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Sample records for beas-2b normal lung

  1. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

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    Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States)

    2015-01-09

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous

  2. Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells

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    Rosseau Simone

    2006-07-01

    Full Text Available Abstract Background Although pneumococcal pneumonia is one of the most common causes of death due to infectious diseases, little is known about pneumococci-lung cell interaction. Herein we tested the hypothesis that pneumococci activated pulmonary epithelial cell cytokine release by c-Jun-NH2-terminal kinase (JNK Methods Human bronchial epithelial cells (BEAS-2B or epithelial HEK293 cells were infected with S. pneumoniae R6x and cytokine induction was measured by RT-PCR, ELISA and Bioplex assay. JNK-phosphorylation was detected by Western blot and nuclear signaling was assessed by electrophoretic mobility shift assay (EMSA and chromatin immunoprecipitation (ChIP. JNK was modulated by the small molecule inhibitor SP600125 and AP1 by transfection of a dominant negative mutant. Results S. pneumoniae induced the release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by human lung epithelial cell line BEAS-2B. Furthermore, pneumococci infection resulted in JNK phosphorylation in BEAS-2B cells. Inhibition of JNK by small molecule inhibitor SP600125 reduced pneumococci-induced IL-8 mRNA expression and release of IL-8 and IL-6. One regulator of the il8 promoter is JNK-phosphorylated activator protein 1 (AP-1. We showed that S. pneumoniae time-dependently induced DNA binding of AP-1 and its phosphorylated subunit c-Jun with a maximum at 3 to 5 h after infection. Recruitment of Ser63/73-phosphorylated c-Jun and RNA polymerase II to the endogenous il8 promoter was found 2 h after S. pneumoniae infection by chromatin immunoprecipitation. AP-1 repressor A-Fos reduced IL-8 release by TLR2-overexpressing HEK293 cells induced by pneumococci but not by TNFα. Antisense-constructs targeting the AP-1 subunits Fra1 and Fra2 had no inhibitory effect on pneumococci-induced IL-8 release. Conclusion S. pneumoniae-induced IL-8 expression by human epithelial BEAS-2B cells depended on activation of JNK and recruitment of phosphorylated c

  3. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

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    Park, Youn-hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo

    2015-01-01

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals-induced carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the mechanistic studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. PMID:26091798

  4. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

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    Park, Youn-hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu

    2015-09-15

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. - Highlights: • Short-term exposure of BEAS-2B cells to arsenic or Cr(VI) activates p53 and p21. • Chronic exposure of BEAS-2B cells to arsenic or Cr(VI) causes cell transformation and tumorigenesis. • Arsenic-transformed cells exhibit

  5. Culture medium type affects endocytosis of multi-walled carbon nanotubes in BEAS-2B cells and subsequent biological response.

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    Haniu, Hisao; Saito, Naoto; Matsuda, Yoshikazu; Tsukahara, Tamotsu; Maruyama, Kayo; Usui, Yuki; Aoki, Kaoru; Takanashi, Seiji; Kobayashi, Shinsuke; Nomura, Hiroki; Okamoto, Masanori; Shimizu, Masayuki; Kato, Hiroyuki

    2013-09-01

    We examined the cytotoxicity of multi-walled carbon nanotubes (MWCNTs) and the resulting cytokine secretion in BEAS-2B cells or normal human bronchial epithelial cells (HBEpCs) in two types of culture media (Ham's F12 containing 10% FBS [Ham's F12] and serum-free growth medium [SFGM]). Cellular uptake of MWCNT was observed by fluorescent microscopy and analyzed using flow cytometry. Moreover, we evaluated whether MWCNT uptake was suppressed by 2 types of endocytosis inhibitors. We found that BEAS-2B cells cultured in Ham's F12 and HBEpCs cultured in SFGM showed similar biological responses, but BEAS-2B cells cultured in SFGM did not internalize MWCNTs, and the 50% inhibitory concentration value, i.e., the cytotoxicity, was increased by more than 10-fold. MWCNT uptake was suppressed by a clathrin-mediated endocytosis inhibitor and a caveolae-mediated endocytosis inhibitor in BEAS-2B cells cultured in Ham's F12 and HBEpCs cultured in SFGM. In conclusion, we suggest that BEAS-2B cells cultured in a medium containing serum should be used for the safety evaluation of nanomaterials as a model of normal human bronchial epithelial cells. However, the culture medium composition may affect the proteins that are expressed on the cytoplasmic membrane, which may influence the biological response to MWCNTs.

  6. RNA-binding motif protein 5 inhibits the proliferation of cigarette smoke-transformed BEAS-2B cells through cell cycle arrest and apoptosis.

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    Lv, Xue-Jiao; Du, Yan-Wei; Hao, Yu-Qiu; Su, Zhen-Zhong; Zhang, Lin; Zhao, Li-Jing; Zhang, Jie

    2016-04-01

    Cigarette smoking has been shown to be the most significant risk factor for lung cancer. Recent studies have also indicated that RNA-binding motif protein 5 (RBM5) can modulate apoptosis and suppress tumor growth. The present study focused on the role of RBM5 in the regulation of cigarette smoke extract (CSE)-induced transformation of bronchial epithelial cells into the cancerous phenotype and its mechanism of action. Herein, we exposed normal BEAS-2B cells for 8 days to varying concentrations of CSE or dimethylsulfoxide (DMSO), followed by a recovery period of 2 weeks. Next, the RBM5 protein was overexpressed in these transformed BEAS-2B cells though lentiviral infection. Later, the morphological changes, cell proliferation, cell cycle, apoptosis, invasion and migration were assessed. In addition, we analyzed the role of RBM5 in xenograft growth. The expression of RBM5 along with the genes related to cell cycle regulation, apoptosis and invasion were also examined. Finally, our results revealed that BEAS-2B cells exposed to 100 µg/ml CSE acquired phenotypic changes and formed tumors in nude mice, indicative of their cancerous transformation and had reduced RBM5 expression. Subsequent overexpression of RBM5 in these cells significantly inhibited their proliferation, induced G1/S arrest, triggered apoptosis and inhibited their invasion and migration, including xenograft growth. Thus, we established an in vitro model of CSE-induced cancerous transformation and concluded that RBM5 overexpression inhibited the growth of these transformed cells through cell cycle arrest and induction of apoptosis. Therefore, our study suggests the importance of RBM5 in the pathogenesis of smoking-related cancer.

  7. Proteomic analysis of proteins associated with tt-DDE induced toxicity in BEAS-2B cells.

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    Lin, Pin-Pin; Yang, Ming-Hui; Liao, Pao-Chi; Wu, Hsin-Yi; Chang, Louis W; Tsai, Hui-Ti; Tyan, Yu-Chang

    2008-11-21

    Trans, trans-2,4-decadienal (tt-DDE), a specific type of dienaldehyde, is abundant in heated oils or cooking oil fumes. Ingestion of heated oils and exposure to cooking oil fumes has been suggested to have a great health impact in a variety of organs, including the lungs. Previous studies have demonstrated that acute exposures to high doses of tt-DDE have induced oxidative stress, genotoxicity, and cytotoxicity in human lung cells. The objective in utilizing proteomic techniques of this study was to identify protein biomarkers associated with tt-DDE-induced oxidative stress and cytotoxicity in human bronchial epithelial cells BEAS-2B. Experimental results suggested that DJ-1 and cofilin proteins were protein biomarkers for tt-DDE-induced cytotoxicity and oxidative stress in lung cells. DJ-1 was especially an early biomarker for tt-DDE exposure.

  8. Proteasome inhibitor MG-132 regulates the expression of VEGF in human bronchial epithelial cell line, BEAS-2B

    Institute of Scientific and Technical Information of China (English)

    Xuefan Cui; Kaisheng Yin; Mao Huang; Linfu Zhou

    2005-01-01

    Objective: To explore the effects of MG-132 on the expression of VEGF in bronchial epithelial cell line, BEAS2B. Methods: Semi-quantitive RT-PCR for VEGF mRNA and enzyme-linked immunosorbent assay (ELISA) for VEGF protein were performed. Results: MG-132 increased the expression of VEGF mRNA and protein BEAS-2B cells in time-and concentration-dependent manners. After 24-h stimulation, 25 μmol/L MG-132 increased the maximal levels of VEGF protein in cell-conditioned medium. When the cells were stimulated with cycloheximide(CHX) before treatment with MG-132, the MG-132-induced production of VEGF protein was inhibited compared to the unstimulated cells. Supernatant of condition-medium treatment with MG-132 enhanced the growth of HUVEC.Conclusion: MG-132 induces VEGF gene expression in human bronchial epithelial cells line, BEAS-2B, and the MG-132-induced expression of VEGF may modulate lung tissue injury due to airway inflammation.

  9. High basal expression of interferon-stimulated genes in human bronchial epithelial (BEAS-2B cells contributes to influenza A virus resistance.

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    Lai-Giea Seng

    Full Text Available Respiratory epithelial cells play a key role in influenza A virus (IAV pathogenesis and host innate response. Transformed human respiratory cell lines are widely used in the study of IAV-host interactions due to their relative convenience, and inherent difficulties in working with primary cells. Transformed cells, however, may have altered susceptibility to virus infection. Proper characterization of different respiratory cell types in their responses to IAV infection is therefore needed to ensure that the cell line chosen will provide results that are of relevance in vivo. We compared replication kinetics of human H1N1 (A/USSR/77 IAVs in normal primary human bronchial epithelial (NHBE and two commonly used respiratory epithelial cell lines namely BEAS-2B and A549 cells. We found that IAV replication was distinctly poor in BEAS-2B cells in comparison with NHBE, A549 and Madin-Darby canine kidney (MDCK cells. IAV resistance in BEAS-2B cells was accompanied by an activated antiviral state with high basal expression of interferon (IFN regulatory factor-7 (IRF-7, stimulator of IFN genes (STING and IFN stimulated genes (ISGs. Treatment of BEAS-2B cells with a pan-Janus-activated-kinase (JAK inhibitor decreased IRF-7 and ISG expression and resulted in increased IAV replication. Therefore, the use of highly resistant BEAS-2B cells in IAV infection may not reflect the cytopathogenicity of IAV in human epithelial cells in vivo.

  10. Long-term exposures to low doses of silver nanoparticles enhanced in vitro malignant cell transformation in non-tumorigenic BEAS-2B cells.

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    Choo, Wun Hak; Park, Cho Hee; Jung, Shi Eun; Moon, Byeonghak; Ahn, Huiyeon; Ryu, Jung Seok; Kim, Keun-Soo; Lee, Yong Hwa; Yu, Il Je; Oh, Seung Min

    2016-12-01

    To predict carcinogenic potential of AgNPs on the respiratory system, BEAS-2B cells (human bronchial epithelial cells) were chronically exposed to low- and non-cytotoxic dose (0.13 and 1.33μg/ml) of AgNPs for 4months (#40 passages). To assess malignant cell transformation of chronic exposure to AgNPs, several bioassays including anchorage independent agar colony formation, cell migration/invasion assay, and epithelial-mesenchymal transition (EMT) were performed in BEAS-2B cells. Chronic exposure to AgNPs showed a significant increase of anchorage independent agar colony formation and cell migration/invasion. EMT, which is the loss of epithelial markers (E-Cadherin and Keratin) and the gain of mesenchymal marker (N-cadherin and Vimentin), was induced by chronic exposure to AgNPs. These responses indicated that chronic exposure to AgNPs could acquire characteristics of tumorigenic cells from normal BEAS-2B cells. In addition, caspase-3, p-p53, p-p38, and p-JNK were significantly decreased, while p-ERK1/2 was significantly increased. MMP-9 related to cell migration/invasion was upregulated, while a MMP-9 inhibitor, TIMP-1 was down-regulated. These results indicated that BEAS-2B cells exposed to AgNPs could induce anti-apoptotic response/anoikis resistance, and cell migration/invasion by complex regulation of MAPK kinase (p38, JNK, and ERK) and p53 signaling pathways. Therefore, we suggested that long-term exposure to low-dose of AgNPs could enhance malignant cell transformation in non-tumorigenic BEAS-2B cells. Our findings provide useful information needed to assess the carcinogenic potential of AgNPs.

  11. The crosstalk between α-irradiated Beas-2B cells and its bystander U937 cells through MAPK and NF-κB signaling pathways

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    Fu, Jiamei; Yuan, Dexiao; Xiao, Linlin; Tu, Wenzhi; Dong, Chen; Liu, Weili; Shao, Chunlin, E-mail: clshao@shmu.edu.cn

    2016-01-15

    Highlights: • α-irradiated Beas-2B cells induced bystander effects in macrophage U937 cells. • The neighboring macrophages enhanced the damage of α-irradiated Beas-2B cells. • MAPK and NF-κB pathways were activated in U937 cells after cell co-culture. • NF-κB and MAPK pathways participated in the bilateral bystander responses. - Abstract: Although accumulated evidence suggests that α-particle irradiation induced bystander effect may relevant to lung injury and cancer risk assessment, the exact mechanisms are not yet elucidated. In the present study, a cell co-culture system was used to investigate the interaction between α-particle irradiated human bronchial epithelial cells (Beas-2B) and its bystander macrophage U937 cells. It was found that the cell co-culture amplified the detrimental effects of α-irradiation including cell viability decrease and apoptosis promotion on both irradiated cells and bystander cells in a feedback loop which was closely relevant to the activation of MAPK and NF-κB pathways in the bystander U937 cells. When these two pathways in U937 cells were disturbed by special pharmacological inhibitors before cell co-culture, it was found that a NF-κB inhibitor of BAY 11-7082 further enhanced the proliferation inhibition and apoptosis induction in bystander U937 cells, but MAPK inhibitors of SP600125 and SB203580 protected cells from viability loss and apoptosis and U0126 presented more beneficial effect on cell protection. For α-irradiated epithelial cells, the activation of NF-κB and MAPK pathways in U937 cells participated in detrimental cellular responses since the above inhibitors could largely attenuate cell viability loss and apoptosis of irradiated cells. Our results demonstrated that there are bilateral bystander responses between irradiated lung epithelial cells and macrophages through MAPK and NF-κB signaling pathways, which accounts for the enhancement of α-irradiation induced damage.

  12. Use of human bronchial epithelial cells (BEAS-2B) to study immunological markers resulting from exposure to PM(2.5) organic extract from Puerto Rico.

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    Fuentes-Mattei, Enrique; Rivera, Evasomary; Gioda, Adriana; Sanchez-Rivera, Diana; Roman-Velazquez, Felix R; Jimenez-Velez, Braulio D

    2010-03-15

    Fine particulate air pollutants, mainly their organic fraction, have been demonstrated to be associated with cardiovascular and respiratory health problems. Puerto Rico has been reported to have the highest prevalence of pulmonary diseases (e.g., asthma) in the United States. The aim of this study was to assess, for the first time, the immunological response of human bronchial epithelial cells (BEAS-2B) to organic extracts isolated from airborne particulate matter (PM(2.5)) in Puerto Rico. Organic extracts from PM(2.5) collected throughout an 8-month period (2000-2001) were pooled (composite) in order to perform chemical analysis and biological activity testing. BEAS-2B cells were exposed to PM(2.5) organic extract to assess cytotoxicity, levels of cytokines and relative gene expression of MHC-II, hPXR and CYP3A5. Our findings show that organic PM(2.5) consist of toxic as well as bioactive components that can regulate the secretion of cytokines in BEAS-2B, which could modulate inflammatory response in the lung. Trace element analyses confirmed the presence of metals in organic extracts highlighting the relative high abundance of Cu and Zn in polar organic extracts. Polar organic extracts exhibited dose-dependant toxicity and were found to significantly induce the release of interleukin 6 (IL-6), IL-1beta and IL-7 while significantly inhibiting the secretion of IL-8, G-CSF and MCP-1. Moreover, MHC-II transcriptional activity was up-regulated after 24 h of exposure, whereas PXR and CYP3A5 were down-regulated. This research provides a new insight into the effects of PM(2.5) organic fractions on specific effectors and their possible role in the development of respiratory inflammatory diseases in Puerto Rico.

  13. Cellular interactions and biological responses to titanium dioxide nanoparticles in HepG2 and BEAS-2B cells: role of cell culture media.

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    Prasad, Raju Y; Simmons, Steven O; Killius, Micaela G; Zucker, Robert M; Kligerman, Andrew D; Blackman, Carl F; Fry, Rebecca C; Demarini, David M

    2014-05-01

    We showed previously that exposure of human lung cells (BEAS-2B) to TiO2 nanoparticles (nano-TiO2 ) produced micronuclei (MN) only when the final concentration of protein in the cell-culture medium was at least 1%. Nanoparticles localize in the liver; thus, we exposed human liver cells (HepG2) to nano-TiO2 and found the same requirement for MN induction. Nano-TiO2 also formed small agglomerates in medium containing as little as 1% protein and caused cellular interaction as measured by side scatter by flow cytometry and DNA damage (comet assay) in HepG2 cells. Nano-TiO2 also increased the activity of the inflammatory factor NFkB but not of AP1 in a reporter-gene HepG2 cell line. Suspension of nano-TiO2 in medium containing 0.1% protein was sufficient for induction of MN by the nanoparticles in either BEAS-2B or HepG2 cells as long the final concentration of protein in the cell-culture medium was at least 1%.

  14. Effect of silymarin and harpagoside on inflammation reaction of BEAS-2B cells, on ciliary beat frequency (CBF) of trachea explants and on mucociliary clearance (MCC).

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    Boeckenholt, Corinna; Begrow, Frank; Verspohl, Eugen J

    2012-05-01

    Silymarin and harpagoside are derived from drugs which are used for their protective effects against hepatotoxicity and inflammatory processes. Both are now investigated with respect to the respiratory tract. They were able to reduce the release of the inflammatory cytokine RANTES (regulated on activation, normal T cells expressed and secreted) from BEAS-2B cells in a concentration-dependent manner when stimulated by a cytokine mix (10 ng/mL of TNF- α and IFN- γ). This effect was not due to a possible toxic effect (control experiments using LDH release as a marker). Silymarin but not harpagoside was able to increase ciliary beat frequency. Effects were comparable to positive controls (isoprenaline and salbutamol). Silymarin also increases mucociliary clearance. In conclusion, silymarin should be further investigated for its clinical use in distinct respiratory diseases.

  15. Genotoxicity of polyvinylpyrrolidone-coated silver nanoparticles in BEAS 2B cells.

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    Nymark, Penny; Catalán, Julia; Suhonen, Satu; Järventaus, Hilkka; Birkedal, Renie; Clausen, Per Axel; Jensen, Keld Alstrup; Vippola, Minnamari; Savolainen, Kai; Norppa, Hannu

    2013-11-08

    Silver nanoparticles (AgNPs) are widely utilized in various consumer products and medical devices, especially due to their antimicrobial properties. However, several studies have associated these particles with toxic effects, such as inflammation and oxidative stress in vivo and cytotoxic and genotoxic effects in vitro. Here, we assessed the genotoxic effects of AgNPs coated with polyvinylpyrrolidone (PVP) (average diameter 42.5±14.5 nm) on human bronchial epithelial BEAS 2B cells in vitro. AgNPs were dispersed in bronchial epithelial growth medium (BEGM) with 0.6 mg/ml bovine serum albumin (BSA). The AgNP were partially well-dispersed in the medium and only limited amounts (ca. 0.02 μg Ag(+) ion/l) could be dissolved after 24h. The zeta-potential of the AgNPs was found to be highly negative in pure water but was at least partially neutralized in BEGM with 0.6 mg BSA/ml. Cytotoxicity was measured by cell number count utilizing Trypan Blue exclusion and by an ATP-based luminescence cell viability assay. Genotoxicity was assessed by the alkaline single cell gel electrophoresis (comet) assay, the cytokinesis-block micronucleus (MN) assay, and the chromosomal aberration (CA) assay. The cells were exposed to various doses (0.5-48 μg/cm(2) corresponding to 2.5-240 μg/ml) of AgNPs for 4 and 24 h in the comet assay, for 48 h in the MN assay, and for 24 and 48 h in the CA assay. DNA damage measured by the percent of DNA in comet tail was induced in a dose-dependent manner after both the 4-h and the 24-h exposures to AgNPs, with a statistically significant increase starting at 16 μg/cm(2) (corresponding to 60.8 μg/ml) and doubling of the percentage of DNA in tail at 48 μg/cm(2). However, no induction of MN or CAs was observed at any of the doses or time points. The lack of induction of chromosome damage by the PVP-coated AgNPs is possibly due to the coating which may protect the cells from direct interaction with the AgNPs, either by reducing ion leaching from the

  16. Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation.

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    Zhou, Wei; Tian, Dongdong; He, Jun; Wang, Yimei; Zhang, Lijun; Cui, Lan; Jia, Li; Zhang, Li; Li, Lizhong; Shu, Yulei; Yu, Shouzhong; Zhao, Jun; Yuan, Xiaoyan; Peng, Shuangqing

    2016-04-12

    Long-term exposure to fine particulate matter (PM2.5) has been reported to be closely associated with the increased lung cancer risk in populations, but the mechanisms underlying PM-associated carcinogenesis are not yet clear. Previous studies have indicated that aberrant epigenetic alterations, such as genome-wide DNA hypomethylation and gene-specific DNA hypermethylation contribute to lung carcinogenesis. And silence or mutation of P53 tumor suppressor gene is the most prevalent oncogenic driver in lung cancer development. To explore the effects of PM2.5 on global and P53 promoter methylation changes and the mechanisms involved, we exposed human bronchial epithelial cells (BEAS-2B) to low concentrations of PM2.5 for 10 days. Our results indicated that PM2.5-induced global DNA hypomethylation was accompanied by reduced DNMT1 expression. PM2.5 also induced hypermethylation of P53 promoter and inhibited its expression by increasing DNMT3B protein level. Furthermore, ROS-induced activation of Akt was involved in PM2.5-induced increase in DNMT3B. In conclusion, our results strongly suggest that repeated exposure to PM2.5 induces epigenetic silencing of P53 through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation, which not only provides a possible explanation for PM-induced lung cancer, but also may help to identify specific interventions to prevent PM-induced lung carcinogenesis.

  17. Identification of PM10 characteristics involved in cellular responses in human bronchial epithelial cells (Beas-2B).

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    Van Den Heuvel, Rosette; Den Hond, Elly; Govarts, Eva; Colles, Ann; Koppen, Gudrun; Staelens, Jeroen; Mampaey, Maja; Janssen, Nicole; Schoeters, Greet

    2016-08-01

    Notwithstanding evidence is present that physicochemical characteristics of ambient particles attribute to adverse health effects, there is still some lack of understanding in this complex relationship. At this moment it is not clear which properties (such as particle size, chemical composition) or sources of the particles are most relevant for health effects. This study investigates the in vitro toxicity of PM10 in relation to PM chemical composition, black carbon (BC), endotoxin content and oxidative potential (OP). In 2013-2014 PM10 was sampled (24h sampling, 108 sampling days) in ambient air at three sites in Flanders (Belgium) with different pollution characteristics: an urban traffic site (Borgerhout), an industrial area (Zelzate) and a rural background location (Houtem). To characterize the toxic potential of PM10, airway epithelial cells (Beas-2B cells) have been exposed to particles in vitro. Different endpoints were studied including cell damage and death (cell viability) using the Neutral red Uptake assay, the production of pro-inflammatory molecules by interleukin 8 (IL-8) induction and DNA-damaging activity using the FPG-modified Comet assay. The endotoxin levels in the collected samples were analysed and the capacity of PM10 particles to produce reactive oxygen species (OP) was evaluated by electron paramagnetic resonance (EPR) spectroscopy. Chemical characteristics of PM10 (BC, As, Cd, Cr, Cu, Mn, Ni, Pb, Zn) and meteorological conditions were recorded on the sampling days. PM10 particles exhibited dose-dependent cytotoxicity in Beas-2B cells and were found to significantly induce the release of IL-8 in samples from the three locations. Oxidatively damaged DNA was observed in exposed Beas-2B cells. Endotoxin levels above the detection limit were detected in half of the samples. OP was measurable in all samples. Associations between PM10 characteristics and biological effects of PM10 were assessed by single and multiple regression analyses. The

  18. Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells

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    Fu, Jiamei; Wang, Juan; Wang, Xiangdong; Wang, Ping; Xu, Jinping; Zhou, Cuiping; Bai, Yang; Shao, Chunlin, E-mail: clshao@shmu.edu.cn

    2016-07-15

    Highlights: • Radiation damage of Beas-2B cells was enhanced by macrophage-mediated bilateral bystander responses. • Expressions of TNF-α and IL-8 in the α-irradiated Beas-2B cells were dependent on ERK and p38 pathways. • The neighboring U937 cells further increased the generation of TNF-α and IL-8 in the α-irradiated Beas-2B cells. • NF-κB dependent upregulation of TNF-α and IL-8 was induced in the bystander U937 cells. - Abstract: Although radiation induced bystander effects (RIBE) have been investigated for decades for their potential health risk, the underlying gene regulation is still largely unclear, especially the roles of immune system and inflammatory response in RIBE. In the present study, macrophage U937 cells and epithelial Beas-2B cells were co-cultured to disclose the cascades of bystander signaling factors and intercellular communications. After α-particle irradiation, both ERK and p38 pathways were activated in Beas-2B cells and were associated with the autocrine and paracrine signaling of TNF-α and IL-8, resulting in direct damage to the irradiated cells. Similar upregulation of TNF-α and IL-8 was induced in the bystander U937 cells after co-culture with α-irradiated Beas-2B cells. This upregulation was dependent on the activation of NF-κB pathway and was responsible for the enhanced damage of α-irradiated Beas-2B cells. Interestingly, the increased expressions of TNF-α and IL-8 mRNAs in the bystander U937 cells were clearly relayed on the activated ERK and p38 pathways in the irradiated Beas-2B cells, and the upregulation of TNF-α and IL-8 mRNAs in co-cultured Beas-2B cells was also partly due to the activated NF-κB pathway in the bystander U937 cells. With the pretreatment of U0126 (MEK1/2 inhibitor), SB203580 (p38 inhibitor) or BAY 11-7082 (NF-κB inhibitor), the aggravated damage in the α-irradiated Beas-2B cells could be largely alleviated. Our results disclosed novel signaling cascades of macrophage-mediated bilateral

  19. Biological responses according to the shape and size of carbon nanotubes in BEAS-2B and MESO-1 cells.

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    Haniu, Hisao; Saito, Naoto; Matsuda, Yoshikazu; Tsukahara, Tamotsu; Usui, Yuki; Maruyama, Kayo; Takanashi, Seiji; Aoki, Kaoru; Kobayashi, Shinsuke; Nomura, Hiroki; Tanaka, Manabu; Okamoto, Masanori; Kato, Hiroyuki

    2014-01-01

    This study aimed to investigate the influence of the shape and size of multi-walled carbon nanotubes (MWCNTs) and cup-stacked carbon nanotubes (CSCNTs) on biological responses in vitro. Three types of MWCNTs - VGCF(®)-X, VGCF(®)-S, and VGCF(®) (vapor grown carbon fibers; with diameters of 15, 80, and 150 nm, respectively) - and three CSCNTs of different lengths (CS-L, 20-80 μm; CS-S, 0.5-20 μm; and CS-M, of intermediate length) were tested. Human bronchial epithelial (BEAS-2B) and malignant pleural mesothelioma cells were exposed to the CNTs (1-50 μg/mL), and cell viability, permeability, uptake, total reactive oxygen species/superoxide production, and intracellular acidity were measured. CSCNTs were less toxic than MWCNTs in both cell types over a 24-hour exposure period. The cytotoxicity of endocytosed MWCNTs varied according to cell type/size, while that of CSCNTs depended on tube length irrespective of cell type. CNT diameter and length influenced cell aggregation and injury extent. Intracellular acidity increased independently of lysosomal activity along with the number of vacuoles in BEAS-2B cells exposed for 24 hours to either CNT (concentration, 10 μg/mL). However, total reactive oxygen species/superoxide generation did not contribute to cytotoxicity. The results demonstrate that CSCNTs could be suitable for biological applications and that CNT shape and size can have differential effects depending on cell type, which can be exploited in the development of highly specialized, biocompatible CNTs.

  20. Biological responses according to the shape and size of carbon nanotubes in BEAS-2B and MESO-1 cells

    Directory of Open Access Journals (Sweden)

    Haniu H

    2014-04-01

    Full Text Available Hisao Haniu,1,2 Naoto Saito,2,3 Yoshikazu Matsuda,4 Tamotsu Tsukahara,5 Yuki Usui,1,6,7 Kayo Maruyama,2,3 Seiji Takanashi,1 Kaoru Aoki,1 Shinsuke Kobayashi,1 Hiroki Nomura,1 Manabu Tanaka,1 Masanori Okamoto,1 Hiroyuki Kato1 1Department of Orthopaedic Surgery, Shinshu University School of Medicine, Nagano, Japan; 2Insutitute for Biomedical Sciences, Shinshu University, Nagano, Japan; 3Department of Applied Physical Therapy, Shinshu University School of Health Sciences, Nagano, Japan; 4Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Saitama, Japan; 5Department of Hematology and Immunology, Kanazawa Medical University, Ishikawa, Japan; 6Research Center for Exotic Nanocarbons, Shinshu University, Nagano, Japan; 7Aizawa Hospital, Sports Medicine Center, Nagano, Japan Abstract: This study aimed to investigate the influence of the shape and size of multi-walled carbon nanotubes (MWCNTs and cup-stacked carbon nanotubes (CSCNTs on biological responses in vitro. Three types of MWCNTs – VGCF®-X, VGCF®-S, and VGCF® (vapor grown carbon fibers; with diameters of 15, 80, and 150 nm, respectively – and three CSCNTs of different lengths (CS-L, 20–80 µm; CS-S, 0.5–20 µm; and CS-M, of intermediate length were tested. Human bronchial epithelial (BEAS-2B and malignant pleural mesothelioma cells were exposed to the CNTs (1–50 µg/mL, and cell viability, permeability, uptake, total reactive oxygen species/superoxide production, and intracellular acidity were measured. CSCNTs were less toxic than MWCNTs in both cell types over a 24-hour exposure period. The cytotoxicity of endocytosed MWCNTs varied according to cell type/size, while that of CSCNTs depended on tube length irrespective of cell type. CNT diameter and length influenced cell aggregation and injury extent. Intracellular acidity increased independently of lysosomal activity along with the number of vacuoles in BEAS-2B cells exposed for 24 hours to either CNT

  1. Poly (I:C, an agonist of toll-like receptor-3, inhibits replication of the Chikungunya virus in BEAS-2B cells

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    Li Yong-Gang

    2012-06-01

    Full Text Available Abstract Background Double-stranded RNA (dsRNA and its mimic, polyinosinic acid: polycytidylic acid [Poly (I:C], are recognized by toll-like receptor 3 (TLR3 and induce interferon (IFN-β in many cell types. Poly (I:C is the most potent IFN inducer. In in vivo mouse studies, intraperitoneal injection of Poly (I:C elicited IFN-α/β production and natural killer (NK cells activation. The TLR3 pathway is suggested to contribute to innate immune responses against many viruses, including influenza virus, respiratory syncytial virus, herpes simplex virus 2, and murine cytomegalovirus. In Chikungunya virus (CHIKV infection, the viruses are cleared within 7–10 days postinfection before adaptive immune responses emerge. The innate immune response is important for CHIKV clearance. Results The effects of Poly (I:C on the replication of CHIKV in human bronchial epithelial cells, BEAS-2B, were studied. Poly (I:C suppressed cytopathic effects (CPE induced by CHIKV infection in BEAS-2B cells in the presence of Poly (I:C and inhibited the replication of CHIKV in the cells. The virus titers of Poly (I:C-treated cells were much lower compared with those of untreated cells. CHIKV infection and Poly (I:C treatment of BEAS-2B cells induced the production of IFN-β and increased the expression of anti-viral genes, including IFN-α, IFN-β, MxA, and OAS. Both Poly (I:C and CHIKV infection upregulate the expression of TLR3 in BEAS-2B cells. Conclusions CHIKV is sensitive to innate immune response induced by Poly (I:C. The inhibition of CHIKV replication by Poly (I:C may be through the induction of TLR3, which triggers the production of IFNs and other anti-viral genes. The innate immune response is important to clear CHIKV in infected cells.

  2. Cadmium induces carcinogenesis in BEAS-2B cells through ROS-dependent activation of PI3K/AKT/GSK-3β/β-catenin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Son, Young-Ok; Wang, Lei; Poyil, Pratheeshkumar; Budhraja, Amit; Hitron, J. Andrew; Zhang, Zhuo [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY (United States); Lee, Jeong-Chae [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY (United States); School of Dentistry and Institute of Oral Biosciences (BK21 program), Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY (United States)

    2012-10-15

    Cadmium has been widely used in industry and is known to be carcinogenic to humans. Although it is widely accepted that chronic exposure to cadmium increases the incidence of cancer, the mechanisms underlying cadmium-induced carcinogenesis are unclear. The main aim of this study was to investigate the role of reactive oxygen species (ROS) in cadmium-induced carcinogenesis and the signal transduction pathways involved. Chronic exposure of human bronchial epithelial BEAS-2B cells to cadmium induced cell transformation, as evidenced by anchorage-independent growth in soft agar and clonogenic assays. Chronic cadmium treatment also increased the potential of these cells to invade and migrate. Injection of cadmium-stimulated cells into nude mice resulted in the formation of tumors. In contrast, the cadmium-mediated increases in colony formation, cell invasion and migration were prevented by transfection with catalase, superoxide dismutase-1 (SOD1), or SOD2. In particular, chronic cadmium exposure led to activation of signaling cascades involving PI3K, AKT, GSK-3β, and β-catenin and transfection with each of the above antioxidant enzymes markedly inhibited cadmium-mediated activation of these signaling proteins. Inhibitors specific for AKT or β-catenin almost completely suppressed the cadmium-mediated increase in total and active β-catenin proteins and colony formation. Moreover, there was a marked induction of AKT, GSK-3β, β-catenin, and carcinogenic markers in tumor tissues formed in mice after injection with cadmium-stimulated cells. Collectively, our findings suggest a direct involvement of ROS in cadmium-induced carcinogenesis and implicate a role of AKT/GSK-3β/β-catenin signaling in this process. -- Highlights: ► Chronic exposure to cadmium induces carcinogenic properties in BEAS-2B cells. ► ROS involved in cadmium-induced tumorigenicity of BEAS-2B cells. ► Cadmium activates ROS-dependent AKT/GSK-3β/β-catenin-mediated signaling. ► ROS

  3. PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kan-o, Keiko [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Matsumoto, Koichiro, E-mail: koichi@kokyu.med.kyushu-u.ac.jp [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Asai-Tajiri, Yukari; Fukuyama, Satoru; Hamano, Saaka; Seki, Nanae; Nakanishi, Yoichi [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Inoue, Hiromasa [Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520 (Japan)

    2013-05-31

    Highlights: •Double-stranded RNA upregulates B7-H1 on BEAS-2B airway epithelial cells. •The upregulation of B7-H1 is attenuated by inhibition of PI3Kδ isoform. •PI3Kδ-mediated upregulation of B7-H1 is independent of NF-κB activation. •Inhibition of PI3Kδ may prevent persistent viral infection induced by B7-H1. -- Abstract: Airway viral infection disturbs the health-related quality of life. B7-H1 (also known as PD-L1) is a coinhibitory molecule associated with the escape of viruses from the mucosal immunity, leading to persistent infection. Most respiratory viruses generate double-stranded (ds) RNA during replication. The stimulation of cultured airway epithelial cells with an analog of viral dsRNA, polyinosinic-polycytidylic acid (poly IC) upregulates the expression of B7-H1 via activation of the nuclear factor κB(NF-κB). The mechanism of upregulation was investigated in association with phosphatidylinositol 3-kinases (PI3Ks). Poly IC-induced upregulation of B7-H1 was profoundly suppressed by a pan-PI3K inhibitor and partially by an inhibitor or a small interfering (si)RNA for PI3Kδ in BEAS-2B cells. Similar results were observed in the respiratory syncytial virus-infected cells. The expression of p110δ was detected by Western blot and suppressed by pretreatment with PI3Kδ siRNA. The activation of PI3Kδ is typically induced by oxidative stress. The generation of reactive oxygen species was increased by poly IC. Poly IC-induced upregulation of B7-H1 was attenuated by N-acetyl-L-cysteine, an antioxidant, or by oxypurinol, an inhibitor of xanthine oxidase. Poly IC-induced activation of NF-κB was suppressed by a pan-PI3K inhibitor but not by a PI3Kδ inhibitor. These results suggest that PI3Kδ mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-κB.

  4. Genome-wide analysis of HIF-2α chromatin binding sites under normoxia in human bronchial epithelial cells (BEAS-2B) suggests its diverse functions.

    Science.gov (United States)

    Lee, Meng-Chang; Huang, Hsin-Ju; Chang, Tzu-Hao; Huang, Hsieh-Chou; Hsieh, Shen-Yuan; Chen, Yi-Siou; Chou, Wei-Yuan; Chiang, Chiao-Hsi; Lai, Ching-Huang; Shiau, Chia-Yang

    2016-01-01

    Constitutive functional HIF-2α was recently identified in cancer and stem cell lines under normoxia. In this study, BEAS-2B, a bronchial epithelial cell line, was shown to constitutively express active HIF-2α under normoxia and exhibit markers of pluripotency including Oct-4, Nanog, and sphere formation. Oct-4 expression was reduced after knockdown of HIF-2α under normoxia. Global enrichment analysis of HIF-2α demonstrated the diverse functions of HIF-2α under normoxia. Bioinformatics analysis of the enriched loci revealed an enhancer role of HIF-2α binding sites, involvement of HIF-2α interacting proteins, and enriched de novo motifs which suggest the diverse role of HIF-2α in pseudohypoxia. The low ratio of the discovered loci overlapping with those revealed in cancer cell lines 786-O (16.1%) and MCF-7 (15.9%) under hypoxia indicated a prevailing non-canonical mechanism. Hypoxia had positive, marginal or adverse effects on the enrichment of the selected loci in ChIP-PCR assays. Deletion of the N-terminal activation domain (N-TAD) of HIF-2α disrupted the reporting activity of two of the loci annotated to ELN and ANKRD31. Hypoxia incurring abundance variation of HIF-2α may misrepresent the N-TAD functions as canonical hypoxia inducible features via C-TAD activation. Elucidation of the pseudohypoxia functions of constitutive HIF-2α is useful for resolving its role in malignancy and pluripotency.

  5. An ShRNA Based Genetic Screen Identified Sesn2 as a Potential Tumor Suppressor in Lung Cancer via Suppression of Akt-mTOR-p70S6K Signaling.

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    Hui Xu

    Full Text Available Lung cancer is emerging rapidly as the leading death cause in Chinese cancer patients. The causal factors for Chinese lung cancer development remain largely unclear. Here we employed an shRNA library-based loss-of-function screen in a genome-wide and unbiased manner to interrogate potential tumor suppressor candidates in the immortalized human lung epithelial cell line BEAS-2B.Soft agar assays were conducted for screening BEAS-2B cells infected with the retroviral shRNA library with the acquired feature of anchorage-independent growth, large (>0.5mm in diameter and well-separated colonies were isolated for proliferation. PCRs were performed to amplify the integrated shRNA fragment from individual genomic DNA extracted from each colony, and each PCR product is submitted for DNA sequencing to reveal the integrated shRNA and its target gene. A total of 6 candidate transformation suppressors including INPP4B, Sesn2, TIAR, ACRC, Nup210, LMTK3 were identified. We validated Sesn2 as the candidate of lung cancer tumor suppressor. Knockdown of Sesn2 by an shRNA targeting 3' UTR of Sesn2 transcript potently stimulated the proliferation and malignant transformation of lung bronchial epithelial cell BEAS-2B via activation of Akt-mTOR-p70S6K signaling, whereas ectopic expression of Sens2 re-suppressed the malignant transformation elicited by the Sesn2 shRNA. Moreover, knockdown of Sesn2 in BEAS-2B cells promoted the BEAS-2B cell-transplanted xenograft tumor growth in nude mice. Lastly, DNA sequencing indicated mutations of Sesn2 gene are rare, the protein levels of Sesn2 of 77 Chinese lung cancer patients varies greatly compared to their adjacent normal tissues, and the low expression level of Sesn2 associates with the poor survival in these examined patients by Kaplan Meier analysis.Our shRNA-based screen has demonstrated Sesn2 is a potential tumor suppressor in lung epithelial cells. The expression level of Sesn2 may serve as a prognostic marker for

  6. Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells.

    Science.gov (United States)

    Bai, Wenlin; Chen, Yujiao; Sun, Pengling; Gao, Ai

    2016-01-01

    Titanium dioxide (TiO2) nanoparticles (TNPs) are manufactured worldwide for a wide range of applications and the toxic effect of TNPs on biological systems is gaining attention. Autophagy is recognized as an emerging toxicity mechanism triggered by nanomaterials. MicroRNA 34a (miR34a) acts as a tumor suppressor gene by targeting many oncogenes, but how it affects autophagy induced by TNPs is not completely understood. Here, we observed the activation of TNP-induced autophagy through monodansylcadaverine staining and LC3-I/LC3-II conversion. Meanwhile, the transmission electron microscope ultrastructural analysis showed typical morphological characteristics in autophagy process. We detected the expression of miR34a and B-cell lymphoma/leukemia-2 (Bcl-2). In addition, the underlying mechanism of TNP-induced autophagy was performed using overexpression of miR34a by lentivirus vector transfection. Results showed that TNPs induced autophagy generation evidently. Typical morphological changes in the process of autophagy were observed by the transmission electron microscope ultrastructural analysis and LC3-I/LC3-II conversion increased significantly in TNP-treated cells. Meanwhile, TNPs induced the downregulation of miR34a and increased the expression of Bcl-2. Furthermore, overexpressed miR34a decreased the expression of Bcl-2 both in messenger RNA and protein level, following which the level of autophagy and cell death rate increased after the transfected cells were incubated with TNPs for 24 hours. These findings provide the first evidence that overexpressed miR34a enhanced TNP-induced autophagy and cell death through targeted downregulation of Bcl-2 in BEAS-2B cells.

  7. Perilla frutescens leaf extract inhibits mite major allergen Der p 2-induced gene expression of pro-allergic and pro-inflammatory cytokines in human bronchial epithelial cell BEAS-2B.

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    Jer-Yuh Liu

    Full Text Available Perilla frutescens has been used in traditional medicine for respiratory diseases due to its anti-bacterial and anti-inflammatory activity. This study aimed to investigate effects of Perilla frutescens leaf extract (PFE on expression of pro-allergic and pro-inflammatory cytokines in airway epithelial cells exposed to mite major allergen Der p 2 (DP2 and the underlying mechanisms. Our results showed that PFE up to 100 µg/mL had no cytotoxic effect on human bronchial epithelial cell BEAS-2B. Further investigations revealed that PFE dose-dependently diminished mRNA expression of pro-allergic cytokine IL-4, IL-5, IL-13 and GM-CSF, as well as pro-inflammatory cytokine IL-6, IL-8 and MCP-1 in BEAS-2B cells treated with DP2. In parallel to mRNA, the DP-2-elevated levels of the tested cytokines were decreased. Further investigation showed that DP2-indued phosphorylation of p38 MAPK (P38 and JNK, but not Erk1/2, was also suppressed by PFE. In addition, PFE elevated cytosolic IκBα level and decreased nuclear NF-κB level in DP2-stimulated BEAS-2B cells. Taken together, these findings revealed that PFE significantly diminished both mRNA expression and protein levels of pro-allergic and pro-inflammatory cytokines in response to DP2 through inhibition of P38/JNK and NK-κB activation. These findings suggest that PFE should be beneficial to alleviate both allergic and inflammatory responses on airway epithelium in response to aeroallergens.

  8. Acute toxicity of silver and carbon nanoaerosols to normal and cystic fibrosis human bronchial epithelial cells.

    Science.gov (United States)

    Jeannet, Natalie; Fierz, Martin; Schneider, Sarah; Künzi, Lisa; Baumlin, Nathalie; Salathe, Matthias; Burtscher, Heinz; Geiser, Marianne

    2016-01-01

    Inhalation of engineered nanoparticles (NP) poses a still unknown risk. Individuals with chronic lung diseases are expected to be more vulnerable to adverse effects of NP than normal subjects, due to altered respiratory structures and functions. Realistic and dose-controlled aerosol exposures were performed using the deposition chamber NACIVT. Well-differentiated normal and cystic fibrosis (CF) human bronchial epithelia (HBE) with established air-liquid interface and the human bronchial epithelial cell line BEAS-2B were exposed to spark-generated silver and carbon nanoaerosols (20 nm diameter) at three different doses. Necrotic and apoptotic cell death, pro-inflammatory response, epithelial function and morphology were assessed within 24 h after aerosol exposure. NP exposure resulted in significantly higher necrosis in CF than normal HBE and BEAS-2B cells. Before and after NP treatment, CF HBE had higher caspase-3 activity and secreted more IL-6 and MCP-1 than normal HBE. Differentiated HBE had higher baseline secretion of IL-8 and less caspase-3 activity and MCP-1 secretion compared to BEAS-2B cells. These biomarkers increased moderately in response to NP exposure, except for MCP-1, which was reduced in HBE after AgNP treatment. No functional and structural alterations of the epithelia were observed in response to NP exposure. Significant differences between cell models suggest that more than one and fully differentiated HBE should be used in future toxicity studies of NP in vitro. Our findings support epidemiologic evidence that subjects with chronic airway diseases are more vulnerable to adverse effects of particulate air pollution. Thus, this sub-population needs to be included in nano-toxicity studies.

  9. Chromosomal Instability of Human Tracheal Epithelia Cells BEAS-2B Induced by Extract of Coal Tar Pitch Fume%煤焦沥青烟提取物致人支气管上皮细胞BEAS-2B染色体不稳定性研究

    Institute of Scientific and Technical Information of China (English)

    李智涛; 冯艳铭; 王威; 王丽霞; 赵勇; 祝寒松; 吴卫东; 吴逸明

    2011-01-01

    .When morphological changes were shown, cell cycle was detected by flow cytometry. Results Half lethal concentration(LC50)of the fume extract of coal tar pitch was 8. 64 mg/L with BEAS-2B cells. BEAS-2B cells were induced at dosage of 2. 0 mg/L. After the cells were cultured for 30 passages, the malignant transformation was shown in the induced cells. At the 30th generation, the cell clone formation rate was 21. 50‰ in the coal tar pitch group, which was significantly higher than those of the normal control group and DMSO group. The Gl phase cell ratio significantly reduced and G2/M phase cell ratio increased significantly in the coal tar pitch group measured by flow cytometry. Beginning from the 10 th generation, the proportion of diploid cells decreased and aneuploid cells increased distinctively in the coal tar pitch induced group.Chromosomal instability increased as the cell passage increased. Cells in soft agar colony formation rate and the percentage of chromosome aberrations showed a positive correlation. Conclusions The fume extract of coal tar pitch could injury the cell DNA, and could induce BEAS-2B cells to produce chromosomal instability and malignant transformation in vitro.

  10. Cellular Interactions and Biological Responses to Titanium Dioxide Nanoparticles in HepG2 and BEAS-2B Cells: Role of Cell Culture Media

    Science.gov (United States)

    ABSTRACT We have shown previously that the composition of the biological medium used in vitro can affect the cellular interaction and biological response of titanium dioxide nanoparticles (nano-TiO2) in human lung epithelial cells. However, it is unclear if these effects are co...

  11. Flagellin of Pseudomonas aeruginosa induces transforming growth factor beta 1 expression in normal bronchial epithelial cells through mitogen activated protein kinase cascades

    Institute of Scientific and Technical Information of China (English)

    YANG Jing-jing; WANG Dan-dan; SUN Tie-ying

    2011-01-01

    Background Acute lung infection due to Pseudomonas aeruginosa (P. Aeruginosa) is a serious problem, especially in patients with structural lung conditions or immune compromised hosts, leading to an overwhelming threat with a high risk of morbidity and mortality. As an outcome of infection, fibrosis can be linked with chronic lung diseases. But some fibrotic manifestations, such as an irreversible decrease of lung function and fibrous bands seen on chest imaging, have been found after an acute infection with P. Aeruginosa. Fibrogenesis/remodeling resulting from acute lung infection by P.aeruginosa is rarely reported. This study was designed to explore the relation between fibrogenesis/remodeling and acute infection by P. Aeruginosa in vitro. We used flagellin protein from P. Aeruginosa, a key initiator of acute P.aeruginosa lung infection, to elucidate mechanisms by which acute lung infection with P. Aeruginosa can cause fibrogenesis/remodeling.Methods We studied the effect of flagellin from P. Aeruginosa (flagellin for short) on the transforming growth factor beta 1 (TGF-β1) and interleukin-8 (IL-8) expression, and the possible involvement of the signaling pathway, tumor necrosis factor receptor-associated factor 6 (TRAF6)/mitogen activated protein kinase (MAPK) pathway. Flagellin was purified from the P. Aeruginosa standard strain, PAO1. Normal bronchial epithelial cells BEAS-2B were challenged with different concentrations of flagellin, and cell viability assessment was performed by cell counting kit-8. BEAS-2B cells were incubated with flagellin with the specific MAPK inhibitors or TRAF6 siRNA. Cell lysates and the cultured supernatant were collected. The level of TGF-β1 and IL-8 were detected by enzyme-linked immunosorbant assay (ELISA). Western blotting was used to detect the protein levels of MAPK signal proteins p38, c-Jun NH2-terminal kinase (JNK) and extracellular regulated kinase (ERK).Results Expression of TGF-β1 in BEAS-2B cells was elevated by

  12. Regional tidal lung strain in mechanically ventilated normal lungs.

    Science.gov (United States)

    Paula, Luis Felipe; Wellman, Tyler J; Winkler, Tilo; Spieth, Peter M; Güldner, Andreas; Venegas, Jose G; Gama de Abreu, Marcelo; Carvalho, Alysson R; Vidal Melo, Marcos F

    2016-12-01

    Parenchymal strain is a key determinant of lung injury produced by mechanical ventilation. However, imaging estimates of volumetric tidal strain (ε = regional tidal volume/reference volume) present substantial conceptual differences in reference volume computation and consideration of tidally recruited lung. We compared current and new methods to estimate tidal volumetric strains with computed tomography, and quantified the effect of tidal volume (VT) and positive end-expiratory pressure (PEEP) on strain estimates. Eight supine pigs were ventilated with VT = 6 and 12 ml/kg and PEEP = 0, 6, and 12 cmH2O. End-expiratory and end-inspiratory scans were analyzed in eight regions of interest along the ventral-dorsal axis. Regional reference volumes were computed at end-expiration (with/without correction of regional VT for intratidal recruitment) and at resting lung volume (PEEP = 0) corrected for intratidal and PEEP-derived recruitment. All strain estimates demonstrated vertical heterogeneity with the largest tidal strains in middependent regions (P < 0.01). Maximal strains for distinct estimates occurred at different lung regions and were differently affected by VT-PEEP conditions. Values consistent with lung injury and inflammation were reached regionally, even when global measurements were below critical levels. Strains increased with VT and were larger in middependent than in nondependent lung regions. PEEP reduced tidal-strain estimates referenced to end-expiratory lung volumes, although it did not affect strains referenced to resting lung volume. These estimates of tidal strains in normal lungs point to middependent lung regions as those at risk for ventilator-induced lung injury. The different conditions and topography at which maximal strain estimates occur allow for testing the importance of each estimate for lung injury.

  13. Diatom-derived polyunsaturated aldehydes activate cell death in human cancer cell lines but not normal cells.

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    Clementina Sansone

    Full Text Available Diatoms are an important class of unicellular algae that produce bioactive polyunsaturated aldehydes (PUAs that induce abortions or malformations in the offspring of invertebrates exposed to them during gestation. Here we compare the effects of the PUAs 2-trans,4-trans-decadienal (DD, 2-trans,4-trans-octadienal (OD and 2-trans,4-trans-heptadienal (HD on the adenocarcinoma cell lines lung A549 and colon COLO 205, and the normal lung/brunch epithelial BEAS-2B cell line. Using the viability MTT/Trypan blue assays, we show that PUAs have a toxic effect on both A549 and COLO 205 tumor cells but not BEAS-2B normal cells. DD was the strongest of the three PUAs tested, at all time-intervals considered, but HD was as strong as DD after 48 h. OD was the least active of the three PUAs. The effect of the three PUAs was somewhat stronger for A549 cells. We therefore studied the death signaling pathway activated in A549 showing that cells treated with DD activated Tumor Necrosis Factor Receptor 1 (TNFR1 and Fas Associated Death Domain (FADD leading to necroptosis via caspase-3 without activating the survival pathway Receptor-Interacting Protein (RIP. The TNFR1/FADD/caspase pathway was also observed with OD, but only after 48 h. This was the only PUA that activated RIP, consistent with the finding that OD causes less damage to the cell compared to DD and HD. In contrast, cells treated with HD activated the Fas/FADD/caspase pathway. This is the first report that PUAs activate an extrinsic apoptotic machinery in contrast to other anticancer drugs that promote an intrinsic death pathway, without affecting the viability of normal cells from the same tissue type. These findings have interesting implications also from the ecological viewpoint considering that HD is one of the most common PUAs produced by diatoms.

  14. Diatom-derived polyunsaturated aldehydes activate cell death in human cancer cell lines but not normal cells.

    Science.gov (United States)

    Sansone, Clementina; Braca, Alessandra; Ercolesi, Elena; Romano, Giovanna; Palumbo, Anna; Casotti, Raffaella; Francone, Maria; Ianora, Adrianna

    2014-01-01

    Diatoms are an important class of unicellular algae that produce bioactive polyunsaturated aldehydes (PUAs) that induce abortions or malformations in the offspring of invertebrates exposed to them during gestation. Here we compare the effects of the PUAs 2-trans,4-trans-decadienal (DD), 2-trans,4-trans-octadienal (OD) and 2-trans,4-trans-heptadienal (HD) on the adenocarcinoma cell lines lung A549 and colon COLO 205, and the normal lung/brunch epithelial BEAS-2B cell line. Using the viability MTT/Trypan blue assays, we show that PUAs have a toxic effect on both A549 and COLO 205 tumor cells but not BEAS-2B normal cells. DD was the strongest of the three PUAs tested, at all time-intervals considered, but HD was as strong as DD after 48 h. OD was the least active of the three PUAs. The effect of the three PUAs was somewhat stronger for A549 cells. We therefore studied the death signaling pathway activated in A549 showing that cells treated with DD activated Tumor Necrosis Factor Receptor 1 (TNFR1) and Fas Associated Death Domain (FADD) leading to necroptosis via caspase-3 without activating the survival pathway Receptor-Interacting Protein (RIP). The TNFR1/FADD/caspase pathway was also observed with OD, but only after 48 h. This was the only PUA that activated RIP, consistent with the finding that OD causes less damage to the cell compared to DD and HD. In contrast, cells treated with HD activated the Fas/FADD/caspase pathway. This is the first report that PUAs activate an extrinsic apoptotic machinery in contrast to other anticancer drugs that promote an intrinsic death pathway, without affecting the viability of normal cells from the same tissue type. These findings have interesting implications also from the ecological viewpoint considering that HD is one of the most common PUAs produced by diatoms.

  15. 卷烟烟气暴露下A549和BEAS-2B细胞促炎性因子的释放变化%Release of proinflammatory cytokines from A549 cells and BEAS-2B cells exposed to mainstream cigarette smoke

    Institute of Scientific and Technical Information of China (English)

    李翔; 张世敏; 赵俊伟; 尚平平; 彭斌; 谢复炜; 刘惠民; 谢剑平

    2016-01-01

    为比较不同类型细胞对卷烟烟气诱导的促炎症反应的应答差异,采用中性红细胞毒性试验测试了卷烟烟气总粒相物(TPM)和全烟气(WS)对人肺腺癌细胞A549和人支气管上皮细胞BEAS-2B的细胞毒性效应;采用酶联免疫法(ELISA)分析了TPM和WS暴露后,A549和BEAS-2B促炎性细胞因子白细胞介素-6(IL-6)和白细胞介素-8(IL-8)的释放水平。结果表明:BEAS-2B细胞较A549细胞对卷烟烟气的细胞毒性效应敏感。卷烟烟气暴露下A549细胞没有增加促炎性细胞因子IL-6和IL-8的释放;而BEAS-2B细胞在TPM和WS暴露下其IL-6和IL-8的释放显著增加。卷烟烟气诱导的促炎症反应存在细胞类型的差异。%In order to compare the differences of response to proinflammatory reaction induced by mainstream cigarette smoke among cells of different types, neutral red uptake (NRU) assay was employed to assess the cytotoxicity of cigarette smoke total particulate matter (TPM) or whole smoke (WS) to A549 cells (human adenocarcinoma cells) and BEAS-2B cells (human bronchial epithelial cells). The levels of proinflammatory cytokines interleukin-6 and interleukin-8 (IL-6 and IL-8) released from A549 and BEAS-2B cells exposed to TPM and WS were analyzed by ELISA. The results showed that BEAS-2B cells were more sensitive to smoke-induced cytotoxicity than A549 cells. The induction of IL-6 and IL-8 released from A549 cells was not impacted by cigarette smoke exposure, while TPM and WS all caused dose-dependently increase of IL-6 and IL-8 released from BEAS-2B cells. The proinflammatory response to cigarette smoke thus might be different depending on cell types.

  16. Proteases and oxidant stress control organic dust induction of inflammatory gene expression in lung epithelial cells

    OpenAIRE

    Natarajan, Kartiga; Gottipati, Koteswara R.; Berhane, Kiflu; Samten, Buka; Pendurthi, Usha; Boggaram, Vijay

    2016-01-01

    Background Persistant inflammatory responses to infectious agents and other components in organic dust underlie lung injury and development of respiratory diseases. Organic dust components responsible for eliciting inflammation and the mechanisms by which they cause lung inflammation are not fully understood. We studied the mechanisms by which protease activities in poultry dust extracts and intracellular oxidant stress induce inflammatory gene expression in A549 and Beas2B lung epithelial ce...

  17. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

    In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

  18. Cellular senescence in normal and premature lung aging.

    Science.gov (United States)

    Bartling, B

    2013-10-01

    The incidence of chronic respiratory diseases (e.g., chronic obstructive pulmonary disease, COPD) and interstitial lung diseases (e.g., pneumonia and lung fibrosis) increases with age. In addition to immune senescence, the accumulation of senescent cells directly in lung tissue might play a critical role in the increased prevalence of these pulmonary diseases. In the last couple of years, detailed studies have identified the presence of senescent cells in the aging lung and in diseased lungs of patients with COPD and lung fibrosis. Cellular senescence has been shown for epithelial cells of bronchi and alveoli as well as mesenchymal and vascular cells. Known risk factors for pulmonary diseases (cigarette smoke, air pollutions, bacterial infections, etc.) were identified in experimental studies as being possible mediators in the development of cellular senescence. The present findings indicate the importance of cellular senescence in normal lung aging and in premature aging of the lung in patients with COPD, lung fibrosis, and probably other respiratory diseases.

  19. Inhibition of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus.

    Science.gov (United States)

    Chang, Hong-Bin; Chen, Bing-Huei

    2015-01-01

    The objectives of this study were to explore the inhibition mechanism of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus. In addition, human bronchus epithelial cell line BEAS-2B (normal cell) was selected for comparison. A high-performance liquid chromatography (HPLC) method was developed to separate and quantify the various curcuminoids in C. longa extract, including curcumin (1,714.5 μg/mL), demethoxycurcumin (1,147.4 μg/mL), and bisdemethoxycurcumin (190.2 μg/mL). A high-stability nanoemulsion composed of Tween 80, water, and curcuminoid extract was prepared, with mean particle size being 12.6 nm. The cell cycle was retarded at G2/M for both the curcuminoid extract and nanoemulsion treatments; however, the inhibition pathway may be different. H460 cells were more susceptible to apoptosis than A549 cells for both curcuminoid extract and nanoemulsion treatments. Growth of BEAS-2B remained unaffected for both the curcuminoid extract and nanoemulsion treatments, with a concentration range from 1 to 4 μg/mL. Also, the activities of caspase-3, caspase-8, and caspase-9 followed a dose-dependent increase for both A549 and H460 cells for both the treatments, accompanied by a dose-dependent increase in cytochrome C expression and a dose-dependent decrease in CDK1 expression. Interestingly, a dose-dependent increase in cyclin B expression was shown for A549 cells for both the treatments, while a reversed trend was found for H460 cells. Both mitochondria and death receptor pathways may be responsible for apoptosis of both A549 and H460 cells.

  20. Nitric oxide- and cisplatin-releasing silica nanoparticles for use against non-small cell lung cancer.

    Science.gov (United States)

    Munaweera, Imalka; Shi, Yi; Koneru, Bhuvaneswari; Patel, Amit; Dang, Mai H; Di Pasqua, Anthony J; Balkus, Kenneth J

    2015-12-01

    Nitric oxide (NO) and cisplatin releasing wrinkle-structured amine-modified mesoporous silica (AMS) nanoparticles have been developed for the treatment of non-small cell lung cancer (NSCLC). The AMS and NO- and cisplatin-loaded AMS materials were characterized using TEM, BET surface area, FTIR and ICP-MS, and tested in cell culture. The results show that for NSCLC cell lines (i.e., H596 and A549), the toxicity of NO- and cisplatin-loaded silica nanoparticles (NO-Si-DETA-cisplatin-AMS) is significantly higher than that of silica nanoparticles loaded with only cisplatin (Si-DETA-cisplatin-AMS). In contrast, the toxicity of NO-Si-DETA-cisplatin-AMS toward normal lung cell lines is not significantly different from that of Si-DETA-cisplatin-AMS (normal lung fibroblast cells WI-38) or is even lower than that of Si-DETA-cisplatin-AMS (normal lung epithelial cells BEAS-2B). The NO-induced sensitization of tumor cell death demonstrates that NO is a promising enhancer of platinum-based lung cancer therapy.

  1. MRI of normal and pathological fetal lung development

    Energy Technology Data Exchange (ETDEWEB)

    Kasprian, Gregor [University Clinic of Radiodiagnostics, Medical University of Vienna (Austria)]. E-mail: gregor.kasprian@meduniwien.ac.at; Balassy, Csilla [University Clinic of Radiodiagnostics, Medical University of Vienna (Austria); Brugger, Peter C. [Center of Anatomy and Cell Biology, Medical University of Vienna (Austria); Prayer, Daniela [University Clinic of Radiodiagnostics, Medical University of Vienna (Austria)

    2006-02-15

    Normal fetal lung development is a complex process influenced by mechanical and many biochemical factors. In addition to ultrasound, fetal magnetic resonance imaging (MRI) constitutes a new method to investigate this process in vivo during the second and third trimester. The techniques of MRI volumetry, assessment of signal intensities, and MRI spectroscopy of the fetal lung have been used to analyze this process and have already been applied clinically to identify abnormal fetal lung growth. Particularly in conditions such as oligohydramnios and congenital diaphragmatic hernia (CDH), pulmonary hypoplasia may be the cause of neonatal death. A precise diagnosis and quantification of compromised fetal lung development may improve post- and perinatal management. The main events in fetal lung development are reviewed and MR volumetric data from 106 normal fetuses, as well as different examples of pathological lung growth, are provided.

  2. Identification of a long non-coding RNA gene, growth hormone secretagogue receptor opposite strand, which stimulates cell migration in non-small cell lung cancer cell lines.

    Science.gov (United States)

    Whiteside, Eliza J; Seim, Inge; Pauli, Jana P; O'Keeffe, Angela J; Thomas, Patrick B; Carter, Shea L; Walpole, Carina M; Fung, Jenny N T; Josh, Peter; Herington, Adrian C; Chopin, Lisa K

    2013-08-01

    The molecular mechanisms involved in non‑small cell lung cancer tumourigenesis are largely unknown; however, recent studies have suggested that long non-coding RNAs (lncRNAs) are likely to play a role. In this study, we used public databases to identify an mRNA-like, candidate long non-coding RNA, GHSROS (GHSR opposite strand), transcribed from the antisense strand of the ghrelin receptor gene, growth hormone secretagogue receptor (GHSR). Quantitative real-time RT-PCR revealed higher expression of GHSROS in lung cancer tissue compared to adjacent, non-tumour lung tissue. In common with many long non-coding RNAs, GHSROS is 5' capped and 3' polyadenylated (mRNA-like), lacks an extensive open reading frame and harbours a transposable element. Engineered overexpression of GHSROS stimulated cell migration in the A549 and NCI-H1299 non-small cell lung cancer cell lines, but suppressed cell migration in the Beas-2B normal lung-derived bronchoepithelial cell line. This suggests that GHSROS function may be dependent on the oncogenic context. The identification of GHSROS, which is expressed in lung cancer and stimulates cell migration in lung cancer cell lines, contributes to the growing number of non-coding RNAs that play a role in the regulation of tumourigenesis and metastatic cancer progression.

  3. H5N1禽流感病毒NS1蛋白与干扰素诱导蛋白10表达的相关性研究%Influence of avian influenza virus NS1 protein on the expression of IP-10 in BEAS-2B cells

    Institute of Scientific and Technical Information of China (English)

    贾晓俊; 周剑芳; 王晶钰; 董婕; 薄洪; 李梓; 李魁彪; 蓝雨; 舒跃龙

    2008-01-01

    目的 研究高致病性禽流感(HPAI)H5N1病毒NS1蛋白对干扰素诱导蛋白10(IP-10)的影响.方法 分别将禽流感病毒A/Anhui/1/2005(H5N1)的NS1基因、插入80-84位缺失氨基酸的NS1突变基因及流感病毒A/Puerto Rico/8/1934(H1N1)的NS1基因克隆至真核表达载体pEGFP-N1,转染人支气管上皮细胞BEAS-2B,流式细胞仪检测转染细胞内IP-10的表达情况.结果 与pEGFP-N1对照组相比,三种NS1蛋白均能下调BEAS-2B细胞IP-10的表达(P0.01).结论 A/Anhui/1/2005(H5N1)禽流感病毒单一NS1蛋白能够抑制BEAS-2B细胞IP-10表达,但这并不能完全阐明其与病毒致病性之间的关系.%Objective To investigate the influence of avian influenza virus (AIV) NS1 protein on the expression of interferon-inducible protein 10 (IP-10). Methods NS1 gene from virus A/Anhui/1/2005 (H5N1),NS1 gene inserted with 80-84 amino acids from virus A/Anhui/1/2005(H5N1)and NS1 gene from virus A/Puerto Rico/8/1934 (H1N1) were cloned into the eukaryotic expression vector pEGFP-N1, and transected into BEAS-2Bcells, IP-10 expression level in transected cells was detected by flow cytometry. Results Compared with the control group pEGFP-N1, Expression of these three different NS1 genes can down-regulate the expression of IP-10in BEAS-2B cells, but there is no significant difference as to the lower level among them. Conclusion NS1protein of A/Anhui/1/2005(H5N1) can down-regulate the expression level of IP-10, but this may not clarify its relationship with the virulence of AIV.

  4. Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Pratheeshkumar, Poyil; Son, Young-Ok; Divya, Sasidharan Padmaja; Roy, Ram Vinod; Hitron, John Andrew; Wang, Lei [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Kim, Donghern; Dai, Jin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Asha, Padmaja [National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Cochin (India); Zhang, Zhuo [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Wang, Yitao [State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau (China); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States)

    2014-12-01

    Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5 μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promoter activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis. - Highlights: • Luteolin inhibited Cr(VI)-induced oxidative stress. • Luteolin inhibited chronic Cr(VI)-induced malignant transformation.

  5. Expression of BCRP Gene in the Normal Lung Tissue and Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the expression of novel multidrugresistance transporter (BCRP gene) from human MCF-7/AdrVp breast cancer cells in normal lung tissue and non-small lung cancer tissue. Methods: RNA was extracted immediately from fresh normal lung tissue and viable tumor tissue harvested from surgically resected specimens of non-small cell lung cancer patients. cDNA of BCRP gene was prepared by RT-PCR and was then amplified by PCR. cDNA products from those specimens were transferred to blotting membrane through electrophoresis and transferring technique and southern blot hybridization was eventually performed to detect the expression of BCRP gene. Results: RNA were extracted from 8 tumor tissue alone and 12 pairs of tumor tissue and normal lung tissue harvested from the same lung. Four patients' RNA samples with poor quality due to degrading were discarded. cDNA products of BCRP gene were obtained by RT-PCR and were then amplified by PCR in the remain 16 patients' RNA samples. Through southern blot hybridization, BCRP gene was found to be slightly expressed in various amounts in all normal lung tissue (10/10) and only in a half of tumor tissue samples (8/16). Conclusion: BCRP gene is slightly expressed in different amount in all normal lung tissue and only in a half of tumor tissue of non-small cell lung cancer patients. It is possible to induce it's overexpression and to develop multidrug resistance during chemotherapy if using anthracycline anticancer drugs.

  6. Protective effects of tea polyphenols on oxidative damage induced by uranium-mineral dust in BEAS-2B cells%茶多酚对铀矿尘致支气管上皮细胞损伤保护作用

    Institute of Scientific and Technical Information of China (English)

    黄波; 龙颖; 罗振华; 黄锐; 贺性鹏

    2011-01-01

    目的 探讨铀矿尘诱发细胞氧化损伤及茶多酚(tea polyphenols,TPs)的保护作用.方法 以人支气管上皮细胞(BEAS-2B)为靶细胞,分别用辣根过氧化物酶介导的酚红氧化法、细胞色素C还原法和番红花红褪色法测定细胞外液过氧化氢、超氧阴离子和羟自由基含量;细胞内H2O2和O2·-分别用2,7-二氯荧光黄双乙酸盐和氢化乙锭标记,荧光法测定荧光产物2,7'-二氯荧光黄和溴乙锭荧光强度,多核细胞法体外研究细胞次黄嘌呤磷核糖基转移酶基因(HPRT)突变,自动生化仪测量乳酸脱氢酶.结果 BEAS-2B细胞经铀矿尘染毒后,细胞内和细胞外ROS含量明显增高,高剂量组细胞上清中超氧阴离子为(10.48±0.75)μmol/L,茶多酚保护组为(9.3l±0.71)μmol/L;细胞乳酸脱氢酶溢出,HPRT突变率升高,高剂量组细胞突变率为1.092%,茶多酚保护组为0.925‰,TPS对铀矿尘诱发的损伤有明显的抑制作用.结论 铀矿尘可造成细胞的氧化损伤,TPS通过清除活性氧而达到保护作用,可为铀矿尘损伤的防护提供有效措施.%Objective To observe oxidative damage of human bronchial epithelial cells (BEAS-2B) induced by uranium-mineral dust(UD) and protective effect of tea polyphenols(TPs). Methods The measurement of extracellular superoxide anions(O2 · - ) was based on the reduction of ferricytochrome C. The quantitation of extracellular hydrogen peroxides( H2O2 ) was based on horseradish peroxidase-dependent oxidation of phenol red. The determination of extracellular hydroxyl radicals(·OH) was based on the decoloration of safranine T. Ethidium bromide, 2,7'-dichlorofluorescein, and fluorescent products of membrane-permeable dyes-hydroethine and 2,7' -dichloroflurescein diacetate were used to monitor intracellular production of O2· and H2 O2 , respectively. The content of lactate dehydrogenase was measured by AUTOLAB. Cytokinesis-block( CB ) assay was used to detect the mutation frequency of

  7. Regional diffusing capacity in normal lungs during a slow exhalation.

    Science.gov (United States)

    MacIntyre, N R; Nadel, J A

    1982-06-01

    From an analysis of carbon monoxide uptake and xenon-133 distribution after two bolus inhalations of these gases, we calculated regional diffusing capacity in the upper and lower volume halves of the lungs during the middle 60% of an exhaled vital capacity in five seated normal subjects. We found that the regional diffusing capacity of the upper half of the lungs was 11.6 +/- 4.2 (mean +/- SD) ml.min-1.Torr-1 and that the regional diffusing capacity of the lower half of the lungs was 24.4 +/- 2.4 ml.min-1.Torr-1 after 25% of the vital capacity had been exhaled. These values remained relatively constant as lung volume decreased from 25 to 75% of the exhaled vital capacity. Diffusing capacity in the upper half of the lungs ranged from 9.4 to 12.4 ml.min-1.Torr-1 during exhalation, and in the lower half of the lungs from 21.0 to 28.6 ml.min-1.Torr-1 during exhalation. These results suggest that total lung diffusing capacity remains relatively constant over this midrange of lung volumes and that this occurs because the regional diffusing capacities in both the upper and lower halves of the lungs remain relatively constant.

  8. SILAC-based quantitative proteomic analysis of human lung cell response to copper oxide nanoparticles.

    Science.gov (United States)

    Edelmann, Mariola J; Shack, Leslie A; Naske, Caitlin D; Walters, Keisha B; Nanduri, Bindu

    2014-01-01

    Copper (II) oxide (CuO) nanoparticles (NP) are widely used in industry and medicine. In our study we evaluated the response of BEAS-2B human lung cells to CuO NP, using Stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics and phosphoproteomics. Pathway modeling of the protein differential expression showed that CuO NP affect proteins relevant in cellular function and maintenance, protein synthesis, cell death and survival, cell cycle and cell morphology. Some of the signaling pathways represented by BEAS-2B proteins responsive to the NP included mTOR signaling, protein ubiquitination pathway, actin cytoskeleton signaling and epithelial adherens junction signaling. Follow-up experiments showed that CuO NP altered actin cytoskeleton, protein phosphorylation and protein ubiquitination level.

  9. SILAC-based quantitative proteomic analysis of human lung cell response to copper oxide nanoparticles.

    Directory of Open Access Journals (Sweden)

    Mariola J Edelmann

    Full Text Available Copper (II oxide (CuO nanoparticles (NP are widely used in industry and medicine. In our study we evaluated the response of BEAS-2B human lung cells to CuO NP, using Stable isotope labeling by amino acids in cell culture (SILAC-based proteomics and phosphoproteomics. Pathway modeling of the protein differential expression showed that CuO NP affect proteins relevant in cellular function and maintenance, protein synthesis, cell death and survival, cell cycle and cell morphology. Some of the signaling pathways represented by BEAS-2B proteins responsive to the NP included mTOR signaling, protein ubiquitination pathway, actin cytoskeleton signaling and epithelial adherens junction signaling. Follow-up experiments showed that CuO NP altered actin cytoskeleton, protein phosphorylation and protein ubiquitination level.

  10. Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Pedersen, S S

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic change...

  11. Toxicity of aged gasoline exhaust particles to normal and diseased airway epithelia

    Science.gov (United States)

    Künzi, Lisa; Krapf, Manuel; Daher, Nancy; Dommen, Josef; Jeannet, Natalie; Schneider, Sarah; Platt, Stephen; Slowik, Jay G.; Baumlin, Nathalie; Salathe, Matthias; Prévôt, André S. H.; Kalberer, Markus; Strähl, Christof; Dümbgen, Lutz; Sioutas, Constantinos; Baltensperger, Urs; Geiser, Marianne

    2015-06-01

    Particulate matter (PM) pollution is a leading cause of premature death, particularly in those with pre-existing lung disease. A causative link between particle properties and adverse health effects remains unestablished mainly due to complex and variable physico-chemical PM parameters. Controlled laboratory experiments are required. Generating atmospherically realistic aerosols and performing cell-exposure studies at relevant particle-doses are challenging. Here we examine gasoline-exhaust particle toxicity from a Euro-5 passenger car in a uniquely realistic exposure scenario, combining a smog chamber simulating atmospheric ageing, an aerosol enrichment system varying particle number concentration independent of particle chemistry, and an aerosol deposition chamber physiologically delivering particles on air-liquid interface (ALI) cultures reproducing normal and susceptible health status. Gasoline-exhaust is an important PM source with largely unknown health effects. We investigated acute responses of fully-differentiated normal, distressed (antibiotics-treated) normal, and cystic fibrosis human bronchial epithelia (HBE), and a proliferating, single-cell type bronchial epithelial cell-line (BEAS-2B). We show that a single, short-term exposure to realistic doses of atmospherically-aged gasoline-exhaust particles impairs epithelial key-defence mechanisms, rendering it more vulnerable to subsequent hazards. We establish dose-response curves at realistic particle-concentration levels. Significant differences between cell models suggest the use of fully-differentiated HBE is most appropriate in future toxicity studies.

  12. TCDD promotes lung tumors via attenuation of apoptosis through activation of the Akt and ERK1/2 signaling pathways.

    Directory of Open Access Journals (Sweden)

    Rong-Jane Chen

    Full Text Available 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD is a multiple-site, multiple-species carcinogen that induces cancer in multiple organs. The molecular mechanisms underlying TCDD-induced lung tumorigenesis remain unclear. In the present study, a two-stage lung tumorigenesis model was established by administrating a single low dose of 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK combined with TCDD to female A/J mice. The results indicated that TCDD combined with low-dose NNK has a significant tumor-promoting effect compared with TCDD or low-dose NNK alone. Resistance to apoptosis is a hallmark of cancer and is thought to be one of the tumor-promoting mechanisms regulated by TCDD. We performed an additional series of experiments in the normal human bronchial epithelial cell line Beas2B cells, in which TCDD was combined with the apoptosis inducer staurosporine. Our in vitro results confirmed that TCDD could rescue cells from apoptosis induced by staurosporine. The inhibition of apoptosis is likely mediated by the activation of the Akt and ERK1/2 pathways, as determined by the effectiveness of pathway-specific inhibitors in abrogating the anti-apoptotic activity of TCDD. In conclusion, we demonstrated that TCDD promoted NNK-induced lung tumorigenesis and revealed that TCDD inhibits staurosporine-induced apoptosis, at least in part, through the Akt and ERK1/2 signaling pathways.

  13. TCDD promotes lung tumors via attenuation of apoptosis through activation of the Akt and ERK1/2 signaling pathways.

    Science.gov (United States)

    Chen, Rong-Jane; Siao, Shih-He; Hsu, Chung-Huei; Chang, Chu-Yung; Chang, Louis W; Wu, Chih-Hsiung; Lin, Pinpin; Wang, Ying-Jan

    2014-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a multiple-site, multiple-species carcinogen that induces cancer in multiple organs. The molecular mechanisms underlying TCDD-induced lung tumorigenesis remain unclear. In the present study, a two-stage lung tumorigenesis model was established by administrating a single low dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) combined with TCDD to female A/J mice. The results indicated that TCDD combined with low-dose NNK has a significant tumor-promoting effect compared with TCDD or low-dose NNK alone. Resistance to apoptosis is a hallmark of cancer and is thought to be one of the tumor-promoting mechanisms regulated by TCDD. We performed an additional series of experiments in the normal human bronchial epithelial cell line Beas2B cells, in which TCDD was combined with the apoptosis inducer staurosporine. Our in vitro results confirmed that TCDD could rescue cells from apoptosis induced by staurosporine. The inhibition of apoptosis is likely mediated by the activation of the Akt and ERK1/2 pathways, as determined by the effectiveness of pathway-specific inhibitors in abrogating the anti-apoptotic activity of TCDD. In conclusion, we demonstrated that TCDD promoted NNK-induced lung tumorigenesis and revealed that TCDD inhibits staurosporine-induced apoptosis, at least in part, through the Akt and ERK1/2 signaling pathways.

  14. Gremlin is overexpressed in lung adenocarcinoma and increases cell growth and proliferation in normal lung cells.

    Directory of Open Access Journals (Sweden)

    Michael S Mulvihill

    Full Text Available BACKGROUND: Gremlin, a member of the Dan family of BMP antagonists, is a glycosylated extracellular protein. Previously Gremlin has been shown to play a role in dorsal-ventral patterning, in tissue remodeling, and recently in angiogenesis. Evidence has previously been presented showing both over- and under-expression of Gremlin in different tumor tissues. Here, we sought to quantify expression of Gremlin in cancers of the lung and performed in vitro experiments to check whether Gremlin promotes cell growth and proliferation. METHODOLOGY/PRINCIPAL FINDINGS: Expression of Gremlin in 161 matched tumor and normal lung cancer specimens is quantified by quantitative real-time PCR and protein level is measured by immunohistochemistry. GREM1 was transfected into lung fibroblast and epithelial cell lines to assess the impact of overexpression of Gremlin in vitro. RESULTS: Lung adenocarcinoma but not squamous cell carcinoma shows a significant increase in Gremlin expression by mRNA and protein level. Lung fibroblast and epithelial cell lines transfected with GREM1 show significantly increased cell proliferation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that Gremlin acts in an oncogenic manner in lung adenocarcinoma and could hold promise as a new diagnostic marker or potential therapeutic target in lung AD or general thoracic malignancies.

  15. Inhibition of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus

    Directory of Open Access Journals (Sweden)

    Chang HB

    2015-08-01

    Full Text Available Hong-Bin Chang,1 Bing-Huei Chen1,21Department of Food Science, 2Graduate Institute of Medicine, Fu Jen Catholic University, Taipei, TaiwanAbstract: The objectives of this study were to explore the inhibition mechanism of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma longa Linnaeus. In addition, human bronchus epithelial cell line BEAS-2B (normal cell was selected for comparison. A high-performance liquid chromatography (HPLC method was developed to separate and quantify the various curcuminoids in C. longa extract, including curcumin (1,714.5 µg/mL, demethoxycurcumin (1,147.4 µg/mL, and bisdemethoxycurcumin (190.2 µg/mL. A high-stability nanoemulsion composed of Tween 80, water, and curcuminoid extract was prepared, with mean particle size being 12.6 nm. The cell cycle was retarded at G2/M for both the curcuminoid extract and nanoemulsion treatments; however, the inhibition pathway may be different. H460 cells were more susceptible to apoptosis than A549 cells for both curcuminoid extract and nanoemulsion treatments. Growth of BEAS-2B remained unaffected for both the curcuminoid extract and nanoemulsion treatments, with a concentration range from 1 to 4 µg/mL. Also, the activities of caspase-3, caspase-8, and caspase-9 followed a dose-dependent increase for both A549 and H460 cells for both the treatments, accompanied by a dose-dependent increase in cytochrome C expression and a dose-dependent decrease in CDK1 expression. Interestingly, a dose-dependent increase in cyclin B expression was shown for A549 cells for both the treatments, while a reversed trend was found for H460 cells. Both mitochondria and death receptor pathways may be responsible for apoptosis of both A549 and H460 cells.Keywords: curcuminoid extract, curcuminoid nanoemulsion, Curcuma longa Linnaeus, lung cancer cell, cell cycle, apoptosis mechanism

  16. Differences in gene expression and cytokine production by crystalline vs. amorphous silica in human lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Perkins Timothy N

    2012-02-01

    Full Text Available Abstract Background Exposure to respirable crystalline silica particles, as opposed to amorphous silica, is associated with lung inflammation, pulmonary fibrosis (silicosis, and potentially with lung cancer. We used Affymetrix/GeneSifter microarray analysis to determine whether gene expression profiles differed in a human bronchial epithelial cell line (BEAS 2B exposed to cristobalite vs. amorphous silica particles at non-toxic and equal surface areas (75 and 150 × 106μm2/cm2. Bio-Plex analysis was also used to determine profiles of secreted cytokines and chemokines in response to both particles. Finally, primary human bronchial epithelial cells (NHBE were used to comparatively assess silica particle-induced alterations in gene expression. Results Microarray analysis at 24 hours in BEAS 2B revealed 333 and 631 significant alterations in gene expression induced by cristobalite at low (75 and high (150 × 106μm2/cm2 amounts, respectively (p 6μm2/cm2 induced 108 significant gene changes. Bio-Plex analysis of 27 human cytokines and chemokines revealed 9 secreted mediators (p FOS, ATF3, IL6 and IL8 early and over time (2, 4, 8, and 24 h. Patterns of gene expression in NHBE cells were similar overall to BEAS 2B cells. At 75 × 106μm2/cm2, there were 339 significant alterations in gene expression induced by cristobalite and 42 by amorphous silica. Comparison of genes in response to cristobalite (75 × 106μm2/cm2 revealed 60 common, significant gene alterations in NHBE and BEAS 2B cells. Conclusions Cristobalite silica, as compared to synthetic amorphous silica particles at equal surface area concentrations, had comparable effects on the viability of human bronchial epithelial cells. However, effects on gene expression, as well as secretion of cytokines and chemokines, drastically differed, as the crystalline silica induced more intense responses. Our studies indicate that toxicological testing of particulates by surveying viability and

  17. Inhibition of normal human lung fibroblast growth by beryllium.

    Science.gov (United States)

    Lehnert, N M; Gary, R K; Marrone, B L; Lehnert, B E

    2001-03-07

    Inhalation of particulate beryllium (Be) and its compounds causes chronic Be disease (CBD) in a relatively small subset ( approximately 1-6%) of exposed individuals. Hallmarks of this pulmonary disease include increases in several cell types, including lung fibroblasts, that contribute to the fibrotic component of the disorder. In this regard, enhancements in cell proliferation appear to play a fundamental role in CBD development and progression. Paradoxically, however, some existing evidence suggests that Be actually has antiproliferative effects. In order to gain further information about the effects of Be on cell growth, we: (1) assessed cell proliferation and cell cycle effects of low concentrations of Be in normal human diploid fibroblasts, and (2) investigated the molecular pathway(s) by which the cell cycle disturbing effects of Be may be mediated. Treatment of human lung and skin fibroblasts with Be added in the soluble form of BeSO(4) (0.1-100 microM) caused inhibitions of their growth in culture in a concentration-dependent manner. Such growth inhibition was found to persist, even after cells were further cultured in Be(2+)-free medium. Flow cytometric analyses of cellular DNA labeled with the DNA-binding fluorochrome DAPI revealed that Be causes a G(0)-G(1)/pre-S phase arrest. Western blot analyses indicated that the Be-induced G(0)-G(1)/pre-S phase arrest involves elevations in TP53 (p53) and the cyclin-dependent kinase inhibitor CDKN1A (p21(Waf-1,Cip1)). That Be at low concentrations inhibits the growth of normal human fibroblasts suggests the possibility of the existence of abnormal cell cycle inhibitory responses to Be in individuals who are sensitive to the metal and ultimately develop CBD.

  18. Rituximab efficiently depletes B cells in lung tumors and normal lung tissue [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Albane Joly-Battaglini

    2016-01-01

    Full Text Available Rituximab is a monoclonal antibody that targets the CD20 B-cell-specific antigen and is widely used as therapy for B-cell lymphoma. Since rituximab depletes both malignant and normal B cells, it is increasingly being used to treat various conditions in which normal B cells have a pathogenic role, such as rheumatoid arthritis and multiple sclerosis. It is well-established that rituximab efficiently eliminates B cells in blood, lymph nodes, and spleen. In contrast, the effect of rituximab in non-lymphoid tissues remains poorly documented and is debated. Here, we report a rheumatoid arthritis patient who was treated with rituximab before receiving thoracic surgery for non-small cell lung cancer. Using flow cytometry and immunohistochemistry, we show that rituximab efficiently depleted CD20-positive B cells in a primary lung tumor, in lung-associated lymph nodes, and in normal lung tissue. We conclude that rituximab may be very efficient at depleting normal B cells in the lungs. This property of rituximab may potentially be exploited for the treatment of conditions in which pathogenic B cells reside in the lungs. On the other hand, the clearance of lung B cells may provide an explanation for the rare cases of severe non-infectious pulmonary toxicity of rituximab.

  19. MRI investigation of normal fetal lung maturation using signal intensities on different imaging sequences.

    Science.gov (United States)

    Balassy, Csilla; Kasprian, Gregor; Brugger, Peter C; Weber, Michael; Csapo, Bence; Mittermayer, Christoph; Hörmann, Marcus; Prayer, Daniela

    2007-03-01

    To purpose of this paper is to study the relation between normal lung maturation signal and changes in intensity ratios (SIR) and to determine which magnetic resonance imaging sequence provides the strongest correlation of normal lung SIs with gestational age. 126 normal singleton pregnancies (20-37 weeks) were examined with a 1.5 Tesla unit. Mean SIs for lungs, liver, and gastric fluid were assessed on six different sequences, and SIRs of lung/liver (LLSIR) and lung/gastric fluid (LGSIR) were correlated with gestational age for each sequence. To evaluate the feasibility of SIRs in the prediction of the state of the lung maturity, accuracy of the predicted SIRs (D*) was measured by calculating relative residuals (D*-D)/D for each sequence. LLSIRs showed significant changes in every sequence (p<0.05), while LGSIRs only on two sequences. Significant differences were shown for the mean of absolute residuals for both LLSIRs (p<0.001) and for LGSIRs (p=0.003). Relative residuals of LLSIRs were significantly smaller on T1-weighted sequence, whereas they were significantly higher for LGSIRs on FLAIR sequence. Fetal liver seems to be adequate reference for the investigation of lung maturation. T1-weighted sequence was the most accurate for the measurement of the lung SIs; thus, we propose to determine LLSIR on T1-weighted sequence when evaluating lung development.

  20. MRI investigation of normal fetal lung maturation using signal intensities on different imaging sequences

    Energy Technology Data Exchange (ETDEWEB)

    Balassy, Csilla; Kasprian, Gregor; Weber, Michael; Hoermann, Marcus; Prayer, Daniela [Medical University of Vienna, Department of Radiology, Vienna (Austria); Brugger, Peter C. [Medical University of Vienna, Center of Anatomy and Cell Biology, Vienna (Austria); Csapo, Bence [Medical University of Vienna, Department of Obstetrics and Gyneocology, Vienna (Austria); Mittermayer, Christoph [Medical University of Vienna, Department of Pediatrics, Vienna (Austria)

    2007-03-15

    To purpose of this paper is to study the relation between normal lung maturation signal and changes in intensity ratios (SIR) and to determine which magnetic resonance imaging sequence provides the strongest correlation of normal lung SIs with gestational age. 126 normal singleton pregnancies (20-37 weeks) were examined with a 1.5 Tesla unit. Mean SIs for lungs, liver, and gastric fluid were assessed on six different sequences, and SIRs of lung/liver (LLSIR) and lung/gastric fluid (LGSIR) were correlated with gestational age for each sequence. To evaluate the feasibility of SIRs in the prediction of the state of the lung maturity, accuracy of the predicted SIRs (D*) was measured by calculating relative residuals (D*-D)/D for each sequence. LLSIRs showed significant changes in every sequence (p<0.05), while LGSIRs only on two sequences. Significant differences were shown for the mean of absolute residuals for both LLSIRs (p<0.001) and for LGSIRs (p=0.003). Relative residuals of LLSIRs were significantly smaller on T1-weighted sequence, whereas they were significantly higher for LGSIRs on FLAIR sequence. Fetal liver seems to be adequate reference for the investigation of lung maturation. T1-weighted sequence was the most accurate for the measurement of the lung SIs; thus, we propose to determine LLSIR on T1-weighted sequence when evaluating lung development. (orig.)

  1. ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

    Science.gov (United States)

    Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

    2016-05-01

    ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells.

  2. Cavitary Lung Cancer Lined with Normal Bronchial Epithelium and Cancer Cells

    OpenAIRE

    Goto, Taichiro; Maeshima, Arafumi; Oyamada, Yoshitaka; Kato, Ryoichi

    2011-01-01

    Reports of cavitary lung cancer are not uncommon, and the cavity generally contains either dilated bronchi or cancer cells. Recently, we encountered a surgical case of cavitary lung cancer whose cavity tended to enlarge during long-term follow-up, and was found to be lined with normal bronchial epithelium and adenocarcinoma cells.

  3. Flow cytometric determination of stem/progenitor content in epithelial tissues: an example from nonsmall lung cancer and normal lung.

    Science.gov (United States)

    Donnenberg, Vera S; Landreneau, Rodney J; Pfeifer, Melanie E; Donnenberg, Albert D

    2013-01-01

    Single cell analysis and cell sorting has enabled the study of development, growth, differentiation, repair and maintenance of "liquid" tissues and their cancers. The application of these methods to solid tissues is equally promising, but several unique technical challenges must be addressed. This report illustrates the application of multidimensional flow cytometry to the identification of candidate stem/progenitor populations in non-small cell lung cancer and paired normal lung tissue. Seventeen paired tumor/normal lung samples were collected at the time of surgical excision and processed immediately. Tissues were mechanically and enzymatically dissociated into single cell suspension and stained with a panel of antibodies used for negative gating (CD45, CD14, CD33, glycophorin A), identification of epithelial cells (intracellular cytokeratin), and detection of stem/progenitor markers (CD44, CD90, CD117, CD133). DAPI was added to measure DNA content. Formalin fixed paraffin embedded tissue samples were stained with key markers (cytokeratin, CD117, DAPI) for immunofluorescent tissue localization of populations detected by flow cytometry. Disaggregated tumor and lung preparations contained a high proportion of events that would interfere with analysis, were they not eliminated by logical gating. We demonstrate how inclusion of doublets, events with hypodiploid DNA, and cytokeratin+ events also staining for hematopoietic markers reduces the ability to quantify epithelial cells and their precursors. Using the lung cancer/normal lung data set, we present an approach to multidimensional data analysis that consists of artifact removal, identification of classes of cells to be studied further (classifiers) and the measurement of outcome variables on these cell classes. The results of bivariate analysis show a striking similarity between the expression of stem/progenitor markers on lung tumor and adjacent tumor-free lung.

  4. Analysis of miRNA profiles identified miR-196a as a crucial mediator of aberrant PI3K/AKT signaling in lung cancer cells.

    Science.gov (United States)

    Guerriero, Ilaria; D'Angelo, Daniela; Pallante, Pierlorenzo; Santos, Mafalda; Scrima, Marianna; Malanga, Donatella; De Marco, Carmela; Ravo, Maria; Weisz, Alessandro; Laudanna, Carmelo; Ceccarelli, Michele; Falco, Geppino; Rizzuto, Antonia; Viglietto, Giuseppe

    2016-11-17

    Hyperactivation of the PI3K/AKT pathway is observed in most human cancer including lung carcinomas. Here we have investigated the role of miRNAs as downstream targets of activated PI3K/AKT signaling in Non Small Cell Lung Cancer (NSCLC). To this aim, miRNA profiling was performed in human lung epithelial cells (BEAS-2B) expressing active AKT1 (BEAS-AKT1-E17K), active PI3KCA (BEAS-PIK3CA-E545K) or with silenced PTEN (BEAS-shPTEN).Twenty-four differentially expressed miRNAs common to BEAS-AKT1-E17K, BEAS-PIK3CA-E545K and BEAS-shPTEN cells were identified through this analysis, with miR-196a being the most consistently up-regulated miRNA. Interestingly, miR-196a was significantly overexpressed also in human NSCLC-derived cell lines (n=11) and primary lung cancer samples (n=28).By manipulating the expression of miR-196a in BEAS-2B and NCI-H460 cells, we obtained compelling evidence that this miRNA acts downstream the PI3K/AKT pathway, mediating some of the proliferative, pro-migratory and tumorigenic activity that this pathway exerts in lung epithelial cells, possibly through the regulation of FoxO1, CDKN1B (hereafter p27) and HOXA9.

  5. Antitumor effect of afatinib, as a human epidermal growth factor receptor 2-targeted therapy, in lung cancers harboring HER2 oncogene alterations.

    Science.gov (United States)

    Suzawa, Ken; Toyooka, Shinichi; Sakaguchi, Masakiyo; Morita, Mizuki; Yamamoto, Hiromasa; Tomida, Shuta; Ohtsuka, Tomoaki; Watanabe, Mototsugu; Hashida, Shinsuke; Maki, Yuho; Soh, Junichi; Asano, Hiroaki; Tsukuda, Kazunori; Miyoshi, Shinichiro

    2016-01-01

    Human epidermal growth factor receptor 2 (HER2) is a member of the HER family of proteins containing four receptor tyrosine kinases. It plays an important role in the pathogenesis of certain human cancers. In non-small-cell lung cancer (NSCLC), HER2 amplification or mutations have been reported. However, little is known about the benefit of HER2-targeted therapy for NSCLCs harboring HER2 alterations. In this study, we investigated the antitumor effect of afatinib, an irreversible epidermal growth factor receptor (EGFR)-HER2 dual inhibitor, in lung cancers harboring HER2 oncogene alterations, including novel HER2 mutations in the transmembrane domain, which we recently identified. Normal bronchial epithelial cells, BEAS-2B, ectopically overexpressing wild-type HER2 or mutants (A775insYVMA, G776VC, G776LC, P780insGSP, V659E, and G660D) showed constitutive autophosphorylation of HER2 and activation of downstream signaling. They were sensitive to afatinib, but insensitive to gefitinib. Furthermore, we examined the antitumor activity of afatinib and gefitinib in several NSCLC cell lines, and investigated the association between their genetic alterations and sensitivity to afatinib treatment. In HER2-altered NSCLC cells (H2170, Calu-3, and H1781), afatinib downregulated the phosphorylation of HER2 and EGFR as well as their downstream signaling, and induced an antiproliferative effect through G1 arrest and apoptotic cell death. In contrast, HER2- or EGFR-non-dependent NSCLC cells were insensitive to afatinib. In addition, these effects were confirmed in vivo by using a xenograft mouse model of HER2-altered lung cancer cells. Our results suggest that afatinib is a therapeutic option as a HER2-targeted therapy for NSCLC harboring HER2 amplification or mutations.

  6. Curcumin increases exosomal TCF21 thus suppressing exosome-induced lung cancer

    Science.gov (United States)

    Zeng, Chao; Wu, Da; Mu, Zhimin; Chen, Baokun; Xie, Yuancai; Ye, Yiwang; Liu, Jixian

    2016-01-01

    Curcumin is a novel drug for lung cancer treatment. However, the mechanism underlying the anti-tumor effect of curcumin remains elusive. Previous evidences indicated that, the methylating transferase DNMT1 is downregulated by curcumin, and the transcription factor 21 (TCF21) is suppressed by DNMT1. We hereby attempt to elucidate the correlation between curcumin treatment and TCF21 expression. Exosomes derived from curcumin-pretreated H1299 cells were used to treat BEAS-2B cells, which induced proliferation, colony formation and migration of BEAS-2B cells. An increase in TCF21 expression in response to curcumin was also seen, as revealed by real-time PCR (RT-PCR) and western blot. Analysis using the GEO database (access #GSE21210) indicated that a positive correlation existed between TCF21 levels and lung cancer patient survival. TCF21 overexpression and knockdown was introduced to H1299 cells through lentiviral system, which led to suppression and promotion of tumor growth, respectively. We also demonstrated that DNMT1 expression was downregulated by curcumin. Therefore, curcumin exerts its anti-cancer function by downregulating DNMT1, thereby upregulating TCF21. PMID:27894084

  7. Inflammatory Response and Barrier Dysfunction by Different e-Cigarette Flavoring Chemicals Identified by Gas Chromatography–Mass Spectrometry in e-Liquids and e-Vapors on Human Lung Epithelial Cells and Fibroblasts

    Science.gov (United States)

    Gerloff, Janice; Sundar, Isaac K.; Freter, Robert; Sekera, Emily R.; Friedman, Alan E.; Robinson, Risa; Pagano, Todd

    2017-01-01

    Abstract Recent studies suggest that electronic cigarette (e-cig) flavors can be harmful to lung tissue by imposing oxidative stress and inflammatory responses. The potential inflammatory response by lung epithelial cells and fibroblasts exposed to e-cig flavoring chemicals in addition to other risk-anticipated flavor enhancers inhaled by e-cig users is not known. The goal of this study was to evaluate the release of the proinflammatory cytokine (interleukin-8 [IL-8]) and epithelial barrier function in response to different e-cig flavoring chemicals identified in various e-cig e-liquid flavorings and vapors by chemical characterization using gas chromatography–mass spectrometry analysis. Flavorings, such as acetoin (butter), diacetyl, pentanedione, maltol (malt), ortho-vanillin (vanilla), coumarin, and cinnamaldehyde in comparison with tumor necrosis factor alpha (TNFα), were used in this study. Human bronchial epithelial cells (Beas2B), human mucoepidermoid carcinoma epithelial cells (H292), and human lung fibroblasts (HFL-1) were treated with each flavoring chemical for 24 hours. The cells and conditioned media were then collected and analyzed for toxicity (viability %), lung epithelial barrier function, and proinflammatory cytokine IL-8 release. Cell viability was not significantly affected by any of the flavoring chemicals tested at a concentration of 10 μM to 1 mM. Acetoin and diacetyl treatment induced IL-8 release in Beas2B cells. Acetoin- and pentanedione-treated HFL-1 cells produced a differential, but significant response for IL-8 release compared to controls and TNFα. Flavorings, such as ortho-vanillin and maltol, induced IL-8 release in Beas2B cells, but not in H292 cells. Of all the flavoring chemicals tested, acetoin and maltol were more potent inducers of IL-8 release than TNFα in Beas2B and HFL-1 cells. Flavoring chemicals rapidly impaired epithelial barrier function in human bronchial epithelial cells (16-HBE) as measured by electric cell

  8. The distribution of amosite asbestos in the periphery of the normal human lung.

    OpenAIRE

    Churg, A

    1990-01-01

    Although theoretical models and experiments on animals exist that predict the distribution of asbestos fibres in the lung, there are few studies in man that relate to this question and they have generated contradictory results. To examine this distribution analytical electron microscopy was employed to determine the amosite fibre concentration, size, surface area, and mass in 29 circumferential sites around the periphery of a mid-sagittal slice from nine morphologically normal left lungs of h...

  9. Automatic Classification of Normal and Cancer Lung CT Images Using Multiscale AM-FM Features.

    Science.gov (United States)

    Magdy, Eman; Zayed, Nourhan; Fakhr, Mahmoud

    2015-01-01

    Computer-aided diagnostic (CAD) systems provide fast and reliable diagnosis for medical images. In this paper, CAD system is proposed to analyze and automatically segment the lungs and classify each lung into normal or cancer. Using 70 different patients' lung CT dataset, Wiener filtering on the original CT images is applied firstly as a preprocessing step. Secondly, we combine histogram analysis with thresholding and morphological operations to segment the lung regions and extract each lung separately. Amplitude-Modulation Frequency-Modulation (AM-FM) method thirdly, has been used to extract features for ROIs. Then, the significant AM-FM features have been selected using Partial Least Squares Regression (PLSR) for classification step. Finally, K-nearest neighbour (KNN), support vector machine (SVM), naïve Bayes, and linear classifiers have been used with the selected AM-FM features. The performance of each classifier in terms of accuracy, sensitivity, and specificity is evaluated. The results indicate that our proposed CAD system succeeded to differentiate between normal and cancer lungs and achieved 95% accuracy in case of the linear classifier.

  10. An experimental randomized study of six different ventilatory modes in a piglet model with normal lungs

    DEFF Research Database (Denmark)

    Nielsen, J B; Sjöstrand, U H; Henneberg, S W

    1991-01-01

    A randomized study of 6 ventilatory modes was made in 7 piglets with normal lungs. Using a Servo HFV 970 (prototype system) and a Servo ventilator 900 C the ventilatory modes examined were as follows: SV-20V, i.e. volume-controlled intermittent positive-pressure ventilation (IPPV); SV-20VIosc, i...

  11. Effect of regional lung inflation on ventilation heterogeneity at different length scales during mechanical ventilation of normal sheep lungs.

    Science.gov (United States)

    Wellman, Tyler J; Winkler, Tilo; Costa, Eduardo L V; Musch, Guido; Harris, R Scott; Venegas, Jose G; Vidal Melo, Marcos F

    2012-09-01

    Heterogeneous, small-airway diameters and alveolar derecruitment in poorly aerated regions of normal lungs could produce ventilation heterogeneity at those anatomic levels. We modeled the washout kinetics of (13)NN with positron emission tomography to examine how specific ventilation (sV) heterogeneity at different length scales is influenced by lung aeration. Three groups of anesthetized, supine sheep were studied: high tidal volume (Vt; 18.4 ± 4.2 ml/kg) and zero end-expiratory pressure (ZEEP) (n = 6); low Vt (9.2 ± 1.0 ml/kg) and ZEEP (n = 6); and low Vt (8.2 ± 0.2 ml/kg) and positive end-expiratory pressure (PEEP; 19 ± 1 cmH(2)O) (n = 4). We quantified fractional gas content with transmission scans, and sV with emission scans of infused (13)NN-saline. Voxel (13)NN-washout curves were fit with one- or two-compartment models to estimate sV. Total heterogeneity, measured as SD[log(10)(sV)], was divided into length-scale ranges by measuring changes in variance of log(10)(sV), resulting from progressive filtering of sV images. High-Vt ZEEP showed higher sV heterogeneity at 36-mm (r = -0.72) length scales (P < 0.001). We conclude that sV heterogeneity at length scales <60 mm increases in poorly aerated regions of mechanically ventilated normal lungs, likely due to heterogeneous small-airway narrowing and alveolar derecruitment. PEEP reduces sV heterogeneity by maintaining lung expansion and airway patency at those small length scales.

  12. Unbiased Selection of Peptide-Peptoid Hybrids Specific for Lung Cancer Compared to Normal Lung Epithelial Cells.

    Science.gov (United States)

    Matharage, Jaya M; Minna, John D; Brekken, Rolf A; Udugamasooriya, D Gomika

    2015-12-18

    To develop widely applicable diagnostic and potentially therapeutic approaches overcoming protein heterogeneity in human cancer, we have developed a technology to unbiasedly select high specificity compound(s) that bind any biomolecule (e.g., proteins, lipids, carbohydrates) presented on the cancer cell surface but not on normal cells. We utilized a peptidomimetic based on-bead two-color (OBTC) combinatorial cell screen that can detect differences between two cell surfaces at high accuracy by looking for beads (where each bead in the library had one peptide-peptoid hybrid on the surface) that only bound cancer but not normal cells. We screened a library of 393 216 compounds targeting HCC4017 lung adenocarcinoma cells (labeled in red) in the presence of HBEC30KT normal bronchial epithelial cells (labeled in green) derived from the same tissue of the same patient. This screen identified a peptide-peptoid hybrid called PPS1 which displayed high specific binding for HCC4017 cancer cells over HBEC30KT cells. Specificity was validated through on-bead, ELISA-like and magnetic bead pulldown studies, while a scrambled version of PPS1 did not show any binding. Of interest, the simple dimeric version (PPS1D1) displayed cytotoxic activity on HCC4017 cells, but not on normal HBEC30KT cells. PPS1D1 also strongly accumulated in HCC4017 lung cancer xenografts in mice over control constructs. We conclude that such combinatorial screens using tumor and normal cells from the same patient have significant potential to develop new reagents for cancer biology, diagnosis, and potentially therapy.

  13. Imaging and Pathological Features of Percutaneous Cryosurgery on Normal Lung Evaluated in a Porcine Model

    Directory of Open Access Journals (Sweden)

    Lizhi NIU

    2010-07-01

    Full Text Available Background and objective Lung cancer is one of the most commonly occurring malignancies and frequent causes of death in the world. Cryoablation is a safe and alternative treatment for unresectable lung cancer. Due to the lung being gas-containing organ and different from solid organs such as liver and pancreas, it is difficult to achieve the freezing range of beyond the tumor edge 1 cm safety border. The aim of this study is to examine the effect of different numbers of freeze cycles on the effectiveness of cryoablation on normal lung tissue and to create an operation guideline that gives the best effect. Methods Six healthy Tibetan miniature pigs were given a CT scan and histological investigation after percutaneous cryosurgery. Cryoablation was performed as 2 cycles of 10 min of active freezing in the left lung; each freeze followed by a 5 min thaw. In the right lung, we performed the same 2 cycles of 5 min of freezing followed by 5 min of thawing. However, for the right lung, we included a third cycle of consisting of 10 min of freezing followed by 5 min of thawing. Three cryoprobes were inserted into the left lung and three cryoprobes in the right lung per animal, one in the upper and two in the lower lobe, so as to be well away from each other. Comparison under the same experimental condition was necessary. During the experiment, observations were made regarding the imaging change of ice-ball. The lungs were removed postoperatively at 3 intervals: 4 h, 3 d of postoperation and 7 d of postoperation, respectively, to view microscopic and pathological change. Results The ice-ball grew gradually in relation to the increase in time, and the increase in number of cycles. The size of the cryolesion (hypothesis necrotic area in specimens, over time, became larger in size than the size of the ice-ball during operation, regardless of whether 2 or 3 freeze-thaw cycles were performed. The area of necrosis was gradually increased over the course of time

  14. Classification of normal and cancerous lung tissues by electrical impendence tomography.

    Science.gov (United States)

    Gao, Jianling; Yue, Shihong; Chen, Jun; Wang, Huaxiang

    2014-01-01

    Biological tissue impedance spectroscopy can provide rich physiological and pathological information by measuring the variation of the complex impedance of biological tissues under various frequencies of driven current. Electrical Impedance Tomography (EIT) technique can measure the impedance spectroscopy of biological tissue in medical field. Before application, a key problem must be solved on how to generally distinguish normal tissues from the cancerous in terms of measurable EIT data. In this paper, the impedance spectroscopy characteristics of human lung tissue are studied. On the basis of the measured data of 109 lung cancer patients, Cole-Cole Circle radius (CCCR) and the complex modulus are extracted. In terms of the two characteristics, 71.6% and 66.4% samples of cancerous and normal tissues can be correctly classified, respectively. Furthermore, two characteristics of the measured EIT data of each patient consist of a two-dimensional vector and all such vectors comprise a set of vectors. When classifying the vector set, the rate of correctly partitioning normal and cancerous tissues can be raised to 78.2%. The main factors to affect the classification results on normal and cancerous tissues are generally analyzed. The proposed method will play an important role in further working out an efficient and feasible diagnostic method for potential lung cancer patients, and provide theoretical basis and reference data for electrical impedance tomography technology in monitoring pulmonary function.

  15. FTIR characterization of animal lung cells: normal and precancerous modified e10 cell line

    Science.gov (United States)

    Zezell, D. M.; Pereira, T. M.; Mennecier, G.; Bachmann, L.; Govone, A. B.; Dagli, M. L. Z.

    2012-06-01

    The chemical carcinogens from tobacco are related to over 90% of lung cancers around the world. The risk of death of this kind of cancer is high because the diagnosis usually is made only in advanced stages. Therefore, it is necessary to develop new diagnostic methods for detecting the lung cancer in earlier stages. The Fourier Transform Infrared Spectroscopy (FTIR) can offer high sensibility and accuracy to detect the minimal chemical changes into the biological sample. The aim of this study is to evaluate the differences on infrared spectra between normal lung cells and precancerous lung cells transformed by NNK. Non-cancerous lung cell line e10 (ATCC) and NNK-transformed e10 cell lines were maintained in complete culture medium (1:1 mixture of Dulbecco's modified Eagle's medium and Ham's F12 [DMEM/Ham's F12], supplemented with 100 ng/ml cholera enterotoxin, 10 lg/ml insulin, 0.5 lg/ml. hydrocortisol, 20 ng/ml epidermal growth factor, and 5% horse serum. The cultures were maintained in alcohol 70%. The infrared spectra were acquired on ATR-FTIR Nicolet 6700 spectrophotometer at 4 cm-1 resolution, 30 scans, in the 1800-900 cm-1 spectral range. Each sample had 3 spectra recorded, 30 infrared spectra were obtained from each cell line. The second derivate of spectra indicates that there are displacement in 1646 cm-1 (amine I) and 1255 cm-1(DNA), allowing the possibility to differentiate the two king of cells, with accuracy of 89,9%. These preliminary results indicate that ATR-FTIR is useful to differentiate normal e10 lung cells from precancerous e10 transformed by NNK.

  16. Spontaneous rupture of a normal spleen following bronchoplastic left lung lower lobectomy.

    Science.gov (United States)

    Stupnik, Tomaz; Vidmar, Stanko; Hari, Petra

    2008-04-01

    Rupture of the spleen is a common event associated with trauma, infectious diseases, neoplasia and many systemic disorders affecting the reticuloendothelial system. A rare subtype of rupture occurring spontaneously and arising from a normal spleen was recognized as a distinct clinicopathologic entity. It has been reported in association with trivial insults such as vomiting and coughing. We report a case of a patient with spontaneous rupture of a normal spleen observed after severe coughing on the 3rd postoperative day following bronchoplastic left lung lower lobectomy combined with S4, S5 segmentectomy.

  17. Differential Response of Mono Mac 6, BEAS-2B, and Jurkat Cells to Indoor Dust

    OpenAIRE

    Riechelmann, Herbert; Deutschle, Tom; Grabow, Ariane; Heinzow, Birger; Butte, Werner; Reiter, Rudolf

    2007-01-01

    Background Airway toxicity of indoor dust is not sufficiently understood. Objectives Our goal in this study was to describe the effects of indoor dust on human monocyte, epithelial, and lymphocyte cell lines. We aimed to a) obtain a comprehensive and intelligible outline of the transcriptional response; b) correlate differential transcription with cellular protein secretion; c) identify cell line–specific features; and d) search for indoor dust–specific responses. Methods Settled dust was sam...

  18. Study of fractal dimension in chest images using normal and interstitial lung disease cases

    Science.gov (United States)

    Tucker, Douglas M.; Correa, Jose L.; Souto, Miguel; Malagari, Katerina S.

    1993-09-01

    A quantitative computerized method which provides accurate discrimination between chest radiographs with positive findings of interstitial disease patterns and normal chest radiographs may increase the efficacy of radiologic screening of the chest and the utility of digital radiographic systems. This report is a comparison of fractal dimension measured in normal chest radiographs and in radiographs with abnormal lungs having reticular, nodular, reticulonodular and linear patterns of interstitial disease. Six regions of interest (ROI's) from each of 33 normal chest radiographs and 33 radiographs with positive findings of interstitial disease were studied. Results indicate that there is a statistically significant difference between the distribution of the fractal dimension in normal radiographs and radiographs where disease is present.

  19. FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung.

    Science.gov (United States)

    Falvella, Felicia S; Frullanti, Elisa; Galvan, Antonella; Spinola, Monica; Noci, Sara; De Cecco, Loris; Nosotti, Mario; Santambrogio, Luigi; Incarbone, Matteo; Alloisio, Marco; Calabrò, Elisa; Pastorino, Ugo; Skaug, Vidar; Haugen, Aage; Taioli, Emanuela; Dragani, Tommaso A

    2009-06-15

    The association of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism with clinical stage and overall survival in a series of 541 Italian lung adenocarcinoma (ADCA) patients indicated a significantly decreased survival in patients carrying the rare Arg388 allele as compared to that in Gly/Gly homozygous patients [hazard ratio (HR) = 1.5; 95% confidence interval (CI) 1.1-1.9], with the decrease related to the association of the same polymorphism with clinical stage (HR = 1.8, 95% CI 1.3-2.6). By contrast, no significant association was detected in small series of either Norwegian lung ADCA patients or Italian lung squamous cell carcinoma (SQCC) patients. Single nucleotide polymorphisms of known FGFR4 ligands expressed in lung (FGF9, FGF18 and FGF19) were not associated with clinical stage or survival and showed no interaction with FGFR4. Analysis of gene expression profile in normal lungs according to FGFR4 genotype indicated a specific transcript pattern associated with the allele carrier status, suggesting a functional role for the FGFR4 polymorphism already detectable in normal lung. These findings confirm the significant association of the FGFR4 Gly388Arg polymorphism with clinical stage and overall survival in an Italian lung ADCA population and demonstrate a FGFR4 genotype-dependent transcriptional profile present in normal lung tissue.

  20. Physico-chemical properties based differential toxicity of graphene oxide/reduced graphene oxide in human lung cells mediated through oxidative stress

    Science.gov (United States)

    Mittal, Sandeep; Kumar, Veeresh; Dhiman, Nitesh; Chauhan, Lalit Kumar Singh; Pasricha, Renu; Pandey, Alok Kumar

    2016-12-01

    Goraphene derivatives (GD) are currently being evaluated for technological and biomedical applications owing to their unique physico-chemical properties over other carbon allotrope such as carbon nanotubes (CNTs). But, the possible association of their properties with underlying in vitro effects have not fully examined. Here, we assessed the comparative interaction of three GD - graphene oxide (GO), thermally reduced GO (TRGO) and chemically reduced GO (CRGO), which significantly differ in their lateral size and functional groups density, with phenotypically different human lung cells; bronchial epithelial cells (BEAS-2B) and alveolar epithelial cells (A549). The cellular studies demonstrate that GD significantly ineternalize and induce oxidative stress mediated cytotoxicity in both cells. The toxicity intensity was in line with the reduced lateral size and increased functional groups revealed more toxicity potential of TRGO and GO respectively. Further, A549 cells showed more susceptibility than BEAS-2B which reflected cell type dependent differential cellular response. Molecular studies revealed that GD induced differential cell death mechanism which was efficiently prevented by their respective inhibitors. This is prior study to the best of our knowledge involving TRGO for its safety evaluation which provided invaluable information and new opportunities for GD based biomedical applications.

  1. Normal Expiratory Flow Rate and Lung Volumes in Patients with Combined Emphysema and Interstitial Lung Disease: A Case Series and Literature Review

    Directory of Open Access Journals (Sweden)

    Karen L Heathcote

    2011-01-01

    Full Text Available Pulmonary function tests in patients with idiopathic pulmonary fibrosis characteristically show a restrictive pattern including small lung volumes and increased expiratory flow rates resulting from a reduction in pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. When the diseases coexist, pulmonary volumes are compensated, and a smaller than expected reduction or even normal lung volumes can be found. The present report describes 10 patients with progressive breathlessness, three of whom experienced severe limitation in their quality of life. All patients showed lung interstitial involvement and emphysema on computed tomography scan of the chest. The 10 patients showed normal spirometry and lung volumes with severe compromise of gas exchange. Normal lung volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

  2. Prenatal assessment of normal fetal pulmonary grey-scale and lung volume by three-dimensional ultrasonography

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To quantitatively analyze the fetal lung echo and right lung volume in the third trimester by real-time three-dimensional ultrasound(3-D US)and evaluate the feasibility of fetal lung maturity.Methods A total of 732 women with normal singleton pregnancies between 28 and 42 weeks of gestation underwent ultrasound examination.The 3-D US equipment with a 3.5-5 MHz transabdominal transducer was used for the fetal biometric measurement.The echogenicity ratio between fetal lung and liver was compared.The...

  3. Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory and immune response genes.

    Science.gov (United States)

    Boggaram, Vijay; Loose, David S; Gottipati, Koteswara R; Natarajan, Kartiga; Mitchell, Courtney T

    2016-04-01

    The intensification and concentration of animal production operations expose workers to high levels of organic dusts in the work environment. Exposure to organic dusts is a risk factor for the development of acute and chronic respiratory symptoms and diseases. Lung epithelium plays important roles in the control of immune and inflammatory responses to environmental agents to maintain lung health. To better understand the effects of organic dust on lung inflammatory responses, we characterized the gene expression profiles of A549 alveolar and Beas2B bronchial epithelial and THP-1 monocytic cells influenced by exposure to poultry dust extract by DNA microarray analysis using Illumina Human HT-12 v4 Expression BeadChip. We found that A549 alveolar and Beas2B bronchial epithelial and THP-1 cells responded with unique changes in the gene expression profiles with regulation of genes encoding inflammatory cytokines, chemokines, and other inflammatory proteins being common to all the three cells. Significantly induced genes included IL-8, IL-6, IL-1β, ICAM-1, CCL2, CCL5, TLR4, and PTGS2. Validation by real-time qRT-PCR, ELISA, Western immunoblotting, and immunohistochemical staining of lung sections from mice exposed to dust extract validated DNA microarray results. Pathway analysis indicated that dust extract induced changes in gene expression influenced functions related to cellular growth and proliferation, cell death and survival, and cellular development. These data show that a broad range of inflammatory mediators produced in response to poultry dust exposure can modulate lung immune and inflammatory responses. This is the first report on organic dust induced changes in expression profiles in lung epithelial and THP-1 monocytic cells.

  4. SU-E-J-190: Characterization of Radiation Induced CT Number Changes in Tumor and Normal Lung During Radiation Therapy for Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, C; Liu, F; Tai, A; Gore, E; Johnstone, C; Li, X [Medical College of Wisconsin Milwaukee WI (United States)

    2014-06-01

    Purpose: To measure CT number (CTN) changes in tumor and normal lung as a function of radiation therapy (RT) dose during the course of RT delivery for lung cancer using daily IGRT CT images and single respiration phase CT images. Methods: 4D CT acquired during planning simulation and daily 3D CT acquired during daily IGRT for 10 lung cancer cases randomly selected in terms of age, caner type and stage, were analyzed using an in-house developed software tool. All patients were treated in 2 Gy fractions to primary tumors and involved nodal regions. Regions enclosed by a series of isodose surfaces in normal lung were delineated. The obtained contours along with target contours (GTVs) were populated to each singlephase planning CT and daily CT. CTN in term of Hounsfield Unit (HU) of each voxel in these delineated regions were collectively analyzed using histogram, mean, mode and linear correlation. Results: Respiration induced normal lung CTN change, as analyzed from single-phase planning CTs, ranged from 9 to 23 (±2) HU for the patients studied. Normal lung CTN change was as large as 50 (±12) HU over the entire treatment course, was dose and patient dependent and was measurable with dose changes as low as 1.5 Gy. For patients with obvious tumor volume regression, CTN within the GTV drops monotonically as much as 10 (±1) HU during the early fractions with a total dose of 20 Gy delivered. The GTV and CTN reductions are significantly correlated with correlation coefficient >0.95. Conclusion: Significant RT dose induced CTN changes in lung tissue and tumor region can be observed during even the early phase of RT delivery, and may potentially be used for early prediction of radiation response. Single respiration phase CT images have dramatically reduced statistical noise in ROIs, making daily dose response evaluation possible.

  5. Quantitative evaluation of berberine subcellular distribution and cellular accumulation in non-small cell lung cancer cells by UPLC-MS/MS.

    Science.gov (United States)

    Yuan, Zhong-Wen; Leung, Elaine Lai-Han; Fan, Xing-Xing; Zhou, Hua; Ma, Wen-Zhe; Liu, Liang; Xie, Ying

    2015-11-01

    Berberine, an isoquinoline alkaloid, has been demonstrated to be a safe anti-cancer agent with multiple effects on mitochondria. Intracellular concentration and distribution around the targeting sites are determinants of efficacy, but subcellular distribution of berberine has not been fully elucidated yet, which relies on the sensitive and robustness assay. In this study, a sensitive and robust UPLC-MS/MS method has been developed and validated with optimized extraction solvents and detection conditions. Key factors such as the purity and integrity of isolated organelle fractions, and the effects of isolation procedures on the subcellular concentration of berberine were systemically evaluated. With the developed assay, we found that the intracellular accumulations of berberine in two gefitinib resistant NSCLC cell lines H1650 and H1975 were 2-3 folds higher than that of normal epithelial cells BEAS-2B. Moreover, significantly different subcellular distribution profiles in NSCLC cancer cells from that of BEAS-2B cells with a striking increase in content in most organelles may contribute to its selective cytotoxicity to cancer cells. Furthermore, a predominant accumulation of berberine was observed for the first time in microsomal fraction for all three cell lines. Therefore, this method could be used for quantitative evaluation of subcellular distribution and cellular accumulation of berberine and for further evaluation of the concentration-effects relationship.

  6. Fetal lung development on MRI. Normal course and impairment due to premature rupture of membranes; Fetale Lungenentwicklung in der MRT. Normaler Verlauf und Beeintraechtigung durch vorzeitigen Blasensprung

    Energy Technology Data Exchange (ETDEWEB)

    Kasprian, G. [Medizinische Universitaet Wien (Austria). Klinik fuer Radiodiagnostik; Zentrum fuer Anatomie und Zellbiologie der Medizinischen Universitaet Wien (Austria). Arbeitsgruppe Integrative Morphologie; Brugger, P.C. [Zentrum fuer Anatomie und Zellbiologie der Medizinischen Universitaet Wien (Austria). Arbeitsgruppe Integrative Morphologie; Helmer, H.; Langer, M. [Medizinische Universitaet Wien (Austria). Klinik fuer Frauenheilkunde; Balassy, C.; Prayer, D. [Medizinische Universitaet Wien (Austria). Klinik fuer Radiodiagnostik

    2006-02-15

    A well-organized interplay between many molecular factors as well as mechanical forces influence fetal lung development. At the end of this complex process a sufficiently sized and structurally mature organ should ensure the postnatal survival of the newborn. Besides prenatal ultrasonography, magnetic resonance imaging (MRI) can now be used to investigate normal and pathological human lung growth in utero. Oligohydramnios, due to premature rupture of membranes (PROM), is an important risk factor for compromised fetal lung growth. In these situations MR volumetry can be used to measure the size of the fetal lung quite accurately. Together with the evaluation of lung signal intensities on T2-weighted sequences, fetuses with pulmonary hypoplasia can be readily detected. (orig.) [German] Die fetale Lungenentwicklung wird einerseits durch eine Vielzahl molekularer Faktoren und andererseits durch mechanisch-physiologische Kraefte beeinflusst. Ein geordnetes Zusammenspiel dieser Mechanismen fuehrt zu einem ausreichend grossen und strukturell reifen Organ, das sofort nach der Geburt das Ueberleben des Neugeborenen sicherstellt. Neben der praenatalen Ultraschalluntersuchung bietet nun auch die Magnetresonanztomographie (MRT) die Moeglichkeit, die normale und pathologische fetale Lungenentwicklung zu untersuchen. Ein wesentlicher Risikofaktor fuer eine Beeintraechtigung der Lungenentwicklung ist die verminderte Fruchtwassermenge nach vorzeitigem Blasensprung. In diesen Faellen kann die MR-Volumetrie dazu eingesetzt werden, die Groesse der fetalen Lungen relativ genau zu bestimmen. Gemeinsam mit der Beurteilung der MR-Signalintensitaeten des Lungengewebes auf T2-gewichteten Sequenzen koennen Feten mit hypoplastischen Lungen mit zunehmender Sicherheit bereits praenatal identifiziert werden. (orig.)

  7. Vasomotor tone does not affect perfusion heterogeneity and gas exchange in normal primate lungs during normoxia

    Science.gov (United States)

    Glenny, R. W.; Robertson, H. T.; Hlastala, M. P.

    2000-01-01

    To determine whether vasoregulation is an important cause of pulmonary perfusion heterogeneity, we measured regional blood flow and gas exchange before and after giving prostacyclin (PGI(2)) to baboons. Four animals were anesthetized with ketamine and mechanically ventilated. Fluorescent microspheres were used to mark regional perfusion before and after PGI(2) infusion. The lungs were subsequently excised, dried inflated, and diced into approximately 2-cm(3) pieces (n = 1,208-1,629 per animal) with the spatial coordinates recorded for each piece. Blood flow to each piece was determined for each condition from the fluorescent signals. Blood flow heterogeneity did not change with PGI(2) infusion. Two other measures of spatial blood flow distribution, the fractal dimension and the spatial correlation, did not change with PGI(2) infusion. Alveolar-arterial O(2) differences did not change with PGI(2) infusion. We conclude that, in normal primate lungs during normoxia, vasomotor tone is not a significant cause of perfusion heterogeneity. Despite the heterogeneous distribution of blood flow, active regulation of regional perfusion is not required for efficient gas exchange.

  8. SU-E-T-572: Normal Lung Tissue Sparing in Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hong, C; Ju, S; Ahn, Y [Samsung Medical Center, Seoul (Korea, Republic of)

    2015-06-15

    Purpose: To compare normal lung-sparing capabilities of three advanced radiation therapy techniques for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Four-dimensional computed tomography (4DCT) was performed in 10 patients with stage IIIb LA-NSCLC. The internal target volume (ITV); planning target volume (PTV); and organs at risks (OARs) such as spinal cord, total normal lung, heart, and esophagus were delineated for each CT data set. Intensity-modulated radiation therapy (IMRT), Tomohelical-IMRT (TH-IMRT), and TomoDirect-IMRT (TD-IMRT) plans were generated (total prescribed dose, 66 Gy in 33 fractions to the PTV) for each patient. To reduce the normal lung dose, complete and directional block function was applied outside the normal lung far from the target for both TH-IMRT and TD-IMRT, while pseudo- OAR was set in the same region for IMRT. Dosimetric characteristics of the three plans were compared in terms of target coverage, the sparing capability for the OAR, and the normal tissue complication probability (NTCP). Beam delivery efficiency was also compared. Results: TH-IMRT and TD-IMRT provided better target coverage than IMRT plans. Lung volume receiving ≥–30 Gy, mean dose, and NTCP were significant with TH-IMRT than with IMRT (p=0.006), and volume receiving ≥20–30 Gy was lower in TD-IMRT than in IMRT (p<0.05). Compared with IMRT, TH-IMRT had better sparing effect on the spinal cord (Dmax, NTCP) and heart (V45) (p<0.05). NTCP for the spinal cord, V45 and V60 for the heart, and Dmax for the esophagus were significantly lower in TD-IMRT than in IMRT. The monitor units per fraction were clearly smaller for IMRT than for TH-IMRT and TD-IMRT (p=0.006). Conclusion: In LA-NSCLC, TH-IMRT gave superior PTV coverage and OAR sparing compared to IMRT. TH-IMRT provided better control of the lung volume receiving ≥5–30 Gy. The delivery time and monitor units were lower in TD-IMRT than in TH-IMRT.

  9. TU-CD-BRB-01: Normal Lung CT Texture Features Improve Predictive Models for Radiation Pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

    Krafft, S [The University of Texas MD Anderson Cancer Center, Houston, TX (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, TX (United States); Briere, T; Court, L; Martel, M [The University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Existing normal tissue complication probability (NTCP) models for radiation pneumonitis (RP) traditionally rely on dosimetric and clinical data but are limited in terms of performance and generalizability. Extraction of pre-treatment image features provides a potential new category of data that can improve NTCP models for RP. We consider quantitative measures of total lung CT intensity and texture in a framework for prediction of RP. Methods: Available clinical and dosimetric data was collected for 198 NSCLC patients treated with definitive radiotherapy. Intensity- and texture-based image features were extracted from the T50 phase of the 4D-CT acquired for treatment planning. A total of 3888 features (15 clinical, 175 dosimetric, and 3698 image features) were gathered and considered candidate predictors for modeling of RP grade≥3. A baseline logistic regression model with mean lung dose (MLD) was first considered. Additionally, a least absolute shrinkage and selection operator (LASSO) logistic regression was applied to the set of clinical and dosimetric features, and subsequently to the full set of clinical, dosimetric, and image features. Model performance was assessed by comparing area under the curve (AUC). Results: A simple logistic fit of MLD was an inadequate model of the data (AUC∼0.5). Including clinical and dosimetric parameters within the framework of the LASSO resulted in improved performance (AUC=0.648). Analysis of the full cohort of clinical, dosimetric, and image features provided further and significant improvement in model performance (AUC=0.727). Conclusions: To achieve significant gains in predictive modeling of RP, new categories of data should be considered in addition to clinical and dosimetric features. We have successfully incorporated CT image features into a framework for modeling RP and have demonstrated improved predictive performance. Validation and further investigation of CT image features in the context of RP NTCP

  10. Current smoking-specific gene expression signature in normal bronchial epithelium is enhanced in squamous cell lung cancer

    NARCIS (Netherlands)

    Boelens, Mirjam C.; van den Berg, Anke; Fehrmann, Rudolf S. N.; Geerlings, Marie; de Jong, Wouter K.; te Meerman, Gerard J; Sietsma, Hannie; Timens, Winn; Postma, Dirkje S.; Groen, Harry J. M.

    2009-01-01

    Cigarette smoking is the main risk factor for the development of squamous cell lung carcinoma (SCC). However, the smoking-related molecular changes in SCC have not been studied. Gene expression studies in both histologically normal bronchial epithelium and SCC epithelial samples identified genes dif

  11. Volúmenes pulmonares normales en pacientes con fibrosis pulmonar idiopática y enfisema Normal lung volumes in patients with idiopathic pulmonary fibrosis and emphysema

    Directory of Open Access Journals (Sweden)

    Juan Pablo Casas

    2008-08-01

    pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. Previous reports suggest that when both diseases coexist, pulmonary volumes are compensated and a smaller than expected reduction or even normal lung volumes can be found. We report 4 male patients of 64, 60, 73 and 70 years, all with heavy cigarette smoking history and progressive breathlessness. Three of them had severe limitation in their quality of life. All four showed advanced lung interstitial involvement, at high resolution CT scan, fibrotic changes predominantly in the subpleural areas of lower lung fields and concomitant emphysema in the upper lobes. Emphysema and pulmonary fibrosis was confirmed by open lung biopsy in one patient. The four patients showed normal spirometry and lung volumes with severe compromise of gas exchange and poor exercise tolerance evaluated by 6 minute walk test. Severe pulmonary arterial hypertension was also confirmed in three patients. Normal lung volumes does not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

  12. Proteomic Comparison of Two-Dimensional Gel Electrophoresis Pro files from Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Tissues

    Institute of Scientific and Technical Information of China (English)

    Cui Li; Ping Chen; Jingyun Xie; Songping Liang; Xianquan Zhan; Maoyu Li; Xiaoying Wu; Feng Li; Jianling Li; Zhiqiang Xiao; Zhuchu Chen; Xueping Feng

    2003-01-01

    Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The results showed that well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-ug protein-load. The average deviation of spot position was 0.733+0.101 mm in IEF direction, and 0.925+0.207 mm in SDS-PAGE direction. For tumor tissue, a total of 1241±88 spots were detected, 987±65 spots were matched with an average matching rate of 79.5%. For control, a total of 1190+72 spots were detected, and 875±48 spots were matched with an average matching rate of 73.5%. A total of 864±34 spots were matched between tumors and controls.Forty-three differential proteins were characterized: some proteins were related to oncogenes, and others involved in the regulation of cell cycle and signal transduction. It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis.These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.

  13. Correlation among regional ventilation, airway resistance and particle deposition in normal and severe asthmatic lungs

    Science.gov (United States)

    Choi, Sanghun; Hoffman, Eric A.; Tawhai, Merryn H.; Lin, Ching-Long

    2012-11-01

    Computational fluid dynamic simulations are performed to investigate flow characteristics and quantify particle deposition with normal and severe asthmatic lungs. Continuity and Navier-Stokes equations are solved with unstructured meshes and finite element method; a large eddy simulation model is adopted to capture turbulent and/or transitional flows created in the glottis. The human airway models are reconstructed from CT volumetric images, and the subject-specific boundary condition is imposed to the 3D ending branches with the aid of an image registration technique. As a result, several constricted airways are captured in CT images of severe asthmatic subjects, causing significant pressure drop with high air speed because the constriction of airways creates high flow resistance. The simulated instantaneous velocity fields obtained are then employed to track transport and deposition of 2.5 μm particles. It is found that high flow resistance regions are correlated with high particle-deposition regions. In other words, the constricted airways can induce high airway resistance and subsequently increase particle deposition in the regions. This result may be applied to understand the characteristics of deposition of pharmaceutical aerosols or bacteria. This work was supported in part by NIH grants R01-HL094315 and S10-RR022421.

  14. Fog2 is required for normal diaphragm and lung development in mice and humans.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Congenital diaphragmatic hernia and other congenital diaphragmatic defects are associated with significant mortality and morbidity in neonates; however, the molecular basis of these developmental anomalies is unknown. In an analysis of E18.5 embryos derived from mice treated with N-ethyl-N-nitrosourea, we identified a mutation that causes pulmonary hypoplasia and abnormal diaphragmatic development. Fog2 (Zfpm2 maps within the recombinant interval carrying the N-ethyl-N-nitrosourea-induced mutation, and DNA sequencing of Fog2 identified a mutation in a splice donor site that generates an abnormal transcript encoding a truncated protein. Human autopsy cases with diaphragmatic defect and pulmonary hypoplasia were evaluated for mutations in FOG2. Sequence analysis revealed a de novo mutation resulting in a premature stop codon in a child who died on the first day of life secondary to severe bilateral pulmonary hypoplasia and an abnormally muscularized diaphragm. Using a phenotype-driven approach, we have established that Fog2 is required for normal diaphragm and lung development, a role that has not been previously appreciated. FOG2 is the first gene implicated in the pathogenesis of nonsyndromic human congenital diaphragmatic defects, and its necessity for pulmonary development validates the hypothesis that neonates with congenital diaphragmatic hernia may also have primary pulmonary developmental abnormalities.

  15. Inhibitory effects of Piper betle on production of allergic mediators by bone marrow-derived mast cells and lung epithelial cells.

    Science.gov (United States)

    Wirotesangthong, Mali; Inagaki, Naoki; Tanaka, Hiroyuki; Thanakijcharoenpath, Witchuda; Nagai, Hiroichi

    2008-03-01

    The leaves of the Piper betle Linn. (Piperaceae) are used in traditional medicine and possess anti-oxidant, anti-bacterial, anti-fungal, anti-diabetic and radioprotective activities. However, little is known about their anti-allergic activity. Therefore, the effects of P. betle ethanolic extract (PE) on the production of histamine and granulocyte macrophage-colony-stimulating factor (GM-CSF) by murine bone marrow mast cells (BMMCs) and on the secretion of eotaxin and IL-8 by the human lung epithelial cell line, BEAS-2B, were investigated in vitro. PE significantly decreased histamine and GM-CSF produced by an IgE-mediated hypersensitive reaction, and inhibited eotaxin and IL-8 secretion in a TNF-alpha and IL-4-induced allergic reaction. The results suggest that P. betle may offer a new therapeutic approach for the control of allergic diseases through inhibition of production of allergic mediators.

  16. AGER -429T/C is associated with an increased lung disease severity in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Julie Beucher

    Full Text Available The clinical course of cystic fibrosis (CF varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV(1 was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C was associated with poorer lung function (p = 0.03. In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells. AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.

  17. SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Q; Lei, Y; Zheng, D; Zhu, X; Wahl, A; Lin, C; Zhou, S; Zhen, W [University of Nebraska Medical Center, Omaha, NE (United States)

    2015-06-15

    Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness were created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing.

  18. Pigment epithelium-derived factor enhances tumor response to radiation through vasculature normalization in allografted lung cancer in mice.

    Science.gov (United States)

    Xu, Z; Dong, Y; Peng, F; Yu, Z; Zuo, Y; Dai, Z; Chen, Y; Wang, J; Hu, X; Zhou, Q; Ma, H; Bao, Y; Gao, G; Chen, M

    2015-03-01

    This study aimed to explore the potential therapeutic effects of the combination of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF and PEDF combined with radiation. The morphologic changes of tumor vasculature and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition of tumor growth was observed when radiation was applied between the 3rd and 7th day (the vasculature normalization window) after the initiation of PEDF treatment. During the vasculature normalization window, the tumor blood vessels in PEDF-treated mice were less tortuous and more uniform than those in the LLC allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness of the basement membrane was remarkably reduced and pericyte coverage was significantly increased with the PEDF treatment. We also found that tumor hypoxic fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting improved intratumoral oxygenation. Taken together, our results show that PEDF improved the effects of radiation therapy on LLC allografts by inducing a vascular normalization window from the 3rd to the 7th day after PEDF treatment. Our findings provide a basis for treating lung cancer with the combination of PEDF and radiation.

  19. Proteomic Comparison of Two—Dimensional Gel Electrophoresis Profiles from Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Tissues

    Institute of Scientific and Technical Information of China (English)

    CuiLi; XianquanZhan; MaoyuLi; XiaoyingWu; FengLi; JianlingLi; ZhiqiangXiao; ZhuchuChen; XuepingFeng; PingChen; JingyunXie; SongpingLiang

    2003-01-01

    Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis(2-D PAGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS).The results showed that well-resolved,reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-mg protein-load.The average deviation of spot position was 0.733±0.101 mm in IEF direction,and 0.925±0.207mm in SDS-PAGE direction.For tumor tissue,a total of 1241±88 spots were detected,987±65 spots were matched with an average matching rate of 79.5%.For control,a total of 1190±72 spots were detected,and 875±48 spots were matched with an average matching rate of 73.5%.A total of 864±34 spots were matched between tumors and controls.Forth-three differential proteins were characterized:some proteins were related to oncogenes,and others involved in the regulation of cell cycle and signal transduction.It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis.These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.

  20. Detection of a novel stem cell probably involved in normal turnover of the lung airway epithelium.

    Science.gov (United States)

    Ortega-Martínez, Marta; Rodríguez-Flores, Laura E; de-la-Garza-González, Carlos; Ancer-Rodríguez, Jesús; Jaramillo-Rangel, Gilberto

    2015-11-01

    Regeneration of the lung airway epithelium after injury has been extensively studied. In contrast, analysis of its turnover in healthy adulthood has received little attention. In the classical view, this epithelium is maintained in the steady-state by the infrequent proliferation of basal or Clara cells. The intermediate filament protein nestin was initially identified as a marker for neural stem cells, but its expression has also been detected in other stem cells. Lungs from CD1 mice at the age of 2, 6, 12, 18 or 24 months were fixed in neutral-buffered formalin and paraffin-embedded. Nestin expression was examined by an immunohistochemical peroxidase-based method. Nestin-positive cells were detected in perivascular areas and in connective tissue that were in close proximity of the airway epithelium. Also, nestin-positive cells were found among the cells lining the airway epithelium. These findings suggest that nestin-positive stem cells circulate in the bloodstream, transmigrate through blood vessels and localize in the lung airway epithelium to participate in its turnover. We previously reported the existence of similar cells able to differentiate into lung chondrocytes. Thus, the stem cell reported here might be a bone marrow-derived mesenchymal stem cell (BMDMSC) able to generate several types of lung tissues. In conclusion, our findings indicate that there exist a BMDMSC in healthy adulthood that participates in the turnover of the lung airway epithelium. These findings may improve our knowledge about the lung stem cell biology and also provide novel approaches to therapy for devastating pulmonary diseases.

  1. Immune-Signatures for Lung Cancer Diagnostics: Evaluation of Protein Microarray Data Normalization Strategies

    OpenAIRE

    2015-01-01

    New minimal invasive diagnostic methods for early detection of lung cancer are urgently needed. It is known that the immune system responds to tumors with production of tumor-autoantibodies. Protein microarrays are a suitable highly multiplexed platform for identification of autoantibody signatures against tumor-associated antigens (TAA). These microarrays can be probed using 0.1 mg immunoglobulin G (IgG), purified from 10 µL of plasma. We used a microarray comprising recombinant proteins der...

  2. Automated characterization of normal and pathologic lung tissue by topological texture analysis of multidetector CT

    Science.gov (United States)

    Boehm, H. F.; Fink, C.; Becker, C.; Reiser, M.

    2007-03-01

    Reliable and accurate methods for objective quantitative assessment of parenchymal alterations in the lung are necessary for diagnosis, treatment and follow-up of pulmonary diseases. Two major types of alterations are pulmonary emphysema and fibrosis, emphysema being characterized by abnormal enlargement of the air spaces distal to the terminal, nonrespiratory bronchiole, accompanied by destructive changes of the alveolar walls. The main characteristic of fibrosis is coursening of the interstitial fibers and compaction of the pulmonary tissue. With the ability to display anatomy free from superimposing structures and greater visual clarity, Multi-Detector-CT has shown to be more sensitive than the chest radiograph in identifying alterations of lung parenchyma. In automated evaluation of pulmonary CT-scans, quantitative image processing techniques are applied for objective evaluation of the data. A number of methods have been proposed in the past, most of which utilize simple densitometric tissue features based on the mean X-ray attenuation coefficients expressed in terms of Hounsfield Units [HU]. Due to partial volume effects, most of the density-based methodologies tend to fail, namely in cases, where emphysema and fibrosis occur within narrow spatial limits. In this study, we propose a methodology based upon the topological assessment of graylevel distribution in the 3D image data of lung tissue which provides a way of improving quantitative CT evaluation. Results are compared to the more established density-based methods.

  3. Correlation of lung collapse and gas exchange - a computer tomographic study in sheep and pigs with atelectasis in otherwise normal lungs.

    Directory of Open Access Journals (Sweden)

    Samuel J Wolf

    Full Text Available Atelectasis can provoke pulmonary and non-pulmonary complications after general anaesthesia. Unfortunately, there is no instrument to estimate atelectasis and prompt changes of mechanical ventilation during general anaesthesia. Although arterial partial pressure of oxygen (PaO2 and intrapulmonary shunt have both been suggested to correlate with atelectasis, studies yielded inconsistent results. Therefore, we investigated these correlations.Shunt, PaO2 and atelectasis were measured in 11 sheep and 23 pigs with otherwise normal lungs. In pigs, contrasting measurements were available 12 hours after induction of acute respiratory distress syndrome (ARDS. Atelectasis was calculated by computed tomography relative to total lung mass (Mtotal. We logarithmically transformed PaO2 (lnPaO2 to linearize its relationships with shunt and atelectasis. Data are given as median (interquartile range.Mtotal was 768 (715-884 g in sheep and 543 (503-583 g in pigs. Atelectasis was 26 (16-47 % in sheep and 18 (13-23 % in pigs. PaO2 (FiO2 = 1.0 was 242 (106-414 mmHg in sheep and 480 (437-514 mmHg in pigs. Shunt was 39 (29-51 % in sheep and 15 (11-20 % in pigs. Atelectasis correlated closely with lnPaO2 (R2 = 0.78 and shunt (R2 = 0.79 in sheep (P-values<0.0001. The correlation of atelectasis with lnPaO2 (R2 = 0.63 and shunt (R2 = 0.34 was weaker in pigs, but R2 increased to 0.71 for lnPaO2 and 0.72 for shunt 12 hours after induction of ARDS. In both, sheep and pigs, changes in atelectasis correlated strongly with corresponding changes in lnPaO2 and shunt.In lung-healthy sheep, atelectasis correlates closely with lnPaO2 and shunt, when blood gases are measured during ventilation with pure oxygen. In lung-healthy pigs, these correlations were significantly weaker, likely because pigs have stronger hypoxic pulmonary vasoconstriction (HPV than sheep and humans. Nevertheless, correlations improved also in pigs after blunting of HPV during ARDS. In humans, the observed

  4. Dependence of lung injury on inflation rate during low-volume ventilation in normal open-chest rabbits.

    Science.gov (United States)

    D'Angelo, Edgardo; Pecchiari, Matteo; Saetta, Marina; Balestro, Elisabetta; Milic-Emili, Joseph

    2004-07-01

    Lung mechanics and morphometry were assessed in two groups of nine normal open-chest rabbits mechanically ventilated (MV) for 3-4 h at zero end-expiratory pressure (ZEEP) with physiological tidal volumes (Vt; 11 ml/kg) and high (group A) or low (group B) inflation flow (44 and 6.1 ml x kg(-1) x s(-1), respectively). Relative to initial MV on positive end-expiratory pressure (PEEP; 2.3 cmH(2)O), MV on ZEEP increased quasi-static elastance and airway and viscoelastic resistance more in group A (+251, +393, and +225%, respectively) than in group B (+180, +247, and +183%, respectively), with no change in viscoelastic time constant. After restoration of PEEP, quasi-static elastance and viscoelastic resistance returned to control, whereas airway resistance, still relative to initial values, remained elevated more in group A (+86%) than in group B (+33%). In contrast, prolonged high-flow MV on PEEP had no effect on lung mechanics of seven open-chest rabbits (group C). Gas exchange on PEEP was equally preserved in all groups, and the lung wet-to-dry ratios were normal. Relative to group C, both groups A and B had an increased percentage of abnormal alveolar-bronchiolar attachments and number of polymorphonuclear leukocytes in alveolar septa, the latter being significantly larger in group A than in group B. Thus prolonged MV on ZEEP with cyclic opening-closing of peripheral airways causes alveolar-bronchiolar uncoupling and parenchymal inflammation with concurrent, persistent increase in airway resistance, which are worsened by high-inflation flow.

  5. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    2012-06-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

  6. A COMPARATIVE STUDY OF LUNG FUNCTIONS IN SWIMMERS AND NORMAL INDIVIDUALS IN AND AROUND HUBLI CITY

    Directory of Open Access Journals (Sweden)

    Basavaraj

    2014-03-01

    Full Text Available BACKGROUND: The thoracic and abdominal muscle strength plays an important role in pulmonary function and diffusing lung capacity. The purpose of this study is to observe chest and abdominal muscles following period of breath holding which is a part of training for swimmers. Aims and objectives: To compare the pulmonary function test among swimmers and non-swimmers. MATERIALS AND METHODS: In this study 30 Males aged between 18 and 30 years who were swimming regularly for at least 3days in a week for a period of 1yr and above were selected as subjects and 30 controls that were in the same age group. Spirolyser - SPL – 95 is used. RESULTS: Statistically parameters were analyzed by student 't' test. There was no significant difference in age, weight, height, BMI between swimmers and non-swimmers. There was a significant difference in mean and standard deviation of pulmonary parameters with the p-value <0.05 in swimmers which shows that they have greater ventilator drive. CONCLUSION: Regular swimming produces a positive effect on the lung by increasing pulmonary capacity

  7. Normal overall leakiness of microvasculature for albumin in patients with chronic obstructive lung disease (COLD)

    DEFF Research Database (Denmark)

    Kok-Jensen, A; Henriksen, Jens Henrik Sahl

    1984-01-01

    .45-1.95), and forced expired volume in first sec was decreased to 21% of expected normal value (median 0.55 litre, range 0.40-0.70). Right-heart catheterization revealed pulmonary hypertension in all but one patient. TER in patients with COLD was median 6.1% IVM/h (range 3.5-10.1) as compared to that of normal...

  8. Tobacco Smoke Activates Human Papillomavirus 16 p97 Promoter and Cooperates with High-Risk E6/E7 for Oxidative DNA Damage in Lung Cells

    Science.gov (United States)

    Muñoz, Juan P.; Chnaiderman, Jonás; Urzúa, Ulises; León, Oscar; Tornesello, Maria L.; Corvalán, Alejandro H.; Soto-Rifo, Ricardo; Aguayo, Francisco

    2015-01-01

    We have previously shown a functional interaction between human papillomavirus type 16 (HPV-16) E6 and E7 oncoproteins and cigarette smoke condensate (CSC) in lung cells suggesting cooperation during carcinogenesis. The molecular mechanisms of such interaction, however, remain to be elucidated. Here we first present evidence showing that cigarette smoke condensate (CSC) has the ability to activate the HPV-16 p97 promoter by acting on the long control region (LCR) in lung epithelial cells. Interestingly, we observed that CSC-induced p97 promoter activation occurs in a dose-dependent manner in both tumor A-549 (lung adenocarcinoma), H-2170 (bronchial carcinoma), SiHa or Hela (cervical carcinoma) cells but not in non-tumor BEAS-2B (bronchial) or NL-20 (alveolar) lung cells unless they ectopically expressed the HPV-16 E6 and E7 oncogenes. In addition, we also observed a significant increase of primary DNA damage in tumor and non-tumor CSC-treated lung cells expressing HPV-16 E6 and E7 oncogenes suggesting a cooperative effect in this process, even though the contribution of E7 was significantly higher. Taken together, our results strongly suggest that tobacco smoke is able to induce the activation of the HPV-16 p97 promoter in cooperation with HPV-16 E6 and E7 oncogenes that, in turn, sensitize lung cells to tobacco smoke-induced DNA damage. PMID:25830243

  9. Mutant AKT1-E17K is oncogenic in lung epithelial cells

    Science.gov (United States)

    De Marco, Carmela; Malanga, Donatella; Rinaldo, Nicola; De Vita, Fernanda; Scrima, Marianna; Lovisa, Sara; Fabris, Linda; Carriero, Maria Vincenza; Franco, Renato; Rizzuto, Antonia; Baldassarre, Gustavo; Viglietto, Giuseppe

    2015-01-01

    The hotspot E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6–2% of human lung cancers. In this manuscript, we sought to determine whether this AKT1 variant is a bona-fide activating mutation and plays a role in the development of lung cancer. Here we report that in immortalized human bronchial epithelial cells (BEAS-2B cells) mutant AKT1-E17K promotes anchorage-dependent and -independent proliferation, increases the ability to migrate, invade as well as to survive and duplicate in stressful conditions, leading to the emergency of cells endowed with the capability to form aggressive tumours at high efficiency. We provide also evidence that the molecular mechanism whereby AKT1-E17K is oncogenic in lung epithelial cells involves phosphorylation and consequent cytoplasmic delocalization of the cyclin-dependent kinase (cdk) inhibitor p27. In agreement with these results, cytoplasmic p27 is preferentially observed in primary NSCLCs with activated AKT and predicts poor survival. PMID:26053093

  10. Local Tumor Control and Normal Tissue Toxicity of Pulsed Low-Dose Rate Radiotherapy for Recurrent Lung Cancer

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    2015-05-01

    Full Text Available Objectives: This study investigates (1 local tumor control and (2 normal tissue toxicity of pulsed low-dose rate radiotherapy (PLDR for recurrent lung cancer. Methods: For study 1, nude mice were implanted with A549 tumors and divided into the following 3 groups: (1 control (n = 10, (2 conventional radiotherapy (RT; n = 10, and (3 PLDR (n = 10. Tumor-bearing mice received 2 Gy daily dose for 2 consecutive days. Weekly magnetic resonance imaging was used for tumor growth monitoring. For study 2, 20 mice received 8 Gy total body irradiation either continuously (n = 10 or 40 × 0.2 Gy pulses with 3-minute intervals (n = 10. Results: For study 1, both conventional RT and PLDR significantly inhibited the growth of A549 xenografts compared with the control group (>35% difference in the mean tumor volume; P .05. For study 2, the average weight was 20.94 ± 1.68 g and 25.69 ± 1.27 g and the survival time was 8 days and 12 days for mice treated with conventional RT and PLDR (P < .05, respectively. Conclusion: This study showed that PLDR could control A549 tumors as effectively as conventional RT, and PLDR induced much less normal tissue toxicity than conventional RT. Thus, PLDR would be a good modality for recurrent lung cancers. Advances in Knowledge: This article reports our results of an in vivo animal investigation of PLDR for the treatment of recurrent cancers, which may not be eligible for treatment because of the dose limitations on nearby healthy organs that have been irradiated in previous treatments. This was the first in vivo study to quantify the tumor control and normal tissue toxicities of PLDR using mice with implanted tumors, and our findings provided evidence to support the clinical trials that employ PLDR treatment techniques.

  11. Base excision repair activities differ in human lung cancer cells and corresponding normal controls

    DEFF Research Database (Denmark)

    Karahalil, Bensu; Bohr, Vilhelm A; De Souza-Pinto, Nadja C

    2010-01-01

    Oxidative damage to DNA is thought to play a role in carcinogenesis by causing mutations, and indeed accumulation of oxidized DNA bases has been observed in samples obtained from tumors but not from surrounding tissue within the same patient. Base excision repair (BER) is the main pathway...... for the repair of oxidized modifications both in nuclear and mitochondrial DNA. In order to ascertain whether diminished BER capacity might account for increased levels of oxidative DNA damage in cancer cells, the activities of BER enzymes in three different lung cancer cell lines and their non......-cancerous counterparts were measured using oligonucleotide substrates with single DNA lesions to assess specific BER enzymes. The activities of four BER enzymes, OGG1, NTH1, UDG and APE1, were compared in mitochondrial and nuclear extracts. For each specific lesion, the repair activities were similar among the three...

  12. Inhaled nitric oxide decreases pulmonary endothelial nitric oxide synthase expression and activity in normal newborn rat lungs

    Directory of Open Access Journals (Sweden)

    Thông Hua-Huy

    2016-02-01

    Full Text Available Inhaled nitric oxide (iNO is commonly used in the treatment of very ill pre-term newborns. Previous studies showed that exogenous NO could affect endothelial NO synthase (eNOS activity and expression in vascular endothelial cell cultures or adult rat models, but this has never been fully described in newborn rat lungs. We therefore aimed to assess the effects of iNO on eNOS expression and activity in newborn rats. Rat pups, post-natal day (P 0 to P7, and their dams were placed in a chamber containing NO at 5 ppm (iNO-5 ppm group or 20 ppm (iNO-20 ppm group, or in room air (control group. Rat pups were sacrificed at P7 and P14 for evaluation of lung eNOS expression and activity. At P7, eNOS protein expression in total lung lysates, in bronchial and arterial sections, was significantly decreased in the iNO-20 ppm versus control group. At P14, eNOS expression was comparable among all three groups. The amounts of eNOS mRNA significantly differed at P7 between the iNO-20 ppm and control groups. NOS activity decreased in the iNO-20 ppm group at P7 and returned to normal levels at P14. There was an imbalance between superoxide dismutase and NOS activities in the iNO-20 ppm group at P7. Inhalation of NO at 20 ppm early after birth decreases eNOS gene transcription, protein expression and enzyme activity. This decrease might account for the rebound phenomenon observed in patients treated with iNO.

  13. Transcriptional mechanisms and protein kinase signaling mediate organic dust induction of IL-8 expression in lung epithelial and THP-1 cells.

    Science.gov (United States)

    Gottipati, Koteswara R; Bandari, Shiva Kumar; Nonnenmann, Matthew W; Levin, Jeffrey L; Dooley, Gregory P; Reynolds, Stephen J; Boggaram, Vijay

    2015-01-01

    Exposure to the agricultural work environment is a risk factor for the development of respiratory symptoms and chronic lung diseases. Inflammation is an important contributor to the pathogenesis of tissue injury and disease. Cellular and molecular mechanisms mediating lung inflammatory responses to agricultural dust are not yet fully understood. We studied the effects of poultry dust extract on molecular regulation of interleukin-8 (IL-8), a proinflammatory cytokine, in A549 and Beas2B lung epithelial and THP-1 monocytic cells. Our findings indicate that poultry dust extract potently induces IL-8 levels by increasing IL-8 gene transcription without altering IL-8 mRNA stability. Increase in IL-8 promoter activity was due to enhanced binding of activator protein 1 and NF-κB. IL-8 induction was associated with protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) activation and inhibited by PKC and MAPK inhibitors. IL-8 increase was not inhibited by polymyxin B or l-nitroarginine methyl ester, indicating lack of involvement of lipopolysaccharide and nitric oxide in the induction. Lung epithelial and THP-1 cells share common mechanisms for induction of IL-8 levels. Our findings identify key roles for transcriptional mechanisms and protein kinase signaling pathways for IL-8 induction and provide insights into the mechanisms regulating lung inflammatory responses to organic dust exposure.

  14. Transthoracic lung ultrasound in normal dogs and dogs with cardiogenic pulmonary edema: a pilot study.

    Science.gov (United States)

    Rademacher, Nathalie; Pariaut, Romain; Pate, Julie; Saelinger, Carley; Kearney, Michael T; Gaschen, Lorrie

    2014-01-01

    Pulmonary edema is the most common complication of left-sided heart failure in dogs and early detection is important for effective clinical management. In people, pulmonary edema is commonly diagnosed based on transthoracic ultrasonography and detection of B line artifacts (vertical, narrow-based, well-defined hyperechoic rays arising from the pleural surface). The purpose of this study was to determine whether B line artifacts could also be useful diagnostic predictors for cardiogenic pulmonary edema in dogs. Thirty-one normal dogs and nine dogs with cardiogenic pulmonary edema were prospectively recruited. For each dog, presence or absence of cardiogenic pulmonary edema was based on physical examination, heartworm testing, thoracic radiographs, and echocardiography. A single observer performed transthoracic ultrasonography in all dogs and recorded video clips and still images for each of four quadrants in each hemithorax. Distribution, sonographic characteristics, and number of B lines per thoracic quadrant were determined and compared between groups. B lines were detected in 31% of normal dogs (mean 0.9 ± 0.3 SD per dog) and 100% of dogs with cardiogenic pulmonary edema (mean 6.2 ± 3.8 SD per dog). Artifacts were more numerous and widely distributed in dogs with congestive heart failure (P edema on radiographs. Findings from the current study supported the use of thoracic ultrasonography and detection of B lines as techniques for diagnosing cardiogenic pulmonary edema in dogs.

  15. Comparison of Radiation-Induced Normal Lung Tissue Density Changes for Patients From Multiple Institutions Receiving Conventional or Hypofractionated Treatments

    Energy Technology Data Exchange (ETDEWEB)

    Diot, Quentin, E-mail: quentin.diot@ucdenver.edu [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Bentzen, Soren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenbaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Lawrence, Michael V. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Miften, Moyed [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado (United States); Palma, David A. [London Regional Cancer Program, London, Ontario (Canada)

    2014-07-01

    Purpose: To quantitatively assess changes in computed tomography (CT)–defined normal lung tissue density after conventional and hypofractionated radiation therapy (RT). Methods and Materials: The pre-RT and post-RT CT scans from 118 and 111 patients receiving conventional and hypofractionated RT, respectively, at 3 institutions were registered to each other and to the 3-dimensional dose distribution to quantify dose-dependent changes in normal lung tissue density. Dose-response curves (DRC) for groups of patients receiving conventional and hypofractionated RT were generated for each institution, and the frequency of density changes >80 Hounsfield Units (HU) was modeled depending on the fractionation type using a Probit model for different follow-up times. Results: For the pooled data from all institutions, there were significant differences in the DRC between the conventional and hypofractionated groups; the respective doses resulting in 50% complication risk (TD{sub 50}) were 62 Gy (95% confidence interval [CI] 57-67) versus 36 Gy (CI 33-39) at <6 months, 48 Gy (CI 46-51) versus 31 Gy (CI 28-33) at 6-12 months, and 47 Gy (CI 45-49) versus 35 Gy (32-37) at >12 months. The corresponding m values (slope of the DRC) were 0.52 (CI 0.46-0.59) versus 0.31 (CI 0.28-0.34) at <6 months, 0.46 (CI 0.42-0.51) versus 0.30 (CI 0.26-0.34) at 6-12 months, and 0.45 (CI 0.42-0.50) versus 0.31 (CI 0.27-0.35) at >12 months (P<.05 for all comparisons). Conclusion: Compared with conventional fractionation, hypofractionation has a lower TD{sub 50} and m value, both suggesting an increased degree of normal tissue density sensitivity with hypofractionation.

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

    Science.gov (United States)

    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...

  17. Extracting the normal lung dose-response curve from clinical DVH data: a possible role for low dose hyper-radiosensitivity, increased radioresistance

    Science.gov (United States)

    Gordon, J. J.; Snyder, K.; Zhong, H.; Barton, K.; Sun, Z.; Chetty, I. J.; Matuszak, M.; Ten Haken, R. K.

    2015-09-01

    In conventionally fractionated radiation therapy for lung cancer, radiation pneumonitis’ (RP) dependence on the normal lung dose-volume histogram (DVH) is not well understood. Complication models alternatively make RP a function of a summary statistic, such as mean lung dose (MLD). This work searches over damage profiles, which quantify sub-volume damage as a function of dose. Profiles that achieve best RP predictive accuracy on a clinical dataset are hypothesized to approximate DVH dependence. Step function damage rate profiles R(D) are generated, having discrete steps at several dose points. A range of profiles is sampled by varying the step heights and dose point locations. Normal lung damage is the integral of R(D) with the cumulative DVH. Each profile is used in conjunction with a damage cutoff to predict grade 2 plus (G2+) RP for DVHs from a University of Michigan clinical trial dataset consisting of 89 CFRT patients, of which 17 were diagnosed with G2+ RP. Optimal profiles achieve a modest increase in predictive accuracy—erroneous RP predictions are reduced from 11 (using MLD) to 8. A novel result is that optimal profiles have a similar distinctive shape: enhanced damage contribution from low doses (curves, which can be modeled using Joiner’s induced repair model. A novel search strategy is employed, which has the potential to estimate RP dependence on the normal lung DVH. When applied to a clinical dataset, identified profiles share a characteristic shape, which resembles HRS/IRR. This suggests that normal lung may have enhanced sensitivity to low doses, and that this sensitivity can affect RP risk.

  18. Lung development in laminin γ2 deficiency: abnormal tracheal hemidesmosomes with normal branching morphogenesis and epithelial differentiation

    Directory of Open Access Journals (Sweden)

    Uitto Jouni

    2006-02-01

    Full Text Available Abstract Background Laminin γ2 (Lamc2, one of the polypeptides in laminin-332 (laminin-5, is prominent in the basement membrane of alveolar walls and airways of developing and adult lung. Laminins are important for lung morphogenesis and based on its localization, a function for laminin γ2 in lung development has been hypothesized. Targeted deletion of the laminin γ2 gene in mice results in skin blistering and neonatal death at 3–5 days after birth due to failure to thrive. Methods Examination of lung development in Lamc2-/- mice through 1–2 days postnatal was accomplished by morphometric analysis, lung bud culture, electron microscopy, immunohistochemical and immunofluorescence staining. Results Compared to littermate controls, Lamc2-/- lungs were similar in morphology during embryonic life. At post-natal day 1–2, distal saccules were mildly dilated by chord length measurements. Epithelial differentiation as evaluated by immunohistochemical staining for markers of ciliated cells, Clara cells, alveolar type I cells and alveolar type II cells did not reveal a difference between Lamc2-/- and littermate control lungs. Likewise, vascular development, smooth muscle cell differentiation, and elastic fiber formation looked similar, as did airway basement membrane ultrastructure. Branching morphogenesis by lung bud culture was similar in Lamc2-/- and littermate control lungs. Since laminin-332 is important for hemidesmosome formation, we examined the structure of tracheal hemidesmosomes by transmission electron microscopy. Compared to littermate controls, Lamc2-/- tracheal hemidesmosomes were less organized and lacked the increased electron density associated with the basement membrane abutting the hemidesmosome. Conclusion These findings indicate that laminin γ2 and laminin-332, despite their prominence in the lung, have a minimal role in lung development through the saccular stage.

  19. Radiation dose response of normal lung assessed by Cone Beam CT - a potential tool for biologically adaptive radiation therapy

    DEFF Research Database (Denmark)

    Bertelsen, Anders; Schytte, Tine; Bentzen, Søren M;

    2011-01-01

    Density changes of healthy lung tissue during radiotherapy as observed by Cone Beam CT (CBCT) might be an early indicator of patient specific lung toxicity. This study investigates the time course of CBCT density changes and tests for a possible correlation with locally delivered dose....

  20. Differences and radiation pneumonitis prediction of lung dosimetric parameters based on three normal lung definitions in 3DCRT treatment planning%3DCRT计划中不同肺定义对肺癌放疗的影响

    Institute of Scientific and Technical Information of China (English)

    王谨; 包勇; 庄婷婷; 张黎; 何智纯; 徐裕金; 马红莲; 胡晓; 周琦超

    2014-01-01

    Objective To compare lung dose-volume histogram (DVH) parameters based on commonly used normal lung definitions,i.e.,lungs-gross tumor volume (GTV),lungs-clinical target volume (CTV),and lungs-planning target volume (PTV),in three-dimensional conformal radiotherapy (3 DCRT) and to determine to what extent they differ in predicting radiation pneumonitis (RP).Methods A total of 147 non-small cell lung cancer patients treated with concurrent chemotherapy and 3DCRT from 2006 to 2010 were collected.RP was diagnosed according to RTOG criteria.Lung DVHs were generated with exclusion of GTV,CTV,or PTV.Independent-samples t test was used to compare DVH parameters based on different normal lung definitions,and the predictive values of these parameters for RP were evaluated with the receiver operating characteristic (ROC) curve.Results There were significant differences in minimum lethal dose (MLD) between lungs-GTV and lungs-CTV/lungs-PTV ((1.16 ± 0.96) Gy vs.(3.45 ± 1.43) Gy).The biggest difference in MLD for the same patient based on different definitions was 8.73 Gy.MLD based on lungs-GTV had a better predictive value for grades ≥2 and ≥3 RP than MLD based on lungs-CTV and lungs-PTV,with larger areas under the ROC curve (lungs-GTV ∶ area =0.614,P=0.024;area =0.678,P=0.056;lungs-CTV∶area =0.556,P=0.269;area =0.602,P=0.226 ; lungs-PTV ∶ area =0.551,P =0.317 ; area =0.616,P =0.167).We drew a similar conclusion when analyzing lung V5-V50.Conclusions There are significant differences between DVH parameters based on various normal lung definitions,which cannot be neglected in the clinical setting.DVH parameters based on lungs-GTV may be the most accurate in predicting RP.%目的 探讨3DCRT计划中双肺-GTV、CTV、PTV三种定义下正常肺DVH参数差异及对RP的预测价值.方法 对2006-2010年间行3DCRT的147例NSCLC患者分别定义双肺-GTV、CTV、PTV正常肺并收集相关DVH剂量学信息,比较参数值差异及其对RP的预测价值.剂量

  1. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  2. Exposure of Human Lung Cells to Tobacco Smoke Condensate Inhibits the Nucleotide Excision Repair Pathway.

    Directory of Open Access Journals (Sweden)

    Nathaniel Holcomb

    Full Text Available Exposure to tobacco smoke is the number one risk factor for lung cancer. Although the DNA damaging properties of tobacco smoke have been well documented, relatively few studies have examined its effect on DNA repair pathways. This is especially true for the nucleotide excision repair (NER pathway which recognizes and removes many structurally diverse DNA lesions, including those introduced by chemical carcinogens present in tobacco smoke. The aim of the present study was to investigate the effect of tobacco smoke on NER in human lung cells. We studied the effect of cigarette smoke condensate (CSC, a surrogate for tobacco smoke, on the NER pathway in two different human lung cell lines; IMR-90 lung fibroblasts and BEAS-2B bronchial epithelial cells. To measure NER, we employed a slot-blot assay to quantify the introduction and removal of UV light-induced 6-4 photoproducts and cyclobutane pyrimidine dimers. We find a dose-dependent inhibition of 6-4 photoproduct repair in both cell lines treated with CSC. Additionally, the impact of CSC on the abundance of various NER proteins and their respective RNAs was investigated. The abundance of XPC protein, which is required for functional NER, is significantly reduced by treatment with CSC while the abundance of XPA protein, also required for NER, is unaffected. Both XPC and XPA RNA levels are modestly reduced by CSC treatment. Finally, treatment of cells with MG-132 abrogates the reduction in the abundance of XPC protein produced by treatment with CSC, suggesting that CSC enhances proteasome-dependent turnover of the protein that is mediated by ubiquitination. Together, these findings indicate that tobacco smoke can inhibit the same DNA repair pathway that is also essential for the removal of some of the carcinogenic DNA damage introduced by smoke itself, increasing the DNA damage burden of cells exposed to tobacco smoke.

  3. Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells.

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    Laura Cartularo

    Full Text Available Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress.

  4. Growth regulation, imprinting, and epigenetic transcription-related gene expression differs in lung of deceased transgenic cloned and normal goats

    NARCIS (Netherlands)

    Meng, L.; Jia, R.X.; Sun, Y.; Wang, Z.Y.; Wan, Y.J.; Zhang, Y.L.; Zhong, B.S.; Wang, F.

    2014-01-01

    Somatic cell nuclear transfer (SCNT) is a promising technique to produce mammalian transgenic clones. Only a small proportion of manipulated embryos, however, can develop into viable offspring. The abnormal growth and development of cloned animals, furthermore, are accompanied by aberrant lung devel

  5. HCY-2在正常人胚呼吸系统中的表达%The Expression of HCY-2 in Normal Human Embryonic Trachea and Lung

    Institute of Scientific and Technical Information of China (English)

    张元元; 李耀康; 王光明

    2015-01-01

    Objective:To investigate the expression of homocysteine induced gene(HCY-2)in the normal human embryonic trachea and lung and to reveal the effects of HCY-2 on the development of respiration system. Methods: The immunohistochemistry ABC method was used to detect the HCY-2 expression in the normal human embryonic trachea and lung. Results:HCY-2 expressed during the whole development of the human embryonic trachea and lung and mainly in the epitheliums of trachea and pulmonary bronchi and glandular epitheliums. Conclusion:HCY-2 expression protein could be closely related to the development of trachea and lung.%目的:研究同型半胱氨酸诱导基因(HCY-2)在发育不同时期的正常人胚气管和肺中的表达,揭示HCY-2基因在呼吸系统发育中的作用.方法:取正常人胚气管和肺,采用免疫组织化学ABC法对气管和肺内HCY-2表达变化进行分析.结果:HCY-2在人胚气管和肺发育的整个时期均表达,其表达部位主要在气管及其各级支气管的上皮和气管腺腺细胞内.结论:HCY-2表达蛋白可能与人胚气管及肺的发育密切相关.

  6. The Akt1/IL-6/STAT3 pathway regulates growth of lung tumor initiating cells.

    Science.gov (United States)

    Malanga, Donatella; De Marco, Carmela; Guerriero, Ilaria; Colelli, Fabiana; Rinaldo, Nicola; Scrima, Marianna; Mirante, Teresa; De Vitis, Claudia; Zoppoli, Pietro; Ceccarelli, Michele; Riccardi, Miriam; Ravo, Maria; Weisz, Alessandro; Federico, Antonella; Franco, Renato; Rocco, Gaetano; Mancini, Rita; Rizzuto, Antonia; Gulletta, Elio; Ciliberto, Gennaro; Viglietto, Giuseppe

    2015-12-15

    Here we report that the PI3K/Akt1/IL-6/STAT3 signalling pathway regulates generation and stem cell-like properties of Non-Small Cell Lung Cancer (NSCLC) tumor initiating cells (TICs). Mutant Akt1, mutant PIK3CA or PTEN loss enhances formation of lung cancer spheroids (LCS), self-renewal, expression of stemness markers and tumorigenic potential of human immortalized bronchial cells (BEAS-2B) whereas Akt inhibition suppresses these activities in established (NCI-H460) and primary NSCLC cells. Matched microarray analysis of Akt1-interfered cells and LCSs identified IL-6 as a critical target of Akt signalling in NSCLC TICs. Accordingly, suppression of Akt in NSCLC cells decreases IL-6 levels, phosphorylation of IkK and IkB, NF-kB transcriptional activity, phosphorylation and transcriptional activity of STAT3 whereas active Akt1 up-regulates them. Exposure of LCSs isolated from NSCLC cells to blocking anti-IL-6 mAbs, shRNA to IL-6 receptor or to STAT3 markedly reduces the capability to generate LCSs, to self-renew and to form tumors, whereas administration of IL-6 to Akt-interfered cells restores the capability to generate LCSs. Finally, immunohistochemical studies in NSCLC patients demonstrated a positive correlative trend between activated Akt, IL-6 expression and STAT3 phosphorylation (n = 94; p < 0.05). In conclusion, our data indicate that aberrant Akt signalling contributes to maintaining stemness in lung cancer TICs through a NF-kB/IL-6/STAT3 pathway and provide novel potential therapeutic targets for eliminating these malignant cells in NSCLC.

  7. The Akt1/IL-6/STAT3 pathway regulates growth of lung tumor initiating cells

    Science.gov (United States)

    Malanga, Donatella; De Marco, Carmela; Guerriero, Ilaria; Colelli, Fabiana; Rinaldo, Nicola; Scrima, Marianna; Mirante, Teresa; De Vitis, Claudia; Zoppoli, Pietro; Ceccarelli, Michele; Riccardi, Miriam; Ravo, Maria; Weisz, Alessandro; Federico, Antonella; Franco, Renato; Rocco, Gaetano; Mancini, Rita; Rizzuto, Antonia; Gulletta, Elio; Ciliberto, Gennaro; Viglietto, Giuseppe

    2015-01-01

    Here we report that the PI3K/Akt1/IL-6/STAT3 signalling pathway regulates generation and stem cell-like properties of Non-Small Cell Lung Cancer (NSCLC) tumor initiating cells (TICs). Mutant Akt1, mutant PIK3CA or PTEN loss enhances formation of lung cancer spheroids (LCS), self-renewal, expression of stemness markers and tumorigenic potential of human immortalized bronchial cells (BEAS-2B) whereas Akt inhibition suppresses these activities in established (NCI-H460) and primary NSCLC cells. Matched microarray analysis of Akt1-interfered cells and LCSs identified IL-6 as a critical target of Akt signalling in NSCLC TICs. Accordingly, suppression of Akt in NSCLC cells decreases IL-6 levels, phosphorylation of IkK and IkB, NF-kB transcriptional activity, phosphorylation and transcriptional activity of STAT3 whereas active Akt1 up-regulates them. Exposure of LCSs isolated from NSCLC cells to blocking anti-IL-6 mAbs, shRNA to IL-6 receptor or to STAT3 markedly reduces the capability to generate LCSs, to self-renew and to form tumors, whereas administration of IL-6 to Akt-interfered cells restores the capability to generate LCSs. Finally, immunohistochemical studies in NSCLC patients demonstrated a positive correlative trend between activated Akt, IL-6 expression and STAT3 phosphorylation (n = 94; p < 0.05). In conclusion, our data indicate that aberrant Akt signalling contributes to maintaining stemness in lung cancer TICs through a NF-kB/IL-6/STAT3 pathway and provide novel potential therapeutic targets for eliminating these malignant cells in NSCLC. PMID:26486080

  8. Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells

    Directory of Open Access Journals (Sweden)

    Yang Jin

    2008-08-01

    Full Text Available Abstract Background Although lung cancer is among the few malignancies for which we know the primary etiological agent (i.e., cigarette smoke, a precise understanding of the temporal sequence of events that drive tumor progression remains elusive. In addition to finding that cigarette smoke (CS impacts the functioning of key pathways with significant roles in redox homeostasis, xenobiotic detoxification, cell cycle control, and endoplasmic reticulum (ER functioning, our data highlighted a defensive role for the unfolded protein response (UPR program. The UPR promotes cell survival by reducing the accumulation of aberrantly folded proteins through translation arrest, production of chaperone proteins, and increased degradation. Importance of the UPR in maintaining tissue health is evidenced by the fact that a chronic increase in defective protein structures plays a pathogenic role in diabetes, cardiovascular disease, Alzheimer's and Parkinson's syndromes, and cancer. Methods Gene and protein expression changes in CS exposed human cell cultures were monitored by high-density microarrays and Western blot analysis. Tissue arrays containing samples from 110 lung cancers were probed with antibodies to proteins of interest using immunohistochemistry. Results We show that: 1 CS induces ER stress and activates components of the UPR; 2 reactive species in CS that promote oxidative stress are primarily responsible for UPR activation; 3 CS exposure results in increased expression of several genes with significant roles in attenuating oxidative stress; and 4 several major UPR regulators are increased either in expression (i.e., BiP and eIF2α or phosphorylation (i.e., phospho-eIF2α in a majority of human lung cancers. Conclusion These data indicate that chronic ER stress and recruitment of one or more UPR effector arms upon exposure to CS may play a pivotal role in the etiology or progression of lung cancers, and that phospho-eIF2α and BiP may have

  9. Normal Lung Quantification in Usual Interstitial Pneumonia Pattern: The Impact of Threshold-based Volumetric CT Analysis for the Staging of Idiopathic Pulmonary Fibrosis.

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    Hirotsugu Ohkubo

    Full Text Available Although several computer-aided computed tomography (CT analysis methods have been reported to objectively assess the disease severity and progression of idiopathic pulmonary fibrosis (IPF, it is unclear which method is most practical. A universal severity classification system has not yet been adopted for IPF.The purpose of this study was to test the correlation between quantitative-CT indices and lung physiology variables and to determine the ability of such indices to predict disease severity in IPF.A total of 27 IPF patients showing radiological UIP pattern on high-resolution (HR CT were retrospectively enrolled. Staging of IPF was performed according to two classification systems: the Japanese and GAP (gender, age, and physiology staging systems. CT images were assessed using a commercially available CT imaging analysis workstation, and the whole-lung mean CT value (MCT, the normally attenuated lung volume as defined from -950 HU to -701 Hounsfield unit (NL, the volume of the whole lung (WL, and the percentage of NL to WL (NL%, were calculated.CT indices (MCT, WL, and NL closely correlated with lung physiology variables. Among them, NL strongly correlated with forced vital capacity (FVC (r = 0.92, P <0.0001. NL% showed a large area under the receiver operating characteristic curve for detecting patients in the moderate or advanced stages of IPF. Multivariable logistic regression analyses showed that NL% is significantly more useful than the percentages of predicted FVC and predicted diffusing capacity of the lungs for carbon monoxide (Japanese stage II/III/IV [odds ratio, 0.73; 95% confidence intervals (CI, 0.48 to 0.92; P < 0.01]; III/IV [odds ratio. 0.80; 95% CI 0.59 to 0.96; P < 0.01]; GAP stage II/III [odds ratio, 0.79; 95% CI, 0.56 to 0.97; P < 0.05].The measurement of NL% by threshold-based volumetric CT analysis may help improve IPF staging.

  10. Loss of the intestinal mucus layer in the normal rat causes gut injury but not toxic mesenteric lymph nor lung injury.

    Science.gov (United States)

    Sharpe, Susan M; Qin, Xiaofa; Lu, Qi; Feketeova, Eleonora; Palange, David C; Dong, Wei; Sheth, Sharvil U; Lee, Marlon A; Reino, Diego; Xu, Da-Zhong; Deitch, Edwin A

    2010-11-01

    There is substantial evidence that gut barrier failure is associated with distant organ injury and systemic inflammation. After major trauma or stress, the factors and mechanisms involved in gut injury are unknown. Our primary hypothesis is that loss of the intestinal mucus layer will result in injury of the normal gut that is exacerbated by the presence of luminal pancreatic proteases. Our secondary hypothesis is that the injury produced in the gut will result in the production of biologically active mesenteric lymph and consequently distant organ (i.e., lung) injury. To test this hypothesis, five groups of rats were studied: 1) uninstrumented naive rats; 2) control rats in which a ligated segment of distal ileum was filled with saline; 3) rats with pancreatic proteases placed in their distal ileal segments; 4) rats with the mucolytic N-acetylcysteine (NAC) placed in their distal ileal segments; and 5) rats exposed to NAC and pancreatic proteases in their ileal segments. The potential systemic consequences of gut injury induced by NAC and proteases were assessed by measuring the biological activity of mesenteric lymph as well as gut-induced lung injury. Exposure of the normal intestine to NAC, but not saline or proteases, led to increased gut permeability, loss of mucus hydrophobicity, a decrease in the mucus layer, as well as morphological evidence of villous injury. Although proteases themselves did not cause gut injury, the combination of pancreatic proteases with NAC caused more severe injury than NAC alone, suggesting that once the mucus barrier is impaired, luminal proteases can injure the now vulnerable gut. Because comparable levels of gut injury caused by systemic insults are associated with gut-induced lung injury, which is mediated by biologically active factors in mesenteric lymph, we next tested whether this local model of gut injury would produce active mesenteric lymph or lead to lung injury. It did not, suggesting that gut injury by itself may not

  11. The role of iron in Libby amphibole-induced acute lung injury and inflammation.

    Science.gov (United States)

    Shannahan, Jonathan H; Ghio, Andrew J; Schladweiler, Mette C; McGee, John K; Richards, Judy H; Gavett, Stephen H; Kodavanti, Urmila P

    2011-05-01

    Complexation of host iron (Fe) on the surface of inhaled asbestos fibers has been postulated to cause oxidative stress contributing to in vivo pulmonary injury and inflammation. We examined the role of Fe in Libby amphibole (LA; mean length 4.99 µm ± 4.53 and width 0.28 µm ± 0.19) asbestos-induced inflammogenic effects in vitro and in vivo. LA contained acid-leachable Fe and silicon. In a cell-free media containing FeCl(3), LA bound #17 µg of Fe/mg of fiber and increased reactive oxygen species generation #3.5 fold, which was reduced by deferoxamine (DEF) treatment. In BEAS-2B cells exposure to LA, LA loaded with Fe (FeLA), or LA with DEF did not increase HO-1 or ferritin mRNA expression. LA increased IL-8 expression, which was reduced by Fe loading but increased by DEF. To determine the role of Fe in LA-induced lung injury in vivo, spontaneously hypertensive rats were exposed intratracheally to either saline (300 µL), DEF (1 mg), FeCl(3) (21 µg), LA (0.5 mg), FeLA (0.5 mg), or LA + DEF (0.5 mg). LA caused BALF neutrophils to increase 24 h post-exposure. Loading of Fe on LA but not chelation slightly decreased neutrophilic influx (LA + DEF > LA > FeLA). At 4 h post-exposure, LA-induced lung expression of MIP-2 was reduced in rats exposed to FeLA but increased by LA + DEF (LA + DEF > LA > FeLA). Ferritin mRNA was elevated in rats exposed to FeLA compared to LA. In conclusion, the acute inflammatory response to respirable fibers and particles may be inhibited in the presence of surface-complexed or cellular bioavailable Fe. Cell and tissue Fe-overload conditions may influence the pulmonary injury and inflammation caused by fibers.

  12. Efficacy evaluation of retrospectively applying the Varian normal breathing predictive filter for volume definition and artifact reduction in 4D CT lung patients.

    Science.gov (United States)

    Malone, Ciaran; Rock, Luke; Skourou, Christina

    2014-05-08

    Phase-based sorting of four-dimensional computed tomography (4D CT) datasets is prone to image artifacts due to patient's breathing irregularities that occur during the image acquisition. The purpose of this study is to investigate the effect of the Varian normal breathing predictive filter (NBPF) as a retrospective phase-sorting parameter in 4D CT. Ten 4D CT lung cancer datasets were obtained. The volumes of all tumors present, as well as the total lung volume, were calculated on the maximum intensity projection (MIP) images as well as each individual phase image. The NBPF was varied retrospectively within the available range, and changes in volume and image quality were recorded. The patients' breathing trace was analysed and the magnitude and location of any breathing irregularities were correlated to the behavior of the NBPF. The NBPF was found to have a considerable effect on the quality of the images in MIP and single-phase datasets. When used appropriately, the NBPF is shown to have the ability to account for and correct image artifacts. However, when turned off (0%) or set above a critical level (approximately 40%), it resulted in erroneous volume reconstructions with variations in tumor volume up to 26.6%. Those phases associated with peak inspiration were found to be more susceptible to changes in the NBPF. The NBPF settings selected prior to exporting the breathing trace for patients evaluated using 4D CT directly affect the accuracy of the targeting and volume estimation of lung tumors. Recommendations are made to address potential errors in patient anatomy introduced by breathing irregularities, specifically deep breath or cough irregularities, by implementing the proper settings and use of this tool.

  13. Effect of mixing scanner types and reconstruction kernels on the characterization of lung parenchymal pathologies: emphysema, interstitial pulmonary fibrosis and normal non-smokers

    Science.gov (United States)

    Xu, Ye; van Beek, Edwin J.; McLennan, Geoffrey; Guo, Junfeng; Sonka, Milan; Hoffman, Eric

    2006-03-01

    In this study we utilize our texture characterization software (3-D AMFM) to characterize interstitial lung diseases (including emphysema) based on MDCT generated volumetric data using 3-dimensional texture features. We have sought to test whether the scanner and reconstruction filter (kernel) type affect the classification of lung diseases using the 3-D AMFM. We collected MDCT images in three subject groups: emphysema (n=9), interstitial pulmonary fibrosis (IPF) (n=10), and normal non-smokers (n=9). In each group, images were scanned either on a Siemens Sensation 16 or 64-slice scanner, (B50f or B30 recon. kernel) or a Philips 4-slice scanner (B recon. kernel). A total of 1516 volumes of interest (VOIs; 21x21 pixels in plane) were marked by two chest imaging experts using the Iowa Pulmonary Analysis Software Suite (PASS). We calculated 24 volumetric features. Bayesian methods were used for classification. Images from different scanners/kernels were combined in all possible combinations to test how robust the tissue classification was relative to the differences in image characteristics. We used 10-fold cross validation for testing the result. Sensitivity, specificity and accuracy were calculated. One-way Analysis of Variances (ANOVA) was used to compare the classification result between the various combinations of scanner and reconstruction kernel types. This study yielded a sensitivity of 94%, 91%, 97%, and 93% for emphysema, ground-glass, honeycombing, and normal non-smoker patterns respectively using a mixture of all three subject groups. The specificity for these characterizations was 97%, 99%, 99%, and 98%, respectively. The F test result of ANOVA shows there is no significant difference (p <0.05) between different combinations of data with respect to scanner and convolution kernel type. Since different MDCT and reconstruction kernel types did not show significant differences in regards to the classification result, this study suggests that the 3-D AMFM can

  14. Bone Morphogenetic Protein (BMP-4 and BMP-7 regulate differentially Transforming Growth Factor (TGF-β1 in normal human lung fibroblasts (NHLF

    Directory of Open Access Journals (Sweden)

    Lloyd Clare M

    2010-06-01

    Full Text Available Abstract Background Airway remodelling is thought to be under the control of a complex group of molecules belonging to the Transforming Growth Factor (TGF-superfamily. The Bone Morphogenetic Proteins (BMPs belong to this family and have been shown to regulate fibrosis in kidney and liver diseases. However, the role of BMPs in lung remodelling remains unclear. BMPs may regulate tissue remodelling in asthma by controlling TGF-β-induced profibrotic functions in lung fibroblasts. Methods Cell cultures were exposed to TGF-β1 alone or in the presence of BMP-4 or BMP-7; control cultures were exposed to medium only. Cell proliferation was assessed by quantification of the incorporation of [3H]-thymidine. The expression of the mRNA encoding collagen type I and IV, tenascin C and fibronectin in normal human lung fibroblasts (NHLF was determined by real-time quantitative PCR and the main results were confirmed by ELISA. Cell differentiation was determined by the analysis of the expression of α-smooth muscle actin (α-SMA by western blot and immunohistochemistry. The effect on matrix metalloproteinase (MMP activity was assessed by zymography. Results We have demonstrated TGF-β1 induced upregulation of mRNAs encoding the extracellular matrix proteins, tenascin C, fibronectin and collagen type I and IV when compared to unstimulated NHLF, and confirmed these results at the protein level. BMP-4, but not BMP-7, reduced TGF-β1-induced extracellular matrix protein production. TGF-β1 induced an increase in the activity of the pro-form of MMP-2 which was inhibited by BMP-7 but not BMP-4. Both BMP-4 and BMP-7 downregulated TGF-β1-induced MMP-13 release compared to untreated and TGF-β1-treated cells. TGF-β1 also induced a myofibroblast-like transformation which was partially inhibited by BMP-7 but not BMP-4. Conclusions Our study suggests that some regulatory properties of BMP-7 may be tissue or cell type specific and unveil a potential regulatory role for

  15. Effect of the normalized prescription isodose line on the magnitude of Monte Carlo vs. pencil beam target dose differences for lung stereotactic body radiotherapy.

    Science.gov (United States)

    Zheng, Dandan; Zhang, Qinghui; Liang, Xiaoying; Zhu, Xiaofeng; Verma, Vivek; Wang, Shuo; Zhou, Sumin

    2016-07-08

    In lung stereotactic body radiotherapy (SBRT) cases, the pencil beam (PB) dose calculation algorithm is known to overestimate target dose as compared to the more accurate Monte Carlo (MC) algorithm. We investigated whether changing the normalized prescription isodose line affected the magnitude of MC vs. PB target dose differences. Forty-eight patient plans and twenty virtual-tumor phantom plans were studied. For patient plans, four alternative plans prescribed to 60%, 70%, 80%, and 90% isodose lines were each created for 12 patients who previously received lung SBRT treatments. Using 6 MV dynamic conformal arcs, the plans were individually optimized to achieve similar dose coverage and conformity for all plans of the same patient, albeit at the different prescription levels. These plans, having used a PB algorithm, were all recalculated with MC to compare the target dose differences. The relative MC vs. PB target dose variations were investigated by comparing PTV D95, Dmean, and D5 loss at the four prescription levels. The MC-to-PB ratio of the plan heterogeneity index (HI) was also evaluated and compared among different isodose levels. To definitively demonstrate the cause of the isodose line dependence, a simulated phantom study was conducted using simple, spherical virtual tumors planned with uniform block margins. The tumor size and beam energy were also altered in the phantom study to investigate the interplay between these confounding factors and the isodose line effect. The magnitude of the target dose overestimation by PB was greater for higher prescription isodose levels. The MC vs. PB reduction in the target dose coverage indices, D95 and V100 of PTV, were found to monotonically increase with increasing isodose lines from 60% to 90%, resulting in more pronounced target dose coverage deficiency at higher isodose prescription levels. No isodose level-dependent trend was observed for the dose errors in the target mean or high dose indices, Dmean or D5. The

  16. Comparative DNA damage and transcriptomic effects of engineered nanoparticles in human lung cells in vitro

    Science.gov (United States)

    A series of six titanium dioxide and two cerium oxide engineered nanomaterials were assessed for their ability to induce cytotoxicity, reactive oxygen species (ROS), various types of DNA damage, and transcriptional changes in human respiratory BEAS-2B cells exposed in vitro at se...

  17. Comparison of molecular signatures in large scale protein interaction networks in normal and cancer conditions of brain, cervix, lung, ovary and prostate

    Directory of Open Access Journals (Sweden)

    Rajat Suvra Banik

    2016-04-01

    Full Text Available Background Cancer, the disease of intricateness, has remained beyond our complete perception so far. Network systems biology (termed NSB is one of the most recent approaches to understand the unsolved problems of cancer development. From this perspective, differential protein networks (PINs have been developed based on the expression and interaction data of brain, cervix, lung, ovary and prostate for normal and cancer conditions. Methods Differential expression database GeneHub-GEPIS and interaction database STRING were applied for primary data retrieval. Cytoscape platform and related plugins named network analyzer; MCODE and ModuLand were used for visualization of complex networks and subsequent analysis. Results Significant differences were observedamong different common network parameters between normal and cancer states. Moreover, molecular complex numbers and overlapping modularization found to be varying significantly between normal and cancerous tissues. The number of the ranked molecular complex and the nodes involved in the overlapping modules were meaningfully higher in cancer condition.We identified79 commonly up regulated and 6 down regulated proteins in all five tissues. Number of nodes, edges; multi edge node pair, and average number of neighbor are found with significant fluctuations in case of cervix and ovarian tissues.Cluster analysis showed that the association of Myc and Cdk4 proteins is very close with other proteins within the network.Cervix and ovarian tissue showed higher increment of the molecular complex number and overlapping module network during cancer in comparison to normal state. Conclusions The differential molecular signatures identified from the work can be studied further to understand the cancer signaling process, and potential therapeutic and detection approach. [Biomed Res Ther 2016; 3(4.000: 605-615

  18. Phloretin Attenuates Allergic Airway Inflammation and Oxidative Stress in Asthmatic Mice

    Science.gov (United States)

    Huang, Wen-Chung; Fang, Li-Wen; Liou, Chian-Jiun

    2017-01-01

    Phloretin (PT), isolated from the apple tree, was previously demonstrated to have antioxidative and anti-inflammatory effects in macrophages and anti-adiposity effects in adipocytes. Inflammatory immune cells generate high levels of reactive oxygen species (ROS) for stimulated severe airway hyperresponsiveness (AHR) and airway inflammation. In this study, we investigated whether PT could reduce oxidative stress, airway inflammation, and eosinophil infiltration in asthmatic mice, and ameliorate oxidative and inflammatory responses in tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin (OVA) to induce asthma symptoms. Mice were randomly assigned to the five experimental groups: normal controls; OVA-induced asthmatic mice; and OVA-induced mice injected intraperitoneally with one of the three PT doses (5, 10, or 20 mg/kg). In addition, we treated inflammatory human tracheal epithelial cells (BEAS-2B cells) with PT to assess oxidative responses and the levels of proinflammatory cytokines and chemokines. We found that PT significantly reduced goblet cell hyperplasia and eosinophil infiltration, which decreased AHR, inflammation, and oxidative responses in the lungs of OVA-sensitized mice. PT also decreased malondialdehyde levels in the lung and reduced Th2 cytokine production in bronchoalveolar lavage fluids. Furthermore, PT reduced ROS, proinflammatory cytokines, and eotaxin production in BEAS-2B cells. PT also suppressed monocyte cell adherence to inflammatory BEAS-2B cells. These findings suggested that PT alleviated pathological changes, inflammation, and oxidative stress by inhibiting Th2 cytokine production in asthmatic mice. PT showed therapeutic potential for ameliorating asthma symptoms in the future. PMID:28243240

  19. The H2S-generating enzymes cystathionine β-synthase and cystathionine γ-lyase play a role in vascular development during normal lung alveolarization.

    Science.gov (United States)

    Madurga, Alicia; Golec, Anita; Pozarska, Agnieszka; Ishii, Isao; Mižíková, Ivana; Nardiello, Claudio; Vadász, István; Herold, Susanne; Mayer, Konstantin; Reichenberger, Frank; Fehrenbach, Heinz; Seeger, Werner; Morty, Rory E

    2015-10-01

    The gasotransmitter hydrogen sulfide (H2S) is emerging as a mediator of lung physiology and disease. Recent studies revealed that H2S administration limited perturbations to lung structure in experimental animal models of bronchopulmonary dysplasia (BPD), partially restoring alveolarization, limiting pulmonary hypertension, limiting inflammation, and promoting epithelial repair. No studies have addressed roles for endogenous H2S in lung development. H2S is endogenously generated by cystathionine β-synthase (Cbs) and cystathionine γ-lyase (Cth). We demonstrate here that the expression of Cbs and Cth in mouse lungs is dynamically regulated during lung alveolarization and that alveolarization is blunted in Cbs(-/-) and Cth(-/-) mouse pups, where a 50% reduction in the total number of alveoli was observed, without any impact on septal thickness. Laser-capture microdissection and immunofluorescence staining indicated that Cbs and Cth were expressed in the airway epithelium and lung vessels. Loss of Cbs and Cth led to a 100-500% increase in the muscularization of small- and medium-sized lung vessels, which was accompanied by increased vessel wall thickness, and an apparent decrease in lung vascular supply. Ablation of Cbs expression using small interfering RNA or pharmacological inhibition of Cth using propargylglycine in lung endothelial cells limited angiogenic capacity, causing a 30-40% decrease in tube length and a 50% decrease in number of tubes formed. In contrast, exogenous administration of H2S with GYY4137 promoted endothelial tube formation. These data confirm a key role for the H2S-generating enzymes Cbs and Cth in pulmonary vascular development and homeostasis and in lung alveolarization.

  20. Macrophages facilitate coal tar pitch extract-induced tumorigenic transformation of human bronchial epithelial cells mediated by NF-κB.

    Directory of Open Access Journals (Sweden)

    Feifei Feng

    Full Text Available OBJECTIVE: Chronic respiratory inflammation has been associated with lung cancer. Tumor-associated macrophages (TAMs play a critical role in the formation of inflammation microenvironment. We sought to characterize the role of TAMs in coal tar pitch extract (CTPE-induced tumorigenic transformation of human bronchial epithelial cells and the underlying mechanisms. METHODS: The expression of TAMs-specific CD68 in lung cancer tissues and paired adjacent tissues from cancer patients was determined using immunostaining. Co-culture of human bronchial epithelial cells (BEAS-2B and macrophage-like THP-1 cells were conducted to evaluate the promotive effect of macrophages on CTPE-induced tumorigenic transformation of BEAS-2B cells. BEAS-2B cells were first treated with 2.4 µg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured either with or without THP-1 cells and passaged using trypsin-EDTA. Alterations of cell cycle, karyotype, colony formation in soft agar and tumor xenograft growth in nude mice of BEAS-2B cells at passages 10, 20 and 30, indicative of tumorigenecity, were determined, respectively. In addition, mRNA and protein levels of NF-κB in BEAS-2B cells were measured with RT-PCR and western blot, respectively. B(aP was used as the positive control. RESULTS: The over-expression of TAMs-specific CD68 around lung tumor tissues was detected and associated with lung cancer progression. The tumorigenic alterations of BEAS-2B cells including increase in cell growth rate, number of cells with aneuploidy, clonogenicity in soft agar, and tumor size in nude mice in vivo occurred at passage 10, becoming significant at passages 20 and 30 of the co-culture following CTPE removal in compared to BEAS-2B cells alone. In addition, the expression levels of NF-κB in BEAS-2B cells were positively correlated to the malignancy of BEAS-2B cells under different conditions of treatment. CONCLUSION: The presence of macrophages

  1. A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Deok Hyo; Lim, Mi-Hee [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Lee, Yu Ran [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Sung, Gi-Ho [Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Suwon 404-707 (Korea, Republic of); Lee, Tae-Ho [R and D Center, Dong-A Pharmaceutical Co, Ltd, Yongin 446-905 (Korea, Republic of); Jeon, Byeong Hwa [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Cho, Jae Youl [Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Song, Won O. [Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Park, Haeil [College of Pharmacy, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Choi, Sunga, E-mail: sachoi@cnu.ac.kr [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Kim, Tae Woong, E-mail: tawkim@kangwon.ac.kr [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2013-12-15

    A synthetic Militarin analog-1[(2R,3R,4R,5R)-1,6-bis(4-(2,4,4-trimethylpentan-2-yl)phenoxy) hexane-2,3,4,5-tetraol] is a novel derivative of constituents from Cordyceps militaris, which has been used to treat a variety of chronic diseases including inflammation, diabetes, hyperglycemia and cancers. Here, we report for the first time the synthesis of Militarin analog-1 (MA-1) and the apoptotic mechanism of MA-1 against human lung cancer cell lines. Treatment with MA-1 significantly inhibited the viability of 3 human lung cancer cell lines. The inhibition of viability and growth in MA-1-treated A549 cells with an IC{sub 50} of 5 μM were mediated through apoptosis induction, as demonstrated by an increase in DNA fragmentation, sub-G{sub 0}/G{sub 1}-DNA fraction, nuclear condensation, and phosphatidylserine exposure. The apoptotic cell death caused mitochondrial membrane permeabilization through regulation of expression of the Bcl-2 family proteins, leading to cytochrome c release in a time-dependent manner. Subsequently, the final stage of apoptosis, activation of caspase-9/-3 and cleavage of poly (ADP ribose) polymerase, was induced. Furthermore, A549 lung cancer cells were more responsive to MA-1 than a bronchial epithelial cell line (BEAS-2B), involving the rapid generation of reactive oxygen species (ROS), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation. The pharmacological inhibition of ROS generation and JNK/p38 MAPK exhibited attenuated DNA fragmentation in MA-1-induced apoptosis. Oral administration of MA-1 also retarded growth of A549 orthotopic xenografts. In conclusion, the present study indicates that the new synthetic derivative MA-1 triggers mitochondrial apoptosis through ROS generation and regulation of MAPKs and may be a potent therapeutic agent against human lung cancer. - Highlights: • We report a novel synthesized derivative, militarin analog-1 (MA-1). • MA-1-induced cancer cell death was triggered by

  2. Differences in Cytotoxic, Genotoxic, and Inflammatory Response of Bronchial and Alveolar Human Lung Epithelial Cells to Pristine and COOH-Functionalized Multiwalled Carbon Nanotubes

    Science.gov (United States)

    Fresegna, Anna Maria; Ciervo, Aureliano; Buresti, Giuliana

    2014-01-01

    Functionalized MWCNTs are used in many commercial and biomedical applications, but their potential health effects are not well defined. We investigated and compared cytotoxic, genotoxic/oxidative, and inflammatory effects of pristine and carboxyl MWCNTs exposing human respiratory (A549 and BEAS-2B) cells to 1–40 μg/mL of CNTs for 24 h. Both MWCNTs induced low viability reduction (by WST1 assay) in A549 cells and only MWCNTs-COOH caused high viability reduction in BEAS-2B cells reaching 28.5% viability at 40 μg/mL. Both CNTs induced membrane damage (by LDH assay) with higher effects in BEAS-2B cells at the highest concentrations reaching 20% cytotoxicity at 40 μg/mL. DNA damage (by Fpg-comet assay) was induced by pristine MWCNTs in A549 cells and by both MWCNTs in BEAS-2B cells reaching for MWCNTs-COOH a tail moment of 22.2 at 40 μg/mL versus 10.2 of unexposed cells. Increases of IL-6 and IL-8 release (by ELISA) were detected in A549 cells exposed to MWCNTs-COOH from 10 μg/mL while IL-8 increased in BEAS-2B cells exposed to pristine MWCNTs at 20 and 40 μg/mL. The results show higher cytogenotoxicity of MWCNTs-COOH in bronchial and of pristine MWCNTs in alveolar cells. Different inflammatory response was also found. The findings suggest the use of in vitro models with different end points and cells to study CNT toxicity. PMID:25147797

  3. Differences in cytotoxic, genotoxic, and inflammatory response of bronchial and alveolar human lung epithelial cells to pristine and COOH-functionalized multiwalled carbon nanotubes.

    Science.gov (United States)

    Ursini, Cinzia Lucia; Cavallo, Delia; Fresegna, Anna Maria; Ciervo, Aureliano; Maiello, Raffaele; Buresti, Giuliana; Casciardi, Stefano; Bellucci, Stefano; Iavicoli, Sergio

    2014-01-01

    Functionalized MWCNTs are used in many commercial and biomedical applications, but their potential health effects are not well defined. We investigated and compared cytotoxic, genotoxic/oxidative, and inflammatory effects of pristine and carboxyl MWCNTs exposing human respiratory (A549 and BEAS-2B) cells to 1-40 μg/mL of CNTs for 24 h. Both MWCNTs induced low viability reduction (by WST1 assay) in A549 cells and only MWCNTs-COOH caused high viability reduction in BEAS-2B cells reaching 28.5% viability at 40 μg/mL. Both CNTs induced membrane damage (by LDH assay) with higher effects in BEAS-2B cells at the highest concentrations reaching 20% cytotoxicity at 40 μg/mL. DNA damage (by Fpg-comet assay) was induced by pristine MWCNTs in A549 cells and by both MWCNTs in BEAS-2B cells reaching for MWCNTs-COOH a tail moment of 22.2 at 40 μg/mL versus 10.2 of unexposed cells. Increases of IL-6 and IL-8 release (by ELISA) were detected in A549 cells exposed to MWCNTs-COOH from 10 μg/mL while IL-8 increased in BEAS-2B cells exposed to pristine MWCNTs at 20 and 40 μg/mL. The results show higher cytogenotoxicity of MWCNTs-COOH in bronchial and of pristine MWCNTs in alveolar cells. Different inflammatory response was also found. The findings suggest the use of in vitro models with different end points and cells to study CNT toxicity.

  4. Cadmium induces cytotoxicity in human bronchial epithelial cells through upregulation of eIF5A1 and NF-kappaB

    Energy Technology Data Exchange (ETDEWEB)

    Chen, De-Ju; Xu, Yan-Ming; Du, Ji-Ying [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Huang, Dong-Yang [Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Lau, Andy T.Y., E-mail: andytylau@stu.edu.cn [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China)

    2014-02-28

    Highlights: • Normal human bronchial epithelial cells (BEAS-2B) were dosed with cadmium (Cd). • A low level (2 μM) of Cd treatment for 36 h elicited negligible cytotoxicity. • High levels (20 or 30 μM) of Cd treatment for 36 h induced cell death. • High levels of Cd can upregulate the protein levels of eIF5A1 and NF-κB p65. • We suggest that eIF5A1 level is possibly modulated by NF-κB. - Abstract: Cadmium (Cd) and Cd compounds are widely-distributed in the environment and well-known carcinogens. Here, we report that in CdCl{sub 2}-exposed human bronchial epithelial cells (BEAS-2B), the level of p53 is dramatically decreased in a time- and dose-dependent manner, suggesting that the observed Cd-induced cytotoxicity is not likely due to the pro-apoptotic function of p53. Therefore, this prompted us to further study the responsive pro-apoptotic factors by proteomic approaches. Interestingly, we identified that high levels (20 or 30 μM) of Cd can significantly upregulate the protein levels of eukaryotic translation initiation factor 5A1 (eIF5A1) and redox-sensitive transcription factor NF-κB p65. Moreover, there is an enhanced NF-κB nuclear translocation as well as chromatin-binding in Cd-treated BEAS-2B cells. We also show that small interfering RNA-specific knockdown of eIF5A1 in Cd-exposed cells attenuated the Cd cytotoxicity, indicating the potential role of eIF5A1 in Cd cytotoxicity. As eIF5A1 is reported to be related with cell apoptosis but little is known about its transcriptional control, we hypothesize that NF-κB might likely modulate eIF5A1 gene expression. Notably, by bioinformatic analysis, several potential NF-κB binding sites on the upstream promoter region of eIF5A1 gene can be found. Subsequent chromatin immunoprecipitation assay revealed that indeed there is enhanced NF-κB binding on eIF5A1 promoter region of Cd-treated BEAS-2B cells. Taken together, our findings suggest for the first time a regulatory mechanism for the pro

  5. Lung transplant - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100120.htm Lung transplant - series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 5 Go to slide 2 out of ... to slide 5 out of 5 Overview The lungs, which reside in the thorax, or chest cavity, ...

  6. Signaling networks associated with AKT activation in non-small cell lung cancer (NSCLC: new insights on the role of phosphatydil-inositol-3 kinase.

    Directory of Open Access Journals (Sweden)

    Marianna Scrima

    Full Text Available Aberrant activation of PI3K/AKT signalling represents one of the most common molecular alterations in lung cancer, though the relative contribution of the single components of the cascade to the NSCLC development is still poorly defined. In this manuscript we have investigated the relationship between expression and genetic alterations of the components of the PI3K/AKT pathway [KRAS, the catalytic subunit of PI3K (p110α, PTEN, AKT1 and AKT2] and the activation of AKT in 107 surgically resected NSCLCs and have analyzed the existing relationships with clinico-pathologic features. Expression analysis was performed by immunohistochemistry on Tissue Micro Arrays (TMA; mutation analysis was performed by DNA sequencing; copy number variation was determined by FISH. We report that activation of PI3K/AKT pathway in Italian NSCLC patients is associated with high grade (G3-G4 compared with G1-G2; n = 83; p<0.05 and more advanced disease (TNM stage III vs. stages I and II; n = 26; p<0.05. In addition, we found that PTEN loss (41/104, 39% and the overexpression of p110α (27/92, 29% represent the most frequent aberration observed in NSCLCs. Less frequent molecular lesions comprised the overexpression of AKT2 (18/83, 22% or AKT1 (17/96, 18%, and KRAS mutation (7/63, 11%. Our results indicate that, among all genes, only p110α overexpression was significantly associated to AKT activation in NSCLCs (p = 0.02. Manipulation of p110α expression in lung cancer cells carrying an active PI3K allele (NCI-H460 efficiently reduced proliferation of NSCLC cells in vitro and tumour growth in vivo. Finally, RNA profiling of lung epithelial cells (BEAS-2B expressing a mutant allele of PIK3 (E545K identified a network of transcription factors such as MYC, FOS and HMGA1, not previously recognised to be associated with aberrant PI3K signalling in lung cancer.

  7. Darkfield-Confocal Microscopy detection of nanoscale particle internalization by human lung cells

    Directory of Open Access Journals (Sweden)

    Samet James M

    2011-01-01

    Full Text Available Abstract Background Concerns over the health effects of nanomaterials in the environment have created a need for microscopy methods capable of examining the biological interactions of nanoparticles (NP. Unfortunately, NP are beyond the diffraction limit of resolution for conventional light microscopy (~200 nm. Fluorescence and electron microscopy techniques commonly used to examine NP interactions with biological substrates have drawbacks that limit their usefulness in toxicological investigation of NP. EM is labor intensive and slow, while fluorescence carries the risk of photobleaching the sample and has size resolution limits. In addition, many relevant particles lack intrinsic fluorescence and therefore can not be detected in this manner. To surmount these limitations, we evaluated the potential of a novel combination of darkfield and confocal laser scanning microscopy (DF-CLSM for the efficient 3D detection of NP in human lung cells. The DF-CLSM approach utilizes the contrast enhancements of darkfield microscopy to detect objects below the diffraction limit of 200 nm based on their light scattering properties and interfaces it with the power of confocal microscopy to resolve objects in the z-plane. Results Validation of the DF-CLSM method using fluorescent polystyrene beads demonstrated spatial colocalization of particle fluorescence (Confocal and scattered transmitted light (Darkfield along the X, Y, and Z axes. DF-CLSM imaging was able to detect and provide reasonable spatial locations of 27 nm TiO2 particles in relation to the stained nuclei of exposed BEAS 2B cells. Statistical analysis of particle proximity to cellular nuclei determined a significant difference between 5 min and 2 hr particle exposures suggesting a time-dependant internalization process. Conclusions DF-CLSM microscopy is an alternative to current conventional light and electron microscopy methods that does not rely on particle fluorescence or contrast in electron

  8. Identification of biomarkers of radioresponse and subsequent progression towards lung cancer in normal human bronchial epithelial cells after HZE particle irradiation

    Science.gov (United States)

    Story, Michael; Ding, Liang-Hao; Park, Seongmi; Minna, John

    mice. Tumors that develop will be examined for radiosensitivity and aggres-siveness and will be also be examined for genomic, epigenomic and proteomic changes. Com-parisons of unirradiated cells, transformed cells, and tumor cells will allow the development of biomarkers of radiation-induced lung cancer, in particular HZE-induced lung tumors, and help to generate risk factors for lung cancer as a result of travel through deep space environments.

  9. Highly purified, multi-wall carbon nanotubes induce light-chain 3B expression in human lung cells

    Energy Technology Data Exchange (ETDEWEB)

    Tsukahara, Tamotsu, E-mail: ttamotsu@kanazawa-med.ac.jp [Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Matsuda, Yoshikazu [Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Ina-machi, Saitama 362-0806 (Japan); Usui, Yuki [Research Center for Exotic Nanocarbons, Shinshu University, 4-17-1 Wakasato, Nagano-shi, Nagano 380-8553 (Japan); Haniu, Hisao [Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan)

    2013-10-18

    Highlights: •HTT2800-treated BEAS-2B cells induced LC3B in a time-dependent manner. •HTT2800-treated BEAS-2B cells showed decreased cell proliferation that was both time- and dose-dependent. •Addition of 3-MA, LC3B-II protein and mRNA levels were significantly decreased. •3-MA and E64-d + pepstatin A, but not brefeldin A, provided protection against HTT2800-induced cell death. •These results suggest that HTT2800 predominantly causes autophagy rather than apoptotic cell death in BEAS-2B cells. -- Abstract: Bronchial epithelial cells are targets of inhalation and play a critical role in the maintenance of mucosal integrity as mechanical barriers against various particles. Our previous result suggest that vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. Increasing evidence suggests that autophagy may critically influence vital cellular processes such as apoptosis, cell proliferation and inflammation and thereby may play a critical role in pulmonary diseases. Autophagy was recently recognized as a critical cell death pathway, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles. In this study, the authors focus on the autophagic responses of HTT2800 exposure. The HTT2800-exposed cells induced LC3B expression and induced cell growth inhibition.

  10. Lung transplant

    Science.gov (United States)

    Solid organ transplant - lung ... the chance that the body will reject the transplant . Lungs can also be given by living donors. ... the person who is receiving it. During lung transplant surgery, you are asleep and pain-free (under ...

  11. Response of right ventricular size, function, and pressure to supine exercise: a comparison of patients with chronic obstructive lung disease and normal subjects

    Energy Technology Data Exchange (ETDEWEB)

    Slutsky, R.; Hooper, W.; Ackerman, W.; Moser, K.

    1982-12-01

    The response of right ventricular ejection fraction (RVEF) and right ventricular end-diastolic volume (RVEDV) to exercise was studied in 11 patients with severe (FEV/sub 25/sub(%)sub(-)/sub 75/sub(%)=0.32+-0.13, mean+-SD) chronic obstructive pulmonary disease (COPD). Using gated radionuclide cardiac blood pool imaging techniques, the response of the patients with COPD was compared with that of 15 control subjects. Arterial blood gases, pulmonary arterial pressures, wedge pressure, and right ventricular pressures also were monitored in patients with COPD. The resting RVEF was lower and the resting RVEDV was higher in patients with COPD than in normals (both, P<0.01). Two of the 11 COPD patients had a RVEF during rest that was below lower limits, while 10 of 11 patients had RV dilation. Right ventricular end-diastolic pressure, measured during rest in patients with COPD, was normal (6.1+-2.1 mm Hg) and cardiac index was within normal limits (3.55+-0.82 l/min/m/sup 2/). With exercise this cardiac index rose to 5.52+-1.7/min/m/sup 2/(P<0.01) due to the increase in heart rate (83+-18 to 125+-25 beats/min; P<0.01) while stroke volume did not significantly change. During exercise, normal subjects showed an increase in RVEF while RVEDV did not change; in patients with COPD, the RVEF fell and the RVEDV increased. In the patients with COPD, mild resting arterial hypoxemia and hypercapnia were both exaggerated during exercise; and mild resting pulmonary arterial hypertension (PAm=24.3+-7.65 mm Hg) also worsened with exercise (PAm=41+-19 mm Hg, P<0.01). Correlation between change in RVEF and PAm was -0.58, and between change in RVEDV and PAm was 0.63. We conclude that patients with severe COPD often have right ventricular dilation at rest and commonly respond to supine exercise with a fall in FV ejection fraction and further dilation of the right ventricle.

  12. Estimation of Lung Ventilation

    Science.gov (United States)

    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.

  13. The IL-5 receptor expression on bronchial epithelial cell line-BEAS-2B%白细胞介素5受体α链在支气管上皮细胞BEAS-2B的表达

    Institute of Scientific and Technical Information of China (English)

    汤葳; Albert Chan; Stanley Chik; Adrain Wu; 邓伟吾

    2007-01-01

    目的 白细胞介素5(IL-5)作为参与嗜酸粒细胞成熟、分化过程的最主要因子,其作用通过特异性受体IL-5Rα介导.本文以支气管上皮细胞株为研究对象,证实该上皮细胞株在炎症因子的刺激下可以表达IL-5Rα.方法 通过促炎症因子TNF-α和TH2型细胞因子IL-4、IL-5、IL-13以及白三烯成分之一的LTCA(白三烯C4)对细胞进行单独或协同刺激,以RT-PCR方法、流式细胞检测技术评价上皮细胞对IL-5Rα的基因和蛋白质的表达,同时评价在IL-5和TNF-α的协同刺激下IL-5Rα、ICAM-1和VCAM-1的协同表达.结果 正常支气管上皮细胞在TH2型细胞因子、LTCA和TNF-α的刺激下可以表达IL-5Rα基因,在TNF-α单独或与其他因子的协同刺激下表达显著增强,更可以表达IL-5Rα蛋白.流式细胞检测分析显示TNF-α单独或协同刺激后16 h IL-5Rα蛋白表达最高,并随时间的延长表达下降.当TNF-α与IL-5协同刺激后上皮细胞可以同时表达VCAM-1和IL-5Rα,而ICAM-1呈持续表达.结论 通过对支气管上皮细胞的研究证实了支气管上皮细胞可以在炎症因子TNF-α和TH2型细胞因子的协同刺激下进一步表达IL-5特异性受体IL-5Rα,并在IL-5和TNF-α的刺激下进一步表达黏附分子VCAM-1,吸引嗜酸粒细胞及其前体细胞浸润至气道参与炎症.说明支气管上皮细胞不仅在哮喘炎症反应中是最主要的受累器官,也是导致炎症的参与者之一.

  14. Advances in Lung Stem Cells and Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Huijing YIN

    2015-10-01

    Full Text Available Cancer stem cells (CSCs are emerging as a hot topic for cancer research. Lung CSCs share many characteristics with normal lung stem cells (SCs, including self-renewal and multi-potency for differentiation. Many molecular markers expressed in various types of CSCs were also found in lung CSCs, such as CD133, CD44, aldehyde dehydrogenase (ALDH and ATP-binding cassette sub-family G member 2 (ABCG2. Similarly, proliferation and expansion of lung CSCs are regulated not only by signal transduction pathways functioning in normal lung SCs, such as Notch, Hedgehog and Wnt pathways, but also by those acting in tumor cells, such as epidermal growth factor receptor (EGFR, signal transducer and activator of transcription 3 (STAT3 and phosphatidylinositol 3 kinase (PI3K pathways. As CSC plays an critical role in tumor recurrence, metastasis and drug-resistance, understanding the difference between lung CSCs and normal lung SCs, identifying and targeting CSC markers or related signaling pathways may increase the efficacy of therapy on lung cancer and improved survival of lung cancer patients.

  15. [Advances in Lung Stem Cells and Lung Cancer Stem Cells].

    Science.gov (United States)

    Yin, Huijing; Deng, Jiong

    2015-10-20

    Cancer stem cells (CSCs) are emerging as a hot topic for cancer research. Lung CSCs share many characteristics with normal lung stem cells (SCs), including self-renewal and multi-potency for differentiation. Many molecular markers expressed in various types of CSCs were also found in lung CSCs, such as CD133, CD44, aldehyde dehydrogenase (ALDH) and ATP-binding cassette sub-family G member 2 (ABCG2). Similarly, proliferation and expansion of lung CSCs are regulated not only by signal transduction pathways functioning in normal lung SCs, such as Notch, Hedgehog and Wnt pathways, but also by those acting in tumor cells, such as epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K) pathways. As CSC plays an critical role in tumor recurrence, metastasis and drug-resistance, understanding the difference between lung CSCs and normal lung SCs, identifying and targeting CSC markers or related signaling pathways may increase the efficacy of therapy on lung cancer and improved survival of lung cancer patients.

  16. Lung Sounds in Bronchial Asthma

    Directory of Open Access Journals (Sweden)

    Yukio Nagasaka

    2012-01-01

    In lung sound analysis, the narrower the airways are, the higher the frequency of breathing sounds is, and, if a patient has higher than normal breathing sounds, i.e., bronchial sounds, he or she may have airway narrowing or airway inflammation. It is sometimes difficult to detect subtle changes in lung sounds; therefore, we anticipate that automated analysis of lung sounds will be used to overcome these difficulties in the near future.

  17. LUNGEOMETRY- GEOMETRICAL INVESTIGATION OF LUNGE

    Directory of Open Access Journals (Sweden)

    R.Vinodh Rajkumar

    2015-02-01

    Full Text Available Physiotherapists must learn the biomechanics of lunge in detail to clearly understand its significance in human life and implement effective training measures to overcome the limiting factors of proper lunge of their clientele. To understand the biomechanical value of every movement, interesting experimental learning methods must be employed to kindle the Physiotherapists to actively take part in research activities from the under-graduate level onwards. Lungeometry is a novel, simple and inexpensive experimental investigation of lunge, applying basic geometrical methods taking near normal lower limb length dimensions and rationale approaches into consideration. Lungeometry can give a foundation to learn other forms of lunges like forward lunge, weighted lunges, lateral lunges. This model of learning biomechanics of movements using fundamental geometry techniques is expected to strongly connect with any futuristic Physiotherapy curricular structure.

  18. Heart-lung transplant - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100147.htm Heart-lung transplant - series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 4 Go to slide 2 out of ... to slide 4 out of 4 Overview The heart and lungs are located in the thorax, or chest cavity. ...

  19. Lung alveolar epithelium and interstitial lung disease.

    Science.gov (United States)

    Corvol, Harriet; Flamein, Florence; Epaud, Ralph; Clement, Annick; Guillot, Loic

    2009-01-01

    Interstitial lung diseases (ILDs) comprise a group of lung disorders characterized by various levels of inflammation and fibrosis. The current understanding of the mechanisms underlying the development and progression of ILD strongly suggests a central role of the alveolar epithelium. Following injury, alveolar epithelial cells (AECs) may actively participate in the restoration of a normal alveolar architecture through a coordinated process of re-epithelialization, or in the development of fibrosis through a process known as epithelial-mesenchymal transition (EMT). Complex networks orchestrate EMT leading to changes in cell architecture and behaviour, loss of epithelial characteristics and gain of mesenchymal properties. In the lung, AECs themselves may serve as a source of fibroblasts and myofibroblasts by acquiring a mesenchymal phenotype. This review covers recent knowledge on the role of alveolar epithelium in the pathogenesis of ILD. The mechanisms underlying disease progression are discussed, with a main focus on the apoptotic pathway, the endoplasmic reticulum stress response and the developmental pathway.

  20. Lung function

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005200 The effect of body position changes on lung function, lung CT imaging and pathology in an oleic acid induced acute lung injury model. JI Xin-ping (戢新平), et al. Dept Emergency, 1st Affili Hosp, China Med Univ, Shenyang 110001. Chin J Tuberc Respir Dis, 2005;28(1) :33-36. Objective: To study the effect of body position changes on lung mechanics, oxygenation, CT images and pathology in an oleic acid-induced acute lung injury (ALl) model. Methods: The study groups con-

  1. Effects of bile acids on human airway epithelial cells: implications for aerodigestive diseases

    Directory of Open Access Journals (Sweden)

    Adil Aldhahrani

    2017-03-01

    Full Text Available Gastro-oesophageal reflux and aspiration have been associated with chronic and end-stage lung disease and with allograft injury following lung transplantation. This raises the possibility that bile acids may cause lung injury by damaging airway epithelium. The aim of this study was to investigate the effect of bile acid challenge using the immortalised human bronchial epithelial cell line (BEAS-2B. The immortalised human bronchial epithelial cell line (BEAS-2B was cultured. A 48-h challenge evaluated the effect of individual primary and secondary bile acids. Post-challenge concentrations of interleukin (IL-8, IL-6 and granulocyte−macrophage colony-stimulating factor were measured using commercial ELISA kits. The viability of the BEAS-2B cells was measured using CellTiter-Blue and MTT assays. Lithocholic acid, deoxycholic acid, chenodeoxycholic acid and cholic acid were successfully used to stimulate cultured BEAS-2B cells at different concentrations. A concentration of lithocholic acid above 10 μmol·L−1 causes cell death, whereas deoxycholic acid, chenodeoxycholic acid and cholic acid above 30 μmol·L−1 was required for cell death. Challenge with bile acids at physiological levels also led to a significant increase in the release of IL-8 and IL6 from BEAS-2B. Aspiration of bile acids could potentially cause cell damage, cell death and inflammation in vivo. This is relevant to an integrated gastrointestinal and lung physiological paradigm of chronic lung disease, where reflux and aspiration are described in both chronic lung diseases and allograft injury.

  2. Treatment of Superior Lobe Central Lung Cancer with Lung Replantation

    Directory of Open Access Journals (Sweden)

    Yulun YANG

    2010-11-01

    Full Text Available Background and objective Patients suffering from lung cancer often have poor quality of life after pneumonectomy. It has clinical significances to preserve maximum lobes of the “healthy” lung. The aim of this study is to report the applications of lung replantation in treatment of superior lobe central lung cancer. Methods Three lung cancer cases were included and analysed. The bronchus and margin of lower lung lobe were encroached by cancer. Pulmonary artery was invaded and surrounded by metastatic lymph node. Complete pneumonectomy, antegrade perfusion and retroperfusion with low-potassium dextran (LPD solution in vitro were performed. The retainable lower pulmonary lobe was selected from the isolated lung and superior pulmonary vein was replaced with inferior pulmonary veins. The bronchus and pulmonary artery were inosculated by turns. Results The operative cumulative time ranged from 220 min to 250 min. The isolated time of lobus inferior pulmonary ranged from 120 min to 150 min. The chest tube was pulled out after chest X-ray confirmed the reimplant lung full re-expansion. The patients were followed up for 4 months to 8 months and accomplished adjuvant chemotherapy for 3 or 4 periodicities. The patients had a sound quality of life. Conclusion Lung replantation removing the extensive tumor tissue and retaining the maximum pulmonary normal tissue is an useful method for treatment of lung cancer.

  3. Injury to the Developing Lung: experimental and clinic al aspects

    NARCIS (Netherlands)

    I.K.M. Reiss (Irwin)

    2008-01-01

    textabstractInjury to the developing lung or disturbance of normal lung development may lead to a chronic lung disease, bronchopulmonary dysplasia (BPD), which may have long-term effects. BPD is characterized by an arrest of development of the lung and the pulmonary vascular system and occurs in aro

  4. Open lung biopsy

    Science.gov (United States)

    ... CT scan Disseminated tuberculosis Granulomatosis with polyangiitis Lung cancer - small cell Lung disease Lung needle biopsy Malignant mesothelioma Pulmonary tuberculosis Rheumatoid lung disease Sarcoidosis Simple pulmonary eosinophilia ...

  5. Clarifying Normalization

    Science.gov (United States)

    Carpenter, Donald A.

    2008-01-01

    Confusion exists among database textbooks as to the goal of normalization as well as to which normal form a designer should aspire. This article discusses such discrepancies with the intention of simplifying normalization for both teacher and student. This author's industry and classroom experiences indicate such simplification yields quicker…

  6. Clinical evaluation of X-ray voxel Monte Carlo versus pencil beam-based dose calculation in stereotactic body radiotherapy of lung cancer under normal and deep inspiration breath hold.

    Science.gov (United States)

    Landoni, V; Borzì, G R; Strolin, S; Bruzzaniti, V; Soriani, A; D'Alessio, D; Ambesi, F; Di Grazia, A M; Strigari, L

    2015-06-01

    The purpose of this study is to evaluate the differences between dose distributions calculated with the pencil beam (PB) and X-ray voxel Monte Carlo (MC) algorithms for patients with lung cancer using intensity-modulated radiotherapy (IMRT) or HybridArc techniques. The 2 algorithms were compared in terms of dose-volume histograms, under normal and deep inspiration breath hold, and in terms of the tumor control probability (TCP). The dependence of the differences in tumor volume and location was investigated. Dosimetric validation was performed using Gafchromic EBT3 (International Specialty Products, ISP, Wayne, NJ). Forty-five Computed Tomography (CT) data sets were used for this study; 40 Gy at 8 Gy/fraction was prescribed with 5 noncoplanar 6-MV IMRT beams or 3 to 4 dynamic conformal arcs with 3 to 5 IMRT beams distributed per arc. The plans were first calculated with PB and then recalculated with MC. The difference between the mean tumor doses was approximately 10% ± 4%; these differences were even larger under deep inspiration breath hold. Differences between the mean tumor dose correlated with tumor volume and path length of the beams. The TCP values changed from 99.87% ± 0.24% to 96.78% ± 4.81% for both PB- and MC-calculated plans (P = .009). When a fraction of hypoxic cells was considered, the mean TCP values changed from 76.01% ± 5.83% to 34.78% ± 18.06% for the differently calculated plans (P < .0001). When the plans were renormalized to the same mean dose at the tumor, the mean TCP for oxic cells was 99.05% ± 1.59% and for hypoxic cells was 60.20% ± 9.53%. This study confirms that the MC algorithm adequately accounts for inhomogeneities. The inclusion of the MC in the process of IMRT optimization could represent a further step in the complex problem of determining the optimal treatment plan.

  7. Clinical characteristics and lung CT imaging features in heart failure patients with normal or reduced left ventricular ejection fraction%左室射血分数正常与减低心力衰竭患者的临床特点及肺CT表现比较分析

    Institute of Scientific and Technical Information of China (English)

    林少华; 郭光远; 董凯; 赵新玲; 孙夫平; 楚存坤; 姜领

    2014-01-01

    对85例左室射血分数正常心力衰竭患者(HFNEF组)与89例左室射血分数减低心力衰竭患者(HFREF组)的危险因素、临床特征以及肺CT表现进行比较分析.结果显示,HFNEF组患者较HFREF组患者既往有高血压、糖尿病、肥胖者比例高;咳嗽、呼吸困难常见;肺部CT表现以肺纹理增多、增重,出现胸膜下线、克氏线以及肺实质磨玻璃样变等间质性肺水肿改变为主.而HFREF患者中冠心病者比例较高,临床以急性左心衰表现为主,肺CT表现以肺泡性肺水肿为主.提示HFNEF组患者临床病史较长,症状隐匿,肺部CT表现有别于HFREF组患者.%The clinical features and lung CT findings of 174 heart failure patients,including 85 cases with normal left ventricular ejection fraction (LVEF) and 89 cases with reduced LVEF were reviewed.Patients with normal LVEF had a higher proportion of hypertension,diabetes and obesity than patients with normal LVEF; and cough and dyspnea were more common.The lung CT findings in patients with normal LVEF were frequently presented as interstitial lung edema,increased pulmonary texture,subpleural line,Kerley lines and diffuse ground-glass opacity.Patients with reduced LVEF had a higher proportion of coronary heart disease and clinical manifestations of acute left heart failure,and central alveolar edema presented in lung CT images.Results suggest that heart failure patients with normal LVEF usually have longer clinical history and occult symptoms,and have a different lung CT imaging features from those in heart failure patients with reduced LVEF.

  8. Lung density

    DEFF Research Database (Denmark)

    Garnett, E S; Webber, C E; Coates, G

    1977-01-01

    breathing in the sitting position ranged from 0.25 to 0.37 g.cm-3. Subnormal values were found in patients with emphsema. In patients with pulmonary congestion and edema, lung density values ranged from 0.33 to 0.93 g.cm-3. The lung density measurement correlated well with the findings in chest radiographs...

  9. Lung Cancer

    Science.gov (United States)

    Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

  10. Lung transplantation

    Science.gov (United States)

    Afonso, José Eduardo; Werebe, Eduardo de Campos; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique de Oliveira Braga; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID:26154550

  11. Lung scintigraphy in differential diagnosis of peripheral lung cancer and community-acquired pneumonia

    Science.gov (United States)

    Krivonogov, Nikolay G.; Efimova, Nataliya Y.; Zavadovsky, Konstantin W.; Lishmanov, Yuri B.

    2016-08-01

    Ventilation/perfusion lung scintigraphy was performed in 39 patients with verified diagnosis of community-acquired pneumonia (CAP) and in 14 patients with peripheral lung cancer. Ventilation/perfusion ratio, apical-basal gradients of ventilation (U/L(V)) and lung perfusion (U/L(P)), and alveolar capillary permeability of radionuclide aerosol were determined based on scintigraphy data. The study demonstrated that main signs of CAP were increases in ventilation/perfusion ratio, perfusion and ventilation gradient on a side of the diseased lung, and two-side increase in alveolar capillary permeability rate for radionuclide aerosol. Unlike this, scintigraphic signs of peripheral lung cancer comprise an increase in ventilation/perfusion ratio over 1.0 on a side of the diseased lung with its simultaneous decrease on a contralateral side, normal values of perfusion and ventilation gradients of both lungs, and delayed alveolar capillary clearance in the diseased lung compared with the intact lung.

  12. Immunotherapy for Lung Cancers

    Directory of Open Access Journals (Sweden)

    Ming-Yi Ho

    2011-01-01

    Full Text Available Lung cancer is the leading cause of cancer-related deaths worldwide. Although treatment methods in surgery, irradiation, and chemotherapy have improved, prognosis remains unsatisfactory and developing new therapeutic strategies is still an urgent demand. Immunotherapy is a novel therapeutic approach wherein activated immune cells can specifically kill tumor cells by recognition of tumor-associated antigens without damage to normal cells. Several lung cancer vaccines have demonstrated prolonged survival time in phase II and phase III trials, and several clinical trials are under investigation. However, many clinical trials involving cancer vaccination with defined tumor antigens work in only a small number of patients. Cancer immunotherapy is not completely effective in eradicating tumor cells because tumor cells escape from host immune scrutiny. Understanding of the mechanism of immune evasion regulated by tumor cells is required for the development of more effective immunotherapeutic approaches against lung cancer. This paper discusses the identification of tumor antigens in lung cancer, tumor immune escape mechanisms, and clinical vaccine trials in lung cancer.

  13. Lung Cancer Screening

    Science.gov (United States)

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease in ...

  14. Lung Cancer Prevention

    Science.gov (United States)

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... to keep cancer from starting. General Information About Lung Cancer Key Points Lung cancer is a disease in ...

  15. What Is Lung Cancer?

    Science.gov (United States)

    ... Graphics Infographic Stay Informed Cancer Home What Is Lung Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet ... cancer starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may ...

  16. Scimitar syndrome with horseshoe lung

    Energy Technology Data Exchange (ETDEWEB)

    Beitzke, A.; Gypser, G.; Sager, W.D.

    1982-03-01

    A combination of two rare malformations of the lung was observed in a four-year-old asymptomatic boy. He had typical scimitar syndrome (dextrocardia, hypoplastic right lung and right-sided anomalous pulmonary venous drainage into the v. cava inferior) together with horseshoe lung. Diagnosis was established by angiocardiography and computerized tomography. In the absence of recurrent pulmonary infections operative intervention is not necessary with normal pulmonary arterial pressure and resistance. To the best of our knowledge this case with both malformations seems to be the fourth which is reported in the literature.

  17. Lung Injury After One-Lung Ventilation: A Review of the Pathophysiologic Mechanisms Affecting the Ventilated and the Collapsed Lung.

    Science.gov (United States)

    Lohser, Jens; Slinger, Peter

    2015-08-01

    Lung injury is the leading cause of death after thoracic surgery. Initially recognized after pneumonectomy, it has since been described after any period of 1-lung ventilation (OLV), even in the absence of lung resection. Overhydration and high tidal volumes were thought to be responsible at various points; however, it is now recognized that the pathophysiology is more complex and multifactorial. All causative mechanisms known to trigger ventilator-induced lung injury have been described in the OLV setting. The ventilated lung is exposed to high strain secondary to large, nonphysiologic tidal volumes and loss of the normal functional residual capacity. In addition, the ventilated lung experiences oxidative stress, as well as capillary shear stress because of hyperperfusion. Surgical manipulation and/or resection of the collapsed lung may induce lung injury. Re-expansion of the collapsed lung at the conclusion of OLV invariably induces duration-dependent, ischemia-reperfusion injury. Inflammatory cytokines are released in response to localized injury and may promote local and contralateral lung injury. Protective ventilation and volatile anesthesia lessen the degree of injury; however, increases in biochemical and histologic markers of lung injury appear unavoidable. The endothelial glycocalyx may represent a common pathway for lung injury creation during OLV, because it is damaged by most of the recognized lung injurious mechanisms. Experimental therapies to stabilize the endothelial glycocalyx may afford the ability to reduce lung injury in the future. In the interim, protective ventilation with tidal volumes of 4 to 5 mL/kg predicted body weight, positive end-expiratory pressure of 5 to 10 cm H2O, and routine lung recruitment should be used during OLV in an attempt to minimize harmful lung stress and strain. Additional strategies to reduce lung injury include routine volatile anesthesia and efforts to minimize OLV duration and hyperoxia.

  18. Birkhoff normalization

    NARCIS (Netherlands)

    Broer, H.; Hoveijn, I.; Lunter, G.; Vegter, G.

    2003-01-01

    The Birkhoff normal form procedure is a widely used tool for approximating a Hamiltonian systems by a simpler one. This chapter starts out with an introduction to Hamiltonian mechanics, followed by an explanation of the Birkhoff normal form procedure. Finally we discuss several algorithms for comput

  19. Nickel oxide nanoparticles induce inflammation and genotoxic effect in lung epithelial cells.

    Science.gov (United States)

    Capasso, Laura; Camatini, Marina; Gualtieri, Maurizio

    2014-04-07

    Nickel oxide nanoparticles (NiONPs) toxicity has been evaluated in the human pulmonary epithelial cell lines: BEAS-2B and A549. The nanoparticles, used at the doses of 20, 40, 60, 80, 100 μg/ml, induced a significant reduction of cell viability and an increase of apoptotic and necrotic cells at 24h. A significant release of interleukin-6 and -8 was assessed after 24h of treatment, even intracellular ROS increased already at 45 min after exposure. The results obtained evidenced that the cytokines release was dependent on mitogen activated protein kinases (MAPK) cascade through the induction of NF-kB pathway. NiONPs induced cell cycle alteration in both the cell lines even in different phases and these modifications may be induced by the NPs genotoxic effect, suggested by the nuclear translocation of phospho-ATM and phospho-ATR. Our results confirm the cytotoxic and pro-inflammatory potential of NiONPs. Moreover their ability in inducing DNA damage responses has been demonstrated. Such effects were present in A549 cells which internalize the NPs and BEAS-2B cells in which endocytosis has not been observed.

  20. Specific single chain variable fragment (ScFv) antibodies to angiotensin II AT(2) receptor: evaluation of the angiotensin II receptor expression in normal and tumor-bearing mouse lung.

    Science.gov (United States)

    Tamura, Masaaki; Yan, Heping; Zegarra-Moro, Ofelia; Edl, Jennifer; Oursler, Stephanie; Chard-Bergstrom, Cindy; Andrews, Gordon; Kanehira, Tsutomu; Takekoshi, Susumu; Mernaugh, Ray

    2008-08-01

    To gain insight into the mechanism by which angiotensin II type 2 receptor (AT(2)) regulates carcinogen-induced lung tumorigenesis, we have newly developed anti-AT(2) single chain variable fragment (ScFv) antibodies using a rodent phage-displayed recombinant antibody library with various peptide fragments of the receptor protein, and investigated the expression of the AT(2) receptor protein. The specificity of the antibodies was verified using AT(2) over-expressing COS-7 cells and AT(2) naturally expressing PC12W cells. In control wild type mouse lung, a stronger immunoreactivity was observed in bronchial epithelial cells. A moderate immunoreactivity was detected in pulmonary vascular walls and vascular endothelial cells. In the lungs possessing tobacco-specific nitrosamine (NNK)-induced tumors, significantly increased AT(2) and AT(1 )immunostaining was observed in adenomatous lesions. These data suggest that the increase in both receptors' expression in the alveolar epithelial cells may be accompanied with the onset of NNK-induced tumorigenesis and hence play important roles in lung tumorigenesis.

  1. Lung Transplant

    Science.gov (United States)

    ... will recover in the hospital’s intensive care unit (ICU) before moving to a hospital room for one to three weeks. Your doctor may recommend pulmonary rehabilitation after your lung transplant surgery to help you ...

  2. Lung water measurements with iodo-antipyrine

    Energy Technology Data Exchange (ETDEWEB)

    Chu, R.Y.L.; Carlile, P.V. Jr.; Gray, B.A.; Allen, E.W.; Basmadjian, G.; Myers, J.

    1988-11-01

    /sup 131/I labeled iodo-antipyrine and /sup 99m/Tc labeled erythrocytes were used to measure water content in lungs. These radioactive tracers were injected into 10 rabbits with normal lungs and 11 rabbits with injured lungs. Blood samples were drawn and the subjects were killed. The lungs were removed, weighed and homogenized. Samples of blood and lung homogenate were assayed for /sup 131/I and /sup 99m/Tc. Samples were also weighed before and after drying to a constant weight at 70-75/sup 0/C. Extravascular lung water was determined by the dual isotope technique and again by gravimetric analysis. The average ratio of the results from the 2 different methods is 1.03+-0.15. The 2 methods were compared by regression analysis and the correlation coefficient was 0.92+-0.09. Our investigation suggests the possibility of measurement of lung water with equilibrium distribution of iodo-antipyrine.

  3. Variations of Lung Fissures: A Cadaveric Study

    Directory of Open Access Journals (Sweden)

    Ambali Manoj P

    2014-01-01

    Full Text Available Background: The presence of fissures in the normal lungs enhances uniform expansion and hence facilitates more air intake. Accessory and incomplete fissures of varying depth can be seen in unusual locations of the lung, delimiting abnormal lobes which correspond to the normal bronchopulmonary segments. The knowledge of anatomical variations of lung fissures is essential for clinicians, surgeons, and for radiologist for recognizing various images of related abnormalities because an accessory or anomalous fissure can be mistaken for a lung lesion or an atypical appearance of pleural effusion. Aims and Objectives: The aim of the present study is to observe the variations of lung fissures in Indian population. Fifty pairs (right- 50; left- 50 of lungs were used for this study. Each lung was studied carefully for number of fissures whether complete or incomplete or absent. Presences of accessory fissures were noted. Results: We observed complete absence of fissures in two right and left lungs. Accessory fissures were present in 38% right lungs and 32% in left lungs. Conclusion: Incidence of absence of oblique fissure and accessory fissure was greater in our present work when compared our results with other authors. Considering this we feel that more elaborative study should be done on this topic which will throw more light on this.

  4. Interstitial Lung Diseases

    Science.gov (United States)

    Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and ... is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among coal ...

  5. Lung Carcinoid Tumor: Surgery

    Science.gov (United States)

    ... Disease Lung Carcinoid Tumor Treating Lung Carcinoid Tumors Surgery to Treat Lung Carcinoid Tumors Surgery is the ... be cured by surgery alone. Types of lung surgery Different operations can be used to treat (and ...

  6. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  7. Usefulness of texture features for segmentation of lungs with severe diffuse interstitial lung disease

    Science.gov (United States)

    Wang, Jiahui; Li, Feng; Li, Qiang

    2010-03-01

    We developed an automated method for the segmentation of lungs with severe diffuse interstitial lung disease (DILD) in multi-detector CT. In this study, we would like to compare the performance levels of this method and a thresholdingbased segmentation method for normal lungs, moderately abnormal lungs, severely abnormal lungs, and all lungs in our database. Our database includes 31 normal cases and 45 abnormal cases with severe DILD. The outlines of lungs were manually delineated by a medical physicist and confirmed by an experienced chest radiologist. These outlines were used as reference standards for the evaluation of the segmentation results. We first employed a thresholding technique for CT value to obtain initial lungs, which contain normal and mildly abnormal lung parenchyma. We then used texture-feature images derived from co-occurrence matrix to further segment lung regions with severe DILD. The segmented lung regions with severe DILD were combined with the initial lungs to generate the final segmentation results. We also identified and removed the airways to improve the accuracy of the segmentation results. We used three metrics, i.e., overlap, volume agreement, and mean absolute distance (MAD) between automatically segmented lung and reference lung to evaluate the performance of our segmentation method and the thresholding-based segmentation method. Our segmentation method achieved a mean overlap of 96.1%, a mean volume agreement of 98.1%, and a mean MAD of 0.96 mm for the 45 abnormal cases. On the other hand the thresholding-based segmentation method achieved a mean overlap of 94.2%, a mean volume agreement of 95.8%, and a mean MAD of 1.51 mm for the 45 abnormal cases. Our new method obtained higher performance level than the thresholding-based segmentation method.

  8. Multiphoton microscopy as a diagnostic imaging modality for lung cancer

    Science.gov (United States)

    Pavlova, Ina; Hume, Kelly R.; Yazinski, Stephanie A.; Peters, Rachel M.; Weiss, Robert S.; Webb, Watt W.

    2010-02-01

    Lung cancer is the leading killer among all cancers for both men and women in the US, and is associated with one of the lowest 5-year survival rates. Current diagnostic techniques, such as histopathological assessment of tissue obtained by computed tomography guided biopsies, have limited accuracy, especially for small lesions. Early diagnosis of lung cancer can be improved by introducing a real-time, optical guidance method based on the in vivo application of multiphoton microscopy (MPM). In particular, we hypothesize that MPM imaging of living lung tissue based on twophoton excited intrinsic fluorescence and second harmonic generation can provide sufficient morphologic and spectroscopic information to distinguish between normal and diseased lung tissue. Here, we used an experimental approach based on MPM with multichannel fluorescence detection for initial discovery that MPM spectral imaging could differentiate between normal and neoplastic lung in ex vivo samples from a murine model of lung cancer. Current results indicate that MPM imaging can directly distinguish normal and neoplastic lung tissues based on their distinct morphologies and fluorescence emission properties in non-processed lung tissue. Moreover, we found initial indication that MPM imaging differentiates between normal alveolar tissue, inflammatory foci, and lung neoplasms. Our long-term goal is to apply results from ex vivo lung specimens to aid in the development of multiphoton endoscopy for in vivo imaging of lung abnormalities in various animal models, and ultimately for the diagnosis of human lung cancer.

  9. 犬烟雾吸入伤早期肺洗出液对大鼠肺损伤作用的研究%Role of BALF from dogs with acute severe smoke inhalation injury in ind ucing lung injury of normal rats

    Institute of Scientific and Technical Information of China (English)

    聂发传; 杨宗城; 刘志远; 罗奇志; 黄跃生

    2001-01-01

    Objective To investigate the existence, intensit y and persisting time of biologic activity of bronchoalveolar lavage fluid (BALF ) collected from dogs with acute severe smoke inhalation injury in early post-i njury stage. Methods BALF was collected 1 h after the est ablishment of acute severe sawdust smoke inhalation injury in 5 dogs, and the fl uid was perfused into the lungs of Wistar rats in the amount of 5 ml/kg (gro up C). Normal saline (group A) and BALF from normal dog (group B) were perfused into the lungs of rats and served as control. The respiratory rate, PaO2, lung water content and the expanding stability of lungs in all rats were determ ined at the time points of 4,12 and 24 h after the purfusion. Results  Compared with the rats in group A and B, the rats in group C had higher mortality, wider range in RR, higher lung water content, PaO2 decreased obviou sly and lower lung expanding stability. The rats in control groups showed sl i ght mechanic obstruction in their airways in the course of experiment. Meanwhile ,the rats in group C showed higher oxidative activities and lower total anti-o xidative activities in lung tissues. Conclusion It is certai n that the BALF collected from dogs with acute severe smoke inhalation injury in early post-injury stage could induce obvious injury in lung structure of norma l rats, showing certain mechanic obstruction in small airways. The injuring act ivity of the BALF can be alleviated ultimately 24 h after the perfusion of the B ALF.%目的研究犬烟雾吸入伤早期肺洗出液是否具有生物学活性及其活性强度和持续时间。方法建立犬急性重度烟雾吸入伤模型,伤后1 h对伤肺进行生理盐水大容量灌洗。将一定量之洗出液经气管注入正常大鼠气道,观察自主呼吸24 h间大鼠呼吸频率、血气及离体肺含水量和肺泡稳定性等变化。结果与正常大鼠、等容量生理盐水或正常犬肺洗出液气道灌注大鼠相比,用

  10. Lung surgery

    Science.gov (United States)

    ... are thoracotomy and video-assisted thoracoscopic surgery (VATS). Robotic surgery may also be used. Lung surgery using a ... clot from the pulmonary artery ( pulmonary embolism ) Treat complications of tuberculosis Video-assisted thoracoscopic surgery can be used to treat many of these ...

  11. [Humidifier lung].

    Science.gov (United States)

    Gerber, P; de Haller, R; Pyrozynski, W J; Sturzenegger, E R; Brändli, O

    1981-02-07

    Breathing air from a humidifier or an air conditioning unit contaminated by various microorganisms can cause an acute lung disease involving fever, cough and dyspnea, termed "humidifier fever". This type of hypersensitivity pneumonitis was first described in 1959 by PESTALOZZI in the Swiss literature and subsequently by BANASZAK et al. in the Anglo-American. Here a chronic form of this disease which led to pulmonary fibrosis is described: A 37-year-old woman who works in a cheese shop presented with dyspnea which had been progressive over two years, weight loss, a diffuse reticular pattern radiographically and a severe restrictive defect in lung function tests. Open lung biopsy revealed chronic interstitial and alveolar inflammation with non-caseating granulomas and fibrotic changes. Circulating immune complexes and precipitins against the contaminated humidifier water and cheese mites were found, but no antibodies suggesting legionnaires' disease. Two out of five otherwise healthy employees of this cheese shop, where a new humidifying system had been installed 7 years earlier, also had precipitins against the contaminated water from the humidifier and the cheese mites. Despite ending of exposure and longterm steroid and immunosuppressive therapy, the signs and symptoms of pulmonary fibrosis persisted. Contrary to the acute disease, this chronic form is termed "humidifier lung". The importance is stressed of investigating the possibility of exposure to contaminated humidifiers or air conditioning units in all cases of newly detected pulmonary fibrosis.

  12. Lung cancer

    DEFF Research Database (Denmark)

    Hansen, H H; Rørth, M

    1999-01-01

    The results of the many clinical trials published in 1997 had only modest impact on the treatment results using either cytostatic agents alone or combined with radiotherapy in lung cancer. In SCLC, combination chemotherapy including platin-compounds (cisplatin, carboplatin) and the podophyllotoxins...

  13. Lung function changes in wildland firefighters working at prescribed burns.

    Energy Technology Data Exchange (ETDEWEB)

    Adetona, Olorunfemi; Hall, Daniel, B.; Naeher, L,P.

    2011-10-01

    Although decline in lung function across workshift has been observed in wildland firefighters, measurements have been restricted to days when they worked at fires. Consequently, such results could have been confounded by normal circadian variation associated with lung function. We investigated the across-shift changes in lung function of wildland firefighters, and the effect of cumulative exposure on lung function during the burn season.

  14. Two novel mutations in surfactant protein-C, lung function and obstructive lung disease

    DEFF Research Database (Denmark)

    Baekvad-Hansen, Marie; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne;

    2010-01-01

    Dominant mutations in the surfactant protein-C(SFTPC) gene have been linked with interstitial lung disease. The frequency of lung disease due to SFTPC mutations in the general population is unknown. The aim of this study was to identify novel SFTPC mutations that are associated with lung function...... pulmonary disease or interstitial lung disease. No Y106X heterozygotes suffered from asthma, chronic obstructive pulmonary disease (COPD), or interstitial lung disease. We identified two novel mutations in highly conserved areas of the SFTPC gene, and show that heterozygotes for the mutations have normal...... lung function and are unaffected by COPD and interstitial lung disease. A53T heterozygotes had increased asthma risk, but further research is required to conclusively determine whether this mutation is associated with asthma....

  15. Differences in cytotoxicity versus pro-inflammatory potency of different PM fractions in human epithelial lung cells.

    Science.gov (United States)

    Gualtieri, Maurizio; Øvrevik, Johan; Holme, Jørn A; Perrone, M Grazia; Bolzacchini, Ezio; Schwarze, Per E; Camatini, Marina

    2010-02-01

    Air pollution in Milan causes health concern due to the high concentrations of particulate matter (PM10 and PM2.5). The aim of this study was to investigate possible seasonal differences in PM10 and PM2.5 chemical composition and their biological effects on pro-inflammatory cytokine release and cytotoxicity. The PM was sampled during winter and summer seasons. The winter PMs had higher levels of PAHs than the summer samples which contained a greater amount of mineral dust elements. The PM toxicity was tested in the human pulmonary epithelial cell lines BEAS-2B and A549. The winter PMs were more cytotoxic than summer samples, whereas the summer PM10 exhibited a higher pro-inflammatory potential, as measured by ELISA. This inflammatory potential seemed partly due to biological components such as bacterial lipopolysaccharides (LPS), as evaluated by the use of Polymixin B. Interestingly, in the BEAS-2B cells the winter PM2.5 reduced proliferation due to a mitotic delay/arrest, while no such effects were observed in the A549 cells. These results underline that the in vitro responsiveness to PM may be cell line dependent and suggest that the PM different properties may trigger different endpoints such as inflammation, perturbation of cell cycle and cell death.

  16. Effect of epithelial cell type on in vitro invasion of non-typeable Haemophilus influenzae.

    Science.gov (United States)

    Singh, Neeraj Kumar; Kunde, Dale A; Tristram, Stephen G

    2016-10-01

    Non-typeable Haemophilus influenzae (NTHi) have been shown to have variable ability for in vitro invasion with a range of epithelial cells, and increased invasion of BEAS-2B cells has been associated with altered penicillin binding protein3 (PBP3), which is concerning as these strains are increasing worldwide. The aim of the study was to investigate the effect of respiratory cell type and the presence of altered PBP3 on the in vitro invasion of NTHi. A collection of 16 clinical NTHi isolates was established, 7 had normal PBP3, and 9 had altered PBP3 as defined by an N526K substitution. The isolates were tested for invasion of BEAS-2B, NHBE, A549 and NCI-H292 respiratory epithelial cells in vitro using a gentamicin survival assay, with invasion measured as the percentage of intracellular organisms relative to the initial inoculum. The overall median invasion for the 16 NTHi isolates for cell types BEAS-2B, NHBE, A549 and NCI-H292 cells were 3.17, 2.31, 0.11 and 1.52 respectively. The differences were statistically significant for BEAS-2B compared to A549 (P=0.015) and A549 compared to NCI-H292 (P=0.015), and there were also very marked differences in invasion for some individual isolates depending on the cell type used. There was a consistent bias for invasion of isolates with normal versus abnormal PBP3: and this was statistically significant for BEAS-2B (0.07 to 9.90, P=0.031) and A549 cells (0.02 to 1.68, P=0.037). These results show that NTHi invasion of respiratory epithelial cells in vitro is both strain dependant and influenced significantly by the cell line used, and that the association between altered PBP3 and increased invasion is conserved across multiple cell lines.

  17. Ectopic expression of a small cell lung cancer transcription factor, INSM1 impairs alveologenesis in lung development

    OpenAIRE

    2016-01-01

    Background Insulinoma associated-1 (INSM1) gene is expressed exclusively in early embryonic neuroendocrine tissues, but has been found highly re-activated in most of the neuroendocrine tumors including small cell lung carcinoma. Methods In order to elucidate the functional effects of INSM1 in normal lung development, we used a conditional lung-specific INSM1 transgenic mouse model. Transgenic (Tet-on system) CMV-INSM1 responder mice were bred with the lung-specific, club cell secretory protei...

  18. Detecting the effect of targeted anti-cancer medicines on single cancer cells using a poly-silicon wire ion sensor integrated with a confined sensitive window.

    Science.gov (United States)

    Wu, You-Lin; Hsu, Po-Yen; Hsu, Chung-Ping; Lin, Jing-Jenn

    2012-10-01

    A mold-cast polydimethylsiloxane (PDMS) confined window was integrated with a poly-silicon wire (PSW) ion sensor. The PSW sensor surface inside the confined window was coated with a 3-aminopropyltriethoxysilane (γ-APTES) sensitive layer which allowed a single living cell to be cultivated. The change in the microenvironment due to the extracellular acidification of the single cell could then be determined by measuring the current flowing through the PSW channel. Based on this, the PSW sensor integrated with a confined sensitive window was used to detect the apoptosis as well as the effect of anti-cancer medicines on the single living non-small-lung-cancer (NSLC) cells including lung adenocarcinoma cancer cells A549 and H1299, and lung squamous-cell carcinoma CH27 cultivated inside the confined window. Single human normal cells including lung fibroblast cells WI38, lung fibroblast cells MRC5, and bronchial epithelium cell Beas-2B were tested for comparison. Two targeted anti-NSCLC cancer medicines, Iressa and Staurosporine, were used in the present study. It was found that the PSW sensor can be used to accurately detect the apoptosis of single cancer cells after the anti-cancer medicines were added. It was also found that Staurosporine is more effective than Iressa in activating the apoptosis of cancer cells.

  19. Lung MRI and impairment of diaphragmatic function in Pompe disease

    DEFF Research Database (Denmark)

    Wens, Stephan C A; Ciet, Pierluigi; Perez-Rovira, Adria;

    2015-01-01

    manually segmented. After normalization for lung size, changes in lung dimensions between inspiration and expiration were used for analysis; normalization was based on the cranial-caudal length ratio (representing vertical diaphragmatic displacement), and the anterior-posterior and left-right length ratios...

  20. Study on 4977-bp deletion mutation of mitochondrial DNA in lung cancer

    Institute of Scientific and Technical Information of China (English)

    DAI Ji-gang; XIAO Ying-bin; MIN Jia-xin; ZHANG Guo-qiang; YAO Ke; ZHOU Ren-jie

    2005-01-01

    Objective: To study the 4977-bp deletion of mitochondiral DNA in lung cancer, adjacent normal tissue and health lung and its significance in the development of cancer. Methods: Thirty-seven matched lung cancer/adjacent histologically normal and 20 "true" normal lung tissue samples from patients without lung cancer were analyzed by long PCR technique. Results: Mitochondrial DNA 4977-bp deletion was detected in 54. 1% (20/37) of lung cancers, 59.5% (22/37) of adjacent normal and 30.0% (6/30) of"true" normal lung tissues. The correlation of 4977-bp deletion with age and smoking factors was present in our data. Conclusion: Mitochondrial DNA 4977-bp deletion is not specific to lung cancer and unlikely to play an important role in carcinogenesis, and may only reflect the environmental and genetic influences during tumor progression.

  1. Lung hyperinflation: foe or friend?

    Science.gov (United States)

    Eichinger, M; Walterspacher, S; Scholz, T; Tetzlaff, K; Röcker, K; Muth, C-M; Puderbach, M; Kauczor, H-U; Sorichter, S

    2008-10-01

    Breath-hold divers employ glossopharyngeal insufflation (GI) in order to prevent the lungs from compressing at great depth and to increase intrapulmonary oxygen stores, thus increasing breath-hold time. The presented case study shows the physiological data and dynamic magnetic resonance imaging (dMRI) findings of acute hyperinflation, deliberately induced by GI, in a breath-hold diver and discusses the current state of knowledge regarding the associated hazards of this unique competitive sport. Static and dynamic lung volumes and expiratory flows were within the normal range, with vital capacity and peak expiratory flow being higher than the predicted values. Airway resistance and diffusing capacity of the lung for carbon monoxide were normal. Static compliance was normal and increased five-fold with hyperinflation. dMRI revealed a preserved shape of the thorax and diaphragm with hyperinflation. A herniation of the lung beneath the sternum and enlargement of the costodiaphragmatic angle were additional findings during the GI manoeuvre. After expiration, complete resolution to baseline was demonstrated. Hyperinflation can be physiological and even protective under abnormal physical conditions in the sense of acute adaptation to deep breath-hold diving. Dynamic magnetic resonance imaging is adequate for visualisation of the sequence of the glossopharyngeal insufflation manoeuvre and the complete reversibility of deliberate hyperinflation.

  2. Multiplexed quantitative high content screening reveals that cigarette smoke condensate induces changes in cell structure and function through alterations in cell signaling pathways in human bronchial cells.

    Science.gov (United States)

    Carter, Charleata A; Hamm, Jonathan T

    2009-07-10

    Human bronchial cells are one of the first cell types exposed to environmental toxins. Toxins often activate nuclear factor-kappaB (NF-kappaB) and protein kinase C (PKC). We evaluated the hypothesis that cigarette smoke condensate (CSC), the particulate fraction of cigarette smoke, activates PKC-alpha and NF-kappaB, and concomitantly disrupts the F-actin cytoskeleton, induces apoptosis and alters cell function in BEAS-2B human bronchial epithelial cells. Compared to controls, exposure of BEAS-2B cells to doses of 30mug/ml CSC significantly activated PKC-alpha, while CSC doses above 20mug/ml CSC significantly activated NF-kappaB. As NF-kappaB was activated, cell number decreased. CSC treatment of BEAS-2B cells induced a decrease in cell size and an increase in cell surface extensions including filopodia and lamellipodia. CSC treatment of BEAS-2B cells induced F-actin rearrangement such that stress fibers were no longer prominent at the cell periphery and throughout the cells, but relocalized to perinuclear regions. Concurrently, CSC induced an increase in the focal adhesion protein vinculin at the cell periphery. CSC doses above 30mug/ml induced a significant increase in apoptosis in BEAS-2B cells evidenced by an increase in activated caspase 3, an increase in mitochondrial mass and a decrease in mitochondrial membrane potential. As caspase 3 increased, cell number decreased. CSC doses above 30mug/ml also induced significant concurrent changes in cell function including decreased cell spreading and motility. CSC initiates a signaling cascade in human bronchial epithelial cells involving PKC-alpha, NF-kappaB and caspase 3, and consequently decreases cell spreading and motility. These CSC-induced alterations in cell structure likely prevent cells from performing their normal function thereby contributing to smoke-induced diseases.

  3. Staging of Lung Cancer

    Science.gov (United States)

    ... is important for two reasons. First, staging your lung cancer helps decide which therapy (or therapies) should be used. Second, lung cancer ... 422-6237 http://www.cancer.gov/cancertopics/wyntk/lung/page8 http://www.cancer.gov/cancertopics/pdq/treatment/non- small-cell-lung/Patient/page2 National Lung ...

  4. Matrix metalloproteinases in lung biology

    Directory of Open Access Journals (Sweden)

    Parks William C

    2000-12-01

    Full Text Available Abstract Despite much information on their catalytic properties and gene regulation, we actually know very little of what matrix metalloproteinases (MMPs do in tissues. The catalytic activity of these enzymes has been implicated to function in normal lung biology by participating in branching morphogenesis, homeostasis, and repair, among other events. Overexpression of MMPs, however, has also been blamed for much of the tissue destruction associated with lung inflammation and disease. Beyond their role in the turnover and degradation of extracellular matrix proteins, MMPs also process, activate, and deactivate a variety of soluble factors, and seldom is it readily apparent by presence alone if a specific proteinase in an inflammatory setting is contributing to a reparative or disease process. An important goal of MMP research will be to identify the actual substrates upon which specific enzymes act. This information, in turn, will lead to a clearer understanding of how these extracellular proteinases function in lung development, repair, and disease.

  5. Lung infection

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950304 The diagnosis and treatment of pulmonaryaspergilloma in the aged—a report of 17 cases.LI Di-anqin(李殿清),et al.Henan Provincial Pulmon DisHosp,Zhengzhou,450003.Chin J Geriatr 1994;13(6):338-339.Seventeen cases of pulmonary aspergilloma in theaged were reported.The primary diseases were pul-monary tuberculosis in 14 cases and pulmonary cyst,cancer of lung and pulmonary abscess in one each.In14 cases,the clinical manifestation was frequenthemoptysis;the occurrence rate was 82.4%.Among

  6. Cytokines in human lung fibrosis.

    Science.gov (United States)

    Martinet, Y; Menard, O; Vaillant, P; Vignaud, J M; Martinet, N

    1996-01-01

    Fibrosis is a pathological process characterized by the replacement of normal tissue by mesenchymal cells and the extracellular matrix produced by these cells. The sequence of events leading to fibrosis of an organ involves the subsequent processes of injury with inflammation and disruption of the normal tissue architecture, followed by tissue repair with accumulation of mesenchymal cells in the area of derangement. The same sequence of events occurs in wound healing with normal granulation tissue and scar formation, but, while normal scar formation is very localized and transient, in contrast, in fibrosis, the repair process is exaggerated and usually widespread and can be chronic. Inflammatory cells (mainly mononuclear phagocytes), platelets, endothelial cells, and type II pneumocytes play a direct and indirect role in tissue injury and repair. The evaluation of three human fibrotic lung diseases, two diffuse [idiopathic pulmonary fibrosis (IPF), and the adult respiratory distress syndrome (ARDS)], and one focal (tumor stroma in lung cancer), has shown that several cytokines participate to the local injury and inflammatory reaction [interleukin-1 (IL-1), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha)], while other cytokines are involved in tissue repair and fibrosis [platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-beta), and basic-fibroblast growth factor (b-FGF)]. A better understanding of the cytokines and cytokine networks involved in lung fibrosis leads to the possibility of new therapeutic approaches.

  7. Strategies for lung regeneration

    Directory of Open Access Journals (Sweden)

    Thomas H. Petersen

    2011-05-01

    Full Text Available Due to the limited ability of the adult lung to regenerate and the frequency of lung disease, the lung is a tissue that can especially benefit from regenerative medicine. Prospects for lung regeneration have made great strides in the past year. In this review, we summarize recent progress and key challenges for approaches in lung regenerative medicine. With a focus on the matrix components critical for the development of regenerative lung tissues, we discuss possible cell sources for lung regeneration, key matrix effects on cell repopulation, and physical stimuli that will aid in the growth of lung tissues in vitro.

  8. 体部γ刀治疗非小细胞肺癌的剂量学分布及正常组织的保护%Dose Distribution and Protection of Normal Tissues of Body Gamma Knife in Treatment of No-small-cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    于得全; 高宏; 邵秋菊; 梁军; 卢飞

    2011-01-01

    Objective To evaluate the relationship between dose distribution and amount of normal tissue receiving dose in the treatment of body gamma knife for non-small-cell lung cancer(NSCLC). Methods 10 patients with non-small-cell lung cancer and the focus of cancer anteroposterior diameter≤5cm were adopted as the subjects. 10 patients accepted body gamma knife treatment and three -dimensional conformal radiation therapy. PTV minimal dose/average dose and the receiving doses of normal pulmonic tissue were evaluated. Results The PTV minimal dose, maximum dose, average dose that patients accepted gamma knife therapy were 56.6%, 99.8%, 76.1% and the lung V20,V25,V30.V35 were 7.02%, 5.11%, 4.24%, 3.02%; PTV minimal dose, maximum dose, average dose that patients accepted three -dimensional conformal radiation therapy were 94.0%, 104.5%, 100.2% and the lung V20,V25,V30,V35 were 14.08%, 10.20, 8.42%, 7.02%. Conclusion For the non-smal-cell lung cancer(NSCLC) that the focus of cancer anteroposterior diameter≤5cm, gammea knife is better than three-dimensional conformal radiation therapy because it can increase radiotherapy dose. Gamma knife is an efficient and desirable therapy.%目的:探讨分析体部γ刀在治疗非小细胞肺癌小病灶时的剂量分布及正常组织的受量情况.方法:选取10例非小细胞肺癌患者,入组条件:病灶大小≤5 cm,10例患者分别设计体部γ刀计划和三维适形计划,分析放疗计划中PTV最小剂量、平均剂量,正常组织肺的受量情况.结果:γ刀组PTV最小剂量、最大剂量、平均剂量分别为56.6%、99.8%、36.1%,肺V20、V25、V30、V35分别为7.02%、5.11%、4.24%、3.02%:适形组PTV最小剂量、最大剂量、平均剂量分别为94.0%、104.5%、100.2%,肺V20、V25、V30、V35分别为14.08%、10.20、8.42%、7.02%.结论:针对非小细胞肺癌≤5 cm的病灶,体部γ刀在保护正常组织上优于适形放疗,可提高放疗剂量,是一种治疗局部

  9. Transcriptomic Microenvironment of Lung Adenocarcinoma.

    Science.gov (United States)

    Bossé, Yohan; Sazonova, Olga; Gaudreault, Nathalie; Bastien, Nathalie; Conti, Massimo; Pagé, Sylvain; Trahan, Sylvain; Couture, Christian; Joubert, Philippe

    2017-03-01

    Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389-96. ©2016 AACR.

  10. Risks of Lung Cancer Screening

    Science.gov (United States)

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease in ...

  11. Radiation Therapy for Lung Cancer

    Science.gov (United States)

    ... are available to help. HELPFUL WEB SITES ON LUNG CANCER American Lung Association www.lung.org Lungcancer.org www.lungcancer.org Lung Cancer Alliance www.lungcanceralliance.org Lung Cancer Online www. ...

  12. Stem cells and repair of lung injuries

    Directory of Open Access Journals (Sweden)

    Randell Scott H

    2004-07-01

    Full Text Available Abstract Fueled by the promise of regenerative medicine, currently there is unprecedented interest in stem cells. Furthermore, there have been revolutionary, but somewhat controversial, advances in our understanding of stem cell biology. Stem cells likely play key roles in the repair of diverse lung injuries. However, due to very low rates of cellular proliferation in vivo in the normal steady state, cellular and architectural complexity of the respiratory tract, and the lack of an intensive research effort, lung stem cells remain poorly understood compared to those in other major organ systems. In the present review, we concisely explore the conceptual framework of stem cell biology and recent advances pertinent to the lungs. We illustrate lung diseases in which manipulation of stem cells may be physiologically significant and highlight the challenges facing stem cell-related therapy in the lung.

  13. Surfactant gene polymorphisms and interstitial lung diseases

    Directory of Open Access Journals (Sweden)

    Pantelidis Panagiotis

    2001-11-01

    Full Text Available Abstract Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs. Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.

  14. Mass Preserving Registration for lung CT

    DEFF Research Database (Denmark)

    Gorbunova, Vladlena; Lo, Pechin Chien Pau; Loeve, Martin;

    2009-01-01

    In this paper, we evaluate a novel image registration method on a set of expiratory-inspiratory pairs of computed tomography (CT) lung scans. A free-form multi resolution image registration technique is used to match two scans of the same subject. To account for the differences in the lung...... and inspiration CT scans of children with cystic fibrosis lung disease. The proposed method with mass preserving adjustment results in significantly better alignment of the vessel trees. Analysis of local volume change for regions with trapped air compared to normally ventilated regions revealed larger...

  15. XB130 translocation to microfilamentous structures mediates NNK-induced migration of human bronchial epithelial cells.

    Science.gov (United States)

    Wu, Qifei; Nadesalingam, Jeya; Moodley, Serisha; Bai, Xiaohui; Liu, Mingyao

    2015-07-20

    Cigarette smoking contributes to the pathogenesis of chronic obstructive pulmonary disease and lung cancer. Nicotine-derived nitrosamine ketone (NNK) is the most potent carcinogen among cigarette smoking components, and is known to enhance migration of cancer cells. However, the effect of NNK on normal human bronchial epithelial cells is not well studied. XB130 is a member of actin filament associated protein family and is involved in cell morphology changes, cytoskeletal rearrangement and outgrowth formation, as well as cell migration. We hypothesized that XB130 mediates NNK-induced migration of normal human bronchial epithelial cells. Our results showed that, after NNK stimulation, XB130 was translocated to the cell periphery and enriched in cell motility-associated structures, such as lamellipodia, in normal human bronchial epithelial BEAS2B cells. Moreover, overexpression of XB130 significantly enhanced NNK-induced migration, which requires both the N- and C-termini of XB130. Overexpression of XB130 enhanced NNK-induced protein tyrosine phosphorylation and promoted matrix metalloproteinase-14 translocation to cell motility-associated cellular structures after NNK stimulation. XB130-mediated NNK-induced cell migration may contribute to airway epithelial repair; however, it may also be involved in cigarette smoking-related chronic obstructive pulmonary disease and lung cancer.

  16. Lung gallium scan

    Science.gov (United States)

    Gallium 67 lung scan; Lung scan; Gallium scan - lung; Scan - lung ... Gallium is injected into a vein. The scan will be taken 6 to 24 hours after the gallium is injected. (Test time depends on whether your condition is acute or chronic .) ...

  17. ROCK2 is involved in accelerated fetal lung development induced by in vivo lung distension.

    Science.gov (United States)

    Cloutier, Marc; Tremblay, Monique; Piedboeuf, Bruno

    2010-10-01

    Lung development is strongly influenced by its state of distension. For instance, increasing distension induced by fetal tracheal occlusion (TO) stimulates lung development. In contrast, oligohydramnios (OH) reduces lung distending forces and results in lung hypoplasia. We hypothesize that Rho/Rho-associated kinase (ROCK) pathway plays an important role as mechanosensor in vivo acting either directly or indirectly in the translation of increased distension into acceleration of lung growth. TO was done in fetal mice sacrificed either 3 or 24 hr later; in a subset of dam, fasudil, a specific ROCK inhibitor, or vehicle was injected intra-peritoneally. OH was done by puncture of the amniotic sac. ROCK2 protein levels were assessed by Western blot and immunohistochemistry (IHC); lung development was assessed by measuring the generation of distal respiratory airway. Significant differences were found in ROCK2 protein levels between TO and Sham-TO at 3 and 24 hr, but not for ROCK1. Indeed, IHC revealed that ROCK2 staining was sparse and restricted to a few mesenchymal cells in Sham-TO, whereas it was strong in acini of TO lungs. OH lungs expressed lower levels of ROCK2 in the acini when compared to untouched controls. In fasudil-treated animals, the degree of lung development following TO was significantly lower than in the group injected with vehicle. At the dose regimen used, fasudil did not affect normal lung development, as observed in the untouched animals. In summary, ROCK2 protein levels was affected by the degree of lung expansion and blunting ROCK activity abolished the response to increased lung distension, suggesting that ROCK is a key regulator in TO-induced accelerated lung development.

  18. Impairment of cell cycle progression by sterigmatocystin in human pulmonary cells in vitro.

    Science.gov (United States)

    Huang, Shujuan; Wang, Juan; Xing, Lingxiao; Shen, Haitao; Yan, Xia; Wang, Junling; Zhang, Xianghong

    2014-04-01

    Sterigmatocystin (ST) is a carcinogenic mycotoxin that is commonly found in human food, animal feed and in the indoor environment. Although the correlation between ST exposure and lung cancer has been widely reported in many studies, the cytotoxicity of ST on human pulmonary cells is not yet fully understood. In the current study, we found that ST could induce DNA double-strand breaks in a human immortalized bronchial epithelial cell line (BEAS-2B cells) and a human lung cancer cell line (A549 cells). In addition, the effects of ST on cell cycle arrest were complex and dependent on the tested ST concentration and cell type. Low concentrations of ST arrested cells in the G2/M phase in BEAS-2B cells and in the S phase in A549 cells, while at high concentration both cells lines were arrested in S and G2/M phases. Furthermore, we observed that the modulation of cyclins and CDK expression showed concomitant changes with cell cycle arrest upon ST exposure in BEAS-2B and A549 cells. In conclusion, ST induced DNA damage and affected key proteins involved in cell cycle regulation to trigger genomic instability, which may be a potential mechanism underlying the developmental basis of lung carcinogenesis.

  19. Quantitative CT characterization of pediatric lung development using routine clinical imaging

    Energy Technology Data Exchange (ETDEWEB)

    Stein, Jill M.; Brody, Alan S.; Fleck, Robert J. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Walkup, Laura L. [Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Pulmonary Medicine and Radiology, Cincinnati, OH (United States); Woods, Jason C. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Cincinnati Children' s Hospital Medical Center, Center for Pulmonary Imaging Research, Pulmonary Medicine and Radiology, Cincinnati, OH (United States)

    2016-12-15

    The use of quantitative CT analysis in children is limited by lack of normal values of lung parenchymal attenuation. These characteristics are important because normal lung development yields significant parenchymal attenuation changes as children age. To perform quantitative characterization of normal pediatric lung parenchymal X-ray CT attenuation under routine clinical conditions in order to establish a baseline comparison to that seen in pathological lung conditions. We conducted a retrospective query of normal CT chest examinations in children ages 0-7 years from 2004 to 2014 using standard clinical protocol. During these examinations semi-automated lung parenchymal segmentation was performed to measure lung volume and mean lung attenuation. We analyzed 42 CT examinations in 39 children, ages 3 days to 83 months (mean ± standard deviation [SD] = 42 ± 27 months). Lung volume ranged 0.10-1.72 liters (L). Mean lung attenuation was much higher in children younger than 12 months, with values as high as -380 Hounsfield units (HU) in neonates (lung volume 0.10 L). Lung volume decreased to approximately -650 HU by age 2 years (lung volume 0.47 L), with subsequently slower exponential decrease toward a relatively constant value of -860 HU as age and lung volume increased. Normal lung parenchymal X-ray CT attenuation decreases with increasing lung volume and age; lung attenuation decreases rapidly in the first 2 years of age and more slowly thereafter. This change in normal lung attenuation should be taken into account as quantitative CT methods are translated to pediatric pulmonary imaging. (orig.)

  20. KLF4 regulates adult lung tumor-initiating cells and represses K-Ras-mediated lung cancer.

    Science.gov (United States)

    Yu, T; Chen, X; Zhang, W; Liu, J; Avdiushko, R; Napier, D L; Liu, A X; Neltner, J M; Wang, C; Cohen, D; Liu, C

    2016-02-01

    Lung cancer is the leading cause of cancer-related mortality in both men and women worldwide. To identify novel factors that contribute to lung cancer pathogenesis, we analyzed a lung cancer database from The Cancer Genome Atlas and found that Krüppel-like Factor 4 (KLF4) expression is significantly lower in patients' lung cancer tissue than in normal lung tissue. In addition, we identified seven missense mutations in the KLF4 gene. KLF4 is a transcription factor that regulates cell proliferation and differentiation as well as the self-renewal of stem cells. To understand the role of KLF4 in the lung, we generated a tamoxifen-induced Klf4 knockout mouse model. We found that KLF4 inhibits lung cancer cell growth and that depletion of Klf4 altered the differentiation pattern in the developing lung. To understand how KLF4 functions during lung tumorigenesis, we generated the K-ras(LSL-G12D/+);Klf4(fl/fl) mouse model, and we used adenovirus-expressed Cre to induce K-ras activation and Klf4 depletion in the lung. Although Klf4 deletion alone or K-ras mutation alone can trigger lung tumor formation, Klf4 deletion combined with K-ras mutation significantly enhanced lung tumor formation. We also found that Klf4 deletion in conjunction with K-ras activation caused lung inflammation. To understand the mechanism whereby KLF4 is regulated during lung tumorigenesis, we analyzed KLF4 promoter methylation and the profiles of epigenetic factors. We found that Class I histone deacetylases (HDACs) are overexpressed in lung cancer and that HDAC inhibitors induced expression of KLF4 and inhibited proliferation of lung cancer cells, suggesting that KLF4 is probably repressed by histone acetylation and that HDACs are valuable drug targets for lung cancer treatment.

  1. Gene expression analysis uncovers novel hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells.

    Science.gov (United States)

    Zhou, Xiaobo; Qiu, Weiliang; Sathirapongsasuti, J Fah; Cho, Michael H; Mancini, John D; Lao, Taotao; Thibault, Derek M; Litonjua, Augusto A; Bakke, Per S; Gulsvik, Amund; Lomas, David A; Beaty, Terri H; Hersh, Craig P; Anderson, Christopher; Geigenmuller, Ute; Raby, Benjamin A; Rennard, Stephen I; Perrella, Mark A; Choi, Augustine M K; Quackenbush, John; Silverman, Edwin K

    2013-05-01

    Hedgehog interacting protein (HHIP) was implicated in chronic obstructive pulmonary disease (COPD) by genome-wide association studies (GWAS). However, it remains unclear how HHIP contributes to COPD pathogenesis. To identify genes regulated by HHIP, we performed gene expression microarray analysis in a human bronchial epithelial cell line (Beas-2B) stably infected with HHIP shRNAs. HHIP silencing led to differential expression of 296 genes; enrichment for variants nominally associated with COPD was found. Eighteen of the differentially expressed genes were validated by real-time PCR in Beas-2B cells. Seven of 11 validated genes tested in human COPD and control lung tissues demonstrated significant gene expression differences. Functional annotation indicated enrichment for extracellular matrix and cell growth genes. Network modeling demonstrated that the extracellular matrix and cell proliferation genes influenced by HHIP tended to be interconnected. Thus, we identified potential HHIP targets in human bronchial epithelial cells that may contribute to COPD pathogenesis.

  2. Protection of lung function by introducing single photon emission computed tomography lung perfusion image into radiotherapy plan of lung cancer

    Institute of Scientific and Technical Information of China (English)

    YIN Yong; CHEN Jin-hu; LI Bao-sheng; LIU Tong-hai; LU jie; BAI Tong; DONG Xiao-ling; YU Jin-ming

    2009-01-01

    Background The lung functional status could be displayed on lung perfusion images. With the images, the radiotherapy plans of lung cancer could be guided to more optimized. This study aimed to assess quantitatively the impact of incorporating functional lung imaging into 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT) planning for non-small cell lung cancer (NSCLC).Methods Ten patients with NSCLC who had undergone radiotherapy were included in this study. Before radiotherapy,each patient underwent CT simulation and lung perfusion imaging with single photon emission computed tomography (SPECT). The SPECT images were registered with simulation planning CT and used to contour functional lung (lung-F) and non-functional lung (lung-NF). Two 3DCRT plans and two IMRT plans were designed and compared in each patient:two anatomic plans using simulation CT alone and two functional plans using SPECT-CT in addition to the simulation CT.Dosimetric parameters of the four types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Total radiation dose was set at 66 Gy (2 Gy×33 fractions).Results In incorporating perfusion information in 3DCRT and IMRT planning, the reductions on average in the mean doses to the functional lung in the functional plan were 168 cGy and 89 cGy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, >20 Gy, >30 Gy and >40 Gy for functional lung in the functional plans were 6.50%, 10.21%, 14.02%, 22.30% and 23.46% in 3DCRT planning,respectively, and 3.05%, 15.52%, 14.16%, 4.87%, and 3.33% in IMRT planning, respectively. No greater degree of sparing of the functional lung was achieved in functional IMRT than in 3DCRT.Conclusion Function-guided 3DCRT and IMRT plannings both appear to be effective in preserving functional lung in NSCLC patients.

  3. Longitudinal micro-CT provides biomarkers of lung disease that can be used to assess the effect of therapy in preclinical mouse models, and reveal compensatory changes in lung volume.

    Science.gov (United States)

    Vande Velde, Greetje; Poelmans, Jennifer; De Langhe, Ellen; Hillen, Amy; Vanoirbeek, Jeroen; Himmelreich, Uwe; Lories, Rik J

    2016-01-01

    In vivo lung micro-computed tomography (micro-CT) is being increasingly embraced in pulmonary research because it provides longitudinal information on dynamic disease processes in a field in which ex vivo assessment of experimental disease models is still the gold standard. To optimize the quantitative monitoring of progression and therapy of lung diseases, we evaluated longitudinal changes in four different micro-CT-derived biomarkers [aerated lung volume, lung tissue (including lesions) volume, total lung volume and mean lung density], describing normal development, lung infections, inflammation, fibrosis and therapy. Free-breathing mice underwent micro-CT before and repeatedly after induction of lung disease (bleomycin-induced fibrosis, invasive pulmonary aspergillosis, pulmonary cryptococcosis) and therapy (imatinib). The four lung biomarkers were quantified. After the last time point, we performed pulmonary function tests and isolated the lungs for histology. None of the biomarkers remained stable during longitudinal follow-up of adult healthy mouse lungs, implying that biomarkers should be compared with age-matched controls upon intervention. Early inflammation and progressive fibrosis led to a substantial increase in total lung volume, which affects the interpretation of aerated lung volume, tissue volume and mean lung density measures. Upon treatment of fibrotic lung disease, the improvement in aerated lung volume and function was not accompanied by a normalization of the increased total lung volume. Significantly enlarged lungs were also present in models of rapidly and slowly progressing lung infections. The data suggest that total lung volume changes could partly reflect a compensatory mechanism that occurs during disease progression in mice. Our findings underscore the importance of quantifying total lung volume in addition to aerated lung or lesion volumes to accurately document growth and potential compensatory mechanisms in mouse models of lung

  4. Haemophilia, AIDS and lung epithelial permeability

    Energy Technology Data Exchange (ETDEWEB)

    O' Doherty, M.J.; Page, C.J.; Harrington, C.; Nunan, T.; Savidge, G. (Haemophilia Centre and Coagulation Research Unit, Department of Nuclear Medicine, Rayne Institute, St. Thomas' Hospital, London (United Kingdom))

    1990-01-01

    Lung {sup 99m}Tc DTPA transfer was measured in HIV antibodypositive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung {sup 99m}Tc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compred to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV-positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung basis in HIV-positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of {sup 99m}Tc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody-positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost-effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow-up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs. (au).

  5. Normal Pressure Hydrocephalus (NPH)

    Science.gov (United States)

    ... local chapter Join our online community Normal Pressure Hydrocephalus (NPH) Normal pressure hydrocephalus is a brain disorder ... Symptoms Diagnosis Causes & risks Treatments About Normal Pressure Hydrocephalus Normal pressure hydrocephalus occurs when excess cerebrospinal fluid ...

  6. MicroRNA-181b stimulates inflammation via the nuclear factor-κB signaling pathway in vitro.

    Science.gov (United States)

    Wang, Yazhen; Mao, Genxiang; Lv, Yuandong; Huang, Qingdong; Wang, Guofu

    2015-10-01

    Acute lung injury (ALI) is characterized by severe lung edema and an increase in the inflammatory reaction. Considerable evidence has indicated that microRNAs (miRNAs or miRs) are involved in various human diseases; however, the expression profile and function of miRNAs in ALI have been rarely reported. The present study used miRNA microarray and reverse transcription-quantitative polymerase chain reaction to demonstrate that miR-181b is the one of the most significantly upregulated miRNA after lipopolysaccharide (LPS) stimulation in human bronchial epithelial cells, BEAS-2B. To elaborate the role of miR-181b in ALI, an assay was performed to investigate the overexpression of miR-181b in BEAS-2B cells, and the expression of inflammatory factors was then analyzed. The overexpression of miR-181b resulted in the induction of an increment in interleukin (IL)-6 levels. p65 was identified to be a primary component of NF-κB, since it was upregulated in the miR-181b overexpression in the BEAS-2B cells, while pyrrolidine dithiocarbamate, a specific inhibitor of NF-κB, was found to be able to abrogate the upregulation of the expression of p65. In conclusion, the findings of the present study suggested that miR-181b may be involved in the process of LPS-induced inflammation in BEAS-2B cells by activating the NF-κB signaling pathway, which implies that it may serve as a potential therapeutic target for ALI.

  7. Genetics Home Reference: lung cancer

    Science.gov (United States)

    ... neoplasm of lung malignant tumor of lung pulmonary cancer pulmonary carcinoma pulmonary neoplasms respiratory carcinoma Related Information How are genetic conditions and genes named? Additional Information & Resources ... Encyclopedia: Lung Cancer--Non-Small Cell Encyclopedia: Lung Cancer--Small Cell ...

  8. Normal lung dose-volume histogram varieties in the former and inter period of three dimensional conformal radiation therapy plans and their clinical significance in non-small cell lung cancer%非小细胞肺癌三维适形后程加速超分割放疗中肺剂量体积变化规律及临床意义探讨

    Institute of Scientific and Technical Information of China (English)

    胡银祥; 卢冰; 周华宁; 甘家应; 洪卫

    2009-01-01

    Objective To analyze the normal lung dose-volume histogram(DVH) varieties in the former and later period(P1 and P2)of three dimensional conformal radiation therapy(3DCRT) plans and the compound (Pc) plan in non-small cell lung cancer(NSCLC),and to access the feasibility to modify the target volume during the treatment course.Methods Twenty-one NSCLC patients who had received accelerated hyper-frationation 3DCRT in P2 were included in the study.Both of the P1 and P2 plans were redesigned to a total dose of 70 Gy with V20 smaller than 35%.When the target volume was modified and P2 plan was rede signed using accelerated hyper-frationation 3DCRT of 30 Gy after P1 plan of 40 Gy,the Pc plan was compoun ded by transmitting the parameters(such as target volume,irradiation field and dose) of P1 plan into P2 plan. Total lung volume and target volumes(GTV,PTV) of P1 and P2 were evaluated.MLD,V5,V10,V20 and V30 of P1,P2 and Pc were calculated.Results The total lung volume in P1 and P2 plans was not significantly dif ferent(t = 0.19,P = 0.850).The volumes of GTV,PTV in P2 were obviously smaller than P1 (t = 2.88,P = 0.009 ; t = 4.01 ,P = 0.001) .When comparing P2 with P1 ,MLD were 16.5 Gy Vs 17.8 Gy (t = 2.60, DOI:10.3760/cma.j.issn.1004-4221.2009.01.057 P = 0.017),V30 was significantly decreased (t = 2.19,P = 0.041),but V5,V10 and V20 had no significant difference.Similar differences were found in MLD,V5 ,V10 ,V20 and V30 when comparing Po to P1.P2 plans had significantly smaller MLD,Vs,V10,V20 and V30 than Pc plans.Fourteen patients with decreased PTV were further analyzed.The V30 and MLD decreased significantly (t = 3.00,P = 0.0 I 0;t = 2.38,P = 0.033), but V5 ,V10,V20 had no difference when comparing P1 and P2 plans.Among these 14 patients,the V10 and V30 decreased significantly(t = 2.76,P = 0.033 ; t = 3.60,P = 0.011) when P2 plans were generated using the same field number and beam angles in P1 plans in 7 patients.The parameters were similar in P1and Pc plans

  9. Farmer's Lung: Causes and Symptoms of Mold and Dust Induced Respiratory Illness

    OpenAIRE

    Grisso, Robert D. (Robert Dwight), 1956-; Gay, Susan Wood; Hetzel, Glen Hayward; Stone, Bruce

    2009-01-01

    Farmer's lung is a noninfectious allergic disease that is caused by inhaling mold spores in the dust from moldy hay, straw, or grain. This debilitating disease disrupts the normal function of the lungs, where oxygen enters and carbon dioxide exits the bloodstream. Many farmers are forced to leave the occupation due to the physical limitations caused by farmer's lung.

  10. Lungs and Respiratory System

    Science.gov (United States)

    ... even smaller tubes called bronchioles. Bronchioles end in tiny air sacs called alveoli, where the exchange of oxygen and carbon dioxide actually takes place. Each lung houses about 300-400 million alveoli. The lungs also ...

  11. Placental Transmogrification of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Woo; Park, Il Hwan; Kwon, Woo Cheol; Eom, Min Seob; Kim, Young Ju; Hwan, Joong Hwan [Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2013-12-15

    Placental transmogrification is a very rare lung disease, where the alveoli resemble the chorionic villi of placenta, and this change is a characteristic finding. A 31-year-old female patient presented with cough and dyspnea that had begun 2 weeks prior to admission. Along with giant bulla found in the left upper lung field, subsegmental consolidation was also identified in the lingular segment on plain chest radiograph and CT scan. Wedge resection was performed to remove the bulla. Pathologic examination of the resected bulla revealed destruction of the normal structures and characteristic villous and papillary changes. These changes led to a diagnosis of placental transmogrification. We made an encounter of an unusual placental transmogrification which had different image findings from other reported transmogrification cases. Thus, we report an atypical placental transmogrification case where both consolidation and giant bulla coexist.

  12. Lung function

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930500 Application of flow volume loops on di-agnosis of pulmonary diseases.WANG Shuchuan(王枢传),et al.Dept Thoraic Med,TianjinChest Hosp,Tianjin,300000.Tianjin Med J1993;21(5):262—263.Seven flow volume loops in patients with vari-ous pulmonary diseases were presented.Case 1showed a normal picture of flow volume loops.Case 2,a patient with chronic bronchitis,pre-sented a typical and characteristic obstructiveconfiguration.Case 3,a patient with asthma,re-sulted in a reversible obstructive picture withgreat change before and after inhalation of abronchodilator.Case 4,a long term smoker,hada picture of small airway obstruction.Though

  13. Lung carcinogenesis from chronic obstructive pulmonary disease: characteristics of lung cancer from COPD and contribution of signal transducers and lung stem cells in the inflammatory microenvironment.

    Science.gov (United States)

    Sekine, Yasuo; Hata, Atsushi; Koh, Eitetsu; Hiroshima, Kenzo

    2014-07-01

    Chronic obstructive pulmonary disease (COPD) and lung cancer are closely related. The annual incidence of lung cancer arising from COPD has been reported to be 0.8-1.7 %. Treatment of lung cancer from COPD is very difficult due to low cardiopulmonary function, rapid tumor growth, and resistance to molecularly targeted therapies. Chronic inflammation caused by toxic gases can induce COPD and lung cancer. Carcinogenesis in the inflammatory microenvironment occurs during cycles of tissue injury and repair. Cellular damage can induce induction of necrotic cell death and loss of tissue integrity. Quiescent normal stem cells or differentiated progenitor cells are introduced to repair injured tissues. However, inflammatory mediators may promote the growth of bronchioalveolar stem cells, and activation of NF-κB and signal transducer and activator of transcription 3 (STAT3) play crucial roles in the development of lung cancer from COPD. Many of the protumorgenic effects of NF-κB and STAT3 activation in immune cells are mediated through paracrine signaling. NF-κB and STAT3 also contribute to epithelial-mesenchymal transition. To improve lung cancer treatment outcomes, lung cancer from COPD must be overcome. In this article, we review the characteristics of lung cancer from COPD and the mechanisms of carcinogenesis in the inflammatory microenvironment. We also propose the necessity of identifying the mechanisms underlying progression of COPD to lung cancer, and comment on the clinical implications with respect to lung cancer prevention, screening, and therapy.

  14. Ectopic expression of C/EBPalpha in the lung epithelium disrupts late lung development.

    Science.gov (United States)

    Berg, Tove; Didon, Lukas; Nord, Magnus

    2006-10-01

    The lung develops from the endoderm through a process of branching morphogenesis. This process is highly active during the pseudoglandular stage of lung development and continues into the canalicular stage, resulting in the formation of terminal sacs. CCAAT/enhancer binding proteins (C/EBPs) are transcription factors regulating central aspects of differentiation and proliferation. We report here the developmental expression of C/EBPalpha, -beta, and -delta in the lung. C/EBPalpha exhibits a dynamic expression pattern and is first detected during the late pseudoglandular stage. At this stage, expression is observed in a subset of epithelial cells in the distal parts of the branching tubules. The expression of C/EBPalpha is confined to nonproliferating cells. To examine the role of C/EBPalpha in lung development, we generated transgenic mice ectopically expressing C/EBPalpha in the lung epithelium using the human surfactant protein C promoter. Lungs from these mice were of normal size but exhibited a phenotype characterized by fewer and larger developing epithelial tubules, indicating that the branching process was affected. No effects on overall proliferation or cellular differentiation were observed. When this phenotype was compared with that of mice carrying a targeted mutation of the Cebpa gene, the Cebpa-/- mice exhibited a similar developmental phenotype. In conclusion, our results show a role for C/EBPalpha in lung development and suggest a function in the later stages of lung branching morphogenesis.

  15. Clinical significance of PHPT1 protein expression in lung cancer

    Institute of Scientific and Technical Information of China (English)

    XU An-jian; XIA Xiang-hou; DU Song-tao; GU Jun-chao

    2010-01-01

    Background in our previous studies, we found the expression of 14-kD phosphohistidine phosphatase (PHPT1) was associated with lung cancer cells migration and invasion, and PHPT1 mRNA expression level in lung cancer tissues clinically correlated with lymph node metastasis. in the present study, we aimed to further investigate the expression of PHPT1 protein in lung cancer.Methods Expression of PHPT1 protein in tissue samples from 146 lung cancers and 30 normal tissues adjacent to lung cancers was assessed using immunohistochemical method. Fisher's exact test was used to analyze expression patterns of PHPT1 protein in these tissue types. Meanwhile, we studied the correlation between expression of PHPT1 protein and clinicopathological features in lung cancer.Results Significantly higher expression levels of PHPT1 protein were found in lung cancer samples (53.42%) than in normal tissues adjacent to lung cancer (23.33%) (P=0.003). Fisher's exact test showed that lung cancer stage positively correlated with expression of PHPT1 protein (P=0.02), and lung cancer samples with lymph node metastasis showed higher PHPT1 protein expression (P=0.016) than the samples without lymph node metastasis.Conclusions The results of this study agree with findings from our previous study of PHPT1 mRNA expression in lung cancer tissues, and strongly suggest that PHPT1 protein is closely associated with the carcinogenesis and metastasis of lung cancer. Thus, therapy targeting PHPT1 (inhibition or silencing) could be potentially benefited for lung cancer patients.

  16. Optimizing treatment scheme for stereotatic treatment with cyberknife in lung cancer patients by analyzing radiobiological parameters determined by tumour locations

    OpenAIRE

    Chan, Chun-lun; 陳俊麟

    2015-01-01

    Objectives: Lung cancer is the leading cause of cancer mortality in the world. Stereotactic Body Radiation Therapy (SBRT) is a novel technique in treatment of inoperable Non-Small Cell Lung Cancer (NSCLC) in which a high dose delivery of 8-30Gy radiation to the lung tumour with one to five fractions precisely, simultaneously, avoiding as much normal tissue as possible. In the present pilot study, lungs were evenly divided into three parts in cranio–caudal direction, namely Upper Lung,...

  17. Differential actions of selenium on Tumor vs. Normal increase radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Ji-Yeon; Song, Jie-Young; Yun, Yeon-Sook [Korea institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Park, Young-Mee [Roswell Park Cancer Institute, Buffalo (United States)

    2006-07-01

    Selenium is an essential trace element required for normal health and is also a promising agent for preventing cancer. In clinical trials, selenium has significantly protective effects against lung, prostate, colon, and head and neck cancer. Solid tumors in hypoxic and hypoxic/reoxygenation condition have long been considered a problem in cancer therapy. Hypoxic tumor cells were shown to be more resistant to radiotherapy (RT) and many conventional chemotherapeutic agents than their normoxic counterparts. Lung cancer is the leading cause of cancer death in both men and women in the United States. Non-small cell lung cancer (NSCLC) accounts for more than 75% of all lung cancers. RT is the routine treatment modality for these lung cancer patients. The goal of RT is to deliver cytotoxicity to the tumor site, while minimizing cytotoxicity to the surrounding normal tissues. Peroxiredoxin I (Prx I) has been reported to be highly elevated in lung cancer compared to that in normal tissues. NF-E2-related factor 2 (Nrf2) assumed as one of the major transcription factors of Prx I. Nrf2 plays a critical role in regulating expression of antioxidant and phase II drug-metabolizing enzymes, thereby contributing to detoxification, elimination, and protection of tissues or cells against environmental oxidative stress or xenobiotics including medicine. In the present study, we demonstrate that pretreatment with selenium has differential effect on tumor and normal tissue that might be associated with different regulation of Nrf2 under the circumstances of surrounding microenvironment.

  18. Normalization: A Preprocessing Stage

    OpenAIRE

    Patro, S. Gopal Krishna; Sahu, Kishore Kumar

    2015-01-01

    As we know that the normalization is a pre-processing stage of any type problem statement. Especially normalization takes important role in the field of soft computing, cloud computing etc. for manipulation of data like scale down or scale up the range of data before it becomes used for further stage. There are so many normalization techniques are there namely Min-Max normalization, Z-score normalization and Decimal scaling normalization. So by referring these normalization techniques we are ...

  19. RELATED GENES IN LUNG CANCER TISSUES ASSOCIATED WITH RESIDENTIAL HIGH RADON EXPOSURE

    Institute of Scientific and Technical Information of China (English)

    夏英; 杨梅英; 张守志; 叶常青

    2002-01-01

    Objective: To investigate the related genes in lung cancer tissues associated with residential high radon exposure. Methods: Differentially expressed gene fragments in lung cancer and normal lung tissues were discovered by differential display and reverse Northern blot hybridization method. The fragments positive in lung cancer and negative in normal lung tissue were determined. Results: Seven differential displayed fragments were sequenced. One of them named NA7 is 95% homologous with AI208667 in EAT of Genbank. Another fragment named NG2 is up to 98% homologous with five fragments. The remained one CA1 may be a new gene fragment. Conclusion: 3 gene fragments were discovered from lung cancer and normal lung tissues of high radon exposure resident.

  20. NHLBI viewpoint: Lung health and disease prevention research starting in childhood.

    Science.gov (United States)

    Blaisdell, Carol J; Weinmann, Gail G

    2015-06-01

    Lung health begins in utero when the complex structure of the airway, alveolar, and vascular structures are formed. To really impact the United States and global burden of chronic lung diseases in both adults and children, we must understand normal and abnormal development, the outcomes of disrupted development, and the effects of in utero and postnatal exposures on lung health. With increasing recognition of early life origins of adult diseases,(1) it is important to know what early events and interventions can alter the trajectory of lung development, growth, and decline to help promote lung health and reduce chronic lung disease.

  1. Dicer function is essential for lung epithelium morphogenesis.

    Science.gov (United States)

    Harris, Kelley S; Zhang, Zhen; McManus, Michael T; Harfe, Brian D; Sun, Xin

    2006-02-14

    DICER is a key enzyme that processes microRNA and small interfering RNA precursors into their short mature forms, enabling them to regulate gene expression. Only a single Dicer gene exists in the mouse genome, and it is broadly expressed in developing tissues. Dicer-null mutants die before gastrulation. Therefore, to study Dicer function in the later event of lung formation, we inactivated it in the mouse lung epithelium using a Dicer conditional allele and the Sonic Hedgehogcre (Shhcre) allele. Branching arrests in these mutant lungs, although epithelial growth continues in distal domains that are expanded compared with normal samples. These defects result in a few large epithelial pouches in the mutant lung instead of numerous fine branches present in a normal lung. Significantly, the initial phenotypes are apparent before an increase in epithelial cell death is observed, leading us to propose that Dicer plays a specific role in regulating lung epithelial morphogenesis independent of its requirement in cell survival. In addition, we found that the expression of Fgf10, a key gene involved in lung development, is up-regulated and expanded in the mesenchyme of Dicer mutant lungs. Previous studies support the hypothesis that precise localization of FGF10 in discrete sites of the lung mesenchyme serves as a chemoattractant for the outgrowth of epithelial branches. The aberrant Fgf10 expression may contribute to the Dicer morphological defects. However, the mechanism by which DICER functions in the epithelium to influence Fgf10 expression in the mesenchyme remains unknown.

  2. Estimation of pulmonary hypertension in lung and valvular heart diseases by perfusion lung scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Tadashige [Shinshu Univ., Matsumoto, Nagano (Japan). School of Allied Medical Sciences; Tanaka, Masao; Yazaki, Yoshikazu; Kitabayashi, Hirosi; Koizumi, Tomonori; Kubo, Keisi; Sekiguchi, Morie; Yano, Kesato

    1999-06-01

    To estimate pulmonary hypertension, we measured postural differences in pulmonary blood flow for the lateral decubitus positions on perfusion lung scintigrams with Tc-99 m macro-aggregated albumin, applying the method devised by Tanaka et al (Eur J Nucl Med 17: 320-326, 1990). Utilizing a scintillation camera coupled to a minicomputer system, changes in the distribution of pulmonary blood flow caused by gravitational effects, namely, changes in the total count ratios for the right lung versus the left lung in the right and left lateral decubitus positions (R/L), were obtained for 44 patients with lung disease, 95 patients with valvular heart disease, and 23 normal subjects. Mean standard deviation in the R/L ratios was 3.09{+-}1.28 for the normal subjects, 1.97{+-}0.89 for the patients with lung disease, and 1.59{+-}0.59 for the patients with valvular heart disease. The R/L ratios correlated with mean pulmonary arterial pressure and cardio-thoracic ratios in the lung disease and valvular heart disease groups, with pulmonary arteriolar resistance in the former, and with pulmonary capillary wedge pressure in the latter. Defining pulmonary hypertension (>20 mmHg) as an R/L ratio of less than 1.81, which is the mean-1 standard deviation for normal subjects, the sensitivity and the specificity of the R/L ratio for the diagnosis of pulmonary hypertension were 62.9% and 76.2%, respectively, for the lung disease patients, and 80.3% and 61.8%, respectively, for the valvular heart disease patients. This method seems to be useful for the pathophysiologic evaluation of pulmonary perfusion in cases of lung disease and valvular heart disease. (author)

  3. Uncovering growth-suppressive MicroRNAs in lung cancer

    DEFF Research Database (Denmark)

    Liu, Xi; Sempere, Lorenzo F; Galimberti, Fabrizio

    2009-01-01

    PURPOSE: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth-suppressive miRNAs in lung cancer. EXPERIMENTAL DESIGN: miRNA arrays were done on normal lung tissues...... and adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each...... transgenic line (designated as ED-1 and ED-2 cells, respectively). Each highlighted miRNA was independently transfected into these cells. Growth-suppressive mechanisms were explored. Expression of a computationally predicted miRNA target was examined. These miRNAs were studied in a paired normal...

  4. Preclinical studies on the use of interstitial laser photocoagulation in the lung parenchyma

    Science.gov (United States)

    Fielding, D. I.; Buonaccorsi, Giovanni A.; Hanby, A.; Hetzel, M. R.; Bown, Stephen G.

    1996-12-01

    A preliminary assessment was made of the effect of interstitial laser photocoagulation on normal lung parenchyma. Using rats lesions were created by passing the laser fiber percutaneously into the normal lung under general anaesthetic. The lungs were removed post mortem at 3 days. The lesions were ellipsoid in shape and well circumscribed. Histology showed central charring surrounded by zones of coagulative and hemorrhagic necrosis. there was a clear margin between the treated and normal tissue. These results indicate that further examination is warranted of the use of ILP for treatment of small primary lung tumors in patients unsuitable for surgery.

  5. SAMHD1 is down regulated in lung cancer by methylation and inhibits tumor cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jia-lei [Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Lu, Fan-zhen [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China); Shen, Xiao-Yong, E-mail: shengxiaoyong_sh@163.com [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China); Wu, Yun, E-mail: WuYun_hd@163.com [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China); Zhao, Li-ting [Department of Thoracic Surgery, The Huadong Hospital, Fudan University, Shanghai 200040 (China)

    2014-12-12

    Highlights: • SAMHD1 expression level is down regulated in lung adenocarcinoma. • The promoter of SAMHD1 is methylated in lung adenocarcinoma. • Over expression of SAMHD1 inhibits the proliferation of lung cancer cells. - Abstract: The function of dNTP hydrolase SAMHD1 as a viral restriction factor to inhibit the replication of several viruses in human immune cells was well established. However, its regulation and function in lung cancer have been elusive. Here, we report that SAMHD1 is down regulated both on protein and mRNA levels in lung adenocarcinoma compared to adjacent normal tissue. We also found that SAMHD1 promoter is highly methylated in lung adenocarcinoma, which may inhibit its gene expression. Furthermore, over expression of the SAMHD1 reduces dNTP level and inhibits the proliferation of lung tumor cells. These results reveal the regulation and function of SAMHD1 in lung cancer, which is important for the proliferation of lung tumor cells.

  6. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas.

    Science.gov (United States)

    Campbell, Joshua D; Alexandrov, Anton; Kim, Jaegil; Wala, Jeremiah; Berger, Alice H; Pedamallu, Chandra Sekhar; Shukla, Sachet A; Guo, Guangwu; Brooks, Angela N; Murray, Bradley A; Imielinski, Marcin; Hu, Xin; Ling, Shiyun; Akbani, Rehan; Rosenberg, Mara; Cibulskis, Carrie; Ramachandran, Aruna; Collisson, Eric A; Kwiatkowski, David J; Lawrence, Michael S; Weinstein, John N; Verhaak, Roel G W; Wu, Catherine J; Hammerman, Peter S; Cherniack, Andrew D; Getz, Gad; Artyomov, Maxim N; Schreiber, Robert; Govindan, Ramaswamy; Meyerson, Matthew

    2016-06-01

    To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined the exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor-normal pairs. Recurrent alterations in lung SqCCs were more similar to those of other squamous carcinomas than to alterations in lung ADCs. New significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types. New amplification peaks encompassed MIR21 in lung ADC, MIR205 in lung SqCC, and MAPK1 in both. Lung ADCs lacking receptor tyrosine kinase-Ras-Raf pathway alterations had mutations in SOS1, VAV1, RASA1, and ARHGAP35. Regarding neoantigens, 47% of the lung ADC and 53% of the lung SqCC tumors had at least five predicted neoepitopes. Although targeted therapies for lung ADC and SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes.

  7. A novel SCID mouse model for studying spontaneous metastasis of human lung cancer to human tissue.

    Science.gov (United States)

    Teraoka, S; Kyoizumi, S; Seyama, T; Yamakido, M; Akiyama, M

    1995-05-01

    We established a novel severe combined immunodeficient (SCID) mouse model for the study of human lung cancer metastasis to human lung. Implantation of both human fetal and adult lung tissue into mammary fat pads of SCID mice showed a 100% rate of engraftment, but only fetal lung implants revealed normal morphology of human lung tissue. Using these chimeric mice, we analyzed human lung cancer metastasis to both mouse and human lungs by subcutaneous inoculation of human squamous cell carcinoma and adenocarcinoma cell lines into the mice. In 60 to 70% of SCID mice injected with human-lung squamous-cell carcinoma, RERF-LC-AI, cancer cells were found to have metastasized to both mouse lungs and human fetal lung implants but not to human adult lung implants 80 days after cancer inoculation. Furthermore, human-lung adenocarcinoma cells, RERF-LC-KJ, metastasized to the human lung implants within 90 days in about 40% of SCID mice, whereas there were no metastases to the lungs of the mice. These results demonstrate the potential of this model for the in vivo study of human lung cancer metastasis.

  8. Differential Gene Expression in Chemically Induced Mouse Lung Adenomas

    Directory of Open Access Journals (Sweden)

    Ruisheng Yao

    2003-01-01

    Full Text Available Because of similarities in histopathology and tumor progression stages between mouse and human lung adenocarcinomas, the mouse lung tumor model with lung adenomas as the endpoint has been used extensively to evaluate the efficacy of putative lung cancer chemopreventive agents. In this study, a competitive cDNA library screening (CCLS was employed to determine changes in the expression of mRNA in chemically induced lung adenomas compared with paired normal lung tissues. A total of 2555 clones having altered expression in tumors were observed following competitive hybridization between normal lung and lung adenomas after primary screening of over 160,000 clones from a mouse lung cDNA library. Among the 755 clones confirmed by dot blot hybridization, 240 clones were underexpressed, whereas 515 clones were overexpressed in tumors. Sixty-five clones with the most frequently altered expression in six individual tumors were confirmed by semiquantitative RT-PCR. When examining the 58 known genes, 39 clones had increased expression and 19 had decreased expression, whereas the 7 novel genes showed overexpression. A high percentage (>60% of overexpressed or underexpressed genes was observed in at least two or three of the lesions. Reproducibly overexpressed genes included ERK-1, JAK-1, surfactant proteins A, B, and C, NFAT1, α-1 protease inhibitor, helix-loop-helix ubiquitous kinase (CHUK, α-adaptin, α-1 PI2, thioether S-methyltransferase, and CYP2C40. Reproducibly underexpressed genes included paroxanase, ALDH II, CC10, von Ebner salivary gland protein, and α- and β-globin. In addition, CCLS identified several novel genes or genes not previously associated with lung carcinogenesis, including a hypothetical protein (FLJ11240 and a guanine nucleotide exchange factor homologue. This study shows the efficacy of this methodology for identifying genes with altered expression. These genes may prove to be helpful in our understanding of the genetic basis of

  9. Bronchoscopic cryobiopsy for the diagnosis of diffuse parenchymal lung disease.

    Directory of Open Access Journals (Sweden)

    Jonathan A Kropski

    Full Text Available BACKGROUND: Although in some cases clinical and radiographic features may be sufficient to establish a diagnosis of diffuse parenchymal lung disease (DPLD, surgical lung biopsy is frequently required. Recently a new technique for bronchoscopic lung biopsy has been developed using flexible cryo-probes. In this study we describe our clinical experience using bronchoscopic cryobiopsy for diagnosis of diffuse lung disease. METHODS: A retrospective study of subjects who had undergone bronchoscopic cryobiopsy for evaluation of DPLD at an academic tertiary care center from January 1, 2012 through January 15, 2013 was performed. The procedure was performed using a flexible bronchoscope to acquire biopsies of lung parenchyma. H&E stained biopsies were reviewed by an expert lung pathologist. RESULTS: Twenty-five eligible subjects were identified. With a mean area of 64.2 mm(2, cryobiopsies were larger than that typically encountered with traditional transbronchial forceps biopsy. In 19 of the 25 subjects, a specific diagnosis was obtained. In one additional subject, biopsies demonstrating normal parenchyma were felt sufficient to exclude diffuse lung disease as a cause of dyspnea. The overall diagnostic yield of bronchoscopic cryobiopsy was 80% (20/25. The most frequent diagnosis was usual interstitial pneumonia (UIP (n = 7. Three of the 25 subjects ultimately required surgical lung biopsy. There were no significant complications. CONCLUSION: In patients with suspected diffuse parenchymal lung disease, bronchoscopic cryobiopsy is a promising and minimally invasive approach to obtain lung tissue with high diagnostic yield.

  10. Lung involvement in systemic connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Plavec Goran

    2008-01-01

    Full Text Available Background/Aim. Systemic connective tissue diseases (SCTD are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory system. The aim of this study was to find out the frequency of respiratory symptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT abnormalities, and their correlation with the duration of the disease and the applied treatment. Methods. In 47 non-randomized consecutive patients standard chest radiography, HRCT, and lung function tests were done. Results. Hypoxemia was present in nine of the patients with respiratory symptoms (20%. In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had symptoms of lung involvement. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung function disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro. Conclusion. Pulmonary fibrosis occurs in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

  11. The lung mucosa: A critical environmental battleground

    Energy Technology Data Exchange (ETDEWEB)

    Bergofsky, E.H. (Pulmonary Disease Division, State University of New York, Stony Brook (United States))

    1991-10-21

    The entirety of the lung mucous membrane and epithelial surface are exposed to the environment; react to noxious environmental gases, vapors, and particles; and are under physiologic and humoral mediator control. In recent years much information has been gained regarding the mucous membrane of the tracheobronchial tree, its physiology, and its reaction to environmental hazards. The pharmacologic control of secretion, ciliary beat rate, and net mucus flow governs both the clearance of mucus and the clearance of particles. The physiologic factors that govern this clearance mechanism can be influenced by pharmacologic agents in patients with lung disease and presumably also in patients with purely environmental injury. The effects of ozone on lung function, lung compliance, and airway resistance have been well documented in adults and children. Environmental ozone also alters mucous membrane function, increasing mucociliary secretion rate and peripheral lung clearance. The speed-up in clearance implies an increase in mucous gland secretion, which may act unfavorably when ciliary beat is damaged, glandular hypertrophy is present, or flow-limiting segments exist, as is usually the case in bronchial asthma and chronic obstructive pulmonary disease. Thus, whereas the consequences of ozone may be modest for a normal, healthy individual, they presumably increase hazards for the individual with lung disease or damage. For this reason, efforts should be made to control or limit damage by ozone or other environmental inhalants in such individuals. This goal may be facilitated by a wider knowledge of the pharmacologic control of the mucous membrane.30 references.

  12. Differential Inequalities, Normality and Quasi-Normality

    CERN Document Server

    Liu, Xiaojun; Pang, Xuecheng

    2011-01-01

    We prove that if D is a domain in C, alpha>1 and c>0, then the family F of functions meromorphic in D such that |f'(z)|/(1+|f(z)|^alpha)>c for every z in D is normalin D. For alpha=1, the same assumptions imply quasi-normality but not necessarily normality.

  13. Silica nanoparticles induce cytokine responses in lung epithelial cells through activation of a p38/TACE/TGF-α/EGFR-pathway and NF-κΒ signalling

    Energy Technology Data Exchange (ETDEWEB)

    Skuland, Tonje, E-mail: tonje.skuland@fhi.no; Øvrevik, Johan; Låg, Marit; Schwarze, Per; Refsnes, Magne

    2014-08-15

    Amorphous silica nanoparticles (SiNPs) have previously been shown to induce marked cytokine (interleukin-6; IL-6 and interleukin-8; CXCL8/IL-8) responses independently of particle uptake in human bronchial epithelial BEAS-2B cells. In this study the involvement of the mitogen-activated protein kinases (MAP-kinases), nuclear factor-kappa Β (NF-κΒ) and in particular tumour necrosis factor-α converting enzyme (TACE) and—epidermal growth factor receptor (EGFR) signalling pathways were examined in triggering of IL-6 and CXCL8 release after exposure to a 50 nm silica nanoparticle (Si50). Exposure to Si50 increased phosphorylation of NF-κΒ p65 and MAP-kinases p38 and JUN-N-terminal protein kinase pathways (JNK), but not extracellular signal regulated kinases (ERK). Inhibition of NF-κΒ and p38 reduced the cytokine responses to Si50, whereas neither JNK- nor ERK-inhibition exerted any significant effect on the responses to Si50. Increases in membrane-bound transforming growth factor-α (TGF-α) release and EGFR phosphorylation were also observed after Si50 exposure, and pre-treatment with inhibitors of these pathways reduced the release of IL-6 and CXCL8, but did not affect the Si50-induced phosphorylation of p38 and p65. In contrast, p38-inhibition partially reduced Si50-induced TGF-α release, while the p65-inhibition was without effect. Overall, our results indicate that Si50-induced IL-6 and CXCL8 responses in BEAS-2B cells were regulated through combined activation of several pathways, including NF-κΒ and p38/TACE/TGF-α/EGFR signalling. The study identifies critical, initial events in the triggering of pro-inflammatory responses by nanoparticles. - Highlights: • Silica nanoparticles induce IL-6 and CXCL8 via NFκB and MAPKinase p38 in BEAS-2B • Silica nanoparticles induce release of the EGF-receptor ligand TGF-α • TGF-α release contributes to the IL-6 and CXCL8 release • Phosphorylation of p38 is involved in release of TGF-α.

  14. Inhibition of Cigarettes Smoke-induced Epithelial to Mesenchymal Transition by the SMO Inhibitor PF-5274857 in Beas-2b Epithelial Cells%PF-5274857阻断香烟烟雾诱导的上皮-间质转化的作用

    Institute of Scientific and Technical Information of China (English)

    周闻捷; 陈娇; 冯云; 樊亚平; 李倩; 傅健; 张平

    2016-01-01

    目的 探讨Smoothened (Smo)抑制剂PF-5274857在香烟烟雾(CS)诱导所致的上皮-间质转化(EMT)转变中的作用,为口腔鳞状细胞癌的临床治疗和预防提供依据.方法 以支气管上皮细胞株Beas-2b建立体外CS诱导EMT模型,实验分为预防实验和治疗实验两部分进行.预防实验:用3μtmol/L PF-5274857预刺激Beas-2b细胞2h后用CS溶液培养8d;治疗实验:CS培养8d后用3μmol/L PF-52748573处理Beas-2b细胞4d.通过Western blot、免疫荧光检测细胞蛋白中EMT标志物E-钙黏蛋白(E-cadherin)、波形蛋白(vimentin)、a平滑肌肌动蛋白(α-SMA)的含量及位置变化,小室迁移实验测定治疗实验中细胞迁移能力改变.结果 PF-5274857预刺激2h,间质标志物vimentin和α-SMA蛋白表达降低,上皮标志物E-cadherin表达升高.而已被CS诱导产生EMT改变的Beas-2b细胞经PF-5274857治疗4d后部分恢复E-cadherin表达,并且vimentin和α-SMA蛋白表达降低,其升高的迁移能力也降低.结论 PF-5274857可以预防和治疗由CS引起的Beas-2b细胞EMT.

  15. Stereotactic Irradiation of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To investigate the best stereotactic irradiation (STI) technique in treatment of small lung tumors, using dose-volume statistics. Methods: Dose-volume histogram (DVH) of the study phantom consisting of CT using the software of FOCUS-3D planning system. The beam was a 6MV X-ray from a Varian 2300C. The analysis data of Dose-volume statistics was from the technique used for: (1) 2- 12 arcs; (2) 20° - 45° separation angle of arcs; (3) 80° - 160° of gantry rotation. Then we studied the difference of DVH with various irradiation techniques and the influence of target positions and field size by calculated to the distribution of dose from 20%- 90% of the six targets in the lung with 3×3 cm2, 4′ 4 cm2 and 5′ 5 cm2 field size. Results: The volume irradiated pulmonary tissue was the smallest using a six non-coplanar 120° arcs with 30° separation between arcs in the hypothetical set up, the non-coplanar SRI was superiority than conventional one's. The six targets were chosen in the right lung, the volume was the largest in geometric center and was decreased in hilus, bottom, anterior chest wall, lateral wall and apex of the lung in such an order. The DVH had significant change with an increasing field size. Conclusion: the irradiation damage of normal pulmonary tissue was the lowest using the six non-coplanar 120° arcs with a 30° separation between arcs by <5×5 cm2 field and the position of target was not a restricting factor.

  16. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter

    2003-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...... with vitamins A, C and E and beta-carotene offers no protection against the development of lung cancer. On the contrary, beta-carotene supplementation has, in two major randomised intervention trials, resulted in an increased mortality. Smoking remains the leading cause of lung cancer. The adverse effects...

  17. Esophagus and contralateral lung-sparing IMRT for locally advanced lung cancer in the community hospital setting

    Directory of Open Access Journals (Sweden)

    Johnny eKao

    2015-06-01

    Full Text Available Background: The optimal technique for performing lung IMRT remains poorly defined. We hypothesize that improved dose distributions associated with normal tissue sparing IMRT can allow for safe dose escalation resulting in decreased acute and late toxicity. Methods: We performed a retrospective analysis of 82 consecutive lung cancer patients treated with curative intent from 1/10 to 9/14. From 1/10 to 4/12, 44 patients were treated with the community standard of 3-dimensional conformal radiotherapy or IMRT without specific esophagus or contralateral lung constraints (standard RT. From 5/12 to 9/14, 38 patients were treated with normal tissue-sparing IMRT with selective sparing of contralateral lung and esophagus. The study endpoints were dosimetry, toxicity and overall survival.Results: Despite higher mean prescribed radiation doses in the normal tissue-sparing IMRT cohort (64.5 Gy vs. 60.8 Gy, p=0.04, patients treated with normal tissue-sparing IMRT had significantly lower lung V20, V10, V5, mean lung, maximum esophagus and mean esophagus doses compared to patients treated with standard RT (p≤0.001. Patients in the normal tissue-sparing IMRT group had reduced acute grade ≥3 esophagitis (0% vs. 11%, p<0.001, acute grade ≥2 weight loss (2% vs. 16%, p=0.04, late grade ≥2 pneumonitis (7% vs. 21%, p=0.02. The 2-year overall survival was 52% with normal tissue-sparing IMRT arm compared to 28% for standard RT (p=0.015.Conclusion: These data provide proof of principle that suboptimal radiation dose distributions are associated with significant acute and late lung and esophageal toxicity that may result in hospitalization or even premature mortality. Strict attention to contralateral lung and esophageal dose volume constraints are feasible in the community hospital setting without sacrificing disease control.

  18. Lung lobe segmentation based on statistical atlas and graph cuts

    Science.gov (United States)

    Nimura, Yukitaka; Kitasaka, Takayuki; Honma, Hirotoshi; Takabatake, Hirotsugu; Mori, Masaki; Natori, Hiroshi; Mori, Kensaku

    2012-03-01

    This paper presents a novel method that can extract lung lobes by utilizing probability atlas and multilabel graph cuts. Information about pulmonary structures plays very important role for decision of the treatment strategy and surgical planning. The human lungs are divided into five anatomical regions, the lung lobes. Precise segmentation and recognition of lung lobes are indispensable tasks in computer aided diagnosis systems and computer aided surgery systems. A lot of methods for lung lobe segmentation are proposed. However, these methods only target the normal cases. Therefore, these methods cannot extract the lung lobes in abnormal cases, such as COPD cases. To extract lung lobes in abnormal cases, this paper propose a lung lobe segmentation method based on probability atlas of lobe location and multilabel graph cuts. The process consists of three components; normalization based on the patient's physique, probability atlas generation, and segmentation based on graph cuts. We apply this method to six cases of chest CT images including COPD cases. Jaccard index was 79.1%.

  19. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter

    2003-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...... are only ameliorated to a minor degree by a healthy diet....

  20. 6 Common Cancers - Lung Cancer

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents For ... Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the next ...

  1. Unilateral facial pain and lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Shakespeare, T.P.; Stevens, M.J. [Royal North Shore Hospital, Crows Nest, NSW (Australia)

    1996-02-01

    Facial pain in lung cancer patients may be secondary to metastatic disease to the brain or skull base. Since 1983 there have been 19 published reports of hemi-facial pain as a non-metastatic complication of lung carcinoma. This report describes an additional case in whom unilateral face pain preceded the diagnosis of lung cancer by 9 months. A clinical diagnosis of trigeminal neuralgia was made after a normal brain CT scan. Later on the patient complained of global lethargy, weight loss and haemoptysis. A chest X-ray disclosed a 6 cm right hilar mass that was further defined with a whole body CT scan. The neural mechanism of the unilateral facial pain is discussed and the literature reviewed. 14 refs., 1 tab.

  2. [THE ROLE OF ESTROGENS IN THE CARCINOGENESIS OF LUNG CANCER].

    Science.gov (United States)

    Uchikova, E; Uchikov, A; Dimitrakova, E; Uchikov, P

    2016-01-01

    Morbidity and mortality from lung cancer has dramatically increased in women as compared to men over the past few years. Historically, smoking has been considered the major risk factor for lung cancer regardless of gender. Several recent lines of evidence implicate gender differences in the observed differences in prevalence and histologic type which cannot be explained based on the carcinogenic action of nicotine. Several recent studies underscore the importance of reproductive and hormonal factors in the carcinogenesis of lung cancer Lung cancer morbidity and mortality in Bulgaria was 16.2/100000 women and 14.6/ 100000 women, resp. Lung cancer morbidity in Europe was 39/100000 women. Lung cancer is extremely sensitive to estrogens. The latter act directly or as effect modifiers for the relationship between smoking and lung cancer. Further research examining the relationship between serum estrogen levels and the estrogen receptor expression in normal and tumor lung tissue samples can help elucidate the importance of reproductive and hormonal (exogenous and endogenous) factors in the carcinogenesis of lung cancer.

  3. Lycopene and Lung Cancer

    Science.gov (United States)

    Although epidemiological studies have shown dietary intake of lycopene is associated with decreased risk of lung cancer, the effect of lycopene on lung carcinogenesis has not been well studied. A better understanding of lycopene metabolism and the mechanistic basis of lycopene chemoprevention must ...

  4. Lung Cancer Indicators Recurrence

    Science.gov (United States)

    This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more

  5. MRI of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Kauczor, Hans-Ulrich (ed.) [University Clinic Heidelberg (Germany). Diagnostic and Interventional Radiology

    2009-07-01

    For a long time, only chest X-ray and CT were used to image lung structure, while nuclear medicine was employed to assess lung function. During the past decade significant developments have been achieved in the field of magnetic resonance imaging (MRI), enabling MRI to enter the clinical arena of chest imaging. Standard protocols can now be implemented on up-to-date scanners, allowing MRI to be used as a first-line imaging modality for various lung diseases, including cystic fibrosis, pulmonary hypertension and even lung cancer. The diagnostic benefits stem from the ability of MRI to visualize changes in lung structure while simultaneously imaging different aspects of lung function, such as perfusion, respiratory motion, ventilation and gas exchange. On this basis, novel quantitative surrogates for lung function can be obtained. This book provides a comprehensive overview of how to use MRI for imaging of lung disease. Special emphasis is placed on benign diseases requiring regular monitoring, given that it is patients with these diseases who derive the greatest benefit from the avoidance of ionizing radiation. (orig.)

  6. Lung needle biopsy

    Science.gov (United States)

    ... biopsy Lung tissue biopsy References Ettinger DS. Lung cancer and other pulmonary neoplasms. In: Goldman L, Schafer AI, eds. Goldman's ... 2010:chap 47. Read More Aspiration ... by: Denis Hadjiliadis, MD, Associate Professor of Medicine, Pulmonary, Allergy, and Critical Care, Perelman School of Medicine, ...

  7. Lung cancer in women

    Directory of Open Access Journals (Sweden)

    Barrera-Rodriguez R

    2012-12-01

    Full Text Available Raúl Barrera-Rodriguez,1 Jorge Morales-Fuentes2 1Biochemistry and Environmental Medicine Laboratory, National Institute of Respiratory Disease, 2Lung Cancer Medical Service, National Institute of Respiratory Disease, Tlalpan, Mexico City, Distrito Federal, Mexico Both authors contributed equally to this workAbstract: Recent biological advances in tumor research provide clear evidence that lung cancer in females is different from that in males. These differences appear to have a direct impact on the clinical presentation, histology, and outcomes of lung cancer. Women are more likely to present with lung adenocarcinoma, tend to receive a diagnosis at an earlier age, and are more likely to be diagnosed with localized disease. Women may also be more predisposed to molecular aberrations resulting from the carcinogenic effects of tobacco, but do not appear to be more susceptible than men to developing lung cancer. The gender differences found in female lung cancer make it mandatory that gender stratification is used in clinical trials in order to improve the survival rates of patients with lung cancer.Keywords: lung cancer, adenocarcinoma, women, genetic susceptibility, genetic differences, tobacco

  8. Screening for lung cancer

    DEFF Research Database (Denmark)

    Infante, Maurizio V; Pedersen, Jesper H

    2010-01-01

    In lung cancer screening with low-dose spiral computed tomography (LDCT), the proportion of stage I disease is 50-85%, and the survival rate for resected stage I disease can exceed 90%, but proof of real benefit in terms of lung cancer mortality reduction must come from the several randomized...

  9. Lung function and bronchial reactivity in farmers.

    Science.gov (United States)

    Iversen, M; Dahl, R; Jensen, E J; Korsgaard, J; Hallas, T

    1989-01-01

    The purpose of this study was to evaluate the prevalence and type of lung function disorders in Danish farmers. Three samples of farmers were drawn from a group of unselected farmers who had participated in an epidemiological study. Group I (47 persons) was a sample of the 8% of all farmers who had reported that they had asthma; group II (63 persons) was a sample of the 28% of farmers who had had wheezing, shortness of breath, or cough without phlegm; and group III (34 persons) a sample of the farmers (64% of the total) who had no asthma and no respiratory symptoms. The farmers with symptoms (groups I and II) had low mean levels of FEV1 and high values for residual volume, whereas the symptomless farmers had normal lung function and no airways obstruction. The proportion of farmers with an FEV1 below the 95% confidence limit for predicted values was 43% in group I and 23% in group II; there were none in group III. Bronchial hyperreactivity to histamine occurred in 96% of asthmatic farmers, 67% of farmers with wheezing or shortness of breath, and 59% of symptomless farmers. A low level of FEV1 was associated with the number of years in pig farming and bronchial hyperreactivity in group II but not group I or III. Most of the bronchial hyperreactivity was explained in the multiple regression analysis by a low FEV1, though this was significant only for farmers in group II. Thus farmers who reported asthma, wheezing, shortness of breath, or a dry cough in general had airways obstruction with an increased residual volume, whereas symptomless farmers had normal lung function. Severe bronchial hyperreactivity was mostly explained by a diagnosis of asthma and poor lung function, though some farmers with normal lung function and no respiratory symptoms had increased bronchial reactivity. PMID:2799744

  10. Immunotherapy in Lung Cancer.

    Science.gov (United States)

    Castellanos, Emily H; Horn, Leora

    2016-01-01

    Lung cancer has not traditionally been viewed as an immune-responsive tumor. However, it is becoming evident that tumor-induced immune suppression is vital to malignant progression. Immunotherapies act by enhancing the patient's innate immune response and hold promise for inducing long-term responses in select patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Immune checkpoint inhibitors, in particular, inhibitors to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) have shown promise in early studies and are currently in clinical trials in both small cell lung cancer and non-small cell lung cancer patients. Two large randomized phase III trials recently demonstrated superior overall survival (OS) in patients treated with anti-PD-1 therapy compared to chemotherapy in the second-line setting.

  11. Study of lung perfusion in colagenosis

    Energy Technology Data Exchange (ETDEWEB)

    Macedo de Carvalho, A.C.; Calegaro, J.U.M. (Fundacao Hospitalar do Distrito Federal, Distrito Federal (Brazil). Unidade de Medicina Nuclear)

    1982-07-01

    The lung involvement in the various types of colagenosis has been widely described in the literature. However, the study of lung perfusion utilizing radionuclides has been only mentioned in a few papers. With the intention of ascertaining the importance of the lung perfusion scanning in colagenosis, ten cases were studied, seven of which were females and three males, with the following pathologies: 4 rheumatoid arthritis, 4 systemic lupus eritematosous, 1 scleroderma and 1 scleroderma plus dermatomyositis. The ages of the patients varied from 20 to 73 years, and the duration of the disease from 1 month to 39 years. The lung scanning showed perfusion defects in 100% of the cases, not related with the type of colagenosis, duration of the disease, sex or age. On the other hand, the X rays study showed alterations in only 2 patients (20% of the cases). The ventilatory and respiratory functions were tested on 7 patients showing alteration (mixed pattern with predominance of the restrictive factor) in only one (14.3%), while the other patients were normal (85.7%). The importance of the lung perfusion scanning study in all patients with collagen vascular diseases is emphasized.

  12. Artificial lung basics: fundamental challenges, alternative designs and future innovations.

    Science.gov (United States)

    Nolan, Heather; Wang, Dongfang; Zwischenberger, Joseph B

    2011-01-01

    There exists a growing demand for new technology that can take over the function of the human lung, from assisting an injured or recently transplanted lung to completely replacing the native organ. Many obstacles must be overcome to achieve the lofty goals and expectations of such a device. An artificial lung must be able to sustain the gas exchange requirements of a normal functioning lung. Pursuant to this purpose, the device must maintain appropriate blood pressure, decrease injury to blood cells and minimize clotting and immunologic response. Attachment methods vary, and ideally researchers want to find a way that minimizes bodily trauma, maximizes gas exchange and utilizes the inherent properties of the native lung. The currently proposed methods include the parallel, in-series and venous double-lumen cannula configurations. For the time being, current research focuses on the extracorporeal (i.e., outside the body) placement, but ultimate long-term goals look toward total implantation.

  13. Normal Range of Emphysema and Air Trapping on CT in Young Men

    NARCIS (Netherlands)

    Mets, O.M.; Hulst, R.A. van; Jacobs, C.; Ginneken, B. van; Jong, P.A. de

    2012-01-01

    The purpose of our study was to assess the normal range of CT measures of emphysema and air trapping in young men with normal lung function.A cohort of 70 young men with high-normal spirometry and body plethysmography underwent paired inspiratory and expiratory CT. Visual and quantitative scores of

  14. Risk of COPD with obstruction in active smokers with normal spirometry and reduced diffusion capacity.

    Science.gov (United States)

    Harvey, Ben-Gary; Strulovici-Barel, Yael; Kaner, Robert J; Sanders, Abraham; Vincent, Thomas L; Mezey, Jason G; Crystal, Ronald G

    2015-12-01

    Smokers are assessed for chronic obstructive pulmonary disease (COPD) using spirometry, with COPD defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as airflow limitation that is not fully reversible with bronchodilators. There is a subset of smokers with normal spirometry (by GOLD criteria), who have a low diffusing capacity of the lung for carbon monoxide (DLCO), a parameter linked to emphysema and small airway disease. The natural history of these "normal spirometry/low DLCO" smokers is unknown.From a cohort of 1570 smokers in the New York City metropolitian area, all of whom had normal spirometry, two groups were randomly selected for lung function follow-up: smokers with normal spirometry/normal DLCO (n=59) and smokers with normal spirometry/low DLCO (n=46). All had normal history, physical examination, complete blood count, urinalysis, HIV status, α1-antitrypsin level, chest radiography, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio and total lung capacity. Throughout the study, all continued to be active smokers.In the normal spirometry/normal DLCO group assessed over 45±20 months, 3% developed GOLD-defined COPD. In contrast, in the normal spirometry/low DLCO group, followed over 41±31 months, 22% developed GOLD-defined COPD.Despite appearing "normal" according to GOLD, smokers with normal spirometry but low DLCO are at significant risk of developing COPD with obstruction to airflow.

  15. [Lung hyperinflation after single lung transplantation to treat emphysema].

    Science.gov (United States)

    Samano, Marcos Naoyuki; Junqueira, Jader Joel Machado; Teixeira, Ricardo Henrique de Oliveira Braga; Caramori, Marlova Luzzi; Pêgo-Fernandes, Paulo Manuel; Jatene, Fabio Biscegli

    2010-01-01

    Despite preventive measures, lung hyperinflation is a relatively common complication following single lung transplantation to treat pulmonary emphysema. The progressive compression of the graft can cause mediastinal shift and respiratory failure. In addition to therapeutic strategies such as independent ventilation, the treatment consists of the reduction of native lung volume by means of lobectomy or lung volume reduction surgery. We report two cases of native lung hyperinflation after single lung transplantation. Both cases were treated by means of lobectomy or lung volume reduction surgery.

  16. A review of cetacean lung morphology and mechanics.

    Science.gov (United States)

    Piscitelli, Marina A; Raverty, Stephen A; Lillie, Margo A; Shadwick, Robert E

    2013-12-01

    Cetaceans possess diverse adaptations in respiratory structure and mechanics that are highly specialized for an array of surfacing and diving behaviors. Some of these adaptations and air management strategies are still not completely understood despite over a century of study. We have compiled the historical and contemporary knowledge of cetacean lung anatomy and mechanics in regards to normal lung function during ventilation and air management while diving. New techniques are emerging utilizing pulmonary mechanics to measure lung function in live cetaceans. Given the diversity of respiratory adaptations in cetaceans, interpretations of these results should consider species-specific anatomy, mechanics, and behavior.

  17. ACCESSORY LOBE OF RIGHT LUNG: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    A.K. Manicka Vasuki

    2015-12-01

    Full Text Available Anatomical variations of lungs in the form of Accessory lobe and abnormality in the fissures are important for the surgeons to avoid possible injuries to the neighbouring structures. We report a case of Accessory lobe of right lung between middle and lower lobe in a male cadaver which was found during routine dissection in the Anatomy department, PSG IMS & R. Fissure and lobes of left lung was normal. Anatomical knowledge of such variations are helpful for Cardiothoracic surgeons in lobectomies, surgical resections involving individual segments and for Radiologists for interpreting X – rays,CT & MRI scans.

  18. Expiratory high-resolution CT in diffuse lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Arakawa, Hiroaki [St. Marianna Univ. School of Medicine, Kawasaki, Kanagawa (Japan)

    2000-08-01

    Expiratory high-resolution computed tomography (HRCT) is a powerful adjunct to inspiratory HRCT in the diagnosis of diffuse lung disease (DLD), revealing air-trapping even when the inspiratory scan is normal. Expiratory scans are also useful in the differentiation of inhomogeneous lung opacity, which is not uncommon in various types of DLD. The history and technique of expiratory HRCT are described as well as the basic understanding of lung attenuation and the diagnostic value of expiratory scans DLD. The clinical significance of the presence of expiratory air-trapping in the absence of inspiratory scan abnormality is also presented. (author)

  19. ROLE OF TRANS BRON CHIAL LUNG BIOPSY IN DIFFUSE PARENCHYMAL LUNG DISEASES

    Directory of Open Access Journals (Sweden)

    Methuku

    2015-08-01

    Full Text Available Diffuse parenchyma lung disease (DPLD encompasses a hetero - geneous group of disorders, characterized by a spectrum of inflammatory and fibrotic changes affecting alveolar walls and air spaces. They comprise over 200 entities and include a wide spectrum of diseases, many uncommon and many of unknown etiology. The incidence and prevalence rates of DPLD have not been precisely estimated due to difficulties in ascertaining a specific diagnosis on a specific disease. MATERIAL & METHODS : Prospective observational study done on 20 adult patients with radiologically diffuse parenchymal lung disease admitted between January 2010 and May 2015 in Govt. General & Chest Hospital, Hyderabad were subjected for Transbronchial Lung Biopsy via flexible fibreoptic bronchoscopy, without fluoroscopic guidance. RESULTS : Out of 20 patients studied adequate lung tissue was obtained in 15 patients, yield of the procedure was 75%. Out of 15 patient’s histopathological diagnosis of chronic interstitial pneumonia is seen in 5 members, interstitial fibrosis is seen in 4 members, non caseating granulomas seen in 4 members, pulmonary alveolar protenosis was seen in 1 member and normal lung histopathology was seen in 1 members. Diagnostic yield of the procedure was 93.3% and overall diagnostic yield was 70%. Two patients developed post procedure pneumothorax. Both of them underwent closed - tube thoracostomy, lung expanded well and ICD was removed in 4 days. No significant bleeding was observed in any patient. No mortality was observed after the procedure . CONCLUSIONS : Transbronchial lung biopsy through flexible bronchoscopy is a simple, safe and effective procedure for the diagnosis of diffuse parenchymal lung diseases. Complications were observed in only few patients out of twenty, which were successfully managed with ICD.

  20. Esophagus and Contralateral Lung-Sparing IMRT for Locally Advanced Lung Cancer in the Community Hospital Setting

    OpenAIRE

    Johnny eKao; Jeffrey ePettit; Soombal eZahid; Gold, Kenneth D.; Terry ePalatt

    2015-01-01

    Background The optimal technique for performing lung IMRT remains poorly defined. We hypothesize that improved dose distributions associated with normal tissue-sparing IMRT can allow safe dose escalation resulting in decreased acute and late toxicity. Methods We performed a retrospective analysis of 82 consecutive lung cancer patients treated with curative intent from 1/10 to 9/14. From 1/10 to 4/12, 44 patients were treated with the community standard of three-dimensional conforma...

  1. Bioengineering Lungs for Transplantation.

    Science.gov (United States)

    Gilpin, Sarah E; Charest, Jonathan M; Ren, Xi; Ott, Harald C

    2016-05-01

    Whole lung extracellular matrix scaffolds can be created by perfusion of cadaveric organs with decellularizing detergents, providing a platform for organ regeneration. Lung epithelial engineering must address both the proximal airway cells that function to metabolize toxins and aid mucociliary clearance and the distal pneumocytes that facilitate gas exchange. Engineered pulmonary vasculature must support in vivo blood perfusion with low resistance and intact barrier function and be antithrombotic. Repopulating the native lung matrix with sufficient cell numbers in appropriate anatomic locations is required to enable organ function.

  2. Microgravity and the lung

    Science.gov (United States)

    West, John B.

    1991-01-01

    Results are presented from studies of the effect of microgravity on the lungs of rats flown on the Cosmos 2044 mission, and from relevant laboratory experiments. The effects of microgravity fall into five categories: topographical structure and function, the lung volumes and mechanics, the intrathoracic blood pressures and volumes, the pulmonary deposition of aerosol, and denitrogenaton during EVA. The ultrastructure of the left lungs of rats flown for 14 days on the Cosmos 2044 spacecraft and that of some tail-suspended rats disclosed presence of red blood cells in the alveolar spaces, indicating that pulmonary hemorrhage and pulmonary edema occurred in these rats. Possible causes for this phenomenon are discussed.

  3. Herniation of malignant lung cavity

    Institute of Scientific and Technical Information of China (English)

    Saurabh Kumar Singh; Rakesh Bhargava; Zuber Ahmad; Deepak K.Pandey; Shirin Naaz; Vibhanshu Gupta

    2008-01-01

    @@ Hernia of the lung is defined as a protrusion of lung tissue,covered by parietal and visceral pleurae,through an abnormal opening in the chest wall,diaphragm or mediastinum.1 It is a relatively uncommon condition.We report a case of lung hernia following cavitation in malignant lung mass.

  4. Lung uptake of thallium-201: a marker of defect reversibility?

    Science.gov (United States)

    Sanderson, R.; Woldman, S.; McCurrach, G.; Martin, W.; Hutton, I.

    1998-06-01

    High lung uptake of thallium-201 at stress is reported to be associated with a large number of perfusion defects and poor prognosis. This study was performed to assess whether the reversibility of stress perfusion defects was related to lung uptake. Gated planar thallium scans at stress and at redistribution from 102 consecutive patients with essentially normal left ventricular ejection fraction (using gated blood pool ventriculography) were graded in terms of defect size. Lung and myocardial uptake of thallium were quantitated by region of interest methods relative to the given activity in a previously validated method. There was no significant correlation (non-parametric) between lung uptake and degree of redistribution (). There was a weak but positive correlation between lung uptake and defect size (). Both exercise time and double product showed a negative correlation with lung uptake (e.g. for double product, ). In conclusion, contrary to our expectation, lung uptake is not related to the degree of redistribution. High lung uptake seems to reflect poor cardiovascular reserve.

  5. Normalization in econometrics

    OpenAIRE

    Hamilton, James D.; Daniel F. Waggoner; Zha, Tao

    2004-01-01

    The issue of normalization arises whenever two different values for a vector of unknown parameters imply the identical economic model. A normalization does not just imply a rule for selecting which point, among equivalent ones, to call the maximum likelihood estimator (MLE). It also governs the topography of the set of points that go into a small-sample confidence interval associated with that MLE. A poor normalization can lead to multimodal distributions, disjoint confidence intervals, and v...

  6. Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung

    Energy Technology Data Exchange (ETDEWEB)

    Dautel, Sydney E.; Kyle, Jennifer E.; Clair, Geremy CD; Sontag, Ryan L.; Weitz, Karl K.; Shukla, Anil K.; Nguyen, Son N.; Kim, Young-Mo; Zink, Erika M.; Luders, Teresa; Frevert, Charles; Gharib, Sina A.; Laskin, Julia; Carson, James P.; Metz, Thomas O.; Corley, Richard A.; Ansong, Charles K.

    2017-02-01

    Lung immaturity is a major cause of morbidity and mortality in premature infants. Understanding the molecular mechanisms driving normal lung development could provide insights on how to ameliorate disrupted development. While transcriptomic and proteomic analyses of normal lung development have been previously reported, characterization of changes in the lipidome is lacking. Lipids play significant roles in the lung, such as dipalmitoylcholine in pulmonary surfactant; however, many of the roles of specific lipid species in normal lung development, as well as in disease states, are not well defined. In this study, we used liquid chromatography-mass spectrometry (LC-MS/MS) to investigate the murine lipidome during normal postnatal lung development. Lipidomics analysis of lungs from post-natal day 7, day 14 and 6-8 week mice (adult) identified 928 unique lipids across 21 lipid subclasses, with dramatic alterations in the lipidome across developmental stages. Our data confirmed previously recognized aspects of post-natal lung development and revealed several insights, including in sphingolipid-mediated apoptosis, inflammation and energy storage/usage. Complementary proteomics, metabolomics and chemical imaging corroborated these observations. This multi-omic view provides a unique resource and deeper insight into normal pulmonary development.

  7. Normalizers of Irreducible Subfactors

    CERN Document Server

    Smith, Roger R; Wiggins, Alan D

    2007-01-01

    We consider normalizers of an irreducible inclusion $N\\subseteq M$ of $\\mathrm{II}_1$ factors. In the infinite index setting an inclusion $uNu^*\\subseteq N$ can be strict, forcing us to also investigate the semigroup of one-sided normalizers. We relate these normalizers of $N$ in $M$ to projections in the basic construction and show that every trace one projection in the relative commutant $N'\\cap $ is of the form $u^*e_Nu$ for some unitary $u\\in M$ with $uNu^*\\subseteq N$. This enables us to identify the normalizers and the algebras they generate in several situations. In particular each normalizer of a tensor product of irreducible subfactors is a tensor product of normalizers modulo a unitary. We also examine normalizers of irreducible subfactors arising from subgroup--group inclusions $H\\subseteq G$. Here the normalizers are the normalizing group elements modulo a unitary from $L(H)$. We are also able to identify the finite trace $L(H)$-bimodules in $\\ell^2(G)$ as double cosets which are also finite union...

  8. Normal cognitive aging.

    Science.gov (United States)

    Harada, Caroline N; Natelson Love, Marissa C; Triebel, Kristen L

    2013-11-01

    Even those who do not experience dementia or mild cognitive impairment may experience subtle cognitive changes associated with aging. Normal cognitive changes can affect an older adult's everyday function and quality of life, and a better understanding of this process may help clinicians distinguish normal from disease states. This article describes the neurocognitive changes observed in normal aging, followed by a description of the structural and functional alterations seen in aging brains. Practical implications of normal cognitive aging are then discussed, followed by a discussion of what is known about factors that may mitigate age-associated cognitive decline.

  9. PEComa of the lung

    Directory of Open Access Journals (Sweden)

    Vijayabhaskar R

    2010-01-01

    Full Text Available Perivascular epithelioid cell tumor (PEComa, also called clear cell ′′sugar′′ tumor of the lung, is a rare benign tumor arising from perivascular epithelioid cells (PECs. We report a case of a 15-year-old boy who presented with right lower lobe lesion which turned out to be a clear cell tumor of the lung. An [18F]-fluoro-2-deoxy-D-glucose (FDG - positron emission tomography (PET scan revealed mild FDG uptake in the lung lesion (SUV< 1 with no active uptake elsewhere in the body. We discuss the clinical, radiologic and immunohistochemical features of clear cell ′′sugar′′ tumor of lung and compare them with published literature.

  10. Immunotherapy for lung cancer.

    Science.gov (United States)

    Steven, Antonius; Fisher, Scott A; Robinson, Bruce W

    2016-07-01

    Treatment of lung cancer remains a challenge, and lung cancer is still the leading cause of cancer-related mortality. Immunotherapy has previously failed in lung cancer but has recently emerged as a very effective new therapy, and there is now growing worldwide enthusiasm in cancer immunotherapy. We summarize why immune checkpoint blockade therapies have generated efficacious and durable responses in clinical trials and why this has reignited interest in this field. Cancer vaccines have also been explored in the past with marginal success. Identification of optimal candidate neoantigens may improve cancer vaccine efficacy and may pave the way to personalized immunotherapy, alone or in combination with other immunotherapy such as immune checkpoint blockade. Understanding the steps in immune recognition and eradication of cancer cells is vital to understanding why previous immunotherapies failed and how current therapies can be used optimally. We hold an optimistic view for the future prospect in lung cancer immunotherapy.

  11. American Lung Association

    Science.gov (United States)

    ... Latest News American Lung Association Pledges to Fight Trump Administration Assault on Clean Air and Climate Protections March 28, 2017 In response to President Trump's announcement on climate change, Harold P. Wimmer, National ...

  12. How Lungs Work

    Science.gov (United States)

    ... occurred while processing XML file."); } }); $.ajax({ type: "GET", url: "http://www.lung.org/related-content.xml?related_ ... eventdate = ''; } var title = $(this).find('title').text(); var url = $(this).find('link').text(); var html = ' Event: ' + title + ...

  13. Protecting Your Lungs

    Science.gov (United States)

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  14. Nutrition for Lung Cancer

    Science.gov (United States)

    ... seeds removed such as applesauce, canned peaches or bananas Breads, crackers and pasta made with refined white ... Downloadable Resources & Video Library Reports Lung Cancer Fact Sheet Our Researchers & Teams Latest News Sign up for ...

  15. Power flow in normal human voice production

    Science.gov (United States)

    Krane, Michael

    2016-11-01

    The principal mechanisms of energy utilization in voicing are quantified using a simplified model, in order to better define voice efficiency. A control volume analysis of energy utilization in phonation is presented to identify the energy transfer mechanisms in terms of their function. Conversion of subglottal airstream potential energy into useful work done (vocal fold vibration, flow work, sound radiation), and into heat (sound radiation absorbed by the lungs, glottal jet dissipation) are described. An approximate numerical model is used to compute the contributions of each of these mechanisms, as a function of subglottal pressure, for normal phonation. Acknowledge support of NIH Grant 2R01DC005642-10A1.

  16. Screening for lung cancer

    DEFF Research Database (Denmark)

    Infante, Maurizio V; Pedersen, Jesper H

    2010-01-01

    In lung cancer screening with low-dose spiral computed tomography (LDCT), the proportion of stage I disease is 50-85%, and the survival rate for resected stage I disease can exceed 90%, but proof of real benefit in terms of lung cancer mortality reduction must come from the several randomized...... trials underway in Europe and in the USA. Our purpose is to update the readers on recent progress in medical knowledge in this field....

  17. Interstitial lung disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008429 The predictive factors and unfavourable prognostic factors of interstitial lung disease in patients with polymyositis/dermatomyositis. WANG Peizhen(王培珍), et al. Dept Rheumatol & Immunol, Changhai Hosp, Milit Med Univ, Shanghai 200433. Chin J Tuberc Respir Dis 2008;31(6):417-420. Objective To analyze the predictive factors and the unfavourable prognostic factors of interstitial lung disease (ILD) in patients with polymyositis

  18. The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung epithelial cells.

    Science.gov (United States)

    Xie, Hong; Smith, Leah J; Holmes, Amie L; Zheng, Tongzhang; Pierce Wise, John

    2016-05-01

    Cobalt is a toxic metal used in various industrial applications leading to adverse lung effects by inhalation. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells, especially normal lung epithelial cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in normal primary human lung epithelial cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble and particulate cobalt induced similar cytotoxicity while soluble cobalt was more genotoxic than particulate cobalt. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung epithelial cells.

  19. Multiple cystic lung disease

    Directory of Open Access Journals (Sweden)

    Flavia Angélica Ferreira Francisco

    2015-12-01

    Full Text Available Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt–Hogg–Dubé; other rare causes of cystic lung disease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lung disease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lung disease, and guides diagnostic evaluation and management.

  20. Yin Yang gene expression ratio signature for lung cancer prognosis.

    Directory of Open Access Journals (Sweden)

    Wayne Xu

    Full Text Available Many studies have established gene expression-based prognostic signatures for lung cancer. All of these signatures were built from training data sets by learning the correlation of gene expression with the patients' survival time. They require all new sample data to be normalized to the training data, ultimately resulting in common problems of low reproducibility and impracticality. To overcome these problems, we propose a new signature model which does not involve data training. We hypothesize that the imbalance of two opposing effects in lung cancer cells, represented by Yin and Yang genes, determines a patient's prognosis. We selected the Yin and Yang genes by comparing expression data from normal lung and lung cancer tissue samples using both unsupervised clustering and pathways analyses. We calculated the Yin and Yang gene expression mean ratio (YMR as patient risk scores. Thirty-one Yin and thirty-two Yang genes were identified and selected for the signature development. In normal lung tissues, the YMR is less than 1.0; in lung cancer cases, the YMR is greater than 1.0. The YMR was tested for lung cancer prognosis prediction in four independent data sets and it significantly stratified patients into high- and low-risk survival groups (p = 0.02, HR = 2.72; p = 0.01, HR = 2.70; p = 0.007, HR = 2.73; p = 0.005, HR = 2.63. It also showed prediction of the chemotherapy outcomes for stage II & III. In multivariate analysis, the YMR risk factor was more successful at predicting clinical outcomes than other commonly used clinical factors, with the exception of tumor stage. The YMR can be measured in an individual patient in the clinic independent of gene expression platform. This study provided a novel insight into the biology of lung cancer and shed light on the clinical applicability.

  1. Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

    Science.gov (United States)

    2014-12-18

    profiles have been described in the normal-appearing bronchial epithelium of healthy smokers (9) including those that were diagnostic of lung cancer...expression is modulated in a site- and a time-dependent manner in the bronchial epithelium of early stage lung cancer patients. • Identified several...in airway epithelium and promotes lung inflammation and tumorigenesis. Cancer Prev Res (Phila). 2010;3(4):424-37. PMID: 20354164. 17. Fujimoto J

  2. Neurotrophins expression is decreased in lungs of human infants with congenital diaphragmatic hernia

    Directory of Open Access Journals (Sweden)

    O'Hanlon LD

    2014-02-01

    Full Text Available Lynn D O'Hanlon, Sherry M Mabry, Ikechukwu I EkekezieChildren's Mercy Hospitals/University of Missouri-Kansas City School of Medicine, Department of Pediatrics, Section of Neonatal-Perinatal Medicine, Kansas City, MO, USAObjectives: To evaluate neurotrophin (NT (nerve growth factor [NGF], NT-3, and brain-derived neurotrophic factor [BDNF] expression in autopsy lung tissues of human congenital diaphragmatic hernia (CDH infants versus that of infants that expired with: 1 "normal" lungs (controls; 2 chronic lung disease (CLD; and 3 pulmonary hypertension (PPHN.Hypothesis: NT expression will be significantly altered in CDH lung tissue compared with normal lung tissue and other neonatal lung diseases.Study design: Immunohistochemical studies for NT proteins NGF, BDNF, and NT-3 were applied to human autopsy neonatal lung tissue samples.Subject selection: The samples included a control group of 18 samples ranging from 23-week gestational age to term, a CDH group of 15 samples, a PPHN group of six samples, and a CLD group of 12 samples.Methodology: The tissue samples were studied, and four representative slide fields of alveoli/saccules and four of bronchioles were recorded from each sample. These slide fields were then graded (from 0 to 3 by three blinded observers for intensity of staining.Results: BDNF, NGF, and NT-3 immunostaining intensity scores were significantly decreased in the CDH lung tissue (n=15 compared with normal neonatal lung tissue (n=18 (P<0.001. The other neonatal pulmonary diseases that were studied, CLD and PPHN, were much less likely to be affected and were much more variable in their neurotrophin expression.Conclusion: NT expression is decreased in CDH lungs. The decreased expression of NT in CDH lung tissue may suggest they contribute to the abnormality in this condition.Keywords: nerve growth factor, NGF, brain-derived neurotrophic factor, BDNF, neurotrophin-3, NT-3, chronic lung disease, persistent pulmonary hypertension, lung

  3. A new method to deliver supraclavicular radiation in breast radiotherapy for lung sparing.

    Science.gov (United States)

    Yang, Bo; Dong, Zhang; Lin, Mu-Han; Ma, C-M

    2011-04-18

    Due to the angulation of the breast board used for tangential breast irradiation, additional normal lung tissues are included in the supraclavicular field. This work investigates a method to reduce the lung volume and dose delivered during supraclavicular irradiation for breast cancer. Ten patients included for this retrospective study received chest wall and supraclavicular irradiation following radical surgery or breast-conserving surgery. Three-dimensional conformal radiation therapy plans were generated using the CMS XiO treatment planning system. The clinical target volume (CTV) of the supraclavicular irradiation is defined as the subcutaneous tissues from 0.5 cm under the anterior skin surface to a 3 cm depth. Only the ipsilateral lung is defined as the organ at risk. In the new method, the couch is rotated 90° and the supraclavicular field is tilted to maintain a normal incident angle to the breast board rather than the couch surface to spare more normal lung tissues. The absolute volume of the ipsilateral lung irradiated, and the volumes of lung tissues receiving 5 Gy and 20 Gy (V5 and V20) are analyzed. The new method can reduce the lung volume irradiated by the supraclavicular field significantly. For the ten patients investigated, only 5.3% of the ipsilateral lung is irradiated with the new method, while 14.9% of the ipsilateral lung is irradiated using the conventional method. Compared with the conventional method, the new method reduces V5 by 53.6% and V20 by 59.0%. Our new method does not alter the patient positioning for breast treatment but rotates the couch to deliver a tilted supraclavicular field to maintain adequate CTV coverage and spare more normal lung tissues. The results of this study demonstrated that our new method is effective, and that the reduction of normal lung tissue volume in the field is significant.

  4. Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues.

    Science.gov (United States)

    Kim, H J; Chae, H Z; Kim, Y J; Kim, Y H; Hwangs, T S; Park, E M; Park, Y M

    2003-10-01

    Transient/chronic microenvironmental hypoxia that exists within a majority of solid tumors has been suggested to have a profound influence on tumor growth and therapeutic outcome. Since the functions of novel antioxidant proteins, peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10 human lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical analysis of the lung cancer tissues confirmed an augmented Prx I and Trx expression in cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in lung cancer cells may well represent an attempt of cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.

  5. The aging lung

    Directory of Open Access Journals (Sweden)

    Lowery EM

    2013-11-01

    Full Text Available Erin M Lowery,1 Aleah L Brubaker,2 Erica Kuhlmann,1 Elizabeth J Kovacs31Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine at Loyola University Medical Center, 2Loyola University Stritch School of Medicine, 3Department of Surgery, Loyola University Medical Center, Maywood, IL, USAAbstract: There are many age-associated changes in the respiratory and pulmonary immune system. These changes include decreases in the volume of the thoracic cavity, reduced lung volumes, and alterations in the muscles that aid respiration. Muscle function on a cellular level in the aging population is less efficient. The elderly population has less pulmonary reserve, and cough strength is decreased in the elderly population due to anatomic changes and muscle atrophy. Clearance of particles from the lung through the mucociliary elevator is decreased and associated with ciliary dysfunction. Many complex changes in immunity with aging contribute to increased susceptibility to infections including a less robust immune response from both the innate and adaptive immune systems. Considering all of these age-related changes to the lungs, pulmonary disease has significant consequences for the aging population. Chronic lower respiratory tract disease is the third leading cause of death in people aged 65 years and older. With a large and growing aging population, it is critical to understand how the body changes with age and how this impacts the entire respiratory system. Understanding the aging process in the lung is necessary in order to provide optimal care to our aging population. This review focuses on the nonpathologic aging process in the lung, including structural changes, changes in muscle function, and pulmonary immunologic function, with special consideration of obstructive lung disease in the elderly.Keywords: aging, lung, pulmonary immunology, COPD

  6. Potential contribution of Type I lung epithelial cells to chronic neonatal lung disease

    Directory of Open Access Journals (Sweden)

    Henry J. Rozycki

    2014-05-01

    Full Text Available The alveolar surface is covered by large flat Type I cells (alveolar epithelial cells 1, AEC1. The normal physiological function of AEC1s involves gas exchange, based on their location in approximation to the capillary endothelium and their thinness, and in ion and water flux, as shown by the presence of solute active transport proteins, water channels, and impermeable tight junctions between cells. With the recent ability to produce relatively pure cultures of AEC1 cells, new functions have been described. These may be relevant to lung injury, repair and the abnormal development that characterizes bronchopulmonary dysplasia. To hypothesize a potential role for AEC1 in the development of lung injury and abnormal repair/development in premature lungs, evidence is presented for their presence in the developing lung, how their source may not be the Type II cell (AEC2 as has been assumed for forty years, and how the cell can be damaged by same type of stressors as those which lead to bronchopulmonary dysplasia (BPD. Recent work shows that the cells are part of the innate immune response, capable of producing pro-inflammatory mediators, which could contribute to the increase in inflammation seen in early bronchopulmonary dysplasia. One of the receptors found exclusively on AEC1 cells in the lung, called RAGE, may also have a role in increased inflammation, and to alveolar simplification. While the current evidence for AEC1 involvement in BPD is circumstantial and limited at present, the accumulating data supports several hypotheses and questions regarding potential differences in the behavior of AEC1 cells from newborn and premature lung compared with the adult lung.

  7. Protein misfolding and obstructive lung disease.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2010-11-01

    The endoplasmic reticulum has evolved a number of mechanisms to manage the accumulation of incorrectly folded proteins. This results in loss of function of these proteins, but occasionally, in conditions such as α-1 antitrpysin (A1AT) deficiency, the misfolded protein can acquire a toxic gain of function promoting exaggerated ER stress responses and inflammation. Mutations leading to deficiency in a second serine proteinase inhibitor, α-1 antichymotrpysin (ACT), can induce potentially similar consequences. A1AT and ACT deficiencies are associated with chronic obstructive lung disease. Until recently, it was thought that the lung diseases associated with these conditions were entirely due to loss of antiprotease protection in the lung (i.e., loss of function), whereas gain of function was the major cause of the liver disease associated with A1AT deficiency. This paradigm is being increasingly challenged because ER stress is being recognized in bronchial epithelial cells and inflammatory cells normally resident in the lung, giving rise to an inflammatory phenotype that adds to the proteolytic burden associated with these conditions. In this article, we describe the cellular mechanisms that are activated to cope with an increasing burden of misfolded proteins within the ER in A1AT and ACT deficiency, show how these events are linked to inflammation, and outline the therapeutic strategies that can potentially interfere with production of misfolded proteins.

  8. Quantitative assessment of irradiated lung volume and lung mass in breast cancer patients treated with tangential fields in combination with deep inspiration breath hold (DIBH)

    Energy Technology Data Exchange (ETDEWEB)

    Kapp, Karin Sigrid [Univ. Clinic of Therapeutic Radiology and Oncology, Medical Univ. of Graz (Austria); Zurl, Brigitte; Stranzl, Heidi; Winkler, Peter

    2010-03-15

    Purpose: Comparison of the amount of irradiated lung tissue volume and mass in patients with breast cancer treated with an optimized tangential-field technique with and without a deep inspiration breath-hold (DIBH) technique and its impact on the normal-tissue complication probability (NTCP). Material and Methods: Computed tomography datasets of 60 patients in normal breathing (NB) and subsequently in DIBH were compared. With a Real-Time Position Management Respiratory Gating System (RPM), anteroposterior movement of the chest wall was monitored and a lower and upper threshold were defined. Ipsilateral lung and a restricted tangential region of the lung were delineated and the mean and maximum doses calculated. Irradiated lung tissue mass was computed based on density values. NTCP for lung was calculated using a modified Lyman-Kutcher-Burman (LKB) model. Results: Mean dose to the ipsilateral lung in DIBH versus NB was significantly reduced by 15%. Mean lung mass calculation in the restricted area receiving {<=} 20 Gy (M{sub 20}) was reduced by 17% in DIBH but associated with an increase in volume. NTCP showed an improvement in DIBH of 20%. The correlation of individual breathing amplitude with NTCP proved to be independent. Conclusion: The delineation of a restricted area provides the lung mass calculation in patients treated with tangential fields. DIBH reduces ipsilateral lung dose by inflation so that less tissue remains in the irradiated region and its efficiency is supported by a decrease of NTCP. (orig.)

  9. Shared values and normality

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wen-hua; PANG Xue-cheng

    2006-01-01

    This paper investigates the relationship between the normality and the shared values for a meromorphic function on the unit disc △.Based on Marty's normality criterion and through a detailed analysis of the meromorphic functions,it is shown that if for every f∈F,f and f(k) share a and b on △ and the zeros of f(z)-a are of multiplicity k≥3,then F is normal on △,where F is a family of meromorphic functions on the unit disc △,and a and b are distinct values.

  10. Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

    Directory of Open Access Journals (Sweden)

    G-Andre Banat

    Full Text Available Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+, cytotoxic-T cells (CD8+, T-helper cells (CD4+, B cells (CD20+, macrophages (CD68+, mast cells (CD117+, mononuclear cells (CD11c+, plasma cells, activated-T cells (MUM1+, B cells, myeloid cells (PD1+ and neutrophilic granulocytes (myeloperoxidase+ compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

  11. Lung clearance index for monitoring early lung disease in alpha-1-antitrypsin deficiency.

    Science.gov (United States)

    Fuchs, Susanne I; Schwerk, Nicolaus; Pittschieler, Klaus; Ahrens, Frank; Baden, Winfried; Bals, Robert; Fähndrich, Sebastian; Gleiber, Wolfgang; Griese, Matthias; Hülskamp, Georg; Köhnlein, Thomas; Reckling, Ludmilla; Rietschel, Ernst; Staab, Doris; Gappa, Monika

    2016-07-01

    Patients with alpha-1-antitrypsin deficiency (AATD) and a PI-ZZ genotype are at high risk to develop severe emphysema during adulthood. However, little is known about early stages of emphysema and disease manifestation in other PI-types. Spirometry is commonly used for monitoring although early manifestation of emphysema is suspected within the peripheral airways that are not accessible by forced expiratory manoeuvres. We hypothesized that the Lung Clearance Index (LCI) derived from multiple breath nitrogen-washout (N2-washout) is useful to bridge this diagnostic gap. Patients from age 4 years onward and different PI-types performed N2-washout and spirometry. Results were compared to controls. 193 patients (4-79 years, 75% PI-ZZ) and 33 controls (8-60 years) were included. Mean (SD) LCI in patients was 9.1 (3.1) and 6.3 (0.6) in controls (p ≤ 0.001). 47% of adult patients with other than PI-ZZ genotypes and 39% of all patients with normal spirometry had abnormal LCIs. The LCI measured by N2-washout discriminates between patients with AATD and controls, reflects AATD related lung disease in all stages and appears to identify early peripheral lung changes in younger age than spirometry. We conclude that a normal spirometry does not exclude presence of AATD related lung disease even in genotypes other than PI-ZZ.

  12. Multislice spiral computed tomography to determine the effects of a recruitment maneuver in experimental lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Henzler, Dietrich; Rossaint, Rolf [University Hospital, RWTH Aachen, Anesthesiology Department, Aachen (Germany); Mahnken, Andreas H.; Wildberger, Joachim E.; Guenther, Rolf W. [University Hospital of the RWTH Aachen, Clinic of Diagnostic Radiology, Aachen (Germany); Kuhlen, Ralf [University Hospital of the RWTH Aachen, Operative Intensive Care Department, Aachen (Germany)

    2006-06-15

    Although recruitment of atelectatic lung is a common aim in acute respiratory distress syndrome (ARDS), the effects of a recruitment maneuver have not been assessed quantitatively. By multislice spiral CT (MSCT), we analyzed the changes in lung volumes calculated from the changes in the CT values of hyperinflated (V{sub HYP}), normally (V{sub NORM}), poorly (V{sub POOR}) and nonaerated (V{sub NON}) lung in eight mechanically ventilated pigs with saline lavage-induced acute lung injury before and after a recruitment maneuver. This was compared to single slice analysis near the diaphragm. The increase in aerated lung was mainly for V{sub POOR} and the less in V{sub NORM}. Total lung volume and intrathoracic gas increased. No differences were found for tidal volumes measured by spirometry or determined by CT. The inspiratory-expiratory volume differences were not different after the recruitment maneuver in V{sub NON} (from 62{+-}18 ml to 43{+-}26 ml, P=0.114), and in V{sub NORM} (from 216{+-}51 ml to 251{+-}37 ml, P=0.102). Single slice analysis significantly underestimated the increase in normally and poorly aerated lung. Quantitative analysis of lung volumes by whole lung MSCT revealed the increase of poorly aerated lung as the main mechanism of a standard recruitment maneuver. MSCT can provide additional information as compared to single slice CT. (orig.)

  13. Contribution of Fetal, but Not Adult, Pulmonary Mesothelium to Mesenchymal Lineages in Lung Homeostasis and Fibrosis.

    Science.gov (United States)

    von Gise, Alexander; Stevens, Sean M; Honor, Leah B; Oh, Jin Hee; Gao, Chi; Zhou, Bin; Pu, William T

    2016-02-01

    The lung is enveloped by a layer of specialized epithelium, the pulmonary mesothelium. In other organs, mesothelial cells undergo epithelial-mesenchymal transition and contribute to organ stromal cells. The contribution of pulmonary mesothelial cells (PMCs) to the developing lung has been evaluated with differing conclusions. PMCs have also been indirectly implicated in lung fibrosis in the progressive, fatal lung disease idiopathic pulmonary fibrosis. We used fetal or postnatal genetic pulse labeling of PMCs to assess their fate in murine development, normal lung homeostasis, and models of pulmonary fibrosis. We found that most fetal PMC-derived mesenchymal cells (PMCDCs) expressed markers of pericytes and fibroblasts, only a small minority expressed smooth muscle markers, and none expressed endothelial cell markers. Postnatal PMCs did not contribute to lung mesenchyme during normal lung homeostasis or in models of lung fibrosis. However, fetal PMCDCs were abundant and actively proliferating within fibrotic regions in lung fibrosis models, suggesting that they actively participate in the fibrotic process. These data clarify the role of fetal and postnatal PMCDCs in lung development and disease.

  14. The early diagnosis of lung cancer.

    Science.gov (United States)

    Petty, T L

    2001-06-01

    Lung cancer is the most common fatal malignancy in both men and women, both in the United States and elsewhere in the world. Today, lung cancer is most often diagnosed on the basis of symptoms of advanced disease or when chest x-rays are taken for a variety of purposes unrelated to lung cancer detection. Unfortunately, in the United States no society or governmental agency recommends screening, even for patients with high risks, such as smokers with airflow obstruction or people with occupational exposures, including asbestos. The origins of this negative attitude toward lung cancer screening are found in 3 studies sponsored by the National Cancer Institute in the mid-1970s and conducted at Johns Hopkins University School of Medicine, the Mayo Clinic, and the Memorial Sloan-Kettering Center. These studies concluded that early identification of lung cancer through chest x-rays and cytologic diagnosis of sputum did not alter disease-specific mortality. However, patients with earlier stage disease were found through screening, which resulted in a higher resectability rate and improved survival in the screening group compared with a control group of patients receiving ordinary care. Patients in the control group often received annual chest x-rays during the course of this study, which was the standard of care at the time. Thus no true nonscreening control group resulted. The patients at highest risk were not enrolled in this study. No specific amount of pack-years of smoking intensity was required. Only men were screened. The studies were inadequately powered to show an improvement in mortality rate of less than 50%. Ninety percent of lung cancer occurs in smokers. The prevalence of lung cancer is 4 to 6 times greater when smokers have airflow obstruction than with normal airflow, when all other background factors, including smoking history, occupational risk, and family history, are the same. Screening heavy smokers (ie, > or = 30 pack-years) with airflow obstruction

  15. Evaluation of uptake, cytotoxicity and inflammatory effects in respiratory cells exposed to pristine and -OH and -COOH functionalized multi-wall carbon nanotubes.

    Science.gov (United States)

    Ursini, Cinzia Lucia; Maiello, Raffaele; Ciervo, Aureliano; Fresegna, Anna Maria; Buresti, Giuliana; Superti, Fabiana; Marchetti, Magda; Iavicoli, Sergio; Cavallo, Delia

    2016-03-01

    Toxic effects were reported for pristine-multi-wall carbon nanotubes (p-MWCNTs) while the role of the functionalization on MWCNT-induced toxicity is not yet well defined. We evaluated on human alveolar (A549) epithelial cells and normal bronchial (BEAS-2B) cells exposed to p-MWCNTs, MWCNTs-OH and MWCNTs-COOH: uptake by TEM, cell viability by different assays, membrane damage by the LDH assay and cytokine release by ELISA. The aims of the present study were to: (i) confirm MWCNT cytotoxicity mechanisms hypothesized in our previous studies; (ii) identify the most reliable viability assay to screen MWCNT toxicity; and (iii) to test our model to clarify the role of functionalization on MWCNT-induced toxicity. In A549 cells, p-MWCNTs and MWCNTs-OH were localized free in the cytoplasm and inside vacuoles whereas MWCNTs-COOH were confined inside filled cytoplasmic vesicles. WST-1 and Trypan blue assays showed in A549 cells a similar slight viability reduction for all MWCNTs whereas in BEAS-2B cells WST1 showed a high viability reduction at the highest concentrations, particularly for MWCNTs-COOH. The MTT assay showed a false cytotoxicity as a result of MWCNTs-interference. Pristine and MWCNTs-COOH induced membrane damage, particularly in BEAS-2B cells. MWCNTs-COOH induced interleukin-6 (IL-6) and IL-8 release in A549 cells whereas p-MWCNTs induced IL-8 release in BEAS-2B cells. MWCNTs intracellular localization in A549 cells confirms the toxicity mechanisms previously hypothesized, with p-MWCNTs disrupting the membrane and vesicle-confined MWCNTs-COOH inducing inflammation. WST-1 was more reliable than MTT to test MWCNT-toxicity. BEAS-2B cells were more susceptible then A549 cells, particularly to MWCNT-COOH cytotoxicity. Our results confirm the toxicity of p-MWCNTs and demonstrate, also for the two kinds of tested functionalized MWCNTs toxic effects with a different mechanism of action.

  16. Normality in analytical psychology.

    Science.gov (United States)

    Myers, Steve

    2013-12-01

    Although C.G. Jung's interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault's criticism, had Foucault chosen to review Jung's work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault's own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung's disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity.

  17. Normal pressure hydrocephalus

    Science.gov (United States)

    Hydrocephalus - occult; Hydrocephalus - idiopathic; Hydrocephalus - adult; Hydrocephalus - communicating; Dementia - hydrocephalus; NPH ... Ferri FF. Normal pressure hydrocephalus. In: Ferri FF, ed. ... Elsevier; 2016:chap 648. Rosenberg GA. Brain edema and disorders ...

  18. Normal Functioning Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  19. Monitoring the normal body

    DEFF Research Database (Denmark)

    Nissen, Nina Konstantin; Holm, Lotte; Baarts, Charlotte

    2015-01-01

    Introduction : An extensive body of literature is concerned with obese people, risk, and weight management. However, little is known about weight management among people not belonging to the extreme BMI categories. Management of weight among normal-weight and moderately overweight individuals...... provides us with knowledge about how to prevent future overweight or obesity. This paper investigates body size ideals and monitoring practices among normal-weight and moderately overweight people. Methods : The study is based on in-depth interviews combined with observations. 24 participants were...... recruited by strategic sampling based on self-reported BMI 18.5-29.9 kg/m2 and socio-demographic factors. Inductive analysis was conducted. Results : Normal-weight and moderately overweight people have clear ideals for their body size. Despite being normal weight or close to this, they construct a variety...

  20. Lung Cancer Statistics.

    Science.gov (United States)

    Torre, Lindsey A; Siegel, Rebecca L; Jemal, Ahmedin

    2016-01-01

    Lung cancer is the leading cause of cancer death among both men and women in the United States. It is also the leading cause of cancer death among men and the second leading cause of cancer death among women worldwide. Lung cancer rates and trends vary substantially by sex, age, race/ethnicity, socioeconomic status, and geography because of differences in historical smoking patterns. Lung cancer mortality rates in the United States are highest among males, blacks, people of lower socioeconomic status, and in the mid-South (e.g., Kentucky, Mississippi, Arkansas, and Tennessee). Globally, rates are highest in countries where smoking uptake began earliest, such as those in North America and Europe. Although rates are now decreasing in most of these countries (e.g., United States, United Kingdom, Australia), especially in men, they are increasing in countries where smoking uptake occurred later. Low- and middle-income countries now account for more than 50% of lung cancer deaths each year. This chapter reviews lung cancer incidence and mortality patterns in the United States and globally.

  1. Lung cancer screening: Update

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyea Young [Dept. of Radiology, Center for Lung Cancer, National Cancer Center, Goyang (Korea, Republic of)

    2015-09-15

    Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers.

  2. Inhalational Lung Disease

    Directory of Open Access Journals (Sweden)

    S Kowsarian

    2010-01-01

    Full Text Available Inhalational lung diseases are among the most important occupational diseases. Pneumoconiosis refers to a group of lung diseases result from inhalation of usually inorganic dusts such as silicon dioxide, asbestos, coal, etc., and their deposition in the lungs. The resultant pulmonary disorders depend on the susceptibility of lungs; size, concentration, solubility and fibrogenic properties of the inhaled particles; and duration of exposure. Radiographic manifestations of pneumoconiosis become apparent several years after exposure to the particles. However, for certain types of dusts, e.g., silicone dioxide crystal and beryllium, heavy exposure within a short period can cause an acute disease. Pulmonary involvement in asbestosis is usually in the lower lobes. On the contrary, in silicosis and coal worker pneumoconiosis, the upper lobes are involved predominantly. For imaging evaluation of pneumoconiosis, high-resolution computed tomography (CT is superior to conventional chest x-ray. Magnetic resonance imaging (MRI and positron emission tomography (PET scan are helpful in those with suspected tumoral lesions. In this essay, we reviewed the imaging aspects of inhalational lung disease.

  3. Hyperspectral imaging of skin and lung cancers

    Science.gov (United States)

    Zherdeva, Larisa A.; Bratchenko, Ivan A.; Alonova, Marina V.; Myakinin, Oleg O.; Artemyev, Dmitry N.; Moryatov, Alexander A.; Kozlov, Sergey V.; Zakharov, Valery P.

    2016-04-01

    The problem of cancer control requires design of new approaches for instrumental diagnostics, as the accuracy of cancer detection on the first step of diagnostics in clinics is slightly more than 50%. In this study, we present a method of visualization and diagnostics of skin and lung tumours based on registration and processing of tissues hyperspectral images. In a series of experiments registration of hyperspectral images of skin and lung tissue samples is carried out. Melanoma, basal cell carcinoma, nevi and benign tumours are studied in skin ex vivo and in vivo experiments; adenocarcinomas and squamous cell carcinomas are studied in ex vivo lung experiments. In a series of experiments the typical features of diffuse reflection spectra for pathological and normal tissues were found. Changes in tissues morphology during the tumour growth lead to the changes of blood and pigments concentration, such as melanin in skin. That is why tumours and normal tissues maybe differentiated with information about spectral response in 500-600 nm and 600 - 670 nm areas. Thus, hyperspectral imaging in the visible region may be a useful tool for cancer detection as it helps to estimate spectral properties of tissues and determine malignant regions for precise resection of tumours.

  4. Idiopathic Normal Pressure Hydrocephalus

    OpenAIRE

    2016-01-01

    Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurodegenerative disease commonly characterized by a triad of dementia, gait, and urinary disturbance. Advancements in diagnosis and treatment have aided in properly identifying and improving symptoms in patients. However, a large proportion of iNPH patients remain either undiagnosed or misdiagnosed. Using PubMed search engine of keywords “normal pressure hydrocephalus,” “diagnosis,” “shunt treatment,” “biomarkers,” ...

  5. Surgical treatment of patients with lung cancer and limited lung function: Preoperative assessment, operative mortality and morbidity

    Directory of Open Access Journals (Sweden)

    Subotić Dragan

    2007-01-01

    Full Text Available Introduction: Lung resection in patients with limited lung function is one of the greatest challenges in general thoracic surgery. Objective. The aim of the study was to analyze the pattern of lung function changes after operation, operative morbidity and mortality and to compare them with control group of patients. Method. The study included 34 patients with limited lung function, operated for primary lung cancer in one-year period. All patients underwent preoperative desobstructive treatment. The type of ventilatory disorder was analyzed depending on preoperative radiographic and bronchoscopic aspect. Statistics: chisquare test, t-test. Results. In patients with lobectomy, the mean difference in forced expiratory volume in the first second (FEV1 between preoperative and postoperative values was 16.81%, whilst in the pneumonectomy group this difference was 39.51%. The mean change in forced vital capacity (FVC in the lobectomy and pneumonectomy group was 15.83% and 42.73% respectively. In the control group of 28 patients with lobectomy, the decrease in FVC and FEV1 was 19.9% and 24.18% respectively. In the control group of 28 patients with pneumonectomy, the decrease in FVC and FEV1 was 43.52% and 41.36% respectively. In patients with limited lung function and lobectomy, changes in FEV1 and VC after resection were significantly lower compared to the control group of patients with lobectomy and normal lung function. None of 34 operated patients with borderline lung function died inside 30 postoperative days. In the same period, of a total number of 344 patients without respiratory function impairment, operative mortality was 3.1%. In the analyzed group, operative morbidity was 32.35%. Cardiovascular and respiratory complications in the analyzed and control groups occurred in 14.7% and 6.1% of patients respectively (p>0.05. Conclusion. Surgery should not be excluded in patients with borderline lung function prior to preoperative treatment and

  6. Unevenness of lung perfusion images and pulmonary diseases

    Energy Technology Data Exchange (ETDEWEB)

    Teshima, Takeo; Isawa, Toyoharu; Hirano, Tomio; Anazawa, Yoshiki; Miki, Makoto; Konno, Kiyoshi; Motomiya, Masakichi (Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis and Cancer)

    1989-07-01

    The purpose of the study was to quantify the unevenness of perfusion distribution in the lungs in conjunction with underlying lung pathology. Twenty-one parameters as described previously were defined out of horizontal radioactive count profiles on perfusion lung image data taken in 64x64 matrixes. Principal component analysis has revealed that the 1st component or Z1 is represented by AREA, the area of the lung, and ANG, the slope of the mean count profile, Z2, by N, the number of peaks, Z3 and Z4, by YG and XG, the barycentric coordinates of count distribution, Z5, by MAC, the maximal count and Z6, by CSD, the degree of scatter in count from the peak count. How those parameters differ in each lung pathology has been determined from 657 lung perfusion image data. In pulmonary emphysema, the lung volumes are larger than those in normal subjects. The AREA and ANG were consequently larger in value and N was also significantly larger, indicating the increased regional alveolar pressure and the compressed or destroyed vascular beds. In diffuse panbronchiolitis (DPB), N was increased probably because the distal airways were either narrowed or obstructed by inflammatory processes inducing regional alveolar hypoxia and/or alveolar hyperinflation. In fibrosis, both AREA and N were significantly smaller. In congestive heart failure with postcapillary pulmonary hypertension, YG was smaller probably because of 'reversal of perfusion'. In pulmonary sarcoidosis, an increase in YG was the only abnormality. (author).

  7. Monte-Carlo-Model for the aerosol bolus dispersion in the human lung. Part 2. Model predictions for the diseased lung; Monte-Carlo-Modell der Aerosolbolusdispersion in der menschlichen Lunge. Teil 2. Modellvorhersagen fuer die kranke Lunge

    Energy Technology Data Exchange (ETDEWEB)

    Sturm, R.; Pawlak, E.; Hofmann, W. [Salzburg Univ. (Austria). Abt. fuer Physik und Biophysik

    2007-07-01

    After a mathematical extension of the existing model for the theoretical description of the aerosol bolus dispersion, the behavior of particle pulses in diseased lung structures was simulated. The geometry used for healthy lungs was modified in two aspects: First, a modelling of possible airway obstructions, which usually occur in patients with chronic bronchitis, chronic asthma or cystic fibrosis, was carried out and, second, a theoretical approximation of the emphysema, being observed in lungs of smokers, but also as an accompanying phenomenon in obstructive diseases, was established. According to the modified model, in lungs with airway obstructions the exhaled bolus exhibited a decreased dispersion with respect to healthy subjects, whereas in emphysematous lungs the respective half-width of the peak was increased. Standard deviation and skewness of the bolus were similarly influenced by the modified lung architecture. A combination of airway obstruction and emphysema caused an extensive compensation of individual dispersion effects, complicating a secure distinction from the healthy lung. According to the model, a special diagnostic value may be assigned to the bolus deposition, showing significant deviations from the normal case for all simulated diseases. (orig.)

  8. Alpha-fetoprotein-producing primary lung carcinoma: A case report

    Directory of Open Access Journals (Sweden)

    Tokusashi Yoshihiko

    2011-05-01

    Full Text Available Abstract Alpha-fetoprotein (AFP-producing lung adenocarcinoma is a rare type of lung cancer, with its characteristics not yet fully clarified. We recently encountered a case of this type of lung cancer. The patient was a 69-year-old man who consulted an internist with the chief complaint of epigastric pain. Chest X-ray and CT revealed a lobulated mass measuring 70 mm in diameter in the right lower lung field and a metastasis in the right hilar lymph nodes. Of the tumor markers, the serum AFP was elevated (4620 ng/ml, and the serum carcinoembryonic antigen and carbohydrate antigen 19-9 were also slightly elevated. Transbronchial lung biopsy revealed the diagnosis of lung cancer. Under thoracoscopic assistance, right lower lobectomy + mediastinal lymph node dissection was carried out. Immunostaining showed the tumor cells to be AFP-positive. The tumor was thus diagnosed as an AFP-producing lung adenocarcinoma. The patient followed an uneventful clinical course after the surgery, with serum AFP decreasing to the normal range by about 2 weeks after the surgery. As of this writing, no sign of tumor recurrence has been noted. This case is presented here with a review of the literature.

  9. NK cell phenotypic modulation in lung cancer environment.

    Directory of Open Access Journals (Sweden)

    Shi Jin

    Full Text Available Nature killer (NK cells play an important role in anti-tumor immunotherapy. But it indicated that tumor cells impacted possibly on NK cell normal functions through some molecules mechanisms in tumor microenvironment.Our study analyzed the change about NK cells surface markers (NK cells receptors through immunofluorescence, flow cytometry and real-time PCR, the killed function from mouse spleen NK cell and human high/low lung cancer cell line by co-culture. Furthermore we certificated the above result on the lung cancer model of SCID mouse.We showed that the infiltration of NK cells in tumor periphery was related with lung cancer patients' prognosis. And the number of NK cell infiltrating in lung cancer tissue is closely related to the pathological types, size of the primary cancer, smoking history and prognosis of the patients with lung cancer. The expression of NK cells inhibitor receptors increased remarkably in tumor micro-environment, in opposite, the expression of NK cells activated receptors decrease magnificently.The survival time of lung cancer patient was positively related to NK cell infiltration degree in lung cancer. Thus, the down-regulation of NKG2D, Ly49I and the up-regulation of NKG2A may indicate immune tolerance mechanism and facilitate metastasis in tumor environment. Our research will offer more theory for clinical strategy about tumor immunotherapy.

  10. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Research shows that smoking marijuana may help cancer cells grow. But there is no direct link between ...

  11. [Cystic adenomatoid malformation of the lung. Importance of prenatal diagnosis].

    Science.gov (United States)

    Cabeza, Beatriz; Oñoro, Gonzalo; Cantarín Extremera, Verónica; Sanz Santiago, Verónica; Sequeiros, Adolfo

    2011-04-01

    Cystic adenomatoid malformation of the lung is a rare malformation of the lung airway which often performed diagnosed in the prenatal period by ultrasound. Ultrasound monitoring should be performed during pregnancy to assess lung development. We report the case of a 4-year-old patient with prenatal diagnosis of cystic adenomatoid malformation of the lung, not confirmed by chest radiograph at birth. The patient underwent surgery at 4 years of age after diagnosis was made for presenting recurrent pneumonia. A normal chest radiograph at birth does not exclude this malformation and a computerized tomography at 4 weeks of birth must be done to confirm or rule out this anomaly. Once the diagnosis is made, surgical treatment should be prompted to avoid complications.

  12. FGFR Signaling as a Target for Lung Cancer Therapy.

    Science.gov (United States)

    Desai, Arpita; Adjei, Alex A

    2016-01-01

    Lung cancer is the leading cause of cancer-related death in developed countries. Recently, molecular targeted therapies have shown promising results in the management of lung cancer. These therapies require a clear understanding of the relevant pathways that drive carcinogenesis and maintenance of the malignant phenotype. The fibroblast growth factor receptor (FGFR) signaling axis is one such pathway that plays a central role in normal cellular function. Alterations in this pathway have been found in many cancers. In this review article, we focus on the role of this pathway in lung cancer. We present the molecular structure of FGFR, the interaction of the receptor with its ligands (the fibroblast growth factors), its downstream signaling, and aberrations in the FGFR pathway. We also discuss clinical trials involving selective and multikinase FGFR inhibitors in lung cancer treatment.

  13. 3D cine magnetic resonance imaging of rat lung ARDS using gradient-modulated SWIFT with retrospective respiratory gating

    Science.gov (United States)

    Kobayashi, Naoharu; Lei, Jianxun; Utecht, Lynn; Garwood, Michael; Ingbar, David H.; Bhargava, Maneesh

    2015-03-01

    SWeep Imaging with Fourier Transformation (SWIFT) with gradient modulation and DC navigator retrospective gating is introduced as a 3D cine magnetic resonance imaging (MRI) method for the lung. In anesthetized normal rats, the quasi-simultaneous excitation and acquisition in SWIFT enabled extremely high sensitivity to the fast-decaying parenchymal signals (TE=~4 μs), which are invisible with conventional MRI techniques. Respiratory motion information was extracted from DC navigator signals and the SWIFT data were reconstructed to 3D cine images with 16 respiratory phases. To test this technique's capabilities, rats exposed to > 95% O2 for 60 hours for induction of acute respiratory distress syndrome (ARDS), were imaged and compared with normal rat lungs (N=7 and 5 for ARDS and normal groups, respectively). SWIFT images showed lung tissue density differences along the gravity direction. In the cine SWIFT images, a parenchymal signal drop at the inhalation phase was consistently observed for both normal and ARDS rats due to lung inflation (i.e. decrease of the proton density), but the drop was less for ARDS rats. Depending on the respiratory phase and lung region, the lungs from the ARDS rats showed 1-24% higher parenchymal signal intensities relative to the normal rat lungs, likely due to accumulated extravascular water (EVLW). Those results demonstrate that SWIFT has high enough sensitivity for detecting the lung proton density changes due to gravity, different phases of respiration and accumulation of EVLW in the rat ARDS lungs.

  14. Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Sharon R. Pine

    2008-01-01

    Full Text Available Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation pathways are maintained within distinct cancer types, and destabilization of this machinery may participate in maintenance of cancer stem cells. Characterization of lung cancer stem cells is an area of active research and is critical for developing novel therapies. This review summarizes the current knowledge on stem cell signaling pathways and cell markers used to identify the lung cancer stem cells.

  15. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan;

    2013-01-01

    Obesity, metabolic syndrome, and asthma are all rapidly increasing globally. Substantial emerging evidence suggests that these three conditions are epidemiologically and mechanistically linked. Since the link between obesity and asthma appears to extend beyond mechanical pulmonary disadvantage......, molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  16. LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION

    Science.gov (United States)

    Chen, Kun; Hoffman, Eric A.; Seetharaman, Indu; Jiao, Feiran; Lin, Ching-Long; Chan, Kung-Sik

    2017-01-01

    The human lung airway is a complex inverted tree-like structure. Detailed airway measurements can be extracted from MDCT-scanned lung images, such as segmental wall thickness, airway diameter, parent-child branch angles, etc. The wealth of lung airway data provides a unique opportunity for advancing our understanding of the fundamental structure-function relationships within the lung. An important problem is to construct and identify important lung airway features in normal subjects and connect these to standardized pulmonary function test results such as FEV1%. Among other things, the problem is complicated by the fact that a particular airway feature may be an important (relevant) predictor only when it pertains to segments of certain generations. Thus, the key is an efficient, consistent method for simultaneously conducting group selection (lung airway feature types) and within-group variable selection (airway generations), i.e., bi-level selection. Here we streamline a comprehensive procedure to process the lung airway data via imputation, normalization, transformation and groupwise principal component analysis, and then adopt a new composite penalized regression approach for conducting bi-level feature selection. As a prototype of composite penalization, the proposed composite bridge regression method is shown to admit an efficient algorithm, enjoy bi-level oracle properties, and outperform several existing methods. We analyze the MDCT lung image data from a cohort of 132 subjects with normal lung function. Our results show that, lung function in terms of FEV1% is promoted by having a less dense and more homogeneous lung comprising an airway whose segments enjoy more heterogeneity in wall thicknesses, larger mean diameters, lumen areas and branch angles. These data hold the potential of defining more accurately the “normal” subject population with borderline atypical lung functions that are clearly influenced by many genetic and environmental factors.

  17. National Lung Screening Trial (NLST)

    Science.gov (United States)

    The National Lung Screening Trial (NLST), a research study sponsored by the National Cancer Institute that used low-dose helical CT scans or chest X-ray to screen men and women at risk for lung cancer.

  18. Drugs Approved for Lung Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Lung Cancer This page lists cancer drugs approved by the ... listed here. Drugs Approved for Non-Small Cell Lung Cancer Abitrexate (Methotrexate) Abraxane (Paclitaxel Albumin-stabilized Nanoparticle Formulation) ...

  19. Lung Cancer Rates by State

    Science.gov (United States)

    ... HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by State Language: English Español (Spanish) Recommend ... incidence data are currently available. Rates of Getting Lung Cancer by State The number of people who get ...

  20. What Are Lung Function Tests?

    Science.gov (United States)

    ... include tests that measure lung size and air flow, such as spirometry and lung volume tests. Other tests measure how well gases such as oxygen get in and out of your blood. These tests include pulse oximetry and arterial blood ...

  1. Multiphoton microscopy and microspectroscopy for diagnostics of inflammatory and neoplastic lung

    Science.gov (United States)

    Pavlova, Ina; Hume, Kelly R.; Yazinski, Stephanie A.; Flanders, James; Southard, Teresa L.; Weiss, Robert S.; Webb, Watt W.

    2012-03-01

    Limitations of current medical procedures for detecting early lung cancers inspire the need for new diagnostic imaging modalities for the direct microscopic visualization of lung nodules. Multiphoton microscopy (MPM) provides for subcellular resolution imaging of intrinsic fluorescence from unprocessed tissue with minimal optical attenuation and photodamage. We demonstrate that MPM detects morphological and spectral features of lung tissue and differentiates between normal, inflammatory and neoplastic lung. Ex vivo MPM imaging of intrinsic two-photon excited fluorescence was performed on mouse and canine neoplastic, inflammatory and tumor-free lung sites. Results showed that MPM detected microanatomical differences between tumor-free and neoplastic lung tissue similar to standard histopathology but without the need for tissue processing. Furthermore, inflammatory sites displayed a distinct red-shifted fluorescence compared to neoplasms in both mouse and canine lung, and adenocarcinomas displayed a less pronounced fluorescence emission in the 500 to 550 nm region compared to adenomas in mouse models of lung cancer. These spectral distinctions were also confirmed by two-photon excited fluorescence microspectroscopy. We demonstrate the feasibility of applying MPM imaging of intrinsic fluorescence for the differentiation of lung neoplasms, inflammatory and tumor-free lung, which motivates the application of multiphoton endoscopy for the in situ imaging of lung nodules.

  2. Bronchoscopic lung volume reduction

    Directory of Open Access Journals (Sweden)

    M. I. Polkey

    2006-12-01

    Full Text Available Surgical lung volume reduction can improve exercise performance and forced expiratory volume in one second in patients with emphysema. However, the procedure is associated with a 5% mortality rate and a nonresponse rate of 25%. Accordingly, interest has focused on alternative ways of reducing lung volume. Two principle approaches are used: collapse of the diseased area using blockers placed endobronchially and the creation of extrapulmonary pathways. Preliminary data from the former approach suggest that it can be successful and that the magnitude of success is related to reduction in dynamic hyperinflation.

  3. Poverty and lung health.

    Science.gov (United States)

    Rusen, I D; Squire, S Bertel; Billo, Nils E

    2010-04-01

    The International Union Against Tuberculosis and Lung Disease (The Union) held its 40th World Conference on Lung Health in Cancun, Mexico, between 3 and 7 December 2009. It was attended by over 2000 delegates from 104 countries around the world. The conference featured four stimulating plenary sessions and an extensive selection of scientific symposia. A total of 1125 abstracts were also presented from five broad categories: clinical trials and TB basic science, clinical research for treatment and care, epidemiology, education, advocacy and social issues, and policy and program implementation. In addition, the conference was preceded by a series of well-attended postgraduate courses and workshops.

  4. Quantification of Proton Dose Calculation Accuracy in the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Grassberger, Clemens, E-mail: Grassberger.Clemens@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Center for Proton Radiotherapy, Paul Scherrer Institute, Villigen (Switzerland); Daartz, Juliane; Dowdell, Stephen; Ruggieri, Thomas; Sharp, Greg; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)

    2014-06-01

    Purpose: To quantify the accuracy of a clinical proton treatment planning system (TPS) as well as Monte Carlo (MC)–based dose calculation through measurements and to assess the clinical impact in a cohort of patients with tumors located in the lung. Methods and Materials: A lung phantom and ion chamber array were used to measure the dose to a plane through a tumor embedded in the lung, and to determine the distal fall-off of the proton beam. Results were compared with TPS and MC calculations. Dose distributions in 19 patients (54 fields total) were simulated using MC and compared to the TPS algorithm. Results: MC increased dose calculation accuracy in lung tissue compared with the TPS and reproduced dose measurements in the target to within ±2%. The average difference between measured and predicted dose in a plane through the center of the target was 5.6% for the TPS and 1.6% for MC. MC recalculations in patients showed a mean dose to the clinical target volume on average 3.4% lower than the TPS, exceeding 5% for small fields. For large tumors, MC also predicted consistently higher V5 and V10 to the normal lung, because of a wider lateral penumbra, which was also observed experimentally. Critical structures located distal to the target could show large deviations, although this effect was highly patient specific. Range measurements showed that MC can reduce range uncertainty by a factor of ∼2: the average (maximum) difference to the measured range was 3.9 mm (7.5 mm) for MC and 7 mm (17 mm) for the TPS in lung tissue. Conclusion: Integration of Monte Carlo dose calculation techniques into the clinic would improve treatment quality in proton therapy for lung cancer by avoiding systematic overestimation of target dose and underestimation of dose to normal lung. In addition, the ability to confidently reduce range margins would benefit all patients by potentially lowering toxicity.

  5. Ratios of Normal Variables

    Directory of Open Access Journals (Sweden)

    George Marsaglia

    2006-05-01

    Full Text Available This article extends and amplifies on results from a paper of over forty years ago. It provides software for evaluating the density and distribution functions of the ratio z/w for any two jointly normal variates z,w, and provides details on methods for transforming a general ratio z/w into a standard form, (a+x/(b+y , with x and y independent standard normal and a, b non-negative constants. It discusses handling general ratios when, in theory, none of the moments exist yet practical considerations suggest there should be approximations whose adequacy can be verified by means of the included software. These approximations show that many of the ratios of normal variates encountered in practice can themselves be taken as normally distributed. A practical rule is developed: If a < 2.256 and 4 < b then the ratio (a+x/(b+y is itself approximately normally distributed with mean μ = a/(1.01b − .2713 and variance 2 = (a2 + 1/(b2 + .108b − 3.795 − μ2.

  6. Ratios of Normal Variables

    Directory of Open Access Journals (Sweden)

    George Marsaglia

    2006-05-01

    Full Text Available This article extends and amplifies on results from a paper of over forty years ago. It provides software for evaluating the density and distribution functions of the ratio z/w for any two jointly normal variates z,w, and provides details on methods for transforming a general ratio z/w into a standard form, (a+x/(b+y , with x and y independent standard normal and a, b non-negative constants. It discusses handling general ratios when, in theory, none of the moments exist yet practical considerations suggest there should be approximations whose adequacy can be verified by means of the included software. These approximations show that many of the ratios of normal variates encountered in practice can themselves be taken as normally distributed. A practical rule is developed: If a < 2.256 and 4 < b then the ratio (a+x/(b+y is itself approximately normally distributed with mean μ = a/(1.01b - .2713 and variance σ2 = (a2 + 1/(b2 + .108b - 3.795 μ2.

  7. Molecular Determinants of Lung Development

    Science.gov (United States)

    Morrisey, Edward E.; Cardoso, Wellington V.; Lane, Robert H.; Rabinovitch, Marlene; Abman, Steven H.; Ai, Xingbin; Albertine, Kurt H.; Bland, Richard D.; Chapman, Harold A.; Checkley, William; Epstein, Jonathan A.; Kintner, Christopher R.; Kumar, Maya; Minoo, Parviz; Mariani, Thomas J.; McDonald, Donald M.; Mukouyama, Yoh-suke; Prince, Lawrence S.; Reese, Jeff; Rossant, Janet; Shi, Wei; Sun, Xin; Werb, Zena; Whitsett, Jeffrey A.; Gail, Dorothy; Blaisdell, Carol J.

    2013-01-01

    Development of the pulmonary system is essential for terrestrial life. The molecular pathways that regulate this complex process are beginning to be defined, and such knowledge is critical to our understanding of congenital and acquired lung diseases. A recent workshop was convened by the National Heart, Lung, and Blood Institute to discuss the developmental principles that regulate the formation of the pulmonary system. Emerging evidence suggests that key developmental pathways not only regulate proper formation of the pulmonary system but are also reactivated upon postnatal injury and repair and in the pathogenesis of human lung diseases. Molecular understanding of early lung development has also led to new advances in areas such as generation of lung epithelium from pluripotent stem cells. The workshop was organized into four different topics, including early lung cell fate and morphogenesis, mechanisms of lung cell differentiation, tissue interactions in lung development, and environmental impact on early lung development. Critical points were raised, including the importance of epigenetic regulation of lung gene expression, the dearth of knowledge on important mesenchymal lineages within the lung, and the interaction between the developing pulmonary and cardiovascular system. This manuscript describes the summary of the discussion along with general recommendations to overcome the gaps in knowledge in lung developmental biology. PMID:23607856

  8. [Unilateral hyperlucent lung induced by a carcinoid tumor: comments on the differential diagnosis and mechanisms of hypoperfusion].

    Science.gov (United States)

    Schmitz, N; Bugnet, A-S; Demian, M; Massard, G; De Blay, F; Pauli, G

    2005-04-01

    We report the case of a 35-year-old woman in whom a systematic thoracic x-ray led to the diagnosis of unilateral hyperlucent lung due to a carcinoid tumor obstructing the main left bronchus almost completely. Injected computed tomography permitted diagnosis of left lung hypoperfusion and visualization of the tumor. After enlarged inferior left lobar resection, normal perfusion was observed six months later on the isotopic lung perfusion scan. Other reported causes of unilateral hyperlucent lung are discussed as well as pathophysiological mechanisms of lung hypoperfusion and hypoxic vasoconstriction.

  9. Normalized Information Distance

    CERN Document Server

    Vitanyi, Paul M B; Cilibrasi, Rudi L; Li, Ming

    2008-01-01

    The normalized information distance is a universal distance measure for objects of all kinds. It is based on Kolmogorov complexity and thus uncomputable, but there are ways to utilize it. First, compression algorithms can be used to approximate the Kolmogorov complexity if the objects have a string representation. Second, for names and abstract concepts, page count statistics from the World Wide Web can be used. These practical realizations of the normalized information distance can then be applied to machine learning tasks, expecially clustering, to perform feature-free and parameter-free data mining. This chapter discusses the theoretical foundations of the normalized information distance and both practical realizations. It presents numerous examples of successful real-world applications based on these distance measures, ranging from bioinformatics to music clustering to machine translation.

  10. A Rare Presentation of Right Lung Hypoplasia Associated with Dextrocardia and Visceral Malposition

    Directory of Open Access Journals (Sweden)

    Ayşe Yıldırım

    2012-08-01

    Full Text Available Lung hypoplasia is often associated with pulmonary venous return abnormalities, referred to as the Scimitar syndrome, in pediatric patients. A two day-old male patient presented to our clinic with respiratory distress and mild cyanosis. Diagnostic studies revealed dextrocardia, right sided hypoplasia of upper and middle lung lobes and enlargement of the left lung due to the compensation, midline liver, right sided stomach and right sided spleen. No pulmonary venous return abnormalities were detected. This is the first report of lung hypoplasia associated with heterotaxy, visceral malposition and normal pulmonary venous return.

  11. Reducing ventilator-induced lung injury and other organ injury by the prone position

    Science.gov (United States)

    Suter, Peter M

    2006-01-01

    Mechanical ventilation can cause structural and functional disturbances in the lung, as well as other vital organ dysfunctions. Apoptosis is thought to be a histological sign of distant organ damage in ventilator-induced lung injury (VILI). Nakos and colleagues observed a protective effect of prone positioning against VILI in normal sheep. Less alteration in the lung architecture and function and in liver transaminases, and lower indices for apoptosis in the liver, the diaphragm and the lung were noted in the prone position compared with the supine position. If confirmed, these data open a new hypothesis for pathogenesis and prevention of VILI and its extrapulmonary complications. PMID:16677405

  12. Normalization of satellite imagery

    Science.gov (United States)

    Kim, Hongsuk H.; Elman, Gregory C.

    1990-01-01

    Sets of Thematic Mapper (TM) imagery taken over the Washington, DC metropolitan area during the months of November, March and May were converted into a form of ground reflectance imagery. This conversion was accomplished by adjusting the incident sunlight and view angles and by applying a pixel-by-pixel correction for atmospheric effects. Seasonal color changes of the area can be better observed when such normalization is applied to space imagery taken in time series. In normalized imagery, the grey scale depicts variations in surface reflectance and tonal signature of multi-band color imagery can be directly interpreted for quantitative information of the target.

  13. QUANTIFYING LOCAL RADIATION-INDUCED LUNG DAMAGE FROM COMPUTED TOMOGRAPHY

    NARCIS (Netherlands)

    Ghobadi, Ghazaleh; Hogeweg, Laurens E.; Faber, Hette; Tukker, Wim G. J.; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Coppes, Robert P.; van Luijk, Peter

    2010-01-01

    Purpose: Optimal implementation of new radiotherapy techniques requires accurate predictive models for normal tissue complications. Since clinically used dose distributions are nonuniform, local tissue damage needs to be measured and related to local tissue dose. In lung, radiation-induced damage re

  14. P53 MUTATIONS IN HUMAN LUNG-TUMORS

    NARCIS (Netherlands)

    MILLER, CW; ASLO, A; KOK, K; YOKOTA, J; BUYS, CHCM; TERADA, M; KOEFFLER, HP; Simon, K.

    1992-01-01

    Mutation of one p53 allele and loss of the normal p53 allele [loss of heterozygosity (LOH)] occur in many tumors including lung cancers. These alterations apparently contribute to development of cancer by interfering with the tumor suppressor activity of p53. We directly sequenced amplified DNA in t

  15. Matrikines and the lungs

    NARCIS (Netherlands)

    Burgess, Janette K; Weckmann, Markus

    2012-01-01

    The extracellular matrix is a complex network of fibrous and nonfibrous molecules that not only provide structure to the lung but also interact with and regulate the behaviour of the cells which it surrounds. Recently it has been recognised that components of the extracellular matrix proteins are re

  16. Lung Cancer Survivorship

    Centers for Disease Control (CDC) Podcasts

    2016-10-20

    A lung cancer survivor shares her story about diagnosis, treatment, and community support. She also gives advice for other cancer survivors.  Created: 10/20/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/20/2016.

  17. Cell polarity and spindle orientation in the distal epithelium of embryonic lung.

    Science.gov (United States)

    El-Hashash, Ahmed H; Warburton, David

    2011-02-01

    A proper balance between self-renewal and differentiation of lung-specific progenitors at the distal epithelial tips is absolutely required for normal lung morphogenesis. Cell polarity and mitotic spindle orientation play a critical role in the self-renewal/differentiation of epithelial cells and can impact normal physiological processes, including epithelial tissue branching and differentiation. Therefore, understanding the behavior of lung distal epithelial progenitors could identify innovative solutions to restoring normal lung morphogenesis. Yet little is known about cell polarity, spindle orientation, and segregation of cell fate determinant in the embryonic lung epithelium, which contains progenitor cells. Herein, we provide the first evidence that embryonic lung distal epithelium is polarized and highly mitotic with characteristic perpendicular cell divisions. Consistent with these findings, mInsc, LGN, and NuMA polarity proteins, which control spindle orientation, are asymmetrically localized in mitotic distal epithelial progenitors of embryonic lungs. Furthermore, the cell fate determinant Numb is asymmetrically distributed at the apical side of distal epithelial progenitors and segregated to one daughter cell in most mitotic cells. These findings provide evidence for polarity in distal epithelial progenitors of embryonic lungs and provide a framework for future translationally oriented studies in this area.

  18. Normality in Analytical Psychology

    Directory of Open Access Journals (Sweden)

    Steve Myers

    2013-11-01

    Full Text Available Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity.

  19. Back to Normal

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Xinjiang officials speed up the investigation of July 5 riot suspects and restore social order Life in Urumqi has gone back to normal one month after the July 5 riot that killed nearly 200 people in the capital city of China’s northwestern

  20. Normalized information distance

    NARCIS (Netherlands)

    Vitányi, P.M.B.; Balbach, F.J.; Cilibrasi, R.L.; Li, M.; Emmert-Streib, F.; Dehmer, M.

    2009-01-01

    The normalized information distance is a universal distance measure for objects of all kinds. It is based on Kolmogorov complexity and thus uncomputable, but there are ways to utilize it. First, compression algorithms can be used to approximate the Kolmogorov complexity if the objects have a string

  1. Normalized information distance

    NARCIS (Netherlands)

    Vitányi, P.M.B.; Balbach, F.J.; Cilibrasi, R.L.; Li, M.

    2008-01-01

    The normalized information distance is a universal distance measure for objects of all kinds. It is based on Kolmogorov complexity and thus uncomputable, but there are ways to utilize it. First, compression algorithms can be used to approximate the Kolmogorov complexity if the objects have a string

  2. Developmental defects of the lungs

    Energy Technology Data Exchange (ETDEWEB)

    DaCosta, H.; Pathak, A.; Noronha, O.; Dalal, S.; Shah, K.; Merchant, S.

    1981-06-01

    Poor lung development was first noted on scintigraphy using sup(99m)Tc-phytate in 32 children. They had all been referred for a hepatosplenic scan but the initial circulatory phase of the radiopharmaceutical was also recorded as a routine procedure. In 3 patients it revealed aplasia of an entire lung; bilateral pulmonary hypolplasia was observed in 14 of 16 patients with diaphragmatic herniae. Six patients with congenital heart enlargement showed a poorly developed ipsilateral lung; 5 of 6 patients with dextrocardia without an intracardiac defect had a larger left lung compared with the right lung; both pulmonary beds appeared equal in a patient with mesocardia.

  3. Establishment of a human lung cancer cell line with high metastatic potential to multiple organs: gene expression associated with metastatic potential in human lung cancer.

    Science.gov (United States)

    Nakano, Tetsuhiro; Shimizu, Kimihiro; Kawashima, Osamu; Kamiyoshihara, Mitsuhiro; Kakegawa, Seiichi; Sugano, Masayuki; Ibe, Takashi; Nagashima, Toshiteru; Kaira, Kyoichi; Sunaga, Noriaki; Ohtaki, Youichi; Atsumi, Jun; Takeyoshi, Izumi

    2012-11-01

    Convenient and reliable multiple organ metastasis model systems might contribute to understanding the mechanism(s) of metastasis of lung cancer, which may lead to overcoming metastasis and improvement in the treatment outcome of lung cancer. We isolated a highly metastatic subline, PC14HM, from the human pulmonary adenocarcinoma cell line, PC14, using an in vivo selection method. The expression of 34,580 genes was compared between PC14HM and parental PC14 by cDNA microarray analysis. Among the differentially expressed genes, expression of four genes in human lung cancer tissues and adjacent normal lung tissues were compared using real-time reverse transcription polymerase chain reaction. Although BALB/c nude mice inoculated with parental PC14 cells had few metastases, almost all mice inoculated with PC14HM cells developed metastases in multiple organs, including the lung, bone and adrenal gland, the same progression seen in human lung cancer. cDNA microarray analysis revealed that 981 genes were differentially (more than 3-fold) expressed between the two cell lines. Functional classification revealed that many of those genes were associated with cell growth, cell communication, development and transcription. Expression of three upregulated genes (HRB-2, HS3ST3A1 and RAB7) was higher in human cancer tissue compared to normal lung tissue, while expression of EDG1, which was downregulated, was lower in the cancer tissue compared to the normal lung. These results suggest that the newly established PC14HM cell line may provide a mouse model of widespread metastasis of lung cancer. This model system may provide insights into the key genetic determinants of widespread metastasis of lung cancer.

  4. ANTICOMPLEMENTARY ACTIVITY IN HUMAN SERUM OF LUNG CANCER PATIENTS AND ITS POSSIBLE CLINICAL SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    Liu Huirong; Liang Feng; Zhang Weifang; Zheng Zhenqun

    1998-01-01

    Objective: To identify whether the level of anticomplementary activity in serum is different between lung cancer patients and normal subjects. Method: With a sensitive immune haemolytic assay, the anticomplementary activity in the sera of 50 normal subjects and 61lung cancer patients were demonstrated. Results: It was found that all samples contained complement-inhibition activity, although some were of low degree. Increased anticomplementary activity was found to be associated significantly with lung cancer. With the progression of cancer the anticomplementary activity in sera increased in different lung cancer patients. Conclusion: Such a higher anticomplementary activity in sera of lung cancer patients might be one of the immunosuppressive contents induced by the tumor cells.

  5. [Normal and Adventitious Breath Sounds].

    Science.gov (United States)

    Koehler, U; Hildebrandt, O; Kerzel, S; Urban, C; Hoehle, L; Weissflog, A; Nikolaizik, W; Koehler, J; Sohrabi, K; Gross, V

    2016-06-01

    Auscultation of the lung is an inexpensive, noninvasive and easy-to-perform tool. It is an important part of the physical examination and is help ful to distinguish physiological respiratory sounds from pathophysiological events. Computerized lung sound analysis is a powerful tool for optimizing and quantifying electronic auscultation based on the specific lung sound spectral characteristics. The automatic analysis of respiratory sounds assumes that physiological and pathological sounds are reliably analyzed based on special algorithms. The development of automated long-term lungsound monitors enables objective assessment of different respiratory symptoms.

  6. Respiratory compliance but not gas exchange correlates with changes in lung aeration after a recruitment maneuver: an experimental study in pigs with saline lavage lung injury

    Science.gov (United States)

    Henzler, Dietrich; Pelosi, Paolo; Dembinski, Rolf; Ullmann, Annette; Mahnken, Andreas H; Rossaint, Rolf; Kuhlen, Ralf

    2005-01-01

    Introduction Atelectasis is a common finding in acute lung injury, leading to increased shunt and hypoxemia. Current treatment strategies aim to recruit alveoli for gas exchange. Improvement in oxygenation is commonly used to detect recruitment, although the assumption that gas exchange parameters adequately represent the mechanical process of alveolar opening has not been proven so far. The aim of this study was to investigate whether commonly used measures of lung mechanics better detect lung tissue collapse and changes in lung aeration after a recruitment maneuver as compared to measures of gas exchange Methods In eight anesthetized and mechanically ventilated pigs, acute lung injury was induced by saline lavage and a recruitment maneuver was performed by inflating the lungs three times with a pressure of 45 cmH2O for 40 s with a constant positive end-expiratory pressure of 10 cmH2O. The association of gas exchange and lung mechanics parameters with the amount and the changes in aerated and nonaerated lung volumes induced by this specific recruitment maneuver was investigated by multi slice CT scan analysis of the whole lung. Results Nonaerated lung correlated with shunt fraction (r = 0.68) and respiratory system compliance (r = 0.59). The arterial partial oxygen pressure (PaO2) and the respiratory system compliance correlated with poorly aerated lung volume (r = 0.57 and 0.72, respectively). The recruitment maneuver caused a decrease in nonaerated lung volume, an increase in normally and poorly aerated lung, but no change in the distribution of a tidal breath to differently aerated lung volumes. The fractional changes in PaO2, arterial partial carbon dioxide pressure (PaCO2) and venous admixture after the recruitment maneuver did not correlate with the changes in lung volumes. Alveolar recruitment correlated only with changes in the plateau pressure (r = 0.89), respiratory system compliance (r = 0.82) and parameters obtained from the pressure-volume curve

  7. Comparative Proteome Analysis of Human Lung Squamous Carcinoma Tissue

    Institute of Scientific and Technical Information of China (English)

    LI Cui; TANG Can'e; DUAN Chaojun; YI Hong; XIAO Zhiqiang; CHEN Zhuchu

    2006-01-01

    Objective: To establish the two-dimensional electrophoresis profiles with high resolution and reproducibility from human lung squamous carcinoma tissue and paired normal tumor-adjacent bronchial epithelial tissue, and to identify differential expression tumor-associated proteins by using proteome analysis. Methods: Comparative proteome analysis with 20 human lung squamous carcinoma tissues and the paired normal bronchial epithelial tissues adjacent to tumors was carried out. The total proteins of human lung squamous carcinoma tissue and paired normal tumor-adjacent bronchial epithelial tissue were separated by means of immobilized pH gradient-based two-dimensional gel electrophoresis (2-DE) and silver staining. The differential expression proteins were analyzed and then identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Results: (1) Well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained. For tumor tissue, average spots of 3 gels were 1567±46, and 1436±54 spots were matched with an average matching rate of 91.6%. For control, average spots of 3 gels were 1349±58, and 1228±35 spots were matched with an average matching rate of 91.03%. The average position deviation of matched spots was 0.924±0.128 mm in IEF direction, and 1.022±0.205 mm in SDS-PAGE direction; (2)A total of 1178±56 spots were matched between the electrophoretic maps of 20 human lung squamous carcinoma tissues and paired normal tumor-adjacent bronchial epithelial tissues. Seventy-six differentially expressed proteins were screened; (3) Sixty-eight differential proteins were identified by PMF, some proteins were the products of oncogenes, and others involved in the regulation of cell cycle and signal transduction;(4) In order to validate the reliability of the identified results, the expression of 3 proteins mdm2, c-jun and EGFR, which was correlated with lung

  8. The Danish Lung Cancer Registry

    DEFF Research Database (Denmark)

    Jakobsen, Erik; Rasmussen, Torben Riis

    2016-01-01

    AIM OF DATABASE: The Danish Lung Cancer Registry (DLCR) was established by the Danish Lung Cancer Group. The primary and first goal of the DLCR was to improve survival and the overall clinical management of Danish lung cancer patients. STUDY POPULATION: All Danish primary lung cancer patients since...... 2000 are included into the registry and the database today contains information on more than 50,000 cases of lung cancer. MAIN VARIABLES: The database contains information on patient characteristics such as age, sex, diagnostic procedures, histology, tumor stage, lung function, performance...... the results are commented for local, regional, and national audits. Indicator results are supported by descriptive reports with details on diagnostics and treatment. CONCLUSION: DLCR has since its creation been used to improve the quality of treatment of lung cancer in Denmark and it is increasingly used...

  9. Independence of sialic acid levels in normal and malignant growth.

    Science.gov (United States)

    Khadapkar, S V; Sheth, N A; Bhide, S V

    1975-06-01

    Sialic acid content in breast or tumor tissue and serum of mouse strains that are either susceptible or resistant to breast cancer was measured at various age periods. Sialic acid content was also studied in normal lung tissue and in lung adenoma and hepatoma. Sialic acid levels during nonmalignant growth of a tissue were measured in breast tissue during pregnancy and lactation, and in regenerating liver, as well as in newborn and postnatal liver. The sialic acid content, when expressed per mg of protein, increased in mammary tumor, lung adenoma, and hepatoma. It also increased in nonmalignant growth of breast tissue during pregnancy and lactation and of regenerating liver and postnatal liver. Increase in sialic acid per mg DNA was observed only in lung tumors, regenerating liver, and postnatal liver. It appears that the changes in sialic acid level are independent of the normal or malignant growth of a tissue and that these changes might be the function of the parameter used to express the sialic acid values, i.e., either the DNA content or protein content of a given tissue.

  10. Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers.

    Directory of Open Access Journals (Sweden)

    Mathewos Tessema

    Full Text Available Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190 and 23% breast (n = 80 tumors were methylated. Expression of two novel TOX2 transcripts identified was significantly reduced in primary lung tumors than distant normal lung (p<0.05. These transcripts were silenced in methylated lung and breast cancer cells and 5-Aza-2-deoxycytidine treatment re-expressed both. Extension of these assays to TOX, TOX3, and TOX4 genes that share similar genomic structure and protein homology with TOX2 revealed distinct methylation profiles by smoking status, histology, and cancer type. TOX was almost exclusively methylated in breast (43% than lung (5% cancer, whereas TOX3 was frequently methylated in lung (58% than breast (30% tumors. TOX4 was unmethylated in all samples and showed the highest expression in normal lung. Compared to TOX4, expression of TOX, TOX2 and TOX3 in normal lung was 25, 44, and 88% lower, respectively, supporting the premise that reduced promoter activity confers increased susceptibility to methylation during lung carcinogenesis. Genome-wide assays revealed that siRNA-mediated TOX2 knockdown modulated multiple pathways while TOX3 inactivation targeted neuronal development and function. Although these knockdowns did not result in further phenotypic changes of lung cancer cells in vitro, the impact on tissue remodeling, inflammatory response, and cell differentiation pathways suggest a potential role for TOX2 in modulating tumor microenvironment.

  11. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

    Science.gov (United States)

    Brune, Kieran A; Ferreira, Fernanda; Mandke, Pooja; Chau, Eric; Aggarwal, Neil R; D'Alessio, Franco R; Lambert, Allison A; Kirk, Gregory; Blankson, Joel; Drummond, M Bradley; Tsibris, Athe M; Sidhaye, Venkataramana K

    2016-01-01

    Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD). We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE) cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI) to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1) and activated extracellular signal-regulated kinase (ERK). We demonstrate that HIV can enter airway

  12. HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

    Directory of Open Access Journals (Sweden)

    Kieran A Brune

    Full Text Available Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD. We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1 and activated extracellular signal-regulated kinase (ERK. We demonstrate that HIV

  13. Increased mean lung density: Another independent predictor of lung cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Sverzellati, Nicola, E-mail: nicola.sverzellati@unipr.it [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Randi, Giorgia, E-mail: giorgia.randi@marionegri.it [Department of Epidemiology, Mario Negri Institute, Via La Masa 19, 20156 Milan (Italy); Spagnolo, Paolo, E-mail: paolo.spagnolo@unimore.it [Respiratory Disease Unit, Center for Rare Lung Disease, Department of Oncology, Hematology and Respiratory Disease, University of Modena and Reggio Emilia, Via del Pozzo 71, 44124 Modena (Italy); Marchianò, Alfonso, E-mail: alfonso.marchiano@istitutotumori.mi.it [Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy); Silva, Mario, E-mail: mac.mario@hotmail.it [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Kuhnigk, Jan-Martin, E-mail: Jan-Martin.Kuhnigk@mevis.fraunhofer.de [Fraunhofer MEVIS, Universitaetsallee 29, 28359 Bremen (Germany); La Vecchia, Carlo, E-mail: carlo.lavecchia@marionegri.it [Department of Occupational Health, University of Milan, Via Venezian 1, 20133 Milan (Italy); Zompatori, Maurizio, E-mail: maurizio.zompatori@unibo.it [Department of Radiology, Cardio-Thoracic Section, S. Orsola-Malpighi Hospital, Via Albertoni 15, 40138 Bologna (Italy); Pastorino, Ugo, E-mail: ugo.pastorino@istitutotumori.mi.it [Department of Surgery, Section of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy)

    2013-08-15

    Objectives: To investigate the relationship between emphysema phenotype, mean lung density (MLD), lung function and lung cancer by using an automated multiple feature analysis tool on thin-section computed tomography (CT) data. Methods: Both emphysema phenotype and MLD evaluated by automated quantitative CT analysis were compared between outpatients and screening participants with lung cancer (n = 119) and controls (n = 989). Emphysema phenotype was defined by assessing features such as extent, distribution on core/peel of the lung and hole size. Adjusted multiple logistic regression models were used to evaluate independent associations of CT densitometric measurements and pulmonary function test (PFT) with lung cancer risk. Results: No emphysema feature was associated with lung cancer. Lung cancer risk increased with decreasing values of forced expiratory volume in 1 s (FEV{sub 1}) independently of MLD (OR 5.37, 95% CI: 2.63–10.97 for FEV{sub 1} < 60% vs. FEV{sub 1} ≥ 90%), and with increasing MLD independently of FEV{sub 1} (OR 3.00, 95% CI: 1.60–5.63 for MLD > −823 vs. MLD < −857 Hounsfield units). Conclusion: Emphysema per se was not associated with lung cancer whereas decreased FEV{sub 1} was confirmed as being a strong and independent risk factor. The cross-sectional association between increased MLD and lung cancer requires future validations.

  14. Normality concerning shared values

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Let F be a family of meromorphic functions in a plane domain D, and a and b be finite non-zero complex values such that a/b ∈ N \\ {1}. If for every f ∈ F, f(z) = a =■ f (z) = a and f (z) = b =■ f (z) = b, then F is normal. We also construct a non-normal family F of meromorphic functions in the unit disk Δ = {|z| < 1} such that for every f ∈ F, f(z) = m + 1  f (z) = m + 1 and f (z) = 1  f (z) = 1 in Δ, where m is a given positive integer. This answers Problem 5.1 in the works of Gu, Pang and Fang.

  15. Normality concerning shared values

    Institute of Scientific and Technical Information of China (English)

    CHANG JianMing

    2009-01-01

    Let F be a family of meromorphic functions in a plane domain D,and a and b be finite non-zero complex values such that a/b ∈ N \\ {1}.If for every f ∈ F,f(z)=a=>(z) = a and f'(z)=b=>f"(z)=b,then F is normal.We also construct a non-normal family F of meromorphic functions in the unit disk △= {|z|<1} such that for every f ∈F,f(z) =m+1f'(z) = m+1and f'(z)=1 f"(z) = 1 in △ A,where m is a given positive integer.This answers Problem 5.1 in the works of Gu,Pang and Fang.

  16. Monitoring the normal body

    DEFF Research Database (Denmark)

    Nissen, Nina Konstantin; Holm, Lotte; Baarts, Charlotte

    2015-01-01

    Introduction : An extensive body of literature is concerned with obese people, risk, and weight management. However, little is known about weight management among people not belonging to the extreme BMI categories. Management of weight among normal-weight and moderately overweight individuals...... provides us with knowledge about how to prevent future overweight or obesity. This paper investigates body size ideals and monitoring practices among normal-weight and moderately overweight people. Methods : The study is based on in-depth interviews combined with observations. 24 participants were...... of practices for monitoring their bodies based on different kinds of calculations of weight and body size, observations of body shape, and measurements of bodily firmness. Biometric measurements are familiar to them as are health authorities' recommendations. Despite not belonging to an extreme BMI category...

  17. Normal Order: Combinatorial Graphs

    CERN Document Server

    Solomon, A I; Blasiak, P; Horzela, A; Penson, K A; Solomon, Allan I.; Duchamp, Gerard; Blasiak, Pawel; Horzela, Andrzej; Penson, Karol A.

    2004-01-01

    A conventional context for supersymmetric problems arises when we consider systems containing both boson and fermion operators. In this note we consider the normal ordering problem for a string of such operators. In the general case, upon which we touch briefly, this problem leads to combinatorial numbers, the so-called Rook numbers. Since we assume that the two species, bosons and fermions, commute, we subsequently restrict ourselves to consideration of a single species, single-mode boson monomials. This problem leads to elegant generalisations of well-known combinatorial numbers, specifically Bell and Stirling numbers. We explicitly give the generating functions for some classes of these numbers. In this note we concentrate on the combinatorial graph approach, showing how some important classical results of graph theory lead to transparent representations of the combinatorial numbers associated with the boson normal ordering problem.

  18. Idiopathic Normal Pressure Hydrocephalus

    Directory of Open Access Journals (Sweden)

    Basant R. Nassar BS

    2016-04-01

    Full Text Available Idiopathic normal pressure hydrocephalus (iNPH is a potentially reversible neurodegenerative disease commonly characterized by a triad of dementia, gait, and urinary disturbance. Advancements in diagnosis and treatment have aided in properly identifying and improving symptoms in patients. However, a large proportion of iNPH patients remain either undiagnosed or misdiagnosed. Using PubMed search engine of keywords “normal pressure hydrocephalus,” “diagnosis,” “shunt treatment,” “biomarkers,” “gait disturbances,” “cognitive function,” “neuropsychology,” “imaging,” and “pathogenesis,” articles were obtained for this review. The majority of the articles were retrieved from the past 10 years. The purpose of this review article is to aid general practitioners in further understanding current findings on the pathogenesis, diagnosis, and treatment of iNPH.

  19. Biomarker Identification and Pathway Analysis by Serum Metabolomics of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yingrong Chen

    2015-01-01

    Full Text Available Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer.

  20. Endotoxin-induced maturation of monocytes in preterm fetal sheep lung.

    Science.gov (United States)

    Kramer, Boris W; Joshi, Shubhada N; Moss, Timothy J M; Newnham, John P; Sindelar, Richard; Jobe, Alan H; Kallapur, Suhas G

    2007-08-01

    The fetal lung normally contains immature monocytes and very few mature macrophages. The chorioamnionitis frequently associated with preterm birth induces monocyte influx into the fetal lung. Previous studies demonstrated that monocytes in the developing lung can mediate lung injury responses that resemble BPD in humans. We hypothesized that chorioamnionitis would induce maturation of immature monocytes in the fetal lung. Groups of three to seven time-mated ewes received saline or 10 mg of endotoxin (Escherichia coli 055:B5) in saline by intra-amniotic injection for intervals from 1 to 14 days before operative delivery at 124 days of gestational age. Monocytic cells from lung tissue were recovered using Percoll gradients. Monocytic cells consistent with macrophages were identified morphologically and by myosin heavy chain class II expression. An increase in macrophages was preceded by induction of granulocyte-macrophage colony-stimulating factor in the lung and subsequent activation of the transcription factor PU.1. The production of IL-6 by monocytes/macrophages in response to endotoxin challenge in vitro increased 7 and 14 days after exposure to intra-amniotic endotoxin. Recombinant TNF-alpha induced IL-6 production by lung monocytic cells exposed to intra-amniotic endotoxin but not in control cells. Monocytic phagocytosis of apoptotic neutrophils also increased 7 and 14 days after exposure to intra-amniotic endotoxin. Intra-amniotic endotoxin induced lung monocytes to develop into functionally mature cells consistent with macrophages. These findings have implications for lung immune responses after exposure to chorioamnionitis.

  1. Neuroethics beyond Normal.

    Science.gov (United States)

    Shook, John R; Giordano, James

    2016-01-01

    An integrated and principled neuroethics offers ethical guidelines able to transcend conventional and medical reliance on normality standards. Elsewhere we have proposed four principles for wise guidance on human transformations. Principles like these are already urgently needed, as bio- and cyberenhancements are rapidly emerging. Context matters. Neither "treatments" nor "enhancements" are objectively identifiable apart from performance expectations, social contexts, and civic orders. Lessons learned from disability studies about enablement and inclusion suggest a fresh way to categorize modifications to the body and its performance. The term "enhancement" should be broken apart to permit recognition of enablements and augmentations, and kinds of radical augmentation for specialized performance. Augmentations affecting the self, self-worth, and self-identity of persons require heightened ethical scrutiny. Reversibility becomes the core problem, not the easy answer, as augmented persons may not cooperate with either decommissioning or displacement into unaccommodating societies. We conclude by indicating how our four principles of self-creativity, nonobsolescence, empowerment, and citizenship establish a neuroethics beyond normal that is better prepared for a future in which humans and their societies are going so far beyond normal.

  2. Regeneration of the lung: Lung stem cells and the development of lung mimicking devices.

    Science.gov (United States)

    Schilders, Kim A A; Eenjes, Evelien; van Riet, Sander; Poot, André A; Stamatialis, Dimitrios; Truckenmüller, Roman; Hiemstra, Pieter S; Rottier, Robbert J

    2016-04-23

    Inspired by the increasing burden of lung associated diseases in society and an growing demand to accommodate patients, great efforts by the scientific community produce an increasing stream of data that are focused on delineating the basic principles of lung development and growth, as well as understanding the biomechanical properties to build artificial lung devices. In addition, the continuing efforts to better define the disease origin, progression and pathology by basic scientists and clinicians contributes to insights in the basic principles of lung biology. However, the use of different model systems, experimental approaches and readout systems may generate somewhat conflicting or contradictory results. In an effort to summarize the latest developments in the lung epithelial stem cell biology, we provide an overview of the current status of the field. We first describe the different stem cells, or progenitor cells, residing in the homeostatic lung. Next, we focus on the plasticity of the different cell types upon several injury-induced activation or repair models, and highlight the regenerative capacity of lung cells. Lastly, we summarize the generation of lung mimics, such as air-liquid interface cultures, organoids and lung on a chip, that are required to test emerging hypotheses. Moreover, the increasing collaboration between distinct specializations will contribute to the eventual development of an artificial lung device capable of assisting reduced lung function and capacity in human patients.

  3. Trans, trans-2,4-decadienal, a product found in cooking oil fumes, induces cell proliferation and cytokine production due to reactive oxygen species in human bronchial epithelial cells.

    Science.gov (United States)

    Chang, Louis W; Lo, Wai-Sze; Lin, Pinpin

    2005-10-01

    Dienaldehydes are by-products of peroxidation of polyunsaturated lipids and commonly found in many foods or food-products. Both National Cancer Institute (NCI) and NTP have expressed great concern on the potential genotoxicity and carcinogenicity of dienaldehydes. Trans, trans-2,4-decadienal (tt-DDE or 2,4-De), a specific type of dienaldehyde, is abundant in heated oils and has been associated with lung adenocarcinoma development in women due to their exposure to oil fumes during cooking. Cultured human bronchial epithelial cells (BEAS-2B cells) were exposed to 0.1 or 1.0 microM tt-DDE for 45 days, and oxidative stress, reactive oxygen species (ROS) production, GSH/GSSG ratio, cell proliferation, and expression of TNFalpha and IL-1beta were measured. The results show that tt-DDE induced oxidative stress, an increase in ROS production, and a decrease in GSH/GSSG ratio (glutathione status) in a dose-dependent manner. Treatment of BEAS-2B cells with 1.0 microM tt-DDE for 45 days increased cell proliferation and the expression and release of pro-inflammatory cytokines TNFalpha and IL-1beta. Cotreatment of BEAS-2B cells with antioxidant N-acetylcysteine prevented tt-DDE-induced cell proliferation and release of cytokines. Therefore, these results suggest that tt-DDE-induced changes may be due to increased ROS production and enhanced oxidative stress. Since increased cell proliferation and the release of TNF-alpha and IL-1beta are believed to be involved in tumor promotion, our results suggest that tt-DDE may play a role in cancer promotion. Previous studies on dienaldehydes have focused on their genotoxic or carcinogenic effects in the gastrointestinal tract; the present study suggests a potential new role of tt-DDE as a tumor promoter in human lung epithelial cells.

  4. Three dimensional conformal radiation therapy may improve the therapeutic ratio of radiation therapy after pneumonectomy for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Trouette, R.; Causse, N.; Elkhadri, M.; Caudry, M.; Maire, J.P.; Houlard, J.P.; Racaldini, L.; Demeaux, H.

    1995-12-01

    Three dimensional conformal radiation therapy would allow to decrease the normal tissue dose while maintaining the same target dose as standard treatment. To evaluate the feasibility of normal tissue dose reduction for ten patients with pneumonectomy for lung cancer, we determined the dose distribution to the normal tissue with 3-dimensional conformal radiation therapy (3-DCRT) and conventional treatment planning (CTP). Dose-volume histograms for target and normal tissue (lung, heart) were used for comparison of the different treatment planning. The mean percentages of lung and heart volumes which received 40 Gy with 3-DCRT were respectively 63% and 37% of the mean percentage of lung and volumes which received the same dose with CTP. These preliminary results suggest that conformal therapy may improve the therapeutic ratio by reducing risk to normal tissue.

  5. Noninvasive measurement of lung carbon-11-serotonin extraction in man

    Energy Technology Data Exchange (ETDEWEB)

    Coates, G.; Firnau, G.; Meyer, G.J.; Gratz, K.F. (McMaster Univ. Medical Centre, Hamilton, Ontario (Canada))

    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 {sup 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.

  6. Glucocorticoids decrease Treg cell numbers in lungs of allergic mice.

    Science.gov (United States)

    Olsen, P C; Kitoko, J Z; Ferreira, T P; de-Azevedo, C T; Arantes, A C; Martins, Μ A

    2015-01-15

    Glucocorticoids have been the hallmark anti-inflammatory drug used to treat asthma. It has been shown that glucocorticoids ameliorate asthma by increasing numbers and activity of Tregs, in contrast recent data show that glucocorticoid might have an opposite effect on Treg cells from normal mice. Since Tregs are target cells that act on the resolution of asthma, the aim of this study was to elucidate the effect of glucocorticoid treatment on lung Tregs in mouse models of asthma. Allergen challenged mice were treated with either oral dexamethasone or nebulized budesonide. Broncoalveolar lavage and airway hyperresponsiveness were evaluated after allergenic challenge. Lung, thymic and lymph node cells were phenotyped on Treg through flow cytometry. Lung cytokine secretion was detected by ELISA. Although dexamethasone inhibited airway inflammation and hyperresponsiveness, improving resolution, we have found that both dexamethasone and budesonide induce a reduction of Treg numbers on lungs and lymphoid organs of allergen challenged mice. The reduction of lung Treg levels was independent of mice strain or type of allergen challenge. Our study also indicates that both glucocorticoids do not increase Treg activity through production of IL-10. Glucocorticoid systemic or localized treatment induced thymic atrophy. Taken together, our results demonstrate that glucocorticoids decrease Treg numbers and activity in different asthma mouse models, probably by reducing thymic production of T cells. Therefore, it is possible that glucocorticoids do not have beneficial effects on lung populations of Treg cells from asthmatic patients.

  7. Lung protection by inhalation of exogenous solubilized extracellular matrix

    Science.gov (United States)

    Wu, Jinglei; Ravikumar, Priya; Nguyen, Kytai T.; Hsia, Connie C. W.

    2017-01-01

    Decellularized extracellular matrix (ECM) contains complex tissue-specific components that work in concert to promote tissue repair and constructive remodeling and has been used experimentally and clinically to accelerate epithelial wound repair, leading us to hypothesize that lung-derived ECM could mitigate acute lung injury. To explore the therapeutic potential of ECM for noninvasive delivery to the lung, we decellularized and solubilized porcine lung ECM, then characterized the composition, concentration, particle size and stability of the preparation. The ECM preparation at 3.2 mg/mL with average particle size <3 μm was tested in vitro on human A549 lung epithelial cells exposed to 95% O2 for 24 hours, and in vivo by tracheal instillation or nebulization into the lungs of rats exposed intermittently or continuously to 90% O2 for a cumulative 72 hours. Our results showed that the preparation was enriched in collagen, reduced in glycosaminoglycans, and contained various bioactive molecules. Particle size was concentration-dependent. Compared to the respective controls treated with cell culture medium in vitro or saline in vivo, ECM inhalation normalized cell survival and alveolar morphology, and reduced hyperoxia-induced apoptosis and oxidative damage. This proof-of-concept study established the methodology, feasibility and therapeutic potential of exogenous solubilized ECM for pulmonary cytoprotection, possibly as an adjunct or potentiator of conventional therapy. PMID:28151947

  8. Persistent disruption of ciliated epithelium following paediatric lung transplantation.

    Science.gov (United States)

    Thomas, Biju; Aurora, Paul; Spencer, Helen; Elliott, Martin; Rutman, Andrew; Hirst, Robert A; O'Callaghan, Christopher

    2012-11-01

    It is unclear whether ciliary function following lung transplantation is normal or not. Our aim was to study the ciliary function and ultrastructure of epithelium above and below the airway anastomosis and the peripheral airway of children following lung transplantation. We studied the ciliary beat frequency (CBF) and beat pattern, using high speed digital video imaging and ultrastructure by transmission electron microscopy, of bronchial epithelium from above and below the airway anastomosis and the peripheral airway of 10 cystic fibrosis (CF) and 10 non-suppurative lung disease (NSLD) paediatric lung transplant recipients. Compared to epithelium below the anastomosis, the epithelium above the anastomosis in the CF group showed reduced CBF (median (interquartile range): 10.5 (9.0-11.4) Hz versus 7.4 (6.4-9.2) Hz; pepithelium above the anastomosis, the epithelium below the anastomosis showed marked ultrastructural abnormalities (median duration post-transplant 7-12 months). Ciliary dysfunction is a feature of native airway epithelium in paediatric CF lung transplant recipients. The epithelium below the airway anastomosis shows profound ultrastructural abnormalities in both CF and NSLD lung transplant recipients, many months after transplantation.

  9. Roles of lung epithelium in neutrophil recruitment during pneumococcal pneumonia.

    Science.gov (United States)

    Yamamoto, Kazuko; Ahyi, Ayele-Nati N; Pepper-Cunningham, Zachary A; Ferrari, Joseph D; Wilson, Andrew A; Jones, Matthew R; Quinton, Lee J; Mizgerd, Joseph P

    2014-02-01

    Epithelial cells line the respiratory tract and interface with the external world. Epithelial cells contribute to pulmonary inflammation, but specific epithelial roles have proven difficult to define. To discover unique epithelial activities that influence immunity during infection, we generated mice with nuclear factor-κB RelA mutated throughout all epithelial cells of the lung and coupled this approach with epithelial cell isolation from infected and uninfected lungs for cell-specific analyses of gene induction. The RelA mutant mice appeared normal basally, but in response to pneumococcus in the lungs they were unable to rapidly recruit neutrophils to the air spaces. Epithelial cells expressed multiple neutrophil-stimulating cytokines during pneumonia, all of which depended on RelA. Cytokine expression by nonepithelial cells was unaltered by the epithelial mutation of RelA. Epithelial cells were the predominant sources of CXCL5 and granulocyte-macrophage colony-stimulating factor (GM-CSF), whereas nonepithelial cells were major sources for other neutrophil-activating cytokines. Epithelial RelA mutation decreased whole lung levels of CXCL5 and GM-CSF during pneumococcal pneumonia, whereas lung levels of other neutrophil-recruiting factors were unaffected. Defective neutrophil recruitment in epithelial mutant mice could be rescued by administration of CXCL5 or GM-CSF. These results reveal a specialized immune function for the pulmonary epithelium, the induction of CXCL5 and GM-CSF, to accelerate neutrophil recruitment in the infected lung.

  10. Integrin αβ3-Targeted Imaging of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoyuan Chen

    2005-03-01

    Full Text Available A series of radiolabeled cyclic arginine-glycineaspartic acid (RGD peptide ligands for cell adhesion molecule integrin αβ3-targeted tumor angiogenesis targeting are being developed in our laboratory. In this study, this effort continues by applying a positron emitter 64Cu-labeled PEGylated dimeric RGD peptide radiotracer 64Cu-DOTA-PEG-E[c(RGDyK]2 for lung cancer imaging. The PEGylated RGD peptide indicated integrin αβ3 avidity, but the PEGylation reduced the receptor binding affinity of this ligand compared to the unmodified RGD dimer. The radiotracer revealed rapid blood clearance and predominant renal clearance route. The minimum nonspecific activity accumulation in normal lung tissue and heart rendered high-quality orthotopic lung cancer tumor images, enabling clear demarcation of both the primary tumor at the upper lobe of the left lung, as well as metastases in the mediastinum, contralateral lung, diaphragm. As a comparison, fluorodeoxyglucose (FDG scans on the same mice were only able to identify the primary tumor, with the metastatic lesions masked by intense cardiac uptake and high lung background. 64Cu-DOTA-PEGE[c(RGDyK]2 is an excellent positron emission tomography (PET tracer for integrin-positive tumor imaging. Further studies to improve the receptor binding affinity of the tracer and subsequently to increase the magnitude of tumor uptake without comprising the favorable in vivo kinetics are currently in progress.

  11. [Metabonomics study of lung cancer cells based on liquid l chromatography-mass spectrometry].

    Science.gov (United States)

    Yu, Xinwei; Wu, Qian; Lu, Wang; Wang, Yan; Ma, Xiaoqiong; Chen, Zhe; Yan, Chao

    2013-07-01

    The metabolic profiles of the polar metabolites and the non-polar metabolites in lung tumor cell lines H358, A549, HCC827, H1299, Calu-3, Calu-l, PC-9 and normal cell line MRC-5 were analyzed separately using high performance liquid chromatography-quadrupole time-of flight mass spectrometry (HPLC-Q-TOF/MS). Partial least square discriminant analysis ( PLS-DA) was used to process the metabolic data. The results showed that the metabolites of the lung cancer cell lines and normal cell line have significant differences. Further, 10 polar metabolites and 21 non-polar metabolites which had a significant contribution to classification were selected and preliminarily identified due to the accurate mass. Comparing with the normal cell line, the lung tumor cell lines present an abnormal metabolism in protein, fatty acid, and phospholipids. These results may provide important information for the early diagnosis of lung cancer.

  12. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

  13. Interstitial lung disease

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950308 Inhibition of mRNA expression of sillicoticcollagen gene by tetrandrine.HE Yuxian(何玉先),etal.Occup Med Instit,CAMS,Beijing,100050.Chin JPrev Med 1995;29(1):18-20.Effects of tetrandrine(TT) on types Ⅰ and Ⅱ col-lagen gene mRNA in lung tissues of silicotic rats werestudied with RNA dot blot and in situ hybridizatin bycDNA coding human and mouse Proα1(Ⅰ) and Proα1(Ⅲ) collagen.Results revealed that types Ⅰ and Ⅲcollagen gene mRNA content in lung tissues of rats ex-posed to silica dust for two to four months was obvi-

  14. Development of Antisense Therapeutic and Imaging Agents to Detect and Suppress Inducible Nitric Oxide Synthase (iNOS) Expression in Acute Lung Injury (ALI)

    Science.gov (United States)

    Shen, Yuefei

    This dissertation focuses on the development and investigation of antisense imaging and therapeutic agents, combined with nanotechnology, to detect and suppress inducible nitric oxide synthase (iNOS) expression for the diagnosis and treatment of acute lung injury (ALI). To achieve this goal, several efforts were made. The first effort was the identification and characterization of high binding affinity antisense peptide nucleic acids (PNAs) and shell-crosslinked knedel-like nanoparticle (SCK)-PNA conjugates to the iNOS mRNA. Antisense binding sites on the iNOS mRNA were first mapped by a procedure for rapidly generating a library of antisense accessible sites on native mRNAs (MASL) which involves reverse transcription of whole cell mRNA extracts with a random oligodeoxynucleotide primer followed by mRNA-specific PCR. Antisense PNAs against the antisense accessible sites were accordingly synthesized and characterized. The second effort was the investigation of cationic shell crosslinked knedel-like nanoparticle (cSCK)-mediated siRNA delivery to suppress iNOS expression for the treatment of ALI. siRNA with its unique gene-specific properties could serve as a promising therapeutic agent, however success in this area has been challenged by a lack of efficient biocompatible transfection agents. cSCK with its nanometer size and positive charge previously showed efficient cellular delivery of phosphorothioate ODNs (oligodeoxynucleotides), plasmid DNA and PNA. Herein, cSCK showed good siRNA binding and facilitated efficient siRNA transfection in HeLa, a mouse macrophage cell line and other human cell lines. cSCK led to greater silencing efficiency than Lipofectamine 2000 in HeLa cells as determined by the viability following transfection with cytotoxic and non-cytotoxic siRNAs, as well in 293T and HEK cells, and was comparable in BEAS-2B and MCF10a cells. The third effort was the preparation of an iNOS imaging probe through electrostatic complexation between a radiolabeled

  15. Nutrition aspects of lung cancer.

    Science.gov (United States)

    Cranganu, Andreea; Camporeale, Jayne

    2009-12-01

    Lung cancer is the most common type of cancer, excluding nonmelanoma skin cancer, and is the leading cause of cancer death in the United States. Notable carcinogens involved in the development of lung cancer include smoking, secondhand smoke, and radon. Lung cancer is divided into 2 major types: non-small-cell lung cancer, the most prevalent, and small-cell lung cancer. Treatment includes surgery, chemotherapy, radiation, or a combination of the same. Medical nutrition therapy is often required for nutrition-related side effects of cancer treatment, which include but are not limited to anorexia, nausea and vomiting, and esophagitis. The best protection against lung cancer is avoidance of airborne carcinogens and increased consumption of fruits and vegetables. Studies have shown that smokers taking large amounts of beta-carotene and vitamin A supplements had increased lung cancer incidence and mortality. However, ingestion of beta-carotene from foods, along with a diet rich in fruits and vegetables, has a protective role against lung disease. The use of complementary and alternative medicine by lung cancer patients is prevalent; therefore, clinicians should investigate whether complementary and alternative therapies are used by patients and advise them on the use of these therapies to avoid any potential side effects and interactions with conventional therapies. The article concludes with a case study of a patient with non-small-cell lung cancer and illustrates the use of medical nutrition therapy in relation to cancer treatment side effects.

  16. Angiosarcoma of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Grafino, Monica; Alves, Paula; Almeida, Margarida Mendes de; Garrido, Patricia; Hasmucrai, Direndra; Teixeira, Encarnacao; Sotto-Mayor, Renato, E-mail: mgrafino@gmail.com [Centro Hospitalar Lisboa Norte, EPE, Lisboa (Portugal)

    2016-06-01

    Angiosarcoma is a rare malignant vascular tumor. Pulmonary involvement is usually attributable to metastasis from other primary sites, primary pulmonary angiosarcoma therefore being quite uncommon. We report a case of angiosarcoma with pulmonary involvement, probably primary to the lung, which had gone untreated for more than two years. We describe this rare neoplasm and its growth, as well as the extensive local invasion and hematogenous metastasis at presentation. We also discuss its poor prognosis. (author)

  17. Lungs in Heart Failure

    Directory of Open Access Journals (Sweden)

    Anna Apostolo

    2012-01-01

    Full Text Available Lung function abnormalities both at rest and during exercise are frequently observed in patients with chronic heart failure, also in the absence of respiratory disease. Alterations of respiratory mechanics and of gas exchange capacity are strictly related to heart failure. Severe heart failure patients often show a restrictive respiratory pattern, secondary to heart enlargement and increased lung fluids, and impairment of alveolar-capillary gas diffusion, mainly due to an increased resistance to molecular diffusion across the alveolar capillary membrane. Reduced gas diffusion contributes to exercise intolerance and to a worse prognosis. Cardiopulmonary exercise test is considered the “gold standard” when studying the cardiovascular, pulmonary, and metabolic adaptations to exercise in cardiac patients. During exercise, hyperventilation and consequent reduction of ventilation efficiency are often observed in heart failure patients, resulting in an increased slope of ventilation/carbon dioxide (VE/VCO2 relationship. Ventilatory efficiency is as strong prognostic and an important stratification marker. This paper describes the pulmonary abnormalities at rest and during exercise in the patients with heart failure, highlighting the principal diagnostic tools for evaluation of lungs function, the possible pharmacological interventions, and the parameters that could be useful in prognostic assessment of heart failure patients.

  18. Discrimination and quantification of autofluorescence spectra of human lung cells

    Science.gov (United States)

    Rahmani, Mahya; Khani, Mohammad Mehdi; Khazaei Koohpar, Zeinab; Molik, Paria

    2016-10-01

    To study laser-induced autofluorescence spectroscopy of the human lung cell line, we evaluated the native fluorescence properties of cancer QU-DB and normal MRC-5 human lung cells during continuous exposure to 405 nm laser light. Two emission bands centered at ~470 nm and ~560 nm were observed. These peaks are most likely attributable to mitochondrial fluorescent reduced nicotinamide adenine dinucleotide and riboflavin fluorophores, respectively. This article highlights lung cell autofluorescence characterization and signal discrimination by collective investigation of different spectral features. The absolute intensity, the spectral shape factor or redox ratio, the full width of half-maximum and the full width of quarter maximum was evaluated. Moreover, the intensity ratio, the area under the peak and the area ratio as a contrast factor for normal and cancerous cells were also calculated. Among all these features it seems that the contrast factor precisely and significantly discriminates the spectral differences of normal and cancerous lung cells. On the other hand, the relative quantum yield for both cell types were found by comparing the quantum yield of an unknown compound with known fluorescein sodium as a reference solution.

  19. Study of differential proteins in lung adenocarcinoma using laser capture microdissection combined with liquid chip-mass spectrometry technology

    Institute of Scientific and Technical Information of China (English)

    BU Li-na; LIN Xiu-li; LIU Yan-feng; LIN Yu-rong; RONG Biao-xue; YANG Shuan-ying; LI Feng-tao; SHANG Wen-li; ZHANG Wei; HUO Shu-fen; NAN Yan-dong; TIAN Ying-xuan; DU Jie

    2010-01-01

    Background In recent years the proportion of lung adenocarcinoma (adCA) which occurs in lung cancer patients has increased. Using laser capture microdissection (LCM) combined with liquid chip-mass spectrometry technology, we aimed to screen lung cancer biomarkers by studying the proteins in the tissues of adCA.Methods We used LCM and magnetic bead based weak cation exchange (MB-WCX) to separate and purify the homogeneous adCA cells and normal calls from six cases of fresh adCA and matched normal lung tissues. The proteins were analyzed and identified by matrix assisted laser desorption/ionization time-of-fight mass spectrometry (MALDI-OF-MS). We screened for the best pattern using a radial basic function neural network algorithm.Results About 2.895x106 and 1.584x106 cells were satisfactorily obtained by LCM from six cases of fresh lung adCA and matched normal lung tissues, respectively. The homogeneities of cell population were estimated to be over 95% as determined by microscopic visualization. Comparing the differentially expressed proteins between the lung adCA and the matched normal lung group, 221 and 239 protein peaks, respectively, were found in the mass-to-charge ration (M/Z)between 800 Da and 10 000 Da. According to t test, the expression of two protein peaks at 7521.5 M/Z and 5079.3 M/Z had the largest difference between tissues. They were more weakly expressed in the lung adCA compared to the matched normal group. The two protein peaks could accurately separate the lung adCA from the matched normal lung group by the sample distribution chart. A discriminatory pattern which can separate the lung adCA from the matched normal lung tissue consisting of three proteins at 3358.1 M/Z, 5079.3 M/Z and 7521.5 M/Z was established by a radial basic function neural network algorithm with a sensitivity of 100% and a specificity of 100%.Conclusions Differential proteins in lung adCA were screened using LCM combined with liquid chip-mass spectrometry technology, and a

  20. Effects of early bronchoalveolar lavage fluid collected from dogs with smoke inhalation injury on the lungs of rats

    Institute of Scientific and Technical Information of China (English)

    NIE Fa-chuan; SU Dong; YANG Zong-cheng; BI Min; HUANG Yue-sheng

    2004-01-01

    Objective: Whether early massive bronchoalveolar lavage can remove the harmful substances from the lungs injured with smoke inhalation remains uncertain. This study was designed to observe the effects of early massive bronchoalveolar lavage fluid (BALF) on the healthy lungs in rats. Methods: Mongrel dogs were inflicted with severe smoke inhalation injury. The injured lungs were lavaged with large amount of normal saline in the first hour after injury and the BALF was collected. The BALF was injected into the healthy lungs of 30 rats (group C) in the dosage of 5 ml/kg. The functions and pathological changes of the lungs were observed 24 h after perfusion with the BALF. The data were compared with those of 23 rats (group B) whose lungs were perfused with the BALF collected from normal dogs and those of 21 rats (group A)whose lungs were perfused with normal saline. Results: The mortality rate 24 h after lung perfusion was higher in group C than in groups A and B. The survivors of group C exhibited fluctuation of respiratory rate (RR), remarkable decrease of PaO2, significantly higher content of lung water, decrease of total static pulmonary compliance and pulmonary expansion index, and increasse of inflammatory cytokines in the tissues of lungs. Only slight mechanic obstructive effect on the airway was observed in rats of group A and B. The pathological changes of the lungs of the rats in group C were similar to those of the dogs with actual smoke inhalation injury. Conclusion: Our findings indicate that the BALF collected from dogs with acute severe smoke inhalation injury in the early stage after injury injured the normal lungs of rats with the bioactive substances in the BALF. These findings show us that it is a valuable therapeutic procedure to apply massive bronchoalveolar fluid lavage in the early stage after inhalation injury.

  1. High-grade primary myxoid lung sarcoma presenting as recurrent hemorrhagic pleural effusions in a young woman.

    Science.gov (United States)

    Tahir, Hassan; Coleman, Cinthia; Sagi, Jahnavi; Wani, Adil; Daruwalla, Vistasp

    2015-01-01

    Primary lung sarcomas are rare but aggressive tumors accounting for less than 0.5% of all lung tumors. The diagnosis of primary lung sarcoma should only be considered after exclusion of other sites. A 32-year-old female presented with recurrent hemorrhagic pleural effusions, shortness of breath and persistent cough. Pleural effusion was drained twice, and each time its analysis was normal. Patient developed atelectasis of left lung with hemothorax for which she underwent video-assisted thoracoscopic surgery. A large mass was found compressing the entire lower lobe of left lung with extension into mediastinum, the biopsy of which showed myxoid sarcoma. The tumor was inoperable and options of chemotherapy or radiotherapy were discussed with the patient. Primary lung sarcoma can rarely present with recurrent hemorrhagic pleural effusion. A high degree of suspicion is required for early diagnosis as large hemothorax on computed tomography or chest X-ray may obscure lung mass and make its diagnosis difficult.

  2. Lung function; Lungenfunktion

    Energy Technology Data Exchange (ETDEWEB)

    Sorichter, S. [Universitaetsklinikum Freiburg, Abteilung Pneumologie, Freiburg (Germany)

    2009-08-15

    The term lung function is often restricted to the assessment of volume time curves measured at the mouth. Spirometry includes the assessment of lung volumes which can be mobilised with the corresponding flow-volume curves. In addition, lung volumes that can not be mobilised, such as the residual volume, or only partially as FRC and TLC can be measured by body plethysmography combined with the determination of the airway resistance. Body plethysmography allows the correct positioning of forced breathing manoeuvres on the volume-axis, e.g. before and after pharmacotherapy. Adding the CO single breath transfer factor (T{sub LCO}), which includes the measurement of the ventilated lung volume using He, enables a clear diagnosis of different obstructive, restrictive or mixed ventilatory defects with and without trapped air. Tests of reversibility and provocation, as well as the assessment of inspiratory mouth pressures (PI{sub max}, P{sub 0.1}) help to classify the underlying disorder and to clarify treatment strategies. For further information and to complete the diagnostic of disturbances of the ventilation, diffusion and/or perfusion (capillar-)arterial bloodgases at rest and under physical strain sometimes amended by ergospirometry are recommended. Ideally, lung function measurements are amended by radiological and nuclear medicine techniques. (orig.) [German] Unter dem Begriff Lungenfunktion wird die Bestimmung der Lungenvolumina am Mund verstanden. Dabei werden die mobilisierbaren Lungenvolumina mit den zugehoerigen Fluss-Volumen-Kurven mittels Spirometrie und Ganzkoerperplethysmographie (GKP) und die nicht (RV) und teilweise mobilisierbaren Lungenvolumina (FRC, TLC) einschliesslich der Atemwegswiderstaende bestimmt. Die GKP ermoeglicht zusaetzlich die korrekte (Volumenachsen-)Positionierung der forcierten Atemmanoever. Dieses erlaubt eine uebersichtlichere graphische Darstellung z. B. vor und nach der Applikation pharmakologisch wirksamer Substanzen. Wird die GKP

  3. Lung function: occupational exposure to wood dust

    Directory of Open Access Journals (Sweden)

    Baran S

    2009-12-01

    Full Text Available Abstract Objectives Occupational exposure to wood dust has been shown to cause several respiratory disorders, such as allergic rhinitis, chronic bronchitis, asthma, sino-nasal adenocarcinoma, and impairment of lung function. The aim of the study was to estimate lung function (in the woodworking industry among workers employed by wood processing, who run the risk of being expose to wood dust. Methods The study concerns a group of 70 workers aged 24-55. All the workers underwent general and laryngological examination. A group of 20 workers, working at the positions where dustiness exceeded TLV (threshold limit value took X-ray of the chest and spirometry. The following parameters were measured: VC, IC, ERV, TV, BF, FEV1, FVC, PEF, MEF25-75, FEV1%FVC, FEV1%VC. The data are presented as means ± SD and the authors applied references values according to ERS guidelines. Results The results show that there was no decline in FEV1 (3.7 ± 0.7 and FVC (4.5 ± 0.8. Normal lung function was defined as FEV1/VC ratio ≥0.7. None of the tested workers had obstructive pattern in spirometry. The mean FEV1%VC was 77.1 ± 10.2. These results suggest that wood dust exposure might not lead to significant pulmonary damage. Conclusions These data do not corroborate that wood dust plays significant role in lung function impairment. Future studies of respiratory health among workers exposed to wood dust are needed.

  4. EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas

    Science.gov (United States)

    Zhang, Yi; Tolani, Bhairavi; Mo, Minli; Zhang, Hua; Zheng, Qingfeng; Yang, Yue; Cheng, Runfen; Jin, Joy Q.; Luh, Thomas W.; Yang, Cathryn; Tseng, Hsin-Hui K.; Giroux-Leprieur, Etienne; Woodard, Gavitt A.; Hao, Xishan; Wang, Changli; Jablons, David M.; He, Biao

    2015-01-01

    Background Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer (NSCLC). Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC. Methods Two independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro. Results EMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration. Conclusions EMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT). EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. PMID:26132438

  5. EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas.

    Directory of Open Access Journals (Sweden)

    Dongsheng Yue

    Full Text Available Squamous cell carcinomas (SCC account for approximately 30% of non-small cell lung cancer (NSCLC. Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC.Two independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro.EMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration.EMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT. EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy.

  6. Lung Cancer Screening and clinical implications

    NARCIS (Netherlands)

    S.C. van 't Westeinde (Susan)

    2012-01-01

    textabstractLung cancer is the most frequently diagnosed major cancer worldwide and the leading cause of death from cancer. Lung cancer is divided into two subgroups: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), accounting for 10-20% and 75% of lung cancer cases, respectivel

  7. The microbiome and the lung.

    Science.gov (United States)

    Cui, Lijia; Morris, Alison; Huang, Laurence; Beck, James M; Twigg, Homer L; von Mutius, Erika; Ghedin, Elodie

    2014-08-01

    Investigation of the human microbiome has become an important field of research facilitated by advances in sequencing technologies. The lung, which is one of the latest body sites being explored for the characterization of human-associated microbial communities, has a microbiome that is suspected to play a substantial role in health and disease. In this review, we provide an overview of the basics of microbiome studies. Challenges in the study of the lung microbiome are highlighted, and further attention is called to the optimization and standardization of methodologies to explore the role of the lung microbiome in health and disease. We also provide examples of lung microbial communities associated with disease or infection status and discuss the role of fungal species in the lung. Finally, we review studies demonstrating that the environmental microbiome can influence lung health and disease, such as the finding that the diversity of microbial exposure correlates inversely with the development of childhood asthma.

  8. Diagnostic Imaging of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Kemal Kara

    2012-12-01

    Full Text Available Lung cancer is the most common cause of cancer related death in men and women. It is frequently seen among men than in women and male-female ratio is 1.5:1. Common epidemiological factors that increase risk of lung cancer is smoking. Early age to start smoking, high number of smoking cigarettes per a day and depth of inhalation increase risk of lung cancer. 25% of patients with lung cancer are nonsmokers that passively exposed to cigarette smoke. Occupational exposure to substances such as asbestos, arsenic, nickel, beryllium, mustard gas increases the risk of lung cancer. The well defined risk factor is exposure to asbestos. In addition advanced age, diffuse pulmonary fibrosis, chronic obstructive pulmonary disease (COPD and genetic predisposition are the risk factors that increases lung cancer. [TAF Prev Med Bull 2012; 11(6.000: 749-756

  9. Nickel accumulation in lung tissues is associated with increased risk of p53 mutation in lung cancer patients.

    Science.gov (United States)

    Chiou, Yu-Hu; Wong, Ruey-Hong; Chao, Mu-Rong; Chen, Chih-Yi; Liou, Saou-Hsing; Lee, Huei

    2014-10-01

    Occupational exposure to nickel compounds has been associated with lung cancer. The correlation between high nickel levels and increased risk of lung cancer has been previously reported in a case-control study. This study assessed whether nickel exposure increased the occurrence of p53 mutations due to DNA repair inhibition by nickel. A total of 189 lung cancer patients were enrolled to determine nickel levels in tumor-adjacent normal lung tissues and p53 mutation status in lung tumors through atomic absorption spectrometry and direct sequencing, respectively. Nickel levels in p53 mutant patients were significantly higher than those in p53 wild-type patients. When patients were divided into high- and low-nickel subgroups by median nickel level, the high-nickel subgroup of patients had an odds ratio (OR) of 3.25 for p53 mutation risk relative to the low-nickel subgroup patients. The OR for p53 mutation risk of lifetime non-smokers, particularly females, in the high-nickel subgroup was greater than that in the low-nickel subgroup. To determine whether nickel affected DNA repair capacity, we conducted the host cell reactivation assay in A549 and H1975 lung cancer cells and showed that the DNA repair activity was reduced by nickel chloride in a dose-dependent manner. This was associated with elevated production of hydrogen peroxide-induced 8-oxo-deoxyguanosine. Therefore, increased risk of p53 mutation due to defective DNA repair caused by high nickel levels in lung tissues may be one mechanism by which nickel exposure contributes to lung cancer development, especially in lifetime female non-smokers.

  10. Morphologic and biochemical changes in male rat lung after surgical and pharmacological castration

    Directory of Open Access Journals (Sweden)

    M.S. Ojeda

    2000-03-01

    Full Text Available The morphology of the rat lung was studied by light microscopy in different situations: after surgical and pharmacological castration and after administration of testosterone to the castrated rat to determine if the androgen is required to maintain the normal morphology of the lung. We also determined the effect of flutamide on the phospholipid composition of both the surfactant and microsomes of the lung. Rats were separated into five groups: I - control non-castrated rats, II - castrated rats sacrificed 21 days after castration, III - castrated rats that received testosterone daily from day 2 to day 21 after castration, IV - castrated rats that received testosterone from day 15 to day 21 after castration, and V - control rats injected with flutamide for 7 days. The amount of different phospholipids in the surfactant and microsomes of the lung was measured in group I and V rats. At the light microscopy level, the surgical and pharmacological castration provoked alterations in the morphology of the lung, similar to that observed in human lung emphysema. The compositions of surfactant and microsomes of the lung were similar to those previously reported by us for the surgically castrated rats. These results indicate that androgens are necessary for the normal morphology as well as for some metabolic aspects of the lung.

  11. Computed tomography of the lungs in acquired immunodeficiency syndrome. An early indicator of interstitial pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Hartelius, H.; Gaub, J.; Jensen, L.I.; Jensen, J.; Faber, V.

    Computed tomography of the chest was performed on 42 occasions as part of the diagnostic work-up in 26 homosexual men with, or suspected of the acquired immunodeficiency syndrome (AIDS). In 17 cases both the chest radiographs and the lung scans were abnormal, and bronchoscopy and/or lung biopsy established an etiologic diagnosis in the majority of these cases. In 9 cases CT of the lungs revealed unequivocal interstitial infiltration in the presence of a normal chest radiography, and subsequently and etiologic agent was demonstrated in all these cases. In 9 cases, patients with symptoms indicative of pulmonary infection had both a normal chest radiograph and a normal lung scan, and in none of these cases did the clinical course or additional diagnostic procedures indicate the presence of current opportunistic lung infection. CT of the lungs seems to identify accurately those patients with severe HIV-related diseases in whom invasive diagnostic procedures such as bronchoalveolar lavage and/or lung biopsy should be done.

  12. Oxygen-sensitive {sup 3}He-MRI in bronchiolitis obliterans after lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Gast, Klaus K. [Klinikum der Johannes Gutenberg-Universitaet, Klinik und Poliklinik fuer diagnostische und interventionelle Radiologie, Mainz (Germany); Biedermann, Alexander [Klinikum der Johannes Gutenberg-Universitaet, 3. Medizinische Klinik, Pulmonologie, Mainz (Germany); Herweling, Annette [Klinikum der Johannes Gutenberg-Universitaet, Klinik fuer Anaesthesiologie, Mainz (Germany); Schreiber, Wolfgang G. [Klinikum der Johannes Gutenberg-Universitaet, Klinik und Poliklinik fuer diagnostische und interventionelle Radiologie, MR-Physik, Mainz (Germany); Schmiedeskamp, Joerg [Max-Planck-Institut fuer Polymerforschung, Mainz (Germany); Mayer, Eckhard [Klinikum der Johannes Gutenberg-Universitaet, Klinik fuer Herz-, Thorax- und Gefaesschirurgie, Mainz (Germany); Heussel, Claus P. [Abteilung fuer Radiologie, Thoraxklinik Heidelberg, Heidelberg (Germany); Markstaller, Klaus; Eberle, Balthasar [Inselspital/Universitaetsspital, Klinik fuer Anaesthesiologie, Bern (Switzerland); Kauczor, Hans-Ulrich [Radiologie, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany)

    2008-03-15

    Oxygen-sensitive {sup 3}He-MRI was studied for the detection of differences in intrapulmonary oxygen partial pressure (pO{sub 2}) between patients with normal lung transplants and those with bronchiolitis obliterans syndrome (BOS). Using software developed in-house, oxygen-sensitive {sup 3}He-MRI datasets from patients with normal lung grafts (n = 8) and with BOS (n = 6) were evaluated quantitatively. Datasets were acquired on a 1.5-T system using a spoiled gradient echo pulse sequence. Underlying diseases were pulmonary emphysema (n = 10 datasets) and fibrosis (n = 4). BOS status was verified by pulmonary function tests. Additionally, {sup 3}He-MRI was assessed blindedly for ventilation defects. Median intrapulmonary pO{sub 2} in patients with normal lung grafts was 146 mbar compared with 108 mbar in patients with BOS. Homogeneity of pO2 distribution was greater in normal grafts (standard deviation pO2 34 versus 43 mbar). Median oxygen decrease rate during breath hold was higher in unaffected patients (-1.75 mbar/s versus -0.38 mbar/s). Normal grafts showed fewer ventilation defects (5% versus 28%, medians). Oxygen-sensitive {sup 3}He-MRI appears capable of demonstrating differences of intrapulmonary pO2 between normal lung grafts and grafts affected by BOS. Oxygen-sensitive {sup 3}He-MRI may add helpful regional information to other diagnostic techniques for the assessment and follow-up of lung transplant recipients. (orig.)

  13. ENO1 Protein Levels in the Tumor Tissues and Circulating Plasma Samples of Non-small Cell Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Ying ZHANG

    2010-12-01

    Full Text Available Background and objective Proper tumor markers are useful to diagnosis, prognosis and treatment for lung cancer. The aim of this study is to examine the levels of alpha-enolase (ENO1 protein in the tumor tissues and peripheral plasma samples obtained from non-small cell lung cancer (NSCLC patients, and evaluate its potential clinical significance. Methods The ENO1 protein levels in the tumor tissues and corresponding normal tissues from 16 cases of lung squamous cell carcinoma were analyzed by Western blot. The ENO1 protein levels in the plasma samples from 42 healthy individuals, 34 patients with lung benign disease and 84 patients with NSCLC were measured by double antibody sandwich enzyme-linked immunosorbent assay. Results For 87.5% (14/16 of the patients with lung squamous cell carcinoma, the ENO1 protein level in the tumor tissues was higher than that in the corresponding normal lung tissues. The ENO1 protein level in the plasma of NSCLC patients was significantly higher than that in the plasma of healthy individuals (P=0.031 and patients with lung benign disease (P=0.019. Furthermore, the ENO1 protein level was significantly higher in the plasma of patients with lung adenocarcinoma than that of patients with lung squamous cell carcinoma. Conclusion The elevated levels of ENO1 protein in the tumor tissues and the plasma samples from NSCLC patients indicate ENO1 may be a candidate biomarker of lung cancer.

  14. Revisiting the Process of Normalization.

    Science.gov (United States)

    Zener, Rita Schaefer

    1999-01-01

    Defines normalization and deviations in child development. Discusses the three different levels in the normalization process. Asserts that guiding the process of normalization should drive the practice of Montessori education. Concludes that whenever there are brief episodes of normalization, the true nature of the child shows itself. (JS)

  15. A treatment planning study of the potential of geometrical tracking for intensity modulated proton therapy of lung cancer

    DEFF Research Database (Denmark)

    af Rosenschöld, Per Munck; Aznar, Marianne C; Nygaard, Ditte E;

    2010-01-01

    Proton therapy of lung cancer holds the potential for a reduction of the volume of irradiated normal lung tissue. In this work we investigate the robustness of intensity modulated proton therapy (IMPT) plans to motion, and evaluate a geometrical tumour tracking method to compensate for tumour...

  16. Normal transmitting boundary conditions

    Institute of Scientific and Technical Information of China (English)

    廖振鹏

    1996-01-01

    The multi-transmitting formula (MTF) governed by a single artificial speed is analytically developed into a generalized MTF governed by a few artificial speeds to improve its capacity in simultaneous simulation of several one-way waves propagating at different speeds.The generalized MTF is then discretized and further generalized using the space extrapolation to improve its accuracies in numerical simulation of transient waves at large angles of incidence.The above two successive generalizitions of MTF based on the notion of normal transmission lead to a compact formula of local non-reflecting boundary condition.The formula not only provides a general representation of the major schemes of existing local boundary conditions but can be used to generate new schemes,which combine advantages of different schemes.

  17. Evaluating the Normal Distribution

    Directory of Open Access Journals (Sweden)

    George Marsaglia

    2004-07-01

    Full Text Available This article provides a little table-free C function that evaluates the normal distribution with absolute error less than 8 x 10 -16 . A small extension provides relative error near the limit available in double precision: 14 to 16 digits, the limits determined mainly by the computer's ability to evaluate exp(-t for large t. Results are compared with those provided by calls to erf or erfc functions, the best of which compare favorably, others do not, and all appear to be much more complicated than need be to get either absolute accuracy less than 10-15 or relative accuracy to the exp(-limited 14 to 16 digits. Also provided: A short history of the error function erf and its intended use, as well as, in the "browse files" attachment, various erf or erfc versions used for comparison.

  18. Size matching in lung transplantation using predicted total lung capacity

    NARCIS (Netherlands)

    Ouwens, JP; van der Mark, TW; van der Bij, W; Koeter, GH

    2002-01-01

    Height is used in allocation of donor lungs as an indirect estimate of thoracic size. Total lung capacity (TLC), determined by both height and sex, could be a more accurate functional estimation of thoracic size. Size-matching criteria based on height versus predicted TLC was retrospectively evaluat

  19. Lung Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of people getting lung cancer or dying from lung cancer varies by race ...

  20. What Are Asbestos-Related Lung Diseases?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Are Asbestos-Related Lung Diseases? Asbestos-related lung diseases are ... as the peritoneum (PER-ih-to-NE-um). Asbestos-Related Lung Diseases Figure A shows the location ...

  1. Potential targets for lung squamous cell carcinoma

    Science.gov (United States)

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  2. Lung Tumor Segmentation Using Electric Flow Lines for Graph Cuts

    DEFF Research Database (Denmark)

    Hollensen, Christian; Cannon, George; Cannon, Donald;

    2012-01-01

    Lung cancer is the most common cause of cancer-related death. A common treatment is radiotherapy where the lung tumors are irradiated with ionizing radiation. The treatment is typically fractionated, i.e. spread out over time, allowing healthy tissue to recover between treatments and allowing tumor...... cells to be hit in their most sensitive phase. Changes in tumors over the course of treatment allows for an adaptation of the radiotherapy plan based on 3D computer tomography imaging. This paper introduces a method for segmentation of lung tumors on consecutive computed tomography images. These images...... are normally only used for correction of movements. The method uses graphs based on electric flow lines. The method offers several advantages when trying to replicate manual segmentations. The method gave a dice coefficient of 0.85 and performed better than level set methods and deformable registration....

  3. Advances in lung ultrasound; Avancos na ultrassonografia pulmonar

    Energy Technology Data Exchange (ETDEWEB)

    Francisco Neto, Miguel Jose; Rahal Junior, Antonio; Vieira, Fabio Augusto Cardillo; Silva, Paulo Savoia Dias da; Funari, Marcelo Buarque de Gusmao, E-mail: miguelneto@einstein.br [Hospital Israelita Albert Einstein, Sao Paulo, SP (Brazil)

    2016-11-01

    Ultrasound examination of the chest has advanced in recent decades. This imaging modality is currently used to diagnose several pathological conditions and provides qualitative and quantitative information. Acoustic barriers represented by the aerated lungs and the bony framework of the chest generate well-described sonographic artifacts that can be used as diagnostic aids. The normal pleural line and A, B, C, E and Z lines (also known as false B lines) are artifacts with specific characteristics. Lung consolidation and pneumothorax sonographic patterns are also well established. Some scanning protocols have been used in patient management. The Blue, FALLS and C.A.U.S.E. protocols are examples of algorithms using artifact combinations to achieve accurate diagnoses. Combined chest ultrasonography and radiography are often sufficient to diagnose and manage lung and chest wall conditions. Chest ultrasonography is a highly valuable diagnostic tool for radiologists, emergency and intensive care physicians. (author)

  4. Interstitial lung disease

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930124 The effect of glycosaminoglycans inthe genesis of pulmonary interstitial fibrosis.LIBaoyu(李保玉),et al.Dept Pathol,Jilin MedColl,132001.Chin J Tuberc & Respir Dis 1992;15(4):204-205.The pulmonary interstitial fibrosis was causedby injecting Bleomycin into mouse trachea.Afterthe injection,the volume of glycosaminoglycans(GAG)in bronchoalveolar lavage fluid and lungtissues was increased.The observation underhistochemical stain and electron microscopeshowed that the distribution of GAG in lung tis-sues was varied at different time after the injec-tion,and related to the volume of collagen pro-teins and the formation of pulmonary interstitialfibrosis.

  5. Interstitial lung disease

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930512 Changes of interleukin—I released bypulmonary alveolar macrophage in patients withinterstitial lung disease.LI Zhenhua(李振华),etal.Respir Dis Instit,China Med Univ,Shengyang,110001.Chin J Tuberc & Respir Dis1993;16(2):90—92.To evaluate the activity of PAM,levels of IL-l released by PAM in patients with ILD(nonsmokers)were measured by usinglipopolysacharide(LPS)stimulation and thymo-cyte proliferation method,with healthy non-smokers as control group.The results showed

  6. Quantitative measurement of regional lung gas volume by synchrotron radiation computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Monfraix, Sylvie [European Synchrotron Radiation Facility, BP 220, F-38043 Grenoble (France); Bayat, Sam [European Synchrotron Radiation Facility, BP 220, F-38043 Grenoble (France); Porra, Liisa [Department of Physical Sciences, University of Helsinki, POB 64, FIN-00014 Helsinki (Finland); Berruyer, Gilles [European Synchrotron Radiation Facility, BP 220, F-38043 Grenoble (France); Nemoz, Christian [European Synchrotron Radiation Facility, BP 220, F-38043 Grenoble (France); Thomlinson, William [Canadian Light Source, 101 Perimeter Road, Saskatoon, SK S7N 0X4 (Canada); Suortti, Pekka [Department of Physical Sciences, University of Helsinki, POB 64, FIN-00014 Helsinki (Finland); Sovijaervi, Anssi R A [Department of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, POB 340, FIN-00029 HUS, Helsinki (Finland)

    2005-01-07

    The aim of this study was to assess the feasibility of a novel respiration-gated spiral synchrotron radiation computed tomography (SRCT) technique for direct quantification of absolute regional lung volumes, using stable xenon (Xe) gas as an inhaled indicator. Spiral SRCT with K-edge subtraction using two monochromatic x-ray beams was used to visualize and directly quantify inhaled Xe concentrations and airspace volumes in three-dimensional (3D) reconstructed lung images. Volume measurements were validated using a hollow Xe-filled phantom. Spiral images spanning 49 mm in lung height were acquired following 60 breaths of an 80% Xe-20% O{sub 2} gas mixture, in two anaesthetized and mechanically ventilated rabbits at baseline and after histamine aerosol inhalation. Volumetric images of 20 mm lung sections were obtained at functional residual capacity (FRC) and at end-inspiration. 3D images showed large patchy filling defects in peripheral airways and alveoli following histamine provocation. Local specific lung compliance was calculated based on FRC/end-inspiration images in normal lung. This study demonstrates spiral SRCT as a new technique for direct determination of regional lung volume, offering possibilities for non-invasive investigation of regional lung function and mechanics, with a uniquely high spatial resolution. An example of non-uniform volume distribution in rabbit lung following histamine inhalation is presented.

  7. Modeling the nuclear magnetic resonance behavior of lung: from electrical engineering to critical care medicine.

    Science.gov (United States)

    Cutillo, A G; Ailion, D C

    1999-01-01

    The present article reviews the basic principles of a new approach to the characterization of pulmonary disease. This approach is based on the unique nuclear magnetic resonance (NMR) properties of the lung and combines experimental measurements (using specially developed NMR techniques) with theoretical simulations. The NMR signal from inflated lungs decays very rapidly compared with the signal from completely collapsed (airless) lungs. This phenomenon is due to the presence of internal magnetic field inhomogeneity produced by the alveolar air-tissue interface (because air and water have different magnetic susceptibilities). The air-tissue interface effects can be detected and quantified by magnetic resonance imaging (MRI) techniques using temporally symmetric and asymmetric spin-echo sequences. Theoretical models developed to explain the internal (tissue-induced) magnetic field inhomogeneity in aerated lungs predict the NMR lung behavior as a function of various technical and physiological factors (e.g., the level of lung inflation) and simulate the effects of various lung disorders (in particular, pulmonary edema) on this behavior. Good agreement has been observed between the predictions obtained from the mathematical models and the results of experimental NMR measurements in normal and diseased lungs. Our theoretical and experimental data have important pathophysiological and clinical implications, especially with respect to the characterization of acute lung disease (e.g., pulmonary edema) and the management of critically ill patients.

  8. Reduction of Pulmonary Function After Surgical Lung Resections of Different Volume

    Science.gov (United States)

    Cukic, Vesna

    2014-01-01

    Introduction: In recent years an increasing number of lung resections are being done because of the rising prevalence of lung cancer that occurs mainly in patients with limited lung function, what is caused with common etiologic factor - smoking cigarettes. Objective: To determine how big the loss of lung function is after surgical resection of lung of different range. Methods: The study was done on 58 patients operated at the Clinic for thoracic surgery KCU Sarajevo, previously treated at the Clinic for pulmonary diseases “Podhrastovi” in the period from 01.06.2012. to 01.06.2014. The following resections were done: pulmectomy (left, right), lobectomy (upper, lower: left and right). The values of postoperative pulmonary function were compared with preoperative ones. As a parameter of lung function we used FEV1 (forced expiratory volume in one second), and changes in FEV1 are expressed in liters and in percentage of the recorded preoperative and normal values of FEV1. Measurements of lung function were performed seven days before and 2 months after surgery. Results: Postoperative FEV1 was decreased compared to preoperative values. After pulmectomy the maximum reduction of FEV1 was 44%, and after lobectomy it was 22% of the preoperative values. Conclusion: Patients with airway obstruction are limited in their daily life before the surgery, and an additional loss of lung tissue after resection contributes to their inability. Potential benefits of lung resection surgery should be balanced in relation to postoperative morbidity and mortality. PMID:25568542

  9. Pressure-volume characteristics of lungs of rats during pregnancy and postpartum.

    Science.gov (United States)

    Faridy, E E

    1981-01-01

    Measurements of lung volumes in pregnant women show that the functional residual capacity and residual volume are reduced by 17-25% at late pregnancy. The present study was conducted to test the hypothesis that a decrease in FRC at pregnancy may result from an increase in retractive forces of the lung. The air and saline pressure-volume characteristics of excised lungs were studied in rats daily during pregnancy and the postpartum period. In comparison to non-pregnancy rats, the air PV measurements indicated that: (1) the retractive forces of the lungs were increased late in pregnancy resulting in reduction in both MLV (lung air volume at 40 cm H2O Ptp) and in V%10 (volume at 10/volume at 40 cm H2O Ptp X 100); (2) MLV was greater in lactating than in non-lactating and in non-pregnant rats. Lung saline volume was also greater in lactating than in non-lactating rats at early postpartum period. Lung phospholipids content was increased at late pregnancy and in lactating rats; (3) there was an increase in MLV and in V% immediately after delivery and 2-3 days after an abrupt cessation of lactation ("dried" rats). The minimal surface tension of lung lavages also decreased in these rats. A shift to that left of the air PV curve in "dried" rats suggest that under normal circumstances lung surface forces are not at their lowest.

  10. Role of hyaluronan and hyaluronan-binding proteins in lung pathobiology.

    Science.gov (United States)

    Lennon, Frances E; Singleton, Patrick A

    2011-08-01

    Hyaluronan (HA) has diverse functions in normal lung homeostasis and pulmonary disease. HA constitutes the major glycosaminoglycan in lung tissue, with HA degradation products, produced by hyaluronidase enzymes and reactive oxygen species, being implicated in several lung diseases, including acute lung injury, asthma, chronic obstructive pulmonary disease, and pulmonary hypertension. The differential activities of HA and its degradation products are due, in part, to regulation of multiple HA-binding proteins, including cluster of differentiation 44 (CD44), Toll-like receptor 4 (TLR4), HA-binding protein 2 (HABP2), and receptor for HA-mediated motility (RHAMM). Recent research indicates that exogenous administration of high-molecular-weight HA can serve as a novel therapeutic intervention for lung diseases, including lipopolysaccharide (LPS)-induced acute lung injury, sepsis/ventilator-induced lung injury, and airway hyperreactivity. This review focuses on the regulatory role of HA and HA-binding proteins in lung pathology and discusses the capacity of HA to augment and inhibit various lung diseases.

  11. Lung Cancer and Interstitial Lung Diseases: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Kostas Archontogeorgis

    2012-01-01

    Full Text Available Interstitial lung diseases (ILDs represent a heterogeneous group of more than two hundred diseases of either known or unknown etiology with different pathogenesis and prognosis. Lung cancer, which is the major cause of cancer death in the developed countries, is mainly attributed to cigarette smoking and exposure to inhaled carcinogens. Different studies suggest a link between ILDs and lung cancer, through different pathogenetic mechanisms, such as inflammation, coagulation, dysregulated apoptosis, focal hypoxia, activation, and accumulation of myofibroblasts as well as extracellular matrix accumulation. This paper reviews current evidence on the association between lung cancer and interstitial lung diseases such as idiopathic pulmonary fibrosis, sarcoidosis, systemic sclerosis, dermatomyositis/polymyositis, rheumatoid arthritis, systemic lupus erythematosus, and pneumoconiosis.

  12. Normal labour: a concept analysis.

    Science.gov (United States)

    Gould, D

    2000-02-01

    Midwives practice within the normal childbirth paradigm. It is argued that midwives failure to define normality has allowed increasing technicalization and medicalization of the normal physiological process of birth because doctors so closely define abnormality. A concept analysis model is used to clarify what is meant by the term 'normal labour'; the emphasis being on understanding what normal labour is as it applies to midwifery practice today. This analysis highlights the importance of movement and the sequential nature of normal labour, and reveals how this is implicit within the other uses of both the words normal and labour. The final definition of normal labour offered is intended to be complimentary to existing medical determinants of progress of normal labour, because as the body of the text stresses, medical knowledge is fundamentally enmeshed in midwifery care.

  13. Expression of Thyroid Transcription Factor-1 (TTF-1) in Lung Carcinomas and Its Correlations with Apoptosis and Angiogenesis

    Institute of Scientific and Technical Information of China (English)

    Xiaoyan Bai; Hong Shen; Chunhui Zhou; Hao Wang

    2009-01-01

    OBJECTIVE To investigate the correlations between the expression of thyroid transcription factor-1 (TTF-1) and apoptosis and angiogenesis in lung carcinomas.METHODS A 829 microarray of the paraffin tissue chips was constructed, which contained 196 lung carcinomas, 10 normal lung tissues, and 1 muscular tissue. Terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) and immunohistochemical SP method were used to detect apoptosis and expression of TTF-1 and CD34 in different types of lung carcinomas. A Leica Q500 MC image analysis system was used to measure and calculate TTF-1 positive unit (PU), apoptotic index (AI) and microvessel density (MVD).RESULTS AI of lung small cell carcinoma and large cell carcinoma were smaller than those of lung adenocarcinoma and squamous cell carcinoma (P = 0.000). AI of lung carcinomas with lymph node metastases was smaller than that of those without (P = 0.039). AI of lung carcinomas in TNM stage I-W was smaller than that in stage Ⅰ (P = 0.008). The PU of the TTF-1 was negatively correlated with AI in small cell lung carcinoma (r = -0.752, P = 0.000). MVD of lung carcinomas without lymph node metastases was smaller than that of those with lymph node metastasis (P= 0.031). MVD of lung carcinomas in TNM stage Ⅰ was smaller than that in stage Ⅰ-Ⅳ (P -- 0.040). The PU of TTF-1 was positively correlated with MVD in lung adenocarcinoma (r = 0.708, P = 0.000).CONCLUSION There is a negative correlation between TTF-1 PU and AI in small cell lung carcinoma. TTF-1 PU and AI may be correlated with each other. There is a positive correlation between TTF-1 PU and MVD in lung adenocarcinoma. TTF-1 may induce the development of lung adenocarcinoma by inducing tumor angiogenesis.

  14. Bricklayers and lung cancer risk

    NARCIS (Netherlands)

    Cremers, Jan

    2014-01-01

    The article ‘Lung cancer risk among bricklayers in a pooled analysis of case–control studies’ in the International Journal of Cancer publishes findings of an epidemiological study (in the frame of a SYNERGY-project) dedicated to the lung cancer risk among bricklayers. The authors conclude that a foc

  15. Epigenetic Therapy in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Stephen V Liu

    2013-05-01

    Full Text Available Epigenetic dysregulation of gene function has been strongly implicated in carcinogenesis and is one of the mechanisms contributing to the development of lung cancer. The inherent reversibility of epigenetic alterations makes them viable therapeutic targets. Here, we review the therapeutic implications of epigenetic changes in lung cancer, and recent advances in therapeutic strategies targeting DNA methylation and histone acetylation.

  16. [Post-traumatic lung herniation

    NARCIS (Netherlands)

    WIjs, M.J. de; Verhagen, A.F.T.M.; Tan, E.C.T.H.

    2012-01-01

    BACKGROUND: Post-traumatic lung herniation due to a pathological defect in the chest wall is rare. CASE DESCRIPTION: We present a 73-year-old polytrauma patient who had extensive chest wall trauma after an accident, resulting in traumatic herniation of the lung. The patient was initially treated acc

  17. A lung function information system

    NARCIS (Netherlands)

    A.F.M. Verbraak (Anton); E.J. Hoorn (Ewout); J. de Vries (Julius); J.M. Bogaard (Jan); A. Versprille (Adrian)

    1991-01-01

    markdownabstractAbstract A lung function information system (LFIS) was developed for the data analysis of pulmonary function tests at different locations. This system was connected to the hospital information system (HIS) for the retrieval of patient data and the storage of the lung function varia

  18. Lung transplantation for cystic fibrosis

    NARCIS (Netherlands)

    Adler, Frederick R; Aurora, Paul; Barker, David H; Barr, Mark L; Blackwell, Laura S; Bosma, Otto H; Brown, Samuel; Cox, D R; Jensen, Judy L; Kurland, Geoffrey; Nossent, George D; Quittner, Alexandra L; Robinson, Walter M; Romero, Sandy L; Spencer, Helen; Sweet, Stuart C; van der Bij, Wim; Vermeulen, J; Verschuuren, Erik A M; Vrijlandt, Elianne J L E; Walsh, William; Woo, Marlyn S; Liou, Theodore G

    2009-01-01

    Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing

  19. SIV Infection of Lung Macrophages.

    Directory of Open Access Journals (Sweden)

    Yue Li

    Full Text Available HIV-1 depletes CD4+ T cells in the blood, lymphatic tissues, gut and lungs. Here we investigated the relationship between depletion and infection of CD4+ T cells in the lung parenchyma. The lungs of 38 Indian rhesus macaques in early to later stages of SIVmac251 infection were examined, and the numbers of CD4+ T cells and macrophages plus the frequency of SIV RNA+ cells were quantified. We showed that SIV infected macrophages in the lung parenchyma, but only in small numbers except in the setting of interstitial inflammation where large numbers of SIV RNA+ macrophages were detected. However, even in this setting, the number of macrophages was not decreased. By contrast, there were few infected CD4+ T cells in lung parenchyma, but CD4+ T cells were nonetheless depleted by unknown mechanisms. The CD4+ T cells in lung parenchyma were depleted even though they were not productively infected, whereas SIV can infect large numbers of macrophages in the setting of interstitial inflammation without depleting them. These observations point to the need for future investigations into mechanisms of CD4+ T cell depletion at this mucosal site, and into mechanisms by which macrophage populations are maintained despite high levels of infection. The large numbers of SIV RNA+ macrophages in lungs in the setting of interstitial inflammation indicates that lung macrophages can be an important source for SIV persistent infection.

  20. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Kai, E-mail: gk161@163.com [Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Department of Respiration, 161th Hospital, PLA, Wuhan 430015 (China); Jin, Faguang, E-mail: jinfag@fmmu.edu.cn [Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)

    2015-09-25

    The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells.

  1. Polonium and lung cancer.

    Science.gov (United States)

    Zagà, Vincenzo; Lygidakis, Charilaos; Chaouachi, Kamal; Gattavecchia, Enrico

    2011-01-01

    The alpha-radioactive polonium 210 (Po-210) is one of the most powerful carcinogenic agents of tobacco smoke and is responsible for the histotype shift of lung cancer from squamous cell type to adenocarcinoma. According to several studies, the principal source of Po-210 is the fertilizers used in tobacco plants, which are rich in polyphosphates containing radio (Ra-226) and its decay products, lead 210 (Pb-210) and Po-210. Tobacco leaves accumulate Pb-210 and Po-210 through their trichomes, and Pb-210 decays into Po-210 over time. With the combustion of the cigarette smoke becomes radioactive and Pb-210 and Po-210 reach the bronchopulmonary apparatus, especially in bifurcations of segmental bronchi. In this place, combined with other agents, it will manifest its carcinogenic activity, especially in patients with compromised mucous-ciliary clearance. Various studies have confirmed that the radiological risk from Po-210 in a smoker of 20 cigarettes per day for a year is equivalent to the one deriving from 300 chest X-rays, with an autonomous oncogenic capability of 4 lung cancers per 10000 smokers. Po-210 can also be found in passive smoke, since part of Po-210 spreads in the surrounding environment during tobacco combustion. Tobacco manufacturers have been aware of the alpha-radioactivity presence in tobacco smoke since the sixties.

  2. Polonium and Lung Cancer

    Directory of Open Access Journals (Sweden)

    Vincenzo Zagà

    2011-01-01

    Full Text Available The alpha-radioactive polonium 210 (Po-210 is one of the most powerful carcinogenic agents of tobacco smoke and is responsible for the histotype shift of lung cancer from squamous cell type to adenocarcinoma. According to several studies, the principal source of Po-210 is the fertilizers used in tobacco plants, which are rich in polyphosphates containing radio (Ra-226 and its decay products, lead 210 (Pb-210 and Po-210. Tobacco leaves accumulate Pb-210 and Po-210 through their trichomes, and Pb-210 decays into Po-210 over time. With the combustion of the cigarette smoke becomes radioactive and Pb-210 and Po-210 reach the bronchopulmonary apparatus, especially in bifurcations of segmental bronchi. In this place, combined with other agents, it will manifest its carcinogenic activity, especially in patients with compromised mucous-ciliary clearance. Various studies have confirmed that the radiological risk from Po-210 in a smoker of 20 cigarettes per day for a year is equivalent to the one deriving from 300 chest X-rays, with an autonomous oncogenic capability of 4 lung cancers per 10000 smokers. Po-210 can also be found in passive smoke, since part of Po-210 spreads in the surrounding environment during tobacco combustion. Tobacco manufacturers have been aware of the alpha-radioactivity presence in tobacco smoke since the sixties.

  3. Mitochondria in lung disease.

    Science.gov (United States)

    Cloonan, Suzanne M; Choi, Augustine M K

    2016-03-01

    Mitochondria are a distinguishing feature of eukaryotic cells. Best known for their critical function in energy production via oxidative phosphorylation (OXPHOS), mitochondria are essential for nutrient and oxygen sensing and for the regulation of critical cellular processes, including cell death and inflammation. Such diverse functional roles for organelles that were once thought to be simple may be attributed to their distinct heteroplasmic genome, exclusive maternal lineage of inheritance, and ability to generate signals to communicate with other cellular organelles. Mitochondria are now thought of as one of the cell's most sophisticated and dynamic responsive sensing systems. Specific signatures of mitochondrial dysfunction that are associated with disease pathogenesis and/or progression are becoming increasingly important. In particular, the centrality of mitochondria in the pathological processes and clinical phenotypes associated with a range of lung diseases is emerging. Understanding the molecular mechanisms regulating the mitochondrial processes of lung cells will help to better define phenotypes and clinical manifestations associated with respiratory disease and to identify potential diagnostic and therapeutic targets.

  4. Lung mechanics and high-resolution computed tomography of the chest in very low birth weight premature infants

    Directory of Open Access Journals (Sweden)

    Rosane Reis de Mello

    Full Text Available CONTEXT: Premature infant lung development may be affected by lung injuries during the first few weeks of life. Lung injuries have been associated with changes in lung mechanics. OBJECTIVE: To evaluate an association between lung mechanics and lung structural alterations in very low birth weight infants (birth weight less than 1500 g. DESIGN: A cross-sectional evaluation of pulmonary mechanics (lung compliance and lung resistance and high resolution computed tomography of the chest at the time of discharge, in 86 very low birth weight infants born at Instituto Fernandes Figueira, a tertiary public healthcare institution in Rio de Janeiro, Brazil. Lung compliance and resistance were measured during quiet sleep. High resolution computed tomography was performed using Pro Speed-S equipment. MAIN MEASUREMENTS: Statistical analysis was performed by means of variance analysis (ANOVA/ Kruskal Wallis. The significance level was set at 0.05. RESULTS: Abnormal values for both lung compliance and lung resistance were found in 34 babies (43%, whereas 20 (23.3% had normal values for both lung compliance and lung resistance. The mean lung compliance and lung resistance for the group were respectively 1.30 ml/cm H2O/kg and 63.7 cm H2O/l/s. Lung alterations were found via high-resolution computed tomography in 62 (72% infants. Most infants showed more than one abnormality, and these were described as ground glass opacity, parenchymal bands, atelectasis and bubble/cyst. The mean compliance values for infants with normal (1.49 ml/cm H2O/kg high resolution computed tomography, 1 or 2 abnormalities (1.31 ml/cm H2O/kg and 3 or more abnormalities (1.16 ml/cm H2O/kg were significantly different (p = 0.015. Our data were insufficient to find any association between lung resistance and the number of alterations via high-resolution computed tomography. CONCLUSION: The results show high prevalence of lung functional and tomographic abnormalities in asymptomatic very low

  5. Lung mechanics and high-resolution computed tomography of the chest in very low birth weight premature infants

    Energy Technology Data Exchange (ETDEWEB)

    Mello, Rosane Reis de; Dutra, Maria Virginia Peixoto; Ramos, Jose Roberto; Daltro, Pedro; Boechat, Marcia; Andrade Lopes, Jose Maria de [Fundacao Inst. Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Instituto Fernandes Figueira

    2003-07-01

    Premature infant lung development may be affected by lung injuries during the first few weeks of life. Lung injuries have been associated with changes in lung mechanics. The objective is to evaluate an association between lung mechanics and lung structural alterations in very low birth weight infants (birth weight less than 1500 g). The design presents a cross-sectional evaluation of pulmonary mechanics (lung compliance and lung resistance) and high resolution computed tomography of the chest at the time of discharge, in 86 very low birth weight infants born at Instituto Fernandes Figueira, a tertiary public health care institution in Rio de Janeiro, Brazil. Lung compliance and resistance were measured during quiet sleep. High resolution computed tomography was performed using Pro Speed-S equipment. Statistical analysis was performed by means of variance analysis (ANOVA/ Kruskal Wallis). The significance level was set at 0.05. The results showed abnormal values for both lung compliance and lung resistance were found in 34 babies (43%), whereas 20 (23.3%) had normal values for both lung compliance and lung resistance. The mean lung compliance and lung resistance for the group were respectively 1.30 ml/cm H{sub 2} O/kg and 63.7 cm H{sub 2} O/l/s. Lung alterations were found via high-resolution computed tomography in 62 (72%) infants. Most infants showed more than one abnormality, and these were described as ground glass opacity, parenchymal bands, atelectasis and bubble/cyst. The mean compliance values for infants with normal (1.49 ml/cm H{sub 2} O/kg) high resolution computed tomography, 1 or 2 abnormalities (1.31 ml/cm H{sub 2} O/kg) and 3 or more abnormalities (1.16 ml/cm H{sub 2} O/kg) were significantly different (p = 0.015). Our data were insufficient to find any association between lung resistance and the number of alterations via high-resolution computed tomography. The conclusion was that the results show high prevalence of lung functional and tomographic

  6. Lung cancer in younger patients

    DEFF Research Database (Denmark)

    Abbasowa, Leda; Madsen, Poul Henning

    2016-01-01

    INTRODUCTION: Lung cancer remains a leading cause of cancer-related death. The incidence increases with age and the occurrence in young patients is relatively low. The clinicopathological features of lung cancer in younger patients have not been fully explored previously. METHODS: To assess the age...... differences in the clinical characteristics of lung cancer, we conducted a retrospective analysis comparing young patients ≤ 65 years of age with an elderly group > 65 years of age. Among 1,232 patients evaluated due to suspicion of lung cancer in our fast-track setting from January-December 2013, 312 newly...... diagnosed lung cancer patients were included. RESULTS: Patients ≤ 65 years had a significantly higher representation of females (p = 0.0021), more frequent familial cancer aggregation (p = 0.028) and a lower incidence of squamous cell carcinoma (p = 0.0133). When excluding pure carcinoid tumours...

  7. Biomarkers in acute lung injury.

    Science.gov (United States)

    Mokra, Daniela; Kosutova, Petra

    2015-04-01

    Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS.

  8. Combinatorial Maps with Normalized Knot

    CERN Document Server

    Zeps, Dainis

    2010-01-01

    We consider combinatorial maps with fixed combinatorial knot numbered with augmenting numeration called normalized knot. We show that knot's normalization doesn't affect combinatorial map what concerns its generality. Knot's normalization leads to more concise numeration of corners in maps, e.g., odd or even corners allow easy to follow distinguished cycles in map caused by the fixation of the knot. Knot's normalization may be applied to edge structuring knot too. If both are normalized then one is fully and other partially normalized mutually.

  9. Institutionalizing Normal: Rethinking Composition's Precedence in Normal Schools

    Science.gov (United States)

    Skinnell, Ryan

    2013-01-01

    Composition historians have recently worked to recover histories of composition in normal schools. This essay argues, however, that historians have inadvertently misconstrued the role of normal schools in American education by inaccurately comparing rhetorical education in normal schools to rhetorical education in colleges and universities.…

  10. [Severe interstitial lung disease from pathologic gastroesophageal reflux in children].

    Science.gov (United States)

    Ahrens, P; Weimer, B; Hofmann, D

    1999-07-01

    Interstitial lung diseases comprise a heterogeneous group of pulmonary conditions that cause restrictive lung disease of poor prognosis, especially if growth failure, pulmonary hypertension and fibrosis appears. We report on the case of a girl of 11 years of age who suffered from severe nonallergic asthma in early childhood and who developed severe interstitial pulmonary disease caused by gastro-oesophageal reflux at the age of 8 years. This diagnosis was established by lung biopsy, bronchoalveolar lavage and a high amount of lipid-laden alveolar macrophages, 2-level pH measurement and oesophageal biopsy. Because therapy with oral and inhaled steroids failed and Omeprazol showed benificial effects, hemifundoplication according to THAL was performed. At present the lung function is clearly normal and there is no need of any medicaments. Following the history, we can assume the pathological gastro-oesophageal reflux to be the cause of the disease. It is important to state that there were no typical symptoms at any time pointing to gastro-oesophageal reflux disease. The development of pulmonary disease by pathological reflux is very often caused by "silent aspiration". Very typically there are no symptoms such as vomiting, heartburn and pain but only signs of chronic lung disease.

  11. Smoking-related interstitial lung diseases: radiologic-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Hidalgo, Alberto [Universidad Autonoma de Barcelona, Department of Radiology, Hospital de Sant Pau, Barcelona (Spain); Hospital de la Santa Creu i Sant Pau, Thoracic Radiology, Department of Radiology, Barcelona (Spain); Franquet, Tomas; Gimenez, Ana; Pineda, Rosa; Madrid, Marta [Universidad Autonoma de Barcelona, Department of Radiology, Hospital de Sant Pau, Barcelona (Spain); Bordes, Ramon [Universidad Autonoma de Barcelona, Department of Pathology, Hospital de Sant Pau, Barcelona (Spain)

    2006-11-15

    Smoking-related interstitial lung diseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lung disease (RB-ILD), pulmonary Langerhans' cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans' histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10 mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal clung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lung diseases (SRILD) allows a more confident and specific diagnosis. (orig.)

  12. Challenging immunosuppression treatment in lung transplant recipients with kidney failure.

    Science.gov (United States)

    Högerle, Benjamin A; Kohli, Neeraj; Habibi-Parker, Kirsty; Lyster, Haifa; Reed, Anna; Carby, Martin; Zeriouh, Mohamed; Weymann, Alexander; Simon, André R; Sabashnikov, Anton; Popov, Aron-Frederik; Soresi, Simona

    2016-03-01

    Kidney failure after lung transplantation is a risk factor for chronic kidney disease. Calcineurin inhibitors are immunosuppressants which play a major role in terms of postoperative kidney failure after lung transplantation. We report our preliminary experience with the anti-interleukin-2 monoclonal antibody Basiliximab utilized as a "calcineurin inhibitor-free window" in the setting of early postoperative kidney failure after lung transplantation. Between 2012 and 2015 nine lung transplant patients who developed kidney failure for more than 14 days were included. Basiliximab was administrated in three doses (Day 0, 4, and 20) whilst Tacrolimus was discontinued or reduced to maintain a serum level between 2 and 4 ng/mL. Baseline glomerular filtration rate pre transplant was normal for all patients. Seven patients completely recovered from kidney failure (67%, mean eGFR pre and post Basiliximab: 42.3 mL/min/1.73 m(2) and 69 mL/min/1.73 m(2)) and were switched back on Tacrolimus. Only one of these patients still needs ongoing renal replacement therapy. Two patients showed no recovery from kidney failure and did not survive. Basiliximab might be a safe and feasible therapeutical option in patients which are affected by calcineurin inhibitor-related kidney failure in the early post lung transplant period. Further studies are necessary to confirm our preliminary results.

  13. Utility of lung ultrasound in near-drowning victims.

    Science.gov (United States)

    Laursen, Christian B; Davidsen, Jesper Rømhild; Madsen, Poul Henning

    2012-06-21

    Drowning and near-drowning are common causes of accidental death worldwide and respiratory complications such as non-cardiogenic pulmonary oedema, acute respiratory distress syndrome and pneumonia are often seen. In other settings lung ultrasound can accurately diagnose these conditions; hence lung ultrasound may have a potential role in the evaluation of drowning or near-drowning victims. In this case report the authors describe a 71-year-old man who was brought to hospital with acute respiratory failure after a near-drowning accident. Lung ultrasound showed multiple B-lines on the anterior and lateral surfaces of both lungs, consistent with pulmonary oedema. Focus assessed transthoracic echocardiography showed no pericardial effusion and a normal global left ventricular function. Based on these findings the patient was diagnosed as having non-cardiogenic pulmonary oedema. Subsequent chest x-ray showed bilateral infiltrates consistent with pulmonary oedema. The case report emphasises the clinical value of lung ultrasound in the evaluation of a near-drowning victim.

  14. An IMRT/VMAT Technique for Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Nan Zhao

    2015-01-01

    Full Text Available The study is to investigate a Hybrid IMRT/VMAT technique which combines intensity modulated radiation therapy (IMRT and volumetric modulated arc therapy (VMAT for the treatment of nonsmall cell lung cancer (NSCLC. Two partial arcs VMAT, 5-field IMRT, and hybrid plans were created for 15 patients with NSCLC. The hybrid plans were combination of 2 partial arcs VMAT and 5-field IMRT. The dose distribution of planning target volume (PTV and organs at risk (OARs for hybrid technique was compared with IMRT and VMAT. The monitor units (MUs and treatment delivery time were also evaluated. Hybrid technique significantly improved the target conformity and homogeneity compared with IMRT and VMAT. The mean delivery time of IMRT, VMAT, and hybrid plans was 280 s, 114 s, and 327 s, respectively. The mean MUs needed for IMRT, VMAT, and hybrid plans were 933, 512, and 737, respectively. Hybrid technique reduced V5, V10, V30, and MLD of normal lung compared with VMAT and spared the OARs better with fewer MUs with the cost of a little higher V5, V10, and mean lung dose (MLD of normal lung compared with IMRT. Hybrid IMRT/VMAT can be a viable radiotherapy technique with better plan quality.

  15. An IMRT/VMAT Technique for Nonsmall Cell Lung Cancer.

    Science.gov (United States)

    Zhao, Nan; Yang, Ruijie; Wang, Junjie; Zhang, Xile; Li, Jinna

    2015-01-01

    The study is to investigate a Hybrid IMRT/VMAT technique which combines intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for the treatment of nonsmall cell lung cancer (NSCLC). Two partial arcs VMAT, 5-field IMRT, and hybrid plans were created for 15 patients with NSCLC. The hybrid plans were combination of 2 partial arcs VMAT and 5-field IMRT. The dose distribution of planning target volume (PTV) and organs at risk (OARs) for hybrid technique was compared with IMRT and VMAT. The monitor units (MUs) and treatment delivery time were also evaluated. Hybrid technique significantly improved the target conformity and homogeneity compared with IMRT and VMAT. The mean delivery time of IMRT, VMAT, and hybrid plans was 280 s, 114 s, and 327 s, respectively. The mean MUs needed for IMRT, VMAT, and hybrid plans were 933, 512, and 737, respectively. Hybrid technique reduced V5, V10, V30, and MLD of normal lung compared with VMAT and spared the OARs better with fewer MUs with the cost of a little higher V5, V10, and mean lung dose (MLD) of normal lung compared with IMRT. Hybrid IMRT/VMAT can be a viable radiotherapy technique with better plan quality.

  16. Camera Embedded Single Lumen Tube as a Rescue Device for Airway Handling during Lung Separation

    DEFF Research Database (Denmark)

    Højberg Holm, Jimmy; Andersen, Claus

    2016-01-01

    for the surgery to proceed (Figure 2). The rest of procedure was uneventful with normal one-lung ventilation and a smooth awakening and extubation. We report a case of unexpected technical difficulties when isolating the lung in pulmonary surgery for lung cancer, a problem that could lead to cancellation......Lung isolation in thoracic surgery will usually be achieved either with a double-lumen tube (DLT) or a bronchial blocker (BB). However, even when conducted by anesthesiologists with particular interest and expertise in thoracic anesthesia, the procedure may be troublesome and time consuming.......Keywords: Thoracic anesthesia; Airway handling; VivaSight; Vivasight-SL; Lobectomy; Camera-embedded tube; Endotracheal; Lung isolation; Video tube Taking the small stature into account, use of a small conventional 35-Fr right sided DLT was planned for the procedure. As it turned out, this tube could not be passed...

  17. LUNG CANCER AND PULMONARY THROMBOEMBOLISM

    Science.gov (United States)

    Cukic, Vesna; Ustamujic, Aida

    2015-01-01

    Introduction: Malignant diseases including lung cancer are the risk for development of pulmonary thromboembolism (PTE). Objective: To show the number of PTE in patients with lung cancer treated in Clinic for pulmonary diseases and TB “Podhrastovi” in three-year period: from 2012-2014. Material and methods: This is the retrospective study in which we present the number of various types of lung cancer treated in three-year period, number and per cent of PTE in different types of lung carcinoma, number and per cent of PTE of all diagnosed PTE in lung carcinoma according to the type of carcinoma. Results: In three-year period (from 2012 to 2014) 1609 patients with lung cancer were treated in Clinic for pulmonary diseases and TB “Podhrastovi” Clinical Centre of Sarajevo University. 42 patients: 25 men middle –aged 64.4 years and 17 women middle- aged 66.7 or 2.61% of all patients with lung cancer had diagnosed PTE. That was the 16. 7% of all patients with PTE treated in Clinic “Podhrastovi “in that three-year period. Of all 42 patients with lung cancer and diagnosed PTE 3 patients (7.14%) had planocellular cancer, 4 patients (9.53%) had squamocellular cancer, 9 (21.43%) had adenocarcinoma, 1 (2.38%) had NSCLC, 3 (7.14 %) had microcellular cancer, 1 (2.38%) had neuroendocrine cancer, 2 (4.76%) had large cell-macrocellular and 19 (45.24%) had histological non-differentiated lung carcinoma. Conclusion: Malignant diseases, including lung cancer, are the risk factor for development of PTE. It is important to consider the including anticoagulant prophylaxis in these patients and so to slow down the course of diseases in these patients. PMID:26622205

  18. Epidermal growth factor and lung development in the offspring of the diabetic rat

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Nexø, Ebba

    2000-01-01

    Fetuses of diabetic mothers who were exposed to excessive glucose show delayed maturation. Under these conditions, altered growth factor expression or signaling may have important regulatory influences. We examined the role of epidermal growth factor (EGF) in lung development and maternal diabetes...... in the rat. In order to evaluate the possible role of glucose for the expression of EGF and the growth of lung tissue, we performed in vitro studies with organotypic cultures of fetal alveolar cells obtained from control rats. Compared to pups of normal rats, the newborn rats of untreated diabetic rats had...... reduced body weight, but normal lung weight relative to body weight. The air:mesenchyme ratio and the average size of alveoli per mm(2) lung tissue were reduced. The immunoreactivity (IR) of EGF, which was quantified using a computerized image analysis system, appeared with increased intensity...

  19. Normal and pathological altruism.

    Science.gov (United States)

    Seelig, B J; Rosof, L S

    2001-01-01

    The psychoanalytic literature on altruism is sparse, although much has been written on this topic from a sociobiological perspective. Freud (1917) first described the concept in "Libido Theory and Narcissism." In 1946 Anna Freud coined the term "altruistic surrender" to describe the psychodynamics of altruistic behavior in a group of inhibited individuals who were neurotically driven to do good for others. The usefulness and clinical applicability of this formulation, in conjunction with the frequent coexistence of masochism and altruism, encouraged psychoanalysts to regard all forms of altruism as having masochistic underpinnings. Since then, there has been a conflation of the two concepts in much of the analytic literature. This paper reexamines the psychoanalytic understanding of altruism and proposes an expansion of the concept to include a normal form. Five types of altruism are described: protoaltruism, generative altruism, conflicted altruism, pseudoaltruism, and psychotic altruism. Protoaltruism has biological roots and can be observed in animals. In humans, protoaltruism includes maternal and paternal nurturing and protectiveness. Generative altruism is the nonconflictual pleasure in fostering the success and/or welfare of another. Conflicted altruism is generative altruism that is drawn into conflict, but in which the pleasure and satisfaction of another (a proxy) is actually enjoyed. Pseudoaltruism originates in conflict and serves as a defensive cloak for underlying sadomasochism. Psychotic altruism is defined as the sometimes bizarre forms of caretaking behavior and associated self-denial seen in psychotic individuals, and often based on delusion. We consider Anna Freud's altruistic surrender to combine features of both conflict-laden altruism and pseudoaltruism. Two clinical illustrations are discussed.

  20. Surface normals and barycentric coordinates

    Directory of Open Access Journals (Sweden)

    Mullineux Glen

    1996-01-01

    Full Text Available The normal to a triangular parametric surface is investigated where the parameters used are barycentric coordinates. Formulae for the normal are obtained for non-rational and rational surfaces.

  1. Cryotherapy in Treating Patients With Lung Cancer That Has Spread to the Other Lung or Parts of the Body

    Science.gov (United States)

    2017-01-17

    Advanced Malignant Mesothelioma; Extensive Stage Small Cell Lung Cancer; Lung Metastases; Recurrent Malignant Mesothelioma; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  2. Facts and promises on lung biomarkers in interstitial lung diseases.

    Science.gov (United States)

    Campo, Ilaria; Zorzetto, Michele; Bonella, Francesco

    2015-08-01

    Interstitial lung diseases (ILDs) are a heterogeneous group of >100 pulmonary disorders. ILDs are characterized by an irreversible architectural distortion and impaired gas exchange; however, there is great variability in the clinical course. ILD diagnosis requires a combination of clinical data, radiological imaging and histological findings (when a lung biopsy is required). At the same time, successful management of ILD patients strictly depends on an accurate and confident diagnosis. In this context, the detection of reliable biomarkers able to identify ILD subtypes, avoiding lung biopsy, as well as the capacity to stratify patients and predict over time the disease course, has become a primary aim for all research studies in this field.

  3. The Lung Immune Response to Nontypeable Haemophilus influenzae (Lung Immunity to NTHi).

    Science.gov (United States)

    King, Paul T; Sharma, Roleen

    2015-01-01

    Haemophilus influenzae is divided into typeable or nontypeable strains based on the presence or absence of a polysaccharide capsule. The typeable strains (such as type b) are an important cause of systemic infection, whilst the nontypeable strains (designated as NTHi) are predominantly respiratory mucosal pathogens. NTHi is present as part of the normal microbiome in the nasopharynx, from where it may spread down to the lower respiratory tract. In this context it is no longer a commensal and becomes an important respiratory pathogen associated with a range of common conditions including bronchitis, bronchiectasis, pneumonia, and particularly chronic obstructive pulmonary disease. NTHi induces a strong inflammatory response in the respiratory tract with activation of immune responses, which often fail to clear the bacteria from the lung. This results in recurrent/persistent infection and chronic inflammation with consequent lung pathology. This review will summarise the current literature about the lung immune response to nontypeable Haemophilus influenzae, a topic that has important implications for patient management.

  4. Identification of ubiquinol cytochrome c reductase hinge (UQCRH) as a potential diagnostic biomarker for lung adenocarcinoma

    OpenAIRE

    Gao, Feng; Liu, Qicai; Li, Guoping; Dong, Feng; Qiu, Minglian; Lv, Xiaoting; Zhang, Sheng; Guo, Zheng

    2016-01-01

    Ubiquinol cytochrome c reductase hinge (UQCRH) is a novel protein that localizes in the mitochondrial membrane and induces mitochondrial reactive oxygen species (ROS) generation. It had a high expression rate of 87.10% (108/124) in lung adenocarcinoma. Moreover, serum UQCRH level in patients with lung adenocarcinoma was significantly increased compared with that of pneumonia patients (p < 0.0001) and normal control subjects (p < 0.0001). Receiver operating characteristic curve analysis using ...

  5. Short proofs of strong normalization

    OpenAIRE

    Wojdyga, Aleksander

    2008-01-01

    This paper presents simple, syntactic strong normalization proofs for the simply-typed lambda-calculus and the polymorphic lambda-calculus (system F) with the full set of logical connectives, and all the permutative reductions. The normalization proofs use translations of terms and types to systems, for which strong normalization property is known.

  6. A gene expression signature that can predict green tea exposure and chemopreventive efficacy of lung cancer in mice.

    Science.gov (United States)

    Lu, Yan; Yao, Ruisheng; Yan, Ying; Wang, Yian; Hara, Yukihiko; Lubet, Ronald A; You, Ming

    2006-02-15

    Green tea has been shown to be a potent chemopreventive agent against lung tumorigenesis in animal models. Previously, we found that treatment of A/J mice with either green tea (0.6% in water) or a defined green tea catechin extract (polyphenon E; 2.0 g/kg in diet) inhibited lung tumor tumorigenesis. Here, we described expression profiling of lung tissues derived from these studies to determine the gene expression signature that can predict the exposure and efficacy of green tea in mice. We first profiled global gene expressions in normal lungs versus lung tumors to determine genes which might be associated with the tumorigenic process (TUM genes). Gene expression in control tumors and green tea-treated tumors (either green tea or polyphenon E) were compared to determine those TUM genes whose expression levels in green tea-treated tumors returned to levels seen in normal lungs. We established a 17-gene expression profile specific for exposure to effective doses of either green tea or polyphenon E. This gene expression signature was altered both in normal lungs and lung adenomas when mice were exposed to green tea or polyphenon E. These experiments identified patterns of gene expressions that both offer clues for green tea's potential mechanisms of action and provide a molecular signature specific for green tea exposure.

  7. Morphofunctional changes and mechanisms of their realization in developing lungs under influence of paracetamol and nimesulid

    Directory of Open Access Journals (Sweden)

    Kharchenko S.V.

    2012-01-01

    Full Text Available Actuality of organs and tissues normality development studying is conditioned on continuous growth of conge-nital abnormalies оn the base of greater drugs distribution. The anomalie s of lungs development unde r influence of paraceta-mol and nimesulide are examined and the possible mechanisms of their appearance are analysed. It is determined that lungs develop more slowly under action of paracetamol than in norm and paracetamol lead to development of bronchial asthma during postnatal period of life. Small in numbers researches of nimesulide influen ce demonstrate changes of lungs histogene-sis, which show up in thei r development deceleration.

  8. Natural history of five children with surfactant protein C mutations and interstitial lung disease.

    Science.gov (United States)

    Avital, Avraham; Hevroni, Avigdor; Godfrey, Simon; Cohen, Shlomo; Maayan, Channa; Nusair, Samir; Nogee, Lawrence M; Springer, Chaim

    2014-11-01

    Interstitial lung diseases in infants and children are uncommon and may be caused by specific inborn errors of surfactant metabolism. Five children with open lung biopsy diagnosed interstitial lung disease were followed (mean of 27.2 years) and evaluated for surfactant protein gene mutations. Four of the children were originally diagnosed as desquamative interstitial pneumonitis and one as chronic interstitial pneumonitis. All had good response to chloroquine or hydroxychloroquine treatment for periods of 7-38 months. Lung function tests, incremental exercise tests, and rentgenological studies were performed in the children. Surfactant protein gene mutations were searched in all the patients and in part of their families. Three of the patients, aged now 32, 29, and 37 years, feel well and have normal lung function, while two of the patients, both females, aged 28 and 37 years, conduct normal activities of daily living, have healthy children but have clinical, physiological and rentgenological evidence of restrictive lung disease. All five patients were found to have surfactant protein C gene (SFTPC) mutations, three of them with the most common mutation (p.I73T) and the other two with new mutations of surfactant protein C gene (p.I38F and p.V39L). We conclude that detection of surfactant protein mutations should be attempted in all children presenting with interstitial lung disease. Furthermore, treatment with hydroxychloroquine should be considered in children with SFTPC mutations. Prospective evaluation of hydroxychloroquine therapy in a greater number of patients is needed.

  9. Overexpression and small molecule-triggered downregulation of CIP2A in lung cancer.

    Directory of Open Access Journals (Sweden)

    Liang Ma

    Full Text Available BACKGROUND: Lung cancer is the leading cause of cancer deaths worldwide, with a five-year overall survival rate of only 15%. Cancerous inhibitor of PP2A (CIP2A is a human oncoprotein inhibiting PP2A in many human malignancies. However, whether CIP2A can be a new drug target for lung cancer is largely unclear. METHODOLOGY/PRINCIPAL FINDINGS: Normal and malignant lung tissues were derived from 60 lung cancer patients from southern China. RT-PCR, Western blotting and immunohistochemistry were used to evaluate the expression of CIP2A. We found that among the 60 patients, CIP2A was undetectable or very low in paratumor normal tissues, but was dramatically elevated in tumor samples in 38 (63.3% patients. CIP2A overexpression was associated with cigarette smoking. Silencing CIP2A by siRNA inhibited the proliferation and clonogenic activity of lung cancer cells. Intriguingly, we found a natural compound, rabdocoetsin B which is extracted from a Traditional Chinese Medicinal herb Rabdosia coetsa, could induce down-regulation of CIP2A and inactivation of Akt pathway, and inhibit proliferation and induce apoptosis in a variety of lung cancer cells. CONCLUSIONS/SIGNIFICANCE: Our findings strongly indicate that CIP2A could be an effective target for lung cancer drug development, and the therapeutic potentials of CIP2A-targeting agents warrant further investigation.

  10. IL-22 is essential for lung epithelial repair following influenza infection.

    Science.gov (United States)

    Pociask, Derek A; Scheller, Erich V; Mandalapu, Sivanarayana; McHugh, Kevin J; Enelow, Richard I; Fattman, Cheryl L; Kolls, Jay K; Alcorn, John F

    2013-04-01

    Influenza infection is widespread in the United States and the world. Despite low mortality rates due to infection, morbidity is common and little is known about the molecular events involved in recovery. Influenza infection results in persistent distal lung remodeling, and the mechanism(s) involved are poorly understood. Recently IL-22 has been found to mediate epithelial repair. We propose that IL-22 is critical for recovery of normal lung function and architecture after influenza infection. Wild-type and IL-22(-/-) mice were infected with influenza A PR8/34 H1N1 and were followed up for up to 21 days post infection. IL-22 receptor was localized to the airway epithelium in naive mice but was expressed at the sites of parenchymal lung remodeling induced by influenza infection. IL-22(-/-) mice displayed exacerbated lung injury compared with wild-type mice, which correlated with decreased lung function 21 days post infection. Epithelial metaplasia was observed in wild-type mice but was not evident in IL-22(-/-) animals that were characterized with an increased fibrotic phenotype. Gene expression analysis revealed aberrant expression of epithelial genes involved in repair processes, among changes in several other biological processes. These data indicate that IL-22 is required for normal lung repair after influenza infection. IL-22 represents a novel pathway involved in interstitial lung disease.

  11. Pulmonary malformation in transgenic mice expressing human keratinocyte growth factor in the lung.

    Science.gov (United States)

    Simonet, W S; DeRose, M L; Bucay, N; Nguyen, H Q; Wert, S E; Zhou, L; Ulich, T R; Thomason, A; Danilenko, D M; Whitsett, J A

    1995-01-01

    Expression of human keratinocyte growth factor (KGF/FGF-7) was directed to epithelial cells of the developing embryonic lung of transgenic mice disrupting normal pulmonary morphogenesis during the pseudoglandular stage of development. By embryonic day 15.5(E15.5), lungs of transgenic surfactant protein C (SP-C)-KGF mice resembled those of humans with pulmonary cystadenoma. Lungs were cystic, filling the thoracic cavity, and were composed of numerous dilated saccules lined with glycogen-containing columnar epithelial cells. The normal distribution of SP-C proprotein in the distal regions of respiratory tubules was disrupted. Columnar epithelial cells lining the papillary structures stained variably and weakly for this distal respiratory cell marker. Mesenchymal components were preserved in the transgenic mouse lungs, yet the architectural relationship of the epithelium to the mesenchyme was altered. SP-C-KGF transgenic mice failed to survive gestation to term, dying before E17.5. Culturing mouse fetal lung explants in the presence of recombinant human KGF also disrupted branching morphogenesis and resulted in similar cystic malformation of the lung. Thus, it appears that precise temporal and spatial expression of KGF is likely to play a crucial role in the control of branching morphogenesis during fetal lung development. Images Fig. 1 Fig. 2 Fig. 3 PMID:8618921

  12. B-lines quantify the lung water content: a lung ultrasound versus lung gravimetry study in acute lung injury.

    Science.gov (United States)

    Jambrik, Zoltán; Gargani, Luna; Adamicza, Agnes; Kaszaki, József; Varga, Albert; Forster, Tamás; Boros, Mihály; Picano, Eugenio

    2010-12-01

    B-lines (also termed ultrasound lung comets) obtained with lung ultrasound detect experimental acute lung injury (ALI) very early and before hemogasanalytic changes, with a simple, noninvasive, nonionizing and real-time method. Our aim was to estimate the correlation between B-lines number and the wet/dry ratio of the lung tissue, measured by gravimetry, in an experimental model of ALI. Seventeen Na-pentobarbital anesthetized, cannulated (central vein and carotid artery) minipigs were studied: five sham-operated animals served as controls and, in 12 animals, ALI was induced by injection of oleic acid (0.1 mL/kg) via the central venous catheter. B-lines were measured by echographic scanner in four predetermined chest scanning sites in each animal. At the end of each experiment, both lungs were dissected, weighed and dried to determine wet/dry weight ratio by gravimetry. After the injection of oleic acid, B-lines number increased over time. A significant correlation was found between the wet/dry ratio and B-lines number (r = 0.91, p < 0.001). These data suggest that in an experimental pig model of ALI/ARDS, B-lines assessed by lung ultrasound provide a simple, semiquantitative, noninvasive index of lung water accumulation, strongly correlated to invasive gravimetric assessment.

  13. [Liposome phospholipid substitution and lung function in surfactant deprived rats].

    Science.gov (United States)

    Obladen, M

    1985-01-01

    In vivo activity of an artificial surfactant was studied in surfactant depleted rats. After tenfold alveolar lavage, PaO2, tidal volume, and compliance of the respiratory system fell to one third of initial value. Substitution of large unilamellar vesicles containing 90% Dipalmitoylphosphatidylcholine and 10% unsaturated phosphatidylglycerol largely restored oxygenation and lung mechanics in most animals. Complete normalization with weaning from the ventilator, however, was achieved neither with liposomes nor with natural surfactant concentrate.

  14. Trasplante pulmonar Lung transplant

    Directory of Open Access Journals (Sweden)

    M. Espinosa

    2006-08-01

    Full Text Available El transplante pulmonar suele ser la última opción terapéutica para pacientes con insuficiencia respiratoria. A pesar de los muchos avances en inmunología y el manejo de las complicaciones, la mortalidad y morbilidad asociadas a este trasplante son muy superiores a los demás. El rechazo agudo es casi un problema universal en el primer año, mientras que la bronquiolitis obliterante limita la supervivencia a largo plazo. Las infecciones respiratorias también cumplen un papel importante en las complicaciones asociadas al trasplante pulmonar por la constante exposición del injerto al medio exterior. No obstante, los éxitos de esta opción terapéutica que depende fundamentalmente de una correcta selección de donante y receptor, son evidentes, sobre todo en cuanto a calidad de vida se refiere.A lung transplant is usually the final therapeutic option for patients with respiratory insufficiency. In spite of the many advances in immunology and the management of complications, mortality and morbidity associated with this transplant are far higher than with others. Acute rejection is an almost universal problem in the first year, while obliterative bronchitis reduces long term survival. Respiratory infections also play a significant role in the complications associated with lung transplants due to the constant exposure of the graft to the outside. However, the success of this therapeutic option, which basically depends on a suitable selection of donor and recipient, are evident, above all with respect to quality of life.

  15. Expression of Syk in non-small cell lung cancer and its relationship with clinicopathological parameters

    Institute of Scientific and Technical Information of China (English)

    Fen LAN; Shengdao XIONG; Weining XIONG; Guopeng XU; Xiaoxia LU

    2009-01-01

    This study aims to research the expression of spleen tyrosine kinase (Syk) in non-small cell lung cancer (NSCLC) and the relationship between Syk and clinico-pathologic factors and p53. Immunohistochemistry was applied to detect the expression of Syk and p53 protein in 39 cases of NSCLC (23 cases of lung squamous cell can-cer, 16 cases of lung adenocarcinoma) and tumor-sur-rounding normal lung tissues. The positive rate of Syk was 46.15% (18/39) and 100% (39/39) in NSCLC and tumor-surrounding normal lung tissues, respectively. The expres-sion level of Syk in NSCLC was significantly lower than that in tumor-surrounding normal lung tissues (P = 0.000). The Syk expression was positively correlated with the p53 expression in NSCLC specimens (P = 0.025). There was no significant association between Syk expression and lymph node metastasis, differentiation degree, tumor size and tumor node metastasis (TNM). The present study demonstrated that Syk was aberrantly expressed in the NSCLC and might have a significant impact on tumor growth and progression.

  16. Pulmonary extraction of propranolol in normal and oxygen-toxic sheep

    Energy Technology Data Exchange (ETDEWEB)

    Howell, R.E.; Lanken, P.N.; Hansen-Flaschen, J.H.; Haselton, F.R.; Albelda, S.M.; Fishman, A.P.

    1989-07-01

    To help define the mechanisms involved in the handling of propranolol by normal and injured lungs, we studied the pulmonary extraction of (/sup 3/H)propranolol in 23 unanesthetized sheep. Extraction of propranolol by normal lungs during a single circulation was characterized by (1) subsequent back-diffusion and pulmonary retention of the drug, (2) no evidence of saturable uptake or binding, (3) no effect of isoproterenol or imipramine, and (4) no effect of increasing cardiac output by treadmill exercise. In lungs damaged by oxygen toxicity, (/sup 3/H)propranolol extraction decreased progressively to 63% of base line, paralleling progressive arterial hypoxemia and hypercapnia. In contrast, (/sup 14/C)serotonin extraction remained unchanged from base line. Our results suggest that in normal unanesthetized sheep, pulmonary extraction of propranolol occurs primarily by passive diffusion that is flow-limited. Also, lung injury induced by oxygen toxicity in sheep reduces the pulmonary extraction of propranolol. Indeed, in oxygen toxicity, the depressed extraction of propranolol is a more sensitive marker of lung injury than is serotonin extraction.

  17. Identification of Gene Biomarkers for Distinguishing Small-Cell Lung Cancer from Non-Small-Cell Lung Cancer Using a Network-Based Approach

    Directory of Open Access Journals (Sweden)

    Fei Long

    2015-01-01

    Full Text Available Lung cancer consists of two main subtypes: small-cell lung cancer (SCLC and non-small-cell lung cancer (NSCLC that are classified according to their physiological phenotypes. In this study, we have developed a network-based approach to identify molecular biomarkers that can distinguish SCLC from NSCLC. By identifying positive and negative coexpression gene pairs in normal lung tissues, SCLC, or NSCLC samples and using functional association information from the STRING network, we first construct a lung cancer-specific gene association network. From the network, we obtain gene modules in which genes are highly functionally associated with each other and are either positively or negatively coexpressed in the three conditions. Then, we identify gene modules that not only are differentially expressed between cancer and normal samples, but also show distinctive expression patterns between SCLC and NSCLC. Finally, we select genes inside those modules with discriminating coexpression patterns between the two lung cancer subtypes and predict them as candidate biomarkers that are of diagnostic use.

  18. Lung toxicity of biodegradable nanoparticles.

    Science.gov (United States)

    Fattal, Elias; Grabowski, Nadége; Mura, Simona; Vergnaud, Juliette; Tsapis, Nicolas; Hillaireau, Hervé

    2014-10-01

    Biodegradable nanoparticles exhibit high potentialities for local or systemic drug delivery through lung administration making them attractive as nanomedicine carriers. However, since particulate matter or some inorganic manufactured nanoparticles exposed to lung cells have provoked cytotoxic effects, inflammatory and oxidative stress responses, it becomes important to investigate nanomedicine toxicity towards the lungs. This is the reason why, in the present review, the behavior of biodegradable nanoparticles towards the different parts of the respiratory tract as well as the toxicological consequences, measured on several models in vitro, ex vivo or in vivo, are described. Taken all together, the different studies carried out so far conclude on no or slight toxicity of biodegradable nanoparticles.

  19. Nanodiamond internalization in cells and the cell uptake mechanism

    Science.gov (United States)

    Perevedentseva, E.; Hong, S.-F.; Huang, K.-J.; Chiang, I.-T.; Lee, C.-Y.; Tseng, Y.-T.; Cheng, C.-L.

    2013-08-01

    Cell type-dependent penetration of nanodiamond in living cells is one of the important factors for using nanodiamond as cellular markers/labels, for drug delivery as well as for other biomedical applications. In this work, internalization of 100 nm nanodiamonds by A549 lung human adenocarcinoma cell, Beas-2b non-tumorigenic human bronchial epithelial cell, and HFL-1 fibroblast-like human fetal lung cell is studied and compared. The penetration of nanodiamond into the cells was observed using confocal fluorescence imaging and Raman imaging methods. Visualization of the nanodiamond in cells allows comparison of the internalization for diamond nanoparticles in cancer A549 cell, non-cancer HFL-1, and Beas-2b cells. The dose-dependent and time-dependent behavior of nanodiamond uptake is observed in both cancer as well as non-cancer cells. The mechanism of nanodiamond uptake by cancer and non-cancer cells is analyzed by blocking different pathways. The uptake of nanodiamond in both cancer and non-cancer cells was found predominantly via clathrin-dependent endocytosis. In spite of observed similarity in the uptake mechanism for cancer and non-cancer cells, the nanodiamond uptake for cancer cell quantitatively exceeds the uptake for non-cancer cells, for the studied cell lines. The observed difference in internalization of nanodiamond by cancer and non-cancer cells is discussed.

  20. Nanodiamond internalization in cells and the cell uptake mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Perevedentseva, E. [National Dong Hwa University, Department of Physics (China); Hong, S.-F.; Huang, K.-J. [National Dong Hwa University, Department of Life Sciences (China); Chiang, I.-T.; Lee, C.-Y. [National Dong Hwa University, Department of Physics (China); Tseng, Y.-T. [National Dong Hwa University, Department of Life Sciences (China); Cheng, C.-L., E-mail: clcheng@mail.ndhu.edu.tw [National Dong Hwa University, Department of Physics (China)

    2013-08-15

    Cell type-dependent penetration of nanodiamond in living cells is one of the important factors for using nanodiamond as cellular markers/labels, for drug delivery as well as for other biomedical applications. In this work, internalization of 100 nm nanodiamonds by A549 lung human adenocarcinoma cell, Beas-2b non-tumorigenic human bronchial epithelial cell, and HFL-1 fibroblast-like human fetal lung cell is studied and compared. The penetration of nanodiamond into the cells was observed using confocal fluorescence imaging and Raman imaging methods. Visualization of the nanodiamond in cells allows comparison of the internalization for diamond nanoparticles in cancer A549 cell, non-cancer HFL-1, and Beas-2b cells. The dose-dependent and time-dependent behavior of nanodiamond uptake is observed in both cancer as well as non-cancer cells. The mechanism of nanodiamond uptake by cancer and non-cancer cells is analyzed by blocking different pathways. The uptake of nanodiamond in both cancer and non-cancer cells was found predominantly via clathrin-dependent endocytosis. In spite of observed similarity in the uptake mechanism for cancer and non-cancer cells, the nanodiamond uptake for cancer cell quantitatively exceeds the uptake for non-cancer cells, for the studied cell lines. The observed difference in internalization of nanodiamond by cancer and non-cancer cells is discussed.