapy, in part because of the lack of evidence-based consensus as to how and when to implement increasing physical activity. This review summarizes the existing evidence on exercise in lung cancer patients.

The role of the ataxia telangiectasia mutated gene in lung cancer: recent advances in research.

PubMed

Xu, Yanling; Gao, Peng; Lv, Xuejiao; Zhang, Lin; Zhang, Jie

2017-09-01

Lung cancer is the leading cause of death due to cancer worldwide. It is estimated that approximately 1.2 million new cases of lung cancer are diagnosed each year. Early detection and treatment are crucial for improvements in both prognosis and quality of life of lung cancer patients. The ataxia telangiectasia mutated (ATM) gene is a cancer-susceptibility gene that encodes a key apical kinase in the DNA damage response pathway. It has recently been shown to play an important role in the development of lung cancer. The main functions of the ATM gene and protein includes participation in cell cycle regulation, and identification and repair of DNA damage. ATM gene mutation can lead to multiple system dysfunctions as well as a concomitant increase in tumor tendency. In recent years, many studies have indicated that single nucleotide polymorphism of the ATM gene is associated with increased incidence of lung cancer. At the same time, the ATM gene and its encoding product ATM protein predicts the response to radiotherapy, chemotherapy, and prognosis of lung cancer, thus suggesting that the ATM gene may be a new potential target for the diagnosis and treatment of lung cancer.

Staging Lung Cancer: Metastasis.

PubMed

Shroff, Girish S; Viswanathan, Chitra; Carter, Brett W; Benveniste, Marcelo F; Truong, Mylene T; Sabloff, Bradley S

2018-05-01

The updated eighth edition of the tumor, node, metastasis (TNM) classification for lung cancer includes revisions to T and M descriptors. In terms of the M descriptor, the classification of intrathoracic metastatic disease as M1a is unchanged from TNM-7. Extrathoracic metastatic disease, which was classified as M1b in TNM-7, is now subdivided into M1b (single metastasis, single organ) and M1c (multiple metastases in one or multiple organs) descriptors. In this article, the rationale for changes in the M descriptors, the utility of preoperative staging with PET/computed tomography, and the treatment options available for patients with oligometastatic disease are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Quantitative consensus of supervised learners for diffuse lung parenchymal HRCT patterns

NASA Astrophysics Data System (ADS)

Raghunath, Sushravya; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Bartholmai, Brian J.; Robb, Richard A.

2013-03-01

Automated lung parenchymal classification usually relies on supervised learning of expert chosen regions representative of the visually differentiable HRCT patterns specific to different pathologies (eg. emphysema, ground glass, honey combing, reticular and normal). Considering the elusiveness of a single most discriminating similarity measure, a plurality of weak learners can be combined to improve the machine learnability. Though a number of quantitative combination strategies exist, their efficacy is data and domain dependent. In this paper, we investigate multiple (N=12) quantitative consensus approaches to combine the clusters obtained with multiple (n=33) probability density-based similarity measures. Our study shows that hypergraph based meta-clustering and probabilistic clustering provides optimal expert-metric agreement.

Convergent evolution of floral signals underlies the success of Neotropical orchids

PubMed Central

Papadopulos, Alexander S. T.; Powell, Martyn P.; Pupulin, Franco; Warner, Jorge; Hawkins, Julie A.; Salamin, Nicolas; Chittka, Lars; Williams, Norris H.; Whitten, W. Mark; Loader, Deniz; Valente, Luis M.; Chase, Mark W.; Savolainen, Vincent

2013-01-01

The great majority of plant species in the tropics require animals to achieve pollination, but the exact role of floral signals in attraction of animal pollinators is often debated. Many plants provide a floral reward to attract a guild of pollinators, and it has been proposed that floral signals of non-rewarding species may converge on those of rewarding species to exploit the relationship of the latter with their pollinators. In the orchid family (Orchidaceae), pollination is almost universally animal-mediated, but a third of species provide no floral reward, which suggests that deceptive pollination mechanisms are prevalent. Here, we examine floral colour and shape convergence in Neotropical plant communities, focusing on certain food-deceptive Oncidiinae orchids (e.g. Trichocentrum ascendens and Oncidium nebulosum) and rewarding species of Malpighiaceae. We show that the species from these two distantly related families are often more similar in floral colour and shape than expected by chance and propose that a system of multifarious floral mimicry—a form of Batesian mimicry that involves multiple models and is more complex than a simple one model–one mimic system—operates in these orchids. The same mimetic pollination system has evolved at least 14 times within the species-rich Oncidiinae throughout the Neotropics. These results help explain the extraordinary diversification of Neotropical orchids and highlight the complexity of plant–animal interactions. PMID:23804617

Convergent evolution of floral signals underlies the success of Neotropical orchids.

PubMed

Papadopulos, Alexander S T; Powell, Martyn P; Pupulin, Franco; Warner, Jorge; Hawkins, Julie A; Salamin, Nicolas; Chittka, Lars; Williams, Norris H; Whitten, W Mark; Loader, Deniz; Valente, Luis M; Chase, Mark W; Savolainen, Vincent

2013-08-22

The great majority of plant species in the tropics require animals to achieve pollination, but the exact role of floral signals in attraction of animal pollinators is often debated. Many plants provide a floral reward to attract a guild of pollinators, and it has been proposed that floral signals of non-rewarding species may converge on those of rewarding species to exploit the relationship of the latter with their pollinators. In the orchid family (Orchidaceae), pollination is almost universally animal-mediated, but a third of species provide no floral reward, which suggests that deceptive pollination mechanisms are prevalent. Here, we examine floral colour and shape convergence in Neotropical plant communities, focusing on certain food-deceptive Oncidiinae orchids (e.g. Trichocentrum ascendens and Oncidium nebulosum) and rewarding species of Malpighiaceae. We show that the species from these two distantly related families are often more similar in floral colour and shape than expected by chance and propose that a system of multifarious floral mimicry--a form of Batesian mimicry that involves multiple models and is more complex than a simple one model-one mimic system--operates in these orchids. The same mimetic pollination system has evolved at least 14 times within the species-rich Oncidiinae throughout the Neotropics. These results help explain the extraordinary diversification of Neotropical orchids and highlight the complexity of plant-animal interactions.

Comparison of Acute Health Effects From Exposures to Diesel and Biodiesel Fuel Emissions

PubMed Central

Mehus, Aaron A.; Reed, Rustin J.; Lee, Vivien S. T.; Littau, Sally R.; Hu, Chengcheng; Lutz, Eric A.

2015-01-01

Objective: To investigate the comparative acute health effects associated with exposures to diesel and 75% biodiesel/25% diesel (B75) blend fuel emissions. Methods: We analyzed multiple health endpoints in 48 healthy adults before and after exposures to diesel and B75 emissions in an underground mine setting—lung function, lung and systemic inflammation, novel biomarkers of exposure, and oxidative stress were assessed. Results: B75 reduced respirable diesel particulate matter by 20%. Lung function declined significantly more after exposure to diesel emissions. Lung inflammatory cells along with sputum and plasma inflammatory mediators increased significantly to similar levels with both exposures. Urinary 8-hydroxydeoxyguanosine, a marker of oxidative stress, was not significantly changed after either exposure. Conclusions: Use of B75 lowered respirable diesel particulate matter exposure and some associated acute health effects, although lung and systemic inflammation were not reduced compared with diesel use. PMID:26147538

The liquid biopsy in lung cancer.

PubMed

Ansari, Junaid; Yun, Jungmi W; Kompelli, Anvesh R; Moufarrej, Youmna E; Alexander, Jonathan S; Herrera, Guillermo A; Shackelford, Rodney E

2016-11-01

The incidence of lung cancer has significantly increased over the last century, largely due to smoking, and remains the most common cause of cancer deaths worldwide. This is often due to lung cancer first presenting at late stages and a lack of curative therapeutic options at these later stages. Delayed diagnoses, inadequate tumor sampling, and lung cancer misdiagnoses are also not uncommon due to the limitations of the tissue biopsy. Our better understanding of the tumor microenvironment and the systemic actions of tumors, combined with the recent advent of the liquid biopsy, may allow molecular diagnostics to be done on circulating tumor markers, particularly circulating tumor DNA. Multiple liquid biopsy molecular methods are presently being examined to determine their efficacy as surrogates to the tumor tissue biopsy. This review will focus on new liquid biopsy technologies and how they may assist in lung cancer detection, diagnosis, and treatment.

Benign metastasizing leiomyomas in the lungs: a case study

PubMed Central

Bruliński, Krzysztof

2016-01-01

Benign metastasizing leiomyoma (BML) is a rare disease that occurs in middle-aged women with a history of uterine myomas. The most common location of BML is the lungs. We report the case of a 44-year-old obese woman (BMI 45.5) who underwent surgery to remove uterine leiomyomata and then continued to take a drug containing the hormone estradiol for a period of 15 years. Computed tomography chest examinations revealed multiple size nodules of varying size in both lungs. Videothoracoscopy and right thoracotomy was performed, and a few nodules were enucleated from each lobe of the right lung. Postoperative histopathological examination revealed benign metastasizing leiomyoma staining positive for estrogen and progesterone receptors (ER+, PR+). Because of the hormonally dependent cell proliferation, the previously used hormonal drug was discontinued. Treatment with a gonadotropin-releasing hormone analog was included, yielding radiological stabilization of the lung lesions. PMID:27212984

Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach

PubMed Central

Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita

2016-01-01

Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers. PMID:27683630

Comparison of Acute Health Effects From Exposures to Diesel and Biodiesel Fuel Emissions.

PubMed

Mehus, Aaron A; Reed, Rustin J; Lee, Vivien S T; Littau, Sally R; Hu, Chengcheng; Lutz, Eric A; Burgess, Jefferey L

2015-07-01

To investigate the comparative acute health effects associated with exposures to diesel and 75% biodiesel/25% diesel (B75) blend fuel emissions. We analyzed multiple health endpoints in 48 healthy adults before and after exposures to diesel and B75 emissions in an underground mine setting-lung function, lung and systemic inflammation, novel biomarkers of exposure, and oxidative stress were assessed. B75 reduced respirable diesel particulate matter by 20%. Lung function declined significantly more after exposure to diesel emissions. Lung inflammatory cells along with sputum and plasma inflammatory mediators increased significantly to similar levels with both exposures. Urinary 8-hydroxydeoxyguanosine, a marker of oxidative stress, was not significantly changed after either exposure. Use of B75 lowered respirable diesel particulate matter exposure and some associated acute health effects, although lung and systemic inflammation were not reduced compared with diesel use.

Type XVIII collagen degradation products in acute lung injury

PubMed Central

Perkins, Gavin D; Nathani, Nazim; Richter, Alex G; Park, Daniel; Shyamsundar, Murali; Heljasvaara, Ritva; Pihlajaniemi, Taina; Manji, Mav; Tunnicliffe, W; McAuley, Danny; Gao, Fang; Thickett, David R

2009-01-01

Introduction In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge. Methods Endostatin was measured by ELISA and western blotting. Results Endostatin is elevated within the plasma and bronchoalveolar lavage fluid of patients with acute lung injury. Lavage endostatin reflected the degree of alveolar neutrophilia and the extent of the loss of protein selectivity of the alveolar-capillary barrier. Plasma levels of endostatin correlated with the severity of physiological derangement. Western blotting confirmed elevated type XVIII collagen precursor levels in the plasma and lavage and multiple endostatin-like fragments in the lavage of patients. One lung ventilation and LPS challenge rapidly induce increases in lung endostatin levels. Conclusions Endostatin may adversely affect both alveolar barrier endothelial and epithelial cells, so its presence within both the circulation and the lung may have a pathophysiological role in acute lung injury that warrants further evaluation. PMID:19358707

miR-34a Inhibits Lung Fibrosis by Inducing Lung Fibroblast Senescence.

PubMed

Cui, Huachun; Ge, Jing; Xie, Na; Banerjee, Sami; Zhou, Yong; Antony, Veena B; Thannickal, Victor J; Liu, Gang

2017-02-01

Cellular senescence has been implicated in diverse pathologies. However, there is conflicting evidence regarding the role of this process in tissue fibrosis. Although dysregulation of microRNAs is a key mechanism in the pathogenesis of lung fibrosis, it is unclear whether microRNAs function by regulating cellular senescence in the disease. In this study, we found that miR-34a demonstrated greater expression in the lungs of patients with idiopathic pulmonary fibrosis and in mice with experimental pulmonary fibrosis, with its primary localization in lung fibroblasts. More importantly, miR-34a was up-regulated significantly in both human and mouse lung myofibroblasts. We found that mice with miR-34a ablation developed more severe pulmonary fibrosis than did wild-type animals after fibrotic lung injury. Mechanistically, we found that miR-34a induced a senescent phenotype in lung fibroblasts because this microRNA increased senescence-associated β-galactosidase activity, enhanced expression of senescence markers, and decreased cell proliferative capacities. Consistently, we found that primary lung fibroblasts from fibrotic lungs of miR-34a-deficient mice had a diminished senescent phenotype and enhanced resistance to apoptosis as compared with those from wild-type animals. We also identified multiple miR-34a targets that likely mediated its activities in inducing senescence in lung fibroblasts. In conclusion, our data suggest that miR-34a functions through a negative feedback mechanism to restrain fibrotic response in the lungs by promoting senescence of pulmonary fibroblasts.

RECOMBINANT FACTOR XIII DIMINISHES MULTIPLE ORGAN DYSFUNCTION IN RATS CAUSED BY GUT ISCHEMIA-REPERFUSION INJURY

PubMed Central

Zaets, Sergey B.; Xu, Da-Zhong; Lu, Qi; Feketova, Eleonora; Berezina, Tamara L.; Gruda, Maryann; Malinina, Inga V.; Deitch, Edwin A.; Olsen, Eva H. N.

2010-01-01

Plasma factor XIII (FXIII) is responsible for stabilization of fibrin clot at the final stage of blood coagulation. Because FXIII has also been shown to modulate inflammation and endothelial permeability, we hypothesized that FXIII diminishes multiple organ dysfunction caused by gut I/R injury. A model of superior mesenteric artery occlusion (SMAO) was used to induce gut I/R injury. Rats were subjected to 45-min SMAO or sham SMAO and treated with recombinant human FXIII A2 subunit (rFXIII) or placebo at the beginning of the reperfusion period. Lung permeability, lung and gut myeloperoxidase activity, gut histology, neutrophil respiratory burst, and microvascular blood flow in the liver and muscles were measured after a 3-h reperfusion period. The effect of activated rFXIII on transendothelial resistance of human umbilical vein endothelial cells was tested in vitro. Superior mesenteric artery occlusion–induced lung permeability as well as lung and gut myeloperoxidase activity was significantly lower in rFXIII-treated versus untreated animals. Similarly, rFXIII-treated rats had lower neutrophil respiratory burst activity and ileal mucosal injury. Rats treated with rFXIII also had higher liver microvascular blood flow compared with the placebo group. Superior mesenteric artery occlusion did not cause FXIII consumption during the study period. In vitro, activated rFXIII caused a dose-dependent increase in human umbilical vein endothelial cell monolayer resistance to thrombin-induced injury. Thus, administration of rFXIII diminishes SMAO-induced multiple organ dysfunction in rats, presumably by preservation of endothelial barrier function and the limitation of polymorphonuclear leukocyte activation. PMID:18948851

Lung Cancer: One Disease or Many.

PubMed

O'Brien, Timothy D; Jia, Peilin; Aldrich, Melinda C; Zhao, Zhongming

2018-06-05

Lung cancer is classified as a single entity comprised of multiple histological subtypes. But how similar are these subtypes on a genetic level? This paper aims to address this question through a concise overview of germline and somatic differences between small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma. We reveal the weak overlap found between these 3 lung cancer subtypes using published data from one of the largest germline genetic studies on lung cancer to date and somatic mutation data from Catalogue of Somatic Mutations in Cancer (COSMIC). These data indicate that these 3 subtypes share very little with each other at the genetic level. At the germline SNP level, only 24 independent SNPs from 2 chromosomes were shared across all 3 subtypes. We also demonstrate that only 30 unique cancer-specific mutations overlap the 3 subtypes from COSMIC, and that this is fewer than overlapping mutations chosen at random. Finally, we show that only 3 somatic mutational signatures are shared between these 3 subtypes. This paper highlights that these 3 lung cancer subtypes may be distinct diseases at the genetic level. In the era of precision medicine, we feel that these genomic differences will be of utmost importance in the choice of lung cancer therapy in the future. © 2018 S. Karger AG, Basel.

A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion.

PubMed

Min, Yugang; Santhanam, Anand; Neelakkantan, Harini; Ruddy, Bari H; Meeks, Sanford L; Kupelian, Patrick A

2010-09-07

In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

A case of septic pulmonary embolism associated with renal abscess mimicking pulmonary metastases of renal malignancy.

PubMed

Jung, Jo Sung; Lee, Sang Mi; Kim, Han Jo; Jang, Si-Hyong; Lee, Jeong Won

2014-05-01

We report the case of a 46-year-old woman with acute febrile symptom who had multiple pulmonary nodules and a renal mass. She underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to find a hidden malignancy and the cause of her fever. FDG PET/CT images demonstrated a renal mass and multiple lung nodules with intense FDG uptake, which was suspicious of a renal malignancy with multiple pulmonary metastatic lesions. CT-guided biopsies of the pulmonary and renal lesions only showed chronic inflammatory infiltrates without evidence of malignancy. She was diagnosed with septic pulmonary embolism from a renal abscess. One month after antibiotic treatment, the follow-up chest and abdomen CT showed improvement of the lung and renal lesions. This is the first case demonstrating the FDG PET/CT finding of septic pulmonary embolism associated with renal abscess in the published literature.

Bovine viral diarrhea virus 1b fetal infection with extensive hemorrhages

USDA-ARS?s Scientific Manuscript database

Bovine viral diarrhea virus (BVDV) subtype 1b was isolated from tissues of a term bovine fetus with hemorrhages in multiple tissues. At autopsy, multiple petechial hemorrhages were observed at gross examination throughout the body and placenta. Lung, kidney, thymus, and liver fresh tissues were exam...

Oxidative Lung Injury in Virus-Induced Wheezing

DTIC Science & Technology

2013-05-01

Yang YC, Barik S. Transcriptional induction of multiple cytokines by human respiratory syncytial virus requires activation of NF-kB and is inhibited by...Dis J 14: 919, 1995. 27. Bitko V, Velazquez A, Yank L, Yang Y-C, and Barik S. Transcriptional induction of multiple cytokines by human respiratory

Chemical ecology of endophytic fungi: origins of secondary metabolites.

PubMed

Kusari, Souvik; Hertweck, Christian; Spiteller, Michael

2012-07-27

Endophytes constitute a remarkably multifarious group of microorganisms ubiquitous in plants and maintain an imperceptible association with their hosts for at least a part of their life cycle. Their enormous biological diversity coupled with their capability to biosynthesize bioactive secondary metabolites has provided the impetus for a number of investigations on endophytes. Here, we highlight the possible current and future strategies of understanding the chemical communication of endophytic fungi with other endophytes (fungi and bacteria) and with their host plants, which might not only allow the discovery and sustainable production of desirable natural products but also other mostly overlooked bioactive secondary metabolites. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Urbanization in tropical countries].

PubMed

Amat-Roze, J M

1983-01-01

Rural populations are still the most numerous in tropical countries. But we can witness an unprecedent process of urbanization. However the dynamics of the phenomenon differs greatly in different countries and in different towns. As a matter of fact, the greatest overcrowded metropolis attract the greatest part of the migrants from rural areas; the attractive factors are multifarious and universal. This not easily controllable trend seems to be irreversible. The migrant farmers will generally find a job within the informed economic sector. The zones of spontaneous and precarious settlement are often their first environmental living conditions. Some of these unhealthy dwelling areas are subject to development plans; some of them being extremely well designed.

Vehicular headways on signalized intersections: theory, models, and reality

NASA Astrophysics Data System (ADS)

Krbálek, Milan; Šleis, Jiří

2015-01-01

We discuss statistical properties of vehicular headways measured on signalized crossroads. On the basis of mathematical approaches, we formulate theoretical and empirically inspired criteria for the acceptability of theoretical headway distributions. Sequentially, the multifarious families of statistical distributions (commonly used to fit real-road headway statistics) are confronted with these criteria, and with original empirical time clearances gauged among neighboring vehicles leaving signal-controlled crossroads after a green signal appears. Using three different numerical schemes, we demonstrate that an arrangement of vehicles on an intersection is a consequence of the general stochastic nature of queueing systems, rather than a consequence of traffic rules, driver estimation processes, or decision-making procedures.

Magnetic carbon nanotubes: preparation, physical properties, and applications in biomedicine.

PubMed

Samadishadlou, Mehrdad; Farshbaf, Masoud; Annabi, Nasim; Kavetskyy, Taras; Khalilov, Rovshan; Saghfi, Siamak; Akbarzadeh, Abolfazl; Mousavi, Sepideh

2017-10-18

Magnetic carbon nanotubes (MCNTs) have been widely studied for their potential applications in medicine, diagnosis, cell biology, analytical chemistry, and environmental technology. Introduction of MCNTs paved the way for the emergence of new approaches in nanobiotechnology and biomedicine as a result of their multifarious properties embedded within either the carbon nanotubes (CNTs) or magnetic parts. Numerous preparation techniques exists for functionalizing CNTs with magnetic nanoparticles, and these versatile strategies lay the ground for the generation of novel and versatile systems which are applicable to many industries and biological areas. Here, we review and discuss the recent papers dealing with MCNTs and their application in biomedical and industrial fields.

Causal cognition in human and nonhuman animals: a comparative, critical review.

PubMed

Penn, Derek C; Povinelli, Daniel J

2007-01-01

In this article, we review some of the most provocative experimental results to have emerged from comparative labs in the past few years, starting with research focusing on contingency learning and finishing with experiments exploring nonhuman animals' understanding of causal-logical relations. Although the theoretical explanation for these results is often inchoate, a clear pattern nevertheless emerges. The comparative evidence does not fit comfortably into either the traditional associationist or inferential alternatives that have dominated comparative debate for many decades now. Indeed, the similarities and differences between human and nonhuman causal cognition seem to be much more multifarious than these dichotomous alternatives allow.

MRI and CT lung biomarkers: Towards an in vivo understanding of lung biomechanics.

PubMed

Young, Heather M; Eddy, Rachel L; Parraga, Grace

2017-09-29

The biomechanical properties of the lung are necessarily dependent on its structure and function, both of which are complex and change over time and space. This makes in vivo evaluation of lung biomechanics and a deep understanding of lung biomarkers, very challenging. In patients and animal models of lung disease, in vivo evaluations of lung structure and function are typically made at the mouth and include spirometry, multiple-breath gas washout tests and the forced oscillation technique. These techniques, and the biomarkers they provide, incorporate the properties of the whole organ system including the parenchyma, large and small airways, mouth, diaphragm and intercostal muscles. Unfortunately, these well-established measurements mask regional differences, limiting their ability to probe the lung's gross and micro-biomechanical properties which vary widely throughout the organ and its subcompartments. Pulmonary imaging has the advantage in providing regional, non-invasive measurements of healthy and diseased lung, in vivo. Here we summarize well-established and emerging lung imaging tools and biomarkers and how they may be used to generate lung biomechanical measurements. We review well-established and emerging lung anatomical, microstructural and functional imaging biomarkers generated using synchrotron x-ray tomographic-microscopy (SRXTM), micro-x-ray computed-tomography (micro-CT), clinical CT as well as magnetic resonance imaging (MRI). Pulmonary imaging provides measurements of lung structure, function and biomechanics with high spatial and temporal resolution. Imaging biomarkers that reflect the biomechanical properties of the lung are now being validated to provide a deeper understanding of the lung that cannot be achieved using measurements made at the mouth. Copyright © 2017 Elsevier Ltd. All rights reserved.

A hybrid approach for fusing 4D-MRI temporal information with 3D-CT for the study of lung and lung tumor motion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Y. X.; Van Reeth, E.; Poh, C. L., E-mail: clpoh@ntu.edu.sg

2015-08-15

Purpose: Accurate visualization of lung motion is important in many clinical applications, such as radiotherapy of lung cancer. Advancement in imaging modalities [e.g., computed tomography (CT) and MRI] has allowed dynamic imaging of lung and lung tumor motion. However, each imaging modality has its advantages and disadvantages. The study presented in this paper aims at generating synthetic 4D-CT dataset for lung cancer patients by combining both continuous three-dimensional (3D) motion captured by 4D-MRI and the high spatial resolution captured by CT using the authors’ proposed approach. Methods: A novel hybrid approach based on deformable image registration (DIR) and finite elementmore » method simulation was developed to fuse a static 3D-CT volume (acquired under breath-hold) and the 3D motion information extracted from 4D-MRI dataset, creating a synthetic 4D-CT dataset. Results: The study focuses on imaging of lung and lung tumor. Comparing the synthetic 4D-CT dataset with the acquired 4D-CT dataset of six lung cancer patients based on 420 landmarks, accurate results (average error <2 mm) were achieved using the authors’ proposed approach. Their hybrid approach achieved a 40% error reduction (based on landmarks assessment) over using only DIR techniques. Conclusions: The synthetic 4D-CT dataset generated has high spatial resolution, has excellent lung details, and is able to show movement of lung and lung tumor over multiple breathing cycles.« less

Pleural plaques and their effect on lung function in Libby vermiculite miners.

PubMed

Clark, Kathleen A; Flynn, J Jay; Goodman, Julie E; Zu, Ke; Karmaus, Wilfried J J; Mohr, Lawrence C

2014-09-01

Multiple studies have investigated the relationship between asbestos-related pleural plaques (PPs) and lung function, with disparate and inconsistent results. Most use chest radiographs to identify PPs and simple spirometry to measure lung function. High-resolution CT (HRCT) scanning improves the accuracy of PP identification. Complete pulmonary function tests (PFTs), including spirometry, lung volumes, and diffusing capacity of the lung for carbon monoxide, provide a more definitive assessment of lung function. The goal of this study was to determine, using HRCT scanning and complete PFTs, the effect of PPs on lung function in Libby vermiculite miners. The results of HRCT scanning and complete PFTs performed between January 2000 and August 2012 were obtained from the medical records of 166 Libby vermiculite miners. Multivariate regression analyses with Tukey multivariate adjustment were used to assess statistical associations between the presence of PPs and lung function. Adjustments were made for age, BMI, smoking history, duration of employment, and years since last occupational asbestos exposure. Nearly 90% of miners (n = 149) had evidence of PPs on HRCT scan. No significant differences in spirometry results, lung volumes, or diffusing capacity of the lung for carbon monoxide were found between miners with PPs alone and miners with normal HRCT scans. Miners with both interstitial fibrosis and the presence of PPs had a significantly decreased total lung capacity in comparison with miners with normal HRCT scans (P = .02). Age, cumulative smoking history, and BMI were significant covariates that contributed to abnormal lung function. Asbestos-related PPs alone have no significant effect on lung function in Libby vermiculite miners.

Cancer Risk Questionnaire

MedlinePlus

... Esophageal Gallbladder Head/Neck Kidney Leukemia Liver Lung Lymphoma Multiple Myeloma Ovarian Pancreatic Prostate Sarcoma/Rare Tumors Skin Stomach Testicular Uterine The Siteman Approach Medical Therapy Radiation ...

Irreparable complex DNA double-strand breaks induce chromosome breakage in organotypic three-dimensional human lung epithelial cell culture

PubMed Central

Asaithamby, Aroumougame; Hu, Burong; Delgado, Oliver; Ding, Liang-Hao; Story, Michael D.; Minna, John D.; Shay, Jerry W.; Chen, David J.

2011-01-01

DNA damage and consequent mutations initiate the multistep carcinogenic process. Differentiated cells have a reduced capacity to repair DNA lesions, but the biological impact of unrepaired DNA lesions in differentiated lung epithelial cells is unclear. Here, we used a novel organotypic human lung three-dimensional (3D) model to investigate the biological significance of unrepaired DNA lesions in differentiated lung epithelial cells. We showed, consistent with existing notions that the kinetics of loss of simple double-strand breaks (DSBs) were significantly reduced in organotypic 3D culture compared to kinetics of repair in two-dimensional (2D) culture. Strikingly, we found that, unlike simple DSBs, a majority of complex DNA lesions were irreparable in organotypic 3D culture. Levels of expression of multiple DNA damage repair pathway genes were significantly reduced in the organotypic 3D culture compared with those in 2D culture providing molecular evidence for the defective DNA damage repair in organotypic culture. Further, when differentiated cells with unrepaired DNA lesions re-entered the cell cycle, they manifested a spectrum of gross-chromosomal aberrations in mitosis. Our data suggest that downregulation of multiple DNA repair pathway genes in differentiated cells renders them vulnerable to DSBs, promoting genome instability that may lead to carcinogenesis. PMID:21421565

Management of EGFR-mutated non-small-cell lung cancer: practical implications from a clinical and pathology perspective

PubMed Central

Cabanero, M.; Sangha, R.; Sheffield, B.S.; Sukhai, M.; Pakkal, M.; Kamel-Reid, S.; Karsan, A.; Ionescu, D.; Juergens, R.A.; Butts, C.; Tsao, M.S.

2017-01-01

Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have evolved from being histologically described to molecularly defined. Management of lung adenocarcinomas now generally requires multiple molecular tests at baseline to define the optimal treatment strategy. More recently, second biopsies performed at progression in patients treated with tyrosine kinase inhibitors (tkis) have further defined the continued use of molecularly targeted therapy. In the present article, we focus on one molecular subtype: EGFR-mutated nsclc. For that patient population, multiple lines of tki therapy are now available either clinically or in clinical trials. Each line of treatment is guided by the specific mutations (for example, L858R, T790M, C797S) identified in EGFR. We first describe the various mechanisms of acquired resistance to EGFR tki treatment. We then focus on strategies that clinicians and pathologists can both use during tissue acquisition and handling to optimize patient results. We also discuss future directions for the molecular characterization of lung cancers with driver mutations, including liquid biopsies. Finally, we provide an algorithm to guide treating physicians managing patients with EGFR-mutated nsclc. The same framework can also be applied to other molecularly defined nsclc subgroups as resistance patterns are elucidated and additional lines of treatment are developed. PMID:28490925

Lung volumes predict survival in patients with chronic lung allograft dysfunction.

PubMed

Kneidinger, Nikolaus; Milger, Katrin; Janitza, Silke; Ceelen, Felix; Leuschner, Gabriela; Dinkel, Julien; Königshoff, Melanie; Weig, Thomas; Schramm, René; Winter, Hauke; Behr, Jürgen; Neurohr, Claus

2017-04-01

Identification of disease phenotypes might improve the understanding of patients with chronic lung allograft dysfunction (CLAD). The aim of the study was to assess the impact of pulmonary restriction and air trapping by lung volume measurements at the onset of CLAD.A total of 396 bilateral lung transplant recipients were analysed. At onset, CLAD was further categorised based on plethysmography. A restrictive CLAD (R-CLAD) was defined as a loss of total lung capacity from baseline. CLAD with air trapping (AT-CLAD) was defined as an increased ratio of residual volume to total lung capacity. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n=95).Of 301 lung transplant recipients, 94 (31.2%) developed CLAD. Patients with R-CLAD (n=20) and AT-CLAD (n=21), respectively, had a significantly worse survival (p<0.001) than patients with non-R/AT-CLAD. Both R-CLAD and AT-CLAD were associated with increased mortality when controlling for multiple confounding variables (hazard ratio (HR) 3.57, 95% CI 1.39-9.18; p=0.008; and HR 2.65, 95% CI 1.05-6.68; p=0.039). Furthermore, measurement of lung volumes was useful to identify patients with combined phenotypes.Measurement of lung volumes in the long-term follow-up of lung transplant recipients allows the identification of patients who are at risk for worse outcome and warrant special consideration. Copyright ©ERS 2017.

Alveolar Edema Fluid Clearance and Acute Lung Injury

PubMed Central

Berthiaume, Yves; Matthay, Michael A.

2009-01-01

Although lung-protective ventilation strategies have substantially reduced mortality of acute lung injury patients there is still a need for new therapies that can further decrease mortality in patients with acute lung injury. Studies of epithelial ion and fluid transport across the distal pulmonary epithelia have provided important new concepts regarding potential new therapies for acute lung injury. Overall, there is convincing evidence that the alveolar epithelium is not only a tight epithelial barrier that resists the movement of edema fluid into the alveoli, but it is also actively involved in the transport of ions and solutes, a process that is essential for edema fluid clearance and the resolution of acute lung injury. The objective of this article is to consider some areas of recent progress in the field of alveolar fluid transport under normal and pathologic conditions. Vectorial ion transport across the alveolar and distal airway epithelia is the primary determinant of alveolar fluid clearance. The general paradigm is that active Na+ and Cl− transport drives net alveolar fluid clearance, as demonstrated in several different species, including the human lung. Although these transport processes can be impaired in severe lung injury, multiple experimental studies suggest that upregulation of Na+ and Cl− transport might be an effective therapy in acute lung injury. We will review mechanisms involved in pharmacological modulation of ion transport in lung injury with a special focus on the use of β-adrenergic agonists which has generated considerable interest and is a promising therapy for clinical acute lung injury. PMID:17604701

Epidermal growth factor receptor expression in radiation-induced dog lung tumors by immunocytochemical localization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leung, F.L.; Park, J.F.; Dagle, G.E.

1993-06-01

In studies to determine the role of growth factors in radiation-induced lung cancer, epidermal growth factor (EGFR) expression was examined by immunocytochemistry in 51 lung tumors from beagle dogs exposed to inhaled plutonium; 21 of 51 (41%) tumors were positive for EGFR. The traction of tumors positive for EGFR and the histological type of EGFR-positive tumors in the plutonium-exposed dogs were not different from spontaneous dog lung tumors, In which 36% were positive for EGFR. EGFR involvement in Pu-induced lung tumors appeared to be similar to that in spontaneous lung tumors. However, EGFR-positive staining was observed in only 1 ofmore » 16 tumors at the three lowest Pu exposure levels, compared to 20 of 35 tumors staining positive at the two highest Pu exposure levels. The results in dogs were in good agreement with the expression of EGFR reported in human non-small cell carcinoma of the lung, suggesting that Pu-induced lung tumors in the dog may be a suitable animal model to investigate the role of EGFR expression in lung carcinogenesis. In humans, EGFR expression in lung tumors has been primarily related to histological tumor types. In individual dogs with multiple primary lung tumors, the tumors were either all EGFR positive or EGFR negative, suggesting that EGFR expression may be related to the response of the individual dog as well as to the histological type of tumor.« less

[Survey and analysis of awareness of lung cancer prevention and control in a LDCT lung cancer screening project in Tianjin Dagang Oilfield of China].

PubMed

Ren, Guanhua; Ye, Jianfei; Fan, Yaguang; Wang, Jing; Sun, Zhijuan; Jia, Hui; Du, Xinxin; Hou, Chaohua; Wang, Ying; Zhao, Yongcheng; Zhou, Qinghua

2014-02-01

It has been proven that increase of the awareness level of lung cancer prevention and control could enhance participation of lung cancer screening of lung cancer high risk group. The aim of this study is to investigate the awareness level of lung cancer prevention and control and the effect of individual characteristics on lung cancer awareness, and to provide evidence for comprehensive lung cancer prevention in high risk areas of lung cancer. Staffs of Tianjin Dagang Oil Field who participate low dose CT (LDCT) lung cancer screening by cluster sampling or according to voluntary principle were surveyed, data of lung cancer awareness were collected by questionnaire. A total of 1,633 valid questionnaires were collected. The average age of respondents was 60.08±6.58. Most participants were males (82.2%) while female only accounted for 17.8%. The proportions of awareness about lung cancer in China, risk factors, screening methods and the knowledge of health examination were 64.5%, 77.1%, 43.7%, 49.6% respectively. Result of multiple logistic regression analysis showed that education level, smoking (pack-year), age, prior tuberculosis were the influencing factors of lung cancer awareness with adjusted Ors for education and age level as of 0.567 (95%CI: 0.439-0.733) and 1.373 (95%CI: 1.084-1.739) respectively. 80.3% of the participants can accept health examination once a year, while the ability to pay the medical expenses was not high. The influencing factors of health examination willingness were gender, age, income, the knowledge of lung cancer. Education level and smoking affect the awareness of lung cancer prevention and control, health education for lung cancer should be conducted especially in population with low education level. Comprehensive lung cancer control in high risk areas should combined lung cancer screening, tobacco control and health education.

Kidney Cancer Risk Questionnaire

MedlinePlus

... Esophageal Gallbladder Head/Neck Kidney Leukemia Liver Lung Lymphoma Multiple Myeloma Ovarian Pancreatic Prostate Sarcoma/Rare Tumors Skin Stomach Testicular Uterine The Siteman Approach Medical Therapy Radiation ...

Your Cervical Cancer Risk

MedlinePlus

... Esophageal Gallbladder Head/Neck Kidney Leukemia Liver Lung Lymphoma Multiple Myeloma Ovarian Pancreatic Prostate Sarcoma/Rare Tumors Skin Stomach Testicular Uterine The Siteman Approach Medical Therapy Radiation ...

Cryptogenic Organizing Pneumonia With Lung Nodules Secondary to Pulmonary Manifestation of Crohn Disease.

PubMed

Zaman, Taufiq; Watson, Joseph; Zaman, Mohammad

2017-01-01

Crohn disease is an immune-mediated inflammatory condition with gastrointestinal and extraintestinal manifestations in patients. Pulmonary involvement of Crohn disease is one manifestation. There have been case reports which have shown Crohn disease and lung nodules which were noted to be histopathological as cryptogenic organizing pneumonia (COP). In our case, a 22-year-old woman with Crohn disease was seen with complaints of chest pain and cough. Computed tomographic scan of chest showed multiple bilateral lung nodules, for which biopsy was done, which showed COP. The case study is followed by a deeper discussion of COP and the extraintestinal manifestation seen in inflammatory bowel disease.

Lung Metastases from Bile Duct Adenocarcinoma Mimicking Chronic Airway Infection and Causing Diagnostic Difficulty.

PubMed

Sato, Mitsuo; Okachi, Shotaro; Fukihara, Jun; Shimoyama, Yoshie; Wakahara, Keiko; Sakakibara, Toshihiro; Hase, Tetsunari; Onishi, Yasuharu; Ogura, Yasuhiro; Maeda, Osamu; Hasegawa, Yoshinori

2018-05-15

We herein report a case of lung metastases with unusual radiological appearances that mimicked those of chronic airway infection, causing diagnostic difficulty. A 60-year-old woman who underwent liver transplantation from a living donor was incidentally diagnosed with bile duct adenocarcinoma after a histopathological analysis of her explanted liver. Six months later, chest computed tomography (CT) revealed bilateral bronchogenic dissemination that had gradually worsened, suggesting chronic airway infection. A biopsy with bronchoscopy from a mass lesion beyond a segmental bronchus revealed adenocarcinoma identical to that of her bile duct adenocarcinoma, leading to the diagnosis of multiple lung metastases from bile duct adenocarcinoma.

Lung Metastases from Bile Duct Adenocarcinoma Mimicking Chronic Airway Infection and Causing Diagnostic Difficulty

PubMed Central

Sato, Mitsuo; Okachi, Shotaro; Fukihara, Jun; Shimoyama, Yoshie; Wakahara, Keiko; Sakakibara, Toshihiro; Hase, Tetsunari; Onishi, Yasuharu; Ogura, Yasuhiro; Maeda, Osamu; Hasegawa, Yoshinori

2017-01-01

We herein report a case of lung metastases with unusual radiological appearances that mimicked those of chronic airway infection, causing diagnostic difficulty. A 60-year-old woman who underwent liver transplantation from a living donor was incidentally diagnosed with bile duct adenocarcinoma after a histopathological analysis of her explanted liver. Six months later, chest computed tomography (CT) revealed bilateral bronchogenic dissemination that had gradually worsened, suggesting chronic airway infection. A biopsy with bronchoscopy from a mass lesion beyond a segmental bronchus revealed adenocarcinoma identical to that of her bile duct adenocarcinoma, leading to the diagnosis of multiple lung metastases from bile duct adenocarcinoma. PMID:29279503

Pulmonary fibrosis in a carpenter with long-lasting exposure to fiberglass.

PubMed

Takahashi, T; Munakata, M; Takekawa, H; Homma, Y; Kawakami, Y

1996-11-01

A 56-year-old male carpenter had a history of glass fiber inhalation for 41 years without any protective device. His chest radiograph showed small nodular opacities in lower lung fields and multiple cystic lesions and low attenuation areas in upper lung fields. Light and polarizing microscopic examinations of his transbronchial lung biopsy specimen revealed mild interstitial fibrosis and mononuclear cell infiltration in alveolar walls without birefringent substances. However, widespread depositions of small glass fibers (< 2.5 microns in length and 0.3 micron in diameter) were detected by analytical electron microscopy, which suggested their possible contribution to the development of his pulmonary fibrosis.

Sarcoidosis with Pancreatic Mass, Endobronchial Nodules, and Miliary Opacities in the Lung.

PubMed

Matsuura, Shun; Mochizuka, Yasutaka; Oishi, Kyohei; Miyashita, Koichi; Naoi, Hyogo; Mochizuki, Eisuke; Mikura, Shinichiro; Tsukui, Masaru; Koshimizu, Naoki; Ohata, Akihiko; Suda, Takahumi

2017-11-15

Sarcoidosis affects multiple organs and rarely has unusual manifestations. A 78-year-old woman was referred to our hospital for coughing symptoms. A chest computed tomography (CT) scan revealed bilateral diffuse miliary patterns and right pleural effusion. Bronchoscopy showed multiple nodules in the carina and the bronchus intermedius. A CT scan of her abdomen revealed hypovascular lesions involving the pancreatic head and body. A transbronchial lung biopsy, bronchial mucosal biopsy, and endoscopic ultrasound-guided fine-needle aspiration of the pancreatic mass demonstrated non-caseating granulomas. We diagnosed the patient with sarcoidosis. She received no treatment for sarcoidosis and has been followed up for one year, during which no pulmonary disease progression had been observed and the pancreatic masses partially regressed.

Astilbin alleviates sepsis-induced acute lung injury by inhibiting the expression of macrophage inhibitory factor in rats.

PubMed

Zhang, Hong-Bo; Sun, Li-Chao; Zhi, Li-da; Wen, Qian-Kuan; Qi, Zhi-Wei; Yan, Sheng-Tao; Li, Wen; Zhang, Guo-Qiang

2017-10-01

Sepsis is a systemic inflammatory response syndrome caused by severe infections. Astilbin is a dihydroflavonol derivative found in many medicinal and food plants with multiple pharmacological functions. To investigate the effects of astilbin on sepsis-induced acute lung injury (ALI), cecal ligation and puncture was performed on rats to establish a sepsis-induced ALI model; these rats were then treated with astilbin at different concentrations. Lung injury scores, including lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration were determined to evaluate the effects of astilbin on sepsis-induced ALI. We found that astilbin treatment significantly attenuates sepsis-induced lung injury and improves survival rate, lung injury scores, lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration. Astilbin treatment also dramatically decreased the production of inflammatory cytokines and chemokines in bronchoalveolar lavage fluid. Further, astilbin treatment inhibited the expression and production of macrophage inhibitory factor (MIF), which inhibits the inflammatory response. Collectively, these data suggest that astilbin has a protective effect against sepsis-induced ALI by inhibiting MIF-mediated inflammatory responses. This study provides a molecular basis for astilbin as a new medical treatment for sepsis-induced ALI.

ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion

PubMed Central

Long, Weiwen; Foulds, Charles E.; Qin, Jun; Liu, Jian; Ding, Chen; Lonard, David M.; Solis, Luisa M.; Wistuba, Ignacio I.; Qin, Jun; Tsai, Sophia Y.; Tsai, Ming-Jer; O’Malley, Bert W.

2012-01-01

In contrast to the well-studied classic MAPKs, such as ERK1/2, little is known concerning the regulation and substrates of the atypical MAPK ERK3 signaling cascade and its function in cancer progression. Here, we report that ERK3 interacted with and phosphorylated steroid receptor coactivator 3 (SRC-3), an oncogenic protein overexpressed in multiple human cancers at serine 857 (S857). This ERK3-mediated phosphorylation at S857 was essential for interaction of SRC-3 with the ETS transcription factor PEA3, which promotes upregulation of MMP gene expression and proinvasive activity in lung cancer cells. Importantly, knockdown of ERK3 or SRC-3 inhibited the ability of lung cancer cells to invade and form tumors in the lung in a xenograft mouse model. In addition, ERK3 was found to be highly upregulated in human lung carcinomas. Our study identifies a previously unknown role for ERK3 in promoting lung cancer cell invasiveness by phosphorylating SRC-3 and regulating SRC-3 proinvasive activity by site-specific phosphorylation. As such, ERK3 protein kinase may be an attractive target for therapeutic treatment of invasive lung cancer. PMID:22505454

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu; Chen, Jing; Schlueter, Connie F.

Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection. Multiple parameters were varied to produce formulations with a wide range of in vitro release kinetics. Testing of selected formulations in chlorine-exposedmore » mice demonstrated efficacy against key aspects of acute lung injury. The results show the feasibility of developing microencapsulated formulations that could be used to treat chlorine-induced acute lung injury by intramuscular injection, which represents a preferred route of administration in a mass casualty situation. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Countermeasures for treatment of chlorine-induced acute lung injury are needed. • Formulations containing rolipram, triptolide, or budesonide were produced. • Formulations with a wide range of release properties were developed. • Countermeasure formulations inhibited chlorine-induced lung injury in mice.« less

Brain-lung crosstalk in critical care: how protective mechanical ventilation can affect the brain homeostasis.

PubMed

Mazzeo, A T; Fanelli, V; Mascia, L

2013-03-01

The maintenance of brain homeostasis against multiple internal and external challenges occurring during the acute phase of acute brain injury may be influenced by critical care management, especially in its respiratory, hemodynamic and metabolic components. The occurrence of acute lung injury represents the most frequent extracranial complication after brain injury and deserves special attention in daily practice as optimal ventilatory strategy for patients with acute brain and lung injury are potentially in conflict. Protecting the lung while protecting the brain is thus a new target in the modern neurointensive care. This article discusses the essentials of brain-lung crosstalk and focuses on how mechanical ventilation may exert an active role in the process of maintaining or treatening brain homeostasis after acute brain injury, highlighting the following points: 1) the role of inflammation as common pathomechanism of both acute lung and brain injury; 2) the recognition of ventilatory induced lung injury as determinant of systemic inflammation affecting distal organs, included the brain; 3) the possible implication of protective mechanical ventilation strategy on the patient with an acute brain injury as an undiscovered area of research in both experimental and clinical settings.

Using YOLO based deep learning network for real time detection and localization of lung nodules from low dose CT scans

NASA Astrophysics Data System (ADS)

Ramachandran S., Sindhu; George, Jose; Skaria, Shibon; V. V., Varun

2018-02-01

Lung cancer is the leading cause of cancer related deaths in the world. The survival rate can be improved if the presence of lung nodules are detected early. This has also led to more focus being given to computer aided detection (CAD) and diagnosis of lung nodules. The arbitrariness of shape, size and texture of lung nodules is a challenge to be faced when developing these detection systems. In the proposed work we use convolutional neural networks to learn the features for nodule detection, replacing the traditional method of handcrafting features like geometric shape or texture. Our network uses the DetectNet architecture based on YOLO (You Only Look Once) to detect the nodules in CT scans of lung. In this architecture, object detection is treated as a regression problem with a single convolutional network simultaneously predicting multiple bounding boxes and class probabilities for those boxes. By performing training using chest CT scans from Lung Image Database Consortium (LIDC), NVIDIA DIGITS and Caffe deep learning framework, we show that nodule detection using this single neural network can result in reasonably low false positive rates with high sensitivity and precision.

EFFECT OF THE LESION DUE TO INFLUENZA VIRUS ON THE RESISTANCE OF MICE TO INHALED PNEUMOCOCCI

PubMed Central

Harford, Carl G.; Leidler, Virginia; Hara, Mary

1949-01-01

1. The normal lung of the mouse possesses the power of reducing markedly its content of Type I pneumococci within 3 hours after inhalation of the organisms in the form of fine droplets. 2. Lungs with fully developed influenza viral pneumonia not only fail to reduce the pulmonary content of pneumococci administered in this manner but, on the contrary, support their growth. 3. After intrabronchial inoculation into mice, influenza virus multiplies rapidly in the lung within 24 hours. 4. Criteria have been established for distinction between true viral lesions of the lung and changes due to the inoculation of diluents as vehicles for the virus. 5. 24 hours after inoculation of virus, there are no macroscopic lesions in the lung and the microscopic changes are due to the diluent. 6. Presence and multiplication of the virus in the lung 24 hours after inoculation have no apparent effect on the power of the lung to reduce rapidly its content of inhaled pneumococci. 7. The effect of the virus in lowering resistance to secondary bacterial infection appears to be due to the presence of the lesion produced by the virus. PMID:18099165

Aspergillus Colonization of the Lung Allograft is a Risk Factor for Bronchiolitis Obliterans Syndrome

PubMed Central

Weigt, S. Samuel; Elashoff, Robert M.; Huang, Cathy; Ardehali, Abbas; Gregson, Aric L.; Kubak, Bernard; Fishbein, Michael C.; Saggar, Rajeev; Keane, Michael P.; Saggar, Rajan; Lynch, Joseph P.; Zisman, David A.; Ross, David J.; Belperio, John A.

2014-01-01

Multiple infections have been linked with the development of bronchiolitis obliterans syndrome (BOS) post-lung transplantation. Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We hypothesized that Aspergillus colonization may promote the development of BOS and may decrease survival post-lung transplantation. We reviewed all lung transplant recipients transplanted in our center between 1/2000 and 6/2006. Bronchoscopy was performed according to a surveillance protocol and when clinically indicated. Aspergillus colonization was defined as a positive culture from bronchoalveolar lavage or two sputum cultures positive for the same Aspergillus species, in the absence of invasive pulmonary Aspergillosis. We found that Aspergillus colonization was strongly associated with BOS and BOS related mortality in Cox regression analyses. Aspergillus colonization typically preceded the development of BOS by a median of 261 days (95% CI 87 to 520). Furthermore, in a multivariate Cox regression model, Aspergillus colonization was a distinct risk factor for BOS, independent of acute rejection. These data suggest a potential causative role for Aspergillus colonization in the development of BOS post-lung transplantation and raise the possibility that strategies aimed to prevent Aspergillus colonization may help delay or reduce the incidence of BOS. PMID:19459819

Silica dust, diesel exhaust, and painting work are the significant occupational risk factors for lung cancer in nonsmoking Chinese men.

PubMed

Tse, L A; Yu, It-S; Au, J S K; Qiu, H; Wang, X-R

2011-01-04

Few epidemiological studies have explored the associations between occupational exposures and lung cancer in lifelong nonsmoking men. We obtained lifetime occupational history and other relevant information for 132 newly diagnosed lung cancer cases among nonsmoking Chinese men and 536 nonsmoking community referents. Unconditional multiple logistic regression analysis was performed to estimate the odds ratio (OR) of lung cancer for specific occupational exposures. Significantly increased lung cancer risk was found for nonsmoking workers occupationally exposed to silica dust (OR=2.58, 95% confidence interval (CI): 1.11, 6.01), diesel exhaust (OR=3.47, 95% CI: 1.08, 11.14), spray painting (OR=2.81, 95% CI: 1.14, 6.93), and nonspray painting work (OR=2.36, 95% CI: 1.04, 5.37). Silica dust exposure was associated with a significantly increased risk of adenocarcinoma (OR=2.91, 95% CI: 1.10, 7.68). We observed a positive gradient of all lung cancers and of adenocarcinoma with duration of employment for workers exposed to silica dust and spray painting. This study found an increased risk of lung cancer among nonsmoking Chinese men occupationally exposed to silica dust, diesel exhaust, and painting work.

Computed tomographic findings of cerebral fat embolism following multiple bone fractures.

PubMed

Law, Huong Ling; Wong, Siong Lung; Tan, Suzet

2013-02-01

Fat embolism to the lungs and brain is an uncommon complication following fractures. Few reports with descriptions of computed tomographic (CT) findings of emboli to the brain or cerebral fat embolism are available. We report a case of cerebral fat embolism following multiple skeletal fractures and present its CT findings here.

Low tumour cell content in a lung tumour bank: implications for molecular characterisation.

PubMed

Goh, Felicia; Duhig, Edwina E; Clarke, Belinda E; McCaul, Elizabeth; Passmore, Linda; Courtney, Deborah; Windsor, Morgan; Naidoo, Rishendren; Franz, Louise; Parsonson, Kylie; Yang, Ian A; Bowman, Rayleen V; Fong, Kwun M

2017-10-01

Lung cancer encompasses multiple malignant epithelial tumour types, each with specific targetable, potentially actionable mutations, such that precision management mandates accurate tumour typing. Molecular characterisation studies require high tumour cell content and low necrosis content, yet lung cancers are frequently a heterogeneous mixture of tumour and stromal cells. We hypothesised that there may be systematic differences in tumour cell content according to histological subtype, and that this may have implications for tumour banks as a resource for comprehensive molecular characterisation studies in lung cancer. To investigate this, we estimated tumour cell and necrosis content of 4267 samples resected from 752 primary lung tumour specimens contributed to a lung tissue bank. We found that banked lung cancer samples had low tumour cell content (33%) generally, although it was higher in carcinoids (77.5%) than other lung cancer subtypes. Tumour cells comprise a variable and often small component of banked resected tumour samples, and are accompanied by stromal reaction, inflammation, fibrosis, and normal structures. This has implications for the adequacy of unselected tumour bank samples for diagnostic and molecular investigations, and further research is needed to determine whether tumour cell content has a significant impact on analytical results in studies using tissue from tumour bank resources. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Chemically-induced mouse lung tumors: applications to ...

EPA Pesticide Factsheets

A state-of-the-science workshop on chemically-induced mouse lung tumors was conducted by U.S. Environmental Protection Agency to discuss issues related to the use of mouse lung tumor data in human health assessments. Naphthalene, styrene, and ethylbenzene were chosen for the analysis due to the commonality of mouse lung tumors in all these three environmental chemicals. The goals of the workshop were to: identify the evidence, from multiple scientific disciplines, regarding formation of chemically-induced lung tumors in mice; discuss analysis and interpretation of the evidence; discuss how such evidence informs human health assessments; and identify commonalities, linkages, or differences between the evidence from various disciplines and across the chemicals. Evidence informing the association between occupational exposure to styrene, ethylbenzene, or naphthalene and lung cancer; comparative biology of mouse lung tumors, associated pathologic effects, issues related to tissue and species concordance; mode of action analysis and biological mechanisms including pharmacokinetics and pharmacodynamics; and evidence from cellular, genetic and molecular toxicity was discussed. In summary, although consensus was not sought, the panelists agreed that data showing mouse lung tumors with chemical exposures can be relevant for human health risk evaluation on an individual chemical basis. Key data gaps were identified that would assist in further understanding the mechanism

The lung is a site of platelet biogenesis and a reservoir for hematopoietic progenitors

PubMed Central

Lefrançais, Emma; Ortiz-Muñoz, Guadalupe; Caudrillier, Axelle; Mallavia, Beñat; Liu, Fengchun; Sayah, David M.; Thornton, Emily E.; Headley, Mark B.; David, Tovo; Coughlin, Shaun R.; Krummel, Matthew F.; Leavitt, Andrew D.; Passegué, Emmanuelle; Looney, Mark R.

2017-01-01

Platelets are critical for hemostasis, thrombosis, and inflammatory responses1,2, yet the events leading to mature platelet production remain incompletely understood3. The bone marrow (BM) is proposed to be a major site of platelet production although indirect evidence points towards a potential pulmonary contribution to platelet biogenesis4-7. By directly imaging the lung microcirculation in mice8, we discovered that a large number of megakaryocytes (MKs) circulate through the lungs where they dynamically release platelets. MKs releasing platelets in the lung are of extrapulmonary origin, such as the BM, where we observed large MKs migrating out of the BM space. The lung contribution to platelet biogenesis is substantial with approximately 50% of total platelet production or 10 million platelets per hour. Furthermore, we identified populations of mature and immature MKs along with hematopoietic progenitors that reside in the extravascular spaces of the lung. Under conditions of thrombocytopenia and relative stem cell deficiency in the BM9, these progenitors can migrate out of the lung, repopulate the BM, completely reconstitute blood platelet counts, and contribute to multiple hematopoietic lineages. These results position the lung as a primary site of terminal platelet production and an organ with considerable hematopoietic potential. PMID:28329764

Multiple template-based fluoroscopic tracking of lung tumor mass without implanted fiducial markers

NASA Astrophysics Data System (ADS)

Cui, Ying; Dy, Jennifer G.; Sharp, Gregory C.; Alexander, Brian; Jiang, Steve B.

2007-10-01

Precise lung tumor localization in real time is particularly important for some motion management techniques, such as respiratory gating or beam tracking with a dynamic multi-leaf collimator, due to the reduced clinical tumor volume (CTV) to planning target volume (PTV) margin and/or the escalated dose. There might be large uncertainties in deriving tumor position from external respiratory surrogates. While tracking implanted fiducial markers has sufficient accuracy, this procedure may not be widely accepted due to the risk of pneumothorax. Previously, we have developed a technique to generate gating signals from fluoroscopic images without implanted fiducial markers using a template matching method (Berbeco et al 2005 Phys. Med. Biol. 50 4481-90, Cui et al 2007 Phys. Med. Biol. 52 741-55). In this paper, we present an extension of this method to multiple-template matching for directly tracking the lung tumor mass in fluoroscopy video. The basic idea is as follows: (i) during the patient setup session, a pair of orthogonal fluoroscopic image sequences are taken and processed off-line to generate a set of reference templates that correspond to different breathing phases and tumor positions; (ii) during treatment delivery, fluoroscopic images are continuously acquired and processed; (iii) the similarity between each reference template and the processed incoming image is calculated; (iv) the tumor position in the incoming image is then estimated by combining the tumor centroid coordinates in reference templates with proper weights based on the measured similarities. With different handling of image processing and similarity calculation, two such multiple-template tracking techniques have been developed: one based on motion-enhanced templates and Pearson's correlation score while the other based on eigen templates and mean-squared error. The developed techniques have been tested on six sequences of fluoroscopic images from six lung cancer patients against the reference tumor positions manually determined by a radiation oncologist. The tumor centroid coordinates automatically detected using both methods agree well with the manually marked reference locations. The eigenspace tracking method performs slightly better than the motion-enhanced method, with average localization errors less than 2 pixels (1 mm) and the error at a 95% confidence level of about 2-4 pixels (1-2 mm). This work demonstrates the feasibility of direct tracking of a lung tumor mass in fluoroscopic images without implanted fiducial markers using multiple reference templates.

[Extracorporeal membrane oxygenation in primary graft dysfunction in a paediatric double lung transplant: presentation of a case].

PubMed

López-Cantero, M; Grisolía, A L; Vicente, R; Moreno, I; Ramos, F; Porta, J; Torregrosa, S

2014-04-01

Primary graft dysfunction is a leading cause of morbimortality in the immediate postoperative period of patients undergoing lung transplantation. Among the treatment options are: lung protective ventilatory strategies, nitric oxide, lung surfactant therapy, and supportive treatment with extracorporeal membrane oxygenation (ECMO) as a bridge to recovery of lung function or re-transplant. We report the case of a 9-year-old girl affected by cystic fibrosis who underwent double-lung transplantation complicated with a severe primary graft dysfunction in the immediate postoperative period and refractory to standard therapies. Due to development of multiple organ failure, it was decided to insert arteriovenous ECMO catheters (pulmonary artery-right atrium). The postoperative course was satisfactory, allowing withdrawal of ECMO on the 5th post-surgical day. Currently the patient survives free of rejection and with an excellent quality of life after 600 days of follow up. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Immunotherapy for lung cancer: advances and prospects.

PubMed

Yang, Li; Wang, Liping; Zhang, Yi

2016-01-01

Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths worldwide. To date, surgery is the first choice treatment, but most clinically diagnosed cases are inoperable. While chemotherapy and/or radiotherapy are the next considered options for such cases, these treatment modalities have adverse effects and are sometimes lethal to patients. Thus, new effective strategies with minimal side effects are urgently needed. Cancer immunotherapy provides either active or passive immunity to target tumors. Multiple immunotherapy agents have been proposed and tested for potential therapeutic benefit against lung cancer, and some pose fewer side effects as compared to conventional chemotherapy and radiotherapy. In this article, we discuss studies focusing on interactions between lung cancer and the immune system, and we place an emphasis on outcome evidence in order to create a knowledge base well-grounded in clinical reality. Overall, this review highlights the need for new lung cancer treatment options, with much ground to be paved for future advances in the field. We believe that immunotherapy agents alone or with other forms of treatment can be recognized as next modality of lung cancer treatment.

Esophageal Dysmotility, Gastro-esophageal Reflux Disease, and Lung Transplantation: What Is the Evidence?

PubMed

Wood, Richard K

2015-12-01

Lung transplantation is an effective and life-prolonging therapy for patients with advanced lung disease (ALD). However, long-term patient survival following lung transplantation is primarily limited by development of an inflammatory and fibrotic process involving the lung allograft known as bronchiolitis obliterans syndrome (BOS). Although the precise cause of BOS remains uncertain and is likely multifactorial, chronic aspiration of gastro-duodenal contents is one possible contributing factor. Multiple small, cross-sectional studies performed over the past two decades have reported a high prevalence of gastro-esophageal reflux disease (GERD) and esophageal dysmotility in the ALD population and several investigations suggest the prevalence may increase following lung transplantation. More recent studies evaluating the direct effect of gastro-duodenal contents on airways have demonstrated a possible biologic link between GERD and BOS. Despite the recent advances in our understanding of BOS, further investigations are needed to establish GERD as a causative factor in its development. This review will discuss the existing literature that has identified an association of GERD with ALD and post-transplant populations, with a focus on recent advances in the field.

KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target.

PubMed

Román, Marta; Baraibar, Iosune; López, Inés; Nadal, Ernest; Rolfo, Christian; Vicent, Silvestre; Gil-Bazo, Ignacio

2018-02-19

Lung neoplasms are the leading cause of death by cancer worldwide. Non-small cell lung cancer (NSCLC) constitutes more than 80% of all lung malignancies and the majority of patients present advanced disease at onset. However, in the last decade, multiple oncogenic driver alterations have been discovered and each of them represents a potential therapeutic target. Although KRAS mutations are the most frequently oncogene aberrations in lung adenocarcinoma patients, effective therapies targeting KRAS have yet to be developed. Moreover, the role of KRAS oncogene in NSCLC remains unclear and its predictive and prognostic impact remains controversial. The study of the underlying biology of KRAS in NSCLC patients could help to determine potential candidates to evaluate novel targeted agents and combinations that may allow a tailored treatment for these patients. The aim of this review is to update the current knowledge about KRAS-mutated lung adenocarcinoma, including a historical overview, the biology of the molecular pathways involved, the clinical relevance of KRAS mutations as a prognostic and predictive marker and the potential therapeutic approaches for a personalized treatment of KRAS-mutated NSCLC patients.

Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds.

PubMed

Fröhlich, Eleonore; Mercuri, Annalisa; Wu, Shengqian; Salar-Behzadi, Sharareh

2016-01-01

Modern strategies in drug development employ in silico techniques in the design of compounds as well as estimations of pharmacokinetics, pharmacodynamics and toxicity parameters. The quality of the results depends on software algorithm, data library and input data. Compared to simulations of absorption, distribution, metabolism, excretion, and toxicity of oral drug compounds, relatively few studies report predictions of pharmacokinetics and pharmacodynamics of inhaled substances. For calculation of the drug concentration at the absorption site, the pulmonary epithelium, physiological parameters such as lung surface and distribution volume (lung lining fluid) have to be known. These parameters can only be determined by invasive techniques and by postmortem studies. Very different values have been reported in the literature. This review addresses the state of software programs for simulation of orally inhaled substances and focuses on problems in the determination of particle deposition, lung surface and of lung lining fluid. The different surface areas for deposition and for drug absorption are difficult to include directly into the simulations. As drug levels are influenced by multiple parameters the role of single parameters in the simulations cannot be identified easily.

Pleiotrophin regulates lung epithelial cell proliferation and differentiation during fetal lung development via beta-catenin and Dlk1.

PubMed

Weng, Tingting; Gao, Li; Bhaskaran, Manoj; Guo, Yujie; Gou, Deming; Narayanaperumal, Jeyaparthasarathy; Chintagari, Narendranath Reddy; Zhang, Kexiong; Liu, Lin

2009-10-09

The role of pleiotrophin in fetal lung development was investigated. We found that pleiotrophin and its receptor, protein-tyrosine phosphatase receptor beta/zeta, were highly expressed in mesenchymal and epithelial cells of the fetal lungs, respectively. Using isolated fetal alveolar epithelial type II cells, we demonstrated that pleiotrophin promoted fetal type II cell proliferation and arrested type II cell trans-differentiation into alveolar epithelial type I cells. Pleiotrophin also increased wound healing of injured type II cell monolayer. Knockdown of pleiotrophin influenced lung branching morphogenesis in a fetal lung organ culture model. Pleiotrophin increased the tyrosine phosphorylation of beta-catenin, promoted beta-catenin translocation into the nucleus, and activated T cell factor/lymphoid enhancer factor transcription factors. Dlk1, a membrane ligand that initiates the Notch signaling pathway, was identified as a downstream target of the pleiotrophin/beta-catenin pathway by endogenous dlk1 expression, promoter assay, and chromatin immunoprecipitation. These results provide evidence that pleiotrophin regulates fetal type II cell proliferation and differentiation via integration of multiple signaling pathways including pleiotrophin, beta-catenin, and Notch pathways.

Targeting DDX3 with a small molecule inhibitor for lung cancer therapy

PubMed Central

Bol, Guus M; Vesuna, Farhad; Xie, Min; Zeng, Jing; Aziz, Khaled; Gandhi, Nishant; Levine, Anne; Irving, Ashley; Korz, Dorian; Tantravedi, Saritha; Heerma van Voss, Marise R; Gabrielson, Kathleen; Bordt, Evan A; Polster, Brian M; Cope, Leslie; van der Groep, Petra; Kondaskar, Atul; Rudek, Michelle A; Hosmane, Ramachandra S; van der Wall, Elsken; van Diest, Paul J; Tran, Phuoc T; Raman, Venu

2015-01-01

Lung cancer is the most common malignancy worldwide and is a focus for developing targeted therapies due to its refractory nature to current treatment. We identified a RNA helicase, DDX3, which is overexpressed in many cancer types including lung cancer and is associated with lower survival in lung cancer patients. We designed a first-in-class small molecule inhibitor, RK-33, which binds to DDX3 and abrogates its activity. Inhibition of DDX3 by RK-33 caused G1 cell cycle arrest, induced apoptosis, and promoted radiation sensitization in DDX3-overexpressing cells. Importantly, RK-33 in combination with radiation induced tumor regression in multiple mouse models of lung cancer. Mechanistically, loss of DDX3 function either by shRNA or by RK-33 impaired Wnt signaling through disruption of the DDX3–β-catenin axis and inhibited non-homologous end joining—the major DNA repair pathway in mammalian somatic cells. Overall, inhibition of DDX3 by RK-33 promotes tumor regression, thus providing a compelling argument to develop DDX3 inhibitors for lung cancer therapy. PMID:25820276

Estimating the asbestos-related lung cancer burden from mesothelioma mortality

PubMed Central

McCormack, V; Peto, J; Byrnes, G; Straif, K; Boffetta, P

2012-01-01

Background: Quantifying the asbestos-related lung cancer burden is difficult in the presence of this disease's multiple causes. We explore two methods to estimate this burden using mesothelioma deaths as a proxy for asbestos exposure. Methods: From the follow-up of 55 asbestos cohorts, we estimated ratios of (i) absolute number of asbestos-related lung cancers to mesothelioma deaths; (ii) excess lung cancer relative risk (%) to mesothelioma mortality per 1000 non-asbestos-related deaths. Results: Ratios varied by asbestos type; there were a mean 0.7 (95% confidence interval 0.5, 1.0) asbestos-related lung cancers per mesothelioma death in crocidolite cohorts (n=6 estimates), 6.1 (3.6, 10.5) in chrysotile (n=16), 4.0 (2.8, 5.9) in amosite (n=4) and 1.9 (1.4, 2.6) in mixed asbestos fibre cohorts (n=31). In a population with 2 mesothelioma deaths per 1000 deaths at ages 40–84 years (e.g., US men), the estimated lung cancer population attributable fraction due to mixed asbestos was estimated to be 4.0%. Conclusion: All types of asbestos fibres kill at least twice as many people through lung cancer than through mesothelioma, except for crocidolite. For chrysotile, widely consumed today, asbestos-related lung cancers cannot be robustly estimated from few mesothelioma deaths and the latter cannot be used to infer no excess risk of lung or other cancers. PMID:22233924

IL-17RA in Non-Hematopoietic Cells Controls CXCL-1 and 5 Critical to Recruit Neutrophils to the Lung of Mycobacteria-Infected Mice during the Adaptive Immune Response

PubMed Central

Lombard, Robin; Epardaud, Mathieu; Le Vern, Yves; Buzoni-Gatel, Dominique; Winter, Nathalie

2016-01-01

During chronic infection with Mycobacterium tuberculosis (Mtb), bacilli multiplication is constrained within lung granulomas until excessive inflammation destroys the lung. Neutrophils are recruited early and participate in granuloma formation, but excessive neutrophilia exacerbates the tuberculosis disease. Neutrophils thus appear as potential targets for therapeutic interventions, especially in patients for whom no antibiotic treatment is possible. Signals that regulate neutrophil recruitment to the lung during mycobacterial infection need to be better understood. We demonstrated here, in the mouse model, that neutrophils were recruited to the lung in two waves after intranasal infection with virulent Mtb or the live attenuated vaccine strain Bacillus Calmette Guérin (BCG). A first wave of neutrophils was swiftly recruited, followed by a subsequent adaptive wave that reached the lung together with IFN-γ- and IL-17A-producing T cells. Interestingly, the second neutrophil wave did not participate to mycobacteria control in the lung and established contacts with T cells. The adaptive wave was critically dependent on the expression of IL-17RA, the receptor for IL-17A, expressed in non-hematopoietic cells. In absence of this receptor, curtailed CXCL-1 and 5 production in the lung restrained neutrophil recruitment. CXCL-1 and 5 instillation reconstituted lung neutrophil recruitment in BCG-infected IL17RA-/- mice. PMID:26871571

IL-17RA in Non-Hematopoietic Cells Controls CXCL-1 and 5 Critical to Recruit Neutrophils to the Lung of Mycobacteria-Infected Mice during the Adaptive Immune Response.

PubMed

Lombard, Robin; Doz, Emilie; Carreras, Florence; Epardaud, Mathieu; Le Vern, Yves; Buzoni-Gatel, Dominique; Winter, Nathalie

2016-01-01

During chronic infection with Mycobacterium tuberculosis (Mtb), bacilli multiplication is constrained within lung granulomas until excessive inflammation destroys the lung. Neutrophils are recruited early and participate in granuloma formation, but excessive neutrophilia exacerbates the tuberculosis disease. Neutrophils thus appear as potential targets for therapeutic interventions, especially in patients for whom no antibiotic treatment is possible. Signals that regulate neutrophil recruitment to the lung during mycobacterial infection need to be better understood. We demonstrated here, in the mouse model, that neutrophils were recruited to the lung in two waves after intranasal infection with virulent Mtb or the live attenuated vaccine strain Bacillus Calmette Guérin (BCG). A first wave of neutrophils was swiftly recruited, followed by a subsequent adaptive wave that reached the lung together with IFN-γ- and IL-17A-producing T cells. Interestingly, the second neutrophil wave did not participate to mycobacteria control in the lung and established contacts with T cells. The adaptive wave was critically dependent on the expression of IL-17RA, the receptor for IL-17A, expressed in non-hematopoietic cells. In absence of this receptor, curtailed CXCL-1 and 5 production in the lung restrained neutrophil recruitment. CXCL-1 and 5 instillation reconstituted lung neutrophil recruitment in BCG-infected IL17RA-/- mice.

Dietary Cholesterol Intake and Risk of Lung Cancer: A Meta-Analysis.

PubMed

Lin, Xiaojing; Liu, Lingli; Fu, Youyun; Gao, Jing; He, Yunyun; Wu, Yang; Lian, Xuemei

2018-02-08

Multiple epidemiologic studies have evaluated the relationship between dietary cholesterol and lung cancer risk, but the association is controversial and inconclusive. A meta-analysis of case-control studies and cohort studies was conducted to evaluate the relationship between dietary cholesterol intake and lung cancer risk in this study. A relevant literature search up to October 2017 was performed in Web of Science, PubMed, China National Knowledge Infrastructure, Sinomed, and VIP Journal Integration Platform. Ten case-control studies and six cohort studies were included in the meta-analysis, and the risk estimates were pooled using either fixed or random effects models. The case-control studies with a total of 6894 lung cancer cases and 29,736 controls showed that dietary cholesterol intake was positively associated with lung cancer risk (Odds Ratio = 1.70, 95% Confidence Interval: 1.43-2.03). However, there was no evidence of an association between dietary cholesterol intake and risk of lung cancer among the 241,920 participants and 1769 lung cancer cases in the cohort studies (Relative Risk = 1.08, 95% Confidence Interval: 0.94-1.25). Due to inconsistent results from case-control and cohort studies, it is difficult to draw any conclusion regarding the effects of dietary cholesterol intake on lung cancer risk. Carefully designed and well-conducted cohort studies are needed to identify the association between dietary cholesterol and lung cancer risk.

The association of exposure to hepatitis B and C viruses with lung function and respiratory disease: a population based study from the NHANES III database.

PubMed

Goh, Li Yen; Card, Tim; Fogarty, Andrew W; McKeever, Tricia M

2014-12-01

Globally, 500 million people are chronically infected with Hepatitis B virus (HBV) and Hepatitis C virus (HCV). While these viruses are notorious for their detrimental effect on the liver they are also known to affect multiple organs in the body including the lungs. To investigate if exposure to HBV and HCV is associated with lung function and respiratory diseases. Data from the Third National Health and Nutrition Examination Survey (NHANES III) was analysed using multiple linear regressions to investigate the association between exposure to HBV and HCV with the various measures of lung function, while multiple logistic regressions were used to evaluate the association with the respiratory diseases asthma and chronic obstructive pulmonary disease (COPD). Exposure to HCV was significantly associated with an increase in Forced Expiratory Volume in 1 s, FEV1 (Coef: 97.94 ml, 95% CI: 38.87 to 157.01) and Full Vital Capacity, FVC (Coef: 90 ml, 95% CI: 14.50 to 166.24). Individuals who had been exposed to both HBV and HCV also had a significantly higher FEV1 (Coef: 145.82, CI: 60.68 to 230.94) and FVC (Coef: 195.09, CI: 78.91 to 311.26). There was also a significant association between exposure to HBV and asthma (OR: 1.28, 95% CI: 1.05 to 1.58). These associations were no longer significant after additionally adjusting for cocaine and marijuana use as well as poverty income ratio. Our research implies that hepatotropic viruses may affect the respiratory system, but more work at a population level is needed to further explore these associations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhalation of gas metal arc-stainless steel welding fume promotes lung tumorigenesis in A/J mice.

PubMed

Falcone, Lauryn M; Erdely, Aaron; Meighan, Terence G; Battelli, Lori A; Salmen, Rebecca; McKinney, Walter; Stone, Samuel; Cumpston, Amy; Cumpston, Jared; Andrews, Ronnee N; Kashon, Michael; Antonini, James M; Zeidler-Erdely, Patti C

2017-08-01

Epidemiologic studies suggest an increased risk of lung cancer with exposure to welding fumes, but controlled animal studies are needed to support this association. Oropharyngeal aspiration of collected "aged" gas metal arc-stainless steel (GMA-SS) welding fume has been shown by our laboratory to promote lung tumor formation in vivo using a two-stage initiation-promotion model. Our objective in this study was to determine whether inhalation of freshly generated GMA-SS welding fume also acts as a lung tumor promoter in lung tumor-susceptible mice. Male A/J mice received intraperitoneal (IP) injections of corn oil or the chemical initiator 3-methylcholanthrene (MCA; 10 µg/g) and 1 week later were exposed by whole-body inhalation to air or GMA-SS welding aerosols for 4 h/d × 4 d/w × 9 w at a target concentration of 40 mg/m 3 . Lung nodules were enumerated at 30 weeks post-initiation. GMA-SS fume significantly promoted lung tumor multiplicity in A/J mice initiated with MCA (16.11 ± 1.18) compared to MCA/air-exposed mice (7.93 ± 0.82). Histopathological analysis found that the increased number of lung nodules in the MCA/GMA-SS group were hyperplasias and adenomas, which was consistent with developing lung tumorigenesis. Metal deposition analysis in the lung revealed a lower deposited dose, approximately fivefold compared to our previous aspiration study, still elicited a significant lung tumorigenic response. In conclusion, this study demonstrates that inhaling GMA-SS welding fume promotes lung tumorigenesis in vivo which is consistent with the epidemiologic studies that show welders may be at an increased risk for lung cancer.

Blood culture positive Nocardia asteroides infection: a case report.

PubMed

Höpler, Wolfgang; Laferl, Hermann; Szell, Marton; Pongratz, Peter; Brandl, Irmgard; Tucek, Gerhard; Wenisch, Christoph

2013-01-01

We report a case of nocardiosis in a patient with several risk factors for this rare infection. Radiologically, the patient's multiple lung abscesses were misinterpreted as pulmonary metastases. Diagnosis was finally reached by the growth of Nocardia asteroides in two different blood culture sets. Nocardia bacteraemia is a rare clinical event. Despite initiation of an effective antibiotic therapy, the patient died. Autopsy revealed disseminated nocardial abscesses in the lungs, the kidneys and the brain.

Multilevel Opportunities to Address Lung Cancer Stigma across the Cancer Control Continuum.

PubMed

Hamann, Heidi A; Ver Hoeve, Elizabeth S; Carter-Harris, Lisa; Studts, Jamie L; Ostroff, Jamie S

2018-05-22

The public health imperative to reduce the burden of lung cancer has seen unprecedented progress in recent years. Realizing fully the advances in lung cancer treatment and control requires attention to potential barriers in their momentum and implementation. In this analysis, we present and evaluate the argument that stigma is a highly significant barrier to fulfilling the clinical promise of advanced care and reduced lung cancer burden. This evaluation of lung cancer stigma is based on a multilevel perspective that incorporates the individual, persons in their immediate environment, the healthcare system, and the larger societal structure which shapes perceptions and decisions. We also consider current interventions and interventional needs within and across aspects of the lung cancer continuum, including prevention, screening, diagnosis, treatment, and survivorship. Current evidence suggests that stigma detrimentally impacts psychosocial, communication, and behavioral outcomes over the entire lung cancer control continuum and across multiple levels. Interventional efforts to alleviate stigma in the context of lung cancer show promise, yet more work is needed to evaluate their impact. Understanding and addressing the multi-level role of stigma is a crucial area for future study in order to realize the full benefits offered by lung cancer prevention, control, and treatment. Coordinated, interdisciplinary, and well-conceptualized efforts have the potential to reduce the barrier of stigma in the context of lung cancer and facilitate demonstrable improvements in clinical care and quality of life. Copyright © 2018. Published by Elsevier Inc.

Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury

PubMed Central

Zhang, Yi; Jiang, Ge; Sauler, Maor; Lee, Patty J.

2013-01-01

The lung endothelium is a major target for inflammatory and oxidative stress. Heme oxygenase-1 (HO-1) induction is a crucial defense mechanism during oxidant challenges, such as hyperoxia. The role of lung endothelial HO-1during hyperoxia in vivo is not well defined. We engineered lentiviral vectors with microRNA (miRNA) sequences controlled by vascular endothelium cadherin (VE-cad) to study the specific role of lung endothelial HO-1. Wild-type (WT) murine lung endothelial cells (MLECs) or WT mice were treated with lentivirus and exposed to hyperoxia (95% oxygen). We detected HO-1 knockdown (∼55%) specifically in the lung endothelium. MLECs and lungs showed approximately a 2-fold increase in apoptosis and ROS generation after HO-1 silencing. We also demonstrate for the first time that silencing endothelial HO-1 has the same effect on lung injury and survival as silencing HO-1 in multiple lung cell types and that HO-1 regulates caspase 3 activation and autophagy in endothelium during hyperoxia. These studies demonstrate the utility of endothelial-targeted gene silencing in vivo using lentiviral miRNA constructs to assess gene function and that endothelial HO-1 is an important determinant of survival during hyperoxia.—Zhang, Y., Jiang, G., Sauler, M., Lee, P. J. Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury. PMID:23771928

Mechanical ventilation drives pneumococcal pneumonia into lung injury and sepsis in mice: protection by adrenomedullin.

PubMed

Müller-Redetzky, Holger C; Will, Daniel; Hellwig, Katharina; Kummer, Wolfgang; Tschernig, Thomas; Pfeil, Uwe; Paddenberg, Renate; Menger, Michael D; Kershaw, Olivia; Gruber, Achim D; Weissmann, Norbert; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

2014-04-14

Ventilator-induced lung injury (VILI) contributes to morbidity and mortality in acute respiratory distress syndrome (ARDS). Particularly pre-injured lungs are susceptible to VILI despite protective ventilation. In a previous study, the endogenous peptide adrenomedullin (AM) protected murine lungs from VILI. We hypothesized that mechanical ventilation (MV) contributes to lung injury and sepsis in pneumonia, and that AM may reduce lung injury and multiple organ failure in ventilated mice with pneumococcal pneumonia. We analyzed in mice the impact of MV in established pneumonia on lung injury, inflammation, bacterial burden, hemodynamics and extrapulmonary organ injury, and assessed the therapeutic potential of AM by starting treatment at intubation. In pneumococcal pneumonia, MV increased lung permeability, and worsened lung mechanics and oxygenation failure. MV dramatically increased lung and blood cytokines but not lung leukocyte counts in pneumonia. MV induced systemic leukocytopenia and liver, gut and kidney injury in mice with pneumonia. Lung and blood bacterial burden was not affected by MV pneumonia and MV increased lung AM expression, whereas receptor activity modifying protein (RAMP) 1-3 expression was increased in pneumonia and reduced by MV. Infusion of AM protected against MV-induced lung injury (66% reduction of pulmonary permeability p < 0.01; prevention of pulmonary restriction) and against VILI-induced liver and gut injury in pneumonia (91% reduction of AST levels p < 0.05, 96% reduction of alanine aminotransaminase (ALT) levels p < 0.05, abrogation of histopathological changes and parenchymal apoptosis in liver and gut). MV paved the way for the progression of pneumonia towards ARDS and sepsis by aggravating lung injury and systemic hyperinflammation leading to liver, kidney and gut injury. AM may be a promising therapeutic option to protect against development of lung injury, sepsis and extrapulmonary organ injury in mechanically ventilated individuals with severe pneumonia.

The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease.

PubMed

Pragman, Alexa A; Lyu, Tianmeng; Baller, Joshua A; Gould, Trevor J; Kelly, Rosemary F; Reilly, Cavan S; Isaacson, Richard E; Wendt, Chris H

2018-01-09

Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection. Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R. Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue. This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that aspiration is a source of the COPD lung microbiota.

Setting individualized positive end-expiratory pressure level with a positive end-expiratory pressure decrement trial after a recruitment maneuver improves oxygenation and lung mechanics during one-lung ventilation.

PubMed

Ferrando, Carlos; Mugarra, Ana; Gutierrez, Andrea; Carbonell, Jose Antonio; García, Marisa; Soro, Marina; Tusman, Gerardo; Belda, Francisco Javier

2014-03-01

We investigated whether individualized positive end-expiratory pressure (PEEP) improves oxygenation, ventilation, and lung mechanics during one-lung ventilation compared with standardized PEEP. Thirty patients undergoing thoracic surgery were randomly allocated to the study or control group. Both groups received an alveolar recruitment maneuver at the beginning and end of one-lung ventilation. After the alveolar recruitment maneuver, the control group had their lungs ventilated with a 5 cm·H2O PEEP, while the study group had their lungs ventilated with an individualized PEEP level determined by a PEEP decrement trial. Arterial blood samples, lung mechanics, and volumetric capnography were recorded at multiple timepoints throughout the procedure. The individualized PEEP values in study group were higher than the standardized PEEP values (10 ± 2 vs 5 cm·H2O; P < 0.001). In both groups, arterial oxygenation decreased when bilateral-lung ventilation was switched to one-lung ventilation and increased after the alveolar recruitment maneuver. During one-lung ventilation, oxygenation was maintained in the study group but decreased in the control group. After one-lung ventilation, arterial oxygenation was significantly higher in the study group (306 vs 231 mm·Hg, P = 0.007). Static compliance decreased in both groups when bilateral-lung ventilation was switched to one-lung ventilation. Static compliance increased significantly only in the study group (P < 0.001) after the alveolar recruitment maneuver and optimal PEEP adjustment. The alveolar recruitment maneuver did not decrease cardiac index in any patient. During one-lung ventilation, the improvements in oxygenation and lung mechanics after an alveolar recruitment maneuver were better preserved by ventilation by using individualized PEEP with a PEEP decrement trial than with a standardized 5 cm·H2O of PEEP.

Racial Differences in Tobacco Cessation and Treatment Usage After Lung Screening: An Examination of the National Lung Screening Trial.

PubMed

Kumar, Pallavi; Gareen, Ilana F; Lathan, Christopher; Sicks, JoRean D; Perez, Giselle K; Hyland, Kelly A; Park, Elyse R

2016-01-01

Black smokers have demonstrated greater lung cancer disease burden and poorer smoking cessation outcomes compared with whites. Lung cancer screening represents a unique opportunity to promote cessation among smokers; however, little is known about the differential impact of screening on smoking behaviors among black and white smokers. Using data from the National Lung Screening Trial (NLST), we examined the racial differences in smoking behaviors after screening. We examined racial differences in smoking behavior and cessation activity among 6,316 white and 497 black (median age, 60 and 59 years, respectively) NLST participants who were current smokers at screening using a follow-up survey on 24-hour and 7-day quit attempts, 6-month continuous abstinence, and the use of smoking cessation programs and aids at 12 months after screening. Using multiple regression analyses, we examined the predictors of 24-hour and 7-day quit attempts and 6-month continuous abstinence. At 12 months after screening, blacks were more likely to report a 24-hour (52.7% vs. 41.2%, p < .0001) or 7-day (33.6% vs. 27.2%, p = .002) quit attempt. However, no significant racial differences were found in 6-month continuous abstinence (5.6% blacks vs. 7.2% whites). In multiple regression, black race was predictive of a higher likelihood of a 24-hour (odds ratio [OR], 1.6, 95% confidence interval [CI], 1.2-2.0) and 7-day (OR, 1.5, 95% CI, 1.1-1.8) quit attempt; however, race was not associated with 6-month continuous abstinence. Only a positive screening result for lung cancer was significantly predictive of successful 6-month continuous abstinence (OR, 2.3, 95% CI, 1.8-2.9). Although blacks were more likely than whites to have 24-hour and 7-day quit attempts, the rates of 6-month continuous abstinence did not differ. Targeted interventions are needed at the time of lung cancer screening to promote abstinence among all smokers. Among smokers undergoing screening for lung cancer, blacks were more likely than whites to have 24-hour and 7-day quit attempts; however, these attempts did not translate to increased rates of 6-month continuous abstinence among black smokers. Targeted interventions are needed at the time of lung cancer screening to convert quit attempts to sustained smoking cessation among all smokers. ©AlphaMed Press.

Inhaled nano- and microparticles for drug delivery

PubMed Central

El-Sherbiny, Ibrahim M.; El-Baz, Nancy M.; Yacoub, Magdi H.

2015-01-01

The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems. PMID:26779496

Pulmonary Foreign Body Granulomatosis in Dental Technician.

PubMed

Chung, Sung Jun; Koo, Gun Woo; Park, Dong Won; Kwak, Hyun Jung; Yhi, Ji Young; Moon, Ji-Yong; Kim, Sang-Heon; Sohn, Jang Won; Yoon, Ho Joo; Shin, Dong Ho; Park, Sung Soo; Pyo, Ju Yeon; Oh, Young-Ha; Kim, Tae-Hyung

2015-10-01

Occupational lung diseases are caused by several toxic substances including heavy metals; however, the exact pathologic mechanisms remain unknown. In the workplace, dental technicians are often exposed to heavy metals such as cobalt, nickel, or beryllium and occasionally develop occupational lung diseases. We described a case of occupational lung disease in a patient who was employed as a dental technician for over a decade. A 31-year-old, non-smoking woman presented with productive cough and shortness of breath of several weeks duration. Chest computed tomography revealed a large number of scattered, bilateral small pulmonary nodules throughout the lung field, and multiple mediastinal lymph nodes enlargement. Percutaneous needle biopsy showed multifocal small granulomas with foreign body type giant cells suggestive of heavy metals inhalation. The patient's condition improved on simple avoidance strategy for several months. This case highlighted the importance of proper workplace safety.

Instillation versus Inhalation of Multiwalled Carbon Nanotubes: Exposure-Related Health Effects, Clearance, and the Role of Particle Characteristics

PubMed Central

2015-01-01

Inhaled multiwalled carbon nanotubes (MWCNTs) may cause adverse pulmonary responses due to their nanoscale, fibrous morphology and/or biopersistance. This study tested multiple factors (dose, time, physicochemical characteristics, and administration method) shown to affect MWCNT toxicity with the hypothesis that these factors will influence significantly different responses upon MWCNT exposure. The study is unique in that (1) multiple administration methods were tested using particles from the same stock; (2) bulk MWCNT formulations had few differences (metal content, surface area/functionalization); and (3) MWCNT retention was quantified using a specialized approach for measuring unlabeled MWCNTs in rodent lungs. Male Sprague–Dawley rats were exposed to original (O), purified (P), and carboxylic acid functionalized (F) MWCNTs via intratracheal instillation and inhalation. Blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected at postexposure days 1 and 21 for quantifying biological responses and MWCNTs in lung tissues by programmed thermal analysis. At day 1, MWCNT instillation produced significant BALF neutrophilia and MWCNT-positive macrophages. Instilled O- and P-MWCNTs produced significant inflammation in lung tissues, which resolved by day 21 despite MWCNT retention. MWCNT inhalation produced no BALF neutrophilia and no significant histopathology past day 1. However, on days 1 and 21 postinhalation of nebulized MWCNTs, significantly increased numbers of MWCNT-positive macrophages were observed in BALF. Results suggest (1) MWCNTs produce transient inflammation if any despite persistence in the lungs; (2) instilled O-MWCNTs cause more inflammation than P- or F-MWCNTs; and (3) MWCNT suspension media produce strikingly different effects on physicochemical particle characteristics and pulmonary responses. PMID:25144856

An ecologic study of cancer mortality rates in Spain with respect to indices of solar UVB irradiance and smoking.

PubMed

Grant, William B

2007-03-01

There is increasing evidence that vitamin D reduces the risk of many types of cancer. Geographic variations in cancer mortality rates in Spain are apparently linked to variations in solar ultraviolet (UV) irradiances and other factors. Cancer mortality rates for 48 continental Spanish provinces for 1978-1992 were used in linear regression analyses with respect to mortality rates for latitude (an index of solar UVB levels), skin cancer (an index of high cumulative UVB irradiance), melanoma (an index related to solar UV irradiance and several other factors) and lung cancer (an index of cumulative effects of smoking). The 9 cancers with mortality rates significantly correlated with latitude for 1 or both sexes were brain, gastric, melanoma, nonmelanoma skin cancer (NMSC), non-Hodgkin's lymphoma (NHL), pancreatic, pleural, rectal and thyroid cancer. Inverse correlations with latitude were found for laryngeal, lung and uterine corpus cancer. The 17 cancers inversely correlated with NMSC are bladder, brain, breast, colon, esophageal, gallbladder, Hodgkin's lymphoma, lung, melanoma, multiple myeloma, NHL, ovarian, pancreatic, pleural, rectal, thyroid and uterine corpus cancer. The 16 correlated with melanoma are bladder, brain, breast, colon, gallbladder, leukemia, lung, multiple myeloma, NHL, ovarian, pancreatic, pleural, prostate, rectal, renal and uterine corpus cancer. The results for lung cancer were in accordance with the literature. These results provide more support for the UVB/vitamin D/cancer hypothesis and indicate a new way to investigate the role of solar UV irradiance on cancer risk. They also provide more evidence that melanoma and NMSC have different etiologies. Copyright 2006 Wiley-Liss, Inc.

Associations of interleukin-1 gene cluster polymorphisms with C-reactive protein concentration and lung function decline in smoking-induced chronic obstructive pulmonary disease

PubMed Central

Wang, Yu; Shumansky, Karey; Sin, Don D; Man, SF Paul; Akhabir, Loubna; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Sandford, Andrew J; He, Jian-Qing

2015-01-01

Objective: We reported association of haplotypes formed by IL-1b (IL1B)-511C/T (rs16944) and a variable number of tandem repeats (rs2234663) in intron 3 of IL-1 receptor antagonist (IL1RN) with rate of lung function decline in smoking-induced COPD. The aim of current study was to further investigate this association. Methods: We genotyped an additional 19 polymorphisms in IL1 cluster (including IL1A, IL1B and IL1RN) in non-Hispanic whites who had the fastest (n = 268) and the slowest (n = 292) decline of FEV1% predicted in the same study. We also analyzed the association of all 21 polymorphisms with serum CRP levels. Results: None of 21 polymorphisms showed significant association with rate of decline of lung function or CRP levels after adjusting for multiple comparisons. Before adjusting for multiple comparisons, only IL1RN_19327 (rs315949) showed significant association with lung function decline (P = 0.03, additive model). The frequencies of genotypes containing the IL1RN_19327A allele were 71.9% and 62.2%, respectively in the fast and slow decline groups (P = 0.02, odds ratio = 1.6, 95% confidence interval = 1.1-2.3); the IL1B_5200 (rs1143633) and rs2234663 in IL1RN were associated with serum CRP levels (P=0.04 and 0.03, respectively). Conclusions: No single marker was significantly associated with either rate of lung function decline or serum CRP levels. PMID:26722511

Antibiotic Management of Lung Infections in Cystic Fibrosis. II. Nontuberculous Mycobacteria, Anaerobic Bacteria, and Fungi

PubMed Central

Aksamit, Timothy R.; Chotirmall, Sanjay H.; Dasenbrook, Elliott C.; Elborn, J. Stuart; LiPuma, John J.; Ranganathan, Sarath C.; Waters, Valerie J.; Ratjen, Felix A.

2014-01-01

Airway infections are a key component of cystic fibrosis (CF) lung disease. Whereas the approach to common pathogens such as Pseudomonas aeruginosa is guided by a significant body of evidence, other infections often pose a considerable challenge to treating physicians. In Part I of this series on the antibiotic management of difficult lung infections, we discussed bacterial organisms including methicillin-resistant Staphylococcus aureus, gram-negative bacterial infections, and treatment of multiple bacterial pathogens. Here, we summarize the approach to infections with nontuberculous mycobacteria, anaerobic bacteria, and fungi. Nontuberculous mycobacteria can significantly impact the course of lung disease in patients with CF, but differentiation between colonization and infection is difficult clinically as coinfection with other micro-organisms is common. Treatment consists of different classes of antibiotics, varies in intensity, and is best guided by a team of specialized clinicians and microbiologists. The ability of anaerobic bacteria to contribute to CF lung disease is less clear, even though clinical relevance has been reported in individual patients. Anaerobes detected in CF sputum are often resistant to multiple drugs, and treatment has not yet been shown to positively affect patient outcome. Fungi have gained significant interest as potential CF pathogens. Although the role of Candida is largely unclear, there is mounting evidence that Scedosporium species and Aspergillus fumigatus, beyond the classical presentation of allergic bronchopulmonary aspergillosis, can be relevant in patients with CF and treatment should be considered. At present, however there remains limited information on how best to select patients who could benefit from antifungal therapy. PMID:25167882

Antibiotic management of lung infections in cystic fibrosis. II. Nontuberculous mycobacteria, anaerobic bacteria, and fungi.

PubMed

Chmiel, James F; Aksamit, Timothy R; Chotirmall, Sanjay H; Dasenbrook, Elliott C; Elborn, J Stuart; LiPuma, John J; Ranganathan, Sarath C; Waters, Valerie J; Ratjen, Felix A

2014-10-01

Airway infections are a key component of cystic fibrosis (CF) lung disease. Whereas the approach to common pathogens such as Pseudomonas aeruginosa is guided by a significant body of evidence, other infections often pose a considerable challenge to treating physicians. In Part I of this series on the antibiotic management of difficult lung infections, we discussed bacterial organisms including methicillin-resistant Staphylococcus aureus, gram-negative bacterial infections, and treatment of multiple bacterial pathogens. Here, we summarize the approach to infections with nontuberculous mycobacteria, anaerobic bacteria, and fungi. Nontuberculous mycobacteria can significantly impact the course of lung disease in patients with CF, but differentiation between colonization and infection is difficult clinically as coinfection with other micro-organisms is common. Treatment consists of different classes of antibiotics, varies in intensity, and is best guided by a team of specialized clinicians and microbiologists. The ability of anaerobic bacteria to contribute to CF lung disease is less clear, even though clinical relevance has been reported in individual patients. Anaerobes detected in CF sputum are often resistant to multiple drugs, and treatment has not yet been shown to positively affect patient outcome. Fungi have gained significant interest as potential CF pathogens. Although the role of Candida is largely unclear, there is mounting evidence that Scedosporium species and Aspergillus fumigatus, beyond the classical presentation of allergic bronchopulmonary aspergillosis, can be relevant in patients with CF and treatment should be considered. At present, however there remains limited information on how best to select patients who could benefit from antifungal therapy.

Microfluidic chest cavities reveal that transmural pressure controls the rate of lung development.

PubMed

Nelson, Celeste M; Gleghorn, Jason P; Pang, Mei-Fong; Jaslove, Jacob M; Goodwin, Katharine; Varner, Victor D; Miller, Erin; Radisky, Derek C; Stone, Howard A

2017-12-01

Mechanical forces are increasingly recognized to regulate morphogenesis, but how this is accomplished in the context of the multiple tissue types present within a developing organ remains unclear. Here, we use bioengineered 'microfluidic chest cavities' to precisely control the mechanical environment of the fetal lung. We show that transmural pressure controls airway branching morphogenesis, the frequency of airway smooth muscle contraction, and the rate of developmental maturation of the lungs, as assessed by transcriptional analyses. Time-lapse imaging reveals that branching events are synchronized across distant locations within the lung, and are preceded by long-duration waves of airway smooth muscle contraction. Higher transmural pressure decreases the interval between systemic smooth muscle contractions and increases the rate of morphogenesis of the airway epithelium. These data reveal that the mechanical properties of the microenvironment instruct crosstalk between different tissues to control the development of the embryonic lung. © 2017. Published by The Company of Biologists Ltd.

Signs of antimetastatic activity of palladium complexes of methylenediphosphonic acid in IR spectra

NASA Astrophysics Data System (ADS)

Tolstorozhev, G. B.; Skornyakov, I. V.; Pekhnio, V. I.; Kozachkova, A. N.; Sharykina, N. I.

2012-07-01

We have used Fourier transform IR spectroscopy methods to study normal mouse lung tissue and also after subcutaneous transplantation of a B-16 melanoma tumor in the tissue. We also studied tissues with B-16 melanoma after they were treated with coordination compounds based on palladium complexes of methylenediphosphonic acid. The IR spectra of the lung tissues with metastases in the region of the C = O stretching vibrations are different from the IR spectra of normal tissue. We identified spectroscopic signs of the presence of metastases in the lung. We show that when a cancerous tumor is treated with a preparation of palladium complexes of methylenediphosphonic acid, the spectroscopic signs of the presence of metastases in the lung are missing. After treatment with the optimal dose of this drug, the IR spectrum of the lung tissue in which multiple metastases were present before treatment corresponds to the spectrum of normal tissue. We have determined the efficacy of the antitumor activity of coordination compounds based on palladium complexes of methylenediphosphonic acid.

Genome-wide association study in discordant sibships identifies multiple inherited susceptibility alleles linked to lung cancer.

PubMed

Galvan, Antonella; Falvella, Felicia S; Frullanti, Elisa; Spinola, Monica; Incarbone, Matteo; Nosotti, Mario; Santambrogio, Luigi; Conti, Barbara; Pastorino, Ugo; Gonzalez-Neira, Anna; Dragani, Tommaso A

2010-03-01

We analyzed a series of young (median age = 52 years) non-smoker lung cancer patients and their unaffected siblings as controls, using a genome-wide 620 901 single-nucleotide polymorphism (SNP) array analysis and a case-control DNA pooling approach. We identified 82 putatively associated SNPs that were retested by individual genotyping followed by use of the sib transmission disequilibrium test, pointing to 36 SNPs associated with lung cancer risk in the discordant sibs series. Analysis of these 36 SNPs in a polygenic model characterized by additive and interchangeable effects of rare alleles revealed a highly statistically significant dosage-dependent association between risk allele carrier status and proportion of cancer cases. Replication of the same 36 SNPs in a population-based series confirmed the association with lung cancer for three SNPs, suggesting that phenocopies and genetic heterogeneity can play a major role in the complex genetics of lung cancer risk in the general population.

[Lung and kidney failure. Pathogenesis, interactions, and therapy].

PubMed

John, S; Willam, C

2015-09-01

The lungs and kidneys represent the most often affected organs (acute respiratory distress syndrome, ARDS or kidney failure) in multiple organ failure (MOF) due to shock, trauma, or sepsis with a still unacceptable high mortality for both organ failures. Although the exact pathophysiological mechanisms of MOF are not completely elucidated, it appears that the lungs and kidneys share several pathophysiologic pathways and have the potential to further harm each other (kidney-lung crosstalk). Inflammatory signals in both directions and volume overload with consecutive edema formation in both organs may play a key role in this crosstalk. The organ replacement therapies used in both organ failures have the potential to further injure the other organ (ventilator trauma, dialyte trauma). On the other hand, renal replacement therapy can have positive effects on lung injury by restoring volume and acid-base homeostasis. The new development of "low-flow" extracorporeal CO2 removal on renal replacement therapy platforms may further help to decrease ventilator trauma in the future.

Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors

PubMed Central

Akbay, Esra A; Koyama, Shohei; Carretero, Julian; Altabef, Abigail; Tchaicha, Jeremy H; Christensen, Camilla L; Mikse, Oliver R; Cherniack, Andrew D; Beauchamp, Ellen M; Pugh, Trevor J; Wilkerson, Matthew D; Fecci, Peter E; Butaney, Mohit; Reibel, Jacob B; Soucheray, Margaret; Cohoon, Travis J; Janne, Pasi A; Meyerson, Matthew; Hayes, D. Neil; Shapiro, Geoffrey I; Shimamura, Takeshi; Sholl, Lynette M; Rodig, Scott J; Freeman, Gordon J; Hammerman, Peter S; Dranoff, Glenn; Wong, Kwok-Kin

2013-01-01

The success in lung cancer therapy with Programmed Death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between Epidermal Growth Factor Receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, cytotoxic T lymphocyte antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased cytotoxic T cells and increased markers of T cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T cell function and lowering the levels of tumor-promoting cytokines. Expression of mutant EGFR in bronchial epithelial cells induced PD-L1, and PD-L1 expression was reduced by EGFR inhibitors in non-small cell lung cancer cell lines with activated EGFR. These data suggest that oncogenic EGFR signaling remodels the tumor microenvironment to trigger immune escape, and mechanistically link treatment response to PD-1 inhibition. PMID:24078774

Development and Assessment of Countermeasure Formulations for Treatment of Lung Injury Induced by Chlorine Inhalation

PubMed Central

Hoyle, Gary W.; Chen, Jing; Schlueter, Connie F.; Mo, Yiqun; Humphrey, David M.; Rawson, Greg; Niño, Joe A.; Carson, Kenneth H.

2016-01-01

Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection. Multiple parameters were varied to produce formulations with a wide range of in vitro release kinetics. Testing of selected formulations in chlorine-exposed mice demonstrated efficacy against key aspects of acute lung injury. The results show the feasibility of developing microencapsulated formulations that could be used to treat chlorine-induced acute lung injury by intramuscular injection, which represents a preferred route of administration in a mass casualty situation. PMID:26952014

A 4DCT imaging-based breathing lung model with relative hysteresis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyawaki, Shinjiro; Choi, Sanghun; Hoffman, Eric A.

To reproduce realistic airway motion and airflow, the authors developed a deforming lung computational fluid dynamics (CFD) model based on four-dimensional (4D, space and time) dynamic computed tomography (CT) images. A total of 13 time points within controlled tidal volume respiration were used to account for realistic and irregular lung motion in human volunteers. Because of the irregular motion of 4DCT-based airways, we identified an optimal interpolation method for airway surface deformation during respiration, and implemented a computational solid mechanics-based moving mesh algorithm to produce smooth deforming airway mesh. In addition, we developed physiologically realistic airflow boundary conditions for bothmore » models based on multiple images and a single image. Furthermore, we examined simplified models based on one or two dynamic or static images. By comparing these simplified models with the model based on 13 dynamic images, we investigated the effects of relative hysteresis of lung structure with respect to lung volume, lung deformation, and imaging methods, i.e., dynamic vs. static scans, on CFD-predicted pressure drop. The effect of imaging method on pressure drop was 24 percentage points due to the differences in airflow distribution and airway geometry. - Highlights: • We developed a breathing human lung CFD model based on 4D-dynamic CT images. • The 4DCT-based breathing lung model is able to capture lung relative hysteresis. • A new boundary condition for lung model based on one static CT image was proposed. • The difference between lung models based on 4D and static CT images was quantified.« less

Estimation of Lung Ventilation

NASA Astrophysics Data System (ADS)

Ding, Kai; Cao, Kunlin; Du, Kaifang; Amelon, Ryan; Christensen, Gary E.; Raghavan, Madhavan; Reinhardt, Joseph M.

Since the primary function of the lung is gas exchange, ventilation can be interpreted as an index of lung function in addition to perfusion. Injury and disease processes can alter lung function on a global and/or a local level. MDCT can be used to acquire multiple static breath-hold CT images of the lung taken at different lung volumes, or with proper respiratory control, 4DCT images of the lung reconstructed at different respiratory phases. Image registration can be applied to this data to estimate a deformation field that transforms the lung from one volume configuration to the other. This deformation field can be analyzed to estimate local lung tissue expansion, calculate voxel-by-voxel intensity change, and make biomechanical measurements. The physiologic significance of the registration-based measures of respiratory function can be established by comparing to more conventional measurements, such as nuclear medicine or contrast wash-in/wash-out studies with CT or MR. An important emerging application of these methods is the detection of pulmonary function change in subjects undergoing radiation therapy (RT) for lung cancer. During RT, treatment is commonly limited to sub-therapeutic doses due to unintended toxicity to normal lung tissue. Measurement of pulmonary function may be useful as a planning tool during RT planning, may be useful for tracking the progression of toxicity to nearby normal tissue during RT, and can be used to evaluate the effectiveness of a treatment post-therapy. This chapter reviews the basic measures to estimate regional ventilation from image registration of CT images, the comparison of them to the existing golden standard and the application in radiation therapy.

Fibrocytes Regulate Wilms’ Tumor 1-Positive Cell Accumulation in Severe Fibrotic Lung Disease

PubMed Central

Sontake, Vishwaraj; Shanmukhappa, Shiva K.; DiPasquale, Betsy A.; Reddy, Geereddy B.; Medvedovic, Mario; Hardie, William D.; White, Eric S.; Madala, Satish K.

2015-01-01

Collagen-producing myofibroblast transdifferentiation is considered a crucial determinant in the formation of scar tissue in the lungs of patients with idiopathic pulmonary fibrosis (IPF). Multiple resident pulmonary cell types and bone marrow-derived fibrocytes have been implicated as contributors to fibrotic lesions due to the transdifferentiation potential of these cells into myofibroblasts. In this study, we assessed the expression of Wilms’ tumor 1 (WT1), a known marker of mesothelial cells, in various cell types in normal and fibrotic lungs. We demonstrate that WT1 is expressed by both mesothelial and mesenchymal cells in IPF lungs, but has limited or no expression in normal human lungs. We also demonstrate that WT1-positive cells accumulate in fibrotic lung lesions, using two different mouse models of pulmonary fibrosis and WT1 promoter-driven fluorescent reporter mice. Reconstitution of bone-marrow cells into a transforming growth factor-α transgenic-mouse model demonstrated that fibrocytes do not transform into WT1-positive mesenchymal cells, but do augment accumulation of WT1-positive cells in severe fibrotic lung disease. Importantly, the number of WT1-positive cells in fibrotic lesions were correlated with severity of lung disease as assessed by changes in lung function, histology, and hydroxyproline levels in mice. Finally, inhibition of WT1 expression was sufficient to attenuate collagen and other extracellular-matrix gene production by mesenchymal cells from both murine and human fibrotic lungs. Thus, the results of this study demonstrate a novel association between fibrocyte-driven WT1-positive cell accumulation and severe fibrotic lung disease. PMID:26371248

Unilateral donor lung dysfunction does not preclude successful contralateral single lung transplantation.

PubMed

Puskas, J D; Winton, T L; Miller, J D; Scavuzzo, M; Patterson, G A

1992-05-01

Single lung transplantation remains limited by a severe shortage of suitable donor lungs. Potential lung donors are often deemed unsuitable because accepted criteria (both lungs clear on the chest roentgenogram, arterial oxygen tension greater than 300 mm Hg with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 5 cm H2O, and no purulent secretions) do not distinguish between unilateral and bilateral pulmonary disease. Many adequate single lung grafts may be discarded as a result of contralateral aspiration or pulmonary trauma. We have recently used intraoperative unilateral ventilation and perfusion to assess single lung function in potential donors with contralateral lung disease. In the 11-month period ending October 1, 1990, we performed 18 single lung transplants. In four of these cases (22%), the donor chest roentgenogram or bronchoscopic examination demonstrated significant unilateral lung injury. Donor arterial oxygen tension, (inspired oxygen fraction 1.0; positive end-expiratory pressure 5 cm H2O) was below the accepted level in each case (246 +/- 47 mm Hg, mean +/- standard deviation). Through the sternotomy used for multiple organ harvest, the pulmonary artery to the injured lung was clamped. A double-lumen endotracheal tube or endobronchial balloon occlusion catheter was used to permit ventilation of the uninjured lung alone. A second measurement of arterial oxygen tension (inspired oxygen fraction 1.0; positive end-expiratory pressure 5 cm H2O) revealed excellent unilateral lung function in all four cases (499.5 +/- 43 mm Hg; p less than 0.0004). These single lung grafts (three right, one left) were transplanted uneventfully into four recipients (three with pulmonary fibrosis and one with primary pulmonary hypertension). Lung function early after transplantation was adequate in all patients. Two patients were extubated within 24 hours. There were two late deaths, one caused by rejection and Aspergillus infection and the other caused by cytomegalovirus 6 months after transplantation. Two patients are alive and doing well. We conclude that assessment of unilateral lung function in potential lung donors is indicated in selected cases, may be quickly and easily performed, and may significantly increase the availability of single lung grafts.

A multiscale MDCT image-based breathing lung model with time-varying regional ventilation

PubMed Central

Yin, Youbing; Choi, Jiwoong; Hoffman, Eric A.; Tawhai, Merryn H.; Lin, Ching-Long

2012-01-01

A novel algorithm is presented that links local structural variables (regional ventilation and deforming central airways) to global function (total lung volume) in the lung over three imaged lung volumes, to derive a breathing lung model for computational fluid dynamics simulation. The algorithm constitutes the core of an integrative, image-based computational framework for subject-specific simulation of the breathing lung. For the first time, the algorithm is applied to three multi-detector row computed tomography (MDCT) volumetric lung images of the same individual. A key technique in linking global and local variables over multiple images is an in-house mass-preserving image registration method. Throughout breathing cycles, cubic interpolation is employed to ensure C1 continuity in constructing time-varying regional ventilation at the whole lung level, flow rate fractions exiting the terminal airways, and airway deformation. The imaged exit airway flow rate fractions are derived from regional ventilation with the aid of a three-dimensional (3D) and one-dimensional (1D) coupled airway tree that connects the airways to the alveolar tissue. An in-house parallel large-eddy simulation (LES) technique is adopted to capture turbulent-transitional-laminar flows in both normal and deep breathing conditions. The results obtained by the proposed algorithm when using three lung volume images are compared with those using only one or two volume images. The three-volume-based lung model produces physiologically-consistent time-varying pressure and ventilation distribution. The one-volume-based lung model under-predicts pressure drop and yields un-physiological lobar ventilation. The two-volume-based model can account for airway deformation and non-uniform regional ventilation to some extent, but does not capture the non-linear features of the lung. PMID:23794749

CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation.

PubMed

Sunday, M E; Hua, J; Torday, J S; Reyes, B; Shipp, M A

1992-12-01

The cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) functions in multiple organ systems to downregulate responses to peptide hormones. Recently, CD10/NEP was found to hydrolyze bombesin-like peptides (BLP), which are mitogens for normal bronchial epithelial cells and small cell lung carcinomas. Growth of BLP-responsive small cell lung carcinomas was potentiated by CD10/NEP inhibition, implicating CD10/NEP in regulation of BLP-mediated tumor growth. BLP are also likely to participate in normal lung development because high BLP levels are found in fetal lung, and bombesin induces proliferation and maturation of human fetal lung in organ cultures and murine fetal lung in utero. To explore potential roles for CD10/NEP in regulating peptide-mediated human fetal lung development, we have characterized temporal and cellular patterns of CD10/NEP expression and effects of CD10/NEP inhibition in organ cultures. Peak CD10/NEP transcript levels are identified at 11-13 wk gestation by Northern blots and localized to epithelial cells and mesenchyme of developing airways by in situ hybridization. CD10/NEP immunostaining is most intense in undifferentiated airway epithelium. In human fetal lung organ cultures, inhibition of CD10/NEP with either phosphoramidon or SCH32615 increases thymidine incorporation by 166-182% (P < 0.025). The specific BLP receptor antagonist, [Leu13-psi(CH2NH)Leu14]bombesin abolishes these effects on fetal lung growth, suggesting that CD10/NEP modulates BLP-mediated proliferation. CD10/NEP expression in the growing front of airway epithelium and the effects of CD10/NEP inhibitors in lung explants implicate the enzyme in the regulation of peptide-mediated fetal lung growth.

Meta-markers for the differential diagnosis of lung cancer and lung disease.

PubMed

Kim, Yong-In; Ahn, Jung-Mo; Sung, Hye-Jin; Na, Sang-Su; Hwang, Jaesung; Kim, Yongdai; Cho, Je-Yoel

2016-10-04

Misdiagnosis of lung cancer remains a serious problem due to the difficulty of distinguishing lung cancer from other respiratory lung diseases. As a result, the development of serum-based differential diagnostic biomarkers is in high demand. In this study, 198 clinical serum samples from non-cancer lung disease and lung cancer patients were analyzed using nLC-MRM-MS for the levels of seven lung cancer biomarker candidates. When the candidates were assessed individually, only SERPINEA4 showed statistically significant changes in the serum levels. The MRM results and clinical information were analyzed using a logistic regression analysis to select model for the best 'meta-marker', or combination of biomarkers for differential diagnosis. Also, under consideration of statistical interaction, variables having low significance as a single factor but statistically influencing on meta-marker model were selected. Using this probabilistic classification, the best meta-marker was determined to be made up of two proteins SERPINA4 and PON1 with age factor. This meta-marker showed an enhanced differential diagnostic capability (AUC=0.915) for distinguishing the two patient groups. Our results suggest that a statistical model can determine optimal meta-markers, which may have better specificity and sensitivity than a single biomarker and thus improve the differential diagnosis of lung cancer and lung disease patients. Diagnosing lung cancer commonly involves the use of radiographic methods. However, an imaging-based diagnosis may fail to differentiate lung cancer from non-cancerous lung disease. In this study, we examined several serum proteins in the sera of 198 lung cancer and non-cancerous lung disease patients by multiple-reaction monitoring. We then used a combination of variables to generate a meta-marker model that is useful as a differential diagnostic biomarker. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Pulmonary Sequestration: Early Diagnosis and Management

PubMed Central

Wani, Sajad A.; Mufti, Gowher N.; Bhat, Nisar A.; Baba, Ajaz A.

2015-01-01

Intralobar sequestration is characterized by aberrant formation of nonfunctional lung tissue that has no communication with the bronchial tree and receives systemic arterial blood supply. Failure of earlier diagnosis can lead to recurrent pneumonia, failure to thrive, multiple hospital admissions, and more morbidity. The aim of this case report is to increase the awareness about the lung sequestration, to diagnose and treat it early, so that it is resected before repeated infection, and prevent the morbidity and mortality. PMID:26273485

Development of Welding Fumes Health Index (WFHI) for Welding Workplace's Safety and Health Assessment.

PubMed

Hariri, Azian; Paiman, Nuur Azreen; Leman, Abdul Mutalib; Md Yusof, Mohammad Zainal

2014-08-01

This study aimed to develop an index that can rank welding workplace that associate well with possible health risk of welders. Welding Fumes Health Index (WFHI) were developed based on data from case studies conducted in Plant 1 and Plant 2. Personal sampling of welding fumes to assess the concentration of metal constituents along with series of lung function tests was conducted. Fifteen metal constituents were investigated in each case study. Index values were derived from aggregation analysis of metal constituent concentration while significant lung functions were recognized through statistical analysis in each plant. The results showed none of the metal constituent concentration was exceeding the permissible exposure limit (PEL) for all plants. However, statistical analysis showed significant mean differences of lung functions between welders and non-welders. The index was then applied to one of the welding industry (Plant 3) for verification purpose. The developed index showed its promising ability to rank welding workplace, according to the multiple constituent concentrations of welding fumes that associates well with lung functions of the investigated welders. There was possibility that some of the metal constituents were below the detection limit leading to '0' value of sub index, thus the multiplicative form of aggregation model was not suitable for analysis. On the other hand, maximum or minimum operator forms suffer from compensation issues and were not considered in this study.

Large-scale isotype-specific quantification of Serum amyloid A 1/2 by multiple reaction monitoring in crude sera.

PubMed

Sung, Hye-Jin; Jeon, Seon-Ae; Ahn, Jung-Mo; Seul, Kyung-Jo; Kim, Jin Young; Lee, Ju Yeon; Yoo, Jong Shin; Lee, Soo-Youn; Kim, Hojoong; Cho, Je-Yoel

2012-04-03

Quantification is an essential step in biomarker development. Multiple reaction monitoring (MRM) is a new modified mass spectrometry-based quantification technology that does not require antibody development. Serum amyloid A (SAA) is a positive acute-phase protein identified as a lung cancer biomarker in our previous study. Acute SAA exists in two isoforms with highly similar (92%) amino acid sequences. Until now, studies of SAA have been unable to distinguish between SAA1 and SAA2. To overcome the unavailability of a SAA2-specific antibody, we developed MRM methodology for the verification of SAA1 and SAA2 in clinical crude serum samples from 99 healthy controls and 100 lung adenocarcinoma patients. Differential measurement of SAA1 and SAA2 was made possible for the first time with the developed isotype-specific MRM method. Most healthy control samples had small or no MS/MS peaks of the targeted peptides otherwise, higher peak areas with 10- to 34-fold increase over controls were detected in lung cancer samples. In addition, our SAA1 MRM data demonstrated good agreement with the SAA1 enzyme-linked immunosorbent assay (ELISA) data. Finally, successful quantification of SAA2 in crude serum by MRM, for the first time, shows that SAA2 can be a good biomarker for the detection of lung cancers. Copyright © 2012 Elsevier B.V. All rights reserved.

Repulsive Interaction of Sulfide Layers on Compressor Impeller Blades Remanufactured Through Plasma Spray Welding

NASA Astrophysics Data System (ADS)

Chang, Y.; Zhou, D.; Wang, Y. L.; Huang, H. H.

2016-12-01

This study investigated the repulsive interaction of sulfide layers on compressor impeller blades remanufactured through plasma spray welding (PSW). Sulfide layers on the blades made of FV(520)B steel were prepared through multifarious corrosion experiments, and PSW was utilized to remanufacture blade specimens. The specimens were evaluated through optical microscopy, scanning electron microscopy, energy-dispersive spectroscopy, 3D surface topography, x-ray diffraction, ImageJ software analysis, Vicker's micro-hardness test and tensile tests. Results showed a large number of sulfide inclusions in the fusion zone generated by sulfide layers embodied into the molten pool during PSW. These sulfide inclusions seriously degraded the mechanical performance of the blades remanufactured through PSW.

The suppression of apoptosis by α-herpesvirus

PubMed Central

You, Yu; Cheng, An-Chun; Wang, Ming-Shu; Jia, Ren-Yong; Sun, Kun-Feng; Yang, Qiao; Wu, Ying; Zhu, Dekang; Chen, Shun; Liu, Ma-Feng; Zhao, Xin-Xin; Chen, Xiao-Yue

2017-01-01

Apoptosis, an important innate immune mechanism that eliminates pathogen-infected cells, is primarily triggered by two signalling pathways: the death receptor pathway and the mitochondria-mediated pathway. However, many viruses have evolved various strategies to suppress apoptosis by encoding anti-apoptotic factors or regulating apoptotic signalling pathways, which promote viral propagation and evasion of the host defence. During its life cycle, α-herpesvirus utilizes an elegant multifarious anti-apoptotic strategy to suppress programmed cell death. This progress article primarily focuses on the current understanding of the apoptosis-inhibition mechanisms of α-herpesvirus anti-apoptotic genes and their expression products and discusses future directions, including how the anti-apoptotic function of herpesvirus could be targeted therapeutically. PMID:28406478

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suleimanov, Yury V.; Aoiz, F. Javier; Guo, Hua

This Feature Article presents an overview of the current status of ring polymer molecular dynamics (RPMD) rate theory. We first analyze the RPMD approach and its connection to quantum transition-state theory. We then focus on its practical applications to prototypical chemical reactions in the gas phase, which demonstrate how accurate and reliable RPMD is for calculating thermal chemical reaction rate coefficients in multifarious cases. This review serves as an important checkpoint in RPMD rate theory development, which shows that RPMD is shifting from being just one of recent novel ideas to a well-established and validated alternative to conventional techniques formore » calculating thermal chemical rate coefficients. We also hope it will motivate further applications of RPMD to various chemical reactions.« less

[Advances in researches on mechanism of anti-Toxoplasma Chinese herbal medicine].

PubMed

Yu, Zhao-Yun; Zhang, Bao-de; Ning, Jun-ya; Wang, Yuan-yuan; Yuan, Wen-ying

2015-10-01

Toxoplasma gondii is an opportunity cellular parasite, related to the infection of various animals and human beings and severely impairing agriculture and human health. Because of the complexity of T. gondii life cycle, its different biological characteristics, and multifarious pathogenesis, there are no specific treatment and preventive medicines at present. Chinese herbal medicine can balance "yin-yang" and regulate the immunity and its side-effect is slight. Now, it has been a hot topic of the research on effective and secure medicines in anti-toxoplasmosis. This paper summarizes and analyzes the curative effect and mechanism of anti-Toxoplasma Chinese herbal medicine, such as Scutellaria baicalensis, Inontus obliquus polysaccharide, Radix glycyrrhizae, pumpkin seeds, and Semen arecae.

[Interest of crizotinib in a lung cancer patient with de novo amplification of MET].

PubMed

Rabeau, A; Rouquette, I; Vantelon, J-M; Taranchon-Clermont, E; Mazières, J

2017-01-01

Targeted therapy in lung cancer changes the prognostic and treatment of patients. MET is an oncogene including exon 14 mutations and gene amplification associated with worse prognosis. We here report the case of a 47-year-old former smoker, woman, with a stage IV lung adenocarcinoma with multiple chemotherapy failure. A MET amplification was identified and the patient consequently received crizotinib. A major response was observed after eight weeks of treatment. MET amplification screening appears to be interesting with some oncogenic-addicted tumor response rate. Those patients should be enrolled in clinical trials dedicated to tumor with MET alteration. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Diagnosis and treatment of pulmonary hypertension in infancy

PubMed Central

Steinhorn, Robin H.

2013-01-01

Normal pulmonary vascular development in infancy requires maintenance of low pulmonary vascular resistance after birth, and is necessary for normal lung function and growth. The developing lung is subject to multiple genetic, pathological and/or environmental influences that can adversely affect lung adaptation, development, and growth, leading to pulmonary hypertension. New classifications of pulmonary hypertension are beginning to account for these diverse phenotypes, and or pulmonary hypertension in infants due to PPHN, congenital diaphragmatic hernia, and bronchopulmonary dysplasia (BPD). The most effective pharmacotherapeutic strategies for infants with PPHN are directed at selective reduction of PVR, and take advantage of a rapidly advancing understanding of the altered signaling pathways in the remodeled vasculature. PMID:24083892

Targeted therapy in lung cancer: IPASS and beyond, keeping abreast of the explosion of targeted therapies for lung cancer

PubMed Central

Savas, Peter; Hughes, Brett

2013-01-01

Advances in the treatment of non-small cell lung cancer (NSCLC) over the last decade have predominantly involved the development of therapies directed at molecular targets such as mutations in the epidermal growth factor receptor (EGFR) or rearrangements in the anaplastic lymphoma kinase (ALK) gene. Other targets have been discovered at low frequency, with multiple agents approved or in development for treatment of these rare molecular subtypes. The tumour microenvironment has also provided opportunities for therapies targeting angiogenesis and the host immune response. This review will provide an overview of current targeted therapies in NSCLC and promising treatment approaches on the horizon. PMID:24163750

Lung Motion Model Validation Experiments, Free-Breathing Tissue Densitometry, and Ventilation Mapping using Fast Helical CT Imaging

NASA Astrophysics Data System (ADS)

Dou, Hsiang-Tai

The uncertainties due to respiratory motion present significant challenges to accurate characterization of cancerous tissues both in terms of imaging and treatment. Currently available clinical lung imaging techniques are subject to inferior image quality and incorrect motion estimation, with consequences that can systematically impact the downstream treatment delivery and outcome. The main objective of this thesis is the development of the techniques of fast helical computed tomography (CT) imaging and deformable image registration for the radiotherapy applications in accurate breathing motion modeling, lung tissue density modeling and ventilation imaging. Fast helical CT scanning was performed on 64-slice CT scanner using the shortest available gantry rotation time and largest pitch value such that scanning of the thorax region amounts to just two seconds, which is less than typical breathing cycle in humans. The scanning was conducted under free breathing condition. Any portion of the lung anatomy undergoing such scanning protocol would be irradiated for only a quarter second, effectively removing any motion induced image artifacts. The resulting CT data were pristine volumetric images that record the lung tissue position and density in a fraction of the breathing cycle. Following our developed protocol, multiple fast helical CT scans were acquired to sample the tissue positions in different breathing states. To measure the tissue displacement, deformable image registration was performed that registers the non-reference images to the reference one. In modeling breathing motion, external breathing surrogate signal was recorded synchronously with the CT image slices. This allowed for the tissue-specific displacement to be modeled as parametrization of the recorded breathing signal using the 5D lung motion model. To assess the accuracy of the motion model in describing tissue position change, the model was used to simulate the original high-pitch helical CT scan geometries, employed as ground truth data. Image similarity between the simulated and ground truth scans was evaluated. The model validation experiments were conducted in a patient cohort of seventeen patients to assess the model robustness and inter-patient variation. The model error averaged over multiple tracked positions from several breathing cycles was found to be on the order of one millimeter. In modeling the density change under free breathing condition, the determinant of Jacobian matrix from the registration-derived deformation vector field yielded volume change information of the lung tissues. Correlation of the Jacobian values to the corresponding voxel Housfield units (HU) reveals that the density variation for the majority of lung tissues can be very well described by mass conservation relationship. Different tissue types were identified and separately modeled. Large trials of validation experiments were performed. The averaged deviation between the modeled and the reference lung density was 30 HU, which was estimated to be the background CT noise level. In characterizing the lung ventilation function, a novel method was developed to determine the extent of lung tissue volume change. Information on volume change was derived from the deformable image registration of the fast helical CT images in terms of Jacobian values with respect to a reference image. Assuming the multiple volume change measurements are independently and identically distributed, statistical formulation was derived to model ventilation distribution of each lung voxels and empirical minimum and maximum probability distribution of the Jacobian values was computed. Ventilation characteristic was evaluated as the difference of the expectation value from these extremal distributions. The resulting ventilation map was compared with an independently obtained ventilation image derived directly from the lung intensities and good correlation was found using statistical test. In addition, dynamic ventilation characterization was investigated by estimating the voxel-specific ventilation distribution. Ventilation maps were generated at different percentile levels using the tissue volume expansion metrics.

Apatinib: a promising oral antiangiogenic agent in the treatment of multiple solid tumors.

PubMed

Scott, A J; Messersmith, W A; Jimeno, A

2015-04-01

Aberrant proangiogenic pathways have long been implicated in tumorigenesis and metastasis. Antiangiogenic therapies have shown efficacy in the treatment of a variety of solid tumors including lung, breast, colon, glioblastomas, and other solid tumor types. Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), is an orally bioavailable agent currently being studied in multiple tumor types. Apatinib has shown a survival benefit in gastric cancer in a phase III trial and non-small cell lung cancer in a phase II trial. With a favorable side effect profile and improved outcomes, apatinib has demonstrated a substantial potential to augment therapeutic options in a variety of tumor types. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

[Anesthetic complications in sequential bipulmonary transplantation in patients with cystic fibrosis. Apropos of 6 cases].

PubMed

López, L M; Vicente, R; Ramos, F; Palacios, L; Calvo, A; Hernández, S; Borro, J M; Morales, P; Montero, R

1996-03-01

Cystic fibrosis (CF) is a disease characterized mainly by altered exocrine gland function that eventually produces irreversible dysfunction of the pancreas and lungs. The respiratory insufficiency that develops in CF patients in the advanced stages of disease can only be corrected at this time by lung or heart-lung transplantation. We describe our experience with 6 terminal phase CF patients who underwent sequential double lung transplantation (SDLT). Anesthesia was intravenous, with exhaustive hemodynamic and respiratory monitoring. During surgery the most frequently encountered hemodynamic complications were low minute volume, arterial hypotension and irregular heart rate. The main respiratory complications were hypoxemia, hypercapnia and pulmonary edema of the implanted lung, which developed in all cases to varying degrees related to the organ's state of preservation and duration of ischemia. Other complications were the need for extracorporeal circulation in 1 case, oliguria and blood loss requiring multiple transfusions. The most critical moments were at the time of clamping the pulmonary artery, the period after revascularization of the donated lung, and at the start of patient ventilation through the first implanted lung so that the second could be implanted. Although our series is small, it is of interest given the limited Spanish experience with lung transplantation in CF patients, and the good early results obtained, which are similar to those reported for other diseases.

Over-expression of angiotensin II type 2 receptor gene induces cell death in lung adenocarcinoma cells.

PubMed

Pickel, Lara; Matsuzuka, Takaya; Doi, Chiyo; Ayuzawa, Rie; Maurya, Dharmendra Kumar; Xie, Sheng-Xue; Berkland, Cory; Tamura, Masaaki

2010-02-01

The endogenous angiotensin II (Ang II) type 2 receptor (AT 2) has been shown to mediate apoptosis in cardiovascular tissues. Thus, the aim of this study was to explore the anti-cancer effect of AT 2 over-expression on lung adenocarcinoma cells in vitro using adenoviral (Ad), FuGENE, and nanoparticle vectors. All three gene transfection methods efficiently transfected AT 2 cDNA into lung cancer cells but caused minimal gene transfection in normal lung epithelial cells. Ad-AT 2 significantly attenuated multiple human lung cancer cell growth (A549 and H358) as compared to the control viral vector, Ad-LacZ, when cell viability was examined by direct cell count. Examination of annexin V by flow cytometry revealed the activation of the apoptotic pathway via AT 2 over-expression. Western Blot analysis confirmed the activation of caspase-3. Similarly, poly (lactide-co-glycolic acid) (PLGA) biodegradable nanoparticles encapsulated AT 2 plasmid DNA were shown to be effectively taken up into the lung cancer cell. Nanoparticle-based AT 2 gene transfection markedly increased AT 2 expression and resultant cell death in A549 cells. These results indicate that AT 2 over-expression effectively attenuates growth of lung adenocarcinoma cells through intrinsic apoptosis. Our results also suggest that PLGA nanoparticles can be used as an efficient gene delivery vector for lung adenocarcinoma targeted therapy.

Rationale and Design of the Lung Cancer Screening Implementation. Evaluation of Patient-Centered Care Study.

PubMed

Miranda, Leah S; Datta, Santanu; Melzer, Anne C; Wiener, Renda Soylemez; Davis, James M; Tong, Betty C; Golden, Sara E; Slatore, Christopher G

2017-10-01

Screening for lung cancer using low-dose computed tomography has been demonstrated to reduce lung cancer-related mortality and is being widely implemented. Further research in this area is needed to assess the impact of screening on patient-centered outcomes. Here, we describe the design and rationale for a new study entitled Lung Cancer Screening Implementation: Evaluation of Patient-Centered Care. The protocol is composed of an interconnected series of studies evaluating patients and clinicians who are engaged in lung cancer screening in real-world settings. The primary goal of this study is to evaluate communication processes that are being used in routine care and to identify best practices that can be readily scaled up for implementation in multiple settings. We hypothesize that higher overall quality of patient-clinician communication processes will be associated with lower levels of distress and decisional conflict as patients decide whether or not to participate in lung cancer screening. This work is a critical step toward identifying modifiable mechanisms that are associated with high quality of care for the millions of patients who will consider lung cancer screening. Given the enormous potential benefits and burdens of lung cancer screening on patients, clinicians, and the healthcare system, it is important to identify and then scale up quality communication practices that positively influence patient-centered care.

Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study.

PubMed

Jiang, Cheng-Lan; He, Shui-Wang; Zhang, Yun-Dong; Duan, He-Xian; Huang, Tao; Huang, Yun-Chao; Li, Gao-Feng; Wang, Ping; Ma, Li-Ju; Zhou, Guang-Biao; Cao, Yi

2017-01-03

The lung cancer incidence in the Xuanwei and neighboring region, Yunnan, China, is among the highest in China and is attributed to severe air pollution with high benzo(a)pyrene levels. We systematically and comparatively analyzed DNA methylation alterations at genome and gene levels in Xuanwei lung cancer tissues and cell lines, as well as benzo(a)pyrene-treated cells and mouse samples. We obtained a comprehensive dataset of genome-wide cytosine-phosphate-guanine island methylation in air pollution-related lung cancer samples. Benzo(a)pyrene exposure induced multiple alterations in DNA methylation and in mRNA expressions of DNA methyltransferases and ten-11 translocation proteins; these alterations partially occurred in Xuanwei lung cancer. Furthermore, benzo(a)pyrene-induced DKK2 and EN1 promoter hypermethylation and LPAR2 promoter hypomethylation led to down-regulation and up-regulation of the genes, respectively; the down-regulation of DKK2 and EN1 promoted the cellular proliferation. Thus, DNA methylation alterations induced by benzo(a)pyrene contribute partially to abnormal DNA methylation in air pollution-related lung cancer, and these DNA methylation alterations may affect the development and progression of lung cancer. Additionally, vitamin C and B6 can reduce benzo(a)pyrene-induced DNA methylation alterations and may be used as chemopreventive agents for air pollution-related lung cancer.

Peripheral 5-HT7 receptors as a new target for prevention of lung injury and mortality in septic rats.

PubMed

Cadirci, Elif; Halici, Zekai; Bayir, Yasin; Albayrak, Abdulmecit; Karakus, Emre; Polat, Beyzagul; Unal, Deniz; Atamanalp, Sabri S; Aksak, Selina; Gundogdu, Cemal

2013-10-01

Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality. Copyright © 2013 Elsevier GmbH. All rights reserved.

Noninvasive measurement of lung carbon-11-serotonin extraction in man

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coates, G.; Firnau, G.; Meyer, G.J.

1991-04-01

The fraction of serotonin extracted on a single passage through the lungs is being used as an early indicator of lung endothelial damage but the existing techniques require multiple arterial blood samples. We have developed a noninvasive technique to measure lung serotonin uptake in man. We utilized the double indicator diffusion principle, a positron camera, {sup 11}C-serotonin as the substrate, and {sup 11}CO-erythrocytes as the vascular marker. From regions of interest around each lung, we recorded time-activity curves in 0.5-sec frames for 30 sec after a bolus injection of first the vascular marker {sup 11}CO-erythrocytes and 10 min later {supmore » 11}C-serotonin. A second uptake measurement was made after imipramine 25-35 mg was infused intravenously. In three normal volunteers, the single-pass uptake of {sup 11}C-serotonin was 63.9% +/- 3.6%. This decreased in all subjects to a mean of 53.6% +/- 1.4% after imipramine. The rate of lung washout of {sup 11}C was also significantly prolonged after imipramine. This noninvasive technique can be used to measure lung serotonin uptake to detect early changes in a variety of conditions that alter the integrity of the pulmonary endothelium.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neft, R.E.; Rogers, J.L.; Belinsky, S.A.

Epidemiological studies have shown that combined exposure to radon progeny and tobacco smoke produce a greater than additive or synergistic increase in lung cancer risk. Lung cancer results from multiple genetic changes over a long period of time. An early change that occurs in lung cancer is trisomy 7 which is found in 50% of non-small cell lung cancer and in the far margins of resected lung tumors. The 80% mortality associated with lung cancer is in part related to the high proportion of patients who present with an advanced, unresectable tumor. Therefore, early detection of patients at risk formore » tumor development is critical to improve treatment of this disease. Currently, it is difficult to detect lung cancer early while it is still amendable by surgery. Saccomanno, G. has shown that premalignant cytologic changes in sputum cells collected from uranium miners can be detected by a skilled, highly trained cytopathologist. A more objective alternative for identifying premalignant cells in sputum may be to determine whether an early genetic change such as trisomy 7 is present in these cells. Fluorescence in situ hybridization (FISH) can be used to identify cells with trisomy 7. The results of this investigation indicate that FISH may prove to be an accurate, efficient method to test at-risk individuals for genetic alterations in bronchial epithelial cells from sputum.« less

Silica dust, diesel exhaust, and painting work are the significant occupational risk factors for lung cancer in nonsmoking Chinese men

PubMed Central

Tse, L A; Yu, IT-s; Au, J S K; Qiu, H; Wang, X-r

2011-01-01

Background: Few epidemiological studies have explored the associations between occupational exposures and lung cancer in lifelong nonsmoking men. Methods: We obtained lifetime occupational history and other relevant information for 132 newly diagnosed lung cancer cases among nonsmoking Chinese men and 536 nonsmoking community referents. Unconditional multiple logistic regression analysis was performed to estimate the odds ratio (OR) of lung cancer for specific occupational exposures. Results: Significantly increased lung cancer risk was found for nonsmoking workers occupationally exposed to silica dust (OR=2.58, 95% confidence interval (CI): 1.11, 6.01), diesel exhaust (OR=3.47, 95% CI: 1.08, 11.14), spray painting (OR=2.81, 95% CI: 1.14, 6.93), and nonspray painting work (OR=2.36, 95% CI: 1.04, 5.37). Silica dust exposure was associated with a significantly increased risk of adenocarcinoma (OR=2.91, 95% CI: 1.10, 7.68). We observed a positive gradient of all lung cancers and of adenocarcinoma with duration of employment for workers exposed to silica dust and spray painting. Conclusion: This study found an increased risk of lung cancer among nonsmoking Chinese men occupationally exposed to silica dust, diesel exhaust, and painting work. PMID:21102581

Lung function in type 2 diabetes: the Normative Aging Study.

PubMed

Litonjua, Augusto A; Lazarus, Ross; Sparrow, David; Demolles, Debbie; Weiss, Scott T

2005-12-01

Cross-sectional studies have noted that subjects with diabetes have lower lung function than non-diabetic subjects. We conducted this analysis to determine whether diabetic subjects have different rates of lung function change compared with non-diabetic subjects. We conducted a nested case-control analysis in 352 men who developed diabetes and 352 non-diabetic subjects in a longitudinal observational study of aging in men. We assessed lung function among cases and controls at three time points: Time0, prior to meeting the definition of diabetes; Time1, the point when the definition of diabetes was met; and Time2, the most recent follow-up exam. Cases had lower forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) at all time points, even with adjustment for age, height, weight, and smoking. In multiple linear regression models adjusting for relevant covariates, there were no differences in rates of FEV1 or FVC change over time between cases and controls. Men who are predisposed to develop diabetes have decreased lung function many years prior to the diagnosis, compared with men who do not develop diabetes. This decrement in lung function remains after the development of diabetes. We postulate that mechanisms involved in the insulin resistant state contribute to the diminished lung function observed in our subjects.

Primary lung abscess caused by Staphylococcus lugdunensis.

PubMed

Chou, Deng-Wei; Lee, Chao-Tai

2017-11-01

Staphylococcus lugdunensis, a strain of coagulase-negative staphylococci, is part of the normal flora of human skin but can cause multiple infections at various sites. This microorganism has emerged as a major human pathogen. However, no study has reported primary lung abscess caused by S. lugdunensis. A 54-year-old alcoholic man without relevant past medical history was admitted because of primary lung abscesses. Empirical amoxicillin/clavulanate therapy was initially administered; however, the patient had persistent pleuritic chest pain and fever. He subsequently underwent resection of the lung abscess and removal of exudative pleural effusion on the fourth hospital day. Histopathologic examination confirmed the diagnosis of lung abscess, and colonies of gram-positive bacteria were identified. The culture specimen from the abscess was positive for S. lugdunensis, which was susceptible to amoxicillin/clavulanate, cefazolin, ciprofloxacin, clindamycin, erythromycin, oxacillin, teicoplanin, tetracycline, and vancomycin. Following resection and 3 weeks of amoxicillin/clavulanate therapy, the patient eventually recovered well without relapse. This case report is the first to describe S. lugdunensis as a cause of primary lung abscess; this microorganism should be considered a potential monomicrobial pathogen in primary lung abscess. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Lung transplantation for lymphangioleiomyomatosis: the European experience.

PubMed

Benden, Christian; Rea, Federico; Behr, Jürgen; Corris, Paul A; Reynaud-Gaubert, Martine; Stern, Marc; Speich, Rudolf; Boehler, Annette

2009-01-01

Lung transplantation has been accepted widely as therapy for end-stage pulmonary lymphangioleiomyomatosis (LAM); however, single-center and national experience is limited due to the rarity of LAM. We report the recent European experience of lung transplantation for LAM. A self-administered questionnaire was distributed to 30 European lung transplant centers to evaluate patients who underwent primary lung transplantation for LAM (1997 to 2007). Seventy percent of centers responded to the questionnaire. A total of 61 lung transplants were undertaken in women only, with mean age at transplant 41.3 years (SD 5.1). Centers performed a median of 2 (0 to 9) transplant operations. Severe pleural adhesions were the most common intra-operative complication. Early deaths (N = 6) were due to primary graft or multiple-organ failure or sepsis. Twelve recipients were diagnosed with bronchiolitis obliterans syndrome at a median of 20 months (range 10 to 86 months) post-transplant. LAM-related complications included renal angiomyolipoma and pneumothorax in the native lung. Recurrence of LAM occurred in 4 recipients. As of December 2007, actuarial Kaplan-Meier survival was 79% at 1 year and 73% at 3 years post-transplant. Post-transplant outcome for pulmonary LAM in the recent era appears to have improved compared with the previous era. LAM-related complications remain common, but recurrence of LAM in the allograft is rare.

Respiratory bronchiolitis-associated interstitial lung disease secondary to electronic nicotine delivery system use confirmed with open lung biopsy.

PubMed

Flower, Mark; Nandakumar, Lakshmy; Singh, Mahendra; Wyld, David; Windsor, Morgan; Fielding, David

2017-05-01

As a modern phenomenon, there is currently limited understanding of the possible toxic effects and broader implications of electronic nicotine delivery systems (ENDS). Large volumes of aerosolized particles are inhaled during "vaping" and there are now an increasing number of case reports demonstrating toxic effects of ENDS, as well as human studies demonstrating impaired lung function in users. This article presents a case of respiratory bronchiolitis interstitial lung disease (RB-ILD) precipitated by vaping in a 33-year-old male with 10 pack years of traditional cigarette and prior treatment for mixed germ cell tumour. The patient had started vaping 10-15 times per day while continuing to smoke 10 traditional cigarettes per day. After 3 months of exposure to e-cigarette vapour, chest computed tomography demonstrated multiple new poorly defined pulmonary nodules with fluffy parenchyma opacification centred along the terminal bronchovascular units. Video-assisted thoracoscopy with lung biopsy of the right upper and right middle lobes was undertaken. The microscopic findings were overall consistent with RB-ILD. This case demonstrates toxicity with use of ENDS on open lung biopsy with resolution of radiographic findings on cessation. We believe that this is the first case where open lung biopsy has demonstrated this and our findings are consistent with RB-ILD.

Longitudinal analysis of the lung microbiota of cynomolgous macaques during long-term SHIV infection.

PubMed

Morris, Alison; Paulson, Joseph N; Talukder, Hisham; Tipton, Laura; Kling, Heather; Cui, Lijia; Fitch, Adam; Pop, Mihai; Norris, Karen A; Ghedin, Elodie

2016-07-08

Longitudinal studies of the lung microbiome are challenging due to the invasive nature of sample collection. In addition, studies of the lung microbiome in human disease are usually performed after disease onset, limiting the ability to determine early events in the lung. We used a non-human primate model to assess lung microbiome alterations over time in response to an HIV-like immunosuppression and determined impact of the lung microbiome on development of obstructive lung disease. Cynomolgous macaques were infected with the SIV-HIV chimeric virus SHIV89.6P. Bronchoalveolar lavage fluid samples were collected pre-infection and every 4 weeks for 53 weeks post-infection. The microbiota was characterized at each time point by 16S ribosomal RNA (rRNA) sequencing. We observed individual variation in the composition of the lung microbiota with a proportion of the macaques having Tropheryma whipplei as the dominant organism in their lungs. Bacterial communities varied over time both within and between animals, but there did not appear to be a systematic alteration due to SHIV infection. Development of obstructive lung disease in the SHIV-infected animals was characterized by a relative increase in abundance of oral anaerobes. Network analysis further identified a difference in community composition that accompanied the development of obstructive disease with negative correlations between members of the obstructed and non-obstructed groups. This emphasizes how species shifts can impact multiple other species, potentially resulting in disease. This study is the first to investigate the dynamics of the lung microbiota over time and in response to immunosuppression in a non-human primate model. The persistence of oral bacteria in the lung and their association with obstruction suggest a potential role in pathogenesis. The lung microbiome in the non-human primate is a valuable tool for examining the impact of the lung microbiome in human health and disease.

Registration-based assessment of regional lung function via volumetric CT images of normal subjects vs. severe asthmatics

PubMed Central

Choi, Sanghun; Hoffman, Eric A.; Wenzel, Sally E.; Tawhai, Merryn H.; Yin, Youbing; Castro, Mario

2013-01-01

The purpose of this work was to explore the use of image registration-derived variables associated with computed tomographic (CT) imaging of the lung acquired at multiple volumes. As an evaluation of the utility of such an imaging approach, we explored two groups at the extremes of population ranging from normal subjects to severe asthmatics. A mass-preserving image registration technique was employed to match CT images at total lung capacity (TLC) and functional residual capacity (FRC) for assessment of regional air volume change and lung deformation between the two states. Fourteen normal subjects and thirty severe asthmatics were analyzed via image registration-derived metrics together with their pulmonary function test (PFT) and CT-based air-trapping. Relative to the normal group, the severely asthmatic group demonstrated reduced air volume change (consistent with air trapping) and more isotropic deformation in the basal lung regions while demonstrating increased air volume change associated with increased anisotropic deformation in the apical lung regions. These differences were found despite the fact that both PFT-derived TLC and FRC in the two groups were nearly 100% of predicted values. Data suggest that reduced basal-lung air volume change in severe asthmatics was compensated by increased apical-lung air volume change and that relative increase in apical-lung air volume change in severe asthmatics was accompanied by enhanced anisotropic deformation. These data suggest that CT-based deformation, assessed via inspiration vs. expiration scans, provides a tool for distinguishing differences in lung mechanics when applied to the extreme ends of a population range. PMID:23743399

Dietary Boron and Hormone Replacement Therapy as Risk Factors for Lung Cancer in Women

PubMed Central

Mahabir, S.; Spitz, M. R.; Barrera, S. L.; Dong, Y. Q.; Eastham, C.; Forman, M. R.

2012-01-01

Hormone replacement therapy (HRT) may reduce lung cancer risk. Dietary boron may have actions similar to those of HRT; however, no previous study has reported the associations between dietary boron intake and lung cancer risk or the joint effects of boron intake and HRT use on lung cancer risk. The authors examined the associations between boron intake and the joint effects of boron intake and HRT on lung cancer risk in women. In an ongoing case-control study in Houston, Texas (July 1995 through April 2005, end date for this analysis), 763 women were diagnosed with lung cancer, and 838 were matched healthy controls with data on both diet and HRT. Multiple logistic regression analyses were conducted to assess the associations between dietary boron and HRT with lung cancer risk. After adjustment for potential confounders, the odds ratios for lung cancer with decreasing quartiles of dietary boron intake were 1.0, 1.39 (95% confidence interval (CI): 1.02, 1.90), 1.64 (95% CI: 1.20, 2.24), and 1.95 (95% CI: 1.42, 2.68) mg/day, respectively, for all women (ptrend < 0.0001). In joint-effects analyses, compared with women with high dietary boron intake who used HRT, the odds ratio for lung cancer for low dietary boron intake and no HRT use was 2.07 (95% CI: 1.53, 2.81). Boron intake was inversely associated with lung cancer in women, whereas women who consumed low boron and did not use HRT were at substantial increased odds. PMID:18343880

The β-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22.

PubMed

Lilly, Lauren M; Gessner, Melissa A; Dunaway, Chad W; Metz, Allison E; Schwiebert, Lisa; Weaver, Casey T; Brown, Gordon D; Steele, Chad

2012-10-01

Sensitization to fungi, such as the mold Aspergillus fumigatus, is increasingly becoming linked with asthma severity. We have previously shown that lung responses generated via the β-glucan receptor Dectin-1 are required for lung defense during acute, invasive A. fumigatus infection. Unexpectedly, in an allergic model of chronic lung exposure to live A. fumigatus conidia, β-glucan recognition via Dectin-1 led to the induction of multiple proallergic (Muc5ac, Clca3, CCL17, CCL22, and IL-33) and proinflammatory (IL-1β and CXCL1) mediators that compromised lung function. Attenuated proallergic and proinflammatory responses in the absence of Dectin-1 were not associated with changes in Ido (IDO), Il12p35/Ebi3 (IL-35), IL-10, or TGF-β levels. Assessment of Th responses demonstrated that purified lung CD4(+) T cells produced IL-4, IL-13, IFN-γ, and IL-17A, but not IL-22, in a Dectin-1-dependent manner. In contrast, we observed robust, Dectin-1-dependent IL-22 production by unfractionated lung digest cells. Intriguingly, the absence of IL-22 alone mimicked the attenuated proallergic and proinflammatory responses observed in the absence of Dectin-1, suggesting that Dectin-1-mediated IL-22 production potentiated responses that led to decrements in lung function. To this end, neutralization of IL-22 improved lung function in normal mice. Collectively, these results indicate that the β-glucan receptor Dectin-1 contributes to lung inflammation and immunopathology associated with persistent fungal exposure via the production of IL-22.

Hypoxia-inducible factors promote alveolar development and regeneration.

PubMed

Vadivel, Arul; Alphonse, Rajesh S; Etches, Nicholas; van Haaften, Timothy; Collins, Jennifer J P; O'Reilly, Megan; Eaton, Farah; Thébaud, Bernard

2014-01-01

Understanding how alveoli and the underlying capillary network develop and how these mechanisms are disrupted in disease states is critical for developing effective therapies for lung regeneration. Recent evidence suggests that lung angiogenesis promotes lung development and repair. Vascular endothelial growth factor (VEGF) preserves lung angiogenesis and alveolarization in experimental O2-induced arrested alveolar growth in newborn rats, but combined VEGF+angiopoietin 1 treatment is necessary to correct VEGF-induced vessel leakiness. Hypoxia-inducible factors (HIFs) are transcription factors that activate multiple O2-sensitive genes, including those encoding for angiogenic growth factors, but their role during postnatal lung growth is incompletely understood. By inducing the expression of a range of angiogenic factors in a coordinated fashion, HIF may orchestrate efficient and safe angiogenesis superior to VEGF. We hypothesized that HIF inhibition impairs alveolarization and that HIF activation regenerates irreversible O2-induced arrested alveolar growth. HIF inhibition by intratracheal dominant-negative adenovirus (dnHIF-1α)-mediated gene transfer or chetomin decreased lung HIF-1α, HIF-2α, and VEGF expression and led to air space enlargement and arrested lung vascular growth. In experimental O2-induced arrested alveolar growth in newborn rats, the characteristic features of air space enlargement and loss of lung capillaries were associated with decreased lung HIF-1α and HIF-2α expression. Intratracheal administration of Ad.HIF-1α restored HIF-1α, endothelial nitric oxide synthase, VEGF, VEGFR2, and Tie2 expression and preserved and rescued alveolar growth and lung capillary formation in this model. HIFs promote normal alveolar development and may be useful targets for alveolar regeneration.

EBUS-TBNA Provides Highest RNA Yield for Multiple Biomarker Testing from Routinely Obtained Small Biopsies in Non-Small Cell Lung Cancer Patients - A Comparative Study of Three Different Minimal Invasive Sampling Methods

PubMed Central

Schmid-Bindert, Gerald; Wang, Yongsheng; Jiang, Hongbin; Sun, Hui; Henzler, Thomas; Wang, Hao; Pilz, Lothar R.; Ren, Shengxiang; Zhou, Caicun

2013-01-01

Background Multiple biomarker testing is necessary to facilitate individualized treatment of lung cancer patients. More than 80% of lung cancers are diagnosed based on very small tumor samples. Often there is not enough tissue for molecular analysis. We compared three minimal invasive sampling methods with respect to RNA quantity for molecular testing. Methods 106 small biopsies were prospectively collected by three different methods forceps biopsy, endobronchial ultrasound (EBUS) guided transbronchial needle aspiration (TBNA), and CT-guided core biopsy. Samples were split into two halves. One part was formalin fixed and paraffin embedded for standard pathological evaluation. The other part was put in RNAlater for immediate RNA/DNA extraction. If the pathologist confirmed the diagnosis of non-small cell lung cancer(NSCLC), the following molecular markers were tested: EGFR mutation, ERCC1, RRM1 and BRCA1. Results Overall, RNA-extraction was possible in 101 out of 106 patients (95.3%). We found 49% adenocarcinomas, 38% squamouscarcinomas, and 14% non-otherwise-specified(NOS). The highest RNA yield came from endobronchial ultrasound guided needle aspiration, which was significantly higher than bronchoscopy (37.74±41.09 vs. 13.74±15.53 ng respectively, P = 0.005) and numerically higher than CT-core biopsy (37.74±41.09 vs. 28.72±44.27 ng respectively, P = 0.244). EGFR mutation testing was feasible in 100% of evaluable patients and its incidence was 40.8%, 7.9% and 14.3% in adenocarcinomas, squamouscarcinomas and NSCLC NOS subgroup respectively. There was no difference in the feasibility of molecular testing between the three sampling methods with feasibility rates for ERCC1, RRM1 and BRCA1 of 91%, 87% and 81% respectively. Conclusion All three methods can provide sufficient tumor material for multiple biomarkers testing from routinely obtained small biopsies in lung cancer patients. In our study EBUS guided needle aspiration provided the highest amount of tumor RNA compared to bronchoscopy or CT guided core biopsy. Thus EBUS should be considered as an acceptable option for tissue acquisition for molecular testing. PMID:24205040

A Comparative Epidemiologic Study on Geographic Distributions of Cancers of the Lung and the Large Intestine in Japan

PubMed Central

Murata, Motoi; Takayama, Kimiko; Fukuma, Seigo; Okamoto, Naoyuki; Kato, Ikuko; Hanai, Aya; Nakayama, Hideaki; Fujiwara, Kouichi; Ikeda, Takayoshi; Fujimoto, Isaburo

1988-01-01

To examine what kinds of factors could have caused the geographic variation observed in lung cancer morbidity in Japan, a correlation study was performed comparing various regional traits. The same study was also conducted on large intestinal cancer, aiming to distinguish the possible urban factors associated with both cancers. Lung cancer was highly correlated with industrialization‐related factors such as localization of manufacturing industries, automobile traffic and air pollution, whereas colon cancer was correlated with the population density of workers in the tertiary industries such as services, trade and government. A multiple regression analysis could not detect any single factor with an exceptionally strong influence on either cancer. The present findings suggest that the hazardous environmental condition of urban areas has, to some extent, contributed to the recent increase of lung cancer cases in this country. PMID:3142830

Pleurotus eryngii Ameliorates Lipopolysaccharide-Induced Lung Inflammation in Mice

PubMed Central

Andoh, Tsugunobu; Ouchi, Kenji; Inatomi, Satoshi

2014-01-01

Pleurotus eryngii (P. eryngii) is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect of P. eryngii in mice with acute lung injury (ALI). Intranasal instillation of lipopolysaccharide (LPS) (10 μg/site/mouse) induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid) as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treated P. eryngii (0.3–1 g/kg, p.o. (HTPE)) 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus, P. eryngii itself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection. PMID:24799939

Triptolide suppresses paraquat induced idiopathic pulmonary fibrosis by inhibiting TGFB1-dependent epithelial mesenchymal transition.

PubMed

Chen, Hong; Chen, Qun; Jiang, Chun-Ming; Shi, Guang-Yue; Sui, Bo-Wen; Zhang, Wei; Yang, Li-Zhen; Li, Zhu-Ying; Liu, Li; Su, Yu-Ming; Zhao, Wen-Cheng; Sun, Hong-Qiang; Li, Zhen-Zi; Fu, Zhou

2018-03-01

Idiopathic pulmonary fibrosis (IPF) and tumor are highly similar to abnormal cell proliferation that damages the body. This malignant cell evolution in a stressful environment closely resembles that of epithelial-mesenchymal transition (EMT). As a popular EMT-inducing factor, TGFβ plays an important role in the progression of multiple diseases. However, the drugs that target TGFB1 are limited. In this study, we found that triptolide (TPL), a Chinese medicine extract, exerts an anti-lung fibrosis effect by inhibiting the EMT of lung epithelial cells. In addition, triptolide directly binds to TGFβ and subsequently increase E-cadherin expression and decrease vimentin expression. In in vivo studies, TPL improves the survival state and inhibits lung fibrosis in mice. In summary, this study revealed the potential therapeutic effect of paraquat induced TPL in lung fibrosis by regulating TGFβ-dependent EMT progression. Copyright © 2017 Elsevier B.V. All rights reserved.

Consecutive Food and Respiratory Allergies Amplify Systemic and Gut but Not Lung Outcomes in Mice.

PubMed

Bouchaud, Gregory; Gourbeyre, Paxcal; Bihouée, Tiphaine; Aubert, Phillippe; Lair, David; Cheminant, Marie-Aude; Denery-Papini, Sandra; Neunlist, Michel; Magnan, Antoine; Bodinier, Marie

2015-07-22

Epidemiological data suggest a link between food allergies and the subsequent development of asthma. Although this progression may result from the additional effects of exposure to multiple allergens, whether both allergies amplify each other's effects remains unknown. This study investigated whether oral exposure to food allergens influences the outcomes of subsequent respiratory exposure to an asthma-inducing allergen. Mice were sensitized and orally challenged with wheat (FA) and then exposed to house dust mite (HDM) extract (RA). Immunoglobulin (Ig), histamine, and cytokine levels were assayed by ELISA. Intestinal and lung physiology was assessed. Ig levels, histamine release, and cytokine secretion were higher after exposure to both allergens than after separate exposure to each. Intestinal permeability was higher, although airway hyper-responsiveness and lung inflammation remained unchanged. Exposure to food and respiratory allergens amplifies systemic and gut allergy-related immune responses without any additional effect on lung function and inflammation.

Pleurotus eryngii Ameliorates Lipopolysaccharide-Induced Lung Inflammation in Mice.

PubMed

Kawai, Junya; Andoh, Tsugunobu; Ouchi, Kenji; Inatomi, Satoshi

2014-01-01

Pleurotus eryngii (P. eryngii) is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect of P. eryngii in mice with acute lung injury (ALI). Intranasal instillation of lipopolysaccharide (LPS) (10  μ g/site/mouse) induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid) as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treated P. eryngii (0.3-1 g/kg, p.o. (HTPE)) 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus, P. eryngii itself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection.

Genomic analysis of lung cell lines exposures to space radiation and the effect of lunar dust on selected fibrosis gene using RT2 PCR Array

NASA Astrophysics Data System (ADS)

Yeshitla, Samrawit

In the United States (U.S.), lung cancer is the number one cause of cancer death among men and women. Previous studies on human and animal epithelial lung cells showed that ionizing radiation and certain environmental pollutants are carcinogens. The surface area of the lungs and the slow turnover rate of the epithelial cells are suggested to play a role in the vulnerability of the cells, which lead to increase in the progenitor cell of the lung. It has been proposed that these progenitor cells, when exposed to radiation undergo multiple alterations that cause the cells to become cancerous. The current thought is that the lungs contain several facultative progenitor cells that are situated throughout the lung epithelium and are regionally restricted in their regenerative capacity. In this study, normal Human Bronchial Epithelial Cells (HBECs) were immortalized through the expression of Cdk4 and hTERT and evaluated for the effects radiation using in vitro study. The HBECs retained its novel multipotent capacity in vitro and represented unrestricted progenitor cells of the adult lungs, which resemble an embryonic progenitor. Analysis of the transformed clones of human bronchial epithelial cell line, HEBC3KT exposed to Fe ions and gamma rays revealed chromosomal abnormality, which was detected with the Multi-color Fluorescent In Situ Hybridization (mFish). In Part two of this study the F344 rats exposed to lunar dust, for 4 weeks (6h/d; 5d/wk.) in nose-only inhalation chambers at concentrations of 0 (control air), 2.1, 6.8, 20.8, and 61 mg/m3 of lunar dust, were used to determine the lunar dust toxicity on the lung tissues and total RNA were prepared from the tissues and used for gene expression. Analysis of gene expression data using Ingenuity Pathway Analysis tool identified multiple pathways of which fibrosis was one of the pathways. The Rat Fibrosis RT 2 Profile PCR Array was used to profile the expression of 84 genes that are relevant to fibrosis in the lung tissue, after removing the infiltrated of the bronchoalveolar lavage (BAL) cells by lavaging. At a dose of 61mg/m 3, 29 genes showed changes and of 29 genes, nine genes, Bmp7, Cc112, Cc13, Itgb8, Serpinel, Smad6, Tgfbrl, Thbs2, and Tnf, showed significant fold change difference of up-regulation or down-regulation. The data in this study showed that iron ions and gamma rays promote chromosomal abnormality in HBEC3KT, and for the first time, the lunar dust altered gene expression of 29 genes that are relevant to fibrosis in the lung tissue.

Polymorphisms in GEMIN4 and AGO1 Genes Are Associated with the Risk of Lung Cancer: A Case-Control Study in Chinese Female Non-Smokers

PubMed Central

Fang, Xue; Yin, Zhihua; Li, Xuelian; Xia, Lingzi; Zhou, Baosen

2016-01-01

MicroRNA biosynthesis genes can affect the regulatory effect of global microRNAs to target mRNA and hence influence the genesis and development of human cancer. Here, we selected five single nucleotide polymorphisms (SNPs) (rs7813, rs2740349, rs2291778, rs910924, rs595961) in two key microRNA biosynthesis genes (GEMIN4 and AGO1) and systematically evaluated the association between these SNPs, the gene-environment interaction and lung cancer risk. To control the impact of cigarette smoking on lung cancer, we recruited Chinese female non-smokers for the study. The total number of lung cancer cases and cancer-free controls were 473 and 395 in the case-control study. Four SNPs showed statistically significant associations with lung cancer risk. After Bonferroni correction, rs7813 and rs595961 were evidently still associated with lung cancer risk. In the stratified analysis, our results revealed that all five SNPs were associated with the risk of lung adenocarcinoma; after Bonferroni correction, significant association was maintained for rs7813, rs910924 and rs595961. Haplotype analysis showed GEMIN4 haplotype C-A-G-T was a protective haplotype for lung cancer. In the combined unfavorable genotype analysis, with the increasing number of unfavorable genotypes, a progressively increased gene-dose effect was observed in lung adenocarcinoma. We also found that individuals exposed to cooking oil fumes showed a relatively high risk of lung cancer, but no interactions were found between cooking oil fume exposure or passive smoking exposure with these SNPs, either on an additive scale or a multiplicative scale. Overall, this is the first study showing that rs7813 and rs595961 could be meaningful as genetic markers for lung cancer risk. PMID:27669275

Valproic acid attenuates acute lung injury induced by ischemia-reperfusion in rats.

PubMed

Wu, Shu-Yu; Tang, Shih-En; Ko, Fu-Chang; Wu, Geng-Chin; Huang, Kun-Lun; Chu, Shi-Jye

2015-06-01

Evidence reveals that histone deacetylase (HDAC) inhibition has potential for the treatment of inflammatory diseases. The protective effect of HDAC inhibition involves multiple mechanisms. Heme oxygenase-1 (HO-1) is protective in lung injury as a key regulator of antioxidant response. The authors examined whether HDAC inhibition provided protection against ischemia-reperfusion (I/R) lung injury in rats by up-regulating HO-1 activity. Acute lung injury was induced by producing 40 min of ischemia followed by 60 min of reperfusion in isolated perfused rat lungs. The rats were randomly allotted to control group, I/R group, or I/R + valproic acid (VPA) group with or without an HO-1 activity inhibitor (zinc protoporphyrin IX) (n = 6 per group). I/R caused significant increases in the lung edema, pulmonary arterial pressure, lung injury scores, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-1 concentrations in bronchoalveolar lavage fluid. Malondialdehyde levels, carbonyl contents, and myeloperoxidase-positive cells in lung tissue were also significantly increased. I/R stimulated the degradation of inhibitor of nuclear factor-κB-α, nuclear translocation of nuclear factor-κB, and up-regulation of HO-1 activity. Furthermore, I/R decreased B-cell lymphoma-2, heat shock protein 70, acetylated histone H3 protein expression, and increased the caspase-3 activity in the rat lungs. In contrast, VPA treatment significantly attenuated all the parameters of lung injury, oxidative stress, apoptosis, and inflammation. In addition, VPA treatment also enhanced HO-1 activity. Treatment with zinc protoporphyrin IX blocked the protective effect of VPA. VPA protected against I/R-induced lung injury. The protective mechanism may be partly due to enhanced HO-1 activity following HDAC inhibition.

Is Previous Respiratory Disease a Risk Factor for Lung Cancer?

PubMed Central

Denholm, Rachel; Schüz, Joachim; Straif, Kurt; Stücker, Isabelle; Jöckel, Karl-Heinz; Brenner, Darren R.; De Matteis, Sara; Boffetta, Paolo; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Landi, Maria Teresa; Caporaso, Neil; Siemiatycki, Jack; Ahrens, Wolfgang; Pohlabeln, Hermann; Zaridze, David; Field, John K.; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Kendzia, Benjamin; Peters, Susan; Behrens, Thomas; Vermeulen, Roel; Brüning, Thomas; Kromhout, Hans

2014-01-01

Rationale: Previous respiratory diseases have been associated with increased risk of lung cancer. Respiratory conditions often co-occur and few studies have investigated multiple conditions simultaneously. Objectives: Investigate lung cancer risk associated with chronic bronchitis, emphysema, tuberculosis, pneumonia, and asthma. Methods: The SYNERGY project pooled information on previous respiratory diseases from 12,739 case subjects and 14,945 control subjects from 7 case–control studies conducted in Europe and Canada. Multivariate logistic regression models were used to investigate the relationship between individual diseases adjusting for co-occurring conditions, and patterns of respiratory disease diagnoses and lung cancer. Analyses were stratified by sex, and adjusted for age, center, ever-employed in a high-risk occupation, education, smoking status, cigarette pack-years, and time since quitting smoking. Measurements and Main Results: Chronic bronchitis and emphysema were positively associated with lung cancer, after accounting for other respiratory diseases and smoking (e.g., in men: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.20–1.48 and OR, 1.50; 95% CI, 1.21–1.87, respectively). A positive relationship was observed between lung cancer and pneumonia diagnosed 2 years or less before lung cancer (OR, 3.31; 95% CI, 2.33–4.70 for men), but not longer. Co-occurrence of chronic bronchitis and emphysema and/or pneumonia had a stronger positive association with lung cancer than chronic bronchitis “only.” Asthma had an inverse association with lung cancer, the association being stronger with an asthma diagnosis 5 years or more before lung cancer compared with shorter. Conclusions: Findings from this large international case–control consortium indicate that after accounting for co-occurring respiratory diseases, chronic bronchitis and emphysema continue to have a positive association with lung cancer. PMID:25054566

Lung Cancer Prognosis in Elderly Solid Organ Transplant Recipients

PubMed Central

Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan

2015-01-01

Background Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Methods Using the Surveillance, Epidemiology and End Results registry linked to Medicare claims we identified 597 patients age ≥65 with NSCLC who had received organ transplants (kidney, liver, heart or lung) prior to cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Results Transplant recipients presented with earlier stage lung cancer (p=0.002) and were more likely to have squamous cell carcinoma (p=0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (p<0.05) while lung transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and non-transplant patients. Conclusions Non-lung solid organ transplant recipients who developed NSCLC had worse OS than non-transplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these two groups. PMID:25839704

The 'cardiac-lung mass' artifact: an echocardiographic sign of lung atelectasis and/or pleural effusion

PubMed Central

Karabinis, Andreas; Saranteas, Theodosios; Karakitsos, Dimitrios; Lichtenstein, Daniel; Poularas, John; Yang, Clifford; Stefanadis, Christodoulos

2008-01-01

Introduction We conducted an ultrasound study to investigate echocardiographic artifacts in mechanically ventilated patients with lung pathology. Methods A total of 205 mechanically ventilated patients who exhibited lung atelectasis and/or pleural effusion were included in this 36-month study. The patients underwent lung echography and transthoracic echocardiography, with a linear 5 to 10 MHz and with a 1.5 to 3.6 MHz wide-angle phased-array transducer, respectively. Patients were examined by two experienced observers who were blinded to each other's interpretation. Results A total of 124 patients (60,48%) were hospitalized because of multiple trauma; 60 patients (29,26%) because of respiratory insufficiency, and 21 (10,24%) because of recent postoperative surgery. The mean duration ( ± standard deviation) of hospitalization was 35 ± 27 days. An intracardiac artifact was documented in 17 out of 205 patients (8.29%) by echocardiography. It was visible only in the apical views, whereas subsequent transesophageal echocardiography revealed no abnormalities. The artifact consisted of a mobile component that exhibited, on M-mode, a pattern of respiratory variation similar to the lung 'sinusoid sign'. Lung echography revealed lung atelectasis and/or pleural effusion adjacent to the heart, and a similar M-mode pattern was observed. The artifact was recorded within the left cardiac chambers in 11 cases and within the right cardiac chambers in six. Conclusions Lung atelectasis and/or pleural effusion may create a mirror image, intracardiac artifact in mechanically ventilated patients. The latter was named the 'cardiac-lung mass' artifact to underline the important diagnostic role of both echocardiography and lung echography in these patients. Trial registration This trial is ISRCTN registered: ISRCTN 49216096. PMID:18826590

Lung vital capacity and oxygen saturation in adults with cerebral palsy

PubMed Central

Lampe, Renée; Blumenstein, Tobias; Turova, Varvara; Alves-Pinto, Ana

2014-01-01

Background Individuals with infantile cerebral palsy have multiple disabilities. The most conspicuous syndrome being investigated from many aspects is motor movement disorder with a spastic gait pattern. The lung function of adults with spasticity attracts less attention in the literature. This is surprising because decreased thoracic mobility and longstanding scoliosis should have an impact on lung function. With increasing age and the level of disability, individuals become susceptible to lung infections and reflux illness, and these are accompanied by increased aspiration risk. This study examined, with different methods, to what extent adults with congenital cerebral palsy and acquired spastic paresis – following traumatic brain injury – showed restriction of lung function. It also assessed the contribution of disability level on this restriction. Methods The oxygen saturation of 46 adults with a diagnosis of cerebral palsy was measured with an oximeter. Lung vital capacity was measured with a mobile spirometer and excursion of the thorax was clinically registered. The gross motor function levels and the presence or absence of scoliosis were determined. Results A significantly positive correlation between lung vital capacity and chest expansion was established. Both the lung vital capacity and the thorax excursion decreased with increases in gross motor function level. Oxygen saturation remained within the normal range in all persons, in spite of reduced values of the measured lung parameters. No statistically significant dependency between lung vital capacity and oxygen saturation, and between chest expansion and oxygen saturation was found. The scoliotic deformities of the spine were associated with an additional decrease in the vital capacity, but this did not affect blood oxygen supply. Conclusion Despite the decreased chest expansion and the significantly reduced lung volume in adults with cerebral palsy, sufficient oxygen supply was registered. PMID:25525345

Quantitative relation between emphysema and lung mineral content in coalworkers.

PubMed Central

Leigh, J; Driscoll, T R; Cole, B D; Beck, R W; Hull, B P; Yang, J

1994-01-01

The relation between quantified emphysema and measured lung content of coal and silica was investigated in the lungs of 264 deceased underground coalworkers who had been exposed to mixed coal and silica dust. Lung specimens obtained at postmortem and inflated and fixed under standard conditions were used to quantify the extent of emphysema and then to measure the amount of coal and silica present in the lungs at the time of death. These data were combined with clinical and other pathological information from the subjects. Multiple regression analysis showed that the extent of emphysema (E score) had a strong positive quantitative relation with coal content of the lungs (p < 0.0003), age (p < 0.0001), and smoking (p < 0.0001). There was a significant negative interaction of uncertain biological importance between coal content of the lungs and smoking (p < 0.004; E score = -1.79 + 0.62 coal + 0.06 age + 0.21 smoking -0.17 coal x smoking; adjusted R2 = 0.25). In lifelong non-smokers emphysema was particularly strongly related to coal content and age (coal: p < 0.001; age: p < 0.002; E score = -1.56 + 0.78 coal + 0.06 age; adjusted R2 = 0.66). The relation was basically unchanged by adding a lung silica content term. Emphysema score was highly negatively correlated with forced expiratory volume in one second (FEV1; % predicted, obtained within five years of death) (r = -0.44, p < 0.0001). Degree of lung fibrosis was highly positively associated with lung silica content (chi 2(1) = 12.9, p < 0.0003). These results provide strong evidence that emphysema in coalworkers is actually related to lung coal content. The role silica in development of emphysema, however remains unclear. PMID:8044232

Quantitative Computerized Two-Point Correlation Analysis of Lung CT Scans Correlates With Pulmonary Function in Pulmonary Sarcoidosis

PubMed Central

Erdal, Barbaros Selnur; Yildiz, Vedat; King, Mark A.; Patterson, Andrew T.; Knopp, Michael V.; Clymer, Bradley D.

2012-01-01

Background: Chest CT scans are commonly used to clinically assess disease severity in patients presenting with pulmonary sarcoidosis. Despite their ability to reliably detect subtle changes in lung disease, the utility of chest CT scans for guiding therapy is limited by the fact that image interpretation by radiologists is qualitative and highly variable. We sought to create a computerized CT image analysis tool that would provide quantitative and clinically relevant information. Methods: We established that a two-point correlation analysis approach reduced the background signal attendant to normal lung structures, such as blood vessels, airways, and lymphatics while highlighting diseased tissue. This approach was applied to multiple lung fields to generate an overall lung texture score (LTS) representing the quantity of diseased lung parenchyma. Using deidentified lung CT scan and pulmonary function test (PFT) data from The Ohio State University Medical Center’s Information Warehouse, we analyzed 71 consecutive CT scans from patients with sarcoidosis for whom simultaneous matching PFTs were available to determine whether the LTS correlated with standard PFT results. Results: We found a high correlation between LTS and FVC, total lung capacity, and diffusing capacity of the lung for carbon monoxide (P < .0001 for all comparisons). Moreover, LTS was equivalent to PFTs for the detection of active lung disease. The image analysis protocol was conducted quickly (< 1 min per study) on a standard laptop computer connected to a publicly available National Institutes of Health ImageJ toolkit. Conclusions: The two-point image analysis tool is highly practical and appears to reliably assess lung disease severity. We predict that this tool will be useful for clinical and research applications. PMID:22628487

Rapid postglacial diversification and long-term stasis within the songbird genus Junco: phylogeographic and phylogenomic evidence.

PubMed

Friis, Guillermo; Aleixandre, Pau; Rodríguez-Estrella, Ricardo; Navarro-Sigüenza, Adolfo G; Milá, Borja

2016-12-01

Natural systems composed of closely related taxa that vary in the degree of phenotypic divergence and geographic isolation provide an opportunity to investigate the rate of phenotypic diversification and the relative roles of selection and drift in driving lineage formation. The genus Junco (Aves: Emberizidae) of North America includes parapatric northern forms that are markedly divergent in plumage pattern and colour, in contrast to geographically isolated southern populations in remote areas that show moderate phenotypic divergence. Here, we quantify patterns of phenotypic divergence in morphology and plumage colour and use mitochondrial DNA genes, a nuclear intron, and genomewide SNPs to reconstruct the demographic and evolutionary history of the genus to infer relative rates of evolutionary divergence among lineages. We found that geographically isolated populations have evolved independently for hundreds of thousands of years despite little differentiation in phenotype, in sharp contrast to phenotypically diverse northern forms, which have diversified within the last few thousand years as a result of the rapid postglacial recolonization of North America. SNP data resolved young northern lineages into reciprocally monophyletic lineages, indicating low rates of gene flow even among closely related parapatric forms, and suggesting a role for strong genetic drift or multifarious selection acting on multiple loci in driving lineage divergence. Juncos represent a compelling example of speciation in action, where the combined effects of historical and selective factors have produced one of the fastest cases of speciation known in vertebrates. © 2016 John Wiley & Sons Ltd.

West Nile virus: a primer for the otolaryngologist.

PubMed

Michaelson, Peter G; Mair, Eric A

2005-03-01

Since recognition in the United States with a 1999 New York City epidemic, West Nile virus has enduringly migrated westward, leaving few states unaffected. Infection rates are rising at an alarming rate, doubling every year since introduction, with more than 9800 cases in 2003 alone and more than 260 deaths. Patients may present with myriad symptoms including a maculopapular rash that affects the face and trunk and diffuse lymphadenopathy, both of which may result in the initial consultation of the otolaryngologist. We review the clinical history of West Nile virus and its epidemiology, laboratory findings, and variable clinical presentation, with an emphasis on otolaryngologic manifestations. STUDY DESIGN AND SETTING COMPREHENSIVE: review of the literature over the past 50 years with an emphasis on what the present-day otolaryngologist needs to know concerning West Nile virus. Clinical manifestations of the head and neck such as encephalitis, meningitis, maculopapular rash, lymphadenopathy and dysphagia are discussed. To date, there are no articles in the otolaryngology literature discussing West Nile virus. These patients may present initially to multiple providers in diverse specialties because of multifarious initial signs and symptoms. The otolaryngologist must be educated on this quickly growing affliction and practice with a high index of suspicion. In this article we describe the clinical manifestations of West Nile virus, with an emphasis on the otolaryngologic manifestations. The otolaryngologist must become educated about this entity to facilitate preventative measures, adequately treat, and assist other providers in hopeful control and potential eradication of this infectious threat.

Targeting DDX3 with a small molecule inhibitor for lung cancer therapy.

PubMed

Bol, Guus M; Vesuna, Farhad; Xie, Min; Zeng, Jing; Aziz, Khaled; Gandhi, Nishant; Levine, Anne; Irving, Ashley; Korz, Dorian; Tantravedi, Saritha; Heerma van Voss, Marise R; Gabrielson, Kathleen; Bordt, Evan A; Polster, Brian M; Cope, Leslie; van der Groep, Petra; Kondaskar, Atul; Rudek, Michelle A; Hosmane, Ramachandra S; van der Wall, Elsken; van Diest, Paul J; Tran, Phuoc T; Raman, Venu

2015-05-01

Lung cancer is the most common malignancy worldwide and is a focus for developing targeted therapies due to its refractory nature to current treatment. We identified a RNA helicase, DDX3, which is overexpressed in many cancer types including lung cancer and is associated with lower survival in lung cancer patients. We designed a first-in-class small molecule inhibitor, RK-33, which binds to DDX3 and abrogates its activity. Inhibition of DDX3 by RK-33 caused G1 cell cycle arrest, induced apoptosis, and promoted radiation sensitization in DDX3-overexpressing cells. Importantly, RK-33 in combination with radiation induced tumor regression in multiple mouse models of lung cancer. Mechanistically, loss of DDX3 function either by shRNA or by RK-33 impaired Wnt signaling through disruption of the DDX3-β-catenin axis and inhibited non-homologous end joining-the major DNA repair pathway in mammalian somatic cells. Overall, inhibition of DDX3 by RK-33 promotes tumor regression, thus providing a compelling argument to develop DDX3 inhibitors for lung cancer therapy. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

Near infrared photoimmunotherapy for lung metastases

PubMed Central

Sato, Kazuhide; Nagaya, Tadanobu; Mitsunaga, Makoto; Choyke, Peter L.; Kobayashi, Hisataka

2015-01-01

Lung metastases are a leading cause of cancer related deaths; nonetheless current treatments are limited. Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies that target tumors with the toxicity induced by photosensitizers activated by NIR-light. Herein, we demonstrate the efficacy of NIR-PIT in a mouse model of lung metastases. Experiments were conducted with a HER2, luciferase and GFP expressing cell line (3T3/HER2-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. With 3D culture, repeated NIR-PIT could eradicate entire spheroids. In vivo anti-tumor effects of NIR-PIT included significant reductions in both tumor volume (p = 0.0141 vs. APC) and bioluminescence image (BLI) (p = 0.0086 vs. APC) in the flank model, and prolonged survival (p < 0.0001). BLI demonstrated a significant reduction in lung metastases volume (p = 0.0117 vs. APC). Multiple NIR-PIT doses significantly prolonged survival in the lung metastases model (p < 0.0001). These results suggested that NIR-PIT is a potential new therapy for the local control of lung metastases. PMID:26021765

A 4DCT imaging-based breathing lung model with relative hysteresis

PubMed Central

Miyawaki, Shinjiro; Choi, Sanghun; Hoffman, Eric A.; Lin, Ching-Long

2016-01-01

To reproduce realistic airway motion and airflow, the authors developed a deforming lung computational fluid dynamics (CFD) model based on four-dimensional (4D, space and time) dynamic computed tomography (CT) images. A total of 13 time points within controlled tidal volume respiration were used to account for realistic and irregular lung motion in human volunteers. Because of the irregular motion of 4DCT-based airways, we identified an optimal interpolation method for airway surface deformation during respiration, and implemented a computational solid mechanics-based moving mesh algorithm to produce smooth deforming airway mesh. In addition, we developed physiologically realistic airflow boundary conditions for both models based on multiple images and a single image. Furthermore, we examined simplified models based on one or two dynamic or static images. By comparing these simplified models with the model based on 13 dynamic images, we investigated the effects of relative hysteresis of lung structure with respect to lung volume, lung deformation, and imaging methods, i.e., dynamic vs. static scans, on CFD-predicted pressure drop. The effect of imaging method on pressure drop was 24 percentage points due to the differences in airflow distribution and airway geometry. PMID:28260811

Loss of Cytoplasmic CDK1 Predicts Poor Survival in Human Lung Cancer and Confers Chemotherapeutic Resistance

PubMed Central

Zhang, Chunyu; Elkahloun, Abdel G.; Robertson, Matthew; Gills, Joell J.; Tsurutani, Junji; Shih, Joanna H.; Fukuoka, Junya; Hollander, M. Christine; Harris, Curtis C.; Travis, William D.; Jen, Jin; Dennis, Phillip A.

2011-01-01

The dismal lethality of lung cancer is due to late stage at diagnosis and inherent therapeutic resistance. The incorporation of targeted therapies has modestly improved clinical outcomes, but the identification of new targets could further improve clinical outcomes by guiding stratification of poor-risk early stage patients and individualizing therapeutic choices. We hypothesized that a sequential, combined microarray approach would be valuable to identify and validate new targets in lung cancer. We profiled gene expression signatures during lung epithelial cell immortalization and transformation, and showed that genes involved in mitosis were progressively enhanced in carcinogenesis. 28 genes were validated by immunoblotting and 4 genes were further evaluated in non-small cell lung cancer tissue microarrays. Although CDK1 was highly expressed in tumor tissues, its loss from the cytoplasm unexpectedly predicted poor survival and conferred resistance to chemotherapy in multiple cell lines, especially microtubule-directed agents. An analysis of expression of CDK1 and CDK1-associated genes in the NCI60 cell line database confirmed the broad association of these genes with chemotherapeutic responsiveness. These results have implications for personalizing lung cancer therapy and highlight the potential of combined approaches for biomarker discovery. PMID:21887332

A 4DCT imaging-based breathing lung model with relative hysteresis

NASA Astrophysics Data System (ADS)

Miyawaki, Shinjiro; Choi, Sanghun; Hoffman, Eric A.; Lin, Ching-Long

2016-12-01

To reproduce realistic airway motion and airflow, the authors developed a deforming lung computational fluid dynamics (CFD) model based on four-dimensional (4D, space and time) dynamic computed tomography (CT) images. A total of 13 time points within controlled tidal volume respiration were used to account for realistic and irregular lung motion in human volunteers. Because of the irregular motion of 4DCT-based airways, we identified an optimal interpolation method for airway surface deformation during respiration, and implemented a computational solid mechanics-based moving mesh algorithm to produce smooth deforming airway mesh. In addition, we developed physiologically realistic airflow boundary conditions for both models based on multiple images and a single image. Furthermore, we examined simplified models based on one or two dynamic or static images. By comparing these simplified models with the model based on 13 dynamic images, we investigated the effects of relative hysteresis of lung structure with respect to lung volume, lung deformation, and imaging methods, i.e., dynamic vs. static scans, on CFD-predicted pressure drop. The effect of imaging method on pressure drop was 24 percentage points due to the differences in airflow distribution and airway geometry.

Measurements of Deposition, Lung Surface Area and Lung Fluid for Simulation of Inhaled Compounds

PubMed Central

Fröhlich, Eleonore; Mercuri, Annalisa; Wu, Shengqian; Salar-Behzadi, Sharareh

2016-01-01

Modern strategies in drug development employ in silico techniques in the design of compounds as well as estimations of pharmacokinetics, pharmacodynamics and toxicity parameters. The quality of the results depends on software algorithm, data library and input data. Compared to simulations of absorption, distribution, metabolism, excretion, and toxicity of oral drug compounds, relatively few studies report predictions of pharmacokinetics and pharmacodynamics of inhaled substances. For calculation of the drug concentration at the absorption site, the pulmonary epithelium, physiological parameters such as lung surface and distribution volume (lung lining fluid) have to be known. These parameters can only be determined by invasive techniques and by postmortem studies. Very different values have been reported in the literature. This review addresses the state of software programs for simulation of orally inhaled substances and focuses on problems in the determination of particle deposition, lung surface and of lung lining fluid. The different surface areas for deposition and for drug absorption are difficult to include directly into the simulations. As drug levels are influenced by multiple parameters the role of single parameters in the simulations cannot be identified easily. PMID:27445817

An accurate and rapid radiographic method of determining total lung capacity

PubMed Central

Reger, R. B.; Young, A.; Morgan, W. K. C.

1972-01-01

The accuracy and reliability of Barnhard's radiographic method of determining total lung capacity have been confirmed by several groups of investigators. Despite its simplicity and general reliability, it has several shortcomings, especially when used in large-scale epidemiological surveys. Of these, the most serious is related to film technique; thus, when the cardiac and diaphragmatic shadows are poorly defined, the appropriate measurements cannot be made accurately. A further drawback involves the time needed to measure the segments and to perform the necessary calculations. We therefore set out to develop an abbreviated and simpler radiographic method for determining total lung capacity. This uses a step-wise multiple regression model which allows total lung capacity to be derived as follows: posteroanterior and lateral films are divided into the standard sections as described in the text, the width, depth, and height of sections 1 and 4 are measured in centimetres, finally the necessary derivations and substitutions are made and applied to the formula Ŷ = −1·41148 + (0·00479 X1) + (0·00097 X4), where Ŷ is the total lung capacity. In our hands this method has provided a simple, rapid, and acceptable method of determining total lung capacity. PMID:5034594

Semi-automatic 3D lung nodule segmentation in CT using dynamic programming

NASA Astrophysics Data System (ADS)

Sargent, Dustin; Park, Sun Young

2017-02-01

We present a method for semi-automatic segmentation of lung nodules in chest CT that can be extended to general lesion segmentation in multiple modalities. Most semi-automatic algorithms for lesion segmentation or similar tasks use region-growing or edge-based contour finding methods such as level-set. However, lung nodules and other lesions are often connected to surrounding tissues, which makes these algorithms prone to growing the nodule boundary into the surrounding tissue. To solve this problem, we apply a 3D extension of the 2D edge linking method with dynamic programming to find a closed surface in a spherical representation of the nodule ROI. The algorithm requires a user to draw a maximal diameter across the nodule in the slice in which the nodule cross section is the largest. We report the lesion volume estimation accuracy of our algorithm on the FDA lung phantom dataset, and the RECIST diameter estimation accuracy on the lung nodule dataset from the SPIE 2016 lung nodule classification challenge. The phantom results in particular demonstrate that our algorithm has the potential to mitigate the disparity in measurements performed by different radiologists on the same lesions, which could improve the accuracy of disease progression tracking.

Robert R. Shaw, MD: thoracic surgical hero, Afghanistan medical pioneer, champion for the patient, never a surgical society president.

PubMed

Urschel, Harold C; Urschel, Betsey Bradley

2012-06-01

Dr Robert R. Shaw arrived in Dallas to practice Thoracic Surgery in 1937, as John Alexander's 7th Thoracic Surgical Resident from Michigan University Medical Center. Dr Shaw's modus operandi was, "You can accomplish almost anything, if you don't care who gets the credit." He was a remarkable individual who cared the most about the patient and very little about getting credit for himself. From 1937 to 1970, Dr Shaw established one of the largest lung cancer surgical centers in the world in Dallas, Texas. It was larger than M.D. Anderson and Memorial Sloan-Kettering Hospitals put together regarding the surgical treatment of lung cancer patients. To accomplish this, he had the help of Dr Donald L. Paulson, who trained at the Mayo Clinic and served as Chief of Thoracic Surgery at Brook Army Hospital during the Second World War. Following the War, because of his love for Texas, he ended up as a partner of Dr Shaw in Dallas. Together, they pursued the development of this very large surgical lung cancer center. Dr Shaw and his wife Ruth went to Afghanistan with Medico multiple times to teach men modern cardiac and thoracic surgery. They also served as consultants on Medico's Ship of Hope in Africa. Dr Shaw initiated multiple new operations including: 1) resection of Pancoast's cancer of the lung after preoperative irradiation; 2) upper lobe of the lung bronchoplasty, reattaching (and saving) the lower lobe to prevent the "disabling" pneumonectomy; and 3) resections of pulmonary mucoid impaction of the lung in asthmatics. Because of his humility and giving "the credit to others," Dr Shaw was never President of a major medical or surgical association. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Association Between Four Polymorphisms in lncRNA and Risk of Lung Cancer in a Chinese Never-Smoking Female Population.

PubMed

Gao, Min; Li, Hang; Lv, Xiaoting; Zhou, Baosen; Yin, Zhihua

2018-06-07

Long noncoding RNAs (lncRNAs) play important roles in the development of human cancers. This is the first case-control study of the association between specific polymorphisms in lncRNA genes and the risk of lung cancer, as well as the gene-environment interaction between the polymorphisms and cooking oil fume exposure in Chinese never-smoking females. A hospital-based case-control study was carried out in Shenyang, Liaoning province. The study included 395 cases and 556 controls. The polymorphisms of rs4785367, rs3803662, rs10750417, and rs1814343 in lncRNA genes were analyzed. The gene-environment interactions were explored on both additive and multiplicative scale. In addition, the results were listed as follows: for rs3803662, compared with the individuals carrying homozygous TT genotype, those with homozygous CC genotype had the decreased risk of lung cancer (adjusted odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.40-0.92, p = 0.018). As for rs4785367, compared with homozygous TT, homozygous CC could lessen the risk of lung cancer (adjusted OR = 0.54, 95% CI = 0.33-0.89, p = 0.016). The recessive models of rs3803662 and rs4785367 showed significant association (adjusted OR = 0.65, 95% CIs = 0.44-0.97, p = 0.033; adjusted OR = 0.54, 95% CIs = 0.33-0.88, p = 0.014). The C allele of rs3803662 was suggested to be protective allele of lung cancer (adjusted OR = 0.80, 95% CI = 0.66-0.97, p = 0.023). However, rs10750417 and rs1814343 polymorphisms were not significantly associated with lung cancer risks. The measures of additive interaction and logistic models suggested that the gene-environment interactions were not statistically significant on both additive and multiplicative scales.

A Voxel-Based Approach to Explore Local Dose Differences Associated With Radiation-Induced Lung Damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palma, Giuseppe; Monti, Serena; D'Avino, Vittoria

Purpose: To apply a voxel-based (VB) approach aimed at exploring local dose differences associated with late radiation-induced lung damage (RILD). Methods and Materials: An interinstitutional database of 98 patients who were Hodgkin lymphoma (HL) survivors treated with postchemotherapy supradiaphragmatic radiation therapy was analyzed in the study. Eighteen patients experienced late RILD, classified according to the Radiation Therapy Oncology Group scoring system. Each patient's computed tomographic (CT) scan was normalized to a single reference case anatomy (common coordinate system, CCS) through a log-diffeomorphic approach. The obtained deformation fields were used to map the dose of each patient into the CCS. Themore » coregistration robustness and the dose mapping accuracy were evaluated by geometric and dose scores. Two different statistical mapping schemes for nonparametric multiple permutation inference on dose maps were applied, and the corresponding P<.05 significance lung subregions were generated. A receiver operating characteristic (ROC)-based test was performed on the mean dose extracted from each subregion. Results: The coregistration process resulted in a geometrically robust and accurate dose warping. A significantly higher dose was consistently delivered to RILD patients in voxel clusters near the peripheral medial-basal portion of the lungs. The area under the ROC curves (AUC) from the mean dose of the voxel clusters was higher than the corresponding AUC derived from the total lung mean dose. Conclusions: We implemented a framework including a robust registration process and a VB approach accounting for the multiple comparison problem in dose-response modeling, and applied it to a cohort of HL survivors to explore a local dose–RILD relationship in the lungs. Patients with RILD received a significantly greater dose in parenchymal regions where low doses (∼6 Gy) were delivered. Interestingly, the relation between differences in the high-dose range and RILD seems to lack a clear spatial signature.« less

Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

NASA Technical Reports Server (NTRS)

Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

2014-01-01

The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

Assessment of lung injury in the adult respiratory distress syndrome using multiple indicator dilution curves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rinaldo, J.E.; Borovetz, H.S.; Mancini, M.C.

1986-06-01

To assess its usefulness as an index of lung injury in critically ill patients with respiratory failure, the lung microvascular permeability surface area product for urea (/sup 14/C-PSu) was measured using a multiple radioisotopic indicator dilution technique in 10 patients with the adult respiratory distress syndrome (ARDS) and in a control population of 5 patients without ARDS. The mean values for /sup 14/C-PSu and for extravascular lung water (EVLW) were both significantly elevated in patients with ARDS compared with those in control patients (/sup 14/C-PSu: 18.7 +/- 4.4 versus 7.6 +/- 0.7, p less than 0.05; EVLW: 676 +/- 55more » versus 269 +/- 53, p less than 0.001); /sup 14/C-PSu and EVLW were significantly correlated (R = 0.52, p less than 0.001). In the patients with ARDS, /sup 14/C-PSu and oxygenation, assessed as the alveolar-arterial oxygen difference, did not appear to be correlated. Repeated measurements of /sup 14/C-PSu were variable in the 3 control patients in whom 4 or more measurements were obtained (SD = 50, 57, and 54% of the mean values, respectively); /sup 14/C-PSu did not predict clinical outcome assessed by survival of individual patients with ARDS. These data suggest that measurement of /sup 14/C-PSu in critically ill patients is a clinically applicable parameter that reflects the degree of microvascular injury in groups of patients. However, our study did not indicate a clear advantage of /sup 14/C-PSu over EVLW in assessing lung injury in this patient population. The variability in /sup 14/C-PSu control patients also suggests that directional changes in /sup 14/C-PSu, as a measure of changes in the degree of lung microvascular dysfunction, should be interpreted with caution.« less

Comprehensive integrated spirometry using raised volume passive and forced expirations and multiple-breath nitrogen washout in infants

PubMed Central

Morris, Mohy G.

2009-01-01

With the rapid somatic growth and development in infants, simultaneous accurate measurements of lung volume and airway function are essential. Raised volume rapid thoracoabdominal compression (RTC) is widely used to generate forced expiration from an airway opening pressure of 30 cm H2O (V30). The (dynamic) functional residual capacity (FRCdyn) remains the lung volume most routinely measured. The aim of this study was to develop comprehensive integrated spirometry that included all subdivisions of lung volume at V30 or total lung capacity (TLC30). Measurements were performed on seventeen healthy infants aged 8.6–119.7 weeks. A commercial system for multiple-breath nitrogen washout (MBNW) to measure lung volumes and a custom made system to perform RTC were used in unison. A refined automated raised volume RTC and the following two novel single maneuvers with dual volume measurements were performed from V30 during a brief post-hyperventilation apneic pause: (1) the passive expiratory flow was integrated to produce the inspiratory capacity (IC) and the static (passive) FRC (FRCst) was estimated by initiating MBNW after end-passive expiration; (2) RTC was initiated late during passive expiration, flow was integrated to produce the slow vital capacity (jSVC) and the residual volume (RV) was measured by initiating MBNW after end-expiration while the jacket (j) was inflated. Intrasubject FRCdyn and FRCst measurements overlapped (p= 0.6420) but neither did with the RV (p<0.0001). Means (95% confidence interval) of FRCdyn, IC, FRCst, jSVC, RV, forced vital capacity and tidal volume were 21.2 (19.7–22.7), 36.7 (33.0–40.4), 21.2 (19.6–22.8), 40.7 (37.2–44.2), 18.1 (16.6–19.7), 40.7 (37.1–44.2) and 10.2 (9.6–10.7) ml/kg, respectively. Static lung volumes and capacities at V30 and variables from the best forced expiratory flow-volume curve were dependent on age, body length and weight. In conclusion, we developed a comprehensive physiologically-integrated approach for in-depth investigation of lung function at V30 in infants. PMID:19897058

Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.

PubMed

Saccone, Nancy L; Culverhouse, Robert C; Schwantes-An, Tae-Hwi; Cannon, Dale S; Chen, Xiangning; Cichon, Sven; Giegling, Ina; Han, Shizhong; Han, Younghun; Keskitalo-Vuokko, Kaisu; Kong, Xiangyang; Landi, Maria Teresa; Ma, Jennie Z; Short, Susan E; Stephens, Sarah H; Stevens, Victoria L; Sun, Lingwei; Wang, Yufei; Wenzlaff, Angela S; Aggen, Steven H; Breslau, Naomi; Broderick, Peter; Chatterjee, Nilanjan; Chen, Jingchun; Heath, Andrew C; Heliövaara, Markku; Hoft, Nicole R; Hunter, David J; Jensen, Majken K; Martin, Nicholas G; Montgomery, Grant W; Niu, Tianhua; Payne, Thomas J; Peltonen, Leena; Pergadia, Michele L; Rice, John P; Sherva, Richard; Spitz, Margaret R; Sun, Juzhong; Wang, Jen C; Weiss, Robert B; Wheeler, William; Witt, Stephanie H; Yang, Bao-Zhu; Caporaso, Neil E; Ehringer, Marissa A; Eisen, Tim; Gapstur, Susan M; Gelernter, Joel; Houlston, Richard; Kaprio, Jaakko; Kendler, Kenneth S; Kraft, Peter; Leppert, Mark F; Li, Ming D; Madden, Pamela A F; Nöthen, Markus M; Pillai, Sreekumar; Rietschel, Marcella; Rujescu, Dan; Schwartz, Ann; Amos, Christopher I; Bierut, Laura J

2010-08-05

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10(-35) and <10(-8) respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10(-6)). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10(-20)) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue.

Single-port thoracoscopic surgery for pneumothorax under two-lung ventilation with carbon dioxide insufflation

PubMed Central

Han, Kook Nam; Lee, Hyun Joo; Lee, Dong Kyu; Kim, Heezoo; Lim, Sang Ho; Choi, Young Ho

2016-01-01

Background The development of single-port thoracoscopic surgery and two-lung ventilation reduced the invasiveness of minor thoracic surgery. This study aimed to evaluate the feasibility and safety of single-port thoracoscopic bleb resection for primary spontaneous pneumothorax using two-lung ventilation with carbon dioxide insufflation. Methods Between February 2009 and May 2014, 130 patients underwent single-port thoracoscopic bleb resection under two-lung ventilation with carbon dioxide insufflation. Access was gained using a commercial multiple-access single port through a 2.5-cm incision; carbon dioxide gas was insufflated through a port channel. A 5-mm thoracoscope, articulating endoscopic devices, and flexible endoscopic staplers were introduced through a multiple-access single port for bulla resection. Results The mean time from endotracheal intubation to incision was 29.2±7.8 minutes, the mean operative time was 30.9±8.2 minutes, and the mean total anesthetic time was 75.5±14.4 minutes. There were no anesthesia-related complications or wound problems. The chest drain was removed after a mean of 3.7±1.4 days and patients were discharged without complications 4.8±1.5 days from the operative day. During a mean 7.5±10.1 months of follow-up, there were five recurrences (3.8%) in operated thorax. Conclusions The anesthetic strategy of single-lumen intubation with carbon dioxide gas insufflation can be a safe and feasible option for single-port thoracoscopic bulla resection as it represents the least invasive surgical option with the potential advantages of reducing operative time and one-lung ventilation-related complications without diminishing surgical outcomes. PMID:27293823

MULTI-FREQUENCY OSCILLATORY VENTILATION IN THE PREMATURE LUNG: EFFECTS ON GAS EXCHANGE, MECHANICS, AND VENTILATION DISTRIBUTION

PubMed Central

Kaczka, David W.; Herrmann, Jacob; Zonneveld, C. Elroy; Tingay, David G.; Lavizzari, Anna; Noble, Peter B.; Pillow, J. Jane

2015-01-01

Background Despite the theoretical benefits of high-frequency oscillatory ventilation (HFOV) in preterm infants, systematic reviews of randomized clinical trials do not confirm improved outcomes. We hypothesized that oscillating a premature lung with multiple frequencies simultaneously would improve gas exchange compared to traditional single-frequency oscillatory ventilation (SFOV). The goal of this study was to develop a novel method for HFOV, termed ‘multi-frequency oscillatory ventilation’ (MFOV), which relies on a broadband flow waveform more suitable for the heterogeneous mechanics of the immature lung. Methods Thirteen intubated preterm lambs were randomized to either SFOV or MFOV for 1 hour, followed by crossover to the alternative regimen for 1 hour. The SFOV waveform consisted of a pure sinusoidal flow at 5 Hz, while the customized MFOV waveform consisted of a 5 Hz fundamental with additional energy at 10 and 15 Hz. Per standardized protocol, mean pressure at airway opening (P̅ao) and inspired O2 fraction were adjusted as needed, and root mean square of the delivered oscillatory volume waveform (Vrms) was adjusted 15-minute intervals. A ventilatory cost function for SFOV and MFOV was defined as VC=(Vrms2PaCO2)Wt−1, where Wt denotes body weight. Results Averaged over all time points, MFOV resulted in significantly lower VC (246.9±6.0 vs. 363.5±15.9 mL2 mmHg kg−1) and P̅ao (12.8±0.3 vs. 14.1±0.5 cmH2O) compared to SFOV, suggesting more efficient gas exchange and enhanced lung recruitment at lower mean airway pressures. Conclusions Oscillation with simultaneous multiple frequencies may be a more efficient ventilator modality in premature lungs compared to traditional single-frequency HFOV. PMID:26495977

Clinical and genetic spectrum of Birt–Hogg–Dubé syndrome patients in whom pneumothorax and/or multiple lung cysts are the presenting feature

PubMed Central

Kunogi, Makiko; Kurihara, Masatoshi; Ikegami, Takako Shigihara; Kobayashi, Toshiyuki; Shindo, Noriko; Kumasaka, Toshio; Gunji, Yoko; Kikkawa, Mika; Iwakami, Shin-ichiro; Hino, Okio; Takahashi, Kazuhisa

2010-01-01

Background Birt–Hogg–Dubé syndrome (BHDS) is an inherited autosomal genodermatosis characterised by fibrofolliculomas of the skin, renal tumours and multiple lung cysts. Genetic studies have disclosed that the clinical picture as well as responsible germline FLCN mutations are diverse. Objectives BHDS may be caused by a germline deletion which cannot be detected by a conventional genetic approach. Real-time quantitative polymerase chain reaction (qPCR) may be able to identify such a mutation and thus provide us with a more accurate clinical picture of BHDS. Methods This study analysed 36 patients with multiple lung cysts of undetermined causes. Denaturing high performance liquid chromatography (DHPLC) was applied for mutation screening. If no abnormality was detected by DHPLC, the amount of each FLCN exon in genome was quantified by qPCR. Results An FLCN germline mutation was found in 23 (63.9%) of the 36 patients by DHPLC and direct sequencing (13 unique small nucleotide alterations which included 11 novel mutations). A large genomic deletion was identified in two of the remaining 13 patients by qPCR (one patient with exon 14 deletion and one patient with a deletion encompassing exons 9 to 14). Mutations including genomic deletions were most frequently identified in the 3′-end of the FLCN gene including exons 12 and 13 (13/25=52.0%). The BHDS patients whose multiple cysts prompted the diagnosis in this study showed a very low incidence of skin and renal involvement. Conclusions BHDS is due to large deletions as well as small nucleotide alterations. Racial differences may occur between Japanese and patients of European decent in terms of FLCN mutations and clinical manifestations. PMID:20413710

Precision Cut Mouse Lung Slices to Visualize Live Pulmonary Dendritic Cells

PubMed Central

Lyons-Cohen, Miranda R.; Thomas, Seddon Y.; Cook, Donald N.; Nakano, Hideki

2017-01-01

SHORT ABSTRACT We describe a method for generating precision-cut lung slices (PCLS) and immunostaining them to visualize the localization of various immune cell types in the lung. Our protocol can be extended to visualize the location and function of many different cell types under a variety of conditions. LONG ABSTRACT Inhalation of allergens and pathogens elicits multiple changes in a variety of immune cell types in the lung. Flow cytometry is a powerful technique for quantitative analysis of cell surface proteins on immune cells, but it provides no information on the localization and migration patterns of these cells within the lung. Similarly, in vitro chemotaxis assays can be performed to study the potential of cells to respond to chemotactic factors in vitro, but these assays do not reproduce the complex environment of the intact lung. In contrast to these aforementioned techniques, the location of individual cell types within the lung can be readily visualized by generating precision-cut lung slices (PCLS), staining them with commercially available, fluorescently tagged antibodies, and visualizing the sections by confocal microscopy. PCLS can be used for both live and fixed lung tissue, and the slices can encompass areas as large as a cross section of an entire lobe. We have used this protocol to successfully visualize the location of a wide variety of cell types in the lung, including distinct types of dendritic cells, macrophages, neutrophils, T cells and B cells, as well as structural cells such as lymphatic, endothelial, and epithelial cells. The ability to visualize cellular interactions, such as those between dendritic cells and T cells, in live, three-dimensional lung tissue, can reveal how cells move within the lung and interact with one another at steady state and during inflammation. Thus, when used in combination with other procedures, such as flow cytometry and quantitative PCR, PCLS can contribute to a comprehensive understanding of cellular events that underlie allergic and inflammatory diseases of the lung. PMID:28448013

Increased Expression of FoxM1 Transcription Factor in Respiratory Epithelium Inhibits Lung Sacculation and Causes Clara Cell Hyperplasia

PubMed Central

Wang, I-Ching; Zhang, Yufang; Snyder, Jonathan; Sutherland, Mardi J.; Burhans, Michael S.; Shannon, John M.; Park, Hyun Jung; Whitsett, Jeffrey A.; Kalinichenko, Vladimir V.

2010-01-01

Foxm1 is a member of the Forkhead Box (Fox) family of transcription factors. Foxm1 (previously called Foxm1b, HFH-11B, Trident, Win, or MPP2) is expressed in multiple cell types and plays important roles in cellular proliferation, differentiation and tumorigenesis. Genetic deletion of Foxm1 from mouse respiratory epithelium during initial stages of lung development inhibits lung maturation and causes respiratory failure after birth. However, the role of Foxm1 during postnatal lung morphogenesis remains unknown. In the present study, Foxm1 expression was detected in epithelial cells of conducting and peripheral airways and changing dynamically with lung maturation. To discern the biological role of Foxm1 in the prenatal and postnatal lung, a novel transgenic mouse line that expresses a constitutively active form of FoxM1 (FoxM1 N-terminal deletion mutant or FoxM1-ΔN) under the control of lung epithelial-specific SPC promoter was produced. Expression of the FoxM1-ΔN transgene during embryogenesis caused epithelial hyperplasia, inhibited lung sacculation and expression of the type II epithelial marker, pro-SPC. Expression of FoxM1-ΔN mutant during the postnatal period did not influence alveologenesis but caused focal airway hyperplasia and increased proliferation of Clara cells. Likewise, expression of FoxM1-ΔN mutant in conducting airways with Scgb1a1 promoter was sufficient to induce Clara cell hyperplasia. Furthermore, FoxM1-ΔN cooperated with activated K-Ras to induce lung tumor growth in vivo. Increased activity of Foxm1 altered lung sacculation, induced proliferation in the respiratory epithelium and accelerated lung tumor growth, indicating that precise regulation of Foxm1 is critical for normal lung morphogenesis and development of lung cancer. PMID:20816795

Sarcoid-like lung granulomas in a hemodialysis patient treated with a dipeptidyl peptidase-4 inhibitor.

PubMed

Sada, Ken-Ei; Wada, Jun; Morinaga, Hiroshi; Tuchimochi, Shigeyuki; Uka, Mayu; Makino, Hirofumi

2014-04-01

It has been reported that the inhibition of dipeptidyl peptidase-4 (DPP-4)/CD26 on T-cells by DPP-4 enzymatic inhibitors suppresses lymphocyte proliferation and reduces the production of various cytokines, including tumor necrosis factor (TNF)-α. A 72-year-old female with diabetic nephropathy on hemodialysis developed multiple lung nodules following the administration of vildagliptin. A biopsy demonstrated the histology of granulomas without caseous necrosis. The discontinuation of vildagliptin resulted in the disappearance of the granulomas within 4 months. As granulomatosis often develops in patients under anti-TNF-α therapy, the accumulation of DPP-4 inhibitors or its metabolites is possibly linked to unrecognized complications, such as sarcoid-like lung granulomas.

Sarcoid-like lung granulomas in a hemodialysis patient treated with a dipeptidyl peptidase-4 inhibitor

PubMed Central

Sada, Ken-ei; Wada, Jun; Morinaga, Hiroshi; Tuchimochi, Shigeyuki; Uka, Mayu; Makino, Hirofumi

2014-01-01

It has been reported that the inhibition of dipeptidyl peptidase-4 (DPP-4)/CD26 on T-cells by DPP-4 enzymatic inhibitors suppresses lymphocyte proliferation and reduces the production of various cytokines, including tumor necrosis factor (TNF)-α. A 72-year-old female with diabetic nephropathy on hemodialysis developed multiple lung nodules following the administration of vildagliptin. A biopsy demonstrated the histology of granulomas without caseous necrosis. The discontinuation of vildagliptin resulted in the disappearance of the granulomas within 4 months. As granulomatosis often develops in patients under anti-TNF-α therapy, the accumulation of DPP-4 inhibitors or its metabolites is possibly linked to unrecognized complications, such as sarcoid-like lung granulomas. PMID:25852868

Sterile nodular panniculitis with lung and lymph node involvement in a Siberian tiger (Panthera tigris altica)

PubMed Central

HU, Shou-Ping; ZHANG, Zhuo; ZHANG, Jiao-Er; CAI, Xue-Hui; NAKAYAMA, Hiroyuki; HE, Xi-Jun

2017-01-01

A 2- to 4-year-old uncastrated male Siberian tiger (Panthera tigris altica) bred in a local wild animal park presented with generalized clinical signs including abdominal pain, fever, lethargy, and anorexia, along with subcutaneous nodules along the trunk. The patient subsequently died of chronic, progressive dyspnea despite 45 days of antibiotic treatment. At necropsy, mesenteric fat inflammation and multiple subcutaneous, peritoneal, and intraabdominal nodules were observed. The lungs demonstrated congestion and heavy coagulation, and necrotic foci were observed on the cut surface. Histopathologically, the nodules were identified as granulomatous fatty tissue with numerous lymphocytes, infiltration with lipid-laden macrophages, and fibrosis. These changes were also noted in the lung. The etiology of this condition remains undetermined. PMID:29081476

The diagnosis and treatment of brain metastases in EGFR mutant lung cancer.

PubMed

Minchom, Anna; Yu, Ken C; Bhosle, Jaishree; O'Brien, Mary

2014-05-01

The epidemiology of non-small-cell lung cancer (NSCLC) has changed with a new pattern of disease emerging - a form of adenocarcinoma in mostly younger female patients, who are never or light smokers and more frequently in East Asian populations. Description of EGF receptor (EGFR) mutations has allowed new management strategies to evolve. Oral targeted therapies have broadened the treatment options in the advanced setting with the potential for periods of long term response. The brain is a common site of metastases with EGFR mutated lung cancer typically displaying asymptomatic, small volume, multiple lesions that respond to treatment. We explore the role of local and system therapies for brain metastases in this disease including the role of EGFR inhibitors.

Electromagnetic Tracking Navigation to Guide Radiofrequency Ablation (RFA) of a Lung Tumor

PubMed Central

Amalou, Hayet; Wood, Bradford J.

2013-01-01

Radiofrequency ablation (RFA) may be an option for patients with lung tumors who have unresectable disease and are not suitable for available palliative modalities. RFA electrode positioning may take several attempts, necessitating multiple imaging acquisitions or continuous use of CT (Computed Tomography). Electromagnetic tracking utilizes miniature sensors integrated with RFA equipment to guide tools in real-time, while referencing to pre-procedure imaging. This technology was demonstrated successfully during a lung tumor ablation, and was more accurate at targeting the tumor, compared to traditional freehand needle insertion. It is possible, although speculative and anecdotal, that more accuracy could prevent unnecessary repositioning punctures and decrease radiation exposure. Electromagnetic tracking has theoretical potential to benefit minimally invasive interventions. PMID:23207535

Toxoplasmosis complicating lung cancer: a case report.

PubMed

Lu, Nianhong; Liu, Caihong; Wang, Jiangyuan; Ding, Ying; Ai, Qing

2015-01-01

Toxoplasmosis complicating lung cancer has been described only rarely. Here, we report a case of acute Toxoplasma gondii infection in a patient with squamous lung cancer. A 64-year-old woman was admitted to our hospital with a history of cough of 6 months' duration and chest pain of 1 week's duration. Further examination revealed multiple swollen lymph nodes, palpable on the top of the right collarbone and without tenderness. The chest X-ray, bronchoscopy, and computed tomography scan confirmed squamous carcinoma of the right lung. The Wright-stained bronchoalveolar-lavage fluid cytology diagnosis was positive for T. gondii and tachyzoites were detected. All of them were of free type (ectocytic), without intracellular parasites. Serological examination revealed that the anti-T. gondii immunoglobulin (Ig) M and IgG antibodies were positive. Unfortunately the patient did not continue treatment and was lost to follow-up. Toxoplasmosis is a life-threatening opportunistic infection in patients with lung cancer. Prompt recognition of T. gondii infection among cancer patients with subsequent targeted treatment of toxoplasmosis could help alleviate symptoms and improve survival.

xCT (SLC7A11)-mediated metabolic reprogramming promotes non-small cell lung cancer progression.

PubMed

Ji, Xiangming; Qian, Jun; Rahman, S M Jamshedur; Siska, Peter J; Zou, Yong; Harris, Bradford K; Hoeksema, Megan D; Trenary, Irina A; Heidi, Chen; Eisenberg, Rosana; Rathmell, Jeffrey C; Young, Jamey D; Massion, Pierre P

2018-05-23

Many tumors increase uptake and dependence on glucose, cystine or glutamine. These basic observations on cancer cell metabolism have opened multiple new diagnostic and therapeutic avenues in cancer research. Recent studies demonstrated that smoking could induce the expression of xCT (SLC7A11) in oral cancer cells, suggesting that overexpression of xCT may support lung tumor progression. We hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival. Our results demonstrated that 1) xCT was highly expressed at the cytoplasmic membrane in non-small cell lung cancer (NSCLC), 2) the expression of xCT was correlated with advanced stage and predicted a worse 5-year survival, 3) targeting xCT transport activity in xCT overexpressing NSCLC cells with sulfasalazine decreased cell proliferation and invasion in vitro and in vivo and 4) increased dependence on glutamine was observed in xCT overexpressed normal airway epithelial cells. These results suggested that xCT regulate metabolic requirements during lung cancer progression and be a potential therapeutic target in NSCLC.

78 FR 7438 - Prospective Grant of Exclusive License: Development of Human Monoclonal Antibodies Against DR4

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-01

... cancer, lung cancer, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease''. DATES: Only written comments and/or applications for a...

ECMO support for right main bronchial disruption in multiple trauma patient with brain injury--a case report and literature review.

PubMed

Zhou, R; Liu, B; Lin, K; Wang, R; Qin, Z; Liao, R; Qiu, Y

2015-07-01

Extracorporeal membrane oxygenation (ECMO) may offer life-saving treatment in severe pulmonary contusion or acute respiratory distress syndrome when conventional treatments have failed. However, because of the bleeding risk of systemic anticoagulation, ECMO should be performed only as a last resort in multiple trauma victims. Here, we report ECMO as a bridge for right main bronchus reconstruction and recovery of traumatic wet lung in a 31-year-old male multi-trauma patient with right main bronchial disruption, bilateral pulmonary contusion, cerebral contusion and long bone fracture. The patient was discharged without any obvious complication. ECMO support in a traumatic brain injured patient with severe hypoxemia caused by lung contusion and/or tracheal bronchus disruption is not an absolute contraindication. © The Author(s) 2014.

Management of Resistance to Crizotinib in Anaplastic Lymphoma Kinase-Positive Non-Small-cell Lung Cancer.

PubMed

Matikas, Alexios; Kentepozidis, Nikolaos; Georgoulias, Vassilis; Kotsakis, Athanasios

2016-11-01

During the past decade, the recognition of an ever-expanding list of driver oncogenic mutations in non-small-cell lung cancer has resulted in rapid therapeutic advances. Since the first description of the echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement in 4% of cases of non-small-cell lung cancer in 2007, a highly potent and selective ALK inhibitor, crizotinib, was developed and approved in record time. However, it soon became apparent that although the responses can be dramatic and durable and primary intrinsic resistance to crizotinib is uncommon, the emergence of secondary resistance is inevitable. Efforts to elucidate the specific mechanisms that confer acquired resistance to crizotinib are underway. These have led to the recognition of the role of secondary resistance mutations, of ALK amplification, and of activation of bypass signaling, all of which contribute to resistance to crizotinib. Moreover, the rapid preclinical and clinical development of multiple second-generation ALK inhibitors that exhibit significant clinical activity against crizotinib-resistant disease has provided multiple options to treating physicians, with the ultimate goal the delivery of tailored medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Audio Coaching on Correlation of Abdominal Displacement With Lung Tumor Motion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, Mitsuhiro; Narita, Yuichiro; Matsuo, Yukinori

2009-10-01

Purpose: To assess the effect of audio coaching on the time-dependent behavior of the correlation between abdominal motion and lung tumor motion and the corresponding lung tumor position mismatches. Methods and Materials: Six patients who had a lung tumor with a motion range >8 mm were enrolled in the present study. Breathing-synchronized fluoroscopy was performed initially without audio coaching, followed by fluoroscopy with recorded audio coaching for multiple days. Two different measurements, anteroposterior abdominal displacement using the real-time positioning management system and superoinferior (SI) lung tumor motion by X-ray fluoroscopy, were performed simultaneously. Their sequential images were recorded using onemore » display system. The lung tumor position was automatically detected with a template matching technique. The relationship between the abdominal and lung tumor motion was analyzed with and without audio coaching. Results: The mean SI tumor displacement was 10.4 mm without audio coaching and increased to 23.0 mm with audio coaching (p < .01). The correlation coefficients ranged from 0.89 to 0.97 with free breathing. Applying audio coaching, the correlation coefficients improved significantly (range, 0.93-0.99; p < .01), and the SI lung tumor position mismatches became larger in 75% of all sessions. Conclusion: Audio coaching served to increase the degree of correlation and make it more reproducible. In addition, the phase shifts between tumor motion and abdominal displacement were improved; however, all patients breathed more deeply, and the SI lung tumor position mismatches became slightly larger with audio coaching than without audio coaching.« less

Association of high-level humidifier disinfectant exposure with lung injury in preschool children.

PubMed

Park, Dong-Uk; Ryu, Seung-Hun; Roh, Hyun-Suk; Lee, Eun; Cho, Hyun-Ju; Yoon, Jisun; Lee, So-Yeon; Cho, Young Ah; Do, Kyung-Hyun; Hong, Soo-Jong

2018-03-01

Children aged ≤6years reportedly account for 52% of victims of humidifier disinfectant-associated lung injuries. To evaluate the association of humidifier disinfectants with lung injury risk among children aged ≤6years. Patients with humidifier disinfectant-associated lung injuries (n=214) who were clinically evaluated to have a definite (n=108), probable (n=49), or possible (n=57) association with humidifier disinfectants as well as control patients (n=123) with lung injury deemed unlikely to be associated with humidifier disinfectant use were evaluated to determine factors associated with increased risk of humidifier disinfectant-associated lung injury using unconditional multiple logistic regression analysis. For estimated airborne humidifier disinfectant concentrations, risk of humidifier disinfectant-associated lung injury increased ≥two-fold in a dose-dependent manner in the highest quartile (Q4, 135-1443μg/m 3 ) compared with that in the lowest quartile (Q1, ≤33μg/m 3 ). Registered patients using more than two humidifier disinfectant brands were at an increased risk of humidifier disinfectant-associated lung injury (adjusted OR, 2.2; 95% confidence interval, 1.3-3.8) compared with those using only one brand. With respect to the duration of humidifier disinfectant use, risk of humidifier disinfectant-associated lung injury increased ≥two-fold in the lowest quartile (≤5months) compared with that in the highest quartile (≥14months; adjusted OR 0.3; 95% confidence interval, 0.2-0.6). Younger children are more vulnerable to HDLI when exposed to HD chemicals within short period in early life. Copyright © 2017 Elsevier B.V. All rights reserved.

Benefits and harms of lung cancer screening in HIV-infected individuals with CD4+ ≥ 500: a simulation study.

PubMed

Kong, Chung Yin; Sigel, Keith; Criss, Steven D; Sheehan, Deirdre F; Triplette, Matthew; Silverberg, Michael J; Henschke, Claudia I; Justice, Amy; Braithwaite, R Scott; Wisnivesky, Juan; Crothers, Kristina

2018-04-19

Lung cancer is the leading cause of non-AIDS-defining cancer deaths among HIV-infected individuals. Although lung cancer screening with low-dose computed tomography (LDCT) is endorsed by multiple national organizations, whether HIV-infected individuals would have similar benefit as uninfected individuals from lung cancer screening is unknown. Our objective was to determine the benefits and harms of lung cancer screening among HIV-infected individuals. We modified an existing simulation model, the Lung Cancer Policy Model, for HIV-infected patients. Veterans Aging Cohort Study, Kaiser Permanente Northern California HIV Cohort, and medical literature. Target population: HIV-infected current and former smokers. Lifetime. Population. Annual LDCT screening from ages 45, 50, or 55 until ages 72 or 77 years. Benefits assessed included lung cancer mortality reduction and life-years gained; harms assessed included numbers of LDCT examinations, false-positive results, and overdiagnosed cases. For HIV-infected patients with CD4 at least 500 and 100% antiretroviral therapy adherence, screening using the Centers for Medicare & Medicaid Services criteria (age 55-77, 30 pack-years of smoking, current smoker or quit within 15 years of screening) would reduce lung cancer mortality by 18.9%, similar to the mortality reduction of uninfected individuals. Alternative screening strategies utilizing lower screening age and/or pack-years criteria increase mortality reduction, but require more LDCT examinations. Strategies assumed 100% screening adherence. Lung cancer screening reduces mortality in HIV-infected patients with CD4 at least l500, with a number of efficient strategies for eligibility, including the current Centers for Medicare & Medicaid Services criteria.

[Lung perfusion studies after percutaneous closure of patent ductus arteriosus using the Amplatzer Duct Occluder in children].

PubMed

Parra-Bravo, José Rafael; Apolonio-Martínez, Adriana; Estrada-Loza, María de Jesús; Beirana-Palencia, Luisa Gracia; Ramírez-Portillo, César Iván

2015-01-01

The closure of patent ductus arteriosus with multiple devices has been associated with a reduction in lung perfusion. We evaluated the pulmonary perfusion after percutaneous closure of patent ductus arteriosus with the Amplatzer Duct Occluder device using perfusion lung scan. Thirty patients underwent successful percutaneous patent ductus arteriosus occlusions using the Amplatzer Duct Occluder device were included in this study. Lung perfusion scans were preformed 6 months after the procedure. Peak flow velocities and protrusion of the device were analyzed by Doppler echocardiography. A left lung perfusion<40% was considered abnormal. The device implantation was successful in all patients. Average perfusion of left lung was 44.7±4.9% (37.8-61.4). Five patients (16.6%) showed decreased perfusion of the left lung. Age, low weight, the length of the ductus arteriosus and the minimum and maximum diameter/length of the ductus arteriosus ratio were statistically significant in patients with abnormalities of lung perfusion. It was observed protrusion the device in 6 patients with a higher maximum flow rate in the left pulmonary artery. The left lung perfusion may be compromised after percutaneous closure of patent ductus arteriosus with the Amplatzer Duct Occluder. The increased flow velocity in the origin of the left pulmonary artery can be a poor indicator of reduction in pulmonary perfusion and can occur in the absence of protrusion of the device. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

An Ultrasound Surface Wave Technique for Assessing Skin and Lung Diseases.

PubMed

Zhang, Xiaoming; Zhou, Boran; Kalra, Sanjay; Bartholmai, Brian; Greenleaf, James; Osborn, Thomas

2018-02-01

Systemic sclerosis (SSc) is a multi-organ connective tissue disease characterized by immune dysregulation and organ fibrosis. Severe organ involvement, especially of the skin and lung, is the cause of morbidity and mortality in SSc. Interstitial lung disease (ILD) includes multiple lung disorders in which the lung tissue is fibrotic and stiffened. The purpose of this study was to translate ultrasound surface wave elastography (USWE) for assessing patients with SSc and/or ILD via measuring surface wave speeds of both skin and superficial lung tissue. Forty-one patients with both SSc and ILD and 30 healthy patients were enrolled in this study. An external harmonic vibration was used to generate the wave propagation on the skin or lung. Three excitation frequencies of 100, 150 and 200 Hz were used. An ultrasound probe was used to measure the wave propagation in the tissue non-invasively. Surface wave speeds were measured on the forearm and upper arm of both left and right arm, as well as the upper and lower lungs, through six intercostal spaces of patients and healthy patients. Viscoelasticity of the skin was calculated by the wave speed dispersion with frequency using the Voigt model. The magnitudes of surface wave speed and viscoelasticity of patients' skin were significantly higher than those of healthy patients (p <0.0001) for each location and each frequency. The surface wave speeds of patients' lung were significantly higher than those of healthy patients (p <0.0001) for each location and each frequency. USWE is a non-invasive and non-ionizing technique for measuring both skin and lung surface wave speed and may be useful for quantitative assessment of SSc and/or ILD. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Hydrogen Gas Inhalation Attenuates Seawater Instillation-Induced Acute Lung Injury via the Nrf2 Pathway in Rabbits.

PubMed

Diao, Mengyuan; Zhang, Sheng; Wu, Lifeng; Huan, Le; Huang, Fenglou; Cui, Yunliang; Lin, Zhaofen

2016-12-01

Seawater instillation-induced acute lung injury involves oxidative stress and apoptosis. Although hydrogen gas inhalation is reportedly protective in multiple types of lung injury, the effect of hydrogen gas inhalation on seawater instillation-induced acute lung injury remains unknown. This study investigated the effect of hydrogen gas on seawater instillation-induced acute lung injury and explored the mechanisms involved. Rabbits were randomly assigned to control, hydrogen (2 % hydrogen gas inhalation), seawater (3 mL/kg seawater instillation), and seawater + hydrogen (3 mL/kg seawater instillation + 2 % hydrogen gas inhalation) groups. Arterial partial oxygen pressure and lung wet/dry weight ratio were detected. Protein content in bronchoalveolar lavage fluid (BALF) and serum as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were determined. Hematoxylin-eosin staining was used to monitor changes in lung specimens, and malondialdehyde (MDA) content and myeloperoxidase (MPO) activity were assayed. In addition, NF-E2-related factor (Nrf) 2 and heme oxygenase (HO)-1 mRNA and protein expression were measured, and apoptosis was assessed by measuring caspase-3 expression and using terminal deoxy-nucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. Hydrogen gas inhalation markedly improved lung endothelial permeability and decreased both MDA content and MPO activity in lung tissue; these changes were associated with decreases in TNF-α, IL-1β, and IL-6 in BALF. Hydrogen gas also alleviated histopathological changes and cell apoptosis. Moreover, Nrf2 and HO-1 expressions were significantly activated and caspase-3 expression was inhibited. These results demonstrate that hydrogen gas inhalation attenuates seawater instillation-induced acute lung injury in rabbits and that the protective effects observed may be related to the activation of the Nrf2 pathway.

Alterations in gene expression and DNA methylation during murine and human lung alveolar septation.

PubMed

Cuna, Alain; Halloran, Brian; Faye-Petersen, Ona; Kelly, David; Crossman, David K; Cui, Xiangqin; Pandit, Kusum; Kaminski, Naftali; Bhattacharya, Soumyaroop; Ahmad, Ausaf; Mariani, Thomas J; Ambalavanan, Namasivayam

2015-07-01

DNA methylation, a major epigenetic mechanism, may regulate coordinated expression of multiple genes at specific time points during alveolar septation in lung development. The objective of this study was to identify genes regulated by methylation during normal septation in mice and during disordered septation in bronchopulmonary dysplasia. In mice, newborn lungs (preseptation) and adult lungs (postseptation) were evaluated by microarray analysis of gene expression and immunoprecipitation of methylated DNA followed by sequencing (MeDIP-Seq). In humans, microarray gene expression data were integrated with genome-wide DNA methylation data from bronchopulmonary dysplasia versus preterm and term lung. Genes with reciprocal changes in expression and methylation, suggesting regulation by DNA methylation, were identified. In mice, 95 genes with inverse correlation between expression and methylation during normal septation were identified. In addition to genes known to be important in lung development (Wnt signaling, Angpt2, Sox9, etc.) and its extracellular matrix (Tnc, Eln, etc.), genes involved with immune and antioxidant defense (Stat4, Sod3, Prdx6, etc.) were also observed. In humans, 23 genes were differentially methylated with reciprocal changes in expression in bronchopulmonary dysplasia compared with preterm or term lung. Genes of interest included those involved with detoxifying enzymes (Gstm3) and transforming growth factor-β signaling (bone morphogenetic protein 7 [Bmp7]). In terms of overlap, 20 genes and three pathways methylated during mouse lung development also demonstrated changes in methylation between preterm and term human lung. Changes in methylation correspond to altered expression of a number of genes associated with lung development, suggesting that DNA methylation of these genes may regulate normal and abnormal alveolar septation.

Rho inhibition by lovastatin affects apoptosis and DSB repair of primary human lung cells in vitro and lung tissue in vivo following fractionated irradiation

PubMed Central

Ziegler, Verena; Henninger, Christian; Simiantonakis, Ioannis; Buchholzer, Marcel; Ahmadian, Mohammad Reza; Budach, Wilfried; Fritz, Gerhard

2017-01-01

Thoracic radiotherapy causes damage of normal lung tissue, which limits the cumulative radiation dose and, hence, confines the anticancer efficacy of radiotherapy and impacts the quality of life of tumor patients. Ras-homologous (Rho) small GTPases regulate multiple stress responses and cell death. Therefore, we investigated whether pharmacological targeting of Rho signaling by the HMG-CoA-reductase inhibitor lovastatin influences ionizing radiation (IR)-induced toxicity in primary human lung fibroblasts, lung epithelial and lung microvascular endothelial cells in vitro and subchronic mouse lung tissue damage following hypo-fractionated irradiation (4x4 Gy). The statin improved the repair of radiation-induced DNA double-strand breaks (DSBs) in all cell types and, moreover, protected lung endothelial cells from IR-induced caspase-dependent apoptosis, likely involving p53-regulated mechanisms. Under the in vivo situation, treatment with lovastatin or the Rac1-specific small molecule inhibitor EHT1864 attenuated the IR-induced increase in breathing frequency and reduced the percentage of γH2AX and 53BP1-positive cells. This indicates that inhibition of Rac1 signaling lowers IR-induced residual DNA damage by promoting DNA repair. Moreover, lovastatin and EHT1864 protected lung tissue from IR-triggered apoptosis and mitigated the IR-stimulated increase in regenerative proliferation. Our data document beneficial anti-apoptotic and genoprotective effects of pharmacological targeting of Rho signaling following hypo-fractionated irradiation of lung cells in vitro and in vivo. Rac1-targeting drugs might be particular useful for supportive care in radiation oncology and, moreover, applicable to improve the anticancer efficacy of radiotherapy by widening the therapeutic window of thoracic radiation exposure. PMID:28796249

[Restriction polymorphism of the proto-oncogene c-Ha-ras-1 in patients with multiple primary malignant neoplasms and non-small-cell lung cancer].

PubMed

Gaspar'ian, A V; Sel'chuk, V Iu; Iakubovskaia, M G; Zborovskaia, I B; Tatosian, A G

1997-01-01

Restriction fragment length polymorphism in the human c-Ha-ras-1 locus, associated with a minisatellite sequence, was examined in 45 multiple primary cancer (MPC) patients, 56 patients with squamous cell lung cancer (SCLC), 21 patients with lung adenocarcinoma (LAC), and 53 individuals having no oncopathology. Southern analysis of cellular DNA revealed the presence of 4 common alleles (with collective allele frequency close to 94% in the control group) and a set of rare alleles. Allele a3, (2.1 kb in size under MspI/HpaII digestion) was shown to be more frequent in the MPC than in the control group. The same tendency was observed in the patients with highly differentiated cell lung cancer. An increased frequency of the a4 allele (2.5 kb under MspI/HpaII digestion) was observed in the patients with adenocarcinomas as well as in the patients with metastases and low levels of tumor tissue differentiation. The elevated frequencies of a3 in the MPC group and of a4 in the LAC patients did not correlate with increased risk of the cancers mentioned above but was associated with type of tumor progression. Previously, it was reported that the mini-satellite sequence within the c-Ha-ras-1 locus possesses enhancer activity. Our data indirectly confirm the hypothesis that the efficiency of minisatellite modulator activity is associated with fragment size.

Development of Welding Fumes Health Index (WFHI) for Welding Workplace’s Safety and Health Assessment

PubMed Central

HARIRI, Azian; PAIMAN, Nuur Azreen; LEMAN, Abdul Mutalib; MD. YUSOF, Mohammad Zainal

2014-01-01

Abstract Background This study aimed to develop an index that can rank welding workplace that associate well with possible health risk of welders. Methods Welding Fumes Health Index (WFHI) were developed based on data from case studies conducted in Plant 1 and Plant 2. Personal sampling of welding fumes to assess the concentration of metal constituents along with series of lung function tests was conducted. Fifteen metal constituents were investigated in each case study. Index values were derived from aggregation analysis of metal constituent concentration while significant lung functions were recognized through statistical analysis in each plant. Results The results showed none of the metal constituent concentration was exceeding the permissible exposure limit (PEL) for all plants. However, statistical analysis showed significant mean differences of lung functions between welders and non-welders. The index was then applied to one of the welding industry (Plant 3) for verification purpose. The developed index showed its promising ability to rank welding workplace, according to the multiple constituent concentrations of welding fumes that associates well with lung functions of the investigated welders. Conclusion There was possibility that some of the metal constituents were below the detection limit leading to ‘0’ value of sub index, thus the multiplicative form of aggregation model was not suitable for analysis. On the other hand, maximum or minimum operator forms suffer from compensation issues and were not considered in this study. PMID:25927034

Autophagy in lung disease pathogenesis and therapeutics

PubMed Central

Ryter, Stefan W.; Choi, Augustine M.K.

2015-01-01

Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, and immune system functions. Selective pathways for autophagic degradation of cargoes may have variable significance in disease pathogenesis. Among these, the autophagic clearance of bacteria (xenophagy) may represent a crucial host defense mechanism in the pathogenesis of sepsis and inflammatory diseases. Our recent studies indicate that the autophagic clearance of mitochondria, a potentially protective program, may aggravate the pathogenesis of chronic obstructive pulmonary disease by activating cell death programs. We report similar findings with respect to the autophagic clearance of cilia components, which can contribute to airways dysfunction in chronic lung disease. In certain diseases such as pulmonary hypertension, autophagy may confer protection by modulating proliferation and cell death. In other disorders, such as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may contribute to pathogenesis. In lung cancer, autophagy has multiple consequences by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting tumor cell survival. In this review we highlight the multiple functions of autophagy and its selective autophagy subtypes that may be of significance to the pathogenesis of human disease, with an emphasis on lung disease and therapeutics. PMID:25617802

Multidimensional analysis of the effect of occupational exposure to organic solvents on lung cancer risk: the ICARE study

PubMed Central

Mattei, Francesca; Liverani, Silvia; Guida, Florence; Matrat, Mireille; Cenée, Sylvie; Azizi, Lamiae; Menvielle, Gwenn; Sanchez, Marie; Pilorget, Corinne; Lapôtre-Ledoux, Bénédicte; Luce, Danièle; Richardson, Sylvia; Stücker, Isabelle

2016-01-01

Background The association between lung cancer and occupational exposure to organic solvents is discussed. Since different solvents are often used simultaneously, it is difficult to assess the role of individual substances. Objectives The present study is focused on an in-depth investigation of the potential association between lung cancer risk and occupational exposure to a large group of organic solvents, taking into account the well-known risk factors for lung cancer, tobacco smoking and occupational exposure to asbestos. Methods We analysed data from the Investigation of occupational and environmental causes of respiratory cancers (ICARE) study, a large French population-based case–control study, set up between 2001 and 2007. A total of 2276 male cases and 2780 male controls were interviewed, and long-life occupational history was collected. In order to overcome the analytical difficulties created by multiple correlated exposures, we carried out a novel type of analysis based on Bayesian profile regression. Results After analysis with conventional logistic regression methods, none of the 11 solvents examined were associated with lung cancer risk. Through a profile regression approach, we did not observe any significant association between solvent exposure and lung cancer. However, we identified clusters at high risk that are related to occupations known to be at risk of developing lung cancer, such as painters. Conclusions Organic solvents do not appear to be substantial contributors to the occupational risk of lung cancer for the occupations known to be at risk. PMID:26911986

Impact of obstructive sleep apnea on lung volumes and mechanical properties of the respiratory system in overweight and obese individuals.

PubMed

Abdeyrim, Arikin; Zhang, Yongping; Li, Nanfang; Zhao, Minghua; Wang, Yinchun; Yao, Xiaoguang; Keyoumu, Youledusi; Yin, Ting

2015-07-25

Even through narrowing of the upper-airway plays an important role in the generation of obstructive sleep apnea (OSA), the peripheral airways is implicated in pre-obese and obese OSA patients, as a result of decreased lung volume and increased lung elastic recoil pressure, which, in turn, may aggravate upper-airway collapsibility. A total of 263 male (n = 193) and female (n = 70) subjects who were obese to various degrees without a history of lung diseases and an expiratory flow limitation, but troubled with snoring or suspicion of OSA were included in this cross-sectional study. According to nocturnal-polysomnography the subjects were distributed into OSA and non-OSA groups, and were further sub-grouped by gender because of differences between males and females, in term of, lung volume size, airway resistance, and the prevalence of OSA among genders. Lung volume and respiratory mechanical properties at different-frequencies were evaluated by plethysmograph and an impulse oscillation system, respectively. Functional residual capacity (FRC) and expiratory reserve volume were significantly decreased in the OSA group compared to the non-OSA group among males and females. As weight and BMI in males in the OSA group were greater than in the non-OSA group (90 ± 14.8 kg vs. 82 ± 10.4 kg, p < 0.001; 30.5 ± 4.2 kg/m(2) vs. 28.0 ± 3.0 kg/m(2), p < 0.001), multiple regression analysis was required to adjust for BMI or weight and demonstrated that these lung volumes decreases were independent from BMI and associated with the severity of OSA. This result was further confirmed by the female cohort. Significant increases in total respiratory resistance and decreases in respiratory conductance (Grs) were observed with increasing severity of OSA, as defined by the apnea-hypopnea index (AHI) in both genders. The specific Grs (sGrs) stayed relatively constant between the two groups in woman, and there was only a weak association between AHI and sGrs among man. Multiple-stepwise-regression showed that reactance at 5 Hz was highly correlated with AHI in males and females or hypopnea index in females, independently-highly correlated with peripheral-airway resistance and significantly associated with decreasing FRC. Total respiratory resistance and peripheral airway resistance significantly increase, and its inverse Grs decrease, in obese patients with OSA in comparison with those without OSA, and are independently associated with OSA severity. These results might be attributed to the abnormally increased lung elasticity recoil pressure on exhalation, due to increase in lung elasticity and decreased lung volume in obese OSA.

THE 5-LIPOXYGENASE PATHWAY IS REQUIRED FOR ACUTE LUNG INJURY FOLLOWING HEMORRHAGIC SHOCK

PubMed Central

Eun, John C.; Moore, Ernest E.; Mauchley, David C.; Johnson, Chris A.; Meng, Xianzhong; Banerjee, Anirban; Wohlauer, Max V.; Zarini, Simona; Gijón, Miguel A.; Murphy, Robert C.

2012-01-01

The cellular and biochemical mechanisms leading to acute lung injury and subsequent multiple organ failure are only partially understood. In order to study the potential role of eicosanoids, particularly leukotrienes, as possible mediators of acute lung injury, we used a murine experimental model of acute lung injury induced by hemorrhagic shock after blood removal via cardiac puncture. Neutrophil sequestration as shown by immunofluorescence, and protein leakage into the alveolar space, were measured as markers of injury. We used liquid chromatography coupled to tandem mass spectrometry to unequivocally identify several eicosanoids in the bronchoalveolar lavage fluid of experimental animals. MK886, a specific inhibitor of the 5-lipoxygenase pathway, as well as transgenic mice deficient in 5-lipoxygenase, were used to determine the role of this enzymatic pathway in this model. Leukotriene B4 and leukotriene C4 were consistently elevated in shock-treated mice compared to sham-treated mice. MK886 attenuated neutrophil infiltration and protein extravasation induced by hemorrhagic shock. 5-lipoxygenase-deficient mice showed reduced neutrophil infiltration and protein extravasation after shock treatment, indicating greatly reduced lung injury. These results support the hypothesis that 5-lipoxygenase, most likely through the generation of leukotrienes, plays an important role in the pathogenesis of acute lung injury induced by hemorrhagic shock in mice. This pathway could represent a new target for pharmacological intervention to reduce lung damage following severe primary injury. PMID:22392149

Spiritual Well-Being and Correlated Factors in Subjects With Advanced COPD or Lung Cancer.

PubMed

Hasegawa, Takaaki; Kawai, Momoko; Kuzuya, Nanori; Futamura, Yohei; Horiba, Akane; Ishiguro, Takashi; Yoshida, Tsutomu; Sawa, Toshiyuki; Sugiyama, Yasuyuki

2017-05-01

Spiritual care for patients with COPD has rarely been discussed, and thus much remains unknown about their needs. The aims of this study were to identify the factors associated with spiritual well-being and to compare the levels of spiritual well-being between subjects with advanced COPD and those with inoperable lung cancer. A total of 96 subjects with COPD or lung cancer participated in this study, which was conducted between December 2014 and April 2016. Measures included the Japanese version of the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12) scale, the McGill Quality of Life Questionnaire (MQOL), the modified Medical Research Council (mMRC) dyspnea scale, and various other medico-social factors. No significant differences were found between subjects with COPD and those with lung cancer in median FACIT-Sp-12 scores (COPD, 27; lung cancer, 26; P = .81). However, significant differences were found in the 2 MQOL domains, suggesting that subjects with COPD had a better psychological state ( P = .01) and that subjects with lung cancer had a better support state ( P = .002). Multiple regression analysis revealed that mMRC was significantly associated with FACIT-Sp-12 scores in subjects with COPD. These results suggest that subjects with advanced COPD experience spiritual well-being similar to that of subjects with inoperable lung cancer. Copyright © 2017 by Daedalus Enterprises.

Distinguishing the histological and radiological features of cystic lung disease in Birt-Hogg-Dubé syndrome from those of tobacco-related spontaneous pneumothorax.

PubMed

Fabre, Aurelie; Borie, Raphael; Debray, Marie Pierre; Crestani, Bruno; Danel, Claire

2014-04-01

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominantly inherited genodermatosis that predisposes to cystic lung disease, leading to spontaneous pneumothoraces. This retrospective analysis of five BHD cases (two men, three women) compared lung histology and computed tomography (CT) imaging to a matched cohort of non-BHD patients with spontaneous pneumothoraces (SPN). Lung was sampled during pleurodesis to resect bullae. Recurrent pneumothoraces was seen in two patients. Fourteen sets of histological slides (seven in each group) and 10 CT scans (five in each group) were reviewed. CT scans in BHD showed multiple cysts with a basal predominance and intraparenchymal/peribronchial distribution. On histological examination, BHD lungs showed punch-out cysts with no inflammation, and lacked subpleural fibroelastotic scars and smoking changes. In contrast, all SPN cases showed respiratory bronchiolitis and subpleural fibroelastotic scars. This study emphasizes the importance of smoking history and topography of the lesions in assessing cystic lung disease. Pathologists need to remain alert to the possibility of BHD in the setting of recurrent pneumothoraces in a non-smoker, in particular in a woman, at any age, and should take part in a multidisciplinary approach to the diagnosis of cystic lung disease to obtain clinical and CT scan details. © 2013 John Wiley & Sons Ltd.

Establishment of adoptive cell therapy with tumor infiltrating lymphocytes for non-small cell lung cancer patients.

PubMed

Ben-Avi, Ronny; Farhi, Ronit; Ben-Nun, Alon; Gorodner, Marina; Greenberg, Eyal; Markel, Gal; Schachter, Jacob; Itzhaki, Orit; Besser, Michal J

2018-05-29

Adoptive cell therapy (ACT) of tumor infiltration lymphocytes (TIL) yields promising clinical results in metastatic melanoma patients, who failed standard treatments. Due to the fact that metastatic lung cancer has proven to be susceptible to immunotherapy and possesses a high mutation burden, which makes it responsive to T cell attack, we explored the feasibility of TIL ACT in non-small cell lung cancer (NSCLC) patients. Multiple TIL cultures were isolated from tumor specimens of five NSCLC patients undergoing thoracic surgery. We were able to successfully establish TIL cultures by various methods from all patients within an average of 14 days. Fifteen lung TIL cultures were further expanded to treatment levels under good manufacturing practice conditions and functionally and phenotypically characterized. Lung TIL expanded equally well as 103 melanoma TIL obtained from melanoma patients previously treated at our center, and had a similar phenotype regarding PD1, CD28, and 4-1BB expressions, but contained a higher percent of CD4 T cells. Lung carcinoma cell lines were established from three patients of which two possessed TIL cultures with specific in vitro anti-tumor reactivity. Here, we report the successful pre-clinical production of TIL for immunotherapy in the lung cancer setting, which may provide a new treatment modality for patients with metastatic NSCLC. The initiation of a clinical trial is planned for the near future.

Are Lung Imaging Reporting and Data System Categories Clear to Radiologists? A Survey of the Korean Society of Thoracic Radiology Members on Ten Difficult-to-Classify Scenarios.

PubMed

Han, Dae Hee; Goo, Jin Mo; Chong, Semin; Ahn, Myeong Im

2017-01-01

To evaluate possible variability in chest radiologists' interpretations of the Lung Imaging Reporting and Data System (Lung-RADS) on difficult-to-classify scenarios. Ten scenarios of difficult-to-classify imaginary lung nodules were prepared as an online survey that targeted Korean Society of Thoracic Radiology members. In each question, a description was provided of the size, consistency, and interval change (new or growing) of a lung nodule observed using annual repeat computed tomography, and the respondent was instructed to choose one answer from five choices: category 2, 3, 4A, or 4B, or "un-categorizable." Consensus answers were established by members of the Korean Imaging Study Group for Lung Cancer. Of the 420 answers from 42 respondents (excluding multiple submissions), 310 (73.8%) agreed with the consensus answers; eleven (26.2%) respondents agreed with the consensus answers to six or fewer questions. Assigning the imaginary nodules to categories higher than the consensus answer was more frequent (16.0%) than assigning them to lower categories (5.5%), and the agreement rate was below 50% for two scenarios. When given difficult-to-classify scenarios, chest radiologists showed large variability in their interpretations of the Lung-RADS categories, with high frequencies of disagreement in some specific scenarios.

Supine posture changes lung volumes and increases ventilation heterogeneity in cystic fibrosis.

PubMed

Smith, Laurie J; Macleod, Kenneth A; Collier, Guilhem J; Horn, Felix C; Sheridan, Helen; Aldag, Ina; Taylor, Chris J; Cunningham, Steve; Wild, Jim M; Horsley, Alex

2017-01-01

Lung Clearance Index (LCI) is recognised as an early marker of cystic fibrosis (CF) lung disease. The effect of posture on LCI however is important when considering longitudinal measurements from infancy and when comparing LCI to imaging studies. 35 children with CF and 28 healthy controls (HC) were assessed. Multiple breath washout (MBW) was performed both sitting and supine in triplicate and analysed for LCI, Scond, Sacin, and lung volumes. These values were also corrected for the Fowler dead-space to create 'alveolar' indices. From sitting to supine there was a significant increase in LCI and a significant decrease in FRC for both CF and HC (p<0.01). LCI, when adjusted to estimate 'alveolar' LCI (LCIalv), increased the magnitude of change with posture for both LCIalv and FRCalv in both groups, with a greater effect of change in lung volume in HC compared with children with CF. The % change in LCIalv for all subjects correlated significantly with lung volume % changes, most notably tidal volume/functional residual capacity (Vtalv/FRCalv (r = 0.54,p<0.001)). There is a significant increase in LCI from sitting to supine, which we believe to be in part due to changes in lung volume and also increasing ventilation heterogeneity related to posture. This may have implications in longitudinal measurements from infancy to older childhood and for studies comparing supine imaging methods to LCI.

Hope in the Context of Lung Cancer: Relationships of Hope to Symptoms and Psychological Distress

PubMed Central

Berendes, David; Keefe, Francis J.; Somers, Tamara J.; Kothadia, Sejal M.; Porter, Laura S.; Cheavens, Jennifer S.

2010-01-01

Context Hope may be important in explaining the variability in how patients adjust to lung cancer. Objectives The aim of this study was to examine how hope, as conceptualized by Snyder and colleagues, is associated with multiple indices of adjustment to lung cancer. This theoretical model of hope suggests that people with high levels of hope are able to think about the pathways to goals (pathways) and feel confident that they can pursue those pathways to reach their goals (agency). Methods We hypothesized that higher levels of hope, as measured by Snyder et al.’s hope scale, would be related to lower levels of pain and other lung cancer symptoms (i.e., fatigue, cough) and lower psychological distress (i.e., depression). Participants in this study included patients with a diagnosis of lung cancer (n = 51). All participants provided demographic and medical information and completed measures of hope, lung cancer symptoms, and psychological distress. Results Data analyses found that hope was inversely associated with major symptoms of cancer (i.e., pain, fatigue, cough) and psychological distress (i.e., depression), even after accounting for important demographic and medical variables (i.e., age, cancer stage). Conclusion The findings of this cross-sectional study highlight the potential importance of hope in understanding adjustment to lung cancer. Future longitudinal research could help reveal how hope and adjustment interact over the course of cancer survivorship. PMID:20579840

Mouse double minute-2 homolog (MDM2)-rs2279744 polymorphism associated with lung cancer risk in a Northeastern Chinese population.

PubMed

Wang, Xu; Jin, Lina; Cui, Jiuwei; Ma, Kewei; Chen, Xiao; Li, Wei

2015-01-01

Altered expression or function of mouse double minute-2 (MDM2) protein could contribute to lung carcinogenesis; thus, this study investigated MDM2-rs2279744 polymorphism together with other epidemiologic factors for their association with lung cancer risk. A total of 500 lung cancer patients and 500 age and gender-matched healthy controls living in Northeastern China were recruited for genotyping of MDM2-rs2279744. Clinicopathological data was collected and subjected to univariate and multivariate analyses. In univariate analysis, the MDM2-rs2279744 G/G genotype versus T/T + T/G genotypes showed a tendency toward a higher incidence of lung cancer in the recessive model (P = 0.043). However, there were no significant differences when it was analyzed by the dominant, additive, or multiplicative models. A significantly increased lung cancer risk was observed associated with lower education level, lower body mass index, cancer family history, prior diagnosis of chronic obstructive pulmonary disease and pneumonia, exposure to pesticide or gasoline/diesel, tobacco smoking, and heavy cooking emissions when assessed by multivariate analyses. Moreover, MDM2-rs2279744 was still a significant risk factor even after incorporating environmental and lifestyle factors. However, there was no association between MDM2-rs2279744 and other factors. The MDM2-rs2279744 G/G genotype was associated with a higher lung cancer risk, even after incorporating other epidemiologic factors.

In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line

PubMed Central

Nanjo, Shigeki; Nakagawa, Takayuki; Takeuchi, Shinji; Kita, Kenji; Fukuda, Koji; Nakada, Mitsutoshi; Uehara, Hisanori; Nishihara, Hiroshi; Hara, Eiji; Uramoto, Hidetaka; Tanaka, Fumihiro; Yano, Seiji

2015-01-01

EML4-ALK lung cancer accounts for approximately 3–7% of non-small-cell lung cancer cases. To investigate the molecular mechanism underlying tumor progression and targeted drug sensitivity/resistance in EML4-ALK lung cancer, clinically relevant animal models are indispensable. In this study, we found that the lung adenocarcinoma cell line A925L expresses an EML4-ALK gene fusion (variant 5a, E2:A20) and is sensitive to the ALK inhibitors crizotinib and alectinib. We further established highly tumorigenic A925LPE3 cells, which also have the EML4-ALK gene fusion (variant 5a) and are sensitive to ALK inhibitors. By using A925LPE3 cells with luciferase gene transfection, we established in vivo imaging models for pleural carcinomatosis, bone metastasis, and brain metastasis, all of which are significant clinical concerns of advanced EML4-ALK lung cancer. Interestingly, crizotinib caused tumors to shrink in the pleural carcinomatosis model, but not in bone and brain metastasis models, whereas alectinib showed remarkable efficacy in all three models, indicative of the clinical efficacy of these ALK inhibitors. Our in vivo imaging models of multiple organ sites may provide useful resources to analyze further the pathogenesis of EML4-ALK lung cancer and its response and resistance to ALK inhibitors in various organ microenvironments. PMID:25581823

Patient-provider discussions about lung cancer screening pre- and post-guidelines: Health Information National Trends Survey (HINTS).

PubMed

Carter-Harris, Lisa; Tan, Andy S L; Salloum, Ramzi G; Young-Wolff, Kelly C

2016-11-01

In 2013, the USPSTF issued a Grade B recommendation that long-term current and former smokers receive lung cancer screening. Shared decision-making is important for individuals considering screening, and patient-provider discussions an essential component of the process. We examined prevalence and predictors of lung cancer screening discussions pre- and post-USPSTF guidelines. Data were obtained from two cycles of the Health Information National Trends Survey (2012; 2014). The analyzed sample comprised screening-eligible current and former smokers with no personal history of lung cancer (n=746 in 2012; n=795 in 2014). Descriptive and multiple logistic regression analyses were conducted; patient-reported discussion about lung cancer screening with provider was the outcome of interest. Contrary to expectations, patient-provider discussions about lung cancer screening were more prevalent pre-guideline, but overall patient-provider discussions were low in both years (17% in 2012; 10% in 2014). Current smokers were more likely to have had a discussion than former smokers. Significant predictors of patient-provider discussions included family history of cancer and having healthcare coverage. The prevalence of patient-provider discussions about lung cancer screening is suboptimal. There is a critical need for patient and provider education about shared decision-making and its importance in cancer screening decisions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens.

PubMed

Meliopoulos, Victoria A; Van de Velde, Lee-Ann; Van de Velde, Nicholas C; Karlsson, Erik A; Neale, Geoff; Vogel, Peter; Guy, Cliff; Sharma, Shalini; Duan, Susu; Surman, Sherri L; Jones, Bart G; Johnson, Michael D L; Bosio, Catharine; Jolly, Lisa; Jenkins, R Gisli; Hurwitz, Julia L; Rosch, Jason W; Sheppard, Dean; Thomas, Paul G; Murray, Peter J; Schultz-Cherry, Stacey

2016-08-01

The healthy lung maintains a steady state of immune readiness to rapidly respond to injury from invaders. Integrins are important for setting the parameters of this resting state, particularly the epithelial-restricted αVβ6 integrin, which is upregulated during injury. Once expressed, αVβ6 moderates acute lung injury (ALI) through as yet undefined molecular mechanisms. We show that the upregulation of β6 during influenza infection is involved in disease pathogenesis. β6-deficient mice (β6 KO) have increased survival during influenza infection likely due to the limited viral spread into the alveolar spaces leading to reduced ALI. Although the β6 KO have morphologically normal lungs, they harbor constitutively activated lung CD11b+ alveolar macrophages (AM) and elevated type I IFN signaling activity, which we traced to the loss of β6-activated transforming growth factor-β (TGF-β). Administration of exogenous TGF-β to β6 KO mice leads to reduced numbers of CD11b+ AMs, decreased type I IFN signaling activity and loss of the protective phenotype during influenza infection. Protection extended to other respiratory pathogens such as Sendai virus and bacterial pneumonia. Our studies demonstrate that the loss of one epithelial protein, αVβ6 integrin, can alter the lung microenvironment during both homeostasis and respiratory infection leading to reduced lung injury and improved survival.

Patient and Clinician Perspectives on Shared Decision-making in Early Adopting Lung Cancer Screening Programs: a Qualitative Study.

PubMed

Wiener, Renda Soylemez; Koppelman, Elisa; Bolton, Rendelle; Lasser, Karen E; Borrelli, Belinda; Au, David H; Slatore, Christopher G; Clark, Jack A; Kathuria, Hasmeena

2018-02-21

Guidelines recommend, and Medicare requires, shared decision-making between patients and clinicians before referring individuals at high risk of lung cancer for chest CT screening. However, little is known about the extent to which shared decision-making about lung cancer screening is achieved in real-world settings. To characterize patient and clinician impressions of early experiences with communication and decision-making about lung cancer screening and perceived barriers to achieving shared decision-making. Qualitative study entailing semi-structured interviews and focus groups. We enrolled 36 clinicians who refer patients for lung cancer screening and 49 patients who had undergone lung cancer screening in the prior year. Participants were recruited from lung cancer screening programs at four hospitals (three Veterans Health Administration, one urban safety net). Using content analysis, we analyzed transcripts to characterize communication and decision-making about lung cancer screening. Our analysis focused on the recommended components of shared decision-making (information sharing, deliberation, and decision aid use) and barriers to achieving shared decision-making. Clinicians varied in the information shared with patients, and did not consistently incorporate decision aids. Clinicians believed they explained the rationale and gave some (often purposely limited) information about the trade-offs of lung cancer screening. By contrast, some patients reported receiving little information about screening or its trade-offs and did not realize the CT was intended as a screening test for lung cancer. Clinicians and patients alike did not perceive that significant deliberation typically occurred. Clinicians perceived insufficient time, competing priorities, difficulty accessing decision aids, limited patient comprehension, and anticipated patient emotions as barriers to realizing shared decision-making. Due to multiple perceived barriers, patient-clinician conversations about lung cancer screening may fall short of guideline-recommended shared decision-making supported by a decision aid. Consequently, patients may be left uncertain about lung cancer screening's rationale, trade-offs, and process.

Fibrocytes in the fibrotic lung: altered phenotype detected by flow cytometry.

PubMed

Reese, Charles; Lee, Rebecca; Bonner, Michael; Perry, Beth; Heywood, Jonathan; Silver, Richard M; Tourkina, Elena; Visconti, Richard P; Hoffman, Stanley

2014-01-01

Fibrocytes are bone marrow hematopoietic-derived cells that also express a mesenchymal cell marker (commonly collagen I) and participate in fibrotic diseases of multiple organs. Given their origin, they or their precursors must be circulating cells before recruitment into target tissues. While most previous studies focused on circulating fibrocytes, here we focus on the fibrocyte phenotype in fibrotic tissue. The study's relevance to human disease is heightened by use of a model in which bleomycin is delivered systemically, recapitulating several features of human scleroderma including multi-organ fibrosis not observed when bleomycin is delivered directly into the lungs. Using flow cytometry, we find in the fibrotic lung a large population of CD45(high) fibrocytes (called Region I) rarely found in vehicle-treated control mice. A second population of CD45+ fibrocytes (called Region II) is observed in both control and fibrotic lung. The level of CD45 in circulating fibrocytes is far lower than in either Region I or II lung fibrocytes. The chemokine receptors CXCR4 and CCR5 are expressed at higher levels in Region I than in Region II and are present at very low levels in all other lung cells including CD45+/collagen I- leucocytes. The collagen chaperone HSP47 is present at similar high levels in both Regions I and II, but at a higher level in fibrotic lung than in control lung. There is also a major population of HSP47(high)/CD45- cells in fibrotic lung not present in control lung. CD44 is present at higher levels in Region I than in Region II and at much lower levels in all other cells including CD45+/collagen I- leucocytes. When lung fibrosis is inhibited by restoring caveolin-1 activity using a caveolin-1 scaffolding domain peptide (CSD), a strong correlation is observed between fibrocyte number and fibrosis score. In summary, the distinctive phenotype of fibrotic lung fibrocytes suggests that fibrocyte differentiation occurs primarily within the target organ.

Fibrocytes in the fibrotic lung: altered phenotype detected by flow cytometry

PubMed Central

Reese, Charles; Lee, Rebecca; Bonner, Michael; Perry, Beth; Heywood, Jonathan; Silver, Richard M.; Tourkina, Elena; Visconti, Richard P.; Hoffman, Stanley

2014-01-01

Fibrocytes are bone marrow hematopoietic-derived cells that also express a mesenchymal cell marker (commonly collagen I) and participate in fibrotic diseases of multiple organs. Given their origin, they or their precursors must be circulating cells before recruitment into target tissues. While most previous studies focused on circulating fibrocytes, here we focus on the fibrocyte phenotype in fibrotic tissue. The study's relevance to human disease is heightened by use of a model in which bleomycin is delivered systemically, recapitulating several features of human scleroderma including multi-organ fibrosis not observed when bleomycin is delivered directly into the lungs. Using flow cytometry, we find in the fibrotic lung a large population of CD45high fibrocytes (called Region I) rarely found in vehicle-treated control mice. A second population of CD45+ fibrocytes (called Region II) is observed in both control and fibrotic lung. The level of CD45 in circulating fibrocytes is far lower than in either Region I or II lung fibrocytes. The chemokine receptors CXCR4 and CCR5 are expressed at higher levels in Region I than in Region II and are present at very low levels in all other lung cells including CD45+/collagen I- leucocytes. The collagen chaperone HSP47 is present at similar high levels in both Regions I and II, but at a higher level in fibrotic lung than in control lung. There is also a major population of HSP47high/CD45- cells in fibrotic lung not present in control lung. CD44 is present at higher levels in Region I than in Region II and at much lower levels in all other cells including CD45+/collagen I- leucocytes. When lung fibrosis is inhibited by restoring caveolin-1 activity using a caveolin-1 scaffolding domain peptide (CSD), a strong correlation is observed between fibrocyte number and fibrosis score. In summary, the distinctive phenotype of fibrotic lung fibrocytes suggests that fibrocyte differentiation occurs primarily within the target organ. PMID:24999331

Multifarious immunotherapeutic approaches to cure HIV-1 infection.

PubMed

Imami, Nesrina; Herasimtschuk, Anna A

2015-01-01

Immunotherapy in the context of treated HIV-1 infection aims to improve immune responses to achieve better control of the virus. To date, multifaceted immunotherapeutic approaches have been shown to reduce immune activation and increase CD4 T-lymphocyte counts, further to the effects of antiretroviral therapy alone, in addition to improving HIV-1-specific T-cell responses. While sterilizing cure of HIV-1 would involve elimination of all replication-competent virus, a functional cure in which the host has long-lasting control of viral replication may be more feasible. In this commentary, we discuss novel strategies aimed at targeting the latent viral reservoir with cure of HIV-1 infection being the ultimate goal, an achievement that would have considerable impact on worldwide HIV-1 infection.

Wyoming greater sage-grouse habitat prioritization: A collection of multi-scale seasonal models and geographic information systems land management tools

USGS Publications Warehouse

O'Donnell, Michael S.; Aldridge, Cameron L.; Doherty, Kevin E.; Fedy, Bradley C.

2015-01-01

We deliver all products described herein as online geographic information system data for visualization and downloading. We outline the data properties for each model and their data inputs, describe the process of selecting appropriate data products for multifarious applications, describe all data products and software, provide newly derived model composites, and discuss how land managers may use the models to inform future sage-grouse studies and potentially refine conservation efforts. The models, software tools, and associated opportunities for novel applications of these products should provide a suite of additional, but not exclusive, tools for assessing Wyoming Greater Sage-grouse habitats, which land managers, conservationists, and scientists can apply to myriad applications.

Heterogeneous Catalysis of Polyoxometalate Based Organic–Inorganic Hybrids

PubMed Central

Ren, Yuanhang; Wang, Meiyin; Chen, Xueying; Yue, Bin; He, Heyong

2015-01-01

Organic–inorganic hybrid polyoxometalate (POM) compounds are a subset of materials with unique structures and physical/chemical properties. The combination of metal-organic coordination complexes with classical POMs not only provides a powerful way to gain multifarious new compounds but also affords a new method to modify and functionalize POMs. In parallel with the many reports on the synthesis and structure of new hybrid POM compounds, the application of these compounds for heterogeneous catalysis has also attracted considerable attention. The hybrid POM compounds show noteworthy catalytic performance in acid, oxidation, and even in asymmetric catalytic reactions. This review summarizes the design and synthesis of organic–inorganic hybrid POM compounds and particularly highlights their recent progress in heterogeneous catalysis. PMID:28788017

Newly identified protein Imi1 affects mitochondrial integrity and glutathione homeostasis in Saccharomyces cerevisiae.

PubMed

Kowalec, Piotr; Grynberg, Marcin; Pająk, Beata; Socha, Anna; Winiarska, Katarzyna; Fronk, Jan; Kurlandzka, Anna

2015-09-01

Glutathione homeostasis is crucial for cell functioning. We describe a novel Imi1 protein of Saccharomyces cerevisiae affecting mitochondrial integrity and involved in controlling glutathione level. Imi1 is cytoplasmic and, except for its N-terminal Flo11 domain, has a distinct solenoid structure. A lack of Imi1 leads to mitochondrial lesions comprising aberrant morphology of cristae and multifarious mtDNA rearrangements and impaired respiration. The mitochondrial malfunctioning is coupled to significantly decrease the level of intracellular reduced glutathione without affecting oxidized glutathione, which decreases the reduced/oxidized glutathione ratio. These defects are accompanied by decreased cadmium sensitivity and increased phytochelatin-2 level. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Acclimatization of a mixed-animal manure inoculum to the anaerobic digestion of Axonopus compressus reveals the putative importance of Mesotoga infera and Methanosaeta concilii as elucidated by DGGE and Illumina MiSeq.

PubMed

Lee, Jonathan T E; He, Jianzhong; Tong, Yen Wah

2017-12-01

In this study, a multifarious microbial mix from different sources is acclimatized over a period of three months to digesting cowgrass, and the changes in the community structure are examined with both a traditional denaturing gradient gel electrophoresis method as well as a next generation sequencing MiSeq method. It is shown that the much more in depth analysis by Illumina gives more information about the relative abundance and thus putative importance of the role of various microbes, in particular the bacterium Mesotoga infera and the archaeon Methanosaeta concilii. Copyright © 2017 Elsevier Ltd. All rights reserved.

Deploying Team Science Principles to Optimize Interdisciplinary Lung Cancer Care Delivery: Avoiding the Long and Winding Road to Optimal Care.

PubMed

Osarogiagbon, Raymond U; Rodriguez, Hector P; Hicks, Danielle; Signore, Raymond S; Roark, Kristi; Kedia, Satish K; Ward, Kenneth D; Lathan, Christopher; Santarella, Scott; Gould, Michael K; Krasna, Mark J

2016-11-01

The complexity of lung cancer care mandates interaction between clinicians with different skill sets and practice cultures in the routine delivery of care. Using team science principles and a case-based approach, we exemplify the need for the development of real care teams for patients with lung cancer to foster coordination among the multiple specialists and staff engaged in routine care delivery. Achieving coordinated lung cancer care is a high-priority public health challenge because of the volume of patients, lethality of disease, and well-described disparities in quality and outcomes of care. Coordinating mechanisms need to be cultivated among different types of specialist physicians and care teams, with differing technical expertise and practice cultures, who have traditionally functioned more as coactively working groups than as real teams. Coordinating mechanisms, including shared mental models, high-quality communication, mutual trust, and mutual performance monitoring, highlight the challenge of achieving well-coordinated care and illustrate how team science principles can be used to improve quality and outcomes of lung cancer care. To develop the evidence base to support coordinated lung cancer care, research comparing the effectiveness of a diverse range of multidisciplinary care team approaches and interorganizational coordinating mechanisms should be promoted.

Fruit and vegetable consumption and lung cancer risk: a case-control study in Galicia, Spain.

PubMed

Tarrazo-Antelo, Ana Marina; Ruano-Ravina, Alberto; Abal Arca, José; Barros-Dios, Juan Miguel

2014-01-01

Lung cancer has multiple risk factors and tobacco is the main one. Diet plays a role, but no clear effect has been consistently observed for different fruit and vegetable consumption. We aim to assess the association between fruit and vegetable consumption and lung cancer risk through a hospital-based case-control study in Spanish population. We recruited incident lung cancer cases in 2 Spanish hospitals from 2004 to 2008. Controls were individuals attending hospital for trivial surgery. Cases and controls were older than 30 and did not have a neoplasic history. We collected information on lifestyle with special emphases on tobacco and dietary habits. We included 371 cases and 496 controls. We found no protective effect for overall fruit consumption. For green leafy vegetables, the odds ratio (OR) was 0.92 [95% confidence interval (CI) = 0.32-2.69), and for other vegetables the OR was 0.77 (95% CI = 0.40-1.48) for the categories compared. We observed a reduced risk for broccoli and pumpkin intake. Although fruit consumption does not seem to be associated with a lower lung cancer risk, only the frequent consumption of specific green leafy vegetables and other vegetables might be associated with a reduced risk of lung cancer.

EML4-ALK translocation in both metachronous second primary lung sarcomatoid carcinoma and lung adenocarcinoma: a case report.

PubMed

Alì, Greta; Proietti, Agnese; Niccoli, Cristina; Pelliccioni, Serena; Borrelli, Nicla; Giannini, Riccardo; Lupi, Cristiana; Valetto, Angelo; Bertini, Veronica; Lucchi, Marco; Mussi, Alfredo; Fontanini, Gabriella

2013-08-01

The EML4-ALK gene translocation was described in a non small cell lung cancer (NSCLC) subset, with a potent oncogenic activity. It represents one of the newest molecular targets in NSCLC. We report on the case of a metachronous second primary lung sarcomatoid carcinoma after resection of lung adenocarcinoma both with ALK translocation, in a non-smoking patient. EML4-ALK rearrangement was detected with immunohistochemistry and confirmed with fluorescent in situ hybridization (FISH). To assess the clonal relationship between the two tumors, both adenocarcinoma and sarcomatoid carcinoma were analyzed by array comparative genomic hybridization (aCGH). We observed different genomic profiles suggesting that the tumors arose independently and were thus multiple primaries. To the best of our knowledge, this is the first report concerning the presence of the EML4-ALK fusion gene in a sarcomatoid carcinoma of the lung. Crizotinib, the ALK tyrosine kinase inhibitor, is highly effective in ALK-rearranged NSCLC; therefore, it may be imperative to identify all NSCLC that harbor ALK translocations in the near future. Starting from our evidence, tumors with sarcomatoid histology may need to be screened for the presence of EML4-ALK rearrangement. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The mediation of social influences on smoking cessation and awareness of the early signs of lung cancer.

PubMed

Chatwin, John; Povey, Andrew; Kennedy, Anne; Frank, Tim; Firth, Adam; Booton, Richard; Barber, Phil; Sanders, Caroline

2014-10-07

Whilst there has been no clear consensus on the potential for earlier diagnosis of lung cancer, recent research has suggested that the time between symptom onset and consultation can be long enough to plausibly affect prognosis. In this article, we present findings from a qualitative study involving in-depth interviews with patients who had been diagnosed with lung cancer (n = 11), and people who were at heightened risk of developing the disease (n = 14). A grounded theory methodology was drawn upon to conduct thematic and narrative based approaches to analysis. The paper focuses on three main themes which emerged from the study: i) fatalism and resignation in pathways to help-seeking and the process of diagnosis; ii) Awareness of smoking risk and response to cessation information and advice. iii) The role of social and other networks on help-seeking. Key findings included: poor awareness among participants of the symptoms of lung cancer; ambivalence about the dangers of smoking; the perception of lung cancer as part of a homogenisation of multiple illnesses; close social networks as a key trigger in help-seeking. We suggest that future smoking cessation and lung cancer awareness campaigns could usefully capitalise on the influence of close social networks, and would benefit from taking a 'softer' approach.

[Use of bronchial blocker in emergent thoracotomy in presence of upper airway hemorrhage, and cervical spine fracture: a difficult decision].

PubMed

Almeida, Carlos; Freitas, Maria João; Brandão, Diogo; Assunção, José Pedro

2018-01-13

Female, 85 y.o., weighting 60kg, multiple trauma patient. After an initial laparotomy, an emergent thoracotomy was performed using a bronchial blocker for lung isolation (initial active suction was applied). During surgery, bronchial cuff was deflated, causing a self-limited tracheal blood flooding. A second lung isolation was attempted but it was not as effective as initially. Probably, a lung collapse with the same bronchial blocker was impaired in the second attempt because of the obstruction of bronchial blocker lumen by intraoperative endobronchial hemorrhage. Bronchial blocker active suction may contribute to obtain or accelerate lung collapse, particularly in patients that do not tolerate ventilator disconnection technique or lung surgical compression. The use of bronchial blockers technology was a valuable alternative to double lumen tubes in this case of emergent thoracotomy in the context of a patient having thoracic, abdominal trauma, severe laceration of tongue and apophysis odontoid fracture associated to massive hemorrhage, despite several pitfalls that could compromise its use. The authors intend to discuss the advantages and disadvantages of bronchial blockers comparing to double-lumen tubes for lung isolation, and the risks of our approach, in this complex multitrauma case. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Lung function imaging methods in Cystic Fibrosis pulmonary disease.

PubMed

Kołodziej, Magdalena; de Veer, Michael J; Cholewa, Marian; Egan, Gary F; Thompson, Bruce R

2017-05-17

Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised information. High Resolution Computed Tomography (HRCT) is a well-established current 'gold standard' method for monitoring lung anatomical changes in Cystic Fibrosis patients. HRCT provides excellent morphological information, however, the X-ray radiation dose can become significant if multiple scans are required to monitor chronic diseases such as cystic fibrosis. X-ray phase-contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis lung assessment which provides dynamic morphological and functional information, albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI) is a non-ionising radiation imaging method that is garnering growing interest among researchers and clinicians working with Cystic Fibrosis patients. Recent advances in MRI have opened up the possibilities to observe lung function in real time to potentially allow sensitive and accurate assessment of disease progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be tailored to clinical needs. While MRI offers significant promise it still suffers from poor spatial resolution and the development of an objective scoring system especially for ventilation assessment.

A new multiple trauma model of the mouse.

PubMed

Fitschen-Oestern, Stefanie; Lippross, Sebastian; Klueter, Tim; Weuster, Matthias; Varoga, Deike; Tohidnezhad, Mersedeh; Pufe, Thomas; Rose-John, Stefan; Andruszkow, Hagen; Hildebrand, Frank; Steubesand, Nadine; Seekamp, Andreas; Neunaber, Claudia

2017-11-21

Blunt trauma is the most frequent mechanism of injury in multiple trauma, commonly resulting from road traffic collisions or falls. Two of the most frequent injuries in patients with multiple trauma are chest trauma and extremity fracture. Several trauma mouse models combine chest trauma and head injury, but no trauma mouse model to date includes the combination of long bone fractures and chest trauma. Outcome is essentially determined by the combination of these injuries. In this study, we attempted to establish a reproducible novel multiple trauma model in mice that combines blunt trauma, major injuries and simple practicability. Ninety-six male C57BL/6 N mice (n = 8/group) were subjected to trauma for isolated femur fracture and a combination of femur fracture and chest injury. Serum samples of mice were obtained by heart puncture at defined time points of 0 h (hour), 6 h, 12 h, 24 h, 3 d (days), and 7 d. A tendency toward reduced weight and temperature was observed at 24 h after chest trauma and femur fracture. Blood analyses revealed a decrease in hemoglobin during the first 24 h after trauma. Some animals were killed by heart puncture immediately after chest contusion; these animals showed the most severe lung contusion and hemorrhage. The extent of structural lung injury varied in different mice but was evident in all animals. Representative H&E-stained (Haematoxylin and Eosin-stained) paraffin lung sections of mice with multiple trauma revealed hemorrhage and an inflammatory immune response. Plasma samples of mice with chest trauma and femur fracture showed an up-regulation of IL-1β (Interleukin-1β), IL-6, IL-10, IL-12p70 and TNF-α (Tumor necrosis factor- α) compared with the control group. Mice with femur fracture and chest trauma showed a significant up-regulation of IL-6 compared to group with isolated femur fracture. The multiple trauma mouse model comprising chest trauma and femur fracture enables many analogies to clinical cases of multiple trauma in humans and demonstrates associated characteristic clinical and pathophysiological changes. This model is easy to perform, is economical and can be used for further research examining specific immunological questions.

Early Localization of Bronchogenic Carcinoma

PubMed Central

Macaulay, C.; Leriche, J. C.; Ikeda, N.; Palcic, B.

1994-01-01

The performance of a fluorescence imaging device was compared with conventional white-light bronchoscopy in 100 patients with lung cancer, 46 patients with resected stage I non-small cell lung cancer, 10 patients with head and neck cancer, and 67 volunteers who had smoked at least 1 pack of cigarettes per day for 25 years or more. Using differences in tissue autofluorescence between premalignant, malignant, and normal tissues, fluorescence bronchoscopy was found to detect significantly more areas with moderate/severe dysplasia or carcinoma in situ than conventional white-light bronchoscopy with a similar specificity. Multiple foci of dysplasia or cancer were found in 13–24% of these individuals. Fluorescence bronchoscopy may be an important adjunct to conventional bronchoscopic examination to improve our ability to detect and localize premalignant and early lung cancer lesions. PMID:18493345

Motexafin Gadolinium and Doxorubicin in Treating Patients With Advanced Cancer

ClinicalTrials.gov

2015-09-30

Breast Cancer; Chronic Myeloproliferative Disorders; Colorectal Cancer; Head and Neck Cancer; Leukemia; Lung Cancer; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic/Myeloproliferative Diseases; Prostate Cancer; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Multiple Primary and Histology Coding Rules - SEER

Cancer.gov

Download the coding manual and training resources for cases diagnosed from 2007 to 2017. Sites included are lung, breast, colon, melanoma of the skin, head and neck, kidney, renal pelvis/ureter/bladder, benign brain, and malignant brain.

Lung disease and coal mining: what pulmonologists need to know.

PubMed

Go, Leonard H T; Krefft, Silpa D; Cohen, Robert A; Rose, Cecile S

2016-03-01

Coal mine workers are at risk for a range of chronic respiratory diseases including coal workers' pneumoconiosis, diffuse dust-related fibrosis, and chronic obstructive pulmonary disease. The purpose of this review is to describe coal mining processes and associated exposures to inform the diagnostic evaluation of miners with respiratory symptoms. Although rates of coal workers' pneumoconiosis declined after regulations were enacted in the 1970s, more recent data shows a reversal in this downward trend. Rapidly progressive pneumoconiosis with progressive massive fibrosis (complicated coal workers' pneumoconiosis) is being observed with increased frequency in United States coal miners, with histologic findings of silicosis and mixed-dust pneumoconiosis. There is increasing evidence of decline in lung function in individuals with pneumoconiosis. Multiple recent cohort studies suggest increased risk of lung cancer in coal miners. A detailed understanding of coal mining methods and processes allows clinicians to better evaluate and confirm chronic lung diseases caused by inhalational hazards in the mine atmosphere.

The Link between Reduced Inspiratory Capacity and Exercise Intolerance in Chronic Obstructive Pulmonary Disease.

PubMed

O'Donnell, Denis E; Elbehairy, Amany F; Webb, Katherine A; Neder, J Alberto

2017-07-01

Low inspiratory capacity (IC), chronic dyspnea, and reduced exercise capacity are inextricably linked and are independent predictors of increased mortality in chronic obstructive pulmonary disease. It is no surprise, therefore, that a major goal of management is to improve IC by reducing lung hyperinflation to improve respiratory symptoms and health-related quality of life. The negative effects of lung hyperinflation on respiratory muscle and cardiocirculatory function during exercise are now well established. Moreover, there is growing appreciation that a key mechanism of exertional dyspnea in chronic obstructive pulmonary disease is critical mechanical constraints on tidal volume expansion during exercise when resting IC is reduced. Further evidence for the importance of lung hyperinflation comes from multiple studies, which have reported the clinical benefits of therapeutic interventions that reduce lung hyperinflation and increase IC. A reduced IC in obstructive pulmonary disease is further eroded by exercise and contributes to ventilatory limitation and dyspnea. It is an important outcome for both clinical and research studies.

The treatment of Stage III nonseminomatous testicular tumors. Roswell Park Memorial Institute results (1970-1979).

PubMed

Pontes, J E; Wajsman, Z; Beckley, S; Williams, P; Murphy, G P

1983-04-01

A review of 92 patients with Stage III nonseminomatous tumors treated at Roswell Park Memorial Institute between 1970-1979 was undertaken to verify changes in concepts as related to multiple agent chemotherapy and cytoreductive surgery. Each patient had a minimal follow-up of 18 months. Fifty-three patients were seen before 1975. Eighteen had metastasis to the lungs only. These were treated with a variety of single chemotherapeutic agents and cytoreductive surgery. The survival of this group was 38%. Among 35 patients with lung and visceral involvement seen at the same time, only one patient is alive. Thirty-nine patients were seen after 1975 and treated with multi-drug chemotherapy and cytoreductive surgery. The current survival rate of 23 patients with lung metastasis only is 69%. Among 16 patients with lung and visceral involvement, the present survival rate is 31%. This report confirms the effectiveness of multi-drug therapy in conjunction with cytoreductive surgery in the treatment of disseminated testicular tumors.

Complement-mediated neutrophil activation in sepsis- and trauma-related adult respiratory distress syndrome. Clarification with radioaerosol lung scans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tennenberg, S.D.; Jacobs, M.P.; Solomkin, J.S.

Complement-mediated neutrophil activation (CMNA) has been proposed as an important pathogenic mechanism causing acute microvascular lung injury in the adult respiratory distress syndrome (ARDS). To clarify the relationship between CMNA and evolving lung injury, we studied 26 patients with multiple trauma and sepsis within 24 hours of risk establishment for ARDS. Pulmonary alveolar-capillary permeability (PACP) was quantified as the clearance rate of a particulate radioaerosol. Seventeen patients (65%) had increased PACP (six developed ARDS) while nine (35%) had normal PACP (none developed ARDS; clearance rates of 3.4%/min and 1.5%/min, respectively). These patients, regardless of evidence of early lung injury, hadmore » elevated plasma C3adesArg levels and neutrophil chemotactic desensitization to C5a/C5adesArg. Plasma C3adesArg levels correlated weakly, but significantly, with PACP. Thus, CMNA may be a necessary, but not a sufficient, pathogenic mechanism in the evolution of ARDS.« less

The Role of the Microbiome in Exacerbations of Chronic Lung Diseases

PubMed Central

Dickson, Robert P.; Martinez, Fernando J.; Huffnagle, Gary B.

2014-01-01

Summary Culture-independent microbiological techniques have revealed a previously unappreciated complexity to the bacterial microbiome of the respiratory tract, forcing reconsideration of the interactions between host, bacteria and the pathogenesis of exacerbations of chronic lung disease. The composition of the lung microbiome is determined by microbial immigration, elimination, and the relative growth rates of its members; all of these change dramatically in chronic lung disease and further during exacerbations. Exacerbations lack key features of bacterial infections, including increased bacterial burden and decreased community diversity. We propose instead that exacerbations are occasions of respiratory dysbiosis: a disordered respiratory microbial ecosystem with negative effects on host biology. Respiratory dysbiosis provokes a dysregulated host immune response, which in turn alters microbial growth conditions in patient airways, further promoting dysbiosis and perpetuating a coupled cycle of inflammation and disordered microbiota. Differences in baseline respiratory microbiota may help explain the “frequent-exacerbator” phenotype observed across multiple disease states, and may provide novel targets for therapeutic intervention. PMID:25152271

Pulmonary Actinomyces graevenitzii infection presenting as organizing pneumonia diagnosed by PCR analysis.

PubMed

Fujita, Yu; Iikura, Motoyasu; Horio, Yuko; Ohkusu, Kiyofumi; Kobayashi, Nobuyuki

2012-08-01

We report what is believed to be the first case of pulmonary Actinomyces graevenitzii infection presenting as organizing pneumonia. Fever and night sweats developed in a 69-year-old male. The only abnormal laboratory data were an elevated erythrocyte sedimentation rate and C-reactive protein level. On chest images, multiple consolidations with air bronchograms were seen in the bilateral lungs. Histological examination from lung biopsy revealed a pattern of organizing pneumonia with microabscesses, but definitive diagnosis was not obtained because culture from lung specimen was negative. A. graevenitzii was eventually identified in the lung biopsy specimen by detection of an Actinomyces-specific PCR product followed by 16S rRNA gene sequencing. The patient was treated with high-dose ampicillin intravenously for 1 month, followed by oral amoxicillin and clarithromycin for 6 months, and recovered. We suggest that actinomycosis can present as organizing pneumonia, and identification of infection by PCR analysis and rRNA gene sequencing is a useful strategy in cases that are difficult to diagnose.

Point-of-care sonographic detection of left endobronchial main stem intubation and obstruction versus endotracheal intubation.

PubMed

Blaivas, Michael; Tsung, James W

2008-05-01

Determining the correct position of endotracheal tubes in critically ill patients may be complicated by external factors such as noise, body habitus, and the need for ongoing resuscitation. Multiple detection techniques have been developed to determine the correct endotracheal tube position, recently including the use of sonography to evaluate lung expansion and diaphragmatic excursion. These techniques have also been applied to diagnosis of right endobronchial main stem intubation, which may be confused with a unilateral pneumothorax in some cases. We describe the sonographic findings in a case series of endobronchial main stem intubations and obstruction, highlighting the utility of this sonographic application. Previous literature and future applications are discussed. Sonographic detection of the sliding lung sign, the lung pulse, and diaphragmatic excursion can accurately detect main stem bronchial intubation as well as bronchial obstruction. Clinical use of lung sonography may decrease the need for chest radiography and may allow more rapid diagnosis of main stem intubation and bronchial obstruction.

Associated factors of radiation pneumonitis induced by precise radiotherapy in 186 elderly patients with esophageal cancer.

PubMed

Cui, Zhen; Tian, Ye; He, Bin; Li, Hongwei; Li, Duojie; Liu, Jingjing; Cai, Hanfei; Lou, Jianjun; Jiang, Hao; Shen, Xueming; Peng, Kaigui

2015-01-01

Radiation pneumonitis is one of the most severe complications of esophageal cancer. To explore the factors correlated to radiation pneumonitis induced by precise radiotherapy for elderly patients with esophageal cancer. The retrospective analysis was used to collect clinical data from 186 elderly patients with esophageal cancer. The incidence of radiation pneumonitis was observed, followed by statistical analysis through ANVON or multiple regression analysis. 27 in 186 cases of esophageal cancer suffered from radiation pneumonitis, with incidence of 14.52%. The single factor analysis showed that, Karnofsky performance status (KPS) score, chronic obstructive pulmonary disease, concurrent chemoradiotherapy, gross tumor volume (GTV) dose, lung V20, mean lung dose (MLD) and planning target volume (PTV) were associated with radiation pneumonitis. The logistic regression analysis indicated that, concurrent chemoradiotherapy, GTV dose, lung V20 and PTV were the independent factors of radiation pneumonitis. The concurrent chemoradiotherapy, GTV dose, lung V20, MLD and PTV are the major risk factors of radiation pneumonitis for elderly patients with esophageal cancer.

Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung.

PubMed

Oh, Phil; Borgström, Per; Witkiewicz, Halina; Li, Yan; Borgström, Bengt J; Chrastina, Adrian; Iwata, Koji; Zinn, Kurt R; Baldwin, Richard; Testa, Jacqueline E; Schnitzer, Jan E

2007-03-01

How effectively and quickly endothelial caveolae can transcytose in vivo is unknown, yet critical for understanding their function and potential clinical utility. Here we use quantitative proteomics to identify aminopeptidase P (APP) concentrated in caveolae of lung endothelium. Electron microscopy confirms this and shows that APP antibody targets nanoparticles to caveolae. Dynamic intravital fluorescence microscopy reveals that targeted caveolae operate effectively as pumps, moving antibody within seconds from blood across endothelium into lung tissue, even against a concentration gradient. This active transcytosis requires normal caveolin-1 expression. Whole body gamma-scintigraphic imaging shows rapid, specific delivery into lung well beyond that achieved by standard vascular targeting. This caveolar trafficking in vivo may underscore a key physiological mechanism for selective transvascular exchange and may provide an enhanced delivery system for imaging agents, drugs, gene-therapy vectors and nanomedicines. 'In vivo proteomic imaging' as described here integrates organellar proteomics with multiple imaging techniques to identify an accessible target space that includes the transvascular pumping space of the caveola.

Immunohistochemistry for predictive biomarkers in non-small cell lung cancer.

PubMed

Mino-Kenudson, Mari

2017-10-01

In the era of targeted therapy, predictive biomarker testing has become increasingly important for non-small cell lung cancer. Of multiple predictive biomarker testing methods, immunohistochemistry (IHC) is widely available and technically less challenging, can provide clinically meaningful results with a rapid turn-around-time and is more cost efficient than molecular platforms. In fact, several IHC assays for predictive biomarkers have already been implemented in routine pathology practice. In this review, we will discuss: (I) the details of anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) IHC assays including the performance of multiple antibody clones, pros and cons of IHC platforms and various scoring systems to design an optimal algorithm for predictive biomarker testing; (II) issues associated with programmed death-ligand 1 (PD-L1) IHC assays; (III) appropriate pre-analytical tissue handling and selection of optimal tissue samples for predictive biomarker IHC.

Heterogeneity-based, multiple mechanisms in the resistance to osimertinib (AZD9291): A case report.

PubMed

Liu, Yutao; Hao, Xuezhi; Hu, Xingsheng; Li, Junling; Wang, Yan; Wang, Hongyu; Xing, Puyuan; Li, Weihua; Ying, Jianming; Han, Xiaohong; Shi, Yuankai

2018-04-01

Osimertinib is a novel, irreversible, mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR mutations and the EGFR T790 mutation. Here, we report a woman with EGFR-mutated lung adenocarcinoma who, after 23-month treatment with gefitinib, developed the EGFR T790M mutation, which converted the T790M status from positive to negative before osimertinib treatment and developed MET amplification, leading to rapid progression on osimertinib in two months. Subsequent treatment with crizotinib and c-Met inhibitor plus gefitinib also failed to improve the clinical outcome, suggesting the potential existence of another resistance mechanism. Our findings revealed the underlying multiple and heterogeneous mechanisms in resistance to osimertinib, suggesting combination strategies should be considered post-osimertinib progression. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient.

PubMed

Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

2016-01-01

Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase.

An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient

PubMed Central

Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

2016-01-01

Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase. PMID:27200139

Immunohistochemistry for predictive biomarkers in non-small cell lung cancer

PubMed Central

2017-01-01

In the era of targeted therapy, predictive biomarker testing has become increasingly important for non-small cell lung cancer. Of multiple predictive biomarker testing methods, immunohistochemistry (IHC) is widely available and technically less challenging, can provide clinically meaningful results with a rapid turn-around-time and is more cost efficient than molecular platforms. In fact, several IHC assays for predictive biomarkers have already been implemented in routine pathology practice. In this review, we will discuss: (I) the details of anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) IHC assays including the performance of multiple antibody clones, pros and cons of IHC platforms and various scoring systems to design an optimal algorithm for predictive biomarker testing; (II) issues associated with programmed death-ligand 1 (PD-L1) IHC assays; (III) appropriate pre-analytical tissue handling and selection of optimal tissue samples for predictive biomarker IHC. PMID:29114473

Treatment planning with intensity modulated particle therapy for multiple targets in stage IV non-small cell lung cancer

NASA Astrophysics Data System (ADS)

Anderle, Kristjan; Stroom, Joep; Vieira, Sandra; Pimentel, Nuno; Greco, Carlo; Durante, Marco; Graeff, Christian

2018-01-01

Intensity modulated particle therapy (IMPT) can produce highly conformal plans, but is limited in advanced lung cancer patients with multiple lesions due to motion and planning complexity. A 4D IMPT optimization including all motion states was expanded to include multiple targets, where each target (isocenter) is designated to specific field(s). Furthermore, to achieve stereotactic treatment planning objectives, target and OAR weights plus objective doses were automatically iteratively adapted. Finally, 4D doses were calculated for different motion scenarios. The results from our algorithm were compared to clinical stereotactic body radiation treatment (SBRT) plans. The study included eight patients with 24 lesions in total. Intended dose regimen for SBRT was 24 Gy in one fraction, but lower fractionated doses had to be delivered in three cases due to OAR constraints or failed plan quality assurance. The resulting IMPT treatment plans had no significant difference in target coverage compared to SBRT treatment plans. Average maximum point dose and dose to specific volume in OARs were on average 65% and 22% smaller with IMPT. IMPT could also deliver 24 Gy in one fraction in a patient where SBRT was limited due to the OAR vicinity. The developed algorithm shows the potential of IMPT in treatment of multiple moving targets in a complex geometry.