WorldWideScience

Sample records for lung show enhancing

  1. An efficient Trojan delivery of tetrandrine by poly(N-vinylpyrrolidone-block-poly(ε-caprolactone (PVP-b-PCL nanoparticles shows enhanced apoptotic induction of lung cancer cells and inhibition of its migration and invasion

    Directory of Open Access Journals (Sweden)

    Xu H

    2013-12-01

    Full Text Available Huae Xu,1,2 Zhibo Hou,3 Hao Zhang,4 Hui Kong,2 Xiaolin Li,4 Hong Wang,2 Weiping Xie21Department of Pharmacy, 2Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China; 3First Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, People's Republic of China; 4Department of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of ChinaAbstract: Earlier studies have demonstrated the promising antitumor effect of tetrandrine (Tet against a series of cancers. However, the poor solubility of Tet limits its application, while its hydrophobicity makes Tet a potential model drug for nanodelivery systems. We report on a simple way of preparing drug-loaded nanoparticles formed by amphiphilic poly(N-vinylpyrrolidone-block-poly(ε-caprolactone (PVP-b-PCL copolymers with Tet as a model drug. The mean diameters of Tet-loaded PVP-b-PCL nanoparticles (Tet-NPs were between 110 nm and 125 nm with a negative zeta potential slightly below 0 mV. Tet was incorporated into PVP-b-PCL nanoparticles with high loading efficiency. Different feeding ratios showed different influences on sizes, zeta potentials, and the drug loading efficiencies of Tet-NPs. An in vitro release study shows the sustained release pattern of Tet-NPs. It is shown that the uptake of Tet-NPs is mainly mediated by the endocytosis of nanoparticles, which is more efficient than the filtration of free Tet. Further experiments including fluorescence activated cell sorting and Western blotting indicated that this Trojan strategy of delivering Tet in PVP-b-PCL nanoparticles via endocytosis leads to enhanced induction of apoptosis in the non-small cell lung cancer cell A549 line; enhanced apoptosis is achieved by inhibiting the expression of anti-apoptotic Bcl-2 and Bcl-xL proteins. Moreover, Tet-NPs more efficiently inhibit the ability of cell migration and

  2. Mechanisms of enhanced lung injury during sepsis

    DEFF Research Database (Denmark)

    Czermak, B J; Breckwoldt, M; Ravage, Z B

    1999-01-01

    . Enhanced lung injury was associated with increased accumulation of neutrophils in lung, enhanced production of CXC chemokines (but not tumor necrosis factor-alpha) in bronchoalveolar lavage fluids, and increased expression of lung vascular intercellular adhesion molecule-1 (ICAM-1). Complement depletion...

  3. Soluble ICAM-1 activates lung macrophages and enhances lung injury

    DEFF Research Database (Denmark)

    Schmal, H; Czermak, B J; Lentsch, A B

    1998-01-01

    production of TNF-alpha and the CXC chemokine, macrophage inflammatory protein-2 (MIP-2). Alveolar macrophages exhibited cytokine responses to both sICAM-1 and immobilized sICAM-1, while rat PBMCs failed to demonstrate similar responses. Exposure of alveolar macrophages to sICAM-1 resulted in NFkappa......B activation (which was blocked by the presence of the aldehyde peptide inhibitor of 28S proteosome and by genistein, a tyrosine kinase inhibitor). As expected, cross-linking of CD18 on macrophages with Ab resulted in generation of TNF-alpha and MIP-2. This response was also inhibited in the presence...... of TNF-alpha and MIP-2 and increased neutrophil recruitment. Therefore, through engagement of beta2 integrins, sICAM-1 enhances alveolar macrophage production of MIP-2 and TNF-alpha, the result of which is intensified lung injury after intrapulmonary disposition of immune complexes....

  4. Lung Adenocarcinomas and Lung Cancer Cell Lines Show Association of MMP-1 Expression With STAT3 Activation

    Directory of Open Access Journals (Sweden)

    Alexander Schütz

    2015-04-01

    Full Text Available Signal transducer and activator of transcription 3 (STAT3 is constitutively activated in the majority of lung cancer. This study aims at defining connections between STAT3 function and the malignant properties of non–small cell lung carcinoma (NSCLC cells. To address possible mechanisms by which STAT3 influences invasiveness, the expression of matrix metalloproteinase-1 (MMP-1 was analyzed and correlated with the STAT3 activity status. Studies on both surgical biopsies and on lung cancer cell lines revealed a coincidence of STAT3 activation and strong expression of MMP-1. MMP-1 and tyrosine-phosphorylated activated STAT3 were found co-localized in cancer tissues, most pronounced in tumor fronts, and in particular in adenocarcinomas. STAT3 activity was constitutive, although to different degrees, in the lung cancer cell lines investigated. Three cell lines (BEN, KNS62, and A549 were identified in which STAT3 activitation was inducible by Interleukin-6 (IL-6. In A549 cells, STAT3 activity enhanced the level of MMP-1 mRNA and stimulated transcription from the MMP-1 promoter in IL-6–stimulated A549 cells. STAT3 specificity of this effect was confirmed by STAT3 knockdown through RNA interference. Our results link aberrant activity of STAT3 in lung cancer cells to malignant tumor progression through up-regulation of expression of invasiveness-associated MMPs.

  5. Enhanced tumor growth in the remaining lung after major lung resection.

    Science.gov (United States)

    Sano, Fumiho; Ueda, Kazuhiro; Murakami, Junichi; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

    2016-05-01

    Pneumonectomy induces active growth of the remaining lung in order to compensate for lost lung tissue. We hypothesized that tumor progression is enhanced in the activated local environment. We examined the effects of mechanical strain on the activation of lung growth and tumor progression in mice. The mechanical strain imposed on the right lung after left pneumonectomy was neutralized by filling the empty space that remained after pneumonectomy with a polypropylene prosthesis. The neutralization of the strain prevented active lung growth. According to an angiogenesis array, stronger monocyte chemoattractant protein-1 (MCP-1) expression was found in the strain-induced growing lung. The neutralization of the strain attenuated the release of MCP-1 from the lung cells. The intravenous injection of Lewis lung cancer cells resulted in the enhanced development of metastatic foci in the strain-induced growing lung, but the enhanced development was canceled by the neutralization of the strain. An immunohistochemical analysis revealed the prominent accumulation of tumor-associated macrophages in tumors arising in the strain-induced growing lung, and that there was a relationship between the accumulation and the MCP-1 expression status. Our results suggested that mechanical lung strain, induced by pulmonary resection, triggers active lung growth, thereby creating a tumor-friendly environment. The modification of that environment, as well as the minimizing of surgical stress, may be a meaningful strategy to improve the therapeutic outcome after lung cancer surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Transgenic Mice Overexpressing Vitamin D Receptor (VDR) Show Anti-Inflammatory Effects in Lung Tissues.

    Science.gov (United States)

    Ishii, Masaki; Yamaguchi, Yasuhiro; Isumi, Kyoko; Ogawa, Sumito; Akishita, Masahiro

    2017-12-01

    Vitamin D insufficiency is increasingly recognized as a prevalent problem worldwide, especially in patients with a chronic lung disease. Chronic obstructive pulmonary disease (COPD) is a type of chronic inflammatory lung disease. Previous clinical studies have shown that COPD leads to low vitamin D levels, which further increase the severity of COPD. Vitamin D homeostasis represents one of the most important factors that potentially determine the severity of COPD. Nonetheless, the mechanisms underlying the anti-inflammatory effects of vitamin D receptor (VDR) in lung tissues are still unclear. To investigate the anti-inflammatory effects of VDR, we generated transgenic mice that show lung-specific VDR overexpression under the control of the surfactant protein C promoter (TG mice). The TG mice were used to study the expression patterns of proinflammatory cytokines using real-time polymerase chain reaction and immunohistochemistry. The TG mice had lower levels of T helper 1 (Th1)-related cytokines than wild-type (WT) mice did. No significant differences in the expression of Th2 cytokines were observed between TG and WT mice. This study is the first to achieve lung-specific overexpression of VDR in TG mice: an interesting animal model useful for studying the relation between airway cell inflammation and vitamin D signaling. VDR expression is an important factor that influences anti-inflammatory responses in lung tissues. Our results show the crucial role of VDR in anti-inflammatory effects in lungs; these data are potentially useful for the treatment or prevention of COPD.

  7. Double polymer sheathed carbon nanotube supercapacitors show enhanced cycling stability

    Science.gov (United States)

    Zhao, Wenqi; Wang, Shanshan; Wang, Chunhui; Wu, Shiting; Xu, Wenjing; Zou, Mingchu; Ouyang, An; Cao, Anyuan; Li, Yibin

    2015-12-01

    Pseudo-materials are effective in boosting the specific capacitance of supercapacitors, but during service their degradation may also be very strong, causing reduced cycling stability. Here, we show that a carbon nanotube sponge grafted by two conventional pseudo-polymer layers in sequence can serve as a porous supercapacitor electrode with significantly enhanced cycling stability compared with single polymer grafting. Creating conformal polymer coatings on the nanotube surface and the resulting double-sheath configuration are important structural factors leading to the enhanced performance. Combining different polymers as double sheaths as reported here might be a potential route to circumvent the dilemma of pseudo-materials, and to simultaneously improve the capacitance and stability for various energy storage devices.Pseudo-materials are effective in boosting the specific capacitance of supercapacitors, but during service their degradation may also be very strong, causing reduced cycling stability. Here, we show that a carbon nanotube sponge grafted by two conventional pseudo-polymer layers in sequence can serve as a porous supercapacitor electrode with significantly enhanced cycling stability compared with single polymer grafting. Creating conformal polymer coatings on the nanotube surface and the resulting double-sheath configuration are important structural factors leading to the enhanced performance. Combining different polymers as double sheaths as reported here might be a potential route to circumvent the dilemma of pseudo-materials, and to simultaneously improve the capacitance and stability for various energy storage devices. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05978j

  8. Differential diagnosis between pulmonary tuberculosis and lung abscess by contrast enhanced CT

    International Nuclear Information System (INIS)

    Kanauchi, Tetsu; Hoshi, Toshiko; Konno, Miyuki; Hando, Yumiko

    2001-01-01

    The contrast enhanced CT findings in 14 patients with active tuberculosis and 26 patients with lung abscess were retrospectively analyzed. Reflecting the difference of pathogenesis between tuberculosis and abscess, the findings are widely different. The findings suggesting pulmonary tuberculosis rather than lung abscess were as follows; multiple and irregular necrotic areas, positive CT angiogram sign, no marginal enhancement surrounding necrosis. Contrast enhanced CT may help to distinguish pulmonary tuberculosis from lung abscess, especially in cases of caseous pneumonia showing broad consolidations or mass-like shadows. (author)

  9. Reversible Lansoprazole-Induced Interstitial Lung Disease Showing Improvement after Drug Cessation

    International Nuclear Information System (INIS)

    Hwang, Kyu Won; Woo, Ok Hee; Yong, Hwan Seok; Shin, Bong Kyung; Shim, Jae Jeong; Kang, Eun Young

    2008-01-01

    Lansoprazole is an acid proton-pump inhibitor that is similar to omeprazole. It is used to treat duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease (GERD) or Zollinger-Ellison syndrome. Common adverse effects of lansoprazole are diarrhea, abdominal pain, skin rash and/or itching. Information from U.S. National Library of Medicine warns that this drug can on rare occasion cause cough or cold-like symptoms. The pathophysiological mechanisms of lansoprazole-related pulmonary symptoms are not yet understood. In particular, there are no known reports regarding lansoprazole-induced interstitial lung diseases. We report here a case of interstitial lung disease (ILD) induced by oral administration of lansoprazole, which showed a pattern of nonspecific interstitial pneumonia (NSIP) as detected from a video-assisted thoracoscopic lung biopsy. We believe that this is the first report of a case of pathologically proven lansoprazole-induced ILD for which a surgical lung biopsy was performed. To the best of our knowledge, this is the first description of DI-ILD caused by lansoprazole. The diagnosis was made by considering the radiological, histopathological and clinical findings, including the close temporal relationship between lansoprazole exposure and symptom severity. Other possible causes were excluded due to a lack of a temporal relationship between the symptoms and work history or prednisolone therapy, and no other history of specific allergen exposure. When there is diffuse interstitial lung disease with an unknown etiology, it is important to remember that drugs can be the cause of pulmonary symptoms and it is crucial to take a careful patient history. If there is a recent history of taking lansoprazole in a patient with clinical and radiological findings of diffuse interstitial lung disease, we recommend stopping the medication to see if there is clinical and radiological improvement. That way, one can avoid using invasive procedures to

  10. Reversible Lansoprazole-Induced Interstitial Lung Disease Showing Improvement after Drug Cessation

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Kyu Won; Woo, Ok Hee; Yong, Hwan Seok; Shin, Bong Kyung; Shim, Jae Jeong; Kang, Eun Young [College of Medicine, Korea University, Guro Hospital, Seoul (Korea, Republic of)

    2008-04-15

    Lansoprazole is an acid proton-pump inhibitor that is similar to omeprazole. It is used to treat duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease (GERD) or Zollinger-Ellison syndrome. Common adverse effects of lansoprazole are diarrhea, abdominal pain, skin rash and/or itching. Information from U.S. National Library of Medicine warns that this drug can on rare occasion cause cough or cold-like symptoms. The pathophysiological mechanisms of lansoprazole-related pulmonary symptoms are not yet understood. In particular, there are no known reports regarding lansoprazole-induced interstitial lung diseases. We report here a case of interstitial lung disease (ILD) induced by oral administration of lansoprazole, which showed a pattern of nonspecific interstitial pneumonia (NSIP) as detected from a video-assisted thoracoscopic lung biopsy. We believe that this is the first report of a case of pathologically proven lansoprazole-induced ILD for which a surgical lung biopsy was performed. To the best of our knowledge, this is the first description of DI-ILD caused by lansoprazole. The diagnosis was made by considering the radiological, histopathological and clinical findings, including the close temporal relationship between lansoprazole exposure and symptom severity. Other possible causes were excluded due to a lack of a temporal relationship between the symptoms and work history or prednisolone therapy, and no other history of specific allergen exposure. When there is diffuse interstitial lung disease with an unknown etiology, it is important to remember that drugs can be the cause of pulmonary symptoms and it is crucial to take a careful patient history. If there is a recent history of taking lansoprazole in a patient with clinical and radiological findings of diffuse interstitial lung disease, we recommend stopping the medication to see if there is clinical and radiological improvement. That way, one can avoid using invasive procedures to

  11. Breast Cancer-Derived Lung Metastases Show Increased Pyruvate Carboxylase-Dependent Anaplerosis

    Directory of Open Access Journals (Sweden)

    Stefan Christen

    2016-10-01

    Full Text Available Cellular proliferation depends on refilling the tricarboxylic acid (TCA cycle to support biomass production (anaplerosis. The two major anaplerotic pathways in cells are pyruvate conversion to oxaloacetate via pyruvate carboxylase (PC and glutamine conversion to α-ketoglutarate. Cancers often show an organ-specific reliance on either pathway. However, it remains unknown whether they adapt their mode of anaplerosis when metastasizing to a distant organ. We measured PC-dependent anaplerosis in breast-cancer-derived lung metastases compared to their primary cancers using in vivo 13C tracer analysis. We discovered that lung metastases have higher PC-dependent anaplerosis compared to primary breast cancers. Based on in vitro analysis and a mathematical model for the determination of compartment-specific metabolite concentrations, we found that mitochondrial pyruvate concentrations can promote PC-dependent anaplerosis via enzyme kinetics. In conclusion, we show that breast cancer cells proliferating as lung metastases activate PC-dependent anaplerosis in response to the lung microenvironment.

  12. Low LET protons focused to submicrometer shows enhanced radiobiological effectiveness

    International Nuclear Information System (INIS)

    Schmid, T E; Zlobinskaya, O; Michalski, D; Molls, M; Multhoff, G; Greubel, C; Hable, V; Girst, S; Siebenwirth, C; Dollinger, G; Schmid, E

    2012-01-01

    This study shows that enhanced radiobiological effectiveness (RBE) values can be generated focusing low linear energy transfer (LET) radiation and thus changing the microdose distribution. 20 MeV protons (LET = 2.65 keV µm −1 ) are focused to submicrometer diameter at the ion microprobe superconducting nanoprobe for applied nuclear (Kern) physics experiments of the Munich tandem accelerator. The RBE values, as determined by measuring micronuclei (RBE MN = 1.48 ± 0.07) and dicentrics (RBE D = 1.92 ± 0.15), in human–hamster hybrid (A L ) cells are significantly higher when 117 protons were focused to a submicrometer irradiation field within a 5.4 × 5.4 µm 2 matrix compared to quasi homogeneous in a 1 × 1 µm 2 matrix applied protons (RBE MN = 1.28 ± 0.07; RBE D = 1.41 ± 0.14) at the same average dose of 1.7 Gy. The RBE values are normalized to standard 70 kV (dicentrics) or 200 kV (micronuclei) x-ray irradiation. The 117 protons applied per point deposit the same amount of energy like a 12 C ion with 55 MeV total energy (4.48 MeV u −1 ). The enhancements are about half of that obtained for 12 C ions (RBE MN = 2.20 ± 0.06 and RBE D = 3.21 ± 0.10) and they are attributed to intertrack interactions of the induced damages. The measured RBE values show differences from predictions of the local effect model (LEM III) that is used to calculate RBE values for irradiation plans to treat tumors with high LET particles. (paper)

  13. Low LET protons focused to submicrometer shows enhanced radiobiological effectiveness

    Science.gov (United States)

    Schmid, T. E.; Greubel, C.; Hable, V.; Zlobinskaya, O.; Michalski, D.; Girst, S.; Siebenwirth, C.; Schmid, E.; Molls, M.; Multhoff, G.; Dollinger, G.

    2012-10-01

    This study shows that enhanced radiobiological effectiveness (RBE) values can be generated focusing low linear energy transfer (LET) radiation and thus changing the microdose distribution. 20 MeV protons (LET = 2.65 keV µm-1) are focused to submicrometer diameter at the ion microprobe superconducting nanoprobe for applied nuclear (Kern) physics experiments of the Munich tandem accelerator. The RBE values, as determined by measuring micronuclei (RBEMN = 1.48 ± 0.07) and dicentrics (RBED = 1.92 ± 0.15), in human-hamster hybrid (AL) cells are significantly higher when 117 protons were focused to a submicrometer irradiation field within a 5.4 × 5.4 µm2 matrix compared to quasi homogeneous in a 1 × 1 µm2 matrix applied protons (RBEMN = 1.28 ± 0.07; RBED = 1.41 ± 0.14) at the same average dose of 1.7 Gy. The RBE values are normalized to standard 70 kV (dicentrics) or 200 kV (micronuclei) x-ray irradiation. The 117 protons applied per point deposit the same amount of energy like a 12C ion with 55 MeV total energy (4.48 MeV u-1). The enhancements are about half of that obtained for 12C ions (RBEMN = 2.20 ± 0.06 and RBED = 3.21 ± 0.10) and they are attributed to intertrack interactions of the induced damages. The measured RBE values show differences from predictions of the local effect model (LEM III) that is used to calculate RBE values for irradiation plans to treat tumors with high LET particles.

  14. Computed Tomography Assessment of Ablation Zone Enhancement in Patients With Early-Stage Lung Cancer After Stereotactic Ablative Radiotherapy.

    Science.gov (United States)

    Moore, William; Chaya, Yair; Chaudhry, Ammar; Depasquale, Britney; Glass, Samantha; Lee, Susan; Shin, James; Mikhail, George; Bhattacharji, Priya; Kim, Bong; Bilfinger, Thomas

    2015-01-01

    Stereotactic ablative radiotherapy (SABR) offers a curative treatment for lung cancer in patients who are marginal surgical candidates. However, unlike traditional surgery the lung cancer remains in place after treatment. Thus, imaging follow-up for evaluation of recurrence is of paramount importance. In this retrospective designed Institutional Review Board-approved study, follow-up contrast-enhanced computed tomography (CT) exams were performed on sixty one patients to evaluate enhancement pattern in the ablation zone at 1, 3, 6, and 12 months after SABR. Eleven patients had recurrence within the ablation zone after SABR. The postcontrast enhancement in the recurrence group showed a washin and washout phenomenon, whereas the radiation-induced lung injury group showed continuous enhancement suggesting an inflammatory process. The textural feature of the ablation zone of enhancement and perfusion as demonstrated in computed tomography nodule enhancement may allow early differentiation of recurrence from radiation-induced lung injury in patients' status after SABR or primary lung cancer.

  15. Contrast-enhanced MRI of the lung

    International Nuclear Information System (INIS)

    Kauczor, Hans-Ulrich; Kreitner, Karl-Friedrich

    2000-01-01

    The lung has long been neglected by MR imaging. This is due to unique intrinsic difficulties: (1) signal loss due to cardiac pulsation and respiration; (2) susceptibility artifacts caused by multiple air-tissue interfaces; (3) low proton density. There are many MR strategies to overcome these problems. They consist of breath-hold imaging, respiratory and cardiac gating procedures, use of short repetition and echo times, increase of the relaxivity of existing spins by administration of intravenous contrast agents, and enrichment of spin density by hyperpolarized noble gases or oxygen. Improvements in scanner performance and frequent use of contrast media have increased the interest in MR imaging and MR angiography of the lung. They can be used on a routine basis for the following indications: characterization of pulmonary nodules, staging of bronchogenic carcinoma, in particular assessment of chest wall invasion; evaluation of inflammatory activity in interstitial lung disease; acute pulmonary embolism, chronic thromboembolic pulmonary hypertension, vascular involvement in malignant disease; vascular abnormalities. Future perspectives include perfusion imaging using extracellular or intravascular (blood pool) contrast agents and ventilation imaging using inhalation of hyperpolarized noble gases, of paramagnetic oxygen or of aerosolized contrast agents. These techniques represent new approaches to functional lung imaging. The combination of visualization of morphology and functional assessment of ventilation and perfusion is unequalled by any other technique

  16. Human small-cell lung cancers show amplification and expression of the N-myc gene

    International Nuclear Information System (INIS)

    Nau, M.M.; Brooks, B.J. Jr.; Carney, D.N.; Gazdar, A.F.; Battey, J.F.; Sausville, E.A.; Minna, J.D.

    1986-01-01

    The authors have found that 6 of 31 independently derived human small-cell lung cancer (SCLC) cell lines have 5- to 170-fold amplified N-myc gene sequences. The amplification is seen with probes from two separate exons of N-myc, which are homologous to either the second or the third exon of the c-myc gene. Amplified N-myc sequences were found in a tumor cell line started prior to chemotherapy, in SCLC tumor samples harvested directly from tumor metastases at autopsy, and from a resected primary lung cancer. Several N-myc-amplified tumor cell lines also exhibited N-myc hybridizing fragments not in the germ-line position. In one patient's tumor, an additional amplitifed N-myc DNA fragment was observed and this fragment was heterogeneously distributed in liver metastases. In contrast to SCLC with neuroendocrine properties, no non-small-cell lung cancer lines examined were found to have N-myc amplification. Fragments encoding two N-myc exons also detect increased amounts of a 3.1-kilobase N-myc mRNA in N-myc-amplified SCLC lines and in one cell line that does not show N-myc gene amplification. Both DNA and RNA hybridization experiments, using a 32 P-labelled restriction probe, show that in any one SCLC cell line, only one myc-related gene is amplified and expressed. They conclude that N-myc amplification is both common and potentially significant in the tumorigenesis or tumor progression of SCLC

  17. Psychopaths show enhanced amygdala activation during fear conditioning

    Directory of Open Access Journals (Sweden)

    Douglas eSchultz

    2016-03-01

    Full Text Available Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into primary and secondary psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional fearlessness, while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths.

  18. Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline

    DEFF Research Database (Denmark)

    John, Catherine; Soler Artigas, María; Hui, Jennie

    2017-01-01

    BACKGROUND: Genome-wide association studies have identified numerous genetic regions that influence cross-sectional lung function. Longitudinal decline in lung function also includes a heritable component but the genetic determinants have yet to be defined. OBJECTIVES: We aimed to determine whether...... regions associated with cross-sectional lung function were also associated with longitudinal decline and to seek novel variants which influence decline. METHODS: We analysed genome-wide data from 4167 individuals from the Busselton Health Study cohort, who had undergone spirometry (12 695 observations...... across eight time points). A mixed model was fitted and weighted risk scores were calculated for the joint effect of 26 known regions on baseline and longitudinal changes in FEV1 and FEV1/FVC. Potential additional regions of interest were identified and followed up in two independent cohorts. RESULTS...

  19. MRI contrast enhancement of the lung using as Gd-DTPA aerosol

    International Nuclear Information System (INIS)

    Bockisch, A.; Harvey, R.C.; Davis, M.A.; Kabalka, G.W.

    1993-01-01

    The efficacy of a Gd-DTPA aerosol to enhance ventilated lung parenchyma was evaluated in an MR study in anesthetized female beagle dogs. Ventilation of a 1.0-M Gd-DTPA solution was performed using a commercially available atomizer. MR imaging was performed at a 1.9 T whole body imager with an acquisition mode that was gated to respiration. To quantify the amount of ventilated Gd-DTPA experiments were repeated with 99m Tc-DTPA under identical conditions. Using ventral and dorsal digital scintigraphy, the amount of Gd-DTPA in both lungs were determined. MR imaging showed on increase of signal intensity of 70% following Gd-DTPA ventilation. Because of the inherently low signal intensity of lung parenchyma this degree of contrast enhancement is too small to be clinically useful. (orig.) [de

  20. Myofibroblasts in interstitial lung diseases show diverse electron microscopic and invasive features.

    Science.gov (United States)

    Karvonen, Henna M; Lehtonen, Siri T; Sormunen, Raija T; Harju, Terttu H; Lappi-Blanco, Elisa; Bloigu, Risto S; Kaarteenaho, Riitta L

    2012-09-01

    The characteristic features of myofibroblasts in various lung disorders are poorly understood. We have evaluated the ultrastructure and invasive capacities of myofibroblasts cultured from small volumes of diagnostic bronchoalveolar lavage (BAL) fluid samples from patients with different types of lung diseases. Cells were cultured from samples of BAL fluid collected from 51 patients that had undergone bronchoscopy and BAL for diagnostic purposes. The cells were visualized by transmission electron microscopy and immunoelectron microscopy to achieve ultrastructural localization of alpha-smooth muscle actin (α-SMA) and fibronectin. The levels of α-SMA protein and mRNA and fibronectin mRNA were measured by western blot and quantitative real-time reverse transcriptase polymerase chain reaction. The invasive capacities of the cells were evaluated. The cultured cells were either fibroblasts or myofibroblasts. The structure of the fibronexus, and the amounts of intracellular actin, extracellular fibronectin and cell junctions of myofibroblasts varied in different diseases. In electron and immunoelectron microscopy, cells cultured from interstitial lung diseases (ILDs) expressed more actin filaments and α-SMA than normal lung. The invasive capacity of the cells obtained from patients with idiopathic pulmonary fibrosis was higher than that from patients with other type of ILDs. Cells expressing more actin filaments had a higher invasion capacity. It is concluded that electron and immunoelectron microscopic studies of myofibroblasts can reveal differential features in various diseases. An analysis of myofibroblasts cultured from diagnostic BAL fluid samples may represent a new kind of tool for diagnostics and research into lung diseases.

  1. Oxygen-enhanced MRI of the lungs. Intraindividual comparison between 1.5 and 3 Tesla

    International Nuclear Information System (INIS)

    Dietrich, Olaf; Thieme, S.F.; Maxien, D.; Nikolaou, K.; Reiser, M.; Schoenberg, S.O.; Fink, C.

    2011-01-01

    Purpose: To assess the feasibility of oxygen-enhanced MRI of the lung at 3 Tesla and to compare signal characteristics with 1.5 Tesla. Materials and Methods: 13 volunteers underwent oxygen-enhanced lung MRI at 1.5 and 3 T with a T 1-weighted single-slice non-selective inversion-recovery single-shot half-Fourier fast-spin-echo sequence with simultaneous respiratory and cardiac triggering in coronal orientation. 40 measurements were acquired during room air breathing and subsequently during oxygen breathing (15 L/min, close-fitting face-mask). The signal-to-noise ratio (SNR) of the lung tissue was determined with a difference image method. The image quality of all acquisitions was visually assessed. The mean values of the oxygen-induced relative signal enhancement and its regional coefficient of variation were calculated and the signal enhancement was displayed as color-coded parameter maps. Oxygen-enhancement maps were visually assessed with respect to the distribution and heterogeneity of the oxygen-related signal enhancement at both field strengths. Results: The mean relative signal enhancement due to oxygen breathing was 13 % (± 5.6 %) at 1.5 T and of 9.0 % (± 8.0 %) at 3 T. The regional coefficient of variation was significantly higher at 3 T. Visual and quantitative assessment of the enhancement maps showed considerably less homogeneous distribution of the signal enhancement at 3 T. The SNR was not significantly different but showed a trend to slightly higher values (increase of about 10 %) at 3 T. Conclusion: Oxygen-enhanced pulmonary MRI is feasible at 3 Tesla. However, signal enhancement is currently more heterogeneous and slightly lower at 3 T. (orig.)

  2. Collateral ventilation to congenital hyperlucent lung lesions assessed on xenon-enhanced dynamic dual-energy CT: an initial experience.

    Science.gov (United States)

    Goo, Hyun Woo; Yang, Dong Hyun; Kim, Namkug; Park, Seung Il; Kim, Dong Kwan; Kim, Ellen Ai-Rhan

    2011-01-01

    We wanted to evaluate the resistance to collateral ventilation in congenital hyperlucent lung lesions and to correlate that with the anatomic findings on xenon-enhanced dynamic dual-energy CT. Xenon-enhanced dynamic dual-energy CT was successfully and safely performed in eight children (median age: 5.5 years, 4 boys and 4 girls) with congenital hyperlucent lung lesions. Functional assessment of the lung lesions on the xenon map was done, including performing a time-xenon value curve analysis and assessing the amplitude of xenon enhancement (A) value, the rate of xenon enhancement (K) value and the time of arrival value. Based on the A value, the lung lesions were categorized into high or low (A value > 10 Hounsfield unit [HU]) resistance to collateral ventilation. In addition, the morphologic CT findings of the lung lesions, including cyst, mucocele and an accessory or incomplete fissure, were assessed on the weighted-average CT images. The xenon-enhanced CT radiation dose was estimated. Five of the eight lung lesions were categorized into the high resistance group and three lesions were categorized into the low resistance group. The A and K values in the normal lung were higher than those in the low resistance group. The time of arrival values were delayed in the low resistance group. Cysts were identified in five lesions, mucocele in four, accessory fissure in three and incomplete fissure in two. Either cyst or an accessory fissure was seen in four of the five lesions showing high resistance to collateral ventilation. The xenon-enhanced CT radiation dose was 2.3 ± 0.6 mSv. Xenon-enhanced dynamic dual-energy CT can help visualize and quantitate various degrees of collateral ventilation to congenital hyperlucent lung lesions in addition to assessing the anatomic details of the lung.

  3. Diagnostic Accuracy of Dynamic Contrast Enhanced Magnetic Resonance Imaging in Characterizing Lung Masses

    Science.gov (United States)

    Inan, Nagihan; Arslan, Arzu; Donmez, Muhammed; Sarisoy, Hasan Tahsin

    2016-01-01

    Background Imaging plays a critical role not only in the detection, but also in the characterization of lung masses as benign or malignant. Objectives To determine the diagnostic accuracy of dynamic magnetic resonance imaging (MRI) in the differential diagnosis of benign and malignant lung masses. Patients and Methods Ninety-four masses were included in this prospective study. Five dynamic series of T1-weighted spoiled gradient echo (FFE) images were obtained, followed by a T1-weighted FFE sequence in the late phase (5th minutes). Contrast enhancement patterns in the early (25th second) and late (5th minute) phase images were evaluated. For the quantitative evaluation, signal intensity (SI)-time curves were obtained and the maximum relative enhancement, wash-in rate, and time-to-peak enhancement of masses in both groups were calculated. Results The early phase contrast enhancement patterns were homogeneous in 78.2% of the benign masses, while heterogeneous in 74.4% of the malignant tumors. On the late phase images, 70.8% of the benign masses showed homogeneous enhancement, while most of the malignant masses showed heterogeneous enhancement (82.4%). During the first pass, the maximum relative enhancement and wash-in rate values of malignant masses were significantly higher than those of the benign masses (P = 0.03 and 0.04, respectively). The cutoff value at 15% yielded a sensitivity of 85.4%, specificity of 61.2%, and positive predictive value of 68.7% for the maximum relative enhancement. Conclusion Contrast enhancement patterns and SI-time curve analysis of MRI are helpful in the differential diagnosis of benign and malignant lung masses. PMID:27703654

  4. Contrast-enhanced 3D MRI of lung perfusion in children with cystic fibrosis - initial results

    International Nuclear Information System (INIS)

    Eichinger, Monika; Puderbach, Michael; Zuna, Ivan; Kauczor, Hans-Ulrich; Fink, Christian; Gahr, Julie; Mueller, Frank-Michael; Ley, Sebastian; Plathow, Christian; Tuengerthal, Siegfried

    2006-01-01

    This paper is a feasibility study of magnetic resonance imaging (MRI) of lung perfusion in children with cystic fibrosis (CF) using contrast-enhanced 3D MRI. Correlation assessment of perfusion changes with structural abnormalities. Eleven CF patients (9 f, 2 m; median age 16 years) were examined at 1.5 T. Morphology: HASTE coronal, transversal (TR/TE/α/ST: 600 ms/28 ms/180 /6 mm), breath-hold 18 s. Perfusion: Time-resolved 3D GRE pulse sequence (FLASH, TE/TR/α: 0.8/1.9 ms/40 ), parallel imaging (GRAPPA, PAT 2). Twenty-five data sets were acquired after intravenous injection of 0.1 mmol/kg body weight of gadodiamide, 3-5 ml/s. A total of 198 lung segments were analyzed by two radiologists in consensus and scored for morphological and perfusion changes. Statistical analysis was performed by Mantel-Haenszel chi-square test. Results showed that perfusion defects were observed in all patients and present in 80% of upper, and 39% of lower lobes. Normal lung parenchyma showed homogeneous perfusion (86%, P<0.0001). Severe morphological changes led to perfusion defects (97%, P<0.0001). Segments with moderate morphological changes showed normal (53%) or impaired perfusion (47%). In conclusion, pulmonary perfusion is easy to judge in segments with normal parenchyma or severe changes. In moderately damaged segments, MRI of lung perfusion may help to better assess actual functional impairment. Contrast-enhanced 3D MRI of lung perfusion has the potential for early vascular functional assessment and therapy control in CF patients. (orig.)

  5. Value of radio density determined by enhanced computed tomography for the differential diagnosis of lung masses

    International Nuclear Information System (INIS)

    Xie, Min

    2011-01-01

    Lung masses are often difficult to differentiate when their clinical symptoms and shapes or densities on computed tomography images are similar. However, with different pathological contents, they may appear differently on plain and enhanced computed tomography. Objectives: To determine the value of enhanced computed tomography for the differential diagnosis of lung masses based on the differences in radio density with and without enhancement. Patients and Methods: Thirty-six patients with lung cancer, 36 with pulmonary tuberculosis and 10 with inflammatory lung pseudo tumors diagnosed by computed tomography and confirmed by pathology in our hospital were selected. The mean ±SD radio densities of lung masses in the three groups of patients were calculated based on the results of plain and enhanced computed tomography. Results: There were no significant differences in the radio densities of the masses detected by plain computed tomography among patients with inflammatory lung pseudo tumors, tuberculosis and lung cancer (P> 0.05). However, there were significant differences (P< 0.01)between all the groups in terms of radio densities of masses detected by enhanced computed tomography. Conclusions: The radio densities of lung masses detected by enhanced computed tomography could potentially be used to differentiate between lung cancer, pulmonary tuberculosis and inflammatory lung pseudo tumors.

  6. An actuarial analysis shows that offering lung cancer screening as an insurance benefit would save lives at relatively low cost.

    Science.gov (United States)

    Pyenson, Bruce S; Sander, Marcia S; Jiang, Yiding; Kahn, Howard; Mulshine, James L

    2012-04-01

    Lung cancer screening is not established as a public health practice, yet the results of a recent large randomized controlled trial showed that screening with low-dose spiral computed tomography reduces lung cancer mortality. Using actuarial models, this study estimated the costs and benefits of annual lung cancer screening offered as a commercial insurance benefit in the high-risk US population ages 50-64. Assuming current commercial reimbursement rates for treatment, we found that screening would cost about $1 per insured member per month in 2012 dollars. The cost per life-year saved would be below $19,000, an amount that compares favorably with screening for cervical, breast, and colorectal cancers. Our results suggest that commercial insurers should consider lung cancer screening of high-risk individuals to be high-value coverage and provide it as a benefit to people who are at least fifty years old and have a smoking history of thirty pack-years or more. We also believe that payers and patients should demand screening from high-quality, low-cost providers, thus helping set an example of efficient system innovation.

  7. Modeling serotonin uptake in the lung shows endothelial transporters dominate over cleft permeation

    Science.gov (United States)

    Bassingthwaighte, James B.

    2013-01-01

    A four-region (capillary plasma, endothelium, interstitial fluid, cell) multipath model was configured to describe the kinetics of blood-tissue exchange for small solutes in the lung, accounting for regional flow heterogeneity, permeation of cell membranes and through interendothelial clefts, and intracellular reactions. Serotonin uptake data from the Multiple indicator dilution “bolus sweep” experiments of Rickaby and coworkers (Rickaby DA, Linehan JH, Bronikowski TA, Dawson CA. J Appl Physiol 51: 405–414, 1981; Rickaby DA, Dawson CA, and Linehan JH. J Appl Physiol 56: 1170–1177, 1984) and Malcorps et al. (Malcorps CM, Dawson CA, Linehan JH, Bronikowski TA, Rickaby DA, Herman AG, Will JA. J Appl Physiol 57: 720–730, 1984) were analyzed to distinguish facilitated transport into the endothelial cells (EC) and the inhibition of tracer transport by nontracer serotonin in the bolus of injectate from the free uninhibited permeation through the clefts into the interstitial fluid space. The permeability-surface area products (PS) for serotonin via the inter-EC clefts were ∼0.3 ml·g−1·min−1, low compared with the transporter-mediated maximum PS of 13 ml·g−1·min−1 (with Km = ∼0.3 μM and Vmax = ∼4 nmol·g−1·min−1). The estimates of serotonin PS values for EC transporters from their multiple data sets were similar and were influenced only modestly by accounting for the cleft permeability in parallel. The cleft PS estimates in these Ringer-perfused lungs are less than half of those for anesthetized dogs (Yipintsoi T. Circ Res 39: 523–531, 1976) with normal hematocrits, but are compatible with passive noncarrier-mediated transport observed later in the same laboratory (Dawson CA, Linehan JH, Rickaby DA, Bronikowski TA. Ann Biomed Eng 15: 217–227, 1987; Peeters FAM, Bronikowski TA, Dawson CA, Linehan JH, Bult H, Herman AG. J Appl Physiol 66: 2328–2337, 1989) The identification and quantitation of the cleft pathway conductance from these

  8. Loss of hypoxia-inducible factor 2 alpha in the lung alveolar epithelium of mice leads to enhanced eosinophilic inflammation in cobalt-induced lung injury.

    Science.gov (United States)

    Proper, Steven P; Saini, Yogesh; Greenwood, Krista K; Bramble, Lori A; Downing, Nathaniel J; Harkema, Jack R; Lapres, John J

    2014-02-01

    Hard metal lung disease (HMLD) is an occupational lung disease specific to inhalation of cobalt-containing particles whose mechanism is largely unknown. Cobalt is a known hypoxia mimic and stabilizer of the alpha subunits of hypoxia-inducible factors (HIFs). Previous work revealed that though HIF1α contrib utes to cobalt toxicity in vitro, loss of HIF1α in the alveolar epithelial cells does not provide in vivo protection from cobalt-induced lung inflammation. HIF1α and HIF2α show unique tissue expression profiles, and HIF2α is known to be the predominant HIF mRNA isoform in the adult lung. Thus, if HIF2α activation by cobalt contributes to pathophysiology of HMLD, we hypothesized that loss of HIF2α in lung epithelium would provide protection from cobalt-induced inflammation. Mice with HIF2α-deficiency in Club and alveolar type II epithelial cells (ATIIs) (HIF2α(Δ/Δ)) were exposed to cobalt (60 µg/day) or saline using a subacute occupational exposure model. Bronchoalveolar lavage cellularity, cytokines, qRT-PCR, and histopathology were analyzed. Results show that loss of HIF2α leads to enhanced eosinophilic inflammation and increased goblet cell metaplasia. Additionally, control mice demonstrated a mild recovery from cobalt-induced lung injury compared with HIF2α(Δ/Δ) mice, suggesting a role for epithelial HIF2α in repair mechanisms. The expression of important cytokines, such as interleukin (IL)-5 and IL-10, displayed significant differences following cobalt exposure when HIF2α(Δ/Δ) and control mice were compared. In summary, our data suggest that although loss of HIF2α does not afford protection from cobalt-induced lung inflammation, epithelial HIF2α signaling does play an important role in modulating the inflammatory and repair response in the lung.

  9. Gadolinium-DTPA enhancement of regional lymph nodes of lung cancer in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Iwai, Naomichi; Yamaguchi, Yutaka

    1991-01-01

    Enhanced MR imagings were performed on thirty-one patients with lung cancer by intravenous administration of 0.1 mmol/kg Gadolinium-DTPA (Gd-DTPA). A spin-echo pulse sequence (SE 400/40) with 0.5-T MR system was used. The Gd-DTPA enhancement of lymph nodes was studied for 67 nodes (29 metastatic lymph nodes and 38 non-metastatic lymph nodes) on the hilar and mediastinal region. The mean signal intensity of metastatic lymph nodes was enhanced higher than that of non-metastatic lymph nodes (p<0.001). On the criterion of the signal intensity change (the cutoff point: 800 S.I) at 5 minutes after administration, the diagnostic rates on retrospective study showed a sensitivity of 79 %, a specificity of 84 % and an overall accuracy of 82%. These data show higher rates than those of the size criteria. This study suggests a significant potential for improved detection of lymph node metastasis of lung cancer with Gd-DTPA enhanced MR imaging. (author)

  10. Dose enhancement in radiotherapy of small lung tumors using inline magnetic fields: A Monte Carlo based planning study

    Energy Technology Data Exchange (ETDEWEB)

    Oborn, B. M., E-mail: brad.oborn@gmail.com [Illawarra Cancer Care Centre (ICCC), Wollongong, NSW 2500, Australia and Centre for Medical Radiation Physics (CMRP), University of Wollongong, Wollongong, NSW 2500 (Australia); Ge, Y. [Sydney Medical School, University of Sydney, NSW 2006 (Australia); Hardcastle, N. [Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, NSW 2065 (Australia); Metcalfe, P. E. [Centre for Medical Radiation Physics (CMRP), University of Wollongong, Wollongong NSW 2500, Australia and Ingham Institute for Applied Medical Research, Liverpool, NSW 2170 (Australia); Keall, P. J. [Sydney Medical School, University of Sydney, NSW 2006, Australia and Ingham Institute for Applied Medical Research, Liverpool, NSW 2170 (Australia)

    2016-01-15

    Purpose: To report on significant dose enhancement effects caused by magnetic fields aligned parallel to 6 MV photon beam radiotherapy of small lung tumors. Findings are applicable to future inline MRI-guided radiotherapy systems. Methods: A total of eight clinical lung tumor cases were recalculated using Monte Carlo methods, and external magnetic fields of 0.5, 1.0, and 3 T were included to observe the impact on dose to the planning target volume (PTV) and gross tumor volume (GTV). Three plans were 6 MV 3D-CRT plans while 6 were 6 MV IMRT. The GTV’s ranged from 0.8 to 16 cm{sup 3}, while the PTV’s ranged from 1 to 59 cm{sup 3}. In addition, the dose changes in a 30 cm diameter cylindrical water phantom were investigated for small beams. The central 20 cm of this phantom contained either water or lung density insert. Results: For single beams, an inline magnetic field of 1 T has a small impact in lung dose distributions by reducing the lateral scatter of secondary electrons, resulting in a small dose increase along the beam. Superposition of multiple small beams leads to significant dose enhancements. Clinically, this process occurs in the lung tissue typically surrounding the GTV, resulting in increases to the D{sub 98%} (PTV). Two isolated tumors with very small PTVs (3 and 6 cm{sup 3}) showed increases in D{sub 98%} of 23% and 22%. Larger PTVs of 13, 26, and 59 cm{sup 3} had increases of 9%, 6%, and 4%, describing a natural fall-off in enhancement with increasing PTV size. However, three PTVs bounded to the lung wall showed no significant increase, due to lack of dose enhancement in the denser PTV volume. In general, at 0.5 T, the GTV mean dose enhancement is around 60% lower than that at 1 T, while at 3 T, it is 5%–60% higher than 1 T. Conclusions: Monte Carlo methods have described significant and predictable dose enhancement effects in small lung tumor plans for 6 MV radiotherapy when an external inline magnetic field is included. Results of this study

  11. Hepatic scar in a case of healed candidiasis showing prolonged enhancement on CT

    International Nuclear Information System (INIS)

    Itai, Yuji; Yashiro, Naobumi

    1987-01-01

    A patient with acute myelocytic leukemia recovering from hepatic candidiasis after long-term administration of amphotericin B had large scar in the liver which showed prominent prolonged enhancement on postcontrast CT. Prolonged enhancement can occur in regions other than hepatic masses. (author)

  12. Hepatic scar in a case of healed candidiasis showing prolonged enhancement on CT

    Energy Technology Data Exchange (ETDEWEB)

    Itai, Yuji; Yashiro, Naobumi

    1987-08-01

    A patient with acute myelocytic leukemia recovering from hepatic candidiasis after long-term administration of amphotericin B had large scar in the liver which showed prominent prolonged enhancement on postcontrast CT. Prolonged enhancement can occur in regions other than hepatic masses.

  13. Riboflavin at high doses enhances lung cancer cell proliferation, invasion, and migration.

    Science.gov (United States)

    Yang, Hui-ting; Chao, Pei-chun; Yin, Mei-chin

    2013-02-01

    The influence of riboflavin (vitamin B(2) ) upon growth, invasion, and migration in non-small cell lung cancer cell lines was evaluated. Riboflavin at 1, 10, 25, 50, 100, 200, or 400 μmol/L was added into A549, H3255, or Calu-6 cells. The effects of this compound upon level and/or expression of reactive oxygen species (ROS), inflammatory cytokines, intercellular adhesion molecule (ICAM)-1, fibronectin, matrix metalloproteinase (MMP)-9, MMP-2, focal adhesion kinase (FAK), nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) were examined. Results showed that riboflavin at test doses did not affect the level of ROS and glutathione. Riboflavin at 200 and 400 μmol/L significantly enhanced cell growth in test lung cancer cell lines, and at 400 μmol/L significantly increased the release of interleukin-6, tumor necrosis factor-alpha, and vascular endothelial growth factor. This agent at 200 and 400 μmol/L also upregulated protein production of ICAM-1, fibronectin, MMP-9, MMP-2, NF-κB p50, p-p38 MAPK, and FAK; and at 400 μmol/L enhanced invasion and migration in test cell lines. These findings suggested that riboflavin at high doses might promote lung cancer progression. © 2013 Institute of Food Technologists®

  14. Vessel Enhancement and Segmentation of 4D CT Lung Image Using Stick Tensor Voting

    Science.gov (United States)

    Cong, Tan; Hao, Yang; Jingli, Shi; Xuan, Yang

    2016-12-01

    Vessel enhancement and segmentation plays a significant role in medical image analysis. This paper proposes a novel vessel enhancement and segmentation method for 4D CT lung image using stick tensor voting algorithm, which focuses on addressing the vessel distortion issue of vessel enhancement diffusion (VED) method. Furthermore, the enhanced results are easily segmented using level-set segmentation. In our method, firstly, vessels are filtered using Frangi's filter to reduce intrapulmonary noises and extract rough blood vessels. Secondly, stick tensor voting algorithm is employed to estimate the correct direction along the vessel. Then the estimated direction along the vessel is used as the anisotropic diffusion direction of vessel in VED algorithm, which makes the intensity diffusion of points locating at the vessel wall be consistent with the directions of vessels and enhance the tubular features of vessels. Finally, vessels can be extracted from the enhanced image by applying level-set segmentation method. A number of experiments results show that our method outperforms traditional VED method in vessel enhancement and results in satisfied segmented vessels.

  15. Resolution enhancement of lung 4D-CT via group-sparsity

    International Nuclear Information System (INIS)

    Bhavsar, Arnav; Wu, Guorong; Shen, Dinggang; Lian, Jun

    2013-01-01

    Purpose: 4D-CT typically delivers more accurate information about anatomical structures in the lung, over 3D-CT, due to its ability to capture visual information of the lung motion across different respiratory phases. This helps to better determine the dose during radiation therapy for lung cancer. However, a critical concern with 4D-CT that substantially compromises this advantage is the low superior-inferior resolution due to less number of acquired slices, in order to control the CT radiation dose. To address this limitation, the authors propose an approach to reconstruct missing intermediate slices, so as to improve the superior-inferior resolution.Methods: In this method the authors exploit the observation that sampling information across respiratory phases in 4D-CT can be complimentary due to lung motion. The authors’ approach uses this locally complimentary information across phases in a patch-based sparse-representation framework. Moreover, unlike some recent approaches that treat local patches independently, the authors’ approach employs the group-sparsity framework that imposes neighborhood and similarity constraints between patches. This helps in mitigating the trade-off between noise robustness and structure preservation, which is an important consideration in resolution enhancement. The authors discuss the regularizing ability of group-sparsity, which helps in reducing the effect of noise and enables better structural localization and enhancement.Results: The authors perform extensive experiments on the publicly available DIR-Lab Lung 4D-CT dataset [R. Castillo, E. Castillo, R. Guerra, V. Johnson, T. McPhail, A. Garg, and T. Guerrero, “A framework for evaluation of deformable image registration spatial accuracy using large landmark point sets,” Phys. Med. Biol. 54, 1849–1870 (2009)]. First, the authors carry out empirical parametric analysis of some important parameters in their approach. The authors then demonstrate, qualitatively as well as

  16. MiR-26a enhances invasive capacity by suppressing GSK3β in human lung cancer cells

    International Nuclear Information System (INIS)

    Lin, Gaoyang; Liu, Boning; Meng, Zhaowei; Liu, Yunde; Li, Xuebing; Wu, Xiang; Zhou, Qinghua; Xu, Ke

    2017-01-01

    Lung cancer is the common cause of death from cancer, and most lung cancer patients die of metastasis. MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. There are several studies showed that miR-26a is involved in carcinogenesis, however, its role in tumor metastasis need to be elucidated. In this study, we showed that ectopic expression of miR-26a enhanced migration and invasion of lung cancer cells. Glycogen synthase kinase-3β (GSK3β) was identified as a direct target of miR-26a. GSK3β expression negatively correlated with miR-26a expression in lung cancer tissues. Silencing of GSK3β achieved similar effect as miR-26a over-expression; over-expression of GSK3β reversed the enhanced effect of miR-26a on lung cancer cell migration and invasion. Further study indicated that miR-26a increased β-catenin expression and nuclear translocation. C-myc and cyclin D1, the downstream genes of β-catenin, were also up-regulated by miR-26a. Furthermore, xenograft study showed that miR-26a promoted lung cancer cell growth in vivo, and suppressed GSK3β expression. Collectively, our results demonstrated that miR-26a enhanced metastatic potential of lung cancer cells via activation of β-catenin pathway by targeting GSK3β, suggesting the potential applicability of miR-26a as a target for cancer treatment. - Highlights: • miR-26a enhances migration and invasion of lung cancer cells. • GSK3β is identified as a direct target of miR-26a. • miR-26a activates β-catenin pathway by targeting GSK3β. • miR-26a promotes lung cancer cell growth in vivo.

  17. MiR-26a enhances invasive capacity by suppressing GSK3β in human lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Gaoyang; Liu, Boning [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Meng, Zhaowei [Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin 300052 (China); Liu, Yunde [School of Laboratory Medicine, Tianjin Medical University, Tianjin 300052 (China); Li, Xuebing [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Wu, Xiang [Core Facility Center, Tianjin Medical University General Hospital, Tianjin 300052 (China); Zhou, Qinghua [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Xu, Ke, E-mail: ke_xu@hotmail.com [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China)

    2017-03-15

    Lung cancer is the common cause of death from cancer, and most lung cancer patients die of metastasis. MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. There are several studies showed that miR-26a is involved in carcinogenesis, however, its role in tumor metastasis need to be elucidated. In this study, we showed that ectopic expression of miR-26a enhanced migration and invasion of lung cancer cells. Glycogen synthase kinase-3β (GSK3β) was identified as a direct target of miR-26a. GSK3β expression negatively correlated with miR-26a expression in lung cancer tissues. Silencing of GSK3β achieved similar effect as miR-26a over-expression; over-expression of GSK3β reversed the enhanced effect of miR-26a on lung cancer cell migration and invasion. Further study indicated that miR-26a increased β-catenin expression and nuclear translocation. C-myc and cyclin D1, the downstream genes of β-catenin, were also up-regulated by miR-26a. Furthermore, xenograft study showed that miR-26a promoted lung cancer cell growth in vivo, and suppressed GSK3β expression. Collectively, our results demonstrated that miR-26a enhanced metastatic potential of lung cancer cells via activation of β-catenin pathway by targeting GSK3β, suggesting the potential applicability of miR-26a as a target for cancer treatment. - Highlights: • miR-26a enhances migration and invasion of lung cancer cells. • GSK3β is identified as a direct target of miR-26a. • miR-26a activates β-catenin pathway by targeting GSK3β. • miR-26a promotes lung cancer cell growth in vivo.

  18. Proteomic Analysis Shows Constitutive Secretion of MIF and p53-associated Activity of COX-2−/− Lung Fibroblasts

    Directory of Open Access Journals (Sweden)

    Mandar Dave

    2017-12-01

    Full Text Available The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor (MIF in lung fibroblasts derived from COX-2−/− but not wild-type (WT or COX-1−/− mice. MIF was spontaneously released in high levels into the extracellular milieu of COX2−/− fibroblasts seemingly from the preformed intracellular stores, with no change in the basal gene expression of MIF. The secretion and regulation of MIF in COX-2−/− was “prostaglandin-independent.” GO analysis showed that concurrent with upregulation of MIF, there is a significant surge in expression of genes related to fibroblast growth, FK506 binding proteins, and isomerase activity in COX-2−/− cells. Furthermore, COX-2−/− fibroblasts also exhibit a significant increase in transcriptional activity of various regulators, antagonists, and co-modulators of p53, as well as in the expression of oncogenes and related transcripts. Integrative Oncogenomics Cancer Browser (IntroGen analysis shows downregulation of COX-2 and amplification of MIF and/or p53 activity during development of glioblastomas, ependymoma, and colon adenomas. These data indicate the functional role of the MIF-COX-p53 axis in inflammation and cancer at the genomic and proteomic levels in COX-2-ablated cells. This systematic analysis not only shows the proinflammatory state but also unveils a molecular signature of a pro-oncogenic state of COX-1 in COX-2 ablated cells.

  19. Activated prostaglandin D2 receptors on macrophages enhance neutrophil recruitment into the lung

    Science.gov (United States)

    Jandl, Katharina; Stacher, Elvira; Bálint, Zoltán; Sturm, Eva Maria; Maric, Jovana; Peinhaupt, Miriam; Luschnig, Petra; Aringer, Ida; Fauland, Alexander; Konya, Viktoria; Dahlen, Sven-Erik; Wheelock, Craig E.; Kratky, Dagmar; Olschewski, Andrea; Marsche, Gunther; Schuligoi, Rufina; Heinemann, Akos

    2016-01-01

    Background Prostaglandin (PG) D2 is an early-phase mediator in inflammation, but its action and the roles of the 2 D-type prostanoid receptors (DPs) DP1 and DP2 (also called chemoattractant receptor–homologous molecule expressed on TH2 cells) in regulating macrophages have not been elucidated to date. Objective We investigated the role of PGD2 receptors on primary human macrophages, as well as primary murine lung macrophages, and their ability to influence neutrophil action in vitro and in vivo. Methods In vitro studies, including migration, Ca2+ flux, and cytokine secretion, were conducted with primary human monocyte-derived macrophages and neutrophils and freshly isolated murine alveolar and pulmonary interstitial macrophages. In vivo pulmonary inflammation was assessed in male BALB/c mice. Results Activation of DP1, DP2, or both receptors on human macrophages induced strong intracellular Ca2+ flux, cytokine release, and migration of macrophages. In a murine model of LPS-induced pulmonary inflammation, activation of each PGD2 receptor resulted in aggravated airway neutrophilia, tissue myeloperoxidase activity, cytokine contents, and decreased lung compliance. Selective depletion of alveolar macrophages abolished the PGD2-enhanced inflammatory response. Activation of PGD2 receptors on human macrophages enhanced the migratory capacity and prolonged the survival of neutrophils in vitro. In human lung tissue specimens both DP1 and DP2 receptors were located on alveolar macrophages along with hematopoietic PGD synthase, the rate-limiting enzyme of PGD2 synthesis. Conclusion For the first time, our results show that PGD2 markedly augments disease activity through its ability to enhance the proinflammatory actions of macrophages and subsequent neutrophil activation. PMID:26792210

  20. Resolution enhancement of lung 4D-CT data using multiscale interphase iterative nonlocal means

    International Nuclear Information System (INIS)

    Zhang Yu; Yap, Pew-Thian; Wu Guorong; Feng Qianjin; Chen Wufan; Lian Jun; Shen Dinggang

    2013-01-01

    Purpose: Four-dimensional computer tomography (4D-CT) has been widely used in lung cancer radiotherapy due to its capability in providing important tumor motion information. However, the prolonged scanning duration required by 4D-CT causes considerable increase in radiation dose. To minimize the radiation-related health risk, radiation dose is often reduced at the expense of interslice spatial resolution. However, inadequate resolution in 4D-CT causes artifacts and increases uncertainty in tumor localization, which eventually results in extra damages of healthy tissues during radiotherapy. In this paper, the authors propose a novel postprocessing algorithm to enhance the resolution of lung 4D-CT data. Methods: The authors' premise is that anatomical information missing in one phase can be recovered from the complementary information embedded in other phases. The authors employ a patch-based mechanism to propagate information across phases for the reconstruction of intermediate slices in the longitudinal direction, where resolution is normally the lowest. Specifically, the structurally matching and spatially nearby patches are combined for reconstruction of each patch. For greater sensitivity to anatomical details, the authors employ a quad-tree technique to adaptively partition the image for more fine-grained refinement. The authors further devise an iterative strategy for significant enhancement of anatomical details. Results: The authors evaluated their algorithm using a publicly available lung data that consist of 10 4D-CT cases. The authors’ algorithm gives very promising results with significantly enhanced image structures and much less artifacts. Quantitative analysis shows that the authors’ algorithm increases peak signal-to-noise ratio by 3–4 dB and the structural similarity index by 3%–5% when compared with the standard interpolation-based algorithms. Conclusions: The authors have developed a new algorithm to improve the resolution of 4D-CT. It

  1. Enhanced expression of G-protein coupled estrogen receptor (GPER/GPR30) in lung cancer

    International Nuclear Information System (INIS)

    Jala, Venkatakrishna Rao; Radde, Brandie N; Haribabu, Bodduluri; Klinge, Carolyn M

    2012-01-01

    G-protein-coupled estrogen receptor (GPER/GPR30) was reported to bind 17β-estradiol (E 2 ), tamoxifen, and ICI 182,780 (fulvestrant) and promotes activation of epidermal growth factor receptor (EGFR)-mediated signaling in breast, endometrial and thyroid cancer cells. Although lung adenocarcinomas express estrogen receptors α and β (ERα and ERβ), the expression of GPER in lung cancer has not been investigated. The purpose of this study was to examine the expression of GPER in lung cancer. The expression patterns of GPER in various lung cancer lines and lung tumors were investigated using standard quantitative real time PCR (at mRNA levels), Western blot and immunohistochemistry (IHC) methods (at protein levels). The expression of GPER was scored and the pairwise comparisons (cancer vs adjacent tissues as well as cancer vs normal lung tissues) were performed. Analysis by real-time PCR and Western blotting revealed a significantly higher expression of GPER at both mRNA and protein levels in human non small cell lung cancer cell (NSCLC) lines relative to immortalized normal lung bronchial epithelial cells (HBECs). The virally immortalized human small airway epithelial cell line HPL1D showed higher expression than HBECs and similar expression to NSCLC cells. Immunohistochemical analysis of tissue sections of murine lung adenomas as well as human lung adenocarcinomas, squamous cell carcinomas and non-small cell lung carcinomas showed consistently higher expression of GPER in the tumor relative to the surrounding non-tumor tissue. The results from this study demonstrate increased GPER expression in lung cancer cells and tumors compared to normal lung. Further evaluation of the function and regulation of GPER will be necessary to determine if GPER is a marker of lung cancer progression

  2. Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Costello Joseph F

    2008-07-01

    Full Text Available Abstract Background Hypertonic saline (HTS reduces the severity of lung injury in ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. However, the potential for HTS to modulate the resolution of lung injury is not known. We investigated the potential for hypertonic saline to modulate the evolution and resolution of oleic acid induced lung injury. Methods Adult male Sprague Dawley rats were used in all experiments. Series 1 examined the potential for HTS to reduce the severity of evolving oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 12 or hypertonic saline (HTS, n = 12, and the extent of lung injury assessed after 6 hours. Series 2 examined the potential for HTS to enhance the resolution of oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 6 or hypertonic saline (HTS, n = 6, and the extent of lung injury assessed after 6 hours. Results In Series I, HTS significantly reduced bronchoalveolar lavage (BAL neutrophil count compared to Control [61.5 ± 9.08 versus 102.6 ± 11.89 × 103 cells.ml-1]. However, there were no between group differences with regard to: A-a O2 gradient [11.9 ± 0.5 vs. 12.0 ± 0.5 KPa]; arterial PO2; static lung compliance, or histologic injury. In contrast, in Series 2, hypertonic saline significantly reduced histologic injury and reduced BAL neutrophil count [24.5 ± 5.9 versus 46.8 ± 4.4 × 103 cells.ml-1], and interleukin-6 levels [681.9 ± 190.4 versus 1365.7 ± 246.8 pg.ml-1]. Conclusion These findings demonstrate, for the first time, the potential for HTS to reduce pulmonary inflammation and enhance the resolution of oleic acid induced lung injury.

  3. Differences in MRI findings in cases showing ring-enhancement on a CT scan

    International Nuclear Information System (INIS)

    Tokiwa, Kaichi; Hashimoto, Takashi; Miyasaka, Yoshio; Yada, Kenzoh; Kan, Shinichi; Takagi, Hiroshi.

    1990-01-01

    It is sometimes difficult to differentiate between a brain abscess and a tumor, for both show ring-enhancement on a CT scan. The present authors have studied the benefit of MRI for the differential diagnosis of these two lesions. The subjects of this study were 6 cases of brain abscess and 10 cases of brain tumor, all of them showing ring-enhancement on a CT scan. The MRI findings were compared with those of the CT scan taken at almost the same time, especially focussing on the difference in the ring-enhancement. In 5 out of the 6 cases of brain abscess, T 2 -weighted MRI demonstrated a comparatively thin and homogeneous low-intensity, round rim. In the cases of brain tumor, however, none of the cases demonstrated this typical low-intensity, round rim; rather, in them the rim was thick and irregular. The authors can conclude that those MRI findings can serve as important differential diagnostic findings between brain abscess and tumor; also, MRI may be used as a landmark for terminating the administration of antibiotics in cases of brain abscess. (author)

  4. Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung fibrosis induced by bleomycin.

    Science.gov (United States)

    Chyczewska, E; Chyczewski, L; Bańkowski, E; Sułkowski, S; Nikliński, J

    1993-01-01

    It was found that the BCG vaccine injected subcutaneously to the rats enhances the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this vaccine results in accumulation of activated macrophages in lung interstitium and in the bronchoalveolar spaces. It may be suggested that the activated macrophages release various cytokines which may stimulate the proliferation of fibroblasts and biosynthesis of extracellular matrix components.

  5. Enhancements of a mechanical lung simulator for ex vivo measuring of aerosol deposition in lungs

    Czech Academy of Sciences Publication Activity Database

    Steiner, T.; Forjan, M.; Kopp, T.; Bureš, Zbyněk; Drauschke, A.

    2012-01-01

    Roč. 57, Suppl.1 (2012), s. 799-802 ISSN 0013-5585 Institutional research plan: CEZ:AV0Z50390512 Keywords : aerosol measurement * lung simulator Subject RIV: FS - Medical Facilities ; Equipment Impact factor: 1.157, year: 2012

  6. Semaphorin 4A enhances lung fibrosis through activation of Akt via ...

    Indian Academy of Sciences (India)

    2015-11-28

    Nov 28, 2015 ... In the present study, we show that treatment of Sema4A on normal lung fibroblasts ... of patients with the fibrotic disease Systemic Sclerosis (SSc) showed ... modulated at multiple levels: transcription, translation, and post-.

  7. Increased hydrostatic pressure enhances motility of lung cancer cells.

    Science.gov (United States)

    Kao, Yu-Chiu; Lee, Chau-Hwang; Kuo, Po-Ling

    2014-01-01

    Interstitial fluid pressures within most solid tumors are significantly higher than that in the surrounding normal tissues. Therefore, cancer cells must proliferate and migrate under the influence of elevated hydrostatic pressure while a tumor grows. In this study, we developed a pressurized cell culture device and investigated the influence of hydrostatic pressure on the migration speeds of lung cancer cells (CL1-5 and A549). The migration speeds of lung cancer cells were increased by 50-60% under a 20 mmHg hydrostatic pressure. We also observed that the expressions of aquaporin in CL1-5 and A549 cells were increased under the hydrostatic pressure. Our preliminary results indicate that increased hydrostatic pressure plays an important role in tumor metastasis.

  8. Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute lung injury in mice.

    Science.gov (United States)

    Wakayama, Hirotaka; Hashimoto, Naozumi; Matsushita, Yoshihiro; Matsubara, Kohki; Yamamoto, Noriyuki; Hasegawa, Yoshinori; Ueda, Minoru; Yamamoto, Akihito

    2015-08-01

    Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder characterized by acute respiratory failure, resulting from severe, destructive lung inflammation and irreversible lung fibrosis. We evaluated the use of stem cells derived from human exfoliated deciduous teeth (SHEDs) or SHED-derived serum-free conditioned medium (SHED-CM) as treatments for bleomycin (BLM)-induced mice acute lung injury (ALI), exhibiting several pathogenic features associated with the human disease ARDS. Mice with BLM-induced ALI with or without SHED or SHED-CM treatment were examined for weight loss and survival. The lung tissue was characterized by histological and real-time quantitative polymerase chain reaction analysis. The effects of SHED-CM on macrophage differentiation in vitro were also assessed. A single intravenous administration of either SHEDs or SHED-CM attenuated the lung injury and weight loss in BLM-treated mice and improved their survival rate. Similar recovery levels were seen in the SHEDs and SHED-CM treatment groups, suggesting that SHED improves ALI by paracrine mechanisms. SHED-CM contained multiple therapeutic factors involved in lung-regenerative mechanisms. Importantly, SHED-CM attenuated the BLM-induced pro-inflammatory response and generated an anti-inflammatory/tissue-regenerating environment, accompanied by the induction of anti-inflammatory M2-like lung macrophages. Furthermore, SHED-CM promoted the in vitro differentiation of bone marrow-derived macrophages into M2-like cells, which expressed high levels of Arginase1, CD206 and Ym-1. Our results suggest that SHED-secreted factors provide multifaceted therapeutic effects, including a strong M2-inducing activity, for treating BLM-induced ALI. This work may open new avenues for research on stem cell-based ARDS therapies. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  9. Redox-responsive manganese dioxide nanoparticles for enhanced MR imaging and radiotherapy of lung cancer

    Science.gov (United States)

    Cho, Mi Hyeon; Choi, Eun-Seok; Kim, Sehee; Goh, Sung-Ho; Choi, Yongdoo

    2017-12-01

    In this study, we synthesized manganese dioxide nanoparticles (MnO2 NPs) stabilized with biocompatible polymers (polyvinylpyrrolidone and polyacrylic acid) and analyzed their effect on non-small cell lung cancer (NSCLC) cells with or without gefitinib resistance in vitro. MnO2 NPs showed glutathione (GSH)-responsive dissolution and subsequent enhancement in magnetic resonance (MR) imaging. Of note, treatment with MnO2 NPs induced significant cytotoxic effects on NSCLC cells, and additional dose-dependent therapeutic effects were obtained upon X-ray irradiation. Normal cells treated with MnO2 NPs were viable at the tested concentrations. In addition, increased therapeutic efficacy could be achieved when the cells were treated with MnO2 NPs in hypoxic conditions. Therefore, we conclude that the use of MnO2 NPs in MR imaging and combination radiotherapy may be an efficient strategy for the imaging and therapy of NSCLC.

  10. MRI contrast enhancement of the lung using a Gd-DTPA aerosol

    International Nuclear Information System (INIS)

    Bockisch, A.; Harvey, R.C.; Davis, M.A.; Kabalka, G.W.

    1993-01-01

    A MR imaging study was performed in anesthetized female beagle dogs to investigate the effectiveness of Gd-DTPA aerosol for contrast enhancement in ventilated lungs. Ventilation was performed using a commercially available atomizer to administer Gd-DTPA solution. MR imaging was performed with a 1.9 T whole body imager using respiratory gated acquisition. To define the amount of Gd-DTPA being trapped in the lungs identical experiments were performed with 99m Tc-DTPA. MR imaging confirmed at 70% contrast enhancement following inhalation of Gd-DTPA. Because of the inherently low signal intensity of lung parenchyma the degree of contrast enhancement is not sufficient for clinical application. (orig.) [de

  11. The relationship between microvessels density and CT enhancement of the peripheral lung cancer

    International Nuclear Information System (INIS)

    Liu Shiyuan; Zhou Kangrong; Xiao Xiangsheng; Ye Tingjun; Zhang Zhiyong

    1999-01-01

    Objective: To investigate the relationship between microvessel density (MVD), clinical prognosis and CT enhancement of the peripheral lung cancer. Methods: 127 cases of peripheral lung cancer were examined with CT (87 cases retrospectively and 40 cases prospectively), and MVD were measured with immunohistochemical method by factor VIII on the specimens of the resected tumors. The results were analyzed and compared with CT enhancement, metastasis and prognosis. Results: The MVD was higher in the peripheral junction zone and interstitial areas than that in the parenchymal areas and necrotic zones of the tumors. Patients with nodal metastasis had higher MVD than those without nodal metastasis (56.9 +- 18.1 versus 43.8 +- 23.6, P 0.05); but the enhancement of the lung cancer correlated well with MVD (r 0.8874). Conclusions: Measurement of the microvessel density of tumor can determine the degree of angiogenesis of neoplasm and predict the metastasis or prognosis of the lung cancer. Angiogenesis not only constitutes the basis of enhancement of the tumor, but also determine the various degrees and patterns of enhancement. Spiral dynamic CT is the technique ideal to demonstrate the enhancement features, which might be helpful in making differential diagnosis of pulmonary nodules

  12. Non-contrast-enhanced perfusion and ventilation assessment of the human lung by means of fourier decomposition in proton MRI.

    Science.gov (United States)

    Bauman, Grzegorz; Puderbach, Michael; Deimling, Michael; Jellus, Vladimir; Chefd'hotel, Christophe; Dinkel, Julien; Hintze, Christian; Kauczor, Hans-Ulrich; Schad, Lothar R

    2009-09-01

    Assessment of regional lung perfusion and ventilation has significant clinical value for the diagnosis and follow-up of pulmonary diseases. In this work a new method of non-contrast-enhanced functional lung MRI (not dependent on intravenous or inhalative contrast agents) is proposed. A two-dimensional (2D) true fast imaging with steady precession (TrueFISP) pulse sequence (TR/TE = 1.9 ms/0.8 ms, acquisition time [TA] = 112 ms/image) was implemented on a 1.5T whole-body MR scanner. The imaging protocol comprised sets of 198 lung images acquired with an imaging rate of 3.33 images/s in coronal and sagittal view. No electrocardiogram (ECG) or respiratory triggering was used. A nonrigid image registration algorithm was applied to compensate for respiratory motion. Rapid data acquisition allowed observing intensity changes in corresponding lung areas with respect to the cardiac and respiratory frequencies. After a Fourier analysis along the time domain, two spectral lines corresponding to both frequencies were used to calculate the perfusion- and ventilation-weighted images. The described method was applied in preliminary studies on volunteers and patients showing clinical relevance to obtain non-contrast-enhanced perfusion and ventilation data.

  13. Colloidal graphite/graphene nanostructures using collagen showing enhanced thermal conductivity

    Science.gov (United States)

    Bhattacharya, Soumya; Dhar, Purbarun; Das, Sarit K; Ganguly, Ranjan; Webster, Thomas J; Nayar, Suprabha

    2014-01-01

    In the present study, the exfoliation of natural graphite (GR) directly to colloidal GR/graphene (G) nanostructures using collagen (CL) was studied as a safe and scalable process, akin to numerous natural processes and hence can be termed “biomimetic”. Although the exfoliation and functionalization takes place in just 1 day, it takes about 7 days for the nano GR/G flakes to stabilize. The predominantly aromatic residues of the triple helical CL forms its own special micro and nanoarchitecture in acetic acid dispersions. This, with the help of hydrophobic and electrostatic forces, interacts with GR and breaks it down to nanostructures, forming a stable colloidal dispersion. Surface enhanced Raman spectroscopy, X-ray diffraction, photoluminescence, fluorescence, and X-ray photoelectron spectroscopy of the colloid show the interaction between GR and CL on day 1 and 7. Differential interference contrast images in the liquid state clearly reveal how the GR flakes are entrapped in the CL fibrils, with a corresponding fluorescence image showing the intercalation of CL within GR. Atomic force microscopy of graphene-collagen coated on glass substrates shows an average flake size of 350 nm, and the hexagonal diffraction pattern and thickness contours of the G flakes from transmission electron microscopy confirm ≤ five layers of G. Thermal conductivity of the colloid shows an approximate 17% enhancement for a volume fraction of less than approximately 0.00005 of G. Thus, through the use of CL, this new material and process may improve the use of G in terms of biocompatibility for numerous medical applications that currently employ G, such as internally controlled drug-delivery assisted thermal ablation of carcinoma cells. PMID:24648728

  14. Colloidal graphite/graphene nanostructures using collagen showing enhanced thermal conductivity.

    Science.gov (United States)

    Bhattacharya, Soumya; Dhar, Purbarun; Das, Sarit K; Ganguly, Ranjan; Webster, Thomas J; Nayar, Suprabha

    2014-01-01

    In the present study, the exfoliation of natural graphite (GR) directly to colloidal GR/graphene (G) nanostructures using collagen (CL) was studied as a safe and scalable process, akin to numerous natural processes and hence can be termed "biomimetic". Although the exfoliation and functionalization takes place in just 1 day, it takes about 7 days for the nano GR/G flakes to stabilize. The predominantly aromatic residues of the triple helical CL forms its own special micro and nanoarchitecture in acetic acid dispersions. This, with the help of hydrophobic and electrostatic forces, interacts with GR and breaks it down to nanostructures, forming a stable colloidal dispersion. Surface enhanced Raman spectroscopy, X-ray diffraction, photoluminescence, fluorescence, and X-ray photoelectron spectroscopy of the colloid show the interaction between GR and CL on day 1 and 7. Differential interference contrast images in the liquid state clearly reveal how the GR flakes are entrapped in the CL fibrils, with a corresponding fluorescence image showing the intercalation of CL within GR. Atomic force microscopy of graphene-collagen coated on glass substrates shows an average flake size of 350 nm, and the hexagonal diffraction pattern and thickness contours of the G flakes from transmission electron microscopy confirm ≤ five layers of G. Thermal conductivity of the colloid shows an approximate 17% enhancement for a volume fraction of less than approximately 0.00005 of G. Thus, through the use of CL, this new material and process may improve the use of G in terms of biocompatibility for numerous medical applications that currently employ G, such as internally controlled drug-delivery assisted thermal ablation of carcinoma cells.

  15. Adaptive memory: young children show enhanced retention of fitness-related information.

    Science.gov (United States)

    Aslan, Alp; Bäuml, Karl-Heinz T

    2012-01-01

    Evolutionary psychologists propose that human cognition evolved through natural selection to solve adaptive problems related to survival and reproduction, with its ultimate function being the enhancement of reproductive fitness. Following this proposal and the evolutionary-developmental view that ancestral selection pressures operated not only on reproductive adults, but also on pre-reproductive children, the present study examined whether young children show superior memory for information that is processed in terms of its survival value. In two experiments, we found such survival processing to enhance retention in 4- to 10-year-old children, relative to various control conditions that also required deep, meaningful processing but were not related to survival. These results suggest that, already in very young children, survival processing is a special and extraordinarily effective form of memory encoding. The results support the functional-evolutionary proposal that young children's memory is "tuned" to process and retain fitness-related information. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. The development of adaptive memory: Young children show enhanced retention of animacy-related information.

    Science.gov (United States)

    Aslan, Alp; John, Thomas

    2016-12-01

    Previous developmental work has indicated that animacy is a foundational ontogenetic category that is given priority already early in life. Here, we investigated whether such priority is also present in children's episodic memory, examining whether young children show enhanced retention of animacy-related information. Kindergartners and younger and older elementary school children were presented with fictitious (non)words (e.g., BULA, LAFE) paired with properties characteristic of humans (e.g., "likes music"), (nonhuman) animals (e.g., "builds nests"), and inanimate things (e.g., "has four edges") and were asked to rate the animacy status of each nonword. After a retention interval, a surprise recognition test for the nonwords was administered. We found enhanced recognition of nonwords paired with human and animal properties compared with (the same) nonwords paired with inanimate properties. The size of this animacy advantage was comparable across age groups, suggesting developmental invariance of the advantage over the age range examined (i.e., 4-11years). The results support a functional-evolutionary view on memory, suggesting that already young children's memory is "tuned" to process and retain animacy. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Molecular Velcro constructed from polymer loop brushes showing enhanced adhesion force

    Science.gov (United States)

    Zhou, Tian; Han, Biao; Han, Lin; Li, Christopher; Department of Materials Science; Engineering Team; School of Biomedical Engineering, Science; Health Systems Team

    2015-03-01

    Molecular Velcro is commonly seen in biological systems as the formation of strong physical entanglement at molecular scale could induce strong adhesion, which is crucial to many biological processes. To mimic this structure, we designed, and fabricated polymer loop brushes using polymer single crystals with desired surface functionality and controlled chain folding. Compared with reported loop brushes fabricated using triblock copolymers, the present loop bushes have precise loop sizes, loop grafting density, and well controlled tethering locations on the solid surface. Atomic force microscopy-based force spectroscopy measurements using a polymer chain coated probe reveal that the adhesion force are significantly enhanced on the loop brush surface as compared with its single-strand counterpart. This study directly shows the effect of polymer brush conformation on their properties, and suggests a promising strategy for advanced polymer surface design.

  18. Collateral Ventilation to Congenital Hyperlucent Lung Lesions Assessed on Xenon-Enhanced Dynamic Dual-Energy CT: an Initial Experience

    OpenAIRE

    Goo, Hyun Woo; Yang, Dong Hyun; Kim, Namkug; Park, Seung Il; Kim, Dong Kwan; Kim, Ellen Ai-Rhan

    2011-01-01

    Objective We wanted to evaluate the resistance to collateral ventilation in congenital hyperlucent lung lesions and to correlate that with the anatomic findings on xenon-enhanced dynamic dual-energy CT. Materials and Methods Xenon-enhanced dynamic dual-energy CT was successfully and safely performed in eight children (median age: 5.5 years, 4 boys and 4 girls) with congenital hyperlucent lung lesions. Functional assessment of the lung lesions on the xenon map was done, including performing a ...

  19. Oxygen-enhanced magnetic resonance ventilation imaging of lung

    International Nuclear Information System (INIS)

    Ohno, Yoshiharu; Chen Qun; Hatabu, Hiroto

    2001-01-01

    The oxygen-enhanced magnetic resonance (MR) ventilation imaging is a new technique, and the full extent of its physiological significance has not been elucidated. This review article includes background on (1) respiratory physiology; (2) mechanism and optimization of oxygen-enhanced MR imaging technique; (3) recent applications in animal and human models; and (4) merits and demerits of the technique in comparison with hyperpolarized noble gas MR ventilation imaging. Application of oxygen-enhanced MR ventilation imaging to patients with pulmonary diseases has been very limited. However, we believe that further basic studies, as well as clinical applications of this new technique will define the real significance of oxygen-enhanced MR ventilation imaging in the future of pulmonary functional imaging and its usefulness for diagnostic radiology

  20. Polymeric Nanoparticles Containing Taxanes Enhance Chemoradiotherapeutic Efficacy in Non-small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Jung, Joohee; Park, Sung-Jin; Chung, Hye Kyung; Kang, Hye-Won; Lee, Sa-Won; Seo, Min Hyo; Park, Heon Joo; Song, Si Yeol; Jeong, Seong-Yun; Choi, Eun Kyung

    2012-01-01

    Purpose: To reduce the side effects and improve the efficacy of chemoradiation therapy, taxanes were incorporated into polymeric nanoparticles (PNP), and their synergic effect on radiation therapy in non-small cell lung cancer was evaluated. Methods and Materials: The properties of PNP-taxanes were characterized by transmission electron microscopy and dynamic light scattering. The chemoradiotherapeutic efficacy of PNP-taxanes was determined by clonogenic assay, cellular morphology, and flow cytometry in A549 cells. In mice bearing A549-derived tumors, the tumor growth delay was examined after the treatment of PNP-taxanes and/or ionizing radiation (IR). Results: The PNP-taxanes were found to be approximately 45 nm in average diameter and to have high solubility in water. They showed the properties of active internalization into cells and preserved the anticancer effect of free taxanes. The survival fraction of A549 cells by clonogenic assay was significantly reduced in the group receiving combined treatment of PNP-taxanes and IR. In addition, in vivo radiotherapeutic efficacy was markedly enhanced by the intravenous injection of PNP-taxanes into the xenograft mice. Conclusions: We have demonstrated the feasibility of PNP-taxanes to enhance the efficacy of chemoradiation therapy. These results suggest PNP-taxanes can hold an invaluable and promising position in treating human cancers as a novel and effective chemoradiation therapy agent.

  1. Self-Assembled Complexes of Horseradish Peroxidase with Magnetic Nanoparticles Showing Enhanced Peroxidase Activity

    KAUST Repository

    Corgié, Stéphane C.

    2012-02-15

    Bio-nanocatalysts (BNCs) consisting of horseradish peroxidase (HRP) self-assembled with magnetic nanoparticles (MNPs) enhance enzymatic activity due to the faster turnover and lower inhibition of the enzyme. The size and magnetization of the MNPs affect the formation of the BNCs, and ultimately control the activity of the bound enzymes. Smaller MNPs form small clusters with a low affinity for the HRP. While the turnover for the bound fraction is drastically increased, there is no difference in the H 2O 2 inhibitory concentration. Larger MNPs with a higher magnetization aggregate in larger clusters and have a higher affinity for the enzyme and a lower substrate inhibition. All of the BNCs are more active than the free enzyme or the MNPs (BNCs > HRP ≤laquo; MNPs). Since the BNCs show surprising resilience in various reaction conditions, they may pave the way towards new hybrid biocatalysts with increased activities and unique catalytic properties for magnetosensitive enzymatic reactions. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. A nonself sugar mimic of the HIV glycan shield shows enhanced antigenicity

    Energy Technology Data Exchange (ETDEWEB)

    Doores, Katie J.; Fulton, Zara; Hong, Vu; Patel, Mitul K.; Scanlan, Christopher N.; Wormald, Mark R.; Finn, M.G.; Burton, Dennis R.; Wilson, Ian A.; Davis, Benjamin G. (Scripps); (Oxford)

    2011-08-24

    Antibody 2G12 uniquely neutralizes a broad range of HIV-1 isolates by binding the high-mannose glycans on the HIV-1 surface glycoprotein, gp120. Antigens that resemble these natural epitopes of 2G12 would be highly desirable components for an HIV-1 vaccine. However, host-produced (self)-carbohydrate motifs have been unsuccessful so far at eliciting 2G12-like antibodies that cross-react with gp120. Based on the surprising observation that 2G12 binds nonproteinaceous monosaccharide D-fructose with higher affinity than D-mannose, we show here that a designed set of nonself, synthetic monosaccharides are potent antigens. When introduced to the terminus of the D1 arm of protein glycans recognized by 2G12, their antigenicity is significantly enhanced. Logical variation of these unnatural sugars pinpointed key modifications, and the molecular basis of this increased antigenicity was elucidated using high-resolution crystallographic analyses. Virus-like particle protein conjugates containing such nonself glycans are bound more tightly by 2G12. As immunogens they elicit higher titers of antibodies than those immunogenic conjugates containing the self D1 glycan motif. These antibodies generated from nonself immunogens also cross-react with this self motif, which is found in the glycan shield, when it is presented in a range of different conjugates and glycans. However, these antibodies did not bind this glycan motif when present on gp120.

  3. Potential for enhancing external beam radiotherapy for lung cancer using high-Z nanoparticles administered via inhalation

    Science.gov (United States)

    Hao, Yao; Altundal, Yucel; Moreau, Michele; Sajo, Erno; Kumar, Rajiv; Ngwa, Wilfred

    2015-09-01

    Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs). Using Monte Carlo-generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5-14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected. The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to IV

  4. Self-Assembled Complexes of Horseradish Peroxidase with Magnetic Nanoparticles Showing Enhanced Peroxidase Activity

    KAUST Repository

    Corgié , Sté phane C.; Kahawong, Patarawan; Duan, Xiaonan; Bowser, Daniel; Edward, Joseph B.; Walker, Larry P.; Giannelis, Emmanuel P.

    2012-01-01

    Bio-nanocatalysts (BNCs) consisting of horseradish peroxidase (HRP) self-assembled with magnetic nanoparticles (MNPs) enhance enzymatic activity due to the faster turnover and lower inhibition of the enzyme. The size and magnetization of the MNPs

  5. Mesenchymal stromal cell-derived extracellular vesicles attenuate lung ischemia-reperfusion injury and enhance reconditioning of donor lungs after circulatory death.

    Science.gov (United States)

    Stone, Matthew L; Zhao, Yunge; Robert Smith, J; Weiss, Mark L; Kron, Irving L; Laubach, Victor E; Sharma, Ashish K

    2017-12-21

    Lung ischemia-reperfusion (IR) injury after transplantation as well as acute shortage of suitable donor lungs are two critical issues impacting lung transplant patients. This study investigates the anti-inflammatory and immunomodulatory role of human mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) to attenuate lung IR injury and improve of ex-vivo lung perfusion (EVLP)-mediated rehabilitation in donation after circulatory death (DCD) lungs. C57BL/6 wild-type (WT) mice underwent sham surgery or lung IR using an in vivo hilar-ligation model with or without MSCs or EVs. In vitro studies used primary iNKT cells and macrophages (MH-S cells) were exposed to hypoxia/reoxygenation with/without co-cultures with MSCs or EVs. Also, separate groups of WT mice underwent euthanasia and 1 h of warm ischemia and stored at 4 °C for 1 h followed by 1 h of normothermic EVLP using Steen solution or Steen solution containing MSCs or EVs. Lungs from MSCs or EV-treated mice had significant attenuation of lung dysfunction and injury (decreased edema, neutrophil infiltration and myeloperoxidase levels) compared to IR alone. A significant decrease in proinflammatory cytokines (IL-17, TNF-α, CXCL1 and HMGB1) and upregulation of keratinocyte growth factor, prostaglandin E2 and IL-10 occurred in the BAL fluid from MSC or EV-treated mice after IR compared to IR alone. Furthermore, MSCs or EVs significantly downregulated iNKT cell-produced IL-17 and macrophage-produced HMGB1 and TNF-α after hypoxia/reoxygenation. Finally, EVLP of DCD lungs with Steen solution including MSCs or EVs provided significantly enhanced protection versus Steen solution alone. Co-cultures of MSCs or EVs with lung endothelial cells prevents neutrophil transendothelial migration after exposure to hypoxia/reoxygenation and TNF-α/HMGB1 cytomix. These results suggest that MSC-derived EVs can attenuate lung inflammation and injury after IR as well as enhance EVLP-mediated reconditioning of

  6. Carnosic acid and fisetin combination therapy enhances inhibition of lung cancer through apoptosis induction.

    Science.gov (United States)

    Shi, Bin; Wang, Li-Fang; Meng, Wen-Shu; Chen, Liang; Meng, Zi-Li

    2017-06-01

    Carnosic acid is a phenolic diterpene with anti-inflammation, anticancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, which is generated by many species from Lamiaceae family. Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally flavonoid is abundantly produced in different vegetables and fruits. Fisetin has been reported to have various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Lung cancer is reported as the most common neoplasm in human world-wide. In the present study, the possible benefits of carnosic acid combined with fisetin on lung cancer in vitro and in vivo was explored. Carnosic acid and fisetin combination led to apoptosis in lung cancer cells. Caspase-3 signaling pathway was promoted in carnosic acid and fisetin co-treatment, which was accompanied by anti-apoptotic proteins of Bcl-2 and Bcl-xl decreasing and pro-apoptotic signals of Bax and Bad increasing. The death receptor (DR) of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was enhanced in carnosic acid and fisetin combined treatment. Furthermore, the mouse xenograft model in vivo suggested that carnosic acid and fisetin combined treatment inhibited lung cancer growth in comparison to the carnosic acid or fisetin monotherapy. This study supplies a novel therapy to induce apoptosis to inhibit lung cancer through caspase-3 activation.

  7. Lung cancer in hilar region: the resectability evaluation with dual phase enhanced EBCT scan

    International Nuclear Information System (INIS)

    Tan Guosheng; Zhou Xuhui; Li Xiangmin; Fan Miao; Meng Quanfei; Peng Qian; Tan Zhiyu

    2005-01-01

    Objective: To explore the clinical value of duralphase enhanced electronic beam computed tomography (EBCT) scans in resectability evaluation of lung cancer located in hilar region. Methods: Dual phase enhanced EBCT scans were available for 40 cases that were initially diagnosed as 'carcinoma of lung' in hilar region. The relations between masses and trachea, bronchi, hilar and mediastinal great vessels were analyzed and compared with operation. Results: 38 cases in our series confirmed by operation and pathological examination were divided two groups: respectable (28 cases) and non-resectable (10 cases) groups. 25 cases in the former group were consistent with operation, accounting for 89.3%, and 8 cases, in the latter group, accounting for 80%. The sensitivity, specificity and accuracy of dural-phase enhanced EBCT scan evaluating the relations between masses and hilar and mediastinal structure were as follows: 92.6%, 72.7% and 86.8%. Conclusion: Dural-phase enhanced EBCT scans can provide precise and feasible pre-operative evaluation of lung cancer in hilar region. (authors)

  8. Pulmonary cavitary mass containing a mural nodule: differential diagnosis between intracavitary aspergilloma and cavitating lung cancer on contrast-enhanced computed tomography

    International Nuclear Information System (INIS)

    Park, Y.; Kim, T.S.; Yi, C.A.; Cho, E.Y.; Kim, H.; Choi, Y.S.

    2007-01-01

    Aim: The objective of this study was to identify whether there were any significant differences in the computed tomography (CT) findings of an intracavitary aspergilloma and a cavitating lung cancer containing a mural nodule. Materials and methods: The CT and histopathological findings of 12 patients (male:female ratio 3:9; aged 51-76 years) with cavitating lung cancer containing a mural nodule and 26 patients (male:female ratio 14:12; aged 29-72 years) with intracavitary aspergilloma were retrospectively reviewed. Results: The mural nodules within cavitating lung cancer were more enhanced (p < 0.001) and showed a nondependent location more frequently (p = 0.012) than those of intracavitary aspergillomas. The cavitary walls were thicker in cavitating lung cancer (mean 5.8 mm thick) than those in intracavitary aspergillomas (mean 2.6 mm thick; p = 0.035). Adjacent bronchiectasis and volume decrease of the involved lobe were observed more frequently in intracavitary aspergillomas than in cavitating lung cancers (p < 0.001 and p = 0.008, respectively). Conclusion: Whether a mural nodule within a cavitary lesion is contrast-enhanced or not is one of the most important features in making a differential diagnosis between an intracavitary aspergilloma and a cavitating lung cancer. Assessment of dependent location of a mural nodule within the cavity and wall thickness of the cavity itself can also be helpful for differentiation

  9. Pulmonary cavitary mass containing a mural nodule: differential diagnosis between intracavitary aspergilloma and cavitating lung cancer on contrast-enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Park, Y. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of); Kim, T.S. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of)]. E-mail: tskim.kim@samsung.com; Yi, C.A. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of); Cho, E.Y. [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of); Kim, H. [Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of); Choi, Y.S. [Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710 (Korea, Republic of)

    2007-03-15

    Aim: The objective of this study was to identify whether there were any significant differences in the computed tomography (CT) findings of an intracavitary aspergilloma and a cavitating lung cancer containing a mural nodule. Materials and methods: The CT and histopathological findings of 12 patients (male:female ratio 3:9; aged 51-76 years) with cavitating lung cancer containing a mural nodule and 26 patients (male:female ratio 14:12; aged 29-72 years) with intracavitary aspergilloma were retrospectively reviewed. Results: The mural nodules within cavitating lung cancer were more enhanced (p < 0.001) and showed a nondependent location more frequently (p = 0.012) than those of intracavitary aspergillomas. The cavitary walls were thicker in cavitating lung cancer (mean 5.8 mm thick) than those in intracavitary aspergillomas (mean 2.6 mm thick; p = 0.035). Adjacent bronchiectasis and volume decrease of the involved lobe were observed more frequently in intracavitary aspergillomas than in cavitating lung cancers (p < 0.001 and p = 0.008, respectively). Conclusion: Whether a mural nodule within a cavitary lesion is contrast-enhanced or not is one of the most important features in making a differential diagnosis between an intracavitary aspergilloma and a cavitating lung cancer. Assessment of dependent location of a mural nodule within the cavity and wall thickness of the cavity itself can also be helpful for differentiation.

  10. Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

    Directory of Open Access Journals (Sweden)

    Anja Kafka

    2014-06-01

    Full Text Available The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1, Dishevelled-3 (DVL3, E-cadherin (CDH1 and beta-catenin (CTNNB1. Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR/loss of heterozygosity (LOH. Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001. Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC were significantly associated to CDH1 LOH (p = 0.001. Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

  11. Acacetin enhances the therapeutic efficacy of doxorubicin in non-small-cell lung carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Reenu Punia

    Full Text Available Anthracyclines are efficient and potent agents to treat broad range of cancers but cytotoxicity induced by them limits their use in therapeutics. Use of plant-derived agents help to prevent or delay the process of cancer progression and their combination increases the anti-cancer potential of mainstream compound. However, multidrug resistance is major cause of treatment failure in cancer patients.In this study, combination treatments of fisetin or acacetin with doxorubicin were explored for their potential synergistic effect on non-small-cell lung carcinoma (NSCLC cells.During this study, NSCLC model cell lines A549 and H1299 were used to determine the combinatorial effect of phytochemicals namly acacetin and fisetin with doxorubicin.The effects of individual compounds and their combination on cell viability, clonogenic potential and cell cycle progression were studied. Efflux of doxorubicin was measured by spectrofluorophotometer, whereas accumulation inside the cells was analyzed by flow cytometry and confocal microscopy. Expression of MDR1 was checked by semi-quantitative PCR.The results showed that the cell viability of A549 and H1299 cells were significantly decreased in time- and dose-dependent manner, although A549 cells showed more sensitivity toward doxorubicin than H1299 cells. Mostly, combination of doxorubicin showed good synergy with acacetin in both the cell lines whereas, fisetin exerted synergistic effect only at 72 h of treatment in H1299 cells. Acacetin with doxorubicin caused G2/M arrest by downregulating CDK-cyclin complex in A549 cells. Acacetin-doxorubicin combination decreased the clonogenic potential of A549 and H1299 cells upto 82% and 59%, respectively, as compared to control. Acacetin also decreased efflux of doxorubicin by 59% after 30 mins of exposure to A549 cells and further increased accumulation of doxorubicin inside the cells upto 55% in 2 h. The modulatory effect of acacetin-doxorubicin combination on

  12. Enhanced Radiosensitization Effect of Curcumin Delivered by PVP-PCL Nanoparticle in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Cuixia Wen

    2017-01-01

    Full Text Available Curcumin, the principal polyphenolic curcuminoid, has been reported in numerous studies for its antitumor effect in a series of cancers. It is also reported that curcumin possesses radiosensitization effect in some cancers. However, the poor solubility and unsatisfied bioavailability of curcumin significantly undermine its potential application. Here we prepared curcumin loaded nanoparticles by employing PVP-PCL as drug carrier. Characterization studies indicated the satisfied drug loading efficiency and a sustained in vitro release pattern. Quantification uptake study showed that the uptake efficiency of Cum-NPs by lung cancer cells was time- and dose-dependent. In vitro anticancer study demonstrated the superior cytotoxic effect of Cum-NPs with stronger apoptotic induction over free Cum. Most importantly, there is almost no report on the radiosensitization effect of curcumin loaded nanoparticles. Here, Cum-NPs led to more inhibition of the colony forming ability of A549 cells as compared to the equivalent concentration of free Cum as shown in clonogenic assay. Furthermore, Cum-NPs are much more effective in enhancing the tumor growth inhibitory effect of radiation therapy in a A549 xenograft model. Therefore, results from the current study seem to be the first report on the radiosensitization effect of Cum-NPs and paved the way for a curcumin nanodrug delivery system as a potential radiation adjuvant.

  13. In vivo fluorescence enhanced optical tomography reconstruction of lung cancer of non immersed small animals

    Science.gov (United States)

    Hervé, L.; Koenig, A.; Da Silva, A.; Berger, M.; Boutet, J.; Dinten, J. M.; Peltié, P.; Rizo, P.

    2007-02-01

    Fluorescence enhanced diffuse optical tomography (fDOT) is envisioned to be useful to collect functional information from small animal models. For oncology applications, cancer-targeted fluorescent markers can be used as a surrogate of the cancer activity. We are developing a continuous wave fDOT bench intended to be integrated in systems dedicated to whole body small animal fluorescence analyses. The focus is currently put on the reconstruction of non immersed small animals imaged by a CCD camera. The reconstruction stage already corrects the tissue heterogeneity artifacts through the computation of an optical heterogeneity map. We will show how this formalism coupled with the determination of the animal boundaries performed by a laser scanner, can be used to manage non contact acquisitions. The time of reconstruction for a 10 × 9 laser source positions, 45 × 40 detector elements and 14 × 11 × 14 mesh voxels is typically 10 minutes on a 3GHz PCs corresponding to the acquisition time allowing the two tasks to be performed in parallel. The system is validated on an in vivo experiment performed on three healthy nude mice and a mouse bearing a lung tumor at 10, 12 and 14 days after implantation allowing the follow up of the disease. The 3D fluorescence reconstructions of this mouse are presented and the total fluorescence amounts are compared.

  14. Feasibility of using intravenous contrast-enhanced computed tomography (CT) scans in lung cancer treatment planning

    International Nuclear Information System (INIS)

    Xiao Jianghong; Zhang Hong; Gong Youling; Fu Yuchuan; Tang Bin; Wang Shichao; Jiang Qingfeng; Li Ping

    2010-01-01

    Background and purpose: To investigate the feasibility of using intravenous contrast-enhanced computed tomography (CT) scans in 3-dimensional conformal radiotherapy (3D-CRT), stereotactic body radiation therapy (SBRT) and intensity-modulated radiotherapy (IMRT) treatment planning for lung cancers, respectively. Materials and methods: Twelve patients with bulky lung tumors and 14 patients with small lung tumors were retrospectively analyzed. Each patient took two sets of CT in the same position with active breathing control (ABC) technique before and after intravenous contrast agent (CA) injections. Bulky tumors were planned with 3D-CRT, while SBRT plans were generated for patients with small tumors based on CT scans with intravenous CA. In addition, IMRT plans were generated for patients with bulky tumors to continue on a planning study. All plans were copied and replaced on the scans without intravenous CA. The radiation doses calculated from the two sets of CTs were compared with regard to planning volumes (PTV), the organ at-risk (OAR) and the lungs using Wilcoxon's signed rank test. Results: In comparisons for 3D-CRT plans, CT scans with intravenous CA reduced the mean dose and the maximum dose of PTV with significant differences (p 95 ) for targets, respectively (p < 0.05). There was no statistical significance for lung parameters between two sets of scans in SBRT plans and IMRT plans. Conclusions: The enhanced CT scans can be used for both target delineation and treatment planning in 3D-CRT. The dose difference caused by intravenous CA is small. But for SBRT and IMRT, the minimum irradiation dose in targets may be estimated to be increased up to 2.71% while the maximum dose may be estimated to be decreased up to 1.36%. However, the difference in dose distribution in most cases were found to be clinical tolerable.

  15. Enhanced suppression of tumor growth by concomitant treatment of human lung cancer cells with suberoylanilide hydroxamic acid and arsenic trioxide

    International Nuclear Information System (INIS)

    Chien, Chia-Wen; Yao, Ju-Hsien; Chang, Shih-Yu; Lee, Pei-Chih; Lee, Te-Chang

    2011-01-01

    The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL) and relapsed APL has been well documented. ATO may cause DNA damage by generating reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, modulates gene and protein expression via histone-dependent or -independent pathways that may result in chromatin decondensation, cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO and SAHA act synergistically to enhance the death of cancer cells. Our current findings showed that combined treatment with ATO and SAHA resulted in enhanced suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivo in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed that apoptotic cell death was significantly enhanced after combined treatment with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells; however, co-treatment with SAHA significantly increased ATO-induced DNA damage. Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation and increase cellular susceptibility to ATO-induced DNA damage. Combined administration of SAHA and ATO may be an effective approach to the treatment of lung cancer. -- Highlights: ► ATO and SAHA are therapeutic agents with different action modes. ► Combination of ATO and SAHA synergistically inhibits tumor cell growth. ► SAHA loosens chromatin structure resulting in increased sensitivity to DNase I. ► ATO-induced DNA damage and apoptosis are enhanced by co-treatment with SAHA.

  16. Dynamic oxygen-enhanced magnetic resonance imaging of the lung in asthma—Initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wei-Juan, E-mail: weijuan.zhang@postgrad.manchester.ac.uk [Centre for Imaging Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom); Biomedical Imaging Institute, The University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom); Niven, Robert M., E-mail: robert.niven@uhsm.nhs.uk [North West Lung Research Centre, University Hospital of South Manchester, Southmoor Road, Manchester M23 9LT (United Kingdom); Young, Simon S., E-mail: Simon.Young1@astrazeneca.com [Personalised Healthcare and Biomarkers, AstraZeneca R and D, Alderley Park, Macclesfield SK10 4TF (United Kingdom); Liu, Yu-Zhen, E-mail: yu-zhen.liu@astrazeneca.com [Personalised Healthcare and Biomarkers, AstraZeneca R and D, Alderley Park, Macclesfield SK10 4TF (United Kingdom); Parker, Geoffrey J.M., E-mail: Geoff.parker@manchester.ac.uk [Centre for Imaging Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom); Biomedical Imaging Institute, The University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom); Bioxydyn Limited, Rutherford House, Pencroft Way, Manchester M15 6SZ (United Kingdom); Naish, Josephine H., E-mail: Josephine.naish@manchester.ac.uk [Centre for Imaging Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom); Biomedical Imaging Institute, The University of Manchester, Oxford Road, Manchester M13 9PT (United Kingdom)

    2015-02-15

    Highlights: • Oxygen-enhanced MRI may have a role in the estimation of disease severity in asthma. • Heterogeneity of parameter maps reflects localized functional impairment in asthma. • OE-MRI provides non-ionising, spatial and temporal information on oxygen delivery. - Abstract: Objectives: To prospectively estimate the feasibility and reproducibility of dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) in the assessment of regional oxygen delivery, uptake and washout in asthmatic lungs. Materials and methods: The study was approved by the National Research Ethics Committee and written informed consent was obtained. Dynamic OE-MRI was performed twice at one month apart on four mild asthmatic patients (23 ± 5 years old, FEV{sub 1} = 96 ± 3% of predicted value) and six severe asthmatic patients (41 ± 12 years old, FEV{sub 1} = 60 ± 14% of predicted value) on a 1.5 T MR scanner using a two-dimensional T{sub 1}-weighted inversion-recovery turbo spin echo sequence. The enhancing fraction (EF), the maximal change in the partial pressure of oxygen in lung tissue (ΔPO{sub 2max{sub l}}) and arterial blood of the aorta (ΔPO{sub 2max{sub a}}), and the oxygen wash-in (τ{sub up{sub l}}, τ{sub up{sub a}}) and wash-out (τ{sub down{sub l}}, τ{sub down{sub a}}) time constants were extracted and compared between groups using the independent-samples t-test (two-tailed). Correlations between imaging readouts and clinical measurements were assessed by Pearson's correlation analysis. Bland–Altman analysis was used to estimate the levels of agreement between the repeat scans and the intra-observer agreement in the MR imaging readouts. Results: The severe asthmatic group had significantly smaller EF (70 ± 16%) and median ΔPO{sub 2max{sub l}} (156 ± 52 mmHg) and significantly larger interquartile range of τ{sub up{sub l}} (0.84 ± 0.26 min) than the mild asthmatic group (95 ± 3%, P = 0.014; 281 ± 40 mmHg, P = 0.004; 0.20 ± 0.07 min, P = 0

  17. Dynamic oxygen-enhanced magnetic resonance imaging of the lung in asthma—Initial experience

    International Nuclear Information System (INIS)

    Zhang, Wei-Juan; Niven, Robert M.; Young, Simon S.; Liu, Yu-Zhen; Parker, Geoffrey J.M.; Naish, Josephine H.

    2015-01-01

    Highlights: • Oxygen-enhanced MRI may have a role in the estimation of disease severity in asthma. • Heterogeneity of parameter maps reflects localized functional impairment in asthma. • OE-MRI provides non-ionising, spatial and temporal information on oxygen delivery. - Abstract: Objectives: To prospectively estimate the feasibility and reproducibility of dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) in the assessment of regional oxygen delivery, uptake and washout in asthmatic lungs. Materials and methods: The study was approved by the National Research Ethics Committee and written informed consent was obtained. Dynamic OE-MRI was performed twice at one month apart on four mild asthmatic patients (23 ± 5 years old, FEV 1 = 96 ± 3% of predicted value) and six severe asthmatic patients (41 ± 12 years old, FEV 1 = 60 ± 14% of predicted value) on a 1.5 T MR scanner using a two-dimensional T 1 -weighted inversion-recovery turbo spin echo sequence. The enhancing fraction (EF), the maximal change in the partial pressure of oxygen in lung tissue (ΔPO 2max l ) and arterial blood of the aorta (ΔPO 2max a ), and the oxygen wash-in (τ up l , τ up a ) and wash-out (τ down l , τ down a ) time constants were extracted and compared between groups using the independent-samples t-test (two-tailed). Correlations between imaging readouts and clinical measurements were assessed by Pearson's correlation analysis. Bland–Altman analysis was used to estimate the levels of agreement between the repeat scans and the intra-observer agreement in the MR imaging readouts. Results: The severe asthmatic group had significantly smaller EF (70 ± 16%) and median ΔPO 2max l (156 ± 52 mmHg) and significantly larger interquartile range of τ up l (0.84 ± 0.26 min) than the mild asthmatic group (95 ± 3%, P = 0.014; 281 ± 40 mmHg, P = 0.004; 0.20 ± 0.07 min, P = 0.001, respectively). EF, median ΔPO 2max l and τ down l and the interquartile range of τ up l

  18. Pyocyanina contributory factor in haem acquisition and virulence enhancement of Porphyromonas gingivalis in the lung [corrected].

    Directory of Open Access Journals (Sweden)

    Malgorzata Benedyk

    Full Text Available Several recent studies show that the lungs infected with Pseudomonas aeruginosa are often co-colonised by oral bacteria including black-pigmenting anaerobic (BPA Porphyromonas species. The BPAs have an absolute haem requirement and their presence in the infected lung indicates that sufficient haem, a virulence up-regulator in BPAs, must be present to support growth. Haemoglobin from micro-bleeds occurring during infection is the most likely source of haem in the lung. Porphyromonas gingivalis displays a novel haem acquisition paradigm whereby haemoglobin must be firstly oxidised to methaemoglobin, facilitating haem release, either by gingipain proteolysis or capture via the haem-binding haemophore HmuY. P. aeruginosa produces the blue phenazine redox compound, pyocyanin. Since phenazines can oxidise haemoglobin, it follows that pyocyanin may also facilitate haem acquisition by promoting methaemoglobin production. Here we show that pyocyanin at concentrations found in the CF lung during P. aeruginosa infections rapidly oxidises oxyhaemoglobin in a dose-dependent manner. We demonstrate that methaemoglobin formed by pyocyanin is also susceptible to proteolysis by P. gingivalis Kgp gingipain and neutrophil elastase, thus releasing haem. Importantly, co-incubation of oxyhaemoglobin with pyocyanin facilitates haem pickup from the resulting methemoglobin by the P. gingivalis HmuY haemophore. Mice intra-tracheally challenged with viable P. gingivalis cells plus pyocyanin displayed increased mortality compared to those administered P. gingivalis alone. Pyocyanin significantly elevated both methaemoglobin and total haem levels in homogenates of mouse lungs and increased the level of arginine-specific gingipain activity from mice inoculated with viable P. gingivalis cells plus pyocyanin compared with mice inoculated with P. gingivalis only. These findings indicate that pyocyanin, by promoting haem availability through methaemoglobin formation and

  19. Enhanced Heme Function and Mitochondrial Respiration Promote the Progression of Lung Cancer Cells

    Science.gov (United States)

    Alam, Md Maksudul; Shah, Ajit; Cao, Thai M.; Sullivan, Laura A.; Brekken, Rolf; Zhang, Li

    2013-01-01

    Lung cancer is the leading cause of cancer-related mortality, and about 85% of the cases are non-small-cell lung cancer (NSCLC). Importantly, recent advance in cancer research suggests that altering cancer cell bioenergetics can provide an effective way to target such advanced cancer cells that have acquired mutations in multiple cellular regulators. This study aims to identify bioenergetic alterations in lung cancer cells by directly measuring and comparing key metabolic activities in a pair of cell lines representing normal and NSCLC cells developed from the same patient. We found that the rates of oxygen consumption and heme biosynthesis were intensified in NSCLC cells. Additionally, the NSCLC cells exhibited substantially increased levels in an array of proteins promoting heme synthesis, uptake and function. These proteins include the rate-limiting heme biosynthetic enzyme ALAS, transporter proteins HRG1 and HCP1 that are involved in heme uptake, and various types of oxygen-utilizing hemoproteins such as cytoglobin and cytochromes. Several types of human tumor xenografts also displayed increased levels of such proteins. Furthermore, we found that lowering heme biosynthesis and uptake, like lowering mitochondrial respiration, effectively reduced oxygen consumption, cancer cell proliferation, migration and colony formation. In contrast, lowering heme degradation does not have an effect on lung cancer cells. These results show that increased heme flux and function are a key feature of NSCLC cells. Further, increased generation and supply of heme and oxygen-utilizing hemoproteins in cancer cells will lead to intensified oxygen consumption and cellular energy production by mitochondrial respiration, which would fuel cancer cell proliferation and progression. The results show that inhibiting heme and respiratory function can effectively arrest the progression of lung cancer cells. Hence, understanding heme function can positively impact on research in lung cancer

  20. Thioredoxin reductase 1 knockdown enhances selenazolidine cytotoxicity in human lung cancer cells via mitochondrial dysfunction

    Science.gov (United States)

    Poerschke, Robyn L.; Moos, Philip J.

    2010-01-01

    Thioredoxin reductase (TR1) is a selenoprotein that is involved in cellular redox status control and deoxyribonucleotide biosynthesis. Many cancers, including lung, overexpress TR1, making it a potential cancer therapy target. Previous work has shown that TR1 knockdown enhances the sensitivity of cancer cells to anticancer treatments, as well as certain selenocompounds. However, it is unknown if TR1 knockdown produces similar effect on the sensitivity of human lung cancer cells. To further elucidate the role of TR1 in the mechanism of selenocompounds in lung cancer, a lentiviral microRNA delivery system to knockdown TR1 expression in A549 human lung adenocarcinoma cells was utilized. Cell viability was assessed after 48 hr treatment with the selenocysteine prodrug selenazolidines 2-butylselenazolidine-4(R)-carboxylic acid (BSCA) and 2-cyclohexylselenazolidine-4-(R)-carboxylic acid (ChSCA), selenocystine (SECY), methylseleninic acid (MSA), 1,4-phenylenebis(methylene)selenocyanate (p-XSC), and selenomethionine (SEM). TR1 knockdown increased the cytotoxicity of BSCA, ChSCA, and SECY but did not sensitize cells to MSA, SEM, or p-XSC. GSH and TR1 depletion together decreased cell viability, while no change was observed with GSH depletion alone. Reactive oxygen species generation was induced only in TR1 knockdown cells treated with the selenazolidines or SECY. These three compounds also decreased total intracellular glutathione levels and oxidized thioredoxin, but in a TR1 independent manner. TR1 knockdown increased selenazolidine and SECY-induced mitochondrial membrane depolarization, as well as DNA strand breaks and AIF translocation from the mitochondria. These results indicate the ability of TR1 to modulate the cytotoxic effects of BSCA, ChSCA and SECY in human lung cancer cells through mitochondrial dysfunction. PMID:20920480

  1. Assessing Tumor Response to Treatment in Patients with Lung Cancer Using Dynamic Contrast-Enhanced CT

    DEFF Research Database (Denmark)

    Strauch, Louise S; Eriksen, Rie Ø; Sandgaard, Michael

    2016-01-01

    Reviews and Meta-Analyses (PRISMA) guidelines. Only original research articles concerning treatment response in patients with lung cancer assessed with DCE-CT were included. To assess the validity of each study we implemented Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The initial search......The aim of this study was to provide an overview of the literature available on dynamic contrast-enhanced computed tomography (DCE-CT) as a tool to evaluate treatment response in patients with lung cancer. This systematic review was compiled according to Preferred Reporting Items for Systematic...... yielded 651 publications, and 16 articles were included in this study. The articles were divided into groups of treatment. In studies where patients were treated with systemic chemotherapy with or without anti-angiogenic drugs, four out of the seven studies found a significant decrease in permeability...

  2. Lectin enhancement of the lipofection efficiency in human lung carcinoma cells.

    Science.gov (United States)

    Yanagihara, K; Cheng, P W

    1999-10-18

    Poor transfection efficiency of human lung carcinoma cells by lipofection begs further development of more efficient gene delivery strategies. The purpose of this study was to determine whether lectins can improve the lipofection efficiency in lung carcinoma cells. A549, Calu3, and H292 cells grown to 90% confluence were transfected for 18 h with a plasmid DNA containing a beta-galactosidase reporter gene (pCMVlacZ) using lipofectin plus a lectin as the vector. Ten different lectins, which exhibit a wide range of carbohydrate-binding specificities, were examined for their abilities to enhance the efficiency of lipofection. The transfected cells were assessed for transfection efficiency by beta-galactosidase activity (units/microg protein) and % blue cells following X-Gal stain. Lipofectin supplemented with Griffonia simplicifolia-I (GS-I) yields largest enhancement of the lipofection efficiency in A549 and Calu3 cells (5.3- and 28-fold, respectively). Maackia amurensis gives the largest enhancement (6.5-fold) of lipofection efficiency in H292 cells. The transfection efficiency correlates with the amounts of DNA delivered to the nucleus. Binding of FITC-labeled GS-I and the enhancement of the lipofection efficiency by GS-I were inhibited by alpha-methyl-D-galactopyranoside, indicating an alpha-galactoside-mediated gene transfer to lung carcinoma cells. We conclude that lectin-facilitated lipofection is an efficient gene delivery strategy. Employment of cell type-specific lectins may allow for efficient cell type-specific gene targeting.

  3. Soil bacteria showing a potential of chlorpyrifos degradation and plant growth enhancement

    Directory of Open Access Journals (Sweden)

    Shamsa Akbar

    Full Text Available ABSTRACT Background: Since 1960s, the organophosphate pesticide chlorpyrifos has been widely used for the purpose of pest control. However, given its persistence and toxicity towards life forms, the elimination of chlorpyrifos from contaminated sites has become an urgent issue. For this process bioremediation is the method of choice. Results: Two bacterial strains, JCp4 and FCp1, exhibiting chlorpyrifos-degradation potential were isolated from pesticide contaminated agricultural fields. These isolates were able to degrade 84.4% and 78.6% of the initial concentration of chlorpyrifos (100 mg L-1 within a period of only 10 days. Based on 16S rRNA sequence analysis, these strains were identified as Achromobacter xylosoxidans (JCp4 and Ochrobactrum sp. (FCp1. These strains exhibited the ability to degrade chlorpyrifos in sterilized as well as non-sterilized soils, and were able to degrade 93-100% of the input concentration (200 mg kg-1 within 42 days. The rate of degradation in inoculated soils ranged from 4.40 to 4.76 mg-1 kg-1 d-1 with rate constants varying between 0.047 and 0.069 d-1. These strains also displayed substantial plant growth promoting traits such as phosphate solubilization, indole acetic acid production and ammonia production both in absence as well as in the presence of chlorpyrifos. However, presence of chlorpyrifos (100 and 200 mg L-1 was found to have a negative effect on indole acetic acid production and phosphate solubilization with percentage reduction values ranging between 2.65-10.6% and 4.5-17.6%, respectively. Plant growth experiment demonstrated that chlorpyrifos has a negative effect on plant growth and causes a decrease in parameters such as percentage germination, plant height and biomass. Inoculation of soil with chlorpyrifos-degrading strains was found to enhance plant growth significantly in terms of plant length and weight. Moreover, it was noted that these strains degraded chlorpyrifos at an increased rate (5

  4. Soil bacteria showing a potential of chlorpyrifos degradation and plant growth enhancement.

    Science.gov (United States)

    Akbar, Shamsa; Sultan, Sikander

    2016-01-01

    Since 1960s, the organophosphate pesticide chlorpyrifos has been widely used for the purpose of pest control. However, given its persistence and toxicity towards life forms, the elimination of chlorpyrifos from contaminated sites has become an urgent issue. For this process bioremediation is the method of choice. Two bacterial strains, JCp4 and FCp1, exhibiting chlorpyrifos-degradation potential were isolated from pesticide contaminated agricultural fields. These isolates were able to degrade 84.4% and 78.6% of the initial concentration of chlorpyrifos (100mgL(-1)) within a period of only 10 days. Based on 16S rRNA sequence analysis, these strains were identified as Achromobacter xylosoxidans (JCp4) and Ochrobactrum sp. (FCp1). These strains exhibited the ability to degrade chlorpyrifos in sterilized as well as non-sterilized soils, and were able to degrade 93-100% of the input concentration (200mgkg(-1)) within 42 days. The rate of degradation in inoculated soils ranged from 4.40 to 4.76mg(-1)kg(-1)d(-1) with rate constants varying between 0.047 and 0.069d(-1). These strains also displayed substantial plant growth promoting traits such as phosphate solubilization, indole acetic acid production and ammonia production both in absence as well as in the presence of chlorpyrifos. However, presence of chlorpyrifos (100 and 200mgL(-1)) was found to have a negative effect on indole acetic acid production and phosphate solubilization with percentage reduction values ranging between 2.65-10.6% and 4.5-17.6%, respectively. Plant growth experiment demonstrated that chlorpyrifos has a negative effect on plant growth and causes a decrease in parameters such as percentage germination, plant height and biomass. Inoculation of soil with chlorpyrifos-degrading strains was found to enhance plant growth significantly in terms of plant length and weight. Moreover, it was noted that these strains degraded chlorpyrifos at an increased rate (5.69mg(-1)kg(-1)d(-1)) in planted soil. The

  5. Autophagy deficiency in macrophages enhances NLRP3 inflammasome activity and chronic lung disease following silica exposure

    International Nuclear Information System (INIS)

    Jessop, Forrest; Hamilton, Raymond F.; Rhoderick, Joseph F.; Shaw, Pamela K.; Holian, Andrij

    2016-01-01

    Autophagy is an important metabolic mechanism that can promote cellular survival following injury. The specific contribution of autophagy to silica-induced inflammation and disease is not known. The objective of these studies was to determine the effects of silica exposure on the autophagic pathway in macrophages, as well as the general contribution of autophagy in macrophages to inflammation and disease. Silica exposure enhanced autophagic activity in vitro in Bone Marrow derived Macrophages and in vivo in Alveolar Macrophages isolated from silica-exposed mice. Impairment of autophagy in myeloid cells in vivo using Atg5 fl/fl LysM-Cre + mice resulted in enhanced cytotoxicity and inflammation after silica exposure compared to littermate controls, including elevated IL-18 and the alarmin HMGB1 in the whole lavage fluid. Autophagy deficiency caused some spontaneous inflammation and disease. Greater silica-induced acute inflammation in Atg5 fl/fl LysM-Cre + mice correlated with increased fibrosis and chronic lung disease. These studies demonstrate a critical role for autophagy in suppressing silica-induced cytotoxicity and inflammation in disease development. Furthermore, this data highlights the importance of basal autophagy in macrophages and other myeloid cells in maintaining lung homeostasis. - Highlights: • Silica exposure increases autophagy in macrophages. • Autophagy deficient mice have enhanced inflammation and silicosis. • Autophagy deficiency in macrophages results in greater silica-induced cytotoxicity. • Autophagy deficiency in macrophages increases extracellular IL-18 and HMGB1.

  6. Dynamic Gd-DTPA enhanced breath-hold 1.5 t MRI of normal lungs and patients with interstitial lung disease and pulmonary nodules: preliminary results

    International Nuclear Information System (INIS)

    Semelka, R.C.; Maycher, B.; Shoenut, J.P.; Kroeker, R.; Griffin, P.; Lertzman, M.

    1992-01-01

    A FLASH technique was used, which encompassed the entire thorax in the transverse plane, before and after dynamic intravenous injection of godalinium DTPA (Gd-DTPA) to study 7 patients with normal lungs, 12 patients with interstitial lung disease (ILD), and 11 patients with pulmonary nodules. Comparative CT studies were obtained within 2 weeks of the MRI study in the patients with lung disease. Quantitative signal intensity (SI) measurements were performed. Qualitative evaluation of lung parenchyma was determined in a prospective blinded fashion, and in the normal group comparison was made with the CT images. In normal patients, SI of lung parenchyma increased by 7.7±1.3%. On precontrast images, second-order pulmonary branchings were visible while post-contrast, fifth- to sixth-order branches were apparent. In patients with ILD, interstitial changes enhanced to a variable extent, increases in SI ranging from minimal (49.9%) to substantial (308.4%). Detection of pulmonary nodules improved following contrast injection. The minimum lesion size detectable decreased from 8 mm precontrast to 5 mm post-contrast. Percentage contrast enhancement was greater for malignant nodules (124.2±79.7%) than benign nodules (5.8±4.7%) (p<0.01). (orig.)

  7. Saline-enhanced radiofrequency thermal ablation of the lung: a feasibility study in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Min; Kim, Sang Won; Li, Chun Ai; Youk, Ji Hyun; Kim, Young Kon; Jin, Zhewu; Chung, Myoung Ja [Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Mi Suk [Yangi Hospital, Seoul (Korea, Republic of)

    2002-12-01

    To assess the feasibility and safety of CT-guided percutaneous transthoracic radiofrequency ablation (RFA) with saline infusion of pulmonary tissue in rabbits. Twenty-eight New Zealand White rabbits were divided into two groups: an RFA group (n=10) and a saline-enhanced RFA (SRFA) group (n=18). In the RFA group, percutaneous RFA of the lung was performed under CT guidance and using a 17-gauge internally cooled electrode. In the SRFA group, 1.5 ml of 0.9% saline was infused slowly through a 21-gauge, polyteflon-coated Chiba needle prior to and during RFA. Lesion size and the healing process were studied in rabbits sacrificed at times from the day following treatment to three weeks after, and any complications were noted. In the SRFA group, the mean diameter (12.5{+-}1.6 mm) of acute RF lesions was greater than that of RFA lesions (8.5{+-}1.4 mm) (p < .05). The complications arising in 12 cases were pneumothorax (n=8), thermal injury to the chest wall (n=2), hemothorax (n=1), and lung abscess (n=1). Although procedure-related complications tended to occur more frequently in the SRFA group (55.6%) than in the RFA group (20%), the difference was not statistically significant (p .11). Saline-enhanced RFA of pulmonary tissue in rabbits produces more extensive coagulation necrosis than conventional RFA procedures, without adding substantial risk of serious complications.

  8. Lung

    International Nuclear Information System (INIS)

    DeNardo, G.L.; Blankenship, W.J.; Burdine, J.A. Jr.; DeNardo, S.J.

    1975-01-01

    At present no simple statement can be made relative to the role of radionuclidic lung studies in the pediatric population. It is safe to assume that they will be used with increasing frequency for research and clinical applications because of their sensitivity and ready applicability to the pediatric patient. Methods comparable to those used in adults can be used in children older than 4 years. In younger children, however, a single injection of 133 Xe in solution provides an index of both regional perfusion and ventilation which is easier to accomplish. This method is particularly valuable in infants and neonates because it is rapid, requires no patient cooperation, results in a very low radiation dose, and can be repeated in serial studies. Radionuclidic studies of ventilation and perfusion can be performed in almost all children if the pediatrician and the nuclear medicine specialist have motivation and ingenuity. S []ontaneous pulmonary vascular occlusive disease which occurs in infants and pulmonary emboli in children are easily detected using radionuclides. The pathophysiologic defects of pulmonary agenesis, bronchopulmonary sequestration, and foreign body aspiration may be demonstrated by these techniques. These techniques also appear to be useful in following patients with bronchial asthma, cystic fibrosis, congenital emphysema, and postinfection pulmonary abnormalities. (auth)

  9. Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Kocdor H

    2015-07-01

    Full Text Available Hilal Kocdor,1,2 Halil Ates,1 Suleyman Aydin,3 Ruksan Cehreli,1 Firat Soyarat,2 Pinar Kemanli,2 Duygu Harmanci,2 Hakan Cengiz,2 Mehmet Ali Kocdor4 1Institute of Oncology, Dokuz Eylul University, 2Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University, Izmir Turkey; 3Department of Biochemistry, Firat University School of Medicine, Elazig, 4Department of Surgery, School of Medicine, Dokuz Eylul University, Izmir, Turkey Background: Exposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells.Methods: Here, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549 and p53-null (H1299 cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels.Results: Zinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC50 values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50 µM and 100 µM.Conclusion: Zinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells. Keywords: lung cancer, zinc, docetaxel, A549, H1299

  10. Defective bacterial clearance is responsible for the enhanced lung pathology characteristic of Mannheimia haemolytica pneumonia in bighorn sheep.

    Science.gov (United States)

    Subramaniam, Renuka; Herndon, Caroline N; Shanthalingam, Sudarvili; Dassanayake, Rohana P; Bavananthasivam, Jegarubee; Potter, Kathleen A; Knowles, Donald P; Foreyt, William J; Srikumaran, Subramaniam

    2011-12-15

    The molecular and cellular basis for the enhanced lung pathology and mortality caused by Mannheimia haemolytica in bighorn sheep (BHS, Ovis canadenesis), in comparison to domestic sheep (DS, Ovis aries), is not clear. Polymorphonuclear leukocytes (PMNs) of BHS are four- to eight-fold more susceptible to M. haemolytica leukotoxin-induced cytolysis, which is likely to reduce the number of functional phagocytes in the lung. We hypothesized that enhanced lung pathology is due to defective clearance of M. haemolytica from the lungs of BHS. To test this hypothesis, M. haemolytica (1 × 10(7) colony forming units [cfu]) were inoculated intra-tracheally into three groups each of BHS and DS, which were euthanized and necropsied at 4, 12, and 18 h post-inoculation (hpi). Bacterial and leukocyte counts were performed on broncho-alveolar lavage fluid (BALF) collected at necropsy. BALF from BHS euthanized at 4 and 12 hpi contained a significantly higher number of M. haemolytica than that from DS. More importantly, DS did not have any bacteria in BALF at 18 hpi, while the BHS still had significant numbers. As expected, the BHS did exhibit more extensive lung lesions at 12 and 18 hpi when compared to DS. At 18 hpi, necrotic PMNs were observed in the lesional lung tissues of BHS, but not DS. Furthermore, BALF from BHS had significantly lower titers of antibodies to Lkt and surface antigens of M. haemolytica, than that of DS. These findings suggest that the enhanced pathology in BHS lungs is due to defective clearance of M. haemolytica from the lungs. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Overcoming drug-tolerant cancer cell subpopulations showing AXL activation and epithelial–mesenchymal transition is critical in conquering ALK-positive lung cancer

    Science.gov (United States)

    Nakamichi, Shinji; Seike, Masahiro; Miyanaga, Akihiko; Chiba, Mika; Zou, Fenfei; Takahashi, Akiko; Ishikawa, Arimi; Kunugi, Shinobu; Noro, Rintaro; Kubota, Kaoru; Gemma, Akihiko

    2018-01-01

    Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) induce a dramatic response in non–small cell lung cancer (NSCLC) patients with the ALK fusion gene. However, acquired resistance to ALK-TKIs remains an inevitable problem. In this study, we aimed to discover novel therapeutic targets to conquer ALK-positive lung cancer. We established three types of ALK-TKI (crizotinib, alectinib and ceritinib)-resistant H2228 NSCLC cell lines by high exposure and stepwise methods. We found these cells showed a loss of ALK signaling, overexpressed AXL with epithelial-mesenchymal transition (EMT), and had cancer stem cell-like (CSC) properties, suggesting drug-tolerant cancer cell subpopulations. Similarly, we demonstrated that TGF-β1 treated H2228 cells also showed AXL overexpression with EMT features and ALK-TKI resistance. The AXL inhibitor, R428, or HSP90 inhibitor, ganetespib, were effective in reversing ALK-TKI resistance and EMT changes in both ALK-TKI-resistant and TGF-β1-exposed H2228 cells. Tumor volumes of xenograft mice implanted with established H2228-ceritinib-resistant (H2228-CER) cells were significantly reduced after treatment with ganetespib, or ganetespib in combination with ceritinib. Some ALK-positive NSCLC patients with AXL overexpression showed a poorer response to crizotinib therapy than patients with a low expression of AXL. ALK signaling-independent AXL overexpressed in drug-tolerant cancer cell subpopulations with EMT and CSC features may be commonly involved commonly involved in intrinsic and acquired resistance to ALK-TKIs. This suggests AXL and HSP90 inhibitors may be promising therapeutic drugs to overcome drug-tolerant cancer cell subpopulations in ALK-positive NSCLC patients for the reason that ALK-positive NSCLC cells do not live through ALK-TKI therapy. PMID:29930762

  12. 8-aminoadenosine enhances radiation-induced cell death in human lung carcinoma A549 cells

    International Nuclear Information System (INIS)

    Meike, Shunsuke; Yamamori, Tohru; Yasui, Hironobu; Eitaki, Masato; Inanami, Osamu; Matsuda, Akira

    2011-01-01

    The combination of a chemotherapeutic agent and radiation is widely applied to enhance cell death in solid tumor cells in cancer treatment. The purine analogue 8-aminoadenosine (8-NH 2 -Ado) is known to be a transcription inhibitor that has proved very effective in multiple myeloma cell lines and primary indolent leukemia cells. In this report, to examine whether 8-NH 2 -Ado had the ability to enhance the radiation-induced cell killing in solid tumor cells, human lung adenocarcinoma A549 cells were irradiated in the presence and absence of 8-NH 2 -Ado. 8-NH 2 -Ado significantly increased reproductive cell death and apoptosis in A549 cells exposed to X-rays. When peptide inhibitors against caspase-3, -8, and -9 were utilized to evaluate the involvement of caspases, all inhibitors suppressed the enhancement of radiation-induced apoptosis, suggesting that not only mitochondria-mediated apoptotic signal transduction pathways but also death receptor-mediated pathways were involved in this enhancement of apoptosis. In addition, in the cells exposed to the treatment combining X-irradiation and 8-NH 2 -Ado, reduction of the intracellular ATP concentration was essential for survival, and down-regulation of the expression of antiapoptotic proteins such as survivin and X-linked inhibitor of apoptosis protein (XIAP) was observed. These results indicate that 8-NH 2 -Ado has potential not only as an anti-tumor drug for leukemia and lymphoma but also as a radiosensitizing agent for solid tumors. (author)

  13. Endothelial Protein C–Targeting Liposomes Show Enhanced Uptake and Improved Therapeutic Efficacy in Human Retinal Endothelial Cells

    DEFF Research Database (Denmark)

    Arta, Anthoula; Eriksen, Anne Z.; Melander, Fredrik

    2018-01-01

    PURPOSE. To determine whether human retinal endothelial cells (HRECs) express the endothelial cell protein C receptor (EPCR) and to realize its potential as a targeting moiety by developing novel single and dual corticosteroid–loaded functionalized liposomes that exhibit both enhanced uptake by H...... of cell tube formations in contrast to nontargeting liposomes. CONCLUSIONS. We show that HRECs express EPCR and this receptor could be a promising nanomedicine target in ocular diseases where the endothelial barrier of the retina is compromised....

  14. Brain metastasis of small cell lung carcinoma. Comparison of Gd-DTPA enhanced magnetic resonance imaging and enhanced computerized tomography

    International Nuclear Information System (INIS)

    Nomoto, Yasushi; Yamaguchi, Yutaka; Miyamoto, Tadaaki.

    1994-01-01

    Small cell carcinoma of the lung (SCLC) frequently metastasizes into the brain, resulting in serious influences upon prognosis. Delayed brain damage caused by prophylactic cranial irradiation (PCI) is also problematic. Gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI) was performed to detect early brain metastasis from SCLC, and its usefulness was compared with contrast computerized tomography (CT). Among 25 SCLC patients, brain metastasis was detected in 11 by MRI and in 10 by CT, although six of them were completely asymptomatic. In the 11 patients, 6.3 and 2.4 lesions were respectively detected on average by MRI and CT. The ability of MRI to detect metastatic lesions of ≥15 mm diameter did not differ from that of CT, but became different as lesions became smaller (P<0.002), and MRI had a decided advantage over CT because as many as 30 lesions of ≤5 mm diameter were detected by MRI, whereas such lesions visualized on CT numbered only one (P<0.0001). MRI was incomparably superior to CT (P<0.0004) for subtentorial lesions since 18 lesions were detected on MRI, but only three, measuring ≥25 mm in diameter, were demonstrated on CT. Gd-DTPA enhanced MRI was determined to be extremely useful in the early diagnosis of SCLC brain metastasis. MRI was thought to reduce delayed brain damage caused by PCI if performed according to an adequate schedule. (author)

  15. Silencing hyperoxia-induced C/EBPα in neonatal mice improves lung architecture via enhanced proliferation of alveolar epithelial cells

    Science.gov (United States)

    Yang, Guang; Hinson, Maurice D.; Bordner, Jessica E.; Lin, Qing S.; Fernando, Amal P.; La, Ping; Wright, Clyde J.

    2011-01-01

    Postnatal lung development requires proliferation and differentiation of specific cell types at precise times to promote proper alveolar formation. Hyperoxic exposure can disrupt alveolarization by inhibiting cell growth; however, it is not fully understood how this is mediated. The transcription factor CCAAT/enhancer binding protein-α (C/EBPα) is highly expressed in the lung and plays a role in cell proliferation and differentiation in many tissues. After 72 h of hyperoxia, C/EBPα expression was significantly enhanced in the lungs of newborn mice. The increased C/EBPα protein was predominantly located in alveolar type II cells. Silencing of C/EBPα with a transpulmonary injection of C/EBPα small interfering RNA (siRNA) prior to hyperoxic exposure reduced expression of markers of type I cell and differentiation typically observed after hyperoxia but did not rescue the altered lung morphology at 72 h. Nevertheless, when C/EBPα hyperoxia-exposed siRNA-injected mice were allowed to recover for 2 wk in room air, lung epithelial cell proliferation was increased and lung morphology was restored compared with hyperoxia-exposed control siRNA-injected mice. These data suggest that C/EBPα is an important regulator of postnatal alveolar epithelial cell proliferation and differentiation during injury and repair. PMID:21571903

  16. Prevalence of Enhancer of Zeste Homolog 2 in Patients with Resected Small Cell Lung Cancer.

    Science.gov (United States)

    Toyokawa, Gouji; Takada, Kazuki; Tagawa, Tetsuzo; Kinoshita, Fumihiko; Kozuma, Yuka; Matsubara, Taichi; Haratake, Naoki; Takamori, Shinkichi; Akamine, Takaki; Hirai, Fumihiko; Yamada, Yuichi; Hamamoto, Ryuji; Oda, Yoshinao; Maehara, Yoshihiko

    2018-06-01

    Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in cancer pathogenesis. Although clinicopathological significance of EZH2 in non-small cell lung cancer has been gradually elucidated, such significance in small cell lung cancer (SCLC) has yet to be fully investigated. Forty patients with resected SCLC were analyzed for EZH2. EZH2 expression was evaluated using the Allred score (0-8) and was classified into negative (0-6) and positive (7 and 8). We evaluated the association between EZH2 and the clinicopathological characteristics and postoperative survivals. Among 40 patients, 15 (37.5%) and 25 (62.5%) were classified as being negative and positive for EZH2, respectively. Fisher's exact test demonstrated no significant associations between the positivity for EZH2 and clinicopathological characteristics. No significant differences were observed in recurrence-free and overall survivals between EZH2-negative/low and EZH2-high patients. EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  17. Lung cancer mimicking lung abscess formation on CT images.

    Science.gov (United States)

    Taira, Naohiro; Kawabata, Tsutomu; Gabe, Atsushi; Ichi, Takaharu; Kushi, Kazuaki; Yohena, Tomofumi; Kawasaki, Hidenori; Yamashiro, Toshimitsu; Ishikawa, Kiyoshi

    2014-01-01

    Male, 64 FINAL DIAGNOSIS: Lung pleomorphic carcinoma Symptoms: Cough • fever - Clinical Procedure: - Specialty: Oncology. Unusual clinical course. The diagnosis of lung cancer is often made based on computed tomography (CT) image findings if it cannot be confirmed on pathological examinations, such as bronchoscopy. However, the CT image findings of cancerous lesions are similar to those of abscesses.We herein report a case of lung cancer that resembled a lung abscess on CT. We herein describe the case of 64-year-old male who was diagnosed with lung cancer using surgery. In this case, it was quite difficult to distinguish between the lung cancer and a lung abscess on CT images, and a lung abscess was initially suspected due to symptoms, such as fever and coughing, contrast-enhanced CT image findings showing a ring-enhancing mass in the right upper lobe and the patient's laboratory test results. However, a pathological diagnosis of lung cancer was confirmed according to the results of a rapid frozen section biopsy of the lesion. This case suggests that physicians should not suspect both a lung abscesses and malignancy in cases involving masses presenting as ring-enhancing lesions on contrast-enhanced CT.

  18. Perfusion magnetic resonance imaging and magnetic resonance spectroscopy of cerebral gliomas showing imperceptible contrast enhancement on conventional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Batra, A.; Tripathi, R.P.; Singh, A.K.

    2004-01-01

    The purpose of the present paper was to evaluate the utility of perfusion MRI in cerebral gliomas showing imperceptible contrast enhancement on conventional MRI, and to evaluate the relationships of perfusion MRI and magnetic resonance (MR) spectroscopic results in these tumours. Twenty-two patients with histopathologically proven cerebral gliomas and showing insignificant contrast enhancement on conventional MR were included in the present study. All patients underwent perfusion MRI and MR spectroscopy on a 1.5-T MR system. Significant differences of the relative cerebral blood volume (rCBV) values and the choline : creatine ratios were noted between low-grade and anaplastic gliomas (P < 0.01). Good correlation was found between the rCBV values and the choline : creatine values (y = 0. 532x + 1.5643; r = 0.67). Perfusion MRI can be a useful tool in assessing the histopathological grade of non-contrast-enhancing cerebral gliomas. Along with MR spectroscopic imaging it can serve as an important technique for preoperative characterization of such gliomas, so that accurate targeting by stereotactic biopsies is possible. Copyright (2004) Blackwell Science Pty Ltd

  19. Supplementation with vitamin A enhances oxidative stress in the lungs of rats submitted to aerobic exercise.

    Science.gov (United States)

    Gasparotto, Juciano; Petiz, Lyvia Lintzmaier; Girardi, Carolina Saibro; Bortolin, Rafael Calixto; de Vargas, Amanda Rodrigues; Henkin, Bernardo Saldanha; Chaves, Paloma Rodrigues; Roncato, Sabrina; Matté, Cristiane; Zanotto-Filho, Alfeu; Moreira, José Cláudio Fonseca; Gelain, Daniel Pens

    2015-12-01

    Exercise training induces reactive oxygen species production and low levels of oxidative damage, which are required for induction of antioxidant defenses and tissue adaptation. This process is physiological and essential to improve physical conditioning and performance. During exercise, endogenous antioxidants are recruited to prevent excessive oxidative stress, demanding appropriate intake of antioxidants from diet or supplements; in this context, the search for vitamin supplements that enhance the antioxidant defenses and improve exercise performance has been continuously increasing. On the other hand, excess of antioxidants may hinder the pro-oxidant signals necessary for this process of adaptation. The aim of this study was to investigate the effects of vitamin A supplementation (2000 IU/kg, oral) upon oxidative stress and parameters of pro-inflammatory signaling in lungs of rats submitted to aerobic exercise (swimming protocol). When combined with exercise, vitamin A inhibited biochemical parameters of adaptation/conditioning by attenuating exercise-induced antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and decreasing the content of the receptor for advanced glycation end-products. Increased oxidative damage to proteins (carbonylation) and lipids (lipoperoxidation) was also observed in these animals. In sedentary animals, vitamin A decreased superoxide dismutase and increased lipoperoxidation. Vitamin A also enhanced the levels of tumor necrosis factor alpha and decreased interleukin-10, effects partially reversed by aerobic training. Taken together, the results presented herein point to negative effects associated with vitamin A supplementation at the specific dose here used upon oxidative stress and pro-inflammatory cytokines in lung tissues of rats submitted to aerobic exercise.

  20. Salinomycin enhances cisplatin-induced cytotoxicity in human lung cancer cells via down-regulation of AKT-dependent thymidylate synthase expression.

    Science.gov (United States)

    Ko, Jen-Chung; Zheng, Hao-Yu; Chen, Wen-Ching; Peng, Yi-Shuan; Wu, Chia-Hung; Wei, Chia-Li; Chen, Jyh-Cheng; Lin, Yun-Wei

    2016-12-15

    Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore and has anticancer activity on various cancer cell lines. Cisplatin has been proved as chemotherapy drug for advanced human non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) is a key enzyme in the pyrimidine salvage pathway, and increased expression of TS is thought to be associated with resistance to cisplatin. In this study, we showed that salinomycin (0.5-2μg/mL) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells. Knockdown of TS using small interfering RNA (siRNA) or inhibiting AKT activity with PI3K inhibitor LY294002 enhanced the cytotoxicity and cell growth inhibition of salinomycin. A combination of cisplatin and salinomycin resulted in synergistic enhancement of cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced activation of phospho-AKT, and TS expression. Overexpression of a constitutive active AKT (AKT-CA) expression vector reversed the salinomycin and cisplatin-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in salinomycin and cisplatin cotreated cells. Our findings suggested that the down-regulation of AKT-mediated TS expression by salinomycin enhanced the cisplatin-induced cytotoxicity in NSCLC cells. These results may provide a rationale to combine salinomycin with cisplatin for lung cancer treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Enhancement in in vitro anti-angiogenesis activity and cytotoxicity in lung cancer cell by pectin-PVP based curcumin particulates.

    Science.gov (United States)

    Gaikwad, Dinanath; Shewale, Rajnita; Patil, Vinit; Mali, Dipak; Gaikwad, Uday; Jadhav, Namdeo

    2017-11-01

    The aim of this work was to prepare pectin-poly (vinyl pyrrolidone) [PVP] based curcumin particulates to enhance the anticancer potential of curcumin, solubility and allow its localized controlled release. Pectin-PVP based curcumin particulates (PECTIN-PVP CUR) were prepared by spray drying technique in different ratios and were evaluated for surface morphology, micromeritics, flowability, particle size, drug content, in vitro dissolution, inhalable fraction, anti-angiogenesis/angiolysis and cytotoxicity. Results of micromeritic properties, Carr's index, Hausner's ratio and angle of repose were satisfactory. The batch CP3 was considered as optimum, due to excellent flowability, acceptable aggregation and enhanced solubility. The particle size and size distribution data of selected batch CP3 showed 90% of curcumin particulates having size less than 2.74μm, which may deposit to lungs. Twin Impinger studies showed that 29% of respirable fraction was generated, which could be directly delivered to lungs. The in vitro dissolution data showed many fold increase in dissolution rate. Angiolytic activity and MTT assay of PECTIN-PVP CUR have demonstrated enhancement in the anti-tumor potential, compared to curcumin alone. Altogether, PECTIN-PVP CUR were found suitable for local delivery and enhance its anticancer potential of curcumin. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Enhancement of CD147 on M1 macrophages induces differentiation of Th17 cells in the lung interstitial fibrosis.

    Science.gov (United States)

    Geng, Jie-jie; Zhang, Kui; Chen, Li-na; Miao, Jin-lin; Yao, Meng; Ren, Ying; Fu, Zhi-guang; Chen, Zhi-nan; Zhu, Ping

    2014-09-01

    Lung interstitial fibrosis is a chronic lung disease, and few effective therapies are available to halt or reverse the progression of the disease. In murine and human lung fibrosis, the expression of CD147 is increased. However, the role of CD147 in lung fibrosis has not been identified, and it remains to be determined whether lung fibrosis would be improved by decreasing the expression of CD147. A murine bleomycin-induced lung interstitial fibrosis model was used in the experiments, and HAb18 mAbs and CsA were administered during the induction of lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow cytometry analysis showed that M1 macrophages induced higher Th17 differentiation than M2 macrophages. After treatment with HAb18 mAbs or after reducing the expression of CD147 by lentivirus interference in M1 macrophages, the level of Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage and induced the differentiation of Th17 cells in lung interstitial fibrosis, perhaps by regulating some cytokines such as IL-6, IL-1β, IL-12 and IL-23. These results indicated that CD147 may play an important role in the development of lung interstitial fibrosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Vorinostat enhances the cisplatin-mediated anticancer effects in small cell lung cancer cells.

    Science.gov (United States)

    Pan, Chun-Hao; Chang, Ying-Fang; Lee, Ming-Shuo; Wen, B-Chen; Ko, Jen-Chung; Liang, Sheng-Kai; Liang, Mei-Chih

    2016-11-07

    Vorinostat, a histone deacetylase (HDAC) inhibitor, is a promising agent for cancer therapy. Combining vorinostat with cisplatin may relax the chromatin structure and facilitate the accessibility of cisplatin, thus enhancing its cytotoxicity. Studies have not yet investigated the effects of the combination of vorinostat and cisplatin on small cell lung cancer (SCLC). We first assessed the efficacy of vorinostat with etoposide/cisplatin (EP; triple combination) and then investigated the effects of cotreatment with vorinostat and cisplatin on H209 and H146 SCLC cell lines. The anticancer effects of various combinations were determined in terms of cell viability, apoptosis, cell cycle distribution, and vorinostat-regulated proteins. We also evaluated the efficacy of vorinostat/cisplatin combination in H209 xenograft nude mice. Our data revealed that the triple combination engendered a significant reduction of cell viability and high apoptotic cell death. In addition, vorinostat combined with cisplatin enhanced cell growth inhibition, induced apoptosis, and promoted cell cycle arrest. We observed that the acetylation levels of histone H3 and α-tubulin were higher in combination treatments than in vorinostat treatment alone. Moreover, vorinostat reduced the expression of thymidylate synthase (TS), and TS remained inhibited after cotreament with cisplatin. Furthermore, an in vivo study revealed that the combination of vorinostat and cisplatin significantly inhibited tumor growth in xenograft nude mice (tumor growth inhibition T/C% = 20.5 %). Combined treatments with vorinostat promote the cytotoxicity of cisplatin and induce the expression of vorinostat-regulated acetyl proteins, eventually enhancing antitumor effects in SCLC cell lines. Triple combinations with a low dosage of cisplatin demonstrate similar therapeutic effects. Such triple combinations, if applied clinically, may reduce the undesired adverse effects of cisplatin. The effects of the combination of

  4. Improving the Lung Delivery of Nasally Administered Aerosols During Noninvasive Ventilation—An Application of Enhanced Condensational Growth (ECG)

    Science.gov (United States)

    Tian, Geng; Hindle, Michael

    2011-01-01

    Abstract Background Aerosol drug delivery during noninvasive ventilation (NIV) is known to be inefficient due to high depositional losses. To improve drug delivery efficiency, the concept of enhanced condensational growth (ECG) was recently proposed in which a submicrometer or nanoaerosol reduces extrathoracic deposition and subsequent droplet size increase promotes lung retention. The objective of this study was to provide proof-of-concept that the ECG approach could improve lung delivery of nasally administered aerosols under conditions consistent with NIV. Methods Aerosol deposition and size increase were evaluated in an adult nose–mouth–throat (NMT) replica geometry using both in vitro experiments and CFD simulations. For the ECG delivery approach, separate streams of a submicrometer aerosol and warm (39°C) saturated air were generated and delivered to the right and left nostril inlets, respectively. A control case was also considered in which an aerosol with a mass median aerodynamic diameter (MMAD) of 4.67 μm was delivered to the model. Results In vitro experiments showed that the ECG approach significantly reduced the drug deposition fraction in the NMT geometry compared with the control case [14.8 (1.83)%—ECG vs. 72.6 (3.7)%—control]. Aerosol size increased from an initial MMAD of 900 nm to a size of approximately 2 μm at the exit of the NMT geometry. Results of the CFD model were generally in good agreement with the experimental findings. Based on CFD predictions, increasing the delivery temperature of the aerosol stream from 21 to 35°C under ECG conditions further reduced the total NMT drug deposition to 5% and maintained aerosol growth by ECG to approximately 2 μm. Conclusions Application of the ECG approach may significantly improve the delivery of pharmaceutical aerosols during NIV and may open the door for using the nasal route to routinely deliver pulmonary medications. PMID:21410327

  5. Enhanced Anticancer Activity of PF-04691502, a Dual PI3K/mTOR Inhibitor, in Combination With VEGF siRNA Against Non–small-cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Laura Espana-Serrano

    2016-01-01

    Full Text Available Lung cancer is the leading cause of cancer deaths in both men and women in the United States accounting for about 27% of all cancer deceases. In our effort to develop newer therapy for lung cancer, we evaluated the combinatory antitumor effect of siRNA targeting VEGF and the PI3K/mTOR dual inhibitor PF-04691502. We analyzed the anticancer effect of siRNA VEGF and PF-04691502 combination on proliferation, colony formation and migration of A549 and H460 lung cancer cells. Additionally, we assessed the combination treatment antiangiogenic effect on human umbilical vein endothelial cells. Here, we show for the first time that the antiangiogenic siRNA VEGF potentiates the PF-04691502 anticancer activity against non–small-cell lung cancer. We observed a significant (P < 0.05 decrease in cell viability, colony formation, and migration for the combination comparing with the single drug treatment. We also showed a significant (P < 0.05 enhanced effect of the combination treatment inhibiting angiogenesis progression and tube formation organization compared to the single drug treatment groups. Our findings demonstrated an enhanced synergistic anticancer effect of siRNA VEGF and PF-04691502 combination therapy by targeting two main pathways involved in lung cancer cell survival and angiogenesis which will be useful for future preclinical studies and potentially for lung cancer patient management.

  6. The Replacement of five Consecutive Amino Acids in the Cyt1A Protein of Bacillus thuringiensis Enhances its Cytotoxic Activity against Lung Epithelial Cancer Cells

    Directory of Open Access Journals (Sweden)

    Kavita Nair

    2018-03-01

    Full Text Available Cyt1A protein is a cytolytic protein encoded by the cyt gene of Bacillus thuringiensis subsp. israelensis (Bti as part of the parasporal crystal proteins produced during the sporulation. Cyt1A protein is unique compared to the other endotoxins present in these parasporal crystals. Unlike δ-endotoxins, Cyt1A protein does not require receptors to bind to the target cell and activate the toxicity. It has the ability to affect a broad range of cell types and organisms, due to this characteristic. Cyt1A has been recognized to not only target the insect cells directly, but also recruit other endotoxins by acting as receptors. Due to these mode of actions, Cyt1A has been studied for its cytolytic activity against human cancer cell lines, although not extensively. In this study, we report a novel Cyt1A protein produced by a Bti strain QBT229 isolated from Qatar. When tested for its cytotoxicity against lung cancer cells, this local strain showed considerably higher activity compared to that of the reference Bti and other strains tested. The possible reasons for such enhanced activity were explored at the gene and protein levels. It was evidenced that five consecutive amino acid replacements in the β8 sheet of the Cyt1A protein enhanced the cytotoxicity against the lung epithelial cancer cells. Such novel Cyt1A protein with high cytotoxicity against lung cancer cells has been characterized and reported through this study.

  7. Rab22a enhances CD147 recycling and is required for lung cancer cell migration and invasion.

    Science.gov (United States)

    Zhou, Yang; Wu, Bo; Li, Jiang-Hua; Nan, Gang; Jiang, Jian-Li; Chen, Zhi-Nan

    2017-08-01

    Rab22a is a member of the Ras-related small GTPase family, which plays a key role in regulating the recycling of cargo proteins entering cells through clathrin-independent endocytosis (CIE). Rab22a is overexpressed in different cancer types, including liver cancer, malignant melanoma, ovarian cancer and osteosarcoma. However, its oncogenic role remains unknown. In this study, we found that silencing of Rab22a suppressed the migration and invasion of lung cancer cells. Furthermore, Rab22a interacts with CD147, and knockdown of Rab22a blocks CD147 recycling and promotes CD147 degradation. Taken together, our findings indicate that Rab22a enhances recycling of CD147, which is required for lung cancer cell migration and invasion,and targeting CD147 recycling may be a rational strategy for lung cancer therapy. Copyright © 2017. Published by Elsevier Inc.

  8. The vascular disrupting agent ZD6126 shows increased antitumor efficacy and enhanced radiation response in large, advanced tumors

    International Nuclear Information System (INIS)

    Siemann, Dietmar W.; Rojiani, Amyn M.

    2005-01-01

    Purpose: ZD6126 is a vascular-targeting agent that induces selective effects on the morphology of proliferating and immature endothelial cells by disrupting the tubulin cytoskeleton. The efficacy of ZD6126 was investigated in large vs. small tumors in a variety of animal models. Methods and Materials: Three rodent tumor models (KHT, SCCVII, RIF-1) and three human tumor xenografts (Caki-1, KSY-1, SKBR3) were used. Mice bearing leg tumors ranging in size from 0.1-2.0 g were injected intraperitoneally with a single 150 mg/kg dose of ZD6126. The response was assessed by morphologic and morphometric means as well as an in vivo to in vitro clonogenic cell survival assay. To examine the impact of tumor size on the extent of enhancement of radiation efficacy by ZD6126, KHT sarcomas of three different sizes were irradiated locally with a range of radiation doses, and cell survival was determined. Results: All rodent tumors and human tumor xenografts evaluated showed a strong correlation between increasing tumor size and treatment effect as determined by clonogenic cell survival. Detailed evaluation of KHT sarcomas treated with ZD6126 showed a reduction in patent tumor blood vessels that was ∼20% in small ( 90% in large (>1.0 g) tumors. Histologic assessment revealed that the extent of tumor necrosis after ZD6126 treatment, although minimal in small KHT sarcomas, became more extensive with increasing tumor size. Clonogenic cell survival after ZD6126 exposure showed a decrease in tumor surviving fraction from approximately 3 x 10 -1 to 1 x 10 -4 with increasing tumor size. When combined with radiotherapy, ZD6126 treatment resulted in little enhancement of the antitumor effect of radiation in small (<0.3 g) tumors but marked increases in cell kill in tumors larger than 1.0 g. Conclusions: Because bulky neoplastic disease is typically the most difficult to manage, the present findings provide further support for the continued development of vascular disrupting agents such as

  9. The defense-responsive genes showing enhanced and repressed expression after pathogen infection in rice (Oryza sativa L.)

    Institute of Scientific and Technical Information of China (English)

    ZHOU; Bin(周斌); PENG; Kaiman(彭开蔓); CHU; Zhaohui(储昭晖); WANG; Shiping(王石平); ZHANG; Qifa(张启发)

    2002-01-01

    Despite large numbers of studies about defense response, processes involved in the resistance of plants to incompatible pathogens are still largely uncharacterized. The objective of this study was to identify genes involved in defense response by cDNA array analysis and to gain knowledge about the functions of the genes involved in defense response. Approximately 20000 rice cDNA clones were arrayed on nylon filters. RNA samples isolated from different rice lines after infection with incompatible strains or isolates of Xanthomonas oryzae pv. oryzae or Pyricularia grisea, respectively, were used to synthesize cDNA as probes for screening the cDNA arrays. A total of 100 differentially expressed unique sequences were identified from 5 pathogen-host combinations. Fifty-three sequences were detected as showing enhanced expression and 47 sequences were detected as showing repressed expression after pathogen infection. Sequence analysis revealed that most of the 100 sequences had various degrees of homology with genes in databases which encode or putatively encode transcription regulating proteins, translation regulating proteins, transport proteins, kinases, metabolic enzymes, and proteins involved in other functions. Most of the genes have not been previously reported as being involved in the disease resistance response in rice. The results from cDNA arrays, reverse transcription-polymerase chain reaction, and RNA gel blot analysis suggest that activation or repression of most of these genes might occur commonly in the defense response.

  10. Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation.

    Science.gov (United States)

    Miyata, Kenichi; Takemoto, Ai; Okumura, Sakae; Nishio, Makoto; Fujita, Naoya

    2017-06-22

    Podoplanin/Aggrus, known as a platelet aggregation-inducing factor, is frequently overexpressed in lung squamous cell carcinomas (LSCC) and glioblastomas among other tumours, and its expression has been reported to be correlated with poor prognosis. However, the contribution of podoplanin to malignant progression has been elusive. Here we demonstrate that in podoplanin-positive LSCC cells, their growth was abrogated by podoplanin knockout in vivo but not in vitro. Conversely, ectopic expression of podoplanin promoted cell growth in vivo and facilitated intratumoral platelet activation. Consistently, LSCC cells evoked podoplanin-mediated platelet aggregation (PMPA), and the releasates from platelets during PMPA promoted the growth of LSCC cells in vitro. Phospho-receptor-tyrosine-kinase array analysis revealed that epidermal growth factor receptor (EGFR) phosphorylation of LSCC cells was responsible for the growth promotion induced by platelet releasates. Treatment with an antiplatelet agent or podoplanin-neutralizing antibody depressed the growth of an LSCC tumour xenograft via suppression of EGFR phosphorylation. These results suggested that podoplanin in LSCC enhanced cell growth by inducing PMPA in vivo and contributed to malignant progression.

  11. Reduction of nitric oxide level enhances the radiosensitivity of hypoxic non-small cell lung cancer

    International Nuclear Information System (INIS)

    Saleem, Wael; Suzuki, Yoshiyuki; Mobaraki, Abdulelah; Yoshida, Yukari; Noda, Shinei; Saitoh, Jun-ichi; Nakano, Takashi

    2011-01-01

    The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (E-TKI) resistance has emerged as an important clinical issue. To overcome this resistance, researchers have examined different modalities, either for use as a monotherapy or in combination with E-TKI therapy. In the present study, we investigated whether a decrease in nitric oxide (NO) levels affects the radiosensitization of non-small cell lung cancer (NSCLC) cell lines. A549 and H3255 NSCLC cells were examined. They were subjected to hypoxic conditions and monotherapy, or combined therapy using radiation and N G -monomethyl- L -arginine, monoacetate (LNMMA). Reductions in nitric oxide levels enhanced the radiosensitivity of both cell lines and significantly reduced the expression of both hypoxia-inducible factor-1α (HIF-1α) and EGFR in H3255 cells compared to A549 cells. Since NO is significantly associated with cell metabolism, we measured the levels of pyruvate dehydrogenase kinase-1 (PDK-1), reactive oxygen species, and oxygen and observed that the expression of PDK-1 was significantly reduced. This reduction was seen simultaneously after the silencing of HIF-1α; however, not following LNMMA treatment. The oxygen concentration was significantly increased in the treated cells, and their viability decreased in parallel. Reactive oxygen species were decreased after LNMMA and radiation treatment. Adding EGFR-TKI to cells with reduced NO levels further suppressed cell viability when combined with radiation. This study suggests that a reduction in the NO level might substantially overcome the radioresistance of mutant NSCLC cells. (author)

  12. Simulation of enhanced deposition due to magnetic field alignment of ellipsoidal particles in a lung bifurcation.

    Science.gov (United States)

    Martinez, R C; Roshchenko, A; Minev, P; Finlay, W H

    2013-02-01

    Aerosolized chemotherapy has been recognized as a potential treatment for lung cancer. The challenge of providing sufficient therapeutic effects without reaching dose-limiting toxicity levels hinders the development of aerosolized chemotherapy. This could be mitigated by increasing drug-delivery efficiency with a noninvasive drug-targeting delivery method. The purpose of this study is to use direct numerical simulations to study the resulting local enhancement of deposition due to magnetic field alignment of high aspect ratio particles. High aspect ratio particles were approximated by a rigid ellipsoid with a minor diameter of 0.5 μm and fluid particle density ratio of 1,000. Particle trajectories were calculated by solving the coupled fluid particle equations using an in-house micro-macro grid finite element algorithm based on a previously developed fictitious domain approach. Particle trajectories were simulated in a morphologically realistic geometry modeling a symmetrical terminal bronchiole bifurcation. Flow conditions were steady inspiratory air flow due to typical breathing at 18 L/min. Deposition efficiency was estimated for two different cases: [1] particles aligned with the streamlines and [2] particles with fixed angular orientation simulating the magnetic field alignment of our previous in vitro study. The local enhancement factor defined as the ratio between deposition efficiency of Case [1] and Case [2] was found to be 1.43 and 3.46 for particles with an aspect ratio of 6 and 20, respectively. Results indicate that externally forcing local alignment of high aspect ratio particles can increase local deposition considerably.

  13. T-peptide Enhances the Killing Effects of Cisplatinum on Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hongyi ZHANG

    2017-02-01

    Full Text Available Background and objective T peptide is extensively used in anti-tumor treatment. The aims of this study were to investigate whether T peptide enhances cisplatinum efficiency while reducing its side effects and to identify its effective mechanisms. Methods (1 Human macrophage U937 cells were treated with T peptide and/or cisplatinum. The levels of tumor necrosis factor-α (TNF-α and interferon-γ (IFN-γ of each group were detected by enzyme-linked immunosorbent assay (ELISA; (2 Xenograft mouse models of human lung cancer were treated with T peptide and/or cisplatinum once every five days for three times. Tumor volumes were measured during treatment; (3 The percentages of macrophages in the peripheral blood of the xenograft mouse models were measured by FACS. Results (1 Compared with other groups, the level of TNF-α was significantly higher in the human macrophage U937 cells that were treated with T peptide combined with cisplatinum. The levels of IFN-γ were significantly higher in human macrophage U937 cells that were treated with T peptide alone or T peptide combined with cisplatinum; (2 In the xenograft mouse models, T peptide combined with cisplatinum treatment significantly inhibited tumor growth without weight loss compared with the other groups; (3 The percentages of macrophages in the peripheral blood were significantly higher in the xenograft mouse models that were treated with T peptide combined with cisplatinum compared with in the other groups. Conclusion T peptide promotes macrophage proliferation and increases tumor cell killing factors (TNF-α, IFN-γ in vitro. Moreover, T peptide enhances the efficacy of cisplatin and reduces its toxicity in vivo.

  14. Transgenic alfalfa (Medicago sativa) with increased sucrose phosphate synthase activity shows enhanced growth when grown under N2-fixing conditions.

    Science.gov (United States)

    Gebril, Sayed; Seger, Mark; Villanueva, Fabiola Muro; Ortega, Jose Luis; Bagga, Suman; Sengupta-Gopalan, Champa

    2015-10-01

    Overexpression of SPS in alfalfa is accompanied by early flowering, increased plant growth and an increase in elemental N and protein content when grown under N2-fixing conditions. Sucrose phosphate synthase (SPS; EC 2.3.1.14) is the key enzyme in the synthesis of sucrose in plants. The outcome of overexpression of SPS in different plants using transgenic approaches has been quite varied, but the general consensus is that increased SPS activity is associated with the production of new sinks and increased sink strength. In legumes, the root nodule is a strong C sink and in this study our objective was to see how increasing SPS activity in a legume would affect nodule number and function. Here we have transformed alfalfa (Medicago sativa, cv. Regen SY), with a maize SPS gene driven by the constitutive CaMV35S promoter. Our results showed that overexpression of SPS in alfalfa, is accompanied by an increase in nodule number and mass and an overall increase in nitrogenase activity at the whole plant level. The nodules exhibited an increase in the level of key enzymes contributing to N assimilation including glutamine synthetase and asparagine synthetase. Moreover, the stems of the transformants showed higher level of the transport amino acids, Asx, indicating increased export of N from the nodules. The transformants exhibited a dramatic increase in growth both of the shoots and roots, and earlier flowering time, leading to increased yields. Moreover, the transformants showed an increase in elemental N and protein content. The overall conclusion is that increased SPS activity improves the N status and plant performance, suggesting that the availability of more C in the form of sucrose enhances N acquisition and assimilation in the nodules.

  15. The Relevance of External Quality Assessment for Molecular Testing for ALK Positive Non-Small Cell Lung Cancer : Results from Two Pilot Rounds Show Room for Optimization

    NARCIS (Netherlands)

    Tembuyser, Lien; Tack, Veronique; Zwaenepoel, Karen; Pauwels, Patrick; Miller, Keith; Bubendorf, Lukas; Kerr, Keith; Schuuring, Ed; Thunnissen, Erik; Dequeker, Elisabeth M. C.

    2014-01-01

    Background and Purpose: Molecular profiling should be performed on all advanced non-small cell lung cancer with non-squamous histology to allow treatment selection. Currently, this should include EGFR mutation testing and testing for ALK rearrangements. ROS1 is another emerging target. ALK

  16. Bronchus-associated lymphoid tissue (BALT) lymphoma of the lung showing mosaic pattern of inhomogeneous attenuation on thin-section CT: a case report

    International Nuclear Information System (INIS)

    Lee, In Jae; Kim, Sung Hwan; Koo, Soo Hyun; Kim, Hyun Beom; Hwang, Dae Hyun; Lee, Kwan Seop; Lee, Yul; Jang, Kee Taek; Kim, Duck Hwan

    2000-01-01

    The authors present a case of histologically proven bronchus-associated lymphoid tissue (BALT) lymphoma of the lung in a patient with primary Sjogren's syndrome that manifested on thin-section CT scan as a mosaic pattern of inhomogeneous attenuation due to mixed small airway and infiltrative abnormalities

  17. Bronchus-associated lymphoid tissue (BALT) lymphoma of the lung showing mosaic pattern of inhomogeneous attenuation on thin-section CT: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, In Jae; Kim, Sung Hwan; Koo, Soo Hyun; Kim, Hyun Beom; Hwang, Dae Hyun; Lee, Kwan Seop; Lee, Yul; Jang, Kee Taek; Kim, Duck Hwan [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2000-09-01

    The authors present a case of histologically proven bronchus-associated lymphoid tissue (BALT) lymphoma of the lung in a patient with primary Sjogren's syndrome that manifested on thin-section CT scan as a mosaic pattern of inhomogeneous attenuation due to mixed small airway and infiltrative abnormalities.

  18. In planta Transformed Cumin (Cuminum cyminum L.) Plants, Overexpressing the SbNHX1 Gene Showed Enhanced Salt Endurance.

    Science.gov (United States)

    Pandey, Sonika; Patel, Manish Kumar; Mishra, Avinash; Jha, Bhavanath

    2016-01-01

    Cumin is an annual, herbaceous, medicinal, aromatic, spice glycophyte that contains diverse applications as a food and flavoring additive, and therapeutic agents. An efficient, less time consuming, Agrobacterium-mediated, a tissue culture-independent in planta genetic transformation method was established for the first time using cumin seeds. The SbNHX1 gene, cloned from an extreme halophyte Salicornia brachiata was transformed in cumin using optimized in planta transformation method. The SbNHX1 gene encodes a vacuolar Na+/H+ antiporter and is involved in the compartmentalization of excess Na+ ions into the vacuole and maintenance of ion homeostasis Transgenic cumin plants were confirmed by PCR using gene (SbNHX1, uidA and hptII) specific primers. The single gene integration event and overexpression of the gene were confirmed by Southern hybridization and competitive RT-PCR, respectively. Transgenic lines L3 and L13 showed high expression of the SbNHX1 gene compared to L6 whereas moderate expression was detected in L5 and L10 transgenic lines. Transgenic lines (L3, L5, L10 and L13), overexpressing the SbNHX1 gene, showed higher photosynthetic pigments (chlorophyll a, b and carotenoid), and lower electrolytic leakage, lipid peroxidation (MDA content) and proline content as compared to wild type plants under salinity stress. Though transgenic lines were also affected by salinity stress but performed better compared to WT plants. The ectopic expression of the SbNHX1 gene confirmed enhanced salinity stress tolerance in cumin as compared to wild type plants under stress condition. The present study is the first report of engineering salt tolerance in cumin, so far and the plant may be utilized for the cultivation in saline areas.

  19. In planta Transformed Cumin (Cuminum cyminum L. Plants, Overexpressing the SbNHX1 Gene Showed Enhanced Salt Endurance.

    Directory of Open Access Journals (Sweden)

    Sonika Pandey

    Full Text Available Cumin is an annual, herbaceous, medicinal, aromatic, spice glycophyte that contains diverse applications as a food and flavoring additive, and therapeutic agents. An efficient, less time consuming, Agrobacterium-mediated, a tissue culture-independent in planta genetic transformation method was established for the first time using cumin seeds. The SbNHX1 gene, cloned from an extreme halophyte Salicornia brachiata was transformed in cumin using optimized in planta transformation method. The SbNHX1 gene encodes a vacuolar Na+/H+ antiporter and is involved in the compartmentalization of excess Na+ ions into the vacuole and maintenance of ion homeostasis Transgenic cumin plants were confirmed by PCR using gene (SbNHX1, uidA and hptII specific primers. The single gene integration event and overexpression of the gene were confirmed by Southern hybridization and competitive RT-PCR, respectively. Transgenic lines L3 and L13 showed high expression of the SbNHX1 gene compared to L6 whereas moderate expression was detected in L5 and L10 transgenic lines. Transgenic lines (L3, L5, L10 and L13, overexpressing the SbNHX1 gene, showed higher photosynthetic pigments (chlorophyll a, b and carotenoid, and lower electrolytic leakage, lipid peroxidation (MDA content and proline content as compared to wild type plants under salinity stress. Though transgenic lines were also affected by salinity stress but performed better compared to WT plants. The ectopic expression of the SbNHX1 gene confirmed enhanced salinity stress tolerance in cumin as compared to wild type plants under stress condition. The present study is the first report of engineering salt tolerance in cumin, so far and the plant may be utilized for the cultivation in saline areas.

  20. Characterization of tumor heterogeneity using dynamic contrast enhanced CT and FDG-PET in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Elmpt, Wouter van; Das, Marco; Hüllner, Martin; Sharifi, Hoda; Zegers, Catharina M.L.; Reymen, Bart; Lambin, Philippe; Wildberger, Joachim E.; Troost, Esther G.C.; Veit-Haibach, Patrick; De Ruysscher, Dirk

    2013-01-01

    Purpose: Dynamic contrast-enhanced CT (DCE-CT) quantifies vasculature properties of tumors, whereas static FDG-PET/CT defines metabolic activity. Both imaging modalities are capable of showing intra-tumor heterogeneity. We investigated differences in vasculature properties within primary non-small cell lung cancer (NSCLC) tumors measured by DCE-CT and metabolic activity from FDG-PET/CT. Methods: Thirty three NSCLC patients were analyzed prior to treatment. FDG-PET/CT and DCE-CT were co-registered. The tumor was delineated and metabolic activity was segmented on the FDG-PET/CT in two regions: low (<50% maximum SUV) and high (⩾50% maximum SUV) metabolic uptake. Blood flow, blood volume and permeability were calculated using a maximum slope, deconvolution algorithm and a Patlak model. Correlations were assessed between perfusion parameters for the regions of interest. Results: DCE-CT provided additional information on vasculature and tumor heterogeneity that was not correlated to metabolic tumor activity. There was no significant difference between low and high metabolic active regions for any of the DCE-CT parameters. Furthermore, only moderate correlations between maximum SUV and DCE-CT parameters were observed. Conclusions: No direct correlation was observed between FDG-uptake and parameters extracted from DCE-CT. DCE-CT may provide complementary information to the characterization of primary NSCLC tumors over FDG-PET/CT imaging

  1. Icotinib enhances lung cancer cell radiosensitivity in vitro and in vivo by inhibiting MAPK/ERK and AKT activation.

    Science.gov (United States)

    Fu, Yonghong; Zhang, Sen; Wang, Dongjie; Wang, Jing

    2018-05-16

    Icotinib hydrochloride is a small epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that was developed by Chinese scientists. While clinical trials have revealed its efficacy in the treatment of lung cancer, very little is known about its role in enhancing radiosensitivity. In this study, we investigated the effectiveness of Icotinib in enhancing lung cancer cell radiosensitivity and have detailed its underlying molecular mechanism. The lung cancer cell line H1650 was pretreated with or without Icotinib for 24 hours before radiation, and clonogenic survival assay was performed. Cell apoptosis was also analyzed by flow cytometry, while western blotting was performed to examine the activation of EGFR and its downstream kinases in H1650 cells after Icotinib and radiation treatment. Furthermore, a xenograft animal model was established to evaluate the radiosensitivity of Icotinib in vivo and to confirm its mechanism. Our results demonstrate that pretreatment with Icotinib reduced clonogenic survival after radiation, inhibited EGFR activation, and increased radiation-induced apoptosis in H1650 cells. The phosphorylation of protein kinase B (AKT), extracellular regulated protein kinase 1/2 (ERK1/2), and EGFR was inhibited after Icotinib and radiation combination treatment in vitro and in vivo compared with individual treatments. Combination treatment also affected the expression of the DNA repair protein H2A histone family member X (γ-H2AX). In conclusion, our results reveal that Icotinib enhances radiosensitivity in lung cancers in vitro and in vivo and the mechanism of this may involve blocking the EGFR-AKT and MAPK-ERK pathways and limiting DNA repair. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Differential diagnosis of solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomograph

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Zhi-gang; Sheng, Bo; Liu, Meng-qi; Lv, Fa-jin; Li, Qi; Ouyang, Yu, E-mail: cyscitg@163.com [Hospital of Chongqing Medical University, Department of Radiology, Chongqing (China)

    2016-10-15

    Objectives: To clarify differences between solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomography. Methods: In total, 64 and 132 patients with solitary pulmonary inflammatory masses/nodules and peripheral lung cancers, respectively, were enrolled in this study. Their computed tomographic findings were summarized and compared retrospectively. Results: Compared with the peripheral lung cancers, the inflammatory lesions were located closer to the pleura (p<0.0001). The majority of the inflammatory lesions were patchy and oval-shaped (82.8%), whereas most of the tumors were lobulated (82.6%). Almost all the inflammatory cases were unclear (93.8%), whereas most of the tumors had speculated margins (72.7%). Computed tomography values were significantly higher for the inflammatory lesions than for the cancers (p<0.0001). More than half of the inflammatory lesions had defined necrosis (59.3%). Furthermore, 49.2% of the cancers enhanced inhomogeneously, but only 24.6% had ill-defined necrosis or cavities. The peripheral zones of 98.4% of the inflammatory lesions and 72.7% of the tumors were unclear, with peripheral scattered patches (92.2%) and beam-shaped opacity (66.7%) being the most common findings, respectively. Adjacent pleural thickening was more frequent for the inflammatory lesions than the cancers (95.3% vs. 21.1%, p<0.0001), whereas pleural indentation was found in 67.4% of the subjects with cancer. In addition, hilar (p=0.034) and mediastinal (p=0.003) lymphadenopathy were more commonly detected in the cancers than in the inflammatory cases. Conclusions: Contrast-enhanced computed tomography findings for pulmonary inflammatory lesions and peripheral lung cancers were significantly different in many aspects. Developing a comprehensive understanding of these differences is helpful for directing their management. (author)

  3. Enhancement of radiosensitivity of recombinant Ad-p53 gene on human lung adenocarcinoma cell with different p53 status

    International Nuclear Information System (INIS)

    Pang Dequan; Wang Peiguo; Wang Ping; Zhang Weiming

    2008-01-01

    Objective: To investigate the enhancement of radiosensitivity of recombinant Ad-p53 gene on human lung adenocarcinoma cell lines(A549 and GLC-82) with different p53 status in vitro. Methods: Two human lung adenocarcinoma cell lines of A549 and GLC-82 were examined on their difference in p53 status with immunohistochemistry stain and PCR-SSCP technique. Expand Ad-wtp53 was transfected into tumor cells. Clonogenic assays were performed to evaluate the inhibition effect on cell growth and the degree of sensitization to irradiation. Apoptosis and cell cycle changes were determined using the flow cytometry assay. Results: The A549 cell line presented positive P53 expression while GLC-82 negative. GLC-82 bore mutant p53 on the exon 7. The wtp53 gene could be efficiently expressed in the two cell lines and greatly inhibit the cell growth. Its efficiency didn't depend on the intrinsic p53 genetic status. After irradiation, its function of inducing G 1 arrest and apoptosis on GLC-82 cell line was much stronger than the A549 cell line. In both the A549 and GLC-82 cell lines, the combination of Ad-p53 plus radiation resulted in more apoptosis than the others. There was no significant difference between two groups. Conclusions: Ad-p53 can depress the tumor growth and enhance the radiosensitivity of human lung adenocarcinoma cells. And this effect is independent of endogenous p53 status. (authors)

  4. Matrix metalloproteinase 3 polymorphisms as a potential marker of enhanced susceptibility to lung cancer in chronic obstructive pulmonary disease subjects

    Directory of Open Access Journals (Sweden)

    Kamil Brzóska

    2014-09-01

    Full Text Available [b]Introduction and objective[/b]. Chronic obstructive pulmonary disease (COPD is often accompanied by lung cancer. Among the genes that may play a role in the occurrence of COPD and lung cancer are those encoding the proteolytic enzymes, such as matrix metalloproteinases (MMPs and their tissue inhibitors. The objective of this study was to find MMPs-associated markers useful in the identification of COPD subjects with increased susceptibility to developing lung cancer. [b]Materials and methods[/b]. We compared the frequency of single nucleotide polymorphisms in genes coding for matrix proteinases ([i]MMP1, MMP2, MMP3, MMP9, MMP12[/i] as well as tissue inhibitor of metalloproteinases ([i]TIMP1[/i] in two groups of subjects: COPD patients (54 subjects and COPD patients diagnosed for lung cancer occurrence (53 subjects.The levels of the respective proteins in blood serum were also analyzed. [b]Results[/b]. The frequencies of 2 genotypes, [i]MMP3[/i] rs3025058 and MMP3 rs678815, were significantly different between the studied groups. In both cases, more heterozygotes and less homozygotes (both types were observed in the COPD group than in the COPD + cancer group. A significantly higher TIMP1 level in blood serum was observed in the COPD + cancer group than in the COPD group. There were no statistically significant differences in[i] MMPs[/i] blood levels between the studied groups. In addition, no genotype-associated differences in [i]TIMP1[/i] or[i] MMPs[/i] blood levels were observed. [b]Conclusions[/b]. Homozygocity for [i]MMP3[/i] rs3025058 and rs678815 polymorphisms is a potential marker of enhanced susceptibility to lung cancer development among COPD subjects.

  5. Synergistic enhancement of chemokine generation and lung injury by C5a or the membrane attack complex of complement

    DEFF Research Database (Denmark)

    Czermak, B J; Lentsch, A B; Bless, N M

    1999-01-01

    demonstrated synergistic production of C-X-C (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) and C-C (macrophage inflammatory protein-1alpha and monocyte chemoattractant-1) chemokines. In the absence of the costimulus, C5a or MAC did not induce chemokine generation....... In in vivo studies, C5a and MAC alone caused limited or no intrapulmonary generation of chemokines, but in the presence of a costimulus (IgG immune complexes) C5a and MAC caused synergistic intrapulmonary generation of C-X-C and C-C chemokines but not of tumor necrosis factor alpha. Under these conditions...... increased neutrophil accumulation occurred, as did lung injury. These observations suggest that C5a and MAC function synergistically with a costimulus to enhance chemokine generation and the intensity of the lung inflammatory response....

  6. Transcriptomic Analysis of Lung Tissue from Cigarette Smoke-Induced Emphysema Murine Models and Human Chronic Obstructive Pulmonary Disease Show Shared and Distinct Pathways.

    Science.gov (United States)

    Yun, Jeong H; Morrow, Jarrett; Owen, Caroline A; Qiu, Weiliang; Glass, Kimberly; Lao, Taotao; Jiang, Zhiqiang; Perrella, Mark A; Silverman, Edwin K; Zhou, Xiaobo; Hersh, Craig P

    2017-07-01

    Although cigarette smoke (CS) is the primary risk factor for chronic obstructive pulmonary disease (COPD), the underlying molecular mechanisms for the significant variability in developing COPD in response to CS are incompletely understood. We performed lung gene expression profiling of two different wild-type murine strains (C57BL/6 and NZW/LacJ) and two genetic models with mutations in COPD genome-wide association study genes (HHIP and FAM13A) after 6 months of chronic CS exposure and compared the results to human COPD lung tissues. We identified gene expression patterns that correlate with severity of emphysema in murine and human lungs. Xenobiotic metabolism and nuclear erythroid 2-related factor 2-mediated oxidative stress response were commonly regulated molecular response patterns in C57BL/6, Hhip +/- , and Fam13a -/- murine strains exposed chronically to CS. The CS-resistant Fam13a -/- mouse and NZW/LacJ strain revealed gene expression response pattern differences. The Fam13a -/- strain diverged in gene expression compared with C57BL/6 control only after CS exposure. However, the NZW/LacJ strain had a unique baseline expression pattern, enriched for nuclear erythroid 2-related factor 2-mediated oxidative stress response and xenobiotic metabolism, and converged to a gene expression pattern similar to the more susceptible wild-type C57BL/6 after CS exposure. These results suggest that distinct molecular pathways may account for resistance to emphysema. Surprisingly, there were few genes commonly modulated in mice and humans. Our study suggests that gene expression responses to CS may be largely species and model dependent, yet shared pathways could provide biologically significant insights underlying individual susceptibility to CS.

  7. GSK3β-dependent inhibition of AMPK potentiates activation of neutrophils and macrophages and enhances severity of acute lung injury

    Science.gov (United States)

    Park, Dae Won; Jiang, Shaoning; Liu, Yanping; Siegal, Gene P.; Inoki, Ken; Abraham, Edward

    2014-01-01

    Although AMP-activated protein kinase (AMPK) is involved in regulating carbohydrate and lipid metabolism, activated AMPK also plays an anti-inflammatory role in many cell populations. However, despite the ability of AMPK activation to diminish the severity of inflammatory responses, previous studies have found that AMPK activity is diminished in LPS-treated neutrophils and also in lungs of mice with LPS-induced acute lung injury (ALI). Since GSK3β participates in regulating AMPK activity, we examined potential roles for GSK3β in modulating LPS-induced activation of neutrophils and macrophages and in influencing severity of ALI. We found that GSK3β-dependent phosphorylation of T479-AMPK was associated with pT172 dephosphorylation and inactivation of AMPK following TLR4 engagement. GSK3β inhibitors BIO (6-bromoindirubin-3′-oxime), SB216763, or siRNA knockdown of GSK3β, but not the PI3K/AKT inhibitor LY294002, prevented Thr172-AMPK dephosphorylation. Exposure to LPS resulted in rapid binding between IKKβ and AMPKα, and phosphorylation of S485-AMPK by IKKβ. These results suggest that IKKβ-dependent phosphorylation of S485-AMPK was an essential step in subsequent phosphorylation and inactivation AMPK by GSK3β. Inhibition of GSK3β activity delayed IκBα degradation and diminished expression of the proinflammatory TNF-α in LPS-stimulated neutrophils and macrophages. In vivo, inhibition of GSK3β decreased the severity of LPS-induced lung injury as assessed by development of pulmonary edema, production of TNF-α and MIP-2, and release of the alarmins HMGB1 and histone 3 in the lungs. These results show that inhibition of AMPK by GSK3β plays an important contributory role in enhancing LPS-induced inflammatory responses, including worsening the severity of ALI. PMID:25239914

  8. Regulator of G-protein signaling 5 (RGS5) inhibits cell proliferation and enhances radiosensitivity of human lung cancer cells

    International Nuclear Information System (INIS)

    Xu Zumin; Wang Jin; Zuo Yufang; Yu Zhonghua; Peng Fang; Hu Xiao; Zhou Qichao; Ma Honglian; Bao Yong; Chen Ming

    2014-01-01

    Objective: To investigate the effects of regulator and the underlying molecular mechanisms of G-protein signaling 5 (RGS5) on radiation response in human lung cancer cells. Methods: The effects of RGS5 on viability were determined by MTT assay, and apoptosis rate was detected by flow cytometry, in human lung cancer cells. The combined effect of ionizing radiation and RGS5 on tumor cells was detected by colony formation assay. The protein expression was detected by Western blot. Results: RGS5 overexpression remarkably inhibited the survival of human lung cancer cells, and the growth inhibition rate of RGS5 overexpression on A549 and Calu-3 cells were 44.4% (F = 29.18, P < 0.05) and 39.27% (F = 23.04, P < 0.05) at 48 h, and 54.3%(F = 103.45, P < 0.05), 44.7%(F = 108.02, P < 0.05) at 72 h post-irradiation, respectively. RGS5 might exert its inhibitory effects on human lung cancer cells by inducing tumor cell apoptosis, while the apoptotic cells rate in A549 and Calu-3 cells in control group, pTRiEX group and pTRiEX-RGS5 group were (1.3±0.2)%, (3.4±0.6)%, (19.6±2.3)% (F = 86.62, P < 0.05), and (3.2±0.8)%, (3.0±0.9)%, (12.8±1.8)% (F = 28.80, P < 0.05) at 36 h post-irradiation, respectively. Furthermore, RGS5 could sensitize the lung cancer cells to radiation. Conclusions: RGS5 might play an inhibitory role in human lung cancer cell proliferation, which may explain the pathoclinical observation thet high expression of RGSS is a favorable prognostic factor in NSCLC patients. In addition, RGS5 also enhance the anti-tumor effects of radiation in human lung cancer cells. (authors)

  9. Prognostic Significance of Clinical/Pathological Stage IA Non-Small-Cell Lung Cancer Showing Partially Solid or Solid Tumours on Radiological Exam

    Science.gov (United States)

    Matsuura, Yosuke; Nakao, Masayuki; Mun, Mingyon; Nakagawa, Ken; Ishikawa, Yuichi; Okumura, Sakae

    2015-01-01

    Purpose: Although curative resection is expected to be effective in patients with clinical (c-) stage IA/pathological (p-) stage IA non-small-cell lung cancers, recurrence is often observed. Hence, the aim of this study was to identify predictors of recurrence. Methods: Between 2005 and 2009, 138 patients with c-stage IA/p-stage IA non-small-cell lung cancers underwent resection. Recurrence and recurrence-free survival (RFS) were compared with clinical, radiographic and pathological findings. Results: The 5-year cancer-specific survival rate was 97% and the RFS rate was 89% at a median follow-up time of 91 months. Recurrence was observed in 10 patients (7.2%). Significant differences were observed in RFS according to tumour dimensions on the mediastinal window image (>1.5 cm), serum carcinoembryonic antigen levels (>5.0 ng/mL), maximum standardised uptake values (SUVmax >2.5) and angiolymphatic invasion. Patients were grouped according to the number of risk factors for poor RFS. Patients with 0–1 of the identified risk factors had an RFS of 97%, where those with 2–4 factors had an RFS of 68% (p <0.001). Conclusion: Prognosis of patients exhibiting more than two of these risk factors is considerably poor. Thus, close observation and individualised adjuvant therapy may be beneficial to these patients. PMID:25740451

  10. Enhancement of cell death by TNF α-related apoptosis-inducing ligand (TRAIL) in human lung carcinoma A549 cells exposed to X rays under hypoxia

    International Nuclear Information System (INIS)

    Takahashi, Momoko; Inanami, Osamu; Yasui, Hironobu; Ogura, Aki; Kuwabara, Mikinori; Kubota, Nobuo; Tsujitani, Michihiko

    2007-01-01

    Our previous study showed that ionizing radiation induced the expression of death receptor DR5 on the cell surface in tumor cell lines and that the death receptor of the TNF α-related apoptosis-inducing ligand TRAIL enhanced the apoptotic pathway (Hamasu et al., (2005) Journal of Radiation Research, 46:103-110). The present experiments were performed to examine whether treatment with TRAIL enhanced the cell killing in tumor cells exposed to ionizing radiation under hypoxia, since the presence of radioresistant cells in hypoxic regions of solid tumors is a serious problem in radiation therapy for tumors. When human lung carcinoma A549 cells were irradiated under normoxia and hypoxia, respectively, radiation-induced enhancement of expression of DR5 was observed under both conditions. Incubation in the presence of TRAIL enhanced the caspase-dependent and chymotrypsin-like-protease-dependent apoptotic cell death in A549 cells exposed to X rays. Furthermore, it was shown that treatment with TRAIL enhanced apoptotic cell death and loss of clonogenic ability in A549 cells exposed to X rays not only under normoxia but also under hypoxia, suggesting that combination treatment with TRAIL and X irradiation is effective for hypoxic tumor cells. (author)

  11. Enhanced pulmonary toxicity with bleomycin and radiotherapy in oat cell lung cancer

    International Nuclear Information System (INIS)

    Einhorn, L.; Krause, M.; Hornback, N.; Furnas, B.

    1976-01-01

    In a recently completed study, combination chemotherapy consisting of bleomycin, adriamycin, cyclophosphamide, and vincristine was given to 29 patients with oat cell lung cancer. There were no cases of pulmonary fibrosis in these 29 patients. Although several of these patients had prior radiotherapy, none had concomitant radiotherapy and chemotherapy. This same four-drug chemotherapy regimen was combined with concomitant radiotherapy in 13 patients with oat cell lung cancer. There were three cases of fatal pulmonary fibrosis and two other cases of clinically significant pulmonary fibrosis. All five cases of pulmonary fibrosis occurred several weeks after completion of a six-week course of bleomycin (total dosage 90 units). It is concluded that bleomycin cannot be safely administered while patients are receiving radiotherapy of the lung

  12. Enhancement of lung cancer by cigarette smoking in uranium and other miners

    International Nuclear Information System (INIS)

    Archer, V.E.

    1985-01-01

    There are substantial animal and epidemiological data related to cigarette smoking and lung cancer among miners exposed to elevated levels of radon daughters that appears to be in disagreement. An hypothesis is advanced that explains most of this disagreement as being derived from temporal differences of cancer expression. The hypothesis is that a given radiation exposure induced a finite number of lung cancers, which have shorter latent periods due to the cancer promotion activity of smoke among cigarette smokers. According to this hypothesis, the life-shortening effect is greater among smoking miners than nonsmoking miners, and the ultimate number of lung cancers among smoking miners will be only a little larger than among nonsmokers. The greater number will derive from the additive effect of radiation and smoking, plus the greater force of competing causes of death among elderly nonsmokers

  13. Deficiency of CCAAT/enhancer binding protein family DNA binding prevents malignant conversion of adenoma to carcinoma in NNK-induced lung carcinogenesis in the mouse

    Directory of Open Access Journals (Sweden)

    Kimura Shioko

    2012-12-01

    Full Text Available Abstract Background The CCAAT/enhancer binding proteins (C/EBPs play important roles in carcinogenesis of many tumors including the lung. Since multiple C/EBPs are expressed in lung, the combinatorial expression of these C/EBPs on lung carcinogenesis is not known. Methods A transgenic mouse line expressing a dominant negative A-C/EBP under the promoter of lung epithelial Clara cell secretory protein (CCSP gene in doxycycline dependent fashion was subjected to 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK-induced lung carcinogenesis bioassay in the presence and absence of doxycycline, and the effect of abolition of DNA binding activities of C/EBPs on lung carcinogenesis was examined. Results A-C/EBP expression was found not to interfere with tumor development; however, it suppressed the malignant conversion of adenoma to carcinoma during NNK-induced lung carcinogenesis. The results suggested that Ki67 may be used as a marker for lung carcinomas in mouse. Conclusions The DNA binding of C/EBP family members can be used as a potential molecular target for lung cancer therapy.

  14. MicroRNA-449a enhances radiosensitivity in CL1-0 lung adenocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Yi-Jyun Liu

    Full Text Available Lung cancer is the leading cause of cancer-related mortality worldwide. Radiotherapy is often applied for treating lung cancer, but it often fails because of the relative non-susceptibility of lung cancer cells to radiation. MicroRNAs (miRNAs have been reported to modulate the radiosensitivity of lung cancer cells and have the potential to improve the efficacy of radiotherapy. The purpose of this study was to identify a miRNA that can adjust radiosensitivity in lung adenocarcinoma cells. Two lung adenocarcinoma cell lines (CL1-0 and CL1-5 with different metastatic ability and radiosensitivity were used. In order to understand the regulatory mechanisms of differential radiosensitivity in these isogenic tumor cells, both CL1-0 and CL1-5 were treated with 10 Gy radiation, and were harvested respectively at 0, 1, 4, and 24 h after radiation exposure. The changes in expression of miRNA upon irradiation were examined using Illumina Human microRNA BeadChips. Twenty-six miRNAs were identified as having differential expression post-irradiation in CL1-0 or CL1-5 cells. Among these miRNAs, miR-449a, which was down-regulated in CL1-0 cells at 24 h after irradiation, was chosen for further investigation. Overexpression of miR-449a in CL1-0 cells effectively increased irradiation-induced DNA damage and apoptosis, altered the cell cycle distribution and eventually led to sensitization of CL1-0 to irradiation.

  15. Enhanced oral bioavailability and anticancer activity of novel curcumin loaded mixed micelles in human lung cancer cells.

    Science.gov (United States)

    Patil, Sharvil; Choudhary, Bhavana; Rathore, Atul; Roy, Krishtey; Mahadik, Kakasaheb

    2015-11-15

    Curcumin has a wide range of pharmacological activities including antioxidant, anti-inflammatory, antidiabetic, antibacterial, wound healing, antiatherosclerotic, hepatoprotective and anti-carcinogenic. However, its clinical applications are limited owing to its poor aqueous solubility, multidrug pump P-gp efflux, extensive in vivo metabolism and rapid elimination due to glucuronidation/sulfation. The objective of the current work was to prepare novel curcumin loaded mixed micelles (CUR-MM) of Pluronic F-127 (PF127) and Gelucire® 44/14 (GL44) in order to enhance its oral bioavailability and cytotoxicity in human lung cancer cell line A549. 3(2) Factorial design was used to assess the effect of formulation variables for optimization of mixed micelle batch. CUR-MM was prepared by a solvent evaporation method. The optimized CUR-MM was evaluated for size, entrapment efficiency (EE), in vitro curcumin release, cytotoxicity and oral bioavailability in rats. The average size of CUR-MM was found to be around 188 ± 3 nm with an EE of about 76.45 ± 1.18% w/w. In vitro dissolution profile of CUR-MM revealed controlled release of curcumin. Additionally, CUR-MM showed significant improvement in cytotoxic activity (3-folds) and oral bioavailability (around 55-folds) of curcumin as compared to curcumin alone. Such significant improvement in cytotoxic activity and oral bioavailability of curcumin when formulated into mixed micelles could be attributed to solubilization of hydrophobic curcumin into micelle core along with P-gp inhibition effect of both, PF127 and GL44. Thus the present work propose the formulation of mixed micelles of PF127 and GL44 which can act as promising carrier systems for hydrophobic drugs such as curcumin with significant improvement in their oral bioavailability. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. The high-grade interpolator: a means for enhancing the resolution of helical computed tomography images of the lung

    International Nuclear Information System (INIS)

    Garcia-Santos, J. M.; Torres del rio, S.; Blanco, A.; Rodriguez, R.; Parlorio, E.; Garcia, A.; Girela, E.; Hernandez, M. D.; Canteras, M.

    2002-01-01

    The purpose of this study was to demonstrate that the use of a high-grade interpolator in the reconstruction of images of the chest increases the resolution, independently of the high-resolution filter. Eight independent observers in two groups (experts and non experts) assessed (two readings separated by a time interval) the same section of the chest reconstructed four times (st-st, st-xs, b-st, b-xs), combining standard (st) and high-resolution (b) filters and standard (st) and high-grade (xs) interpolators. The images were classified from greater to lesser in terms of the resolution perceived. The results were used to compare the degree of resolution introduced by the interpolator and the filter and to determine whether or not there existed variability between observers and between the observations of each, and whether experience played a role in the findings. Six of the eight observers assigned the b-xs images the highest degree of resolution in the majority of cases, followed by the b-st image, the st-xs image and, finally, the st-st image). The other tow observers (one expert and one nonexpert) different only with respect to the order of the st-xs and b-st images, which they assigned the second and third places, respectively. The expert group showed no intra observer variability, while two of the nonexpert observers did. The high-grade interpolator enhances the resolution of images of the chest regardless of who evaluates them, while it does not substantially increase image noise. Thus, its use is recommended in helical computed tomography imaging of the lung. (Author) 10 refs

  17. Enhanced recovery programs in lung cancer surgery: systematic review and meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Li S

    2017-11-01

    Full Text Available Shuangjiang Li,1 Kun Zhou,1 Guowei Che,1 Mei Yang,1 Jianhua Su,2 Cheng Shen,1 Pengming Yu2 1Department of Thoracic Surgery, 2Department of Rehabilitation, Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, China Background: Enhanced recovery after surgery (ERAS program is an effective evidence-based multidisciplinary protocol of perioperative care, but its roles in thoracic surgery remain unclear. This systematic review of randomized controlled trials (RCTs aims to investigate the efficacy and safety of the ERAS programs for lung cancer surgery. Materials and methods: We searched the PubMed and EMBASE databases to identify the RCTs that implemented an ERAS program encompassing more than four care elements within at least two phases of perioperative care in lung cancer surgery. The heterogeneity levels between studies were estimated by the Cochrane Collaborations. A qualitative review was performed if considerable heterogeneity was revealed. Relative risk (RR and weighted mean difference served as the summarized statistics for the meta-analyses. Additional analyses were also performed to perceive potential bias risks. Results: A total of seven RCTs enrolling 486 patients were included. The meta-analysis indicated that the ERAS group patients had significantly lower morbidity rates (RR=0.64; p<0.001, especially the rates of pulmonary (RR=0.43; p<0.001 and surgical complications (RR=0.46; p=0.010, than those of control group patients. No significant reduction was found in the in-hospital mortality (RR=0.70; p=0.58 or cardiovascular complications (RR=1.46; p=0.25. In the qualitative review, most of the evidence reported significantly shortened length of hospital and intensive care unit stay and decreased hospitalization costs in the ERAS-treated patients. No significant publication bias was detected in the meta-analyses. Conclusion: Our review demonstrates that the implementation of an ERAS program for lung cancer

  18. Pulmonary hilar lymph nodes in lung cancer: assessment with 3D-dynamic contrast-enhanced MR imaging

    International Nuclear Information System (INIS)

    Hasegawa, Ichiro; Eguchi, Keisuke; Kohda, Ehiichi; Tanami, Yutaka; Mori, Toru; Hatabu, Hiroto; Kuribayashi, Sachio

    2003-01-01

    Purpose: We performed 3D-dynamic MRI on patients with primary lung cancer to identify its usefulness for detecting hilar adenopathy shown at surgery. Methods and materials: 30 consecutive patients with peripheral lung cancer underwent preoperative 3D-dynamic Gd-DTPA-enhanced MRI. Two thoracic radiologists blinded to histopathologic findings reviewed those studies independently for hilar adenopathy visualization. The results were correlated with surgical and histopathologic findings. Interreader agreement for the detection of hilar adenopathy was assessed by means of the κ statistic. Results: Dynamic MRI demonstrated hilar adenopathy, with or without metastasis revealed at surgery, in all of 15 patients. Adenopathy without metastasis was shown in four patients. Dynamic MRI also revealed metastatic adenopathy in 11 of 12 patients with pathologically proven metastasis. There was only one case with lymph node metastasis that did not have adenopathy either on MRI or even at surgery. The diagnostic accuracy of dynamic MRI for adenopathy with or without metastases revealed at surgery were as follows; sensitivity, 100%; specificity, 100%; positive predictive value, 100%; and negative predictive value, 100%, respectively. The diagnostic accuracy of dynamic MRI for hilar lymph nodes metastasis were as follows; sensitivity, 92%; specificity, 78%; positive predictive value, 73%; and negative predictive value, 93%. Interreader agreement was substantial (κ=0.73) for detection of hilar adenopathy. Conclusion: Hilar adenopathy on 3D-dynamic MRI correlated well with that of surgical finding on patients with primary lung cancer. It may have the potential to make an accurate preoperative evaluation of hilar lymph node metastasis from lung cancer

  19. Study of 201 Non-Small Cell Lung Cancer Patients Given Stereotactic Ablative Radiation Therapy Shows Local Control Dependence on Dose Calculation Algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Latifi, Kujtim, E-mail: Kujtim.Latifi@Moffitt.org [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Oliver, Jasmine [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Department of Physics, University of South Florida, Tampa, Florida (United States); Baker, Ryan [University of South Florida School of Medicine, Tampa, Florida (United States); Dilling, Thomas J.; Stevens, Craig W. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Kim, Jongphil; Yue, Binglin [Department of Biostatics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); DeMarco, MaryLou; Zhang, Geoffrey G.; Moros, Eduardo G.; Feygelman, Vladimir [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States)

    2014-04-01

    Purpose: Pencil beam (PB) and collapsed cone convolution (CCC) dose calculation algorithms differ significantly when used in the thorax. However, such differences have seldom been previously directly correlated with outcomes of lung stereotactic ablative body radiation (SABR). Methods and Materials: Data for 201 non-small cell lung cancer patients treated with SABR were analyzed retrospectively. All patients were treated with 50 Gy in 5 fractions of 10 Gy each. The radiation prescription mandated that 95% of the planning target volume (PTV) receive the prescribed dose. One hundred sixteen patients were planned with BrainLab treatment planning software (TPS) with the PB algorithm and treated on a Novalis unit. The other 85 were planned on the Pinnacle TPS with the CCC algorithm and treated on a Varian linac. Treatment planning objectives were numerically identical for both groups. The median follow-up times were 24 and 17 months for the PB and CCC groups, respectively. The primary endpoint was local/marginal control of the irradiated lesion. Gray's competing risk method was used to determine the statistical differences in local/marginal control rates between the PB and CCC groups. Results: Twenty-five patients planned with PB and 4 patients planned with the CCC algorithms to the same nominal doses experienced local recurrence. There was a statistically significant difference in recurrence rates between the PB and CCC groups (hazard ratio 3.4 [95% confidence interval: 1.18-9.83], Gray's test P=.019). The differences (Δ) between the 2 algorithms for target coverage were as follows: ΔD99{sub GITV} = 7.4 Gy, ΔD99{sub PTV} = 10.4 Gy, ΔV90{sub GITV} = 13.7%, ΔV90{sub PTV} = 37.6%, ΔD95{sub PTV} = 9.8 Gy, and ΔD{sub ISO} = 3.4 Gy. GITV = gross internal tumor volume. Conclusions: Local control in patients receiving who were planned to the same nominal dose with PB and CCC algorithms were statistically significantly different. Possible

  20. Peripheral blood cells from children with RASopathies show enhanced spontaneous colonies growth in vitro and hyperactive RAS signaling

    International Nuclear Information System (INIS)

    Gaipa, G; Bugarin, C; Cianci, P; Sarno, J; Bonaccorso, P; Biondi, A; Selicorni, A

    2015-01-01

    Germline mutations in genes coding for molecules involved in the RAS/RAF/MEK/ERK pathway are the hallmarks of a newly classified family of autosomal dominant syndromes termed RASopathies. Myeloproliferative disorders (MPDs), in particular, juvenile myelomonocytic leukemia, can lead to potentially severe complications in children with Noonan syndrome (NS). We studied 27 children with NS or other RASopathies and 35 age-matched children as control subjects. Peripheral blood (PB) cells from these patients were studied for in vitro colony-forming units (CFUs) activity, as well as for intracellular phosphosignaling. Higher spontaneous growth of both burst-forming units-erythroid (BFU-E) and CFU-granulocyte/macrophage (CFU-GM) colonies from RAS-mutated patients were observed as compared with control subjects. We also observed a significantly higher amount of GM-colony-stimulating factor-induced p-ERK in children with RASopathies. Our findings demonstrate for the first time that PB cells isolated from children suffering from NS or other RASopathies without MPD display enhanced BFU-E and CFU-GM colony formation in vitro. The biological significance of these findings clearly awaits further studies. Collectively, our data provide a basis for further investigating of only partially characterized hematological alterations present in children suffering from RASopathies, and may provide new markers for progression toward malignant MPD in these patients

  1. Ibuprofen enhances the anticancer activity of cisplatin in lung cancer cells by inhibiting the heat shock protein 70

    Science.gov (United States)

    Endo, H; Yano, M; Okumura, Y; Kido, H

    2014-01-01

    Hsp70 is often overexpressed in cancer cells, and the selective cellular survival advantage that it confers may contribute to the process of tumour formation. Thus, the pharmacological manipulation of Hsp70 levels in cancer cells may be an effective means of preventing the progression of tumours. We found that the downregulation of Hsp70 by ibuprofen in vitro enhances the antitumoural activity of cisplatin in lung cancer. Ibuprofen prominently suppressed the expression of Hsp70 in A549 cells derived from lung adenocarcinoma and sensitized them to cisplatin in association with an increase in the mitochondrial apoptotic cascade, whereas ibuprofen alone did not induce cell death. The cisplatin-dependent events occurring up- and downstream of mitochondrial disruption were accelerated by treatment with ibuprofen. The increase in cisplatin-induced apoptosis caused by the depletion of Hsp70 by RNA interference is evidence that the increased apoptosis by ibuprofen is mediated by its effect on Hsp70. Our observations indicate that the suppression of Hsp70 by ibuprofen mediates the sensitivity to cisplatin by enhancing apoptosis at several stages of the mitochondrial cascade. Ibuprofen, therefore, is a potential therapeutic agent that might allow lowering the doses of cisplatin and limiting the many challenge associated with its toxicity and development of drug resistance. PMID:24481441

  2. Bat lung epithelial cells show greater host species-specific innate resistance than MDCK cells to human and avian influenza viruses.

    Science.gov (United States)

    Slater, Tessa; Eckerle, Isabella; Chang, Kin-Chow

    2018-04-10

    With the recent discovery of novel H17N10 and H18N11 influenza viral RNA in bats and report on high frequency of avian H9 seroconversion in a species of free ranging bats, an important issue to address is the extent bats are susceptible to conventional avian and human influenza A viruses. To this end, three bat species (Eidolon helvum, Carollia perspicillata and Tadarida brasiliensis) of lung epithelial cells were separately infected with two avian and two human influenza viruses to determine their relative host innate immune resistance to infection. All three species of bat cells were more resistant than positive control Madin-Darby canine kidney (MDCK) cells to all four influenza viruses. TB1-Lu cells lacked sialic acid α2,6-Gal receptors and were most resistant among the three bat species. Interestingly, avian viruses were relatively more replication permissive in all three bat species of cells than with the use of human viruses which suggest that bats could potentially play a role in the ecology of avian influenza viruses. Chemical inhibition of the JAK-STAT pathway in bat cells had no effect on virus production suggesting that type I interferon signalling is not a major factor in resisting influenza virus infection. Although all three species of bat cells are relatively more resistant to influenza virus infection than control MDCK cells, they are more permissive to avian than human viruses which suggest that bats could have a contributory role in the ecology of avian influenza viruses.

  3. AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations

    International Nuclear Information System (INIS)

    Zhao, Ren; Zhou, Shun; Xia, Bing; Zhang, Cui-ying; Hai, Ping; Zhe, Hong; Wang, Yan-yang

    2016-01-01

    Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have become the standard care of patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC), development of acquired resistance is inevitable. A secondary mutation of threonine 790 (T790M) is associated with approximately half of the cases of acquired resistance. Strategies or agents to overcome this type of resistance are still limited. In this study, enhanced antitumor effect of AT-101, a-pan-Bcl-2 inhibitor, on gefitinib was explored in NSCLC with T790M mutation. The effect of cotreatment with AT-101 and gefitinib on the viability of NSCLC cell lines harboring acquired T790M mutation was investigated using the MTT assay. The cellular apoptosis of NSCLC cells after cotreatment with AT-101 and gefitinib was assessed by FITC-annexin V/PI assay and Western blots analysis. The potential underlying mechanisms of the enhanced therapeutic effect for AT-101 was also studied using Western blots analysis. The in vivo anti-cancer efficacy of the combination with AT-101 and gefitinib was examined in a mouse xenograft model. In this study, we found that treatment with AT-101 in combination with gefitinib significantly inhibited cell proliferation, as well as promoted apoptosis of EGFR TKIs resistant lung cancer cells. The apoptotic effects of the use of AT-101 was related to the blocking of antiapoptotic protein: Bcl-2, Bcl-xl, and Mcl-1 and downregrulation of the molecules in EGFR pathway. The observed enhancements of tumor growth suppression in xenografts supported the reverse effect of AT-101 in NSCLC with T790M mutation, which has been found in in vitro studies before. AT-101 enhances gefitinib sensitivity in NSCLC with EGFR T790M mutations. The addition of AT-101 to gefitinib is a promising strategy to overcome EGFR TKIs resistance in NSCLC with EGFR T790M mutations

  4. Post-cancer Treatment with Condurango 30C Shows Amelioration of Benzo[a]pyrene-induced Lung Cancer in Rats Through the Molecular Pathway of Caspa- se-3-mediated Apoptosis Induction

    Directory of Open Access Journals (Sweden)

    Sikdar Sourav

    2013-09-01

    Full Text Available Objectives: The present investigation aimed at examining if post-cancer treatment with a potentized homeopathic drug, Condurango 30C, which is generally used to treat oesophageal cancer, could also show an ameliorating effect through apoptosis induction on lung cancer induced by benzo[a]pyrene (BaP in white rats (Rattus norvegicus. Methods: Lung cancer was induced after four months by chronic feeding of BaP to rats through gavage at a dose of 50 mg/kg body weight for one month. After four months, the lung-cancer-bearing rats were treated with Condurango 30C for the next one (5th, two (5th-6th and three (5th-7th months, respectively, and were sacrificed at the corresponding time- points. The ameliorating effect, if any, after Condurango 30C treatment for the various periods was evaluated by using protocols such as histology, scanning electron microscopy (SEM, annexinV-FITC/PI assay, flow cytometry of the apoptosis marker, DNA fragmentation, reverse transcriptase-polymerase chain reaction (RT-PCR, immunohistochemistry, and western blot analyses of lung tissue samples. Results: Striking recovery of lung tissue to a near normal status was noticed after post-cancerous drug treatment, as evidenced by SEM and histology, especially after one and two months of drug treatment. Data from the annexinV-FITC/PI and DNA fragmentation assays revealed that Condurango 30C could induce apoptosis in cancer cells after post-cancer treatment. A critical analysis of signalling cascade, evidenced through a RT-PCR study, demonstrated up-regulation and down-regulation of different pro- and anti-apoptotic genes, respectively, related to a caspase-3-mediated apoptotic pathway, which was especially discernible after one-month and two- month drug treatments. Correspondingly, Western blot and immunohistochemistry studies confirmed the ameliorative potential of Condurango 30C by its ability to down-regulate the elevated epidermal growth factor receptor (EGFR expression, a

  5. Liquid culture enhances diagnosis of patients with milder forms of non-tuberculous mycobacterial lung disease.

    Science.gov (United States)

    Lee, H; Han, J-H; Park, H Y; Jeon, K; Huh, H J; Ki, C-S; Lee, N Y; Koh, W-J

    2017-03-01

    To evaluate the proportion and clinical characteristics of patients with non-tuberculous mycobacteria (NTM) lung disease diagnosed based on positive culture results in liquid medium only. We reviewed the medical records of 978 patients diagnosed with NTM lung disease. All clinical samples were cultured in both solid and liquid media. Of the 978 patients, 111 (11.3%) were culture-positive in liquid medium only (liquid culture group), and 867 (88.7%) (solid culture group) on solid medium, regardless of the culture results in liquid medium. At the time of diagnosis, the liquid culture group was less likely than the solid culture group to have haemoptysis (11.7% vs. 20.0%, P = 0.04), positive sputum smear for acid-fast bacilli (14.4% vs. 50.2%, P disease (3.6% vs. 14.6%, P = 0.001). During the median follow-up period of 28.9 months (interquartile range 19.1-41.6), the proportion of patients requiring antibiotic treatment was lower in the liquid culture group than in the solid culture group (44.1% vs. 61.6%, P culture is helpful in the diagnosis of patients with less severe forms of NTM lung disease.

  6. Characterization of Fetal Keratinocytes, Showing Enhanced Stem Cell-Like Properties: A Potential Source of Cells for Skin Reconstruction

    Directory of Open Access Journals (Sweden)

    Kenneth K.B. Tan

    2014-08-01

    Full Text Available Epidermal stem cells have been in clinical application as a source of culture-generated grafts. Although applications for such cells are increasing due to aging populations and the greater incidence of diabetes, current keratinocyte grafting technology is limited by immunological barriers and the time needed for culture amplification. We studied the feasibility of using human fetal skin cells for allogeneic transplantation and showed that fetal keratinocytes have faster expansion times, longer telomeres, lower immunogenicity indicators, and greater clonogenicity with more stem cell indicators than adult keratinocytes. The fetal cells did not induce proliferation of T cells in coculture and were able to suppress the proliferation of stimulated T cells. Nevertheless, fetal keratinocytes could stratify normally in vitro. Experimental transplantation of fetal keratinocytes in vivo seeded on an engineered plasma scaffold yielded a well-stratified epidermal architecture and showed stable skin regeneration. These results support the possibility of using fetal skin cells for cell-based therapeutic grafting.

  7. [A case showing a complete response by weekly paclitaxel associated with severe empyema and mediastinal abscess caused by reduction of a recurrent lung metastatic tumor originating from adenocarcinoma of the esophagogastric junction after primary operation].

    Science.gov (United States)

    Kimura, Akiharu; Hiramatsu, Kiyoshi; Sakuragawa, Tadayuki; Ito, Takaaki; Otsuji, Hidehiko; Tsuchiya, Tomonori; Hara, Tomohiro; Maeda, Takao; Tanaka, Hiroshi; Machiki, Yuichi; Hosoya, Jun; Kojima, Tsuyoshi; Kato, Kenji

    2010-02-01

    The patient was a 57-year-old man who presented with cancer of the esophagogastric junction. He underwent total gastrectomy, lower esophagectomy, distal pancreatectomy and splenectomy with para-aortic lymphnode dissection by the transthoracoabdominal approach. He was given a daily dose of 100 mg of S-1 as adjuvant chemotherapy. About one year after the operation, lung metastasis was recognized by enhanced CT examination. He began weekly paclitaxel as second-line chemotherapy. Paclitaxel was infused once a week. About two weeks after the first infusion therapy, he was admitted to our hospital with fever and dyspnea. A chest enhanced CT revealed remarkable empyema and mediastinal abscess. Chest drainage and mediastinal drainage were performed.After one month of drainage, the empyema and mediastinal abscess had improved. The metastastic tumor of the lung disappeared at the time of discharge. CR has been maintained for more than a year without chemotherapy.This case suggests that remarkable reduction of the tumor induced by chemotherapy may have caused the empyema and mediastinal abscess.

  8. ALS skeletal muscle shows enhanced TGF-β signaling, fibrosis and induction of fibro/adipogenic progenitor markers.

    Directory of Open Access Journals (Sweden)

    David Gonzalez

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis and eventually death from respiratory failure. Several studies indicate that skeletal muscle contributes to disease progression; however the molecular mechanisms remain elusive. Fibrosis is a common feature in skeletal muscle under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, the exact mechanisms of fibrosis induction and the cellular bases of this pathological response are unknown. We show that extracellular matrix (ECM components are augmented in skeletal muscles of symptomatic hSOD1G93A mice, a widely used murine model of ALS. These mice also show increased TGF-β1 mRNA levels, total Smad3 protein levels and p-Smad3 positive nuclei. Furthermore, platelet-derived growth factor receptor-α (PDGFRα, Tcf4 and α-smooth muscle actin (α-SMA levels are augmented in the skeletal muscle of symptomatic hSOD1G93A mice. Additionally, the fibro/adipogenic progenitors (FAPs, which are the main producers of ECM constituents, are also increased in these pathogenic conditions. Therefore, FAPs and ECM components are more abundant in symptomatic stages of the disease than in pre-symptomatic stages. We present evidence that fibrosis observed in skeletal muscle of symptomatic hSOD1G93A mice is accompanied with an induction of TGF-β signaling, and also that FAPs might be involved in triggering a fibrotic response. Co-localization of p-Smad3 positive cells together with PDGFRα was observed in the interstitial cells of skeletal muscles from symptomatic hSOD1G93A mice. Finally, the targeting of pro-fibrotic factors such as TGF-β, CTGF/CCN2 and platelet-derived growth factor (PDGF signaling pathway might be a suitable therapeutic approach to improve muscle function in several degenerative diseases.

  9. Performance evaluation of 3-D enhancement filters for detection of lung cancer from 3-D chest X-ray CT images

    International Nuclear Information System (INIS)

    Shimizu, Akinobu; Hagai, Makoto; Toriwaki, Jun-ichiro; Hasegawa, Jun-ichi.

    1995-01-01

    This paper evaluates the performance of several three dimensional enhancement filters used in procedures for detecting lung cancer shadows from three dimensional (3D) chest X-ray CT images. Two dimensional enhancement filters such as Min-DD filter, Contrast filter and N-Quoit filter have been proposed for enhancing cancer shadows in conventional 2D X-ray images. In this paper, we extend each of these 2D filters to a 3D filter and evaluate its performance experimentally by using CT images with artificial and true lung cancer shadows. As a result, we find that these 3D filters are effective for determining the position of a lung cancer shadow in a 3D chest CT image, as compared with the simple procedure such as smoothing filter, and that the performance of these filters become lower in the hilar area due to the influence of the vessel shadows. (author)

  10. Perfusion- and pattern-based quantitative CT indexes using contrast-enhanced dual-energy computed tomography in diffuse interstitial lung disease: relationships with physiologic impairment and prediction of prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Jung Won [Sungkyunkwan University School of Medicine, Department of Radiology, Kangbuk Samsung Hospital, Seoul (Korea, Republic of); Bae, Jang Pyo; Kim, Namkug; Chang, Yongjun; Seo, Joon Beom [University of Ulsan College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Lee, Ho Yun; Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Chung, Man Pyo; Park, Hye Yun [Sungkyunkwan University School of Medicine, Department of Pulmonology, Samsung Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    To evaluate automated texture-based segmentation of dual-energy CT (DECT) images in diffuse interstitial lung disease (DILD) patients and prognostic stratification by overlapping morphologic and perfusion information of total lung. Suspected DILD patients scheduled for surgical biopsy were prospectively included. Texture patterns included ground-glass opacity (GGO), reticulation and consolidation. Pattern- and perfusion-based CT measurements were assessed to extract quantitative parameters. Accuracy of texture-based segmentation was analysed. Correlations between CT measurements and pulmonary function test or 6-minute walk test (6MWT) were calculated. Parameters of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) and non-IPF/UIP were compared. Survival analysis was performed. Overall accuracy was 90.47 % for whole lung segmentation. Correlations between mean iodine values of total lung, 50-97.5th (%) attenuation and forced vital capacity or 6MWT were significant. Volume of GGO, reticulation and consolidation had significant correlation with DLco or SpO{sub 2} on 6MWT. Significant differences were noted between IPF/UIP and non-IPF/UIP in 6MWT distance, mean iodine value of total lung, 25-75th (%) attenuation and entropy. IPF/UIP diagnosis, GGO ratio, DILD extent, 25-75th (%) attenuation and SpO{sub 2} on 6MWT showed significant correlations with survival. DECT combined with pattern analysis is useful for analysing DILD and predicting survival by provision of morphology and enhancement. (orig.)

  11. A chimeric protein of aluminum-activated malate transporter generated from wheat and Arabidopsis shows enhanced response to trivalent cations.

    Science.gov (United States)

    Sasaki, Takayuki; Tsuchiya, Yoshiyuki; Ariyoshi, Michiyo; Ryan, Peter R; Yamamoto, Yoko

    2016-07-01

    TaALMT1 from wheat (Triticum aestivum) and AtALMT1 from Arabidopsis thaliana encode aluminum (Al)-activated malate transporters, which confer acid-soil tolerance by releasing malate from roots. Chimeric proteins from TaALMT1 and AtALMT1 (Ta::At, At::Ta) were previously analyzed in Xenopus laevis oocytes. Those studies showed that Al could activate malate efflux from the Ta::At chimera but not from At::Ta. Here, functions of TaALMT1, AtALMT1 and the chimeric protein Ta::At were compared in cultured tobacco BY-2 cells. We focused on the sensitivity and specificity of their activation by trivalent cations. The activation of malate efflux by Al was at least two-fold greater in the chimera than the native proteins. All proteins were also activated by lanthanides (erbium, ytterbium, gadolinium, and lanthanum), but the chimera again released more malate than TaALMT1 or AtALMT1. In Xenopus oocytes, Al, ytterbium, and erbium activated inward currents from the native TaALMT1 and the chimeric protein, but gadolinium only activated currents from the chimera. Lanthanum inhibited currents from both proteins. These results demonstrated that function of the chimera protein was altered compared to the native proteins and was more responsive to a range of trivalent cations when expressed in plant cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Ectopic expression of miR-34a enhances radiosensitivity of non-small cell lung cancer cells, partly by suppressing the LyGDI signaling pathway

    International Nuclear Information System (INIS)

    Duan Weiming; Xu Yaxiang; Dong Yujin; Cao Lili; Tong Jian; Zhou Xinwen

    2013-01-01

    miR-34a is transcriptionally induced by the tumor suppressor gene p53, which is often downregulated in non-small cell lung cancer (NSCLC). To address whether the downstream signal of miR-34a is sufficient to induce apoptosis and to alter cellular radiosensitivity, a chemical synthetic miR-34a mimic was delivered into A549 and H1299 cells, with or without co-treatment of γ-irradiation. Results showed that ectopic expression of miR-34a induced dose-dependent cell growth inhibition and apoptosis in a p53-independent manner in both NSCLC cell lines. Interestingly, LyGDI was discovered as a new target gene of miR-34a, and downregulation of LyGDI promoted Rac1 activation and membrane translocation, resulting in cell apoptosis. Furthermore, restoration of miR-34a indirectly reduced cyclooxygenase-2 (COX-2) expression. Taken together, these results demonstrate that restoration of miR-34a expression enhances radiation-induced apoptosis, partly by suppressing the LyGDI signaling pathway, and miR-34a could possibly be used as a radiosensitizer for non-small cell lung cancer therapy. (author)

  13. Eurasian jays do not copy the choices of conspecifics, but they do show evidence of stimulus enhancement

    Directory of Open Access Journals (Sweden)

    Rachael Miller

    2016-12-01

    Full Text Available Corvids (birds in the crow family are hypothesised to have a general cognitive tool-kit because they show a wide range of transferrable skills across social, physical and temporal tasks, despite differences in socioecology. However, it is unknown whether relatively asocial corvids differ from social corvids in their use of social information in the context of copying the choices of others, because only one such test has been conducted in a relatively asocial corvid. We investigated whether relatively asocial Eurasian jays (Garrulus glandarius use social information (i.e., information made available by others. Previous studies have indicated that jays attend to social context in their caching and mate provisioning behaviour; however, it is unknown whether jays copy the choices of others. We tested the jays in two different tasks varying in difficulty, where social corvid species have demonstrated social information use in both tasks. Firstly, an object-dropping task was conducted requiring objects to be dropped down a tube to release a food reward from a collapsible platform, which corvids can learn through explicit training. Only one rook and one New Caledonian crow have learned the task using social information from a demonstrator. Secondly, we tested the birds on a simple colour discrimination task, which should be easy to solve, because it has been shown that corvids can make colour discriminations. Using the same colour discrimination task in a previous study, all common ravens and carrion crows copied the demonstrator. After observing a conspecific demonstrator, none of the jays solved the object-dropping task, though all jays were subsequently able to learn to solve the task in a non-social situation through explicit training, and jays chose the demonstrated colour at chance levels. Our results suggest that social and relatively asocial corvids differ in social information use, indicating that relatively asocial species may have

  14. Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells.

    Science.gov (United States)

    Galindo, Liliana; Moreno, Estefanía; López-Armenta, Fernando; Guinart, Daniel; Cuenca-Royo, Aida; Izquierdo-Serra, Mercè; Xicota, Laura; Fernandez, Cristina; Menoyo, Esther; Fernández-Fernández, José M; Benítez-King, Gloria; Canela, Enric I; Casadó, Vicent; Pérez, Víctor; de la Torre, Rafael; Robledo, Patricia

    2018-01-02

    Cannabinoid CB1 receptors (CB 1 R) and serotonergic 2A receptors (5HT 2A R) form heteromers in the brain of mice where they mediate the cognitive deficits produced by delta-9-tetrahydrocannabinol. However, it is still unknown whether the expression of this heterodimer is modulated by chronic cannabis use in humans. In this study, we investigated the expression levels and functionality of CB 1 R-5HT 2A R heteromers in human olfactory neuroepithelium (ON) cells of cannabis users and control subjects, and determined their molecular characteristics through adenylate cyclase and the ERK 1/2 pathway signaling studies. We also assessed whether heteromer expression levels correlated with cannabis consumption and cognitive performance in neuropsychological tests. ON cells from controls and cannabis users expressed neuronal markers such as βIII-tubulin and nestin, displayed similar expression levels of genes related to cellular self-renewal, stem cell differentiation, and generation of neural crest cells, and showed comparable Na + currents in patch clamp recordings. Interestingly, CB 1 R-5HT 2A R heteromer expression was significantly increased in cannabis users and positively correlated with the amount of cannabis consumed, and negatively with age of onset of cannabis use. In addition, a negative correlation was found between heteromer expression levels and attention and working memory performance in cannabis users and control subjects. Our findings suggest that cannabis consumption regulates the formation of CB 1 R-5HT 2A R heteromers, and may have a key role in cognitive processing. These heterodimers could be potential new targets to develop treatment alternatives for cognitive impairments.

  15. Isolation of baker's yeast mutants with proline accumulation that showed enhanced tolerance to baking-associated stresses.

    Science.gov (United States)

    Tsolmonbaatar, Ariunzaya; Hashida, Keisuke; Sugimoto, Yukiko; Watanabe, Daisuke; Furukawa, Shuhei; Takagi, Hiroshi

    2016-12-05

    During bread-making processes, yeast cells are exposed to baking-associated stresses such as freeze-thaw, air-drying, and high-sucrose concentrations. Previously, we reported that self-cloning diploid baker's yeast strains that accumulate proline retained higher-level fermentation abilities in both frozen and sweet doughs than the wild-type strain. Although self-cloning yeasts do not have to be treated as genetically modified yeasts, the conventional methods for breeding baker's yeasts are more acceptable to consumers than the use of self-cloning yeasts. In this study, we isolated mutants resistant to the proline analogue azetidine-2-carboxylate (AZC) derived from diploid baker's yeast of Saccharomyces cerevisiae. Some of the mutants accumulated a greater amount of intracellular proline, and among them, 5 mutants showed higher cell viability than that observed in the parent wild-type strain under freezing or high-sucrose stress conditions. Two of them carried novel mutations in the PRO1 gene encoding the Pro247Ser or Glu415Lys variant of γ-glutamyl kinase (GK), which is a key enzyme in proline biosynthesis in S. cerevisiae. Interestingly, we found that these mutations resulted in AZC resistance of yeast cells and desensitization to proline feedback inhibition of GK, leading to intracellular proline accumulation. Moreover, baker's yeast cells expressing the PRO1 P247S and PRO1 E415K gene were more tolerant to freezing stress than cells expressing the wild-type PRO1 gene. The approach described here could be a practical method for the breeding of proline-accumulating baker's yeasts with higher tolerance to baking-associated stresses. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Enhanced efficacy of radiation-induced gene therapy in mice bearing lung adenocarcinoma xenografts using hypoxia responsive elements

    International Nuclear Information System (INIS)

    Wang Wei-dong; Chen Zheng-tang; Li De-zhi; Duan Yu-zhong; Cao Zheng-huai; Li Rong

    2005-01-01

    The aim of the present study was to investigate whether the hypoxia responsive element (HRE) could be used to enhance suicide gene (HSV-tk) expression and tumoricidal activity in radiation-controlled gene therapy of human lung adenocarcinoma xenografts. A chimeric promoter, HRE-Egr, was generated by directly linking a 0.3-kb fragment of HRE to a 0.6-kb human Egr-1 promoter. Retroviral vectors containing luciferase or the HSV-tk gene driven by Egr-1 or HRE-Egr were constructed. A human adenocarcinoma cell line (A549) was stably transfected with the above vectors using the lipofectamine method. The sensitivity of transfected cells to prodrug ganciclovir (GCV) and cell survival rates were analyzed after exposure to a dose of 2 Gy radiation and hypoxia (1%). In vivo, tumor xenografts in BALB/c mice were transfected with the constructed retroviruses and irradiated to a total dose of 6 Gy, followed by GCV treatment (20 mg/kg for 14 days). When the HSV-tk gene controlled by the HRE-Egr promoter was introduced into A549 cells by a retroviral vector, the exposure to 1% O 2 and 2 Gy radiation induced significant enhancement of GCV cytotoxicity to the cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors infected with the hybrid promoter-containing virus gradually disappeared after GCV administration and radiation. These results indicate that HRE can enhance transgene expression and tumoricidal activity in HSV-tk gene therapy controlled by ionizing radiation in hypoxic human lung adenocarcinoma. (author)

  17. Diagnostic Value of Early-Phase-Enhanced Computed Tomography for the Differentiation of Pulmonary Metastases from Hepatocellular Carcinoma and Primary Lung Cancer

    International Nuclear Information System (INIS)

    Choi, Joon-Il; Jung, Dae Chul; Kim, Min-Ju; Hong, Eun Kyung; Park, Joong-Won; Kim, Chang-Min; Choi, Hyuck Jae; Jang, Yun-Jin

    2009-01-01

    Background: The lung is the most common site of distant metastases from hepatocellular carcinoma. Correct differentiation between metastatic hepatocellular carcinoma of the lung and primary lung cancer is sometimes difficult without biopsy. Purpose: To evaluate the usefulness of measuring the attenuations of pulmonary nodules on early-phase contrast-enhanced computed tomography (CT) for the differentiation of pulmonary metastases from hepatocellular carcinoma and primary lung cancer. Material and Methods: Thirteen patients with pulmonary metastases from hepatocellular carcinoma (nine men, four women; age 53.9±14.2 years, range 16-70 years) and 25 patients with primary lung cancer (14 men, 11 women; age 62.2±9.4 years, range 43-72 years) were retrospectively evaluated. Contrast-enhanced scans were obtained 35 s after commencing intravenous injection of contrast medium. Attenuation values and the size of the pulmonary nodules were measured on contrast-enhanced CT scans. CT and clinical features were analyzed with regard to age, sex, body surface area of the patients, the attenuation values and size of the nodules, and CT machines using univariate analysis (Fisher's exact test for binary data sets and the Mann-Whitney U test for continuous data sets). Multiple linear regression analysis was used to eliminate confounding factors. Results: The mean attenuation value of metastatic pulmonary nodules from hepatocellular carcinoma (75.7±24.9 HU) was higher than that of primary lung cancer nodules (45.8±14.4 HU) (P<0.01). Other variables such as age, sex, body surface area of the patients, CT device, and nodule size were not significant variables on multiple regression analysis. When a cut-off value of 75 HU was applied, the positive predictive value for diagnosing metastatic nodules from hepatocellular carcinoma was 100%. Conclusion: Pending confirmation in a large study, our findings suggest that there is a difference in contrast enhancement between pulmonary

  18. Genetic blockade of insulin-like growth factor-1 receptor via recombinant adenovirus in lung cancer can be enhanced by the histone deacetylase inhibitor, vorinostat.

    Science.gov (United States)

    Park, Mi-Young; Kim, Dal Rae; Eo, Eun Young; Lim, Hyo Jeong; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho-Il; Lee, Jae Ho; Lee, Choon-Taek

    2013-01-01

    Many approaches have been suggested as anti-tumor therapy for targeting insulin-like growth factor 1 receptor (IGF-1R), such as monoclonal antibodies and tyrosine kinase inhibitor. We introduced recombinant adenoviruses expressing antisense, dominant negative or short hairpin RNA to IGF-1R. Moreover, we demonstrated that histone deacetylase inhibitor (vorinostat) can increase the transduction efficiency of adenoviruses by increasing CAR-induced transduction and by enhancing the transcription of the adenoviral transgene. In the present study, we showed that the combination of ad-sh (short hairpin) IGF-1R with vorinostat leads to a synergistic enhancement of IGF-1R blockade. We measured the change in IGF-1R upon cotreatment with vorinostat and ad-shIGF-1R. Changes in transduction efficiency of ad-shIGF-1R were measured by fluorescent microscopy. Changes in apoptotic proportion and cell survival after the cotreatment were measured by the sub-G1 assay and cell counts. The effect of nuclear factor (NF)-κB activation was also measured by NF-κB p65 activation enzyme-linked immunosorbent assay. Drug interactions were analyzed upon cotreatment with ad-shIGF-1R, vorinostat and cisplatin. Combined treatment of ad-shIGF-1R and vorinostat synergistically suppressed the IGF-1R expression in lung cancer cell lines and also increased the transduction efficiency of ad-shIGF-1R. Ad-shIGF-1R and vorinostat cotreatment increased apoptotic cell death and synergistically suppressed cell growth compared to ad-shIGF-1R or vorinostat treatment alone. Vorinostat suppressed NF-κB activation, which was activated by ad-shIGF-1R. Moreover, triple combination of ad-shIGF-1R, vorinostat and cisplatin demonstrated synergistic cytotoxicity on lung cancer cells. Vorinostat enhanced the blocking capability of ad-shIGF-1R. The combined treatment of vorinostat and ad-sh-IGF-1R appears to have promising potential as a new therapeutic approach for lung cancer. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice

    International Nuclear Information System (INIS)

    Wen Qinglian; Meng Maobin; Tu Lingli; Jia Li; Zhou Lin; Xu Yong; Lu You; Yang Bo

    2009-01-01

    The purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts. Tumor xenografts were established in the hind limb of male athymic nude mice (BALB/c-nu) by subcutaneous transplantation. The tumor-bearing mice were assigned into four treatment groups: sham therapy (control), endostar (20 mg/kg, once daily for 10 days), radiation therapy (6 Gray per day to 30 Gray, once a day for 1 week), and endostar plus radiation therapy (combination). The experiment was repeated and mice were killed at days 3, 6, and 10 after initiation therapy, and the tumor tissues and blood samples were collected to analyze the kinetics of antitumor, antiangiogenesis, and antivascularization responses of different therapies. In human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts, endostar significantly enhanced the effects of tumor growth inhibition, endothelial cell and tumor cell apoptosis induction, and improved tumor cell hypoxia of radiation therapy. Histological analyses demonstrated that endostar plus radiation also induced a significant reduction in microvascular density, microvascular area, and vascular endothelial growth factor and matrix metalloproteinase-2 expression compared with radiation and endostar alone respectively. We concluded that endostar significantly sensitized the function of radiation in antitumor and antiangiogenesis in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts by increasing the apoptosis of the endothelial cell and tumor cell, improving the hypoxia of the tumor cell, and changing the proangiogenic factors. These data provided a rational basis for clinical practice of this multimodality therapy. (author)

  20. Non-small cell lung cancer: evaluation of the relationship between fibrosis and washout feature at dynamic contrast enhanced CT

    International Nuclear Information System (INIS)

    Ye Xiaodan; Yuan Zheng; Ye Jianding; Li Huimin; Zhu Yuzhao; Zhang Shunmin; Liu Shiyuan; Xiao Xiangsheng

    2010-01-01

    Objective: To correlate dynamic parameters at contrast enhanced CT and interstitial fibrosis grade of' non-small cell lung cancer (NSCLC). Methods: Twenty-nine patients with NSCLC were evaluated by multi-slice CT. Images were obtained before and at 20, 30, 45, 60, 75, 90, 120, 180, 300, 540, 720, 900 and 1200 s after the injection of contrast media, which was administered at a rate of 4 ml/s for a total of 420 mg I/kg body weight. Washout parameters were calculated. Lung cancer specimens were stained with hematoxylin-eosin stain and collagen and elastic double stain. Spearman test was made to analyze correlation between dynamic parameters and interstitial fibrosis grade of tumor. Results: Twenty- nine NSCLC demonstrated washout at 20 min 12.1 (0.32-58.0) HU, washout ratio at 20 minutes 15.3% (0.3%-39.2%), slope of washout at 20 minutes 0.0152%/s (0.0007%/s-0.0561%/s). Interstitial fibrosis of 29 lesions was graded as grade Ⅰ (10), grade Ⅱ (14) and grade Ⅲ (5). There were significant correlation between washout at 20 min (r=-0.402, P<0.05), washout ratio at 20 min (r= -0.372, P<0.05), slope of washout ratio (r=-0.459, P<0.05) and interstitial fibrosis grade in tumors. Conclusion: NSCLC washout features at dynamic multi-detector CT correlates with interstitial fibrosis in the tumor. (authors)

  1. Semiautomatic determination of arterial input functions for quantitative dynamic contrast-enhanced magnetic resonance imaging in non-small cell lung cancer patients.

    Science.gov (United States)

    Chung, Julius; Kim, Jae-Hun; Lee, Eun Ju; Kim, Yoo Na; Yi, Chin A

    2015-03-01

    The aim of this study was to validate a semiautomatic detection method for the arterial input functions (AIFs) using Kendall coefficient of concordance (KCC) for quantitative analysis of dynamic contrast-enhanced magnetic resonance imaging in non-small cell lung cancer patients. We prospectively enrolled 28 patients (17 men, 11 women; mean age, 62 years) who had biopsy-proven non-small cell lung cancer. All enrolled patients underwent dynamic contrast-enhanced magnetic resonance imaging of the entire thorax. For the quantitative measurement of pharmacokinetic parameters, K and ve, of the lung cancers, AIFs were determined in 2 different ways: a manual method that involved 3 independent thoracic radiologists selecting a region of interest (ROI) within the aortic arch in the 2D coronal plane and a semiautomatic method that used in-house software to establish a KCC score, which provided a measure of similarity to typical AIF pattern. Three independent readers selected voxel clusters with high KCC scores calculated 3-dimensionally across planes in the data set. K and ve were correlated using intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to examine agreement across methods and reproducibility within a method. Arterial input functions were determined using the data from ROI volumes that were significantly larger in the semiautomatic method (mean ± SD, 3360 ± 768 mm) than in the manual method (677 ± 380 mm) (P < 0.001). K showed very strong agreement (ICC, 0.927) and ve showed moderately strong agreement (ICC, 0.718) between the semiautomatic and manual methods. The reproducibility for K (ICCmanual, 0.813 and ICCsemiautomatic, 0.998; P < 0.001) and ve (ICCmanual, 0.455 and ICCsemiautomatic, 0.985, P < 0.001) was significantly better with the semiautomatic method than the manual method. We found semiautomated detection using KCC to be a robust method for determining the AIF. This method allows for larger ROIs specified in 3D across planes

  2. Celecoxib enhances radiation response of secondary bone tumors of a human non-small cell lung cancer via antiangiogenesis in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Klenke, Frank Michael [Bern Univ. (Switzerland). Dept. of Orthopedic Surgery; Abdollahi, Amir [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Tufts Univ. School of Medicine, Boston, MA (United States). Center of Cancer Systems Biology; Bischof, Marc; Huber, Peter E. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Gebhard, Martha-Maria [Heidelberg Univ. (Germany). Dept. of Experimental Surgery; Ewerbeck, Volker [Heidelberg Univ. (Germany). Dept. of Orthopedic Surgery; Sckell, Axel [Charite Univ. Medical Center, Berlin (Germany). Dept. of Orthopedic, Trauma and Reconstructive Surgery

    2011-01-15

    Purpose: Cyclooxygenase-2 (COX-2) inhibitors mediate a systemic antitumor activity via antiangiogenesis and seem to enhance the response of primary tumors to radiation. Radiosensitizing effects of COX-2 inhibition have not been reported for bone metastases. Therefore, the aim of this study was the investigation of the radiosensitizing effects of the selective COX-2 inhibitor celecoxib in secondary bone tumors of a non-small cell lung carcinoma in vivo. Materials and Methods: Human A549 lung carcinomas were implanted into a cranial window preparation in male SCID mice (n = 24). Animals were treated with either celecoxib or radiation (7 Gy single photon dose) alone or a combination of celecoxib and radiation, respectively. Untreated animals served as controls. The impact of radiation and COX-2 inhibition on angiogenesis, microcirculation, and tumor growth was analyzed over 28 days by means of intravital microscopy and histological methods. Results: Monotherapies with radiation as well as celecoxib had significant antitumor effects compared to untreated controls. Both therapies reduced tumor growth and vascularization to a similar extent. The simultaneous administration of celecoxib and radiation further enhanced the antitumor and antiangiogenic effects of single-beam radiation. With the combined treatment approach, tumor vascularization and tumor size were decreased by 57% and 51%, respectively, as compared to monotherapy with radiation. Conclusion: The combined application of radiation therapy and COX-2 inhibition showed synergistic effects concerning the inhibition of tumor growth and tumor angiogenesis. Therefore, the combination of radiation with COX-2 inhibitor therapy represents a promising approach to improve the therapeutic efficacy of radiotherapy of bone metastases. (orig.)

  3. Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets.

    Science.gov (United States)

    Best, Myron G; Sol, Nik; In 't Veld, Sjors G J G; Vancura, Adrienne; Muller, Mirte; Niemeijer, Anna-Larissa N; Fejes, Aniko V; Tjon Kon Fat, Lee-Ann; Huis In 't Veld, Anna E; Leurs, Cyra; Le Large, Tessa Y; Meijer, Laura L; Kooi, Irsan E; Rustenburg, François; Schellen, Pepijn; Verschueren, Heleen; Post, Edward; Wedekind, Laurine E; Bracht, Jillian; Esenkbrink, Michelle; Wils, Leon; Favaro, Francesca; Schoonhoven, Jilian D; Tannous, Jihane; Meijers-Heijboer, Hanne; Kazemier, Geert; Giovannetti, Elisa; Reijneveld, Jaap C; Idema, Sander; Killestein, Joep; Heger, Michal; de Jager, Saskia C; Urbanus, Rolf T; Hoefer, Imo E; Pasterkamp, Gerard; Mannhalter, Christine; Gomez-Arroyo, Jose; Bogaard, Harm-Jan; Noske, David P; Vandertop, W Peter; van den Broek, Daan; Ylstra, Bauke; Nilsson, R Jonas A; Wesseling, Pieter; Karachaliou, Niki; Rosell, Rafael; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent B; Tannous, Bakhos A; de Langen, Adrianus J; Smit, Egbert F; van den Heuvel, Michel M; Wurdinger, Thomas

    2017-08-14

    Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Arctigenin enhances chemosensitivity to cisplatin in human nonsmall lung cancer H460 cells through downregulation of survivin expression.

    Science.gov (United States)

    Wang, Huan-qin; Jin, Jian-jun; Wang, Jing

    2014-01-01

    Arctigenin, a dibenzylbutyrolactone lignan, enhances cisplatin-mediated cell apoptosis in cancer cells. Here, we sought to investigate the effects of arctigenin on cisplatin-treated non-small-cell lung cancer (NSCLC) H460 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and annexin-V/propidium iodide staining were performed to analyze the proliferation and apoptosis of H460 cells. Arctigenin dose-dependently suppressed cell proliferation and potentiated cell apoptosis, coupled with increased cleavage of caspase-3 and poly(ADP-ribose) polymerase. Moreover, arctigenin sensitized H460 cells to cisplatin-induced proliferation inhibition and apoptosis. Arctigenin alone or in combination with cisplatin had a significantly lower amount of survivin. Ectopic expression of survivin decreased cell apoptosis induced by arctigenin (P arctigenin (P arctigenin has a therapeutic potential in combina-tion with chemotherapeutic agents for NSLC. © 2013 Wiley Periodicals, Inc.

  5. [Immunomodulators of microbial origin enhance cytotoxicity of human mononuclear leukocytes and reduce metastatic progression of Lewis lung carcinoma in mice].

    Science.gov (United States)

    Akhmatova, N K; Semenova, I B; Donenko, F V; Kiselevskiĭ, M V; Kurbatova, E A; Egorova, N B

    2006-01-01

    Effect of immunomodulators for microbial origin on innate immunity and antitumor system was continued to study. Immunomodificator Immunovac VP-4, purified staphylococcal toxoid and glucosaminyl muramyl dipeptide (GMDP) equally enhanced cytotoxicity of mononuclear leukocytes of peripheral blood of healthy donors. Index of cytotoxicity was 2.78, 2.77 and 2.70 respectively. Reduced metastatic progression of Lewis lung carcinoma in mice was observed after Immunovac VP-4 and GMDP administration. Effectiveness was seen when preparations administered according to schedules including their administration before implantation of the tumor. If preparations were administered number of metastases reduced in 4.4-5.6 times and size of metastases reduced in 7-10 times. Interplay between antitumor activity of studied immunomodulators and cytotoxic activity of NK-cells, which are base effectors of antitumor immune response, are discussed.

  6. Immunotherapy with Dendritic Cells Modified with Tumor-Associated Antigen Gene Demonstrates Enhanced Antitumor Effect Against Lung Cancer

    Directory of Open Access Journals (Sweden)

    Tao Jiang

    2017-04-01

    Full Text Available BACKGROUND: Immunotherapy using dendritic cell (DC vaccine has the potential to overcome the bottleneck of cancer therapy. METHODS: We engineered Lewis lung cancer cells (LLCs and bone marrow–derived DCs to express tumor-associated antigen (TAA ovalbumin (OVA via lentiviral vector plasmid encoding OVA gene. We then tested the antitumor effect of modified DCs both in vitro and in vivo. RESULTS: The results demonstrated that in vitro modified DCs could dramatically enhance T-cell proliferation (P < .01 and killing of LLCs than control groups (P < .05. Moreover, modified DCs could reduce tumor size and prolong the survival of LLC tumor-bearing mice than control groups (P < .01 and P < .01, respectively. Mechanistically, modified DCs demonstrated enhanced homing to T-cell–rich compartments and triggered more naive T cells to become cytotoxic T lymphocytes, which exhibited significant infiltration into the tumors. Interestingly, modified DCs also markedly reduced tumor cells harboring stem cell markers in mice (P < .05, suggesting the potential role on cancer stem-like cells. CONCLUSION: These findings suggested that DCs bioengineered with TAA could enhance antitumor effect and therefore represent a novel anticancer strategy that is worth further exploration.

  7. Chrysin enhances doxorubicin-induced cytotoxicity in human lung epithelial cancer cell lines: The role of glutathione

    Energy Technology Data Exchange (ETDEWEB)

    Brechbuhl, Heather M. [Pediatrics, National Jewish Health, Denver, Colorado (United States); Kachadourian, Remy; Min, Elysia [Department of Medicine, National Jewish Health, Denver, Colorado (United States); Chan, Daniel [Medical Oncology, University of Colorado Denver Health Sciences Center (United States); Day, Brian J., E-mail: dayb@njhealth.org [Department of Medicine, University of Colorado Denver Health Sciences Center (United States); Immunology, University of Colorado Denver Health Sciences Center (United States); Pharmaceutical Sciences, University of Colorado Denver Health Sciences Center (United States); Department of Medicine, National Jewish Health, Denver, Colorado (United States)

    2012-01-01

    We hypothesized that flavonoid-induced glutathione (GSH) efflux through multi-drug resistance proteins (MRPs) and subsequent intracellular GSH depletion is a viable mechanism to sensitize cancer cells to chemotherapies. This concept was demonstrated using chrysin (5–25 μM) induced GSH efflux in human non-small cell lung cancer lines exposed to the chemotherapeutic agent, doxorubicin (DOX). Treatment with chrysin resulted in significant and sustained intracellular GSH depletion and the GSH enzyme network in the four cancer cell types was predictive of the severity of chrysin induced intracellular GSH depletion. Gene expression data indicated a positive correlation between basal MRP1, MRP3 and MRP5 expression and total GSH efflux before and after chrysin exposure. Co-treating the cells for 72 h with chrysin (5–30 μM) and DOX (0.025–3.0 μM) significantly enhanced the sensitivity of the cells to DOX as compared to 72-hour DOX alone treatment in all four cell lines. The maximum decrease in the IC{sub 50} values of cells treated with DOX alone compared to co-treatment with chrysin and DOX was 43% in A549 cells, 47% in H157 and H1975 cells and 78% in H460 cells. Chrysin worked synergistically with DOX to induce cancer cell death. This approach could allow for use of lower concentrations and/or sensitize cancer cells to drugs that are typically resistant to therapy. -- Graphical abstract: Possible mechanisms by which chrysin enhances doxorubicin-induced toxicity in cancer cells. Highlights: ► Chyrsin sustains a significant depletion of GSH levels in lung cancer cells. ► Chyrsin synergistically potentiates doxorubicin-induced cancer cell cytotoxicity. ► Cancer cell sensitivity correlated with GSH and MRP gene network expression. ► This approach could allow for lower side effects and targeting resistant tumors.

  8. Exogenous Restoration of TUSC2 Expression Induces Responsiveness to Erlotinib in Wildtype Epidermal Growth Factor Receptor (EGFR Lung Cancer Cells through Context Specific Pathways Resulting in Enhanced Therapeutic Efficacy.

    Directory of Open Access Journals (Sweden)

    Bingbing Dai

    Full Text Available Expression of the tumor suppressor gene TUSC2 is reduced or absent in most lung cancers and is associated with worse overall survival. In this study, we restored TUSC2 gene expression in several wild type EGFR non-small cell lung cancer (NSCLC cell lines resistant to the epidermal growth factor receptor (EGFR tyrosine kinase inhibitor erlotinib and analyzed their sensitivity to erlotinib in vitro and in vivo. A significant inhibition of cell growth and colony formation was observed with TUSC2 transient and stable expression. TUSC2-erlotinib cooperativity in vitro could be reproduced in vivo in subcutaneous tumor growth and lung metastasis formation lung cancer xenograft mouse models. Combination treatment with intravenous TUSC2 nanovesicles and erlotinib synergistically inhibited tumor growth and metastasis, and increased apoptotic activity. High-throughput qRT-PCR array analysis enabling multi-parallel expression profile analysis of eighty six receptor and non-receptor tyrosine kinase genes revealed a significant decrease of FGFR2 expression level, suggesting a potential role of FGFR2 in TUSC2-enhanced sensitivity to erlotinib. Western blots showed inhibition of FGFR2 by TUSC2 transient transfection, and marked increase of PARP, an apoptotic marker, cleavage level after TUSC2-erlotinb combined treatment. Suppression of FGFR2 by AZD4547 or gene knockdown enhanced sensitivity to erlotinib in some but not all tested cell lines. TUSC2 inhibits mTOR activation and the latter cell lines were responsive to the mTOR inhibitor rapamycin combined with erlotinib. These results suggest that TUSC2 restoration in wild type EGFR NSCLC may overcome erlotinib resistance, and identify FGFR2 and mTOR as critical regulators of this activity in varying cellular contexts. The therapeutic activity of TUSC2 could extend the use of erlotinib to lung cancer patients with wildtype EGFR.

  9. Can visual assessment of blood flow patterns by dynamic contrast-enhanced computed tomography distinguish between malignant and benign lung tumors?

    Science.gov (United States)

    Harders, Stefan Walbom; Madsen, Hans Henrik; Nellemann, Hanne Marie; Rasmussen, Torben Riis; Thygesen, Jesper; Hager, Henrik; Andersen, Niels Trolle; Rasmussen, Finn

    2017-05-01

    Dynamic contrast-enhanced computed tomography (DCE-CT) is a tool, which, in theory, can quantify the blood flow and blood volume of tissues. In structured qualitative analysis, parametric color maps yield a visual impression of the blood flow and blood volume within the tissue being studied, allowing for quick identification of the areas with the highest or lowest blood flow and blood volume. To examine whether DCE-CT could be used to distinguish between malignant and benign lung tumors in patients with suspected lung cancer. Fifty-nine patients with suspected lung cancer and a lung tumor on their chest radiograph were included for DCE-CT. The tumors were categorized using structured qualitative analysis of tumor blood flow patterns. Histopathology was used as reference standard. Using structured qualitative analysis of tumor blood flow patterns, it was possible to distinguish between malignant and benign lung tumors (Fisher-Freeman-Halton exact test, P  = 0.022). The inter-reader agreement of this method of analysis was slight to moderate (kappa = 0.30; 95% confidence interval [CI] = 0.13-0.46). DCE-CT in suspected lung cancer using structured qualitative analysis of tumor blood flow patterns is accurate as well as somewhat reproducible. However, there are significant limitations to DCE-CT.

  10. Network-Based Logistic Classification with an Enhanced L1/2 Solver Reveals Biomarker and Subnetwork Signatures for Diagnosing Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hai-Hui Huang

    2015-01-01

    Full Text Available Identifying biomarker and signaling pathway is a critical step in genomic studies, in which the regularization method is a widely used feature extraction approach. However, most of the regularizers are based on L1-norm and their results are not good enough for sparsity and interpretation and are asymptotically biased, especially in genomic research. Recently, we gained a large amount of molecular interaction information about the disease-related biological processes and gathered them through various databases, which focused on many aspects of biological systems. In this paper, we use an enhanced L1/2 penalized solver to penalize network-constrained logistic regression model called an enhanced L1/2 net, where the predictors are based on gene-expression data with biologic network knowledge. Extensive simulation studies showed that our proposed approach outperforms L1 regularization, the old L1/2 penalized solver, and the Elastic net approaches in terms of classification accuracy and stability. Furthermore, we applied our method for lung cancer data analysis and found that our method achieves higher predictive accuracy than L1 regularization, the old L1/2 penalized solver, and the Elastic net approaches, while fewer but informative biomarkers and pathways are selected.

  11. Histone methylation-mediated silencing of miR-139 enhances invasion of non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Watanabe, Kousuke; Amano, Yosuke; Ishikawa, Rie; Sunohara, Mitsuhiro; Kage, Hidenori; Ichinose, Junji; Sano, Atsushi; Nakajima, Jun; Fukayama, Masashi; Yatomi, Yutaka; Nagase, Takahide; Ohishi, Nobuya; Takai, Daiya

    2015-01-01

    MicroRNA expression is frequently altered in human cancers, and some microRNAs act as oncogenes or tumor suppressors. MiR-139-5p (denoted thereafter as miR-139) has recently been reported to function as a tumor suppressor in several types of human cancer (hepatocellular carcinoma, colorectal cancer, breast cancer, and gastric cancer), but its function in non-small-cell lung cancer (NSCLC) and the mechanism of its suppression have not been studied in detail. MiR-139 was suppressed frequently in primary NSCLCs. MiR-139 is located within the intron of PDE2A and its expression was significantly correlated with the expression of PDE2A. A chromatin immunoprecipitation assay revealed that miR-139 was epigenetically silenced by histone H3 lysine 27 trimethylation (H3K27me3) of its host gene PDE2A and this process was independent of promoter DNA methylation. Pharmacological inhibition of both histone methylation and deacetylation-induced miR-139 with its host gene PDE2A. Ectopic expression of miR-139 in lung cancer cell lines did not affect the proliferation nor the migration but significantly suppressed the invasion through the extracellular matrix. In primary NSCLCs, decreased expression of miR-139 was significantly associated with distant lymph node metastasis and histological invasiveness (lymphatic invasion and vascular invasion) on both univariate and multivariate analyses. Collectively, these results suggest that H3K27me3-mediated silencing of miR-139 enhances an invasive and metastatic phenotype of NSCLC

  12. Using dual-energy x-ray imaging to enhance automated lung tumor tracking during real-time adaptive radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Menten, Martin J., E-mail: martin.menten@icr.ac.uk; Fast, Martin F.; Nill, Simeon; Oelfke, Uwe, E-mail: uwe.oelfke@icr.ac.uk [Joint Department of Physics at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London SM2 5NG (United Kingdom)

    2015-12-15

    Purpose: Real-time, markerless localization of lung tumors with kV imaging is often inhibited by ribs obscuring the tumor and poor soft-tissue contrast. This study investigates the use of dual-energy imaging, which can generate radiographs with reduced bone visibility, to enhance automated lung tumor tracking for real-time adaptive radiotherapy. Methods: kV images of an anthropomorphic breathing chest phantom were experimentally acquired and radiographs of actual lung cancer patients were Monte-Carlo-simulated at three imaging settings: low-energy (70 kVp, 1.5 mAs), high-energy (140 kVp, 2.5 mAs, 1 mm additional tin filtration), and clinical (120 kVp, 0.25 mAs). Regular dual-energy images were calculated by weighted logarithmic subtraction of high- and low-energy images and filter-free dual-energy images were generated from clinical and low-energy radiographs. The weighting factor to calculate the dual-energy images was determined by means of a novel objective score. The usefulness of dual-energy imaging for real-time tracking with an automated template matching algorithm was investigated. Results: Regular dual-energy imaging was able to increase tracking accuracy in left–right images of the anthropomorphic phantom as well as in 7 out of 24 investigated patient cases. Tracking accuracy remained comparable in three cases and decreased in five cases. Filter-free dual-energy imaging was only able to increase accuracy in 2 out of 24 cases. In four cases no change in accuracy was observed and tracking accuracy worsened in nine cases. In 9 out of 24 cases, it was not possible to define a tracking template due to poor soft-tissue contrast regardless of input images. The mean localization errors using clinical, regular dual-energy, and filter-free dual-energy radiographs were 3.85, 3.32, and 5.24 mm, respectively. Tracking success was dependent on tumor position, tumor size, imaging beam angle, and patient size. Conclusions: This study has highlighted the influence of

  13. Using dual-energy x-ray imaging to enhance automated lung tumor tracking during real-time adaptive radiotherapy

    International Nuclear Information System (INIS)

    Menten, Martin J.; Fast, Martin F.; Nill, Simeon; Oelfke, Uwe

    2015-01-01

    Purpose: Real-time, markerless localization of lung tumors with kV imaging is often inhibited by ribs obscuring the tumor and poor soft-tissue contrast. This study investigates the use of dual-energy imaging, which can generate radiographs with reduced bone visibility, to enhance automated lung tumor tracking for real-time adaptive radiotherapy. Methods: kV images of an anthropomorphic breathing chest phantom were experimentally acquired and radiographs of actual lung cancer patients were Monte-Carlo-simulated at three imaging settings: low-energy (70 kVp, 1.5 mAs), high-energy (140 kVp, 2.5 mAs, 1 mm additional tin filtration), and clinical (120 kVp, 0.25 mAs). Regular dual-energy images were calculated by weighted logarithmic subtraction of high- and low-energy images and filter-free dual-energy images were generated from clinical and low-energy radiographs. The weighting factor to calculate the dual-energy images was determined by means of a novel objective score. The usefulness of dual-energy imaging for real-time tracking with an automated template matching algorithm was investigated. Results: Regular dual-energy imaging was able to increase tracking accuracy in left–right images of the anthropomorphic phantom as well as in 7 out of 24 investigated patient cases. Tracking accuracy remained comparable in three cases and decreased in five cases. Filter-free dual-energy imaging was only able to increase accuracy in 2 out of 24 cases. In four cases no change in accuracy was observed and tracking accuracy worsened in nine cases. In 9 out of 24 cases, it was not possible to define a tracking template due to poor soft-tissue contrast regardless of input images. The mean localization errors using clinical, regular dual-energy, and filter-free dual-energy radiographs were 3.85, 3.32, and 5.24 mm, respectively. Tracking success was dependent on tumor position, tumor size, imaging beam angle, and patient size. Conclusions: This study has highlighted the influence of

  14. Using dual-energy x-ray imaging to enhance automated lung tumor tracking during real-time adaptive radiotherapy.

    Science.gov (United States)

    Menten, Martin J; Fast, Martin F; Nill, Simeon; Oelfke, Uwe

    2015-12-01

    Real-time, markerless localization of lung tumors with kV imaging is often inhibited by ribs obscuring the tumor and poor soft-tissue contrast. This study investigates the use of dual-energy imaging, which can generate radiographs with reduced bone visibility, to enhance automated lung tumor tracking for real-time adaptive radiotherapy. kV images of an anthropomorphic breathing chest phantom were experimentally acquired and radiographs of actual lung cancer patients were Monte-Carlo-simulated at three imaging settings: low-energy (70 kVp, 1.5 mAs), high-energy (140 kVp, 2.5 mAs, 1 mm additional tin filtration), and clinical (120 kVp, 0.25 mAs). Regular dual-energy images were calculated by weighted logarithmic subtraction of high- and low-energy images and filter-free dual-energy images were generated from clinical and low-energy radiographs. The weighting factor to calculate the dual-energy images was determined by means of a novel objective score. The usefulness of dual-energy imaging for real-time tracking with an automated template matching algorithm was investigated. Regular dual-energy imaging was able to increase tracking accuracy in left-right images of the anthropomorphic phantom as well as in 7 out of 24 investigated patient cases. Tracking accuracy remained comparable in three cases and decreased in five cases. Filter-free dual-energy imaging was only able to increase accuracy in 2 out of 24 cases. In four cases no change in accuracy was observed and tracking accuracy worsened in nine cases. In 9 out of 24 cases, it was not possible to define a tracking template due to poor soft-tissue contrast regardless of input images. The mean localization errors using clinical, regular dual-energy, and filter-free dual-energy radiographs were 3.85, 3.32, and 5.24 mm, respectively. Tracking success was dependent on tumor position, tumor size, imaging beam angle, and patient size. This study has highlighted the influence of patient anatomy on the success rate of real

  15. Dynamic contrast-enhanced CT in advanced lung cancer after chemotherapy with/within radiation therapy: Can it predict treatment responsiveness of the tumor?

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Mi Ri; Whang, Sung Ho; Park, Chul Hwan; Kim, Sang Jin; Kim, Tae Hoon [Dept. of Radiology and Research Institute of Radiological Science, Yonsei University Health System, Seoul (Korea, Republic of)

    2013-08-15

    To evaluate the contrast enhancement patterns of lung cancer after chemotherapy using a dynamic contrast-enhanced (DCE) CT and to determine whether the enhancement patterns of tumors at early stages of treatment can predict treatment responses. Forty-two patients with advanced lung cancers underwent DCE-CT and follow-up CT after chemotherapy. We evaluated peak and net enhancement (PE and NE, respectively) and time-density curves (TDCs) (type A, B, C, and D) on DCE-CT images. Treatment responses were evaluated using revised Response Evaluation Criteria in Solid Tumor criteria. NE and PE values were significantly higher in the progressive disease (PD) groups than in the stable disease (SD) or partial response (PR) groups (p < 0.05). Types B, C, and D on TDCs were observed mostly in the PR and SD groups (96.0%), whereas type A was most frequent in the SD and PD groups (97.2%), which were significantly different in terms of PE and NE. Contrast enhancement pattern regarding the response of treatment on DCE-CT images could be helpful in predicting treatment response of advanced lung cancer after treatment.

  16. Transformation of Lettuce with rol ABC Genes: Extracts Show Enhanced Antioxidant, Analgesic, Anti-Inflammatory, Antidepressant, and Anticoagulant Activities in Rats.

    Science.gov (United States)

    Ismail, Hammad; Dilshad, Erum; Waheed, Mohammad Tahir; Mirza, Bushra

    2017-03-01

    Lettuce is an edible crop that is well known for dietary and antioxidant benefits. The present study was conducted to investigate the effects of rol ABC genes on antioxidant and medicinal potential of lettuce by Agrobacterium-mediated transformation. Transgene integration and expression was confirmed through PCR and real-time RT-PCR, respectively. The transformed plants showed 91-102 % increase in total phenolic contents and 53-65 % increase in total flavonoid contents compared to untransformed plants. Total antioxidant capacity and total reducing power increased up to 112 and 133 % in transformed plants, respectively. Results of DPPH assay showed maximum 51 % increase, and lipid peroxidation assay exhibited 20 % increase in antioxidant activity of transformed plants compared to controls. Different in vivo assays were carried out in rats. The transgenic plants showed up to 80 % inhibition in both hot plate analgesic assay and carrageenan-induced hind paw edema test, while untransformed plants showed only 45 % inhibition. Antidepressant and anticoagulant potential of transformed plants was also significantly enhanced compared to untransformed plants. Taken together, the present work highlights the use of rol genes to enhance the secondary metabolite production in lettuce and improve its analgesic, anti-inflammatory, antidepressant, and anticoagulatory properties.

  17. Asian sand dust enhances murine lung inflammation caused by Klebsiella pneumoniae

    International Nuclear Information System (INIS)

    He, Miao; Ichinose, Takamichi; Yoshida, Seiichi; Yamamoto, Shoji; Inoue, Ken-ichiro; Takano, Hirohisa; Yanagisawa, Rie; Nishikawa, Masataka; Mori, Ikuko; Sun, Guifan; Shibamoto, Takayuki

    2012-01-01

    Inhaling concomitants from Asian sand dust (ASD) may result in exacerbation of pneumonia by the pathogen. The exacerbating effect of ASD on pneumonia induced by Klebsiella pneumoniae (KP) was investigated in ICR mice. The organic substances adsorbed onto ASD collected from the atmosphere of Iki-island in Japan were excluded by heat treatment at 360 °C for 30 min. ICR mice were instilled intratracheally with ASD at doses of 0.05 mg or 0.2 mg/mouse four times at 2-week intervals (total dose of 0.2 mg or 0.8 mg/mouse) and were administrated with ASD in the presence or absence of KP at the last intratracheal instillation. Pathologically, ASD caused exacerbation of pneumonia by KP as shown by increased inflammatory cells within the bronchiolar and the alveolar compartments. ASD enhanced the neutrophil number dose dependently as well as the expression of cytokines (IL-1β, IL-6, IL-12, IFN-γ, TNF-α) and chemokines (KC, MCP-1, MIP-1α) related to KP in BALF. In an in vitro study using RAW264.7 cells, combined treatment of ASD and KP increased gene expression of IL-1β, IL-6, IFN-β, KC, MCP-1, and MIP-1α. The same treatment tended to increase the protein level of IL-1β, TNF-α and MCP-1 in a culture medium compared to each treatment alone. The combined treatment tended to increase the gene expression of Toll-like receptor 2 (TLR2), and NALP3, ASC and caspase-1 compared with KP alone. These results suggest that the exacerbation of pneumonia by ASD + KP was due to the enhanced production of pro-inflammatory mediators via activation of TLR2 and NALP3 inflammasome pathways in alveolar macrophages.

  18. Asian sand dust enhances murine lung inflammation caused by Klebsiella pneumoniae

    Energy Technology Data Exchange (ETDEWEB)

    He, Miao [Department of Environmental and Occupational Health, College of Public Health, China Medical University, 11001, Shenyang (China); Ichinose, Takamichi; Yoshida, Seiichi [Department of Health Sciences, Oita University of Nursing and Health Sciences, 870-1201, Oita (Japan); Yamamoto, Shoji; Inoue, Ken-ichiro; Takano, Hirohisa; Yanagisawa, Rie [Pathophysiology Research Team, National Institute for Environmental Studies, 305-8506, Tsukuba, Ibaraki (Japan); Nishikawa, Masataka; Mori, Ikuko [Environmental Chemistry Division, National Institute for Environmental Studies, 305-8506, Tsukuba, Ibaraki (Japan); Sun, Guifan [Department of Environmental and Occupational Health, College of Public Health, China Medical University, 11001, Shenyang (China); Shibamoto, Takayuki, E-mail: tshibamoto@ucdavis.edu [Department of Environmental Toxicology, University of California, Davis, CA 95616 (United States)

    2012-01-15

    Inhaling concomitants from Asian sand dust (ASD) may result in exacerbation of pneumonia by the pathogen. The exacerbating effect of ASD on pneumonia induced by Klebsiella pneumoniae (KP) was investigated in ICR mice. The organic substances adsorbed onto ASD collected from the atmosphere of Iki-island in Japan were excluded by heat treatment at 360 °C for 30 min. ICR mice were instilled intratracheally with ASD at doses of 0.05 mg or 0.2 mg/mouse four times at 2-week intervals (total dose of 0.2 mg or 0.8 mg/mouse) and were administrated with ASD in the presence or absence of KP at the last intratracheal instillation. Pathologically, ASD caused exacerbation of pneumonia by KP as shown by increased inflammatory cells within the bronchiolar and the alveolar compartments. ASD enhanced the neutrophil number dose dependently as well as the expression of cytokines (IL-1β, IL-6, IL-12, IFN-γ, TNF-α) and chemokines (KC, MCP-1, MIP-1α) related to KP in BALF. In an in vitro study using RAW264.7 cells, combined treatment of ASD and KP increased gene expression of IL-1β, IL-6, IFN-β, KC, MCP-1, and MIP-1α. The same treatment tended to increase the protein level of IL-1β, TNF-α and MCP-1 in a culture medium compared to each treatment alone. The combined treatment tended to increase the gene expression of Toll-like receptor 2 (TLR2), and NALP3, ASC and caspase-1 compared with KP alone. These results suggest that the exacerbation of pneumonia by ASD + KP was due to the enhanced production of pro-inflammatory mediators via activation of TLR2 and NALP3 inflammasome pathways in alveolar macrophages.

  19. Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner's syndrome protein.

    Science.gov (United States)

    Jang, Jun-Ho; Bruse, Shannon; Huneidi, Salam; Schrader, Ronald M; Monick, Martha M; Lin, Yong; Carter, A Brent; Klingelhutz, Aloysius J; Nyunoya, Toru

    2014-09-01

    Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence. We examined whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF). We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated β-galactosidase activity, the known senescence-inducing pathways (e.g., p53, p21), and telomere length. We found that acrolein induced cellular senescence by increasing both p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner's syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening. These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation.

  20. Human lung fibroblast-derived matrix facilitates vascular morphogenesis in 3D environment and enhances skin wound healing.

    Science.gov (United States)

    Du, Ping; Suhaeri, Muhammad; Ha, Sang Su; Oh, Seung Ja; Kim, Sang-Heon; Park, Kwideok

    2017-05-01

    Extracellular matrix (ECM) is crucial to many aspects of vascular morphogenesis and maintenance of vasculature function. Currently the recapitulation of angiogenic ECM microenvironment is still challenging, due mainly to its diverse components and complex organization. Here we investigate the angiogenic potential of human lung fibroblast-derived matrix (hFDM) in creating a three-dimensional (3D) vascular construct. hFDM was obtained via decellularization of in vitro cultured human lung fibroblasts and analyzed via immunofluorescence staining and ELISA, which detect multiple ECM macromolecules and angiogenic growth factors (GFs). Human umbilical vein endothelial cells (HUVECs) morphology was more elongated and better proliferative on hFDM than on gelatin-coated substrate. To prepare 3D construct, hFDM is collected, quantitatively analyzed, and incorporated in collagen hydrogel (Col) with HUVECs. Capillary-like structure (CLS) formation at 7day was significantly better with the groups containing higher doses of hFDM compared to the Col group (control). Moreover, the group (Col/hFDM/GFs) with both hFDM and angiogenic GFs (VEGF, bFGF, SDF-1) showed the synergistic activity on CLS formation and found much larger capillary lumen diameters with time. Further analysis of hFDM via angiogenesis antibody array kit reveals abundant biochemical cues, such as angiogenesis-related cytokines, GFs, and proteolytic enzymes. Significantly up-regulated expression of VE-cadherin and ECM-specific integrin subunits was also noticed in Col/hFDM/GFs. In addition, transplantation of Col/hFMD/GFs with HUVECs in skin wound model presents more effective re-epithelialization, many regenerated hair follicles, better transplanted cells viability, and advanced neovascularization. We believe that current system is a very promising platform for 3D vasculature construction in vitro and for cell delivery toward therapeutic applications in vivo. Functional 3D vasculature construction in vitro is still

  1. WE-G-BRE-06: New Potential for Enhancing External Beam Radiotherapy for Lung Cancer Using FDA-Approved Concentrations of Cisplatin Or Carboplatin Nanoparticles Administered Via Inhalation

    International Nuclear Information System (INIS)

    Hao, Y; Altundal, Y; Sajo, E; Detappe, A; Makrigiorgos, G; Berbeco, R; Ngwa, W

    2014-01-01

    Purpose: This study investigates, for the first time, the dose enhancement to lung tumors due to cisplatin nanoparticles (CNPs) and carboplatin nanoparticles (CBNPs) administered via inhalation route (IR) during external beam radiotherapy. Methods: Using Monte Carlo generated 6 MV energy fluence spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumor due to radiation-induced photoelectrons from CNPs administered via IR in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung tumor via IV. Meanwhile recent experimental studies indicate that 3.5–14.6 times higher concentrations of CNPs can reach the lung tumors by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the dose with and without CNPs was calculated for field size of 10 cm × 10 cm (sweeping gap), for a range of tumor depths and tumor sizes. Similar calculations were done for CBNPs. Results: For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of 1.19–1.30 were obtained for CNPs at 3–10 cm depth, respectively, in comparison to 1.06–1.09 for IV. For CBNPs, DEF values of 1.26–1.41 were obtained in comparison to 1.07–1.12 for IV. For IR with 14.6 times higher concentrations, higher DEF values were obtained e.g. 1.81–2.27 for CNPs. DEF increased with increasing field size or decreasing tumor size. Conclusions: Our preliminary results indicate that major dose enhancement to lung tumors can be achieved using CNPs/CBNPs administered via IR, in contrast to IV administration during external beam radiotherapy. These findings highlight a potential new approach for radiation boosting to lung tumors using CNPs/CBNPs administered via IR. This would, especially, be applicable during concomitant chemoradiotherapy, potentially allowing for dose enhancement while

  2. Co-exposure to nickel and cobalt chloride enhances cytotoxicity and oxidative stress in human lung epithelial cells

    International Nuclear Information System (INIS)

    Patel, Eshan; Lynch, Christine; Ruff, Victoria; Reynolds, Mindy

    2012-01-01

    Nickel and cobalt are heavy metals found in land, water, and air that can enter the body primarily through the respiratory tract and accumulate to toxic levels. Nickel compounds are known to be carcinogenic to humans and animals, while cobalt compounds produce tumors in animals and are probably carcinogenic to humans. People working in industrial and manufacturing settings have an increased risk of exposure to these metals. The cytotoxicity of nickel and cobalt has individually been demonstrated; however, the underlying mechanisms of co-exposure to these heavy metals have not been explored. In this study, we investigated the effect of exposure of H460 human lung epithelial cells to nickel and cobalt, both alone and in combination, on cell survival, apoptotic mechanisms, and the generation of reactive oxygen species and double strand breaks. For simultaneous exposure, cells were exposed to a constant dose of 150 μM cobalt or nickel, which was found to be relatively nontoxic in single exposure experiments. We demonstrated that cells exposed simultaneously to cobalt and nickel exhibit a dose-dependent decrease in survival compared to the cells exposed to a single metal. The decrease in survival was the result of enhanced caspase 3 and 7 activation and cleavage of poly (ADP-ribose) polymerase. Co-exposure increased the production of ROS and the formation of double strand breaks. Pretreatment with N-acetyl cysteine alleviated the toxic responses. Collectively, this study demonstrates that co-exposure to cobalt and nickel is significantly more toxic than single exposure and that toxicity is related to the formation of ROS and DSB. -- Highlights: ► Decreased survival following simultaneous exposure to NiCl 2 and CoCl 2 . ► Enhanced caspase and PARP cleavage following co-exposure. ► Increased formation of ROS in dual exposed cells. ► N-acetyl cysteine pretreatment decreases Co and Ni toxicity. ► Co-exposure to Ni and Co enhances the formation of double strand

  3. Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Choe, Tae-Boo [Department of Microbiological Engineering, Kon-Kuk University, Gwangjin-gu, Seoul (Korea, Republic of); Hong, Seok-Il [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Yi, Jae-Youn [Laboratory of Modulation of Radiobiological Responses, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Lee, Hyun-Gyu [Department of Microbiology and Immunology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Lee, Yun-Han, E-mail: yhlee87@yuhs.ac [Department of Radiation Oncology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Park, In-Chul, E-mail: parkic@kcch.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of)

    2014-07-11

    Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

  4. Predicting the prognosis of non-small cell lung cancer patient treated with conservative therapy using contrast-enhanced MR imaging

    International Nuclear Information System (INIS)

    Ohno, Y.; Adachi, S.; Motoyama, A.; Sugimura, K.; Kono, M.; Kusumoto, M.

    2000-01-01

    The aim of this study was to evaluate the therapeutic effect more accurately and predict the prognosis of treated non-small cell lung cancer by using contrast-enhanced magnetic resonance imaging (CE-MRI). Contrast-enhanced computed tomography (CE-CT) and CE-MRI were examined 90 non-small cell lung cancer patients treated with conservative therapies. Enhancement patterns of CE-MRI were classified into three types: peripheral; mottled; and homogeneous. Reduction ratio of tumor size (RRT) based on the World Health Organization response criteria and a new response rate; reduction ratio of viable tumor size (RRVT) which evaluates not only the reduction of tumor size but also changes in necrosis and/or cavity size, were evaluated. Changes of enhancement pattern were compared and correlated with pathological diagnosis. The RRTs, RRVTs, and interobserver agreements evaluated by all modalities were compared. The RRTs and RRVTs in each subgroup were correlated and compared with prognoses. Change of enhancement pattern depended on therapy had no tendency (p = 0.06). Enhancement pattern had significant correlation with pathological diagnosis (p < 0.0001). Partial response (PR) case of RRVT had significant difference between imaging techniques (p = 0.04). The RRVT of other cases and RRT had no significant difference. Interobserver agreements of RRT and RRVT were almost perfect (κ≥ 0.93). Prognosis had better correlation with RRVT than with RRT. Differences of relapse-free survival and survival between patients considered as having no change (NC) by RRT and PR by RRVT (NC-PR) and patients considered as having NC by RRT and RRVT were significant (p = 0.03, p = 0.01). There were no significant differences of relapse-free survival and survival between NC-PR patients and patients considered as having PR by RRT and RRVT. The CE-MRI technique could accurately evaluate the therapeutic effect and predict the prognosis of treated non-small cell lung cancer. (orig.)

  5. CT imaging of coexisting pulmonary tuberculosis and lung cancer

    International Nuclear Information System (INIS)

    Lv Yan; Xie Ruming; Zhou Xinhua; Zhou Zhen; Xu Jinping; He Wei; Guo Lifang; Ning Fenggang

    2013-01-01

    Objective: To study the CT characteristics of coexisting pulmonary tuberculosis and lung cancer. Methods: One hundred and four patients of coexisting pulmonary tuberculosis and lung cancer proved by histology, cytology or clinical underwent CT examination. All patients were divided into two groups, group Ⅰ were the patients with the lung cancer after tuberculosis or both found simultaneously (group Ⅰ a with peripheral lung cancer and group Ⅰ b with central lung cancer), group Ⅱ with tuberculosis during lung cancer chemotherapy (group Ⅱ a with peripheral lung cancer and group Ⅱ b with central lung cancer). Imaging characteristics of tuberculosis and lung cancer were compared. χ"2 test and t test were used for the statistical analysis. Results: Of 104 patients, there were 92 patients (88.5%) in group Ⅰ and 12 patients (11.5%) in group Ⅱ. Seventy patients (76.1%) of lung cancer and tuberculosis were located in the same lobe and 22 patients (23.9%) in the different lobes in group Ⅰ. There was no significant difference in distribution of tuberculosis between group Ⅰ and group Ⅱ (χ"2 = 4.302, P = 0.507). The fibrous stripes, nodules of calcification and pleural adhesion of tuberculosis were statistically significant between the two groups (χ"2 = 22.737, 15.193, 27.792, P < 0.05). There were 33 central lung cancers and 71 peripheral lung cancers. In group Ⅰ a (64 patients of peripheral lung cancers), 39 patients (60.9%) had typical manifestations and most of the lesions were ≥ 3 cm (n = 49, 76.6%), solid lesions showed variable enhancement. Conclusions: Secondary tuberculosis during lung cancer chemotherapy has the same CT characteristics with the common active tuberculosis. The morphology, enhancement pattern of lesion and follow-up are helpful for the diagnosis of lung cancer after tuberculosis. (authors)

  6. Mice expressing a “hyper-sensitive” form of the CB1 cannabinoid receptor (CB1) show modestly enhanced alcohol preference and consumption

    Science.gov (United States)

    Gonek, Maciej; Zee, Michael L.; Farnsworth, Jill C.; Amin, Randa A.; Andrews, Mary-Jeanette; Davis, Brian J.; Mackie, Ken; Morgan, Daniel J.

    2017-01-01

    We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a “hyper-sensitive” form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6%) but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg), morphine (10 mg/kg), and cocaine (10 mg/kg), demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model. PMID:28426670

  7. PIXE analysis showed that the preirradiation enhanced recovery of bone marrow elements after challenging irradiation in C57BL/6N Mice

    International Nuclear Information System (INIS)

    Matsuda, Y.; Yonezawa, M.; Nishiyama, F.

    2000-01-01

    Priming X-irradiation with 0.3-0.5 Gy induces radio-resistance in C57BL/6 strain of mice 2 weeks afterward. Elements in the bone marrow, sampled 11 days after challenging exposure to 5.0 Gy, were determined by PIXE. The challenging irradiation decreased Mg, P, S, K, Ca and Zn as well as dried bone marrow weight. The pre-irradiation enhanced recovery of these levels, indicating stimulated recovery of the metabolism int he tissue. Fe in both control (without pre-irradiation) and experimental groups increased to about twice the original value, showing elevated hemoglobin synthesis after challenging exposure. In previous studies we have reported that recovery of peripheral blood cell counts after sub-lethal irradiation was enhanced by the pre-irradiation. Further, study on accumulation of p53 and Bax proteins, which lead to apoptotic cell death, revealed that the pre-irradiation significantly suppressed accumulation of these proteins in the spleen after challenging irradiation with 3 Gy. These results and our present study suggest that the pre-irradiation decreased the spleen cell death, and favored re-growth of the spleen cells, resulting in stimulated recovery of metabolism for hematopoiesis in the bone marrow as well as in the spleen after challenging high dose irradiation. Stimulated recovery of Mg, P, S, K, Ca and Zn levels might indicate the importance of these elements in hematopoiesis. (author)

  8. Mice expressing a "hyper-sensitive" form of the CB1 cannabinoid receptor (CB1 show modestly enhanced alcohol preference and consumption.

    Directory of Open Access Journals (Sweden)

    David J Marcus

    Full Text Available We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6% but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg, morphine (10 mg/kg, and cocaine (10 mg/kg, demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model.

  9. 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 ...

  10. Expression of neuroimmune semaphorins 4A and 4D and their receptors in the lung is enhanced by allergen and vascular endothelial growth factor

    Directory of Open Access Journals (Sweden)

    Keegan Achsah D

    2011-05-01

    upregulated by allergen. Soluble Sema4D protein was present in the lung lysates and a whole Sema4A protein plus its dimer were readily detected in the bronchoalveolar (BAL fluids under inflammation. Conclusions This study clearly shows that neuroimmune semaphorins Sema4A and Sema4D and their receptors might serve as potential markers for the allergic airway inflammatory diseases. Our current findings pave the way for further investigations of the role of immune semaphorins in inflammation and their use as potential therapeutic targets for the inflammatory lung conditions.

  11. Astaxanthin down-regulates Rad51 expression via inactivation of AKT kinase to enhance mitomycin C-induced cytotoxicity in human non-small cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Chen, Jyh-Cheng; Wang, Tai-Jing; Zheng, Hao-Yu; Chen, Wen-Ching; Chang, Po-Yuan; Lin, Yun-Wei

    2016-04-01

    Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects, including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination, and studies show that chemo-resistant carcinomas exhibit high levels of Rad51 expression. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Astaxanthin treatment (2.5-20 μM) decreased Rad51 expression and phospho-AKT(Ser473) protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector rescued the decreased Rad51 mRNA and protein levels in astaxanthin-treated NSCLC cells. Combined treatment with phosphatidylinositol 3-kinase (PI3K) inhibitors (LY294002 or wortmannin) further decreased the Rad51 expression in astaxanthin-exposed A549 and H1703 cells. Knockdown of Rad51 expression by transfection with si-Rad51 RNA or cotreatment with LY294002 further enhanced the cytotoxicity and cell growth inhibition of astaxanthin. Additionally, mitomycin C (MMC) as an anti-tumor antibiotic is widely used in clinical NSCLC chemotherapy. Combination of MMC and astaxanthin synergistically resulted in cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced phospho-AKT(Ser473) level and Rad51 expression. Overexpression of AKT-CA or Flag-tagged Rad51 reversed the astaxanthin and MMC-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in astaxanthin and MMC co-treated cells. In conclusion, astaxanthin enhances MMC-induced cytotoxicity by decreasing Rad51 expression and AKT activation. These findings may provide rationale to combine astaxanthin with MMC for the treatment of NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. 4-methoxychalcone enhances cisplatin-induced oxidative stress and cytotoxicity by inhibiting the Nrf2/ARE-mediated defense mechanism in A549 lung cancer cells.

    Science.gov (United States)

    Lim, Juhee; Lee, Sung Ho; Cho, Sera; Lee, Ik-Soo; Kang, Bok Yun; Choi, Hyun Jin

    2013-10-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator for the protection of cells against oxidative and xenobiotic stresses. Recent studies have demonstrated that high constitutive expression of Nrf2 is observed in many types of cancer cells showing resistance to anti-cancer drugs, suggesting that the suppression of overexpressed Nrf2 could be an attractive therapeutic strategy to overcome cancer drug resistance. In the present study, we aimed to find small molecule compounds that enhance the sensitivity of tumor cells to cisplatin induced cytotoxicity by suppressing Nrf2-mediated defense mechanism. A549 lung cancer cells were shown to be more resistant to the anti-cancer drug cisplatin than HEK293 cells, with higher Nrf2 signaling activity; constitutively high amounts of Nrf2-downstream target proteins were observed in A549 cells. Among the three chalcone derivatives 4-methoxy-chalcone (4-MC), hesperidin methylchalcone, and neohesperidin dihydrochalcone, 4-MC was found to suppress transcriptional activity of Nrf2 in A549 cells but to activate it in HEK293 cells. 4-MC was also shown to down-regulate expression of Nrf2 and the downstream phase II detoxifying enzyme NQO1 in A549 cells. The PI3K/Akt pathway was found to be involved in the 4-MC-induced inhibition of Nrf2/ARE activity in A549 cells. This inhibition of Nrf2 signaling results in the accelerated generation of reactive oxygen species and exacerbation of cytotoxicity in cisplatin-treated A549 cells. Taken together, these results suggest that the small molecule compound 4-MC could be used to enhance the sensitivity of tumor cells to the therapeutic effect of cisplatin through the regulation of Nrf2/ARE signaling.

  13. Co-exposure to nickel and cobalt chloride enhances cytotoxicity and oxidative stress in human lung epithelial cells.

    Science.gov (United States)

    Patel, Eshan; Lynch, Christine; Ruff, Victoria; Reynolds, Mindy

    2012-02-01

    Nickel and cobalt are heavy metals found in land, water, and air that can enter the body primarily through the respiratory tract and accumulate to toxic levels. Nickel compounds are known to be carcinogenic to humans and animals, while cobalt compounds produce tumors in animals and are probably carcinogenic to humans. People working in industrial and manufacturing settings have an increased risk of exposure to these metals. The cytotoxicity of nickel and cobalt has individually been demonstrated; however, the underlying mechanisms of co-exposure to these heavy metals have not been explored. In this study, we investigated the effect of exposure of H460 human lung epithelial cells to nickel and cobalt, both alone and in combination, on cell survival, apoptotic mechanisms, and the generation of reactive oxygen species and double strand breaks. For simultaneous exposure, cells were exposed to a constant dose of 150 μM cobalt or nickel, which was found to be relatively nontoxic in single exposure experiments. We demonstrated that cells exposed simultaneously to cobalt and nickel exhibit a dose-dependent decrease in survival compared to the cells exposed to a single metal. The decrease in survival was the result of enhanced caspase 3 and 7 activation and cleavage of poly (ADP-ribose) polymerase. Co-exposure increased the production of ROS and the formation of double strand breaks. Pretreatment with N-acetyl cysteine alleviated the toxic responses. Collectively, this study demonstrates that co-exposure to cobalt and nickel is significantly more toxic than single exposure and that toxicity is related to the formation of ROS and DSB. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R.F.; Yu, B.; Zhang, R.Q.; Wang, X.H.; Li, C.; Wang, P.; Zhang, Y.; Han, B.; Gao, X.X.; Zhang, L. [Taian City Central Hospital, Taian, Shandong (China); Jiang, Z.M., E-mail: dmyh2436@126.com [Qianfoshan Hospital of Shandong Province, Shandong University, Ji’nan, Shandong (China)

    2018-02-01

    Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinibWBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (Po0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (Po0.05). Although bevacizumabgefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC. (author)

  15. [Macrophage colony stimulating factor enhances non-small cell lung cancer invasion and metastasis by promoting macrophage M2 polarization].

    Science.gov (United States)

    Li, Y J; Yang, L; Wang, L P; Zhang, Y

    2017-06-23

    Objective: To investigate the key cytokine which polarizes M2 macrophages and promotes invasion and metastasis in non-small cell lung cancer (NSCLC). Methods: After co-culture with A549 cells in vitro, the proportion of CD14(+) CD163(+) M2 macrophages in monocytes and macrophage colony stimulating factor (M-CSF) levels in culture supernatant were detected by flow cytometry, ELISA assay and real-time qPCR, respectively. The effects of CD14(+) CD163(+) M2 macrophages on invasion of A549 cells and angiogenesis of HUVEC cells were measured by transwell assay and tubule formation assay, respectively. The clinical and prognostic significance of M-CSF expression in NSCLC was further analyzed. Results: The percentage of CD14(+) CD163(+) M2 macrophages in monocytes and the concentration of M-CSF in the supernatant followed by co-culture was (12.03±0.46)% and (299.80±73.76)pg/ml, respectively, which were significantly higher than those in control group [(2.80±1.04)% and (43.07±11.22)pg/ml, respectively, P macrophages in vitro . M2 macrophages enhanced the invasion of A549 cells (66 cells/field vs. 26 cells/field) and the angiogenesis of HUVEC cells (22 tubes/field vs. 8 tubes/field). The mRNA expression of M-CSF in stage Ⅰ-Ⅱ patients (16.23±4.83) was significantly lower than that in stage Ⅲ-Ⅳ (53.84±16.08; P macrophages, which can further promote the metastasis and angiogenesis of NSCLC. M-CSF could be used as a potential therapeutic target of NSCLC.

  16. Irradiation and various cytotoxic drugs enhance tyrosine phosphorylation and β1-integrin clustering in human A549 lung cancer cells in a substratum-dependent manner in vitro

    International Nuclear Information System (INIS)

    Cordes, N.; Beinke, C.; Beuningen, D. van; Plasswilm, L.

    2004-01-01

    Background and purpose: interactions of cells with a substratum, especially extracellular matrix proteins, initiate clustering of integrin receptors in the cell membrane. This process represents the initial step for the activation of signaling pathways regulating survival, proliferation, differentiation, adhesion, and migration, and could, furthermore, be important for cellular resistance-mediating mechanisms against radiation or cytotoxic drugs. The lack of data elucidating the impact of irradiation or cytotoxic drugs on this important phenomenon led to this study on human A549 lung cancer cells in vitro. Material and methods: the human lung carcinoma cell line A549 grown on polystyrene or fibronectin (FN) was irradiated with 0-8 Gy or treated with cisplatin (0.1-50 μM), paclitaxel (0.1-50 nM), or mitomycin (0.1-50 μM). Colony formation assays, immunofluorescence staining in combination with activation of integrin clustering using anti-β 1 -integrin antibodies (K20), and Western blotting for tyrosine phosphorylation under treatment of cells with the IC 50 for irradiation (2 Gy; IC 50 = 2.2 Gy), cisplatin (2 μM), paclitaxel (5 nM), or mitomycin (7 μM) were performed. Results: attachment of cells to FN resulted in a significantly reduced radio- and chemosensitivity compared to polystyrene. The clustering of β 1 -integrins examined by immunofluorescence staining was only stimulated by irradiation, cisplatin, paclitaxel, or mitomycin in case of cell attachment to FN. By contrast, tyrosine phosphorylation, as one of the major events following β 1 -integrin clustering, showed a 3.7-fold, FN-related enhancement, and treatment of cells with the IC 50 of radiation, cisplatin, paclitaxel, or mitomycin showed a substratum-dependent induction. Conclusion: for the first time, a strong influence of irradiation and a variety of cytotoxic drugs on the clustering of β 1 -integrins could be shown. This event is a prerequisite for tyrosine phosphorylation and, thus, the

  17. A clue for the diagnosis of lung cancer looking lobar consolidation with emphasis on thickness and enhancement pattern of bronchial wall on CT

    International Nuclear Information System (INIS)

    Yoo, Ho Seok; Kwon, Woo Cheol; Cha, Seung Whan; Kim, Sang Ha; Koh, Sang Baek; Kim, Myung Soon

    2007-01-01

    To differentiate between lung cancer and pneumonia for cases of lobar consolidation, with an emphasis on the thickness and enhancement pattern of the bronchial wall viewed by a CT. We retrospectively analyzed 17 patients with evidence of lobar consolidation, from a simple-chest radiographs, and divided them into groups by condition (lung cancer, n = 5; pneumonia, n 12). CT scans were performed on all patients and bronchial wall thickness, which is the cranio-caudal length of the bronchial wall thickness and the enhancement pattern, were measured and analyzed at the mediastinal window setting. The thickness of the bronchial wall in the lung cancer group (2.46 ± 0.37 mm) was significantly greater than the pneumonia group (1.73 ± 0.36 mm) (ρ = 0.002). Moreover, the bronchial wall thickness was greater than 2.0 mm for all patients in the cancer group. Further, if a diagnostic criterion was set to be larger than 2.0 mm, 100% sensitivity and 66.7% specificity would be achieved for the study subjects. The cranio-caudal length of the bronchial wall thickness in the cancer group was 37.5 ± 16.4 mm, which was significantly greater than the pneumonia group (16.3 ± 6.6 mm) (ρ = 0.001). We found no significant difference for the degree of contrast enhancement between the two groups. A CT scan measurement of the bronchial wall thickness greater than 2 mm in CT scans can be an indicator for diagnosing lung cancer in patients with lobar consolidation

  18. The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Tzu-Chin [Chest Clinic, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Yi-Chin [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Chen, Hsiao-Ling [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Huang, Pei-Ru; Liu, Shang-Yu [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Yeh, Shu-Lan, E-mail: suzyyeh@csmu.edu.tw [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China)

    2016-02-01

    Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.

  19. The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

    International Nuclear Information System (INIS)

    Wu, Tzu-Chin; Lin, Yi-Chin; Chen, Hsiao-Ling; Huang, Pei-Ru; Liu, Shang-Yu; Yeh, Shu-Lan

    2016-01-01

    Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.

  20. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    Science.gov (United States)

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  1. ICAM-1-based rabies virus vaccine shows increased infection and activation of primary murine B cells in vitro and enhanced antibody titers in-vivo.

    Directory of Open Access Journals (Sweden)

    James E Norton

    Full Text Available We have previously shown that live-attenuated rabies virus (RABV-based vaccines infect and directly activate murine and human primary B cells in-vitro, which we propose can be exploited to help develop a single-dose RABV-based vaccine. Here we report on a novel approach to utilize the binding of Intracellular Adhesion Molecule-1 (ICAM-1 to its binding partner, Lymphocyte Function-associated Antigen-1 (LFA-1, on B cells to enhance B cell activation and RABV-specific antibody responses. We used a reverse genetics approach to clone, recover, and characterize a live-attenuated recombinant RABV-based vaccine expressing the murine Icam1 gene (rRABV-mICAM-1. We show that the murine ICAM-1 gene product is incorporated into virus particles, potentially exposing ICAM-1 to extracellular binding partners. While rRABV-mICAM-1 showed 10-100-fold decrease in viral titers on baby hamster kidney cells compared to the parental virus (rRABV, rRABV-mICAM-1 infected and activated primary murine B cells in-vitro more efficiently than rRABV, as indicated by significant upregulation of CD69, CD40, and MHCII on the surface of infected B cells. ICAM-1 expression on the virus surface was responsible for enhanced B cell infection since pre-treating rRABV-mICAM-1 with a neutralizing anti-ICAM-1 antibody reduced B cell infection to levels observed with rRABV alone. Furthermore, 100-fold less rRABV-mICAM-1 was needed to induce antibody titers in immunized mice equivalent to antibody titers observed in rRABV-immunized mice. Of note, only 10(3 focus forming units (ffu/mouse of rRABV-mICAM-1 was needed to induce significant anti-RABV antibody titers as early as five days post-immunization. As both speed and potency of antibody responses are important in controlling human RABV infection in a post-exposure setting, these data show that expression of Icam1 from the RABV genome, which is then incorporated into the virus particle, is a promising strategy for the development of a

  2. Enhancement of the Acrolein-Induced Production of Reactive Oxygen Species and Lung Injury by GADD34

    OpenAIRE

    Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Liu, Lintao; Isobe, Ken-ichi

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing...

  3. Bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions.

    Science.gov (United States)

    Khan, Wasim S; Adesida, Adetola B; Tew, Simon R; Lowe, Emma T; Hardingham, Timothy E

    2010-06-01

    Bone marrow-derived mesenchymal stem cells are a potential source of cells for the repair of articular cartilage defects. Hypoxia has been shown to improve chondrogenesis in some cells. In this study, bone marrow-derived stem cells were characterized and the effects of hypoxia on chondrogenesis investigated. Adherent bone marrow colony-forming cells were characterized for stem cell surface epitopes, and then cultured as cell aggregates in chondrogenic medium under normoxic (20% oxygen) or hypoxic (5% oxygen) conditions. The cells stained strongly for markers of adult mesenchymal stem cells, and a high number of cells were also positive for the pericyte marker 3G5. The cells showed a chondrogenic response in cell aggregate cultures and, in lowered oxygen, there was increased matrix accumulation of proteoglycan, but less cell proliferation. In hypoxia, there was increased expression of key transcription factor SOX6, and of collagens II and XI, and aggrecan. Pericytes are a candidate stem cell in many tissue, and our results show that bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5. The response to chondrogenic culture in these cells was enhanced by lowered oxygen tension. This has important implications for tissue engineering applications of bone marrow-derived stem cells. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  4. A pseudotype baculovirus expressing the capsid protein of foot-and-mouth disease virus and a T-Cell immunogen shows enhanced immunogenicity in mice

    Directory of Open Access Journals (Sweden)

    Liu Xiangtao

    2011-02-01

    Full Text Available Abstract Background Foot-and-mouth disease (FMD is a highly contagious disease of livestock which causes severe economic loss in cloven-hoofed animals. Vaccination is still a major strategy in developing countries to control FMD. Currently, inactivated vaccine of FMDV has been used in many countries with limited success and safety concerns. Development of a novel effective vaccine is must. Methods In the present study, two recombinant pseudotype baculoviruses, one expressing the capsid of foot-and-mouth disease virus (FMDV under the control of a cytomegalovirus immediate early enhancer/promoter (CMV-IE, and the other the caspid plus a T-cell immunogen coding region under a CAG promoter were constructed, and their expression was characterized in mammalian cells. In addition, their immunogenicity in a mouse model was investigated. The humoral and cell-mediated immune responses induced by pseudotype baculovirus were compared with those of inactivated vaccine. Results Indirect immunofluorescence assay (IFA and indirect sandwich-ELISA (IS-ELISA showed both recombinant baculoviruses (with or without T-cell epitopes were transduced efficiently and expressed target proteins in BHK-21 cells. In mice, intramuscular inoculation of recombinants with 1 × 109 or 1 × 1010 PFU/mouse induced the production of FMDV-specific neutralizing antibodies and gamma interferon (IFN-γ. Furthermore, recombinant baculovirus with T-cell epitopes had better immunogenicity than the recombinant without T-cell epitopes as demonstrated by significantly enhanced IFN-γ production (P P Conclusions These results indicate that pseudotype baculovirus-mediated gene delivery could be a alternative strategy to develop a new generation of vaccines against FMDV infection.

  5. Extracellular adenosine production by ecto-5′-nucleotidase (CD73) enhances radiation-induced lung fibrosis

    Science.gov (United States)

    Wirsdörfer, Florian; de Leve, Simone; Cappuccini, Federica; Eldh, Therese; Meyer, Alina V.; Gau, Eva; Thompson, Linda F.; Chen, Ning-Yuan; Karmouty-Quintana, Harry; Fischer, Ute; Kasper, Michael; Klein, Diana; Ritchey, Jerry W.; Blackburn, Michael R.; Westendorf, Astrid M.; Stuschke, Martin; Jendrossek, Verena

    2016-01-01

    Radiation-induced pulmonary fibrosis is a severe side effect of thoracic irradiation, but its pathogenesis remains poorly understood and no effective treatment is available. In this study, we investigated the role of the extracellular adenosine as generated by the ecto-5'-nucleotidase CD73 in fibrosis development after thoracic irradiation. Exposure of wild-type C57BL/6 mice to a single dose (15 Gray) of whole thorax irradiation triggered a progressive increase in CD73 activity in the lung between 3 and 30 weeks post-irradiation. In parallel, adenosine levels in bronchoalveolar lavage fluid (BALF) were increased by approximately three-fold. Histological evidence of lung fibrosis was observed by 25 weeks after irradiation. Conversely, CD73-deficient mice failed to accumulate adenosine in BALF and exhibited significantly less radiation-induced lung fibrosis (P<0.010). Furthermore, treatment of wild-type mice with pegylated adenosine deaminase (PEG-ADA) or CD73 antibodies also significantly reduced radiation-induced lung fibrosis. Taken together, our findings demonstrate that CD73 potentiates radiation-induced lung fibrosis, suggesting that existing pharmacological strategies for modulating adenosine may be effective in limiting lung toxicities associated with the treatment of thoracic malignancies. PMID:26921334

  6. Enhanced and enduring protection against tuberculosis by recombinant BCG-Ag85C and its association with modulation of cytokine profile in lung.

    Directory of Open Access Journals (Sweden)

    Ruchi Jain

    likelihood would show enhanced survival of guinea pigs.

  7. Resveratrol enhances radiosensitivity of human non-small cell lung cancer NCI-H838 cells accompanied by inhibition of nuclear factor-kappa B activation

    International Nuclear Information System (INIS)

    Liao, Hui-Fen; Kuo Cheng-Deng; Yang, Yuh-Cheng; Lin, Chin-Ping; Tai, Hung-Chi; Chen, Yu-Jen; Chen, Yu-Yawn

    2005-01-01

    Resveratrol, a polyphenol in red wine, possesses many pharmacological activities including cardio-protection, chemoprevention, anti-tumor effects, and nuclear factor-kappa B (NF-κB) inactivation. The present study was designed to evaluate the effects and possible mechanism of resveratrol in enhancing radiosensitivity of lung cancer cells. Human non-small cell lung cancer NCI-H838 cells were irradiated with or without resveratrol pretreatment. The surviving fraction and sensitizer enhancement ratio (SER) were estimated by using a colony formation assay and linear-quadratic model. The cell-cycle distribution was evaluated by using prospidium iodide staining and flow cytometry. An enzyme-linked immunosorbent assay (ELISA)-based assay with immobilized oligonucleotide was performed to assess the DNA binding activity of NF-κB. Resveratrol had no direct growth-inhibitory effect on NCI-H838 cells treated for 24 hours with doses up to 25 μM. Pretreatment with resveratrol significantly enhanced cell killing by radiation, with an SER up to 2.2. Radiation activated NF-κB, an effect reversed by resveratrol pretreatment. Resveratrol resulted in a decrease of cells in the G 0 /G 1 phase and an increase in the S phase. Our results demonstrate that resveratrol enhances the radiosensitivity of NCI-H838 cells accompanied by NF-κB inhibition and S-phase arrest. (author)

  8. Hinokitiol Exerts Anticancer Activity through Downregulation of MMPs 9/2 and Enhancement of Catalase and SOD Enzymes: In Vivo Augmentation of Lung Histoarchitecture

    Directory of Open Access Journals (Sweden)

    Chien-Hsun Huang

    2015-09-01

    Full Text Available Melanoma is extremely resistant to chemotherapy and the death rate is increasing hastily worldwide. Extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP-2 and -9. Evidence has shown that natural dietary antioxidants are capable of inhibiting cancer cell growth. Our recent studies showed that hinokitiol, a natural bioactive compound, inhibited vascular smooth muscle cell proliferation and platelets aggregation. The present study is to investigate the anticancer efficacy of hinokitiol against B16-F10 melanoma cells via modulating tumor invasion factors MMPs, antioxidant enzymes in vitro. An in vivo mice model of histological investigation was performed to study the patterns of elastic and collagen fibers. Hinokitiol inhibited the expression and activity of MMPs-2 and -9 in B16-F10 melanoma cells, as measured by western blotting and gelatin zymography, respectively. An observed increase in protein expression of MMPs 2/9 in melanoma cells was significantly inhibited by hinokitiol. Notably, hinokitiol (1–5 μM increased the activities of antioxidant enzymes catalase (CAT and superoxide dismutase (SOD from the reduction in melanoma cells. Also, hinokitiol (2–10 µM concentration dependently reduced in vitro Fenton reaction induced hydroxyl radical (OH· formation. An in vivo study showed that hinokitiol treatment increased elastic fibers (EF, collagens dispersion, and improved alveolar alterations in the lungs of B16/F10 injected mice. Overall, our findings propose that hinokitiol may be a potent anticancer candidate through down regulation of MMPs 9/2, reduction of OH· production and enhancement of antioxidant enzymes SOD and CAT.

  9. Hinokitiol Exerts Anticancer Activity through Downregulation of MMPs 9/2 and Enhancement of Catalase and SOD Enzymes: In Vivo Augmentation of Lung Histoarchitecture.

    Science.gov (United States)

    Huang, Chien-Hsun; Jayakumar, Thanasekaran; Chang, Chao-Chien; Fong, Tsorng-Harn; Lu, Shing-Hwa; Thomas, Philip Aloysius; Choy, Cheuk-Sing; Sheu, Joen-Rong

    2015-09-25

    Melanoma is extremely resistant to chemotherapy and the death rate is increasing hastily worldwide. Extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP)-2 and -9. Evidence has shown that natural dietary antioxidants are capable of inhibiting cancer cell growth. Our recent studies showed that hinokitiol, a natural bioactive compound, inhibited vascular smooth muscle cell proliferation and platelets aggregation. The present study is to investigate the anticancer efficacy of hinokitiol against B16-F10 melanoma cells via modulating tumor invasion factors MMPs, antioxidant enzymes in vitro. An in vivo mice model of histological investigation was performed to study the patterns of elastic and collagen fibers. Hinokitiol inhibited the expression and activity of MMPs-2 and -9 in B16-F10 melanoma cells, as measured by western blotting and gelatin zymography, respectively. An observed increase in protein expression of MMPs 2/9 in melanoma cells was significantly inhibited by hinokitiol. Notably, hinokitiol (1-5 μM) increased the activities of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) from the reduction in melanoma cells. Also, hinokitiol (2-10 µM) concentration dependently reduced in vitro Fenton reaction induced hydroxyl radical (OH·) formation. An in vivo study showed that hinokitiol treatment increased elastic fibers (EF), collagens dispersion, and improved alveolar alterations in the lungs of B16/F10 injected mice. Overall, our findings propose that hinokitiol may be a potent anticancer candidate through down regulation of MMPs 9/2, reduction of OH· production and enhancement of antioxidant enzymes SOD and CAT.

  10. Can visual assessment of blood flow patterns by dynamic contrast-enhanced computed tomography distinguish between malignant and benign lung tumors?

    DEFF Research Database (Denmark)

    Harders, Stefan Walbom; Madsen, Hans Henrik; Nellemann, Hanne Marie

    2017-01-01

    with suspected lung cancer and a lung tumor on their chest radiograph were included for DCE-CT. The tumors were categorized using structured qualitative analysis of tumor blood flow patterns. Histopathology was used as reference standard. RESULTS: Using structured qualitative analysis of tumor blood flow...... using structured qualitative analysis of tumor blood flow patterns is accurate as well as somewhat reproducible. However, there are significant limitations to DCE-CT.......BACKGROUND: Dynamic contrast-enhanced computed tomography (DCE-CT) is a tool, which, in theory, can quantify the blood flow and blood volume of tissues. In structured qualitative analysis, parametric color maps yield a visual impression of the blood flow and blood volume within the tissue being...

  11. AMT1;1 transgenic rice plants with enhanced NH4(+) permeability show superior growth and higher yield under optimal and suboptimal NH4(+) conditions.

    Science.gov (United States)

    Ranathunge, Kosala; El-Kereamy, Ashraf; Gidda, Satinder; Bi, Yong-Mei; Rothstein, Steven J

    2014-03-01

    The major source of nitrogen for rice (Oryza sativa L.) is ammonium (NH4(+)). The NH4(+) uptake of roots is mainly governed by membrane transporters, with OsAMT1;1 being a prominent member of the OsAMT1 gene family that is known to be involved in NH4(+) transport in rice plants. However, little is known about its involvement in NH4(+) uptake in rice roots and subsequent effects on NH4(+) assimilation. This study shows that OsAMT1;1 is a constitutively expressed, nitrogen-responsive gene, and its protein product is localized in the plasma membrane. Its expression level is under the control of circadian rhythm. Transgenic rice lines (L-2 and L-3) overexpressing the OsAMT1;1 gene had the same root structure as the wild type (WT). However, they had 2-fold greater NH4(+) permeability than the WT, whereas OsAMT1;1 gene expression was 20-fold higher than in the WT. Analogous to the expression, transgenic lines had a higher NH4(+) content in the shoots and roots than the WT. Direct NH4(+) fluxes in the xylem showed that the transgenic lines had significantly greater uptake rates than the WT. Higher NH4(+) contents also promoted higher expression levels of genes in the nitrogen assimilation pathway, resulting in greater nitrogen assimilates, chlorophyll, starch, sugars, and grain yield in transgenic lines than in the WT under suboptimal and optimal nitrogen conditions. OsAMT1;1 also enhanced overall plant growth, especially under suboptimal NH4(+) levels. These results suggest that OsAMT1;1 has the potential for improving nitrogen use efficiency, plant growth, and grain yield under both suboptimal and optimal nitrogen fertilizer conditions.

  12. AMT1;1 transgenic rice plants with enhanced NH4 + permeability show superior growth and higher yield under optimal and suboptimal NH4 + conditions

    Science.gov (United States)

    Rothstein, Steven J.

    2014-01-01

    The major source of nitrogen for rice (Oryza sativa L.) is ammonium (NH4 +). The NH4 + uptake of roots is mainly governed by membrane transporters, with OsAMT1;1 being a prominent member of the OsAMT1 gene family that is known to be involved in NH4 + transport in rice plants. However, little is known about its involvement in NH4 + uptake in rice roots and subsequent effects on NH4 + assimilation. This study shows that OsAMT1;1 is a constitutively expressed, nitrogen-responsive gene, and its protein product is localized in the plasma membrane. Its expression level is under the control of circadian rhythm. Transgenic rice lines (L-2 and L-3) overexpressing the OsAMT1;1 gene had the same root structure as the wild type (WT). However, they had 2-fold greater NH4 + permeability than the WT, whereas OsAMT1;1 gene expression was 20-fold higher than in the WT. Analogous to the expression, transgenic lines had a higher NH4 + content in the shoots and roots than the WT. Direct NH4 + fluxes in the xylem showed that the transgenic lines had significantly greater uptake rates than the WT. Higher NH4 + contents also promoted higher expression levels of genes in the nitrogen assimilation pathway, resulting in greater nitrogen assimilates, chlorophyll, starch, sugars, and grain yield in transgenic lines than in the WT under suboptimal and optimal nitrogen conditions. OsAMT1;1 also enhanced overall plant growth, especially under suboptimal NH4 + levels. These results suggest that OsAMT1;1 has the potential for improving nitrogen use efficiency, plant growth, and grain yield under both suboptimal and optimal nitrogen fertilizer conditions. PMID:24420570

  13. Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

    Science.gov (United States)

    Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

    2017-08-01

    Obesity is a significant risk factor for acute respiratory distress syndrome. The mechanisms underlying this association are unknown. We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury. Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice. Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins. Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese

  14. SARS – Lung Pathology

    Indian Academy of Sciences (India)

    Dry nonproductive cough – may show minimal lung infiltration. Recovery; * Lungs get fluid in bronchi- droplets infective and +ve for virus in culture and PCR. May also have co-infection with chlamydia/metapneumoviruses. Recovery; * Lung tissue destroyed due to ? immunological/cytokine mediated damage-Recovery ...

  15. Enhancement of the Acrolein-Induced Production of Reactive Oxygen Species and Lung Injury by GADD34

    Directory of Open Access Journals (Sweden)

    Yang Sun

    2015-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS. Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury.

  16. Enhancement of the acrolein-induced production of reactive oxygen species and lung injury by GADD34.

    Science.gov (United States)

    Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Liu, Lintao; Isobe, Ken-ichi

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS). Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury.

  17. Enhancement of the Acrolein-Induced Production of Reactive Oxygen Species and Lung Injury by GADD34

    Science.gov (United States)

    Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Isobe, Ken-ichi

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS). Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury. PMID:25821552

  18. Enhanced effect of BCG vaccine against pulmonary Mycobacterium tuberculosis infection in mice with lung Th17 response to mycobacterial heparin-binding hemagglutinin adhesin antigen.

    Science.gov (United States)

    Fukui, Masayuki; Shinjo, Kikuko; Umemura, Masayuki; Shigeno, Satoko; Harakuni, Tetsuya; Arakawa, Takeshi; Matsuzaki, Goro

    2015-12-01

    Although the BCG vaccine can prevent tuberculosis (TB) in infants, its ability to prevent adult pulmonary TB is reportedly limited. Therefore, development of a novel effective vaccine against pulmonary TB has become an international research priority. We have previously reported that intranasal vaccination of mice with a mycobacterial heparin-binding hemagglutinin adhesin (HBHA) plus mucosal adjuvant cholera toxin (CT) enhances production of IFN-γ and anti-HBHA antibody and suppresses extrapulmonary bacterial dissemination after intranasal infection with BCG. In the present study, the effects of intranasal HBHA + CT vaccine on murine pulmonary Mycobacterium tuberculosis (Mtb) infection were examined. Intranasal HBHA + CT vaccination alone failed to reduce the bacterial burden in the infected lung. However, a combination vaccine consisting of s.c. BCG priming and an intranasal HBHA + CT booster significantly enhanced protective immunity against pulmonary Mtb infection on day 14 compared with BCG vaccine alone. Further, it was found that intranasal HBHA + CT vaccine enhanced not only IFN-γ but also IL-17A production by HBHA-specific T cells in the lung after pulmonary Mtb infection. Therefore, this combination vaccine may be a good candidate for a new vaccine strategy against pulmonary TB. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  19. Lung cancer

    International Nuclear Information System (INIS)

    Aisner, J.

    1985-01-01

    This book contains 13 chapters. Some of the chapter titles are: The Pathology of Lung Cancer; Radiotherapy for Non-Small-Cell Cancer of the Lung; Chemotherapy for Non-Small-Cell Lung Cancer; Immunotherapy in the Management of Lung Cancer; Preoperative Staging and Surgery for Non-Small-Cell Lung Cancer; and Prognostic Factors in Lung Cancer

  20. Lung Nodule Detection in CT Images using Neuro Fuzzy Classifier

    Directory of Open Access Journals (Sweden)

    M. Usman Akram

    2013-07-01

    Full Text Available Automated lung cancer detection using computer aided diagnosis (CAD is an important area in clinical applications. As the manual nodule detection is very time consuming and costly so computerized systems can be helpful for this purpose. In this paper, we propose a computerized system for lung nodule detection in CT scan images. The automated system consists of two stages i.e. lung segmentation and enhancement, feature extraction and classification. The segmentation process will result in separating lung tissue from rest of the image, and only the lung tissues under examination are considered as candidate regions for detecting malignant nodules in lung portion. A feature vector for possible abnormal regions is calculated and regions are classified using neuro fuzzy classifier. It is a fully automatic system that does not require any manual intervention and experimental results show the validity of our system.

  1. Tumor Seeding Following Lung Radiofrequency Ablation: A Case Report

    International Nuclear Information System (INIS)

    Yamakado, Koichiro; Akeboshi, Masao; Nakatsuka, Atsuhiro; Takaki, Haruyuki; Takao, Motoshi; Kobayashi, Hiroyasu; Taguchi, Osamu; Takeda, Kan

    2005-01-01

    Lung radiofrequency (RF) ablation was performed for the treatment of a primary lung cancer measuring 2.5 cm in maximum diameter in a 78-year-old man. A contrast-enhanced computed tomography (CT) study performed 3 months after RF ablation showed incomplete ablation of the lung tumor and the appearance of a chest wall tumor 4.0 cm in maximum diameter that was considered to be the result of needle-tract seeding. RF ablation was performed for the treatment of both the lung and the chest wall tumors. Although tumor enhancement was eradicated in both of the treated tumors, follow-up CT studies revealed diffuse intra-pulmonary metastases in both lungs 2 months after the second RF session. He is currently receiving systemic chemotherapy

  2. Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

    International Nuclear Information System (INIS)

    Yanamala, Naveena; Hatfield, Meghan K.; Farcas, Mariana T.; Schwegler-Berry, Diane; Hummer, Jon A.; Shurin, Michael R.; Birch, M. Eileen; Gutkin, Dmitriy W.; Kisin, Elena; Kagan, Valerian E.; Bugarski, Aleksandar D.; Shvedova, Anna A.

    2013-01-01

    The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. - Highlights: • Exposure of mice to BDPM caused higher pulmonary toxicity compared to DPM. • Oxidative stress and inflammation were higher in BD vs to D exposed mice. • Inflammatory lymphocyte infiltrates were seen only in lungs of mice exposed to BD. • Ineffective clearance, prolonged PM retention was present only after BD exposure

  3. Enhanced inflammation and attenuated tumor suppressor pathways are associated with oncogene-induced lung tumors in aged mice

    Science.gov (United States)

    Aging is often accompanied by a dramatic increase in cancer susceptibility. To gain insights into how aging affects tumor susceptibility, we generated a conditional mouse model in which oncogenic KrasG12D was activated specifically in lungs of young (3-5 months) and old (19-24 months) mice. Activati...

  4. Enhanced airway dilation by positive-pressure inflation of the lungs compared with active deep inspiration in patients with asthma

    NARCIS (Netherlands)

    Slats, Annelies M.; Janssen, Kirsten; de Jeu, Ronald C.; van der Plas, Dirk T.; Schot, Robert; van den Aardweg, Joost G.; Sterk, Peter J.

    2008-01-01

    Deep inspiration temporarily reduces induced airways obstruction in healthy subjects. This bronchodilatory effect of deep inspiration is impaired in asthma. Passive machine-assisted lung inflation may augment bronchodilation compared with an active deep inspiration in patients with asthma by either

  5. Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

    Energy Technology Data Exchange (ETDEWEB)

    Yanamala, Naveena, E-mail: wqu1@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Hatfield, Meghan K., E-mail: wla4@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Farcas, Mariana T., E-mail: woe7@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Schwegler-Berry, Diane [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Hummer, Jon A., E-mail: qzh3@cdc.gov [Office of Mine Safety and Health Research/NIOSH/CDC, Pittsburgh, PA 15236 (United States); Shurin, Michael R., E-mail: shurinmr@upmc.edu [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Birch, M. Eileen, E-mail: mib2@cdc.gov [NIOSH/CDC, 4676 Columbia Parkway, Cincinnati, OH 45226 (United States); Gutkin, Dmitriy W., E-mail: dwgutkin@hotmail.com [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Kisin, Elena, E-mail: edk8@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Kagan, Valerian E., E-mail: kagan@pitt.edu [Department of Environmental and Occupational Health, University of Pittsburgh, PA (United States); Bugarski, Aleksandar D., E-mail: zjl1@cdc.gov [Office of Mine Safety and Health Research/NIOSH/CDC, Pittsburgh, PA 15236 (United States); Shvedova, Anna A., E-mail: ats1@cdc.gov [Pathology and Physiology Research Branch/NIOSH/CDC, Morgantown, WV 26505 (United States); Department Physiology and Pharmacology, WVU, Morgantown, WV 26505 (United States)

    2013-10-15

    The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. - Highlights: • Exposure of mice to BDPM caused higher pulmonary toxicity compared to DPM. • Oxidative stress and inflammation were higher in BD vs to D exposed mice. • Inflammatory lymphocyte infiltrates were seen only in lungs of mice exposed to BD. • Ineffective clearance, prolonged PM retention was present only after BD exposure.

  6. RGD-modified liposomes enhance efficiency of aclacinomycin A delivery: evaluation of their effect in lung cancer

    Directory of Open Access Journals (Sweden)

    Feng C

    2015-08-01

    Full Text Available Chan Feng,1,* Xiaoyan Li,2,* Chunyan Dong,1 Xuemei Zhang,1 Xie Zhang,1 Yong Gao11Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai, 2Shanghai Tenth People’s Hospital, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: In this study, long-circulating Arg-Gly-Asp (RGD-modified aclacinomycin A (ACM liposomes were prepared by thin film hydration method. Their morphology, particle size, encapsulation efficiency, and in vitro release were investigated. The RGD-ACM liposomes was about 160 nm in size and had the visual appearance of a yellowish suspension. The zeta potential was -22.2 mV and the encapsulation efficiency was more than 93%. The drug-release behavior of the RGD-ACM liposomes showed a biphasic pattern, with an initial burst release and followed by sustained release at a constant rate. After being dissolved in phosphate-buffered saline (pH 7.4 and kept at 4°C for one month, the liposomes did not aggregate and still had the appearance of a milky white colloidal solution. In a pharmacokinetic study, rats treated with RGD-ACM liposomes showed slightly higher plasma concentrations than those treated with ACM liposomes. Maximum plasma concentrations of RGD-ACM liposomes and ACM liposomes were 4,532 and 3,425 ng/mL, respectively. RGD-ACM liposomes had a higher AUC0–∞ (1.54-fold, mean residence time (2.09-fold, and elimination half-life (1.2-fold when compared with ACM liposomes. In an in vivo study in mice, both types of liposomes inhibited growth of human lung adenocarcinoma (A549 cells and markedly decreased tumor size when compared with the control group. There were no obvious pathological tissue changes in any of the treatment groups. Our results indicate that RGD-modified ACM liposomes have a better antitumor effect in vivo than their unmodified counterparts.Keywords: RGD, aclacinomycin A, long-circulating liposomes, pharmacokinetic, tumor

  7. TC-1 (c8orf4) enhances aggressive biologic behavior in lung cancer through the Wnt/β-catenin pathway.

    Science.gov (United States)

    Su, Kai; Huang, Lijun; Li, Wenhai; Yan, Xiaolong; Li, Xiaofei; Zhang, Zhipei; Jin, Faguang; Lei, Jie; Ba, Guangzhen; Liu, Boya; Wang, Xiaoping; Wang, Yunjie

    2013-11-01

    The thyroid cancer-1 (TC-1) or c8orf4 gene encodes a 106-residue naturally disordered protein that has been found to be associated with thyroid, gastric, and breast cancer. A recent study has indicated that the protein functions as a positive regulator in the Wnt/β-catenin signaling pathway in human breast cancer. However, no research has been done in the area of lung cancer. Therefore, the goal of the present study was to confirm the relationship among TC-1, lung cancer, and the Wnt/β-catenin signaling pathway. The expression of TC-1 was immunohistochemically examined in 147 patients with non-small-cell lung cancer. TC-1-overexpressed and silenced A549 cells were infected using lentivirus and MTT cell proliferation analysis, and Matrigel invasion assays and scratch-wound assays were performed to confirm the biologic behavioral changes in different A549 cell subsets. The Wnt/β-catenin signaling pathway, key gene β-catenin, target genes of vascular endothelial growth factor, cyclin D1, matrix metalloproteinase-7, c-myc, and survivin were tested at the mRNA and protein level. TC-1 was detected in 97 of the 147 non-small-cell lung cancer primary tumor specimens, and its expression correlated with the TNM stage and regional lymph node metastasis (P cell line. Furthermore, expression of TC-1 protein affected the Wnt/β-catenin signaling pathway's downstream genes, such as vascular endothelial growth factor and matrix metalloproteinase-7, at the mRNA and protein level. TC-1 expression is associated with aggressive biologic behavior in lung cancer and might coordinate with the Wnt/β-catenin pathway as a positive upstream regulator that induces these behaviors. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Anti-Lung Cancer Activity through Enhancement of Immunomodulation and Induction of Cell Apoptosis of Total Triterpenes Extracted from Ganoderma luncidum (Leyss. ex Fr. Karst.

    Directory of Open Access Journals (Sweden)

    Wei Cao

    2013-08-01

    Full Text Available Ganoderma luncidum (Leyss. ex Fr. Karst. (GLK has been used traditionally for the prevention and treatment of cancers or tumors for a long time in Traditional Chinese Medicine. The triterpenes as main effective components of GLK have been found to be beneficial for the efficacy. The purpose of this study was to examine the anti-lung cancer activity of triterpenes of GLK in vitro and in vivo and to explore their anti-lung cancer effects and potential mechanisms. A549 cells and Lewis tumor-bearing mice were used to evaluate the inhibition effects of triterpenes on cell proliferation and tumor growth. The IC50 of triterpenes of GLK on A549 cells was 24.63 μg/mL. Triterpenes of GLK could significantly inhibit tumor growth in mice (30, 60 and 120 mg/kg. The immune organs indexes including spleen and thymus were increased remarkedly by the treatment with triterpenes. Moreover, they were able to stimulate the immune response by increasing the expressions of IL-6 and TNF-α. Flow cytometric analysis revealed that cell arrest caused by triterpenes treatment (7.5, 15 and 30 μg/mL was in the G2/M phase in A549 cells. Triterpenes induced apoptosis by decreasing the expression of the antiapoptotic protein Bcl-2 and pro-caspase 9 and increasing the levels of cleaved-caspase 9. Our findings suggested that the triterpenes of GLK have anti-lung cancer activity in vitro and in vivo via enhancement of immunomodulation and induction of cell apoptosis. The study provides insights into the mechanism of GLK in the prevention and treatment of lung cancer.

  9. Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zhu WT

    2017-04-01

    Full Text Available Wen-Ting Zhu,1,2,* Sheng-Yao Liu,3,* Lei Wu,1,2 Hua-Li Xu,4 Jun Wang,1,2 Guo-Xin Ni,3,5 Qing-Bing Zeng1,2 1Biomaterial Research Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China; 2Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China; 3Department of Orthopeadics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China; 4Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China; 5Department of Rehabilitation Medicine, First Affiliated Hospital, Fujian Medical University, Fuzhou, China *These authors contributed equally to this work Background: It has been widely reported that curcumin (CUR exhibits anticancer activity and triggers the apoptosis of human A549 non-small-cell lung cancer (NSCLC cells. However, its application is limited owing to its poor solubility and bioavailability. Therefore, there is an urgent need to develop a new CUR formulation with higher water solubility and better biocompatibility for clinical application in the future. Materials and methods: In this study, CUR-loaded methoxy polyethylene glycol–polylactide (CUR/mPEG–PLA polymeric micelles were prepared by a thin-film hydration method. Their characteristics and antitumor effects were evaluated subsequently. Results: The average size of CUR/mPEG–PLA micelles was 34.9±2.1 nm with its polydispersity index (PDI in the range of 0.067–0.168. The encapsulation efficiency and drug loading were 90.2%±0.78% and 9.1%±0.07%, respectively. CUR was constantly released from the CUR/mPEG–PLA micelles, and its cellular uptake in A549 cells was significantly increased. It was also found that CUR/mPEG–PLA micelles inhibited A549 cell proliferation, increased the cell cytotoxicity, induced G2/M stage arrest and promoted cell apoptosis. Moreover, the CUR/mPEG–PLA micelles suppressed the

  10. CpG in Combination with an Inhibitor of Notch Signaling Suppresses Formalin-Inactivated Respiratory Syncytial Virus-Enhanced Airway Hyperresponsiveness and Inflammation by Inhibiting Th17 Memory Responses and Promoting Tissue-Resident Memory Cells in Lungs.

    Science.gov (United States)

    Zhang, Lei; Li, Hongyong; Hai, Yan; Yin, Wei; Li, Wenjian; Zheng, Boyang; Du, Xiaomin; Li, Na; Zhang, Zhengzheng; Deng, Yuqing; Zeng, Ruihong; Wei, Lin

    2017-05-15

    effective killed RSV vaccine. Using adjuvants to regulate innate and adaptive immune responses could be an effective method to prevent ERD. We evaluated the impact of TLR and Notch signaling on ERD by administering CpG, an agonist of TLR9, in combination with L685,458, an inhibitor of Notch signaling, during FI-RSV immunization. The data showed that treatment of TLR or Notch signaling alone did not suppress FI-RSV-enhanced airway inflammation, while CpG plus L685,458 markedly inhibited ERD. The mechanism appears to involve suppressing Th17 memory responses and promoting tissue-resident memory cells. Moreover, these results suggest that regulation of lung immune memory with adjuvant compounds containing more than one immune-stimulatory molecule may be a good strategy to prevent FI-RSV ERD. Copyright © 2017 American Society for Microbiology.

  11. Cerebral staging of lung cancer: is one single contrast-enhanced T1-weighted three-dimensional gradient-echo sequence sufficient?

    Energy Technology Data Exchange (ETDEWEB)

    Ohana, Mickael; Jeung, Mi-Young; Roy, Catherine [Nouvel Hopital Civil-Hopitaux Universitaires de Strasbourg, Service de Radiologie B/Radiology Department, Strasbourg (France); Bazille, Gauthier [Clinique Saint Anne-Groupe Radiologique MIM, Strasbourg (France)

    2014-08-15

    Gadolinium-enhanced magnetic resonance imaging (MRI) is the gold standard for cerebral staging in thoracic oncology. We hypothesize that a minimalist examination, consisting of a single contrast-enhanced T1-weighted three-dimensional gradient-echo sequence (CE 3D-GRE), would be sufficient for the cerebral staging of nonsymptomatic lung cancer patients. Seventy nonsymptomatic patients (50 % men; 62 years ± 10.2) referred for cerebral staging of a lung cancer were retrospectively included. All underwent a standard 3 T MRI examination with T1, FLAIR, T2* GRE, diffusion, and CE 3D-GRE sequences, for a total examination time of 20 min. The sole CE 3D-GRE (acquisition time: 6 min) was extracted and blindly interpreted by two radiologists in search of brain metastases. Hemorrhagic features of potential lesions and relevant incidental findings were also noted. Discrepant cases were reviewed by a third reader. The full MRI examination and follow-up studies were used as a reference to calculate sensitivity and specificity of the sole CE 3D-GRE. Thirty-eight point six percent (27 out of 70) of the patients had brain metastases. Performances and reader's agreement with the sole CE 3D-GRE sequence were excellent for the diagnosis of brain metastases (sensitivity = 96.3 %, specificity = 100 %, κ = 0.91) and incidental findings (sensitivity = 85.7 %, specificity = 100 %, κ = 0.62) but insufficient for the identification of hemorrhages within the metastases (sensitivity = 33.3 %, specificity = 85.7 %, κ = 0.47). In the specific case of lung cancer, cerebral staging in nonsymptomatic patients can be efficiently achieved with a minimalistic protocol consisting of a single CE 3D-GRE sequence, completed if positive with a T2* sequence for hemorrhagic assessment, thus halving appointment delays. (orig.)

  12. Mice Overexpressing Type 1 Adenylyl Cyclase Show Enhanced Spatial Memory Flexibility in the Absence of Intact Synaptic Long-Term Depression

    Science.gov (United States)

    Zhang, Ming; Wang, Hongbing

    2013-01-01

    There is significant interest in understanding the contribution of intracellular signaling and synaptic substrates to memory flexibility, which involves new learning and suppression of obsolete memory. Here, we report that enhancement of Ca[superscript 2+]-stimulated cAMP signaling by overexpressing type 1 adenylyl cyclase (AC1) facilitated…

  13. P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment.

    Science.gov (United States)

    Wada, M; Canals, D; Adada, M; Coant, N; Salama, M F; Helke, K L; Arthur, J S; Shroyer, K R; Kitatani, K; Obeid, L M; Hannun, Y A

    2017-11-23

    The protein p38 mitogen-activated protein kinase (MAPK) delta isoform (p38δ) is a poorly studied member of the MAPK family. Data analysis from The Cancer Genome Atlas database revealed that p38δ is highly expressed in all types of human breast cancers. Using a human breast cancer tissue array, we confirmed elevation in cancer tissue. The breast cancer mouse model, MMTV-PyMT (PyMT), developed breast tumors with lung metastasis; however, mice deleted in p38δ (PyMT/p38δ -/- ) exhibited delayed primary tumor formation and highly reduced lung metastatic burden. At the cellular level, we demonstrate that targeting of p38δ in breast cancer cells, MCF-7 and MDA-MB-231 resulted in a reduced rate of cell proliferation. In addition, cells lacking p38δ also displayed an increased cell-matrix adhesion and reduced cell detachment. This effect on cell adhesion was molecularly supported by the regulation of the focal adhesion kinase by p38δ in the human breast cell lines. These studies define a previously unappreciated role for p38δ in breast cancer development and evolution by regulating tumor growth and altering metastatic properties. This study proposes MAPK p38δ protein as a key factor in breast cancer. Lack of p38δ resulted in reduced primary tumor size and blocked the metastatic potential to the lungs.

  14. 2'-OMe-phosphorodithioate-modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity.

    Science.gov (United States)

    Wu, Sherry Y; Yang, Xianbin; Gharpure, Kshipra M; Hatakeyama, Hiroto; Egli, Martin; McGuire, Michael H; Nagaraja, Archana S; Miyake, Takahito M; Rupaimoole, Rajesha; Pecot, Chad V; Taylor, Morgan; Pradeep, Sunila; Sierant, Malgorzata; Rodriguez-Aguayo, Cristian; Choi, Hyun J; Previs, Rebecca A; Armaiz-Pena, Guillermo N; Huang, Li; Martinez, Carlos; Hassell, Tom; Ivan, Cristina; Sehgal, Vasudha; Singhania, Richa; Han, Hee-Dong; Su, Chang; Kim, Ji Hoon; Dalton, Heather J; Kovvali, Chandra; Keyomarsi, Khandan; McMillan, Nigel A J; Overwijk, Willem W; Liu, Jinsong; Lee, Ju-Seog; Baggerly, Keith A; Lopez-Berestein, Gabriel; Ram, Prahlad T; Nawrot, Barbara; Sood, Anil K

    2014-03-12

    Improving small interfering RNA (siRNA) efficacy in target cell populations remains a challenge to its clinical implementation. Here, we report a chemical modification, consisting of phosphorodithioate (PS2) and 2'-O-Methyl (2'-OMe) MePS2 on one nucleotide that significantly enhances potency and resistance to degradation for various siRNAs. We find enhanced potency stems from an unforeseen increase in siRNA loading to the RNA-induced silencing complex, likely due to the unique interaction mediated by 2'-OMe and PS2. We demonstrate the therapeutic utility of MePS2 siRNAs in chemoresistant ovarian cancer mouse models via targeting GRAM domain containing 1B (GRAMD1B), a protein involved in chemoresistance. GRAMD1B silencing is achieved in tumours following MePS2-modified siRNA treatment, leading to a synergistic anti-tumour effect in combination with paclitaxel. Given the previously limited success in enhancing siRNA potency with chemically modified siRNAs, our findings represent an important advance in siRNA design with the potential for application in numerous cancer types.

  15. 2’f-OMe-phosphorodithioate modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity

    Science.gov (United States)

    Wu, Sherry Y.; Yang, Xianbin; Gharpure, Kshipra M.; Hatakeyama, Hiroto; Egli, Martin; McGuire, Michael H.; Nagaraja, Archana S.; Miyake, Takahito M.; Rupaimoole, Rajesha; Pecot, Chad V.; Taylor, Morgan; Pradeep, Sunila; Sierant, Malgorzata; Rodriguez-Aguayo, Cristian; Choi, Hyun J.; Previs, Rebecca A.; Armaiz-Pena, Guillermo N.; Huang, Li; Martinez, Carlos; Hassell, Tom; Ivan, Cristina; Sehgal, Vasudha; Singhania, Richa; Han, Hee-Dong; Su, Chang; Kim, Ji Hoon; Dalton, Heather J.; Kowali, Chandra; Keyomarsi, Khandan; McMillan, Nigel A.J.; Overwijk, Willem W.; Liu, Jinsong; Lee, Ju-Seog; Baggerly, Keith A.; Lopez-Berestein, Gabriel; Ram, Prahlad T.; Nawrot, Barbara; Sood, Anil K.

    2014-01-01

    Improving small interfering RNA (siRNA) efficacy in target cell populations remains a challenge to its clinical implementation. Here, we report a chemical modification, consisting of phosphorodithioate (PS2) and 2’-O-Methyl (2’-OMe) MePS2 on one nucleotide that significantly enhances potency and resistance to degradation for various siRNAs. We find enhanced potency stems from an unforeseen increase in siRNA loading to the RNA-induced silencing complex, likely due to the unique interaction mediated by 2’-OMe and PS2. We demonstrate the therapeutic utility of MePS2 siRNAs in chemoresistant ovarian cancer mouse models via targeting GRAM Domain Containing 1B (GRAMD1B), a protein involved in chemoresistance. GRAMD1B silencing is achieved in tumors following MePS2-modified siRNA treatment, leading to a synergistic anti-tumor effect in combination with paclitaxel. Given the previously limited success in enhancing siRNA potency with chemically modified siRNAs, our findings represent an important advance in siRNA design with the potential for application in numerous cancer types. PMID:24619206

  16. Lung Emergencies

    Science.gov (United States)

    ... The Marfan Foundation Marfan & Related Disorders What is Marfan Syndrome? What are Related Disorders? What are the Signs? ... Emergencies Lung Emergencies Surgeries Lung Emergencies People with Marfan syndrome can be at increased risk of sudden lung ...

  17. Dynamic contrast-enhanced MR imaging pharmacokinetic parameters as predictors of treatment response of brain metastases in patients with lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kuchcinski, Gregory; Duhal, Romain; Lalisse, Maxime; Dumont, Julien; Lopes, Renaud; Pruvo, Jean-Pierre; Leclerc, Xavier; Delmaire, Christine [University of Lille, CHU Lille, Department of Neuroradiology, Lille (France); Le Rhun, Emilie [University of Lille, CHU Lille, Department of Neurosurgery, Lille (France); Oscar Lambret Center, Department of Medical Oncology, Lille (France); Inserm U1192-PRISM-Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse, Lille (France); Cortot, Alexis B. [University of Lille, CHU Lille, Department of Thoracic Oncology, Lille (France); Drumez, Elodie [University of Lille, CHU Lille, Department of Biostatistics, Lille (France)

    2017-09-15

    To determine the diagnostic accuracy of pharmacokinetic parameters measured by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting the response of brain metastases to antineoplastic therapy in patients with lung cancer. Forty-four consecutive patients with lung cancer, harbouring 123 newly diagnosed brain metastases prospectively underwent conventional 3-T MRI at baseline (within 1 month before treatment), during the early (7-10 weeks) and midterm (5-7 months) post-treatment period. An additional DCE MRI sequence was performed during baseline and early post-treatment MRI to evaluate baseline pharmacokinetic parameters (K{sup trans}, k{sub ep}, v{sub e}, v{sub p}) and their early variation (∇K{sup trans}, ∇k{sub ep}, ∇v{sub e}, ∇v{sub p}). The objective response was judged by the volume variation of each metastasis from baseline to midterm MRI. ROC curve analysis determined the best DCE MRI parameter to predict the objective response. Baseline DCE MRI parameters were not associated with the objective response. Early ∇K{sup trans}, ∇v{sub e} and ∇v{sub p} were significantly associated with the objective response (p = 0.02, p = 0.001 and p = 0.02, respectively). The best predictor of objective response was ∇v{sub e} with an area under the curve of 0.93 [95% CI = 0.87, 0.99]. DCE MRI and early ∇v{sub e} may be a useful tool to predict the objective response of brain metastases in patients with lung cancer. (orig.)

  18. Accuracy and feasibility of dynamic contrast-enhanced 3D MR imaging in the assessment of lung perfusion: comparison with Tc-99 MAA perfusion scintigraphy

    International Nuclear Information System (INIS)

    Yilmaz, E.; Akkoclu, A.; Degirmenci, B.; Cooper, R.A.; Sengun, B.; Gulcu, A.; Osma, E.; Ucan, E.S.

    2005-01-01

    AIM: The aim of this study was to correlate findings of perfusion magnetic resonance imaging (MRI) and perfusion scintigraphy in cases where there was a suspicion of abnormal pulmonary vasculature, and to evaluate the usefulness of MRI in the detection of perfusion deficits of the lung. METHODS: In all, 17 patients with suspected abnormality of the pulmonary vasculature underwent dynamic contrast-enhanced MRI. T1-weighted 3D fast-field echo pulse sequences were obtained (TR/TE 3.3/1.58 ms; flip angle 30 deg ; slice thickness 12 to 15 mm). The dynamic study was acquired in the coronal plane following administration of 0.1 mmol/kg gadopentetate dimeglumine. A total of 8 to 10 sections repeated 20 to 25 times at intervals of 1 s were performed. Perfusion lung scintigraphy was carried out a maximum of 48 h before the MR examination in all cases. Two radiologists, who were blinded to the clinical data and results of other imaging methods, reviewed all coronal sections. MR perfusion images were independently assessed in terms of segmental or lobar perfusion defects in the 85 lobes of the 17 individuals, and the findings were compared with the results of scintigraphy. RESULTS: Of the 17 patients, 8 were found to have pulmonary emboli, 2 chronic obstructive pulmonary disease with emphysema, 2 bullous emphysema, 2 Takayasu arteritis and 1 had a hypoplastic pulmonary artery. Pulmonary perfusion was completely normal in 2 cases. In 35 lobes, perfusion defects were detected using both methods, in 4 with MR alone and in 9 only with scintigraphy. There was good agreement between MRI and scintigraphy findings (kappa=0.695). CONCLUSION: Pulmonary perfusion MRI is a new alternative to scintigraphy in the evaluation of pulmonary perfusion for various lung disorders. In addition, this technique allows measurement and quantification of pulmonary perfusion abnormalities

  19. Trace element load in cancer and normal lung tissue

    International Nuclear Information System (INIS)

    Kubala-Kukus, A.; Braziewicz, J.; Banas, D.; Majewska, U.; Gozdz, S.; Urbaniak, A.

    1999-01-01

    Samples of malignant and benign human lung tissues were analysed by two complementary methods, i.e., particle induced X-ray emission (PIXE) and total reflection X-ray fluorescence (TRXRF). The concentration of trace elements of P, S, K, Ca, Ti, Cr, Mn, Fe, Cu, Zn, Se, Sr, Hg and Pb was determined in squamous cancer of lung tissue from 65 people and in the benign lung tumour tissue from 5 people. Several elements shows enhancement in cancerous lung tissue of women in comparison to men, i.e., titanium show maximum enhancement by 48% followed by Cr (20%) and Mn (36%). At the same time trace element concentration of Sr and Pb are declaimed by 30% and 20% in women population. Physical basis of used analytical methods, experimental set-up and the procedure of sample preparation are described

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

    Science.gov (United States)

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

    2014-02-01

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

  1. Fusion proteins of HIV-1 envelope glycoprotein gp120 with CD4-induced antibodies showed enhanced binding to CD4 and CD4 binding site antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Weizao, E-mail: chenw3@mail.nih.gov [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Feng, Yang [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Wang, Yanping [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); The Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Zhu, Zhongyu; Dimitrov, Dimiter S. [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Some recombinant HIV-1 gp120s do not preserve their conformations on gp140s. Black-Right-Pointing-Pointer We hypothesize that CD4i antibodies could induce conformational changes in gp120. Black-Right-Pointing-Pointer CD4i antibodies enhance binding of CD4 and CD4bs antibodies to gp120. Black-Right-Pointing-Pointer CD4i antibody-gp120 fusion proteins could have potential as vaccine immunogens. -- Abstract: Development of successful AIDS vaccine immunogens continues to be a major challenge. One of the mechanisms by which HIV-1 evades antibody-mediated neutralizing responses is the remarkable conformational flexibility of its envelope glycoprotein (Env) gp120. Some recombinant gp120s do not preserve their conformations on gp140s and functional viral spikes, and exhibit decreased recognition by CD4 and neutralizing antibodies. CD4 binding induces conformational changes in gp120 leading to exposure of the coreceptor-binding site (CoRbs). In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding. However, such interactions in single-chain fusion proteins resulted in gp120 conformations which bound to CD4 and CD4bs antibodies better than the original or mutagenically stabilized gp120s. Moreover, the two molecules in the fusion proteins synergized with each other in neutralizing HIV-1. Therefore, fusion proteins of gp120 with CD4i antibodies could have potential as components of HIV-1 vaccines and inhibitors of HIV-1 entry, and could be used as reagents to explore the conformational flexibility of gp120 and mechanisms of entry and immune evasion.

  2. Foxtail Millet [Setaria italica (L. Beauv.] Grown under Low Nitrogen Shows a Smaller Root System, Enhanced Biomass Accumulation, and Nitrate Transporter Expression

    Directory of Open Access Journals (Sweden)

    Faisal Nadeem

    2018-02-01

    Full Text Available Foxtail millet (FM [Setaria italica (L. Beauv.] is a grain and forage crop well adapted to nutrient-poor soils. To date little is known how FM adapts to low nitrogen (LN at the morphological, physiological, and molecular levels. Using the FM variety Yugu1, we found that LN led to lower chlorophyll contents and N concentrations, and higher root/shoot and C/N ratios and N utilization efficiencies under hydroponic culture. Importantly, enhanced biomass accumulation in the root under LN was in contrast to a smaller root system, as indicated by significant decreases in total root length; crown root number and length; and lateral root number, length, and density. Enhanced carbon allocation toward the root was rather for significant increases in average diameter of the LN root, potentially favorable for wider xylem vessels or other anatomical alterations facilitating nutrient transport. Lower levels of IAA and CKs were consistent with a smaller root system and higher levels of GA may promote root thickening under LN. Further, up-regulation of SiNRT1.1, SiNRT2.1, and SiNAR2.1 expression and nitrate influx in the root and that of SiNRT1.11 and SiNRT1.12 expression in the shoot probably favored nitrate uptake and remobilization as a whole. Lastly, more soluble proteins accumulated in the N-deficient root likely as a result of increases of N utilization efficiencies. Such “excessive” protein-N was possibly available for shoot delivery. Thus, FM may preferentially transport carbon toward the root facilitating root thickening/nutrient transport and allocate N toward the shoot maximizing photosynthesis/carbon fixation as a primary adaptive strategy to N limitation.

  3. Foxtail Millet [Setaria italica (L.) Beauv.] Grown under Low Nitrogen Shows a Smaller Root System, Enhanced Biomass Accumulation, and Nitrate Transporter Expression.

    Science.gov (United States)

    Nadeem, Faisal; Ahmad, Zeeshan; Wang, Ruifeng; Han, Jienan; Shen, Qi; Chang, Feiran; Diao, Xianmin; Zhang, Fusuo; Li, Xuexian

    2018-01-01

    Foxtail millet (FM) [ Setaria italica (L.) Beauv.] is a grain and forage crop well adapted to nutrient-poor soils. To date little is known how FM adapts to low nitrogen (LN) at the morphological, physiological, and molecular levels. Using the FM variety Yugu1, we found that LN led to lower chlorophyll contents and N concentrations, and higher root/shoot and C/N ratios and N utilization efficiencies under hydroponic culture. Importantly, enhanced biomass accumulation in the root under LN was in contrast to a smaller root system, as indicated by significant decreases in total root length; crown root number and length; and lateral root number, length, and density. Enhanced carbon allocation toward the root was rather for significant increases in average diameter of the LN root, potentially favorable for wider xylem vessels or other anatomical alterations facilitating nutrient transport. Lower levels of IAA and CKs were consistent with a smaller root system and higher levels of GA may promote root thickening under LN. Further, up-regulation of SiNRT1.1, SiNRT2.1, and SiNAR2.1 expression and nitrate influx in the root and that of SiNRT1.11 and SiNRT1.12 expression in the shoot probably favored nitrate uptake and remobilization as a whole. Lastly, more soluble proteins accumulated in the N-deficient root likely as a result of increases of N utilization efficiencies. Such "excessive" protein-N was possibly available for shoot delivery. Thus, FM may preferentially transport carbon toward the root facilitating root thickening/nutrient transport and allocate N toward the shoot maximizing photosynthesis/carbon fixation as a primary adaptive strategy to N limitation.

  4. Nutrition for Lung Cancer

    Science.gov (United States)

    ... Become An Advocate Volunteer Ways To Give Lung Cancer www.lung.org > Lung Health and Diseases > Lung Disease Lookup > ... Cancer Learn About Lung Cancer What Is Lung Cancer Lung Cancer Basics Causes & Risk Factors Lung Cancer Staging ...

  5. Texture analysis of advanced non-small cell lung cancer (NSCLC) on contrast-enhanced computed tomography: prediction of the response to the first-line chemotherapy

    International Nuclear Information System (INIS)

    Farina, Davide; Morassi, Mauro; Maroldi, Roberto; Roca, Elisa; Tassi, Gianfranco; Cavalleri, Giuseppe

    2013-01-01

    To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contrast-enhanced computed tomography (CECT), can predict response to chemotherapy in advanced non-small cell lung cancer (NSCLC). Fifty-three CECT studies of patients with advanced NSCLC who had undergone first-line chemotherapy were retrospectively reviewed. Response to chemotherapy was evaluated according to RECIST1.1. Tumour uniformity was assessed by a TA method based on Laplacian of Gaussian filtering. The resulting parameters were correlated with treatment response and overall survival by multivariate analysis. Thirty-one out of 53 patients were non-responders and 22 were responders. Average overall survival was 13 months (4-35), minimum follow-up was 12 months. In the adenocarcinoma group (n = 31), the product of tumour uniformity and grey level (GL*U) was the unique independent variable correlating with treatment response. Dividing the GL*U (range 8.5-46.6) into tertiles, lesions belonging to the second and the third tertiles had an 8.3-fold higher probability of treatment response compared with those in the first tertile. No association between texture features and response to treatment was observed in the non-adenocarcinoma group (n = 22). GL*U did not correlate with overall survival. TA on CECT images in advanced lung adenocarcinoma provides an independent predictive indicator of response to first-line chemotherapy. (orig.)

  6. Bigelovii A Protects against Lipopolysaccharide-Induced Acute Lung Injury by Blocking NF-κB and CCAAT/Enhancer-Binding Protein δ Pathways

    Directory of Open Access Journals (Sweden)

    Chunguang Yan

    2016-01-01

    Full Text Available Optimal methods are applied to acute lung injury (ALI and the acute respiratory distress syndrome (ARDS, but the mortality rate is still high. Accordingly, further studies dedicated to identify novel therapeutic approaches to ALI are urgently needed. Bigelovii A is a new natural product and may exhibit anti-inflammatory activity. Therefore, we sought to investigate its effect on lipopolysaccharide- (LPS- induced ALI and the underlying mechanisms. We found that LPS-induced ALI was significantly alleviated by Bigelovii A treatment, characterized by reduction of proinflammatory mediator production, neutrophil infiltration, and lung permeability. Furthermore, Bigelovii A also downregulated LPS-stimulated inflammatory mediator expressions in vitro. Moreover, both NF-κB and CCAAT/enhancer-binding protein δ (C/EBPδ activation were obviously attenuated by Bigelovii A treatment. Additionally, phosphorylation of both p38 MAPK and ERK1/2 (upstream signals of C/EBPδ activation in response to LPS challenge was also inhibited by Bigelovii A. Therefore, Bigelovii A could attenuate LPS-induced inflammation by suppression of NF-κB, inflammatory mediators, and p38 MAPK/ERK1/2—C/EBPδ, inflammatory mediators signaling pathways, which provide a novel theoretical basis for the possible application of Bigelovii A in clinic.

  7. Response assessment of stereotactic body radiation therapy using dynamic contrast-enhanced integrated MR-PET in non-small cell lung cancer patients.

    Science.gov (United States)

    Huang, Yu-Sen; Chen, Jenny Ling-Yu; Hsu, Feng-Ming; Huang, Jei-Yie; Ko, Wei-Chun; Chen, Yi-Chang; Jaw, Fu-Shan; Yen, Ruoh-Fang; Chang, Yeun-Chung

    2018-01-01

    To evaluate the response in patients undergoing SBRT using dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET). Stereotactic body radiation therapy (SBRT) is efficacious as a front-line local treatment for non-small cell lung cancer (NSCLC). We prospectively enrolled 19 lung tumors in 17 nonmetastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated 3T MR-PET before and 6 weeks after SBRT. The following image parameters were analyzed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, K trans , k ep , v e , v p , and iAUC 60 . Chest computed tomography (CT) was performed at 3 months after SBRT. SBRT treatment led to tumor changes including significant decreases in the SUV max (-61%, P PET SUV max was correlated with the MR k ep mean (P = 0.002) and k ep SD (P 10 (P = 0.083). In patients with NSCLC who are receiving SBRT, DCE-integrated MR-PET can be used to evaluate the response after SBRT and to predict the local treatment outcome. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:191-199. © 2017 International Society for Magnetic Resonance in Medicine.

  8. Establishment of A Malignant Pleural Effusion Mouse Model with Lewis Lung 
Carcinoma Cell Lines Expressing Enhanced Green Fluorescent Protein

    Directory of Open Access Journals (Sweden)

    Xingqun MA

    2012-06-01

    Full Text Available Background and objective Malignant pleural effusion (MPE is a poor prognosis factor in patients with advanced lung cancer. The aim of this study is to establish a mouse model of MPE using Lewis lung carcinoma (LLC cell lines expressing enhanced green fluorescent protein (EGFP. Methods The mouse model was created by injecting LLC-EGFP cells directly into the pleural cavity of mice that were sacrificed periodically. The dynamic growth and metastasis of tumor cells were screened using in vivo fluorescence imaging. The remaining mice were subjected to transverse computed tomography (CT imaging periodically to analyze the formation rate of pleural effusion. The survival rate and tumor metastasis were also observed. Pleural fluid was gently aspirated using a 1 mL syringe and its volume was measured. When two or more mice bore pleural effusion at the same time, we calculated the average volume. The correlation of pleural effusion with the integrated optical density (IOD were analyzed. Results Four days after the inoculation of LLC-EGFP cells, green fluorescence was observed by opening the chest wall. The tumor formation rate was 100%, and the IOD gradually increased after inoculation. The metastasis sites were mediastinal, and the hilar lymph nodes were contralateral pleural as well as pericardial. The metastasis rates were 87%, 73% and 20%, respectively. The CT scan revealed that the formation rates of pleural effusion on days 7, 14 and 21 were 13%, 46% and 53%, respectively. The average volume of pleural effusion increased obviously on day 10 and peaked on day 16 with a value of 0.5 mL. The mean survival time of nude mice was 28.8 days. The volume of pleural effusion and IOD were significantly correlated (r=0.91, P<0.000,1. Conclusion A mouse model of lung cancer malignant pleural effusion was successfully established by injecting LLC lines expressing EGFP into the pleural cavity under a microscope. The model can enable dynamic observations of the

  9. MR Differentiation of Lung Cancer from Progressive Massive Fibrosis in Patients with Coal Worker's Pneumoconiosis

    International Nuclear Information System (INIS)

    Kim, Young Jin; Jung, Jung Im; Park, Seog Hee; Lim, Young; Koo, Jung Wan

    2010-01-01

    To analyze the potential of MR to distinguish lung cancer from progressive massive fibrosis (PMF) in patients with coal worker's pneumoconiosis. The study consisted of 9 patients with pathologically proven lung cancer and 26 PMFs in 17 patients. All the patients had radiologic evidence of pneumoconiosis. T1-weighted FLASH images were obtained before and 0.5, 1, 2, 3, 4, 5, 7.5, 10, 12.5, and 15 minutes after injection of Gd-DTPA. T2-weighted fast spin-echo images were obtained. The imaging findings were evaluated for enhancement time curve, contrast uptake equivalent (CE), and enhancement factor (EF). On T1WI, there was no significant signal intensity difference between lung cancer and PMF. On T2WI, all lung cancer showed high signal intensity, as opposed to all PMFs which showed low signal intensity except for one PMF. Only one PMF showed high signal intensity on T2WI. For the dynamic contrast study, lung cancer showed faster and slightly stronger enhancement than PMFs. For a delayed image, most of the lung cancers (78%) showed washout, as opposed to a plateau in most of PMFs (73%) (p=0.0153). However, no difference was detected between the EFmax of lung cancer and PMFs (p=0.349). MR is potentially a useful tool in distinguishing lung cancer from PMFs in patients with coal worker's pneumoconiosis

  10. Dual-time point scanning of integrated FDG PET/CT for the evaluation of mediastinal and hilar lymph nodes in non-small cell lung cancer diagnosed as operable by contrast-enhanced CT

    Energy Technology Data Exchange (ETDEWEB)

    Kasai, Takami, E-mail: takaby@hotmail.co [Department of Radiology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba-ken 260-8677 (Japan); Motoori, Ken, E-mail: motoorik@faculty.chiba-u.j [Department of Radiology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba-ken 260-8677 (Japan); Horikoshi, Takuro, E-mail: taku_steelfish@yahoo.co.j [Department of Radiology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba-ken 260-8677 (Japan); Uchiyama, Katsuhiro, E-mail: ka-uchiyama@nifty.co [Diagnostic PET Imaging Center, Department of Radiology, Sannoh Medical Center, 166-2 Sannohcho, Inage-ku, Chiba City, Chiba-ken 263-0002 (Japan); Yasufuku, Kazuhiro, E-mail: kyasufuku@faculty.chiba-u.j [Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba-ken 260-8670 (Japan); Takiguchi, Yuichi, E-mail: takiguchi@faculty.chiba-u.j [Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba-ken 260-8670 (Japan); Takahashi, Fumiaki, E-mail: takahashifu@pharm.kitasato-u.ac.j [Division of Biostatistics, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641 (Japan); Kuniyasu, Yoshio, E-mail: kuniyasu@ace.ocn.ne.j [Diagnostic PET Imaging Center, Department of Radiology, Sannoh Medical Center, 166-2 Sannohcho, Inage-ku, Chiba City, Chiba-ken 263-0002 (Japan); Ito, Hisao, E-mail: hisao@faculty.chiba-u.j [Department of Radiology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba-ken 260-8677 (Japan)

    2010-08-15

    Purpose: To evaluate whether dual-time point scanning with integrated fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography and computed tomography (PET/CT) is useful for evaluation of mediastinal and hilar lymph nodes in non-small cell lung cancer diagnosed as operable by contrast-enhanced CT. Materials and methods: PET/CT data and pathological findings of 560 nodal stations in 129 patients with pathologically proven non-small cell lung cancer diagnosed as operable by contrast-enhanced CT were reviewed retrospectively. Standardized uptake values (SUVs) on early scans (SUVe) 1 h, and on delayed scans (SUVd) 2 h after FDG injection of each nodal station were measured. Retention index (RI) (%) was calculated by subtracting SUVe from SUVd and dividing by SUVe. Logistic regression analysis was performed with seven kinds of models, consisting of (1) SUVe, (2) SUVd, (3) RI, (4) SUVe and SUVd, (5) SUVe and RI, (6) SUVd and RI, and (7) SUVe, SUVd and RI. The seven derived models were compared by receiver-operating characteristic (ROC) analysis. k-Fold cross-validation was performed with k values of 5 and 10. p < 0.05 was considered statistically significant. Results: Model (1) including the term of SUVe showed the largest area under the ROC curve among the seven models. The cut-off probability of metastasis of 3.5% with SUVe of 2.5 revealed a sensitivity of 78% and a specificity of 81% on ROC analysis, and approximately 60% and 80% on k-fold cross-validation. Conclusion: Single scanning of PET/CT is sufficiently useful for evaluating mediastinal and hilar nodes for metastasis.

  11. Dual-time point scanning of integrated FDG PET/CT for the evaluation of mediastinal and hilar lymph nodes in non-small cell lung cancer diagnosed as operable by contrast-enhanced CT

    International Nuclear Information System (INIS)

    Kasai, Takami; Motoori, Ken; Horikoshi, Takuro; Uchiyama, Katsuhiro; Yasufuku, Kazuhiro; Takiguchi, Yuichi; Takahashi, Fumiaki; Kuniyasu, Yoshio; Ito, Hisao

    2010-01-01

    Purpose: To evaluate whether dual-time point scanning with integrated fluorine-18 fluorodeoxyglucose ( 18 F-FDG) positron emission tomography and computed tomography (PET/CT) is useful for evaluation of mediastinal and hilar lymph nodes in non-small cell lung cancer diagnosed as operable by contrast-enhanced CT. Materials and methods: PET/CT data and pathological findings of 560 nodal stations in 129 patients with pathologically proven non-small cell lung cancer diagnosed as operable by contrast-enhanced CT were reviewed retrospectively. Standardized uptake values (SUVs) on early scans (SUVe) 1 h, and on delayed scans (SUVd) 2 h after FDG injection of each nodal station were measured. Retention index (RI) (%) was calculated by subtracting SUVe from SUVd and dividing by SUVe. Logistic regression analysis was performed with seven kinds of models, consisting of (1) SUVe, (2) SUVd, (3) RI, (4) SUVe and SUVd, (5) SUVe and RI, (6) SUVd and RI, and (7) SUVe, SUVd and RI. The seven derived models were compared by receiver-operating characteristic (ROC) analysis. k-Fold cross-validation was performed with k values of 5 and 10. p < 0.05 was considered statistically significant. Results: Model (1) including the term of SUVe showed the largest area under the ROC curve among the seven models. The cut-off probability of metastasis of 3.5% with SUVe of 2.5 revealed a sensitivity of 78% and a specificity of 81% on ROC analysis, and approximately 60% and 80% on k-fold cross-validation. Conclusion: Single scanning of PET/CT is sufficiently useful for evaluating mediastinal and hilar nodes for metastasis.

  12. Automatic Solitary Lung Nodule Detection in Computed Tomography Images Slices

    Science.gov (United States)

    Sentana, I. W. B.; Jawas, N.; Asri, S. A.

    2018-01-01

    Lung nodule is an early indicator of some lung diseases, including lung cancer. In Computed Tomography (CT) based image, nodule is known as a shape that appears brighter than lung surrounding. This research aim to develop an application that automatically detect lung nodule in CT images. There are some steps in algorithm such as image acquisition and conversion, image binarization, lung segmentation, blob detection, and classification. Data acquisition is a step to taking image slice by slice from the original *.dicom format and then each image slices is converted into *.tif image format. Binarization that tailoring Otsu algorithm, than separated the background and foreground part of each image slices. After removing the background part, the next step is to segment part of the lung only so the nodule can localized easier. Once again Otsu algorithm is use to detect nodule blob in localized lung area. The final step is tailoring Support Vector Machine (SVM) to classify the nodule. The application has succeed detecting near round nodule with a certain threshold of size. Those detecting result shows drawback in part of thresholding size and shape of nodule that need to enhance in the next part of the research. The algorithm also cannot detect nodule that attached to wall and Lung Chanel, since it depend the searching only on colour differences.

  13. MiR-124 Inhibits Growth and Enhances Radiation-Induced Apoptosis in Non-Small Cell Lung Cancer by Inhibiting STAT3

    Directory of Open Access Journals (Sweden)

    Mengjie Wang

    2017-12-01

    Full Text Available Background/Aims: A growing body of evidence indicates that the abnormal expression of microRNAs (miRNAs play an important role in sensitizing the cellular response to ionizing radiation (IR. The aim of this study was to investigate whether the expression of miR-124 correlated with radiosensitivity in the context of non-small-cell lung carcinoma (NSCLC. Methods: Quantitative reverse transcription polymerase chain reaction (RT-PCR was used to quantify miR-124 expression in NSCLC tissues and cell lines. The role of miR-124 in NSCLC proliferation and radiosensitivity was analyzed using CCK-8 and flow cytometry apoptosis assays. Luciferase activity assays, RT-PCR, and Western blot assays were performed to confirm the target gene of miR-124. Results: In this study, we found that miR-124 was downregulated both in clinical NSCLC samples and in cell lines. miR-124 inhibited the proliferation of NSCLC cells and enhanced the apoptosis of NSCLC cells exposed to ionizing radiation. We identified signal transducer and activator of transcription 3 (STAT3 as a direct target of miR-124 by using target prediction algorithms and luciferase assays. Overexpression of STAT3 in A549 cell lines restored the enhanced radiosensitivity induced by miR-124. Conclusion: Taking these observations into consideration, we illustrated that miR-124 is a potential target for enhancing the radiosensitivity of NSCLC cells by targeting STAT3.

  14. Acrolein-Exposed Normal Human Lung Fibroblasts in Vitro: Cellular Senescence, Enhanced Telomere Erosion, and Degradation of Werner’s Syndrome Protein

    Science.gov (United States)

    Jang, Jun-Ho; Bruse, Shannon; Huneidi, Salam; Schrader, Ronald M.; Monick, Martha M.; Lin, Yong; Carter, A. Brent; Klingelhutz, Aloysius J.

    2014-01-01

    Background: Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence. Objectives: We examined whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF). Methods: We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated β-galactosidase activity, the known senescence-inducing pathways (e.g., p53, p21), and telomere length. Results: We found that acrolein induced cellular senescence by increasing both p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner’s syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening. Conclusions: These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation. Citation: Jang JH, Bruse S, Huneidi S, Schrader RM, Monick MM, Lin Y, Carter AB, Klingelhutz AJ, Nyunoya T. 2014. Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner’s syndrome protein. Environ Health Perspect 122:955–962; http://dx.doi.org/10.1289/ehp.1306911 PMID:24747221

  15. Transgenic wheat expressing Thinopyrum intermedium MYB transcription factor TiMYB2R-1 shows enhanced resistance to the take-all disease.

    Science.gov (United States)

    Liu, Xin; Yang, Lihua; Zhou, Xianyao; Zhou, Miaoping; Lu, Yan; Ma, Lingjian; Ma, Hongxiang; Zhang, Zengyan

    2013-05-01

    The disease take-all, caused by the fungus Gaeumannomyces graminis, is one of the most destructive root diseases of wheat worldwide. Breeding resistant cultivars is an effective way to protect wheat from take-all. However, little progress has been made in improving the disease resistance level in commercial wheat cultivars. MYB transcription factors play important roles in plant responses to environmental stresses. In this study, an R2R3-MYB gene in Thinopyrum intermedium, TiMYB2R-1, was cloned and characterized. The gene sequence includes two exons and an intron. The expression of TiMYB2R-1 was significantly induced following G. graminis infection. An in vitro DNA binding assay proved that TiMYB2R-1 protein could bind to the MYB-binding site cis-element ACI. Subcellular localization assays revealed that TiMYB2R-1 was localized in the nucleus. TiMYB2R-1 transgenic wheat plants were generated, characterized molecularly, and evaluated for take-all resistance. PCR and Southern blot analyses confirmed that TiMYB2R-1 was integrated into the genomes of three independent transgenic wheat lines by distinct patterns and the transgene was heritable. Reverse transcription-PCR and western blot analyses revealed that TiMYB2R-1 was highly expressed in the transgenic wheat lines. Based on disease response assessments for three successive generations, the significantly enhanced resistance to take-all was observed in the three TiMYB2R-1-overexpressing transgenic wheat lines. Furthermore, the transcript levels of at least six wheat defence-related genes were significantly elevated in the TiMYB2R-1 transgenic wheat lines. These results suggest that engineering and overexpression of TiMYB2R-1 may be used for improving take-all resistance of wheat and other cereal crops.

  16. Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells

    Directory of Open Access Journals (Sweden)

    Sarah Fernandes Teixeira

    2013-12-01

    Full Text Available OBJECTIVE: To test the effectiveness of combining conventional antineoplastic drugs (cisplatin and etoposide with metformin in the treatment of non-small cell lung cancer in the NCI-H460 cell line, in order to develop new therapeutic options with high efficacy and low toxicity.METHODS: We used the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and calculated the combination index for the drugs studied.RESULTS: We found that the use of metformin as monotherapy reduced the metabolic viability of the cell line studied. Combining metformin with cisplatin or etoposide produced a synergistic effect and was more effective than was the use of cisplatin or etoposide as monotherapy.CONCLUSIONS: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. When metformin was combined with cisplatin or etoposide, the cell death rate was even higher.

  17. Alpinetin inhibits lung cancer progression and elevates sensitization drug-resistant lung cancer cells to cis-diammined dichloridoplatium

    Directory of Open Access Journals (Sweden)

    Wu L

    2015-11-01

    Full Text Available Lin Wu, Wei Yang, Su-ning Zhang, Ji-bin Lu Department of Thoracic Surgery, Sheng Jing Hospital of China Medical University, Shenyang, People’s Republic of China Objective: Alpinetin is a novel flavonoid that has demonstrated potent antitumor activity in previous studies. However, the efficacy and mechanism of alpinetin in treating lung cancer have not been determined. Methods: We evaluated the impact of different doses and durations of alpinetin treatment on the cell proliferation, the apoptosis of lung cancer cells, as well as the drug-resistant lung cancer cells. Results: This study showed that the alpinetin inhibited the cell proliferation, enhanced the apoptosis, and inhibited the PI3K/Akt signaling in lung cancer cells. Moreover, alpinetin significantly increased the sensitivity of drug-resistant lung cancer cells to the chemotherapeutic effect of cis-diammined dichloridoplatium. Taken together, this study demonstrated that alpinetin significantly suppressed the development of human lung cancer possibly by influencing mitochondria and the PI3K/Akt signaling pathway and sensitized drug-resistant lung cancer cells. Conclusion: Alpinetin may be used as a potential compound for combinatorial therapy or as a complement to other chemotherapeutic agents when multiple lines of treatments have failed to reduce lung cancer. Keywords: alpinetin, cell proliferation and apoptosis, drug resistance reversal, PI3K/Akt, lung cancer

  18. Dual‑sensitive HRE/Egr1 promoter regulates Smac overexpression and enhances radiation‑induced A549 human lung adenocarcinoma cell death under hypoxia.

    Science.gov (United States)

    Li, Chang-Feng; Chen, Li-Bo; Li, Dan-Dan; Yang, Lei; Zhang, Bao-Gang; Jin, Jing-Peng; Zhang, Ying; Zhang, Bin

    2014-08-01

    The aim of this study was to construct an expression vector carrying the hypoxia/radiation dual‑sensitive chimeric hypoxia response element (HRE)/early growth response 1 (Egr‑1) promoter in order to overexpress the therapeutic second mitochondria‑derived activator of caspases (Smac). Using this expression vector, the present study aimed to explore the molecular mechanism underlying radiotherapy‑induced A549 human lung adenocarcinoma cell death and apoptosis under hypoxia. The plasmids, pcDNA3.1‑Egr1‑Smac (pE‑Smac) and pcDNA3.1‑HRE/Egr-1‑Smac (pH/E‑Smac), were constructed and transfected into A549 human lung adenocarcinoma cells using the liposome method. CoCl2 was used to chemically simulate hypoxia, followed by the administration of 2 Gy X‑ray irradiation. An MTT assay was performed to detect cell proliferation and an Annexin V‑fluorescein isothiocyanate apoptosis detection kit was used to detect apoptosis. Quantitative polymerase chain reaction and western blot analyses were used for the detection of mRNA and protein expression, respectively. Infection with the pE‑Smac and pH/E‑Smac plasmids in combination with radiation and/or hypoxia was observed to enhance the expression of Smac. Furthermore, Smac overexpression was found to enhance the radiation‑induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis. The cytochrome c/caspase‑9/caspase‑3 pathway was identified to be involved in this regulation of apoptosis. Plasmid infection in combination with X‑ray irradiation was found to markedly induce cell death under hypoxia. In conclusion, the hypoxia/radiation dual‑sensitive chimeric HRE/Egr‑1 promoter was observed to enhance the expression of the therapeutic Smac, as well as enhance the radiation‑induced inhibition of cell proliferation and promotion of cycle arrest and apoptosis under hypoxia. This apoptosis was found to involve the mitochondrial pathway.

  19. Development of a safe ultraviolet camera system to enhance awareness by showing effects of UV radiation and UV protection of the skin (Conference Presentation)

    Science.gov (United States)

    Verdaasdonk, Rudolf M.; Wedzinga, Rosaline; van Montfrans, Bibi; Stok, Mirte; Klaessens, John; van der Veen, Albert

    2016-03-01

    The significant increase of skin cancer occurring in the western world is attributed to longer sun expose during leisure time. For prevention, people should become aware of the risks of UV light exposure by showing skin damage and the protective effect of sunscreen with an UV camera. An UV awareness imaging system optimized for 365 nm (UV-A) was develop using consumer components being interactive, safe and mobile. A Sony NEX5t camera was adapted to full spectral range. In addition, UV transparent lenses and filters were selected based on spectral characteristics measured (Schott S8612 and Hoya U-340 filters) to obtain the highest contrast for e.g. melanin spots and wrinkles on the skin. For uniform UV illumination, 2 facial tanner units were adapted with UV 365 nm black light fluorescent tubes. Safety of the UV illumination was determined relative to the sun and with absolute irradiance measurements at the working distance. A maximum exposure time over 15 minutes was calculate according the international safety standards. The UV camera was successfully demonstrated during the Dutch National Skin Cancer day and was well received by dermatologists and participating public. Especially, the 'black paint' effect putting sun screen on the face was dramatic and contributed to the awareness of regions on the face what are likely to be missed applying sunscreen. The UV imaging system shows to be promising for diagnostics and clinical studies in dermatology and potentially in other areas (dentistry and ophthalmology)

  20. Adenovirus serotype 5 vectors with Tat-PTD modified hexon and serotype 35 fiber show greatly enhanced transduction capacity of primary cell cultures.

    Directory of Open Access Journals (Sweden)

    Di Yu

    Full Text Available Recombinant adenovirus serotype 5 (Ad5 vectors represent one of the most efficient gene delivery vectors in life sciences. However, Ad5 is dependent on expression of the coxsackievirus-adenovirus-receptor (CAR on the surface of target cell for efficient transduction, which limits it's utility for certain cell types. Herein we present a new vector, Ad5PTDf35, which is an Ad5 vector having serotype 35 fiber-specificity and Tat-PTD hexon-modification. This vector shows dramatically increased transduction capacity of primary human cell cultures including T cells, monocytes, macrophages, dendritic cells, pancreatic islets and exocrine cells, mesenchymal stem cells and tumor initiating cells. Biodistribution in mice following systemic administration (tail-vein injection show significantly reduced uptake in the liver and spleen of Ad5PTDf35 compared to unmodified Ad5. Therefore, replication-competent viruses with these modifications may be further developed as oncolytic agents for cancer therapy. User-friendly backbone plasmids containing these modifications were developed for compatibility to the AdEasy-system to facilitate the development of surface-modified adenoviruses for gene delivery to difficult-to-transduce cells in basic, pre-clinical and clinical research.

  1. Enhanced

    Directory of Open Access Journals (Sweden)

    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  2. Combination of TRAIL and actinomycin D liposomes enhances antitumor effect in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Guo LG

    2012-03-01

    Full Text Available Liangran Guo1,2,4, Li Fan1,2, Jinfeng Ren1,2, Zhiqing Pang1,2, Yulong Ren1,2, Jingwei Li1,2, Ziyi Wen1,3, Yong Qian1,2, Lin Zhang1,2, Hang Ma4, Xinguo Jiang1,2 1School of Pharmacy, Fudan University, Zhangheng Road, Shanghai, 2Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Shanghai, 3School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China; 4College of Pharmacy, University of Rhode Island, RI, USAAbstract: The intractability of non-small cell lung cancer (NSCLC to multimodality treatments plays a large part in its extremely poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is a promising cytokine for selective induction of apoptosis in cancer cells; however, many NSCLC cell lines are resistant to TRAIL-induced apoptosis. The therapeutic effect can be restored by treatments combining TRAIL with chemotherapeutic agents. Actinomycin D (ActD can sensitize NSCLC cells to TRAIL-induced apoptosis by upregulation of death receptor 4 (DR4 or 5 (DR5. However, the use of ActD has significant drawbacks due to the side effects that result from its nonspecific biodistribution in vivo. In addition, the short half-life of TRAIL in serum also limits the antitumor effect of treatments combining TRAIL and ActD. In this study, we designed a combination treatment of long-circulating TRAIL liposomes and ActD liposomes with the aim of resolving these problems. The combination of TRAIL liposomes and ActD liposomes had a synergistic cytotoxic effect against A-549 cells. The mechanism behind this combination treatment includes both increased expression of DR5 and caspase activation. Moreover, systemic administration of the combination of TRAIL liposomes and ActD liposomes suppressed both tumor formation and growth of established subcutaneous NSCLC xenografts in nude mice, inducing apoptosis without causing significant general toxicity. These results provide preclinical proof

  3. Region of interest-based versus whole-lung segmentation-based approach for MR lung perfusion quantification in 2-year-old children after congenital diaphragmatic hernia repair

    Energy Technology Data Exchange (ETDEWEB)

    Weis, M.; Sommer, V.; Hagelstein, C.; Schoenberg, S.O.; Neff, K.W. [Heidelberg University, Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Mannheim (Germany); Zoellner, F.G. [Heidelberg University, Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Mannheim (Germany); Zahn, K. [University of Heidelberg, Department of Paediatric Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Mannheim (Germany); Schaible, T. [Heidelberg University, Department of Paediatrics, University Medical Center Mannheim, Medical Faculty Mannheim, Mannheim (Germany)

    2016-12-15

    With a region of interest (ROI)-based approach 2-year-old children after congenital diaphragmatic hernia (CDH) show reduced MR lung perfusion values on the ipsilateral side compared to the contralateral. This study evaluates whether results can be reproduced by segmentation of whole-lung and whether there are differences between the ROI-based and whole-lung measurements. Using dynamic contrast-enhanced (DCE) MRI, pulmonary blood flow (PBF), pulmonary blood volume (PBV) and mean transit time (MTT) were quantified in 30 children after CDH repair. Quantification results of an ROI-based (six cylindrical ROIs generated of five adjacent slices per lung-side) and a whole-lung segmentation approach were compared. In both approaches PBF and PBV were significantly reduced on the ipsilateral side (p always <0.0001). In ipsilateral lungs, PBF of the ROI-based and the whole-lung segmentation-based approach was equal (p=0.50). In contralateral lungs, the ROI-based approach significantly overestimated PBF in comparison to the whole-lung segmentation approach by approximately 9.5 % (p=0.0013). MR lung perfusion in 2-year-old children after CDH is significantly reduced ipsilaterally. In the contralateral lung, the ROI-based approach significantly overestimates perfusion, which can be explained by exclusion of the most ventral parts of the lung. Therefore whole-lung segmentation should be preferred. (orig.)

  4. Region of interest-based versus whole-lung segmentation-based approach for MR lung perfusion quantification in 2-year-old children after congenital diaphragmatic hernia repair

    International Nuclear Information System (INIS)

    Weis, M.; Sommer, V.; Hagelstein, C.; Schoenberg, S.O.; Neff, K.W.; Zoellner, F.G.; Zahn, K.; Schaible, T.

    2016-01-01

    With a region of interest (ROI)-based approach 2-year-old children after congenital diaphragmatic hernia (CDH) show reduced MR lung perfusion values on the ipsilateral side compared to the contralateral. This study evaluates whether results can be reproduced by segmentation of whole-lung and whether there are differences between the ROI-based and whole-lung measurements. Using dynamic contrast-enhanced (DCE) MRI, pulmonary blood flow (PBF), pulmonary blood volume (PBV) and mean transit time (MTT) were quantified in 30 children after CDH repair. Quantification results of an ROI-based (six cylindrical ROIs generated of five adjacent slices per lung-side) and a whole-lung segmentation approach were compared. In both approaches PBF and PBV were significantly reduced on the ipsilateral side (p always <0.0001). In ipsilateral lungs, PBF of the ROI-based and the whole-lung segmentation-based approach was equal (p=0.50). In contralateral lungs, the ROI-based approach significantly overestimated PBF in comparison to the whole-lung segmentation approach by approximately 9.5 % (p=0.0013). MR lung perfusion in 2-year-old children after CDH is significantly reduced ipsilaterally. In the contralateral lung, the ROI-based approach significantly overestimates perfusion, which can be explained by exclusion of the most ventral parts of the lung. Therefore whole-lung segmentation should be preferred. (orig.)

  5. Transgenic barley (Hordeum vulgare L.) expressing the wheat aluminium resistance gene (TaALMT1) shows enhanced phosphorus nutrition and grain production when grown on an acid soil.

    Science.gov (United States)

    Delhaize, Emmanuel; Taylor, Phillip; Hocking, Peter J; Simpson, Richard J; Ryan, Peter R; Richardson, Alan E

    2009-06-01

    Barley (Hordeum vulgare L.), genetically modified with the Al(3+) resistance gene of wheat (TaALMT1), was compared with a non-transformed sibling line when grown on an acidic and highly phosphate-fixing ferrosol supplied with a range of phosphorus concentrations. In short-term pot trials (26 days), transgenic barley expressing TaALMT1 (GP-ALMT1) was more efficient than a non-transformed sibling line (GP) at taking up phosphorus on acid soil, but the genotypes did not differ when the soil was limed. Differences in phosphorus uptake efficiency on acid soil could be attributed not only to the differential effects of aluminium toxicity on root growth between the genotypes, but also to differences in phosphorus uptake per unit root length. Although GP-ALMT1 out-performed GP on acid soil, it was still not as efficient at taking up phosphorus as plants grown on limed soil. GP-ALMT1 plants grown in acid soil possessed substantially smaller rhizosheaths than those grown in limed soil, suggesting that root hairs were shorter. This is a probable reason for the lower phosphorus uptake efficiency. When grown to maturity in large pots, GP-ALMT1 plants produced more than twice the grain as GP plants grown on acid soil and 80% of the grain produced by limed controls. Expression of TaALMT1 in barley was not associated with a penalty in either total shoot or grain production in the absence of Al(3+), with both genotypes showing equivalent yields in limed soil. These findings demonstrate that an important crop species can be genetically engineered to successfully increase grain production on an acid soil.

  6. Gene expression analysis of two extensively drug-resistant tuberculosis isolates show that two-component response systems enhance drug resistance.

    Science.gov (United States)

    Yu, Guohua; Cui, Zhenling; Sun, Xian; Peng, Jinfu; Jiang, Jun; Wu, Wei; Huang, Wenhua; Chu, Kaili; Zhang, Lu; Ge, Baoxue; Li, Yao

    2015-05-01

    Global analysis of expression profiles using DNA microarrays was performed between a reference strain H37Rv and two clinical extensively drug-resistant isolates in response to three anti-tuberculosis drug exposures (isoniazid, capreomycin, and rifampicin). A deep analysis was then conducted using a combination of genome sequences of the resistant isolates, resistance information, and related public microarray data. Certain known resistance-associated gene sets were significantly overrepresented in upregulated genes in the resistant isolates relative to that observed in H37Rv, which suggested a link between resistance and expression levels of particular genes. In addition, isoniazid and capreomycin response genes, but not rifampicin, either obtained from published works or our data, were highly consistent with the differentially expressed genes of resistant isolates compared to those of H37Rv, indicating a strong association between drug resistance of the isolates and genes differentially regulated by isoniazid and capreomycin exposures. Based on these results, 92 genes of the studied isolates were identified as candidate resistance genes, 10 of which are known resistance-related genes. Regulatory network analysis of candidate resistance genes using published networks and literature mining showed that three two-component regulatory systems and regulator CRP play significant roles in the resistance of the isolates by mediating the production of essential envelope components. Finally, drug sensitivity testing indicated strong correlations between expression levels of these regulatory genes and sensitivity to multiple anti-tuberculosis drugs in Mycobacterium tuberculosis. These findings may provide novel insights into the mechanism underlying the emergence and development of drug resistance in resistant tuberculosis isolates and useful clues for further studies on this issue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets

    NARCIS (Netherlands)

    Best, Myron G.; Sol, Nik; In ‘t Veld, Sjors G.J.G.; Vancura, Adrienne; Muller, Mirte; Niemeijer, Anna Larissa N.; Fejes, Aniko V.; Tjon Kon Fat, Lee Ann; Huis in 't Veld, Anna E; Leurs, Cyra; Le Large, Tessa Y.; Meijer, Laura L.; Kooi, Irsan E.; Rustenburg, François; Schellen, Pepijn; Verschueren, Heleen; Post, Edward; Wedekind, Laurine E.; Bracht, Jillian; Esenkbrink, Michelle; Wils, Leon; Favaro, Francesca; Schoonhoven, Jilian D.; Tannous, Jihane; Meijers-Heijboer, Hanne; Kazemier, Geert; Giovannetti, Elisa; Reijneveld, Jaap C.; Idema, Sander; Killestein, Joep; Heger, Michal; de Jager, Saskia C.; Urbanus, Rolf T.; Hoefer, Imo E.; Pasterkamp, Gerard; Mannhalter, Christine; Gomez-Arroyo, Jose; Bogaard, Harm-Jan; Noske, David P.; Vandertop, W. Peter; van den Broek, Daan; Ylstra, Bauke; Nilsson, R. Jonas A; Wesseling, Pieter; Karachaliou, Niki; Rosell, Rafael; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent B.; Tannous, Bakhos A.; de Langen, Adrianus J.; Smit, Egbert F.; van den Heuvel, Michel M; Wurdinger, Thomas

    2017-01-01

    Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from

  8. Combinational Therapy Enhances the Effects of Anti-IGF-1R mAb Figitumumab to Target Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Hongxin Cao

    Full Text Available Small cell lung cancer (SCLC is a recalcitrant malignancy with distinct biologic properties. Antibody targeting therapy has been actively investigated as a new drug modality.We tested the expression of IGF-1R and calculated the survival in 61 SCLC patients. We also evaluated the anti-tumor effects of anti-IGF-1R monoclonal antibody Figitumumab (CP on SCLC, and tried two drug combinations to improve CP therapy.Our clinical data suggested that high IGF-1R expression was correlated with low SCLC patient survival. We then demonstrated the effect of CP was likely through IGF-1R blockage and down-regulation without IGF-1R auto-phosphorylation and PI3K/AKT activation. However, we observed elevated MEK/ERK activation upon CP treatment in SCLC cells, and this MEK/ERK activation was enhanced by ß-arrestin1 knockdown while attenuated by ß-arrestin2 knockdown. We found both MEK/ERK inhibitor and metformin could enhance CP treatment in SCLC cells. We further illustrated the additive effect of metformin was likely through promoting further IGF-1R down-regulation.Our results highlighted the potential of anti-IGF-1R therapy and the adjuvant therapy strategy with either MEK/ERK inhibitor or metformin to target SCLC, warranting further studies.

  9. Xiao-Ai-Ping, a TCM Injection, Enhances the Antigrowth Effects of Cisplatin on Lewis Lung Cancer Cells through Promoting the Infiltration and Function of CD8+ T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Wanshuai Li

    2013-01-01

    Full Text Available Objectives. To investigate how Xiao-Ai-Ping injection, a traditional Chinese medicine and an ancillary drug in tumor treatment, enhances the antitumor effects of cisplatin on Lewis lung cancer (LLC cells. Methods. LLC-bearing mice were daily intraperitoneally injected with various doses of cisplatin, Xiao-Ai-Ping, or cisplatin plus Xiao-Ai-Ping, respectively. Body weight and tumor volumes were measured every three days. Results. Combination of Xiao-Ai-Ping and cisplatin yielded significantly better antigrowth and proapoptotic effects on LLC xenografts than sole drug treatment did. In addition, we found that Xiao-Ai-Ping triggered the infiltration of CD8+ T cells, a group of cytotoxic T cells, to LLC xenografts. Furthermore, the mRNA levels of interferon-γ (ifn-γ, perforin-1 (prf-1, and granzyme B (gzmb in CD8+ T cells were significantly increased after combination treatment of Xiao-Ai-Ping and cisplatin. In vitro studies showed that Xiao-Ai-Ping markedly upregulated the mRNA levels of ifn-γ, prf-1, and gzmb in CD8+ T cells in a concentration-dependent manner, suggesting that Xiao-Ai-Ping augments the function of CD8+ T cells. Conclusions. Xiao-Ai-Ping promotes the infiltration and function of CD8+ T cells and thus enhances the antigrowth effects of cisplatin on LLC xenografts, which provides new evidence for the combination of Xiao-Ai-Ping and cisplatin in clinic in China.

  10. The environmental carcinogen 3-nitrobenzanthrone and its main metabolite 3-aminobenzanthrone enhance formation of reactive oxygen intermediates in human A549 lung epithelial cells

    International Nuclear Information System (INIS)

    Hansen, Tanja; Seidel, Albrecht; Borlak, Juergen

    2007-01-01

    The environmental contaminant 3-nitrobenzanthrone (3-NBA) is highly mutagenic and a suspected human carcinogen. We aimed to evaluate whether 3-NBA is able to deregulate critical steps in cell cycle control and apoptosis in human lung epithelial A549 cells. Increased intracellular Ca 2+ and caspase activities were detected upon 3-NBA exposure. As shown by cell cycle analysis, an increased number of S-phase cells was observed after 24 h of treatment with 3-NBA. Furthermore, 3-NBA was shown to inhibit cell proliferation when added to subconfluent cell cultures. The main metabolite of 3-NBA, 3-ABA, induced statistically significant increases in tail moment as judged by alkaline comet assay. The potential of 3-NBA and 3-ABA to enhance the production of reactive oxygen species (ROS) was demonstrated by flow cytometry using 2',7'-dichlorofluorescein-diacetate (DCFH-DA). The enzyme inhibitors allopurinol, dicumarol, resveratrol and SKF525A were used to assess the impact of metabolic conversion on 3-NBA-mediated ROS production. Resveratrol decreased dichlorofluorescein (DCF) fluorescence by 50%, suggesting a role for CYP1A1 in 3-NBA-mediated ROS production. Mitochondrial ROS production was significantly attenuated (20% reduction) by addition of rotenone (complex I inhibition) and thenoyltrifluoroacetone (TTFA, complex II inhibition). Taken together, the results of the present study provide evidence for a genotoxic potential of 3-ABA in human epithelial lung cells. Moreover, both compounds lead to increased intracellular ROS and create an environment favorable to DNA damage and the promotion of cancer

  11. National Heart, Lung, and Blood Institute Workshop Summary: Enhancing Opportunities for Training and Retention of a Diverse Biomedical Workforce.

    Science.gov (United States)

    Duncan, Gregg A; Lockett, Angelia; Villegas, Leah R; Almodovar, Sharilyn; Gomez, Jose L; Flores, Sonia C; Wilkes, David S; Tigno, Xenia T

    2016-04-01

    Committed to its mission of conducting and supporting research that addresses the health needs of all sectors of the nation's population, the Division of Lung Diseases, National Heart, Lung, and Blood Institute of the National Institutes of Health (NHLBI/NIH) seeks to identify issues that impact the training and retention of underrepresented individuals in the biomedical research workforce. Early-stage investigators who received grant support through the NIH Research Supplements to Promote Diversity in Health Related Research Program were invited to a workshop held in Bethesda, Maryland in June, 2015, in order to (1) assess the effectiveness of the current NHLBI diversity program, (2) improve its strategies towards achieving its goal, and (3) provide guidance to assist the transition of diversity supplement recipients to independent NIH grant support. Workshop participants participated in five independent focus groups to discuss specific topics affecting underrepresented individuals in the biomedical sciences: (1) Socioeconomic barriers to success for diverse research scientists; (2) role of the academic research community in promoting diversity; (3) life beyond a research project grant: non-primary investigator career paths in research; (4) facilitating career development of diverse independent research scientists through NHLBI diversity programs; and (5) effectiveness of current NHLBI programs for promoting diversity of the biomedical workforce. Several key issues experienced by young, underrepresented biomedical scientists were identified, and solutions were proposed to improve on training and career development for diverse students, from the high school to postdoctoral trainee level, and address limitations of currently available diversity programs. Although some of the challenges mentioned, such as cost of living, limited parental leave, and insecure extramural funding, are also likely faced by nonminority scientists, these issues are magnified among diversity

  12. Knockdown of TC-1 enhances radiosensitivity of non-small cell lung cancer via the Wnt/β-catenin pathway.

    Science.gov (United States)

    Wu, Dapeng; Li, Lei; Yan, Wei

    2016-04-15

    Thyroid cancer 1 (TC-1, C8ofr4) is widely expressed in vertebrates and associated with many kinds of tumors. Previous studies indicated that TC-1 functions as a positive regulator in the Wnt/β-catenin signaling pathway in non-small cell lung cancer (NSCLC). However, its exact role and regulation mechanism in radiosensitivity of NSCLC are still unclear. The expression level of TC-1 was measured by qRT-PCR and western blot in NSCLC cell lines. Proliferation and apoptosis of NSCLC cells in response to TC-1 knockdown or/and radiation were determined by MTT assay and flow cytometry, respectively. The activation of the Wnt/β-catenin signaling pathway was further examined by western blotin vitroandin vivo Compared to TC-1 siRNA or radiotherapy alone, TC-1 silencing combined with radiation inhibited cell proliferation and induced apoptosis in NSCLC cell lines by inactivating of the Wnt/β-catenin signaling pathway. Furthermore, inhibition of the Wnt/β-catenin signaling pathway by XAV939, a Wnt/β-catenin signaling inhibitor, contributed to proliferation inhibition and apoptosis induction in NSCLC A549 cells. Combinative treatment of A549 xenografts with TC-1 siRNA and radiation caused significant tumor regression and inactivation of the Wnt/β-catenin signaling pathway relative to TC-1 siRNA or radiotherapy alone. The results fromin vitroandin vivostudies indicated that TC-1 silencing sensitized NSCLC cell lines to radiotherapy through the Wnt/β-catenin signaling pathway. © 2016. Published by The Company of Biologists Ltd.

  13. Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells

    OpenAIRE

    Baghdadi, Muhammad; Wada, Haruka; Nakanishi, Sayaka; Abe, Hirotake; Han, Nanumi; Putra, Wira Eka; Endo, Daisuke; Watari, Hidemichi; Sakuragi, Noriaki; Hida, Yasuhiro; Kaga, Kichizo; Miyagi, Yohei; Yokose, Tomoyuki; Takano, Atsushi; Daigo, Yataro

    2016-01-01

    The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance lo...

  14. Structural and perfusion magnetic resonance imaging of the lung in cystic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Amaxopoulou, Christina; Gnannt, Ralph; Kellenberger, Christian J. [University Children' s Hospital Zuerich, Department of Diagnostic Imaging, Zuerich, CH (Switzerland); University Children' s Hospital Zuerich, Children' s Research Center, Zuerich (Switzerland); Higashigaito, Kai [University Hospital Zuerich, Institute of Diagnostic and Interventional Radiology, Zuerich (Switzerland); Jung, Andreas [University Children' s Hospital Zuerich, Children' s Research Center, Zuerich (Switzerland); University Children' s Hospital Zuerich, Division of Pneumology, Zuerich (Switzerland)

    2018-02-15

    Because of its absence of ionising radiation and possibility for obtaining functional information, MRI is promising for assessing lung disease in children who require repetitive imaging for long-term follow-up. To describe MRI findings in children with cystic fibrosis and evaluate semi-quantitative dynamic contrast-enhanced lung perfusion. We retrospectively compared lung MRI in 25 children and young adults with cystic fibrosis (median age 3.7 years) to 12 children (median age 2 years) imaged for other pathologies. MRI at 1.5 T included respiratory-gated sequences and contrast-enhanced lung perfusion imaging. We described and graded any morphologic change. Signal enhancement and time to peak values of perfusion abnormalities were compared to those of normally enhancing lung parenchyma. Frequent findings in patients with cystic fibrosis were bronchial wall thickening (24/25, 96%), areas of consolidation (22/25, 88%), enlarged lymph nodes (20/25, 80%), bronchiectasis (5/25, 20%) and mucus plugging (3/25, 12%). Compared to normally enhancing lung, perfusion defects (21/25, 84%), characterised by decreased enhancement, showed prolonged time to peak. Areas of consolidation showed increased enhancement. While time to peak of procedure-related atelectasis was not significantly different from that of normal lung, disease-related consolidation showed prolonged time to peak (P=0.01). Lung MRI demonstrates structural and perfusion abnormalities in children and young people with cystic fibrosis. Semi-quantitative assessment of dynamic contrast-enhanced perfusion imaging might allow differentiation between procedure-related atelectasis and disease-related consolidation. (orig.)

  15. Structural and perfusion magnetic resonance imaging of the lung in cystic fibrosis

    International Nuclear Information System (INIS)

    Amaxopoulou, Christina; Gnannt, Ralph; Kellenberger, Christian J.; Higashigaito, Kai; Jung, Andreas

    2018-01-01

    Because of its absence of ionising radiation and possibility for obtaining functional information, MRI is promising for assessing lung disease in children who require repetitive imaging for long-term follow-up. To describe MRI findings in children with cystic fibrosis and evaluate semi-quantitative dynamic contrast-enhanced lung perfusion. We retrospectively compared lung MRI in 25 children and young adults with cystic fibrosis (median age 3.7 years) to 12 children (median age 2 years) imaged for other pathologies. MRI at 1.5 T included respiratory-gated sequences and contrast-enhanced lung perfusion imaging. We described and graded any morphologic change. Signal enhancement and time to peak values of perfusion abnormalities were compared to those of normally enhancing lung parenchyma. Frequent findings in patients with cystic fibrosis were bronchial wall thickening (24/25, 96%), areas of consolidation (22/25, 88%), enlarged lymph nodes (20/25, 80%), bronchiectasis (5/25, 20%) and mucus plugging (3/25, 12%). Compared to normally enhancing lung, perfusion defects (21/25, 84%), characterised by decreased enhancement, showed prolonged time to peak. Areas of consolidation showed increased enhancement. While time to peak of procedure-related atelectasis was not significantly different from that of normal lung, disease-related consolidation showed prolonged time to peak (P=0.01). Lung MRI demonstrates structural and perfusion abnormalities in children and young people with cystic fibrosis. Semi-quantitative assessment of dynamic contrast-enhanced perfusion imaging might allow differentiation between procedure-related atelectasis and disease-related consolidation. (orig.)

  16. Contrast enhanced CT-scans are not comparable to non-enhanced scans in emphysema quantification

    International Nuclear Information System (INIS)

    Heussel, C.P.; Kappes, J.; Hantusch, R.; Hartlieb, S.; Weinheimer, O.; Kauczor, H.-U.; Eberhardt, R.

    2010-01-01

    Systemic, interventional and surgical treatments have gone new ways in treatment of emphysema. For longitudinal therapy monitoring and as end-points for clinical trials, quantification of the disease is necessary. Sensitive, easy to measure, as well as stable and reproducible parameters have to be characterized. One parameter that might affect emphysema quantification is IV contrast enhancement, which might also be indicated. Whether or not the contrast enhanced scan is also suited for emphysema quantification or an additional scan is necessary, a retrospective analysis of 12 adult patients undergoing clinically indicated both, a non-enhanced and enhanced thin section MSCT within a week (median 0 days, range 0-4 days) was done. The in-house YACTA software was used for automatic quantification of lung and emphysema volume, emphysema index, mean lung density, and 5th, 10th, 15th percentile. After IV contrast administration, the median CT derived lung volume decreased mild by 1.1%, while median emphysema volume decreased by relevant 11%. This results in a decrease of median emphysema index by 9%. The median lung density (15th percentile) increased after contrast application by 18 HU (9 HU). CT quantification delivers emphysema values that are clearly affected by IV contrast application. The detected changes after contrast application show the results of higher density in the lung parenchyma. Therefore the amount of quantified emphysema is reduced and the lung density increased after contrast enhancement. In longitudinal analyses, non-enhanced scans should be the reference, while enhanced scans cannot be used.

  17. LungMAP: The Molecular Atlas of Lung Development Program.

    Science.gov (United States)

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

    2017-11-01

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

  18. Lung scintigraphy

    International Nuclear Information System (INIS)

    Dalenz, Roberto.

    1994-01-01

    A review of lung scintigraphy, perfusion scintigraphy with SPECT, lung ventilation SPECT, blood pool SPECT. The procedure of lung perfusion studies, radiopharmaceutical, administration and clinical applications, imaging processing .Results encountered and evaluation criteria after Biello and Pioped. Recommendations and general considerations have been studied about relation of this radiopharmaceutical with other pathologies

  19. Chemotherapy-Induced IL34 Enhances Immunosuppression by Tumor-Associated Macrophages and Mediates Survival of Chemoresistant Lung Cancer Cells.

    Science.gov (United States)

    Baghdadi, Muhammad; Wada, Haruka; Nakanishi, Sayaka; Abe, Hirotake; Han, Nanumi; Putra, Wira Eka; Endo, Daisuke; Watari, Hidemichi; Sakuragi, Noriaki; Hida, Yasuhiro; Kaga, Kichizo; Miyagi, Yohei; Yokose, Tomoyuki; Takano, Atsushi; Daigo, Yataro; Seino, Ken-Ichiro

    2016-10-15

    The ability of tumor cells to escape immune destruction and their acquired resistance to chemotherapy are major obstacles to effective cancer therapy. Although immune checkpoint therapies such as anti-PD-1 address these issues in part, clinical responses remain limited to a subpopulation of patients. In this report, we identified IL34 produced by cancer cells as a driver of chemoresistance. In particular, we found that IL34 modulated the functions of tumor-associated macrophages to enhance local immunosuppression and to promote the survival of chemoresistant cancer cells by activating AKT signaling. Targeting IL34 in chemoresistant tumors resulted in a remarkable inhibition of tumor growth when accompanied with chemotherapy. Our results define a pathogenic role for IL34 in mediating immunosuppression and chemoresistance and identify it as a tractable target for anticancer therapy. Cancer Res; 76(20); 6030-42. ©2016 AACR. ©2016 American Association for Cancer Research.

  20. Mucosal immunization with the Moraxella catarrhalis porin m35 induces enhanced bacterial clearance from the lung: a possible role for opsonophagocytosis

    Directory of Open Access Journals (Sweden)

    Donna eEaston

    2011-05-01

    Full Text Available Moraxella catarrhalis is a significant cause of respiratory tract infection against which a vaccine is sought. Several outer membrane proteins are currently under investigation as potential vaccine antigens, including the porin M35. We have previously shown that the third external loop of M35 was immunodominant over the remainder of the protein for antibody produced in mice against the refolded recombinant protein. However, as this loop is predicted to fold inside the porin channel we also predicted that it would not be accessible to these antibodies when M35 is expressed on the surface of the bacteria in its native conformation. This study investigated the functional activity of antibodies against M35 and those specific for the loop 3 region of M35 in vitro and in vivo. Antisera from mice immunized with M35 or the loop 3-deletion, M35loop3–, recombinant proteins were not bactericidal but did have enhanced opsonic activity, whereas antibodies raised against the loop 3 peptide were not opsonising indicating that the immunodominant loop 3 of M35 was not accessible to antibody as we had previously predicted. Mucosal immunization with M35, M35 that had an antigenically altered loop 3 (M35(ID78 and M35loop3– enhanced the clearance of M. catarrhalis from the lungs of mice challenged with live M. catarrhalis. The in vivo clearance of bacteria in the mice with the M35-derived protein constructs correlated significantly (p<0.001 with the opsonic activity assessed an in vitro opsonophagocytosis assay. This study has demonstrated that the immunodominat B-cell epitope to loop 3 of the M. catarrhalis outer membrane protein M35 is not associated with immune protection and that M35-specific antibodies are not bactericidal but are opsonising. The opsonising activity correlated with in vivo clearance of the bacteria suggesting that opsonising antibody may be a good correlate of immune protection.

  1. Monocrotaline pyrrole-induced megalocytosis of lung and breast epithelial cells: Disruption of plasma membrane and Golgi dynamics and an enhanced unfolded protein response

    International Nuclear Information System (INIS)

    Mukhopadhyay, Somshuvra; Shah, Mehul; Patel, Kirit; Sehgal, Pravin B.

    2006-01-01

    The pyrrolizidine alkaloid monocrotaline (MCT) initiates pulmonary hypertension by inducing a 'megalocytosis' phenotype in target pulmonary arterial endothelial, smooth muscle and Type II alveolar epithelial cells. In cultured endothelial cells, a single exposure to the pyrrolic derivative of monocrotaline (MCTP) results in large cells with enlarged endoplasmic reticulum (ER) and Golgi and increased vacuoles. However, these cells fail to enter mitosis. Largely based upon data from endothelial cells, we proposed earlier that a disruption of the trafficking and mitosis-sensor functions of the Golgi (the 'Golgi blockade' hypothesis) may represent the subcellular mechanism leading to MCTP-induced megalocytosis. In the present study, we investigated the applicability of the Golgi blockade hypothesis to epithelial cells. MCTP induced marked megalocytosis in cultures of lung A549 and breast MCF-7 cells. This was associated with a change in the distribution of the cis-Golgi scaffolding protein GM130 from a discrete juxtanuclear localization to a circumnuclear distribution consistent with an anterograde block of GM130 trafficking to/through the Golgi. There was also a loss of plasma membrane caveolin-1 and E-cadherin, cortical actin together with a circumnuclear accumulation of clathrin heavy chain (CHC) and α-tubulin. Flotation analyses revealed losses/alterations in the association of caveolin-1, E-cadherin and CHC with raft microdomains. Moreover, megalocytosis was accompanied by an enhanced unfolded protein response (UPR) as evidenced by nuclear translocation of Ire1α and glucose regulated protein 58 (GRP58/ER-60/ERp57) and a circumnuclear accumulation of PERK kinase and protein disulfide isomerase (PDI). These data further support the hypothesis that an MCTP-induced Golgi blockade and enhanced UPR may represent the subcellular mechanism leading to enlargement of ER and Golgi and subsequent megalocytosis

  2. The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis

    Science.gov (United States)

    Yates, Laura L.; Schnatwinkel, Carsten; Murdoch, Jennifer N.; Bogani, Debora; Formstone, Caroline J.; Townsend, Stuart; Greenfield, Andy; Niswander, Lee A.; Dean, Charlotte H.

    2010-01-01

    The lungs are generated by branching morphogenesis as a result of reciprocal signalling interactions between the epithelium and mesenchyme during development. Mutations that disrupt formation of either the correct number or shape of epithelial branches affect lung function. This, in turn, can lead to congenital abnormalities such as cystadenomatoid malformations, pulmonary hypertension or lung hypoplasia. Defects in lung architecture are also associated with adult lung disease, particularly in cases of idiopathic lung fibrosis. Identifying the signalling pathways which drive epithelial tube formation will likely shed light on both congenital and adult lung disease. Here we show that mutations in the planar cell polarity (PCP) genes Celsr1 and Vangl2 lead to disrupted lung development and defects in lung architecture. Lungs from Celsr1Crsh and Vangl2Lp mouse mutants are small and misshapen with fewer branches, and by late gestation exhibit thickened interstitial mesenchyme and defective saccular formation. We observe a recapitulation of these branching defects following inhibition of Rho kinase, an important downstream effector of the PCP signalling pathway. Moreover, epithelial integrity is disrupted, cytoskeletal remodelling perturbed and mutant endoderm does not branch normally in response to the chemoattractant FGF10. We further show that Celsr1 and Vangl2 proteins are present in restricted spatial domains within lung epithelium. Our data show that the PCP genes Celsr1 and Vangl2 are required for foetal lung development thereby revealing a novel signalling pathway critical for this process that will enhance our understanding of congenital and adult lung diseases and may in future lead to novel therapeutic strategies. PMID:20223754

  3. Lung density

    DEFF Research Database (Denmark)

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

    1977-01-01

    The density of a defined volume of the human lung can be measured in vivo by a new noninvasive technique. A beam of gamma-rays is directed at the lung and, by measuring the scattered gamma-rays, lung density is calculated. The density in the lower lobe of the right lung in normal man during quiet...... 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...... but the lung density values were more sensitive indices. This was particularly evident in serial observations of individual patients....

  4. What Is Lung Cancer?

    Science.gov (United States)

    ... Shareable Graphics Infographics “African-American Men and Lung Cancer” “Lung Cancer Is the Biggest Cancer Killer in Both ... starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may spread ...

  5. Abscess in the Lungs

    Science.gov (United States)

    ... Home Lung and Airway Disorders Abscess in the Lungs Abscess in the Lungs Causes Symptoms Diagnosis Treatment Resources ... here for the Professional Version Abscess in the Lungs Abscess in the Lungs A lung abscess is a ...

  6. Focal Adhesion Kinase Inhibitors in Combination with Erlotinib Demonstrate Enhanced Anti-Tumor Activity in Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Grant A Howe

    Full Text Available Blockade of epidermal growth factor receptor (EGFR activity has been a primary therapeutic target for non-small cell lung cancers (NSCLC. As patients with wild-type EGFR have demonstrated only modest benefit from EGFR tyrosine kinase inhibitors (TKIs, there is a need for additional therapeutic approaches in patients with wild-type EGFR. As a key component of downstream integrin signalling and known receptor cross-talk with EGFR, we hypothesized that targeting focal adhesion kinase (FAK activity, which has also been shown to correlate with aggressive stage in NSCLC, would lead to enhanced activity of EGFR TKIs. As such, EGFR TKI-resistant NSCLC cells (A549, H1299, H1975 were treated with the EGFR TKI erlotinib and FAK inhibitors (PF-573,228 or PF-562,271 both as single agents and in combination. We determined cell viability, apoptosis and 3-dimensional growth in vitro and assessed tumor growth in vivo. Treatment of EGFR TKI-resistant NSCLC cells with FAK inhibitor alone effectively inhibited cell viability in all cell lines tested; however, its use in combination with the EGFR TKI erlotinib was more effective at reducing cell viability than either treatment alone when tested in both 2- and 3-dimensional assays in vitro, with enhanced benefit seen in A549 cells. This increased efficacy may be due in part to the observed inhibition of Akt phosphorylation when the drugs were used in combination, where again A549 cells demonstrated the most inhibition following treatment with the drug combination. Combining erlotinib with FAK inhibitor was also potent in vivo as evidenced by reduced tumor growth in the A549 mouse xenograft model. We further ascertained that the enhanced sensitivity was irrespective of the LKB1 mutational status. In summary, we demonstrate the effectiveness of combining erlotinib and FAK inhibitors for use in known EGFR wild-type, EGFR TKI resistant cells, with the potential that a subset of cell types, which includes A549, could be

  7. Chemoradiotherapy for lung cancer. Current status and perspectives

    International Nuclear Information System (INIS)

    Ohe, Yuichiro

    2004-01-01

    For many years, thoracic radiotherapy had been regarded as the standard treatment for patients with unresectable locally advanced non-small cell lung cancer. However, meta-analyses show that cisplatin-containing chemoradiotherapy is significantly superior to radiotherapy alone in terms of survival. Moreover, concurrent chemoradiotherapy yields a significantly increased response rate and enhanced survival duration when compared with the sequential approach. Cisplatin-based chemotherapy with concurrent thoracic radiotherapy yields a 5-year survival rate of approximately 15% for patients with unresectable locally advanced non-small cell lung cancer. The state-of-the-art treatment for limited-stage small cell lung cancer is considered to be four cycles of combination chemotherapy with cisplatin plus etoposide combined with early concurrent twice-daily thoracic irradiation (45 Gy). If patients achieve complete remission, prophylactic cranial irradiation should be administered. A 5-year survival rate of approximately 25% is expected with the state-of-the-art treatment for limited-stage small cell lung cancer. Chemoradiotherapy is considered to be a standard treatment for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer. Several new strategies are currently being investigated to improve the survival of these patients. The incorporation of target-based drugs such as gefitinib is considered to be the most promising strategy for unresectable locally advanced non-small cell lung cancer. The incorporation of irinotecan is also a promising strategy to improve the survival of patients with limited-stage small cell lung cancer. The Japan Clinical Oncology Group is conducting clinical trials to develop new treatment strategies for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer. (author)

  8. Progressive massive fibrosis in patients with pneumoconiosis: utility of MRI in differentiating from lung cancer.

    Science.gov (United States)

    Ogihara, Yukihiro; Ashizawa, Kazuto; Hayashi, Hideyuki; Nagayasu, Takeshi; Hayashi, Tomayoshi; Honda, Sumihisa; Uetani, Masataka

    2018-01-01

    Background It is occasionally difficult to distinguish progressive massive fibrosis (PMF) from lung cancer on computed tomography (CT) in patients with pneumoconiosis. Purpose To evaluate the magnetic resonance imaging (MRI) features of PMF and to assess its ability to differentiate PMF from lung cancer. Material and Methods Between 2000 and 2014, 40 pulmonary lesions suspected to be lung cancer on the basis of CT in 28 patients with known pneumoconiosis were evaluated. Twenty-four of the 40 lesions were pathologically or clinically diagnosed as PMF. The signal pattern on T2-weighted (T2W) images, post-contrast enhancement pattern on T1-weighted (T1W) images, and the pattern of the time intensity curve (TIC) on contrast-enhanced dynamic studies were evaluated. All images were analyzed independently by two chest radiologists. Results All 24 PMF lesions showed low signal intensity (SI) on T2W images (sensitivity, 100%), while 15 of 16 lung cancer lesions showed intermediate or high SI on T2W images (specificity, 94%) when PMF was regarded as a positive result. Six of 17 PMF lesions showed a homogeneous enhancement pattern (sensitivity, 35%), and 4/9 lung cancer lesions showed an inhomogeneous or a ring-like enhancement pattern (specificity, 44%). Six of 16 PMF lesions showed a gradually increasing enhancement pattern (sensitivity, 38%), and 7/9 lung cancer lesions showed rapid enhancement pattern (specificity, 78%). Conclusion When differentiation between PMF and lung cancer in patients with pneumoconiosis is difficult on CT, an additional MRI study, particularly the T2W imaging sequence, may help differentiate between the two.

  9. Additional value of FDG-PET to contrast enhanced-computed tomography (CT) for the diagnosis of mediastinal lymph node metastasis in non-small cell lung cancer. A Japanese multicenter clinical study

    International Nuclear Information System (INIS)

    Kubota, Kazuo; Murakami, Koji; Inoue, Tomio; Itoh, Harumi; Saga, Tsuneo; Shiomi, Susumu; Hatazawa, Jun

    2011-01-01

    This study was a controlled multicenter clinical study to verify the diagnostic effects of additional fluorodeoxyglucose-positron emission tomography (FDG-PET) to contrast-enhanced CT for mediastinal lymph node metastasis in patients with operable non-small cell lung cancer (NSCLC). NSCLC patients with enlarged mediastinal lymph nodes (short diameter, 7-20 mm), confirmed using contrast-enhanced CT, were examined using FDG-PET to detect metastases prior to surgery. The primary endpoint was the accuracy for concomitantly used CT and FDG-PET showing the additional effects of FDG, compared with CT alone. The secondary endpoints were the clinical impact of FDG-PET on therapeutic decisions and adverse reaction from FDG administration. The images were interpreted by investigators at each institution. Moreover, blinded readings were performed by an image interpretation committee independent of the institutions. The gold standard was the pathological diagnosis determined by surgery or biopsy after PET, and patients in whom a pathological diagnosis was not obtained were excluded from the analysis. Among 99 subjects, the results for 81 subjects eligible for analysis showed that the accuracy improved from 69.1% (56/81) for CT alone to 75.3% (61/81) for CT + PET (p=0.404). These findings contributed to treatment decisions in 63.0% (51/81) of the cases, mainly with regard to the selection of the operative procedure. The results of the image interpretation committee showed that the accuracy improved from 64.2% (52/81) (95% confidence interval (CI) 52.8-74.6) for CT to 75.3% (61/81) (95% CI 64.5-84.2) for CT + PET. The accuracy for 106 mediastinal lymph nodes improved significantly from 62.3% (66/106) (95% CI 52.3-71.5) for CT to 79.2% (84/106) (95% CI 70.3-86.5) for CT + PET (p<0.05). We found that no serious adverse drug reactions appeared in any of the 99 patients who received FDG, except for transient mild outliers in the laboratory data for two patients. The addition of FDG

  10. Enhanced expression in vivo of HLA-ABC antigens and beta 2-microglobulin on human lymphoid cells induced by human interferon-alpha in patients with lung cancer. Enhanced expression of class I major histocompatibility antigens prior to treatment

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Plesner, T; Larsen, J K

    1985-01-01

    than 0.5, respectively) by day-to-day analysis of an untreated healthy control group. An increased expression of both HLA-ABC (mean 55%, P less than 0.0005) and beta 2m (mean 23%, P less than 0.01) was also observed prior to treatment in the lung cancer patients when compared to a group of age matched......The effect of cloned human interferon-alpha (IFN-alpha) on the expression of HLA-ABC antigens (HLA-ABC) and beta 2-microglobulin (beta 2m) on human peripheral lymphoid cells in vivo was studied by cytofluorometry using monoclonal antibodies and fluorescein-labelled rabbit anti-mouse immunoglobulin....... A significant increase in the mean fluorescence intensity of HLA-ABC (median 59%, P less than 0.001) and beta 2m (median 57%, P less than 0.001) on small lymphoid cells was observed 24 h after initiation of IFN-alpha treatment (50 X 10(6) units IFN-alpha/m2 three times a week). The enhanced expression...

  11. Lung cancer

    International Nuclear Information System (INIS)

    Kato, Toshio

    1982-01-01

    Based on the own experience and world literatures, contribution of radiation in the treatment of lung cancer was reviewed and discussed. Although the patients with advanced cancer were referred to radiation usually, the results of radiotherapy were superior to those by chemotherapy. Of course the radiotherapy was a local one, radiation combined with chemotherapy was highly recommended, besides systemic administration of chemotherapeutics, special methods such as bronchial arterial infusion (BAI) and chemoembolization would be more favourable in selected patients. Treatment of undifferentiated small cell carcinoma was becoming more dependent on chemotherapy, radiation showed as excellent local control as ever. To treat locally extended cancer patients with involvement of the thoracic wall and Pancoast's syndrome, external radiation alone were not successful, interstitial radiation or a single exposure with a large dose during the thoracotomy would be promising. Finally, data indicated that aged and poor risk patients in early stage of cancer might be treated by radiation instead of unjustifiable operation. (author)

  12. Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Chiu, Hsien-Chun; Syu, Jhan-Jhang; Jian, Yi-Jun; Chen, Chien-Yu; Jian, Yun-Ting; Huang, Yi-Jhen; Wo, Ting-Yu; Lin, Yun-Wei

    2014-03-01

    Tamoxifen is a triphenylethylene nonsteroidal estrogen receptor (ER) antagonist used worldwide as an adjuvant hormone therapeutic agent in the treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Thymidine phosphorylase (TP) is an enzyme of the pyrimidine salvage pathway which is upregulated in cancers. In this study, tamoxifen treatment inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with tamoxifen decreased TP mRNA and protein levels through AKT inactivation. Furthermore, expression of constitutively active AKT (AKT-CA) vectors significantly rescued the decreased TP protein and mRNA levels in tamoxifen-treated NSCLC cells. In contrast, combination treatment with PI3K inhibitors (LY294002 or wortmannin) and tamoxifen further decreased the TP expression and cell viability of NSCLC cells. Knocking down TP expression by transfection with small interfering RNA of TP enhanced the cytotoxicity and cell growth inhibition of tamoxifen. Erlotinib (Tarceva, OSI-774), an orally available small molecular inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is approved for clinical treatment of NSCLC. Compared to a single agent alone, tamoxifen combined with erlotinib resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-AKT and phospho-ERK1/2, and reduced TP protein levels. These findings may have implications for the rational design of future drug regimens incorporating tamoxifen and erlotinib for the treatment of NSCLC. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Minocycline enhances mitomycin C-induced cytotoxicity through down-regulating ERK1/2-mediated Rad51 expression in human non-small cell lung cancer cells.

    Science.gov (United States)

    Ko, Jen-Chung; Wang, Tai-Jing; Chang, Po-Yuan; Syu, Jhan-Jhang; Chen, Jyh-Cheng; Chen, Chien-Yu; Jian, Yun-Ting; Jian, Yi-Jun; Zheng, Hao-Yu; Chen, Wen-Ching; Lin, Yun-Wei

    2015-10-01

    Minocycline is a semisynthetic tetracycline derivative; it has anti-inflammatory and anti-cancer effects distinct from its antimicrobial function. However, the molecular mechanism of minocycline-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. Our previous studies have shown that the MKK1/2-ERK1/2 signal pathway maintains the expression of Rad51 in NSCLC cells. In this study, minocycline treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1975. Treatment with minocycline decreased Rad51 mRNA and protein levels through MKK1/2-ERK1/2 inactivation. Furthermore, expression of constitutively active MKK1 (MKK1-CA) vectors significantly rescued the decreased Rad51 protein and mRNA levels in minocycline-treated NSCLC cells. However, combined treatment with MKK1/2 inhibitor U0126 and minocycline further decreased the Rad51 expression and cell viability of NSCLC cells. Knocking down Rad51 expression by transfection with small interfering RNA of Rad51 enhanced the cytotoxicity and cell growth inhibition of minocycline. Mitomycin C (MMC) is typically used as a first or second line regimen to treat NSCLC. Compared to a single agent alone, MMC combined with minocycline resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-ERK1/2, and reduced Rad51 protein levels. Overexpression of MKK1-CA or Flag-tagged Rad51 could reverse the minocycline and MMC-induced synergistic cytotoxicity. These findings may have implications for the rational design of future drug regimens incorporating minocycline and MMC for the treatment of NSCLC. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Lung Cancer

    International Nuclear Information System (INIS)

    Maghfoor, Irfan; Perry, M.C.

    2005-01-01

    Lung cancer is the leading cause of cancer-related mortality. Since tobacco smoking is the cause in vast majority of cases, the incidence of lung cancer is expected to rise in those countries with high or rising incidence of tobacco smoking. Even though population at a risk of developing lung cancer are easily identified, mass screening for lung cancer is not supported by currently available evidence. In case of non-small cell lung cancer, a cure may be possible with surgical resection followed by post-operative chemotherapy in those diagnosed at an early stage. A small minority of patients who present with locally advanced disease may also benefit from preoperative chemotherapy and/or radiation therapy to down stage the tumor to render it potentially operable. In a vast majority of patients, however, lung cancer presents at an advanced stage and a cure is not possible with currently available therapeutic strategies. Similarly small cell lung cancer confined to one hemi-thorax may be curable with a combination of chemotherapy and thoracic irradiation followed by prophylactic cranial irradiation, if complete remission is achieved at the primary site. Small cell lung cancer that is spread beyond the confines of one hemi-thorax is however, considered incurable. In this era of molecular targeted therapies, new agents are constantly undergoing pre-clinical and clinical testing with the aim of targeting the molecular pathways thought to involved in etiology and pathogenesis of lung cancer. (author)

  15. Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b{sup +} myeloid cells to the lungs and facilitates B16-F10 melanoma colonization

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Lucas E.B., E-mail: lucasebsouza@usp.br [Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Almeida, Danilo C., E-mail: gudaalmeida@gmail.com [Department of Medicine – Nephrology, Laboratory of Clinical and Experimental Immunology, Federal University of São Paulo, São Paulo, SP (Brazil); Yaochite, Juliana N.U., E-mail: ueda.juliana@gmail.com [Department of Biochemistry and Immunology, Basic and Applied Immunology Program, School of Medicine of Ribeirão Preto, University of São Paulo (Brazil); Covas, Dimas T., E-mail: dimas@fmrp.usp.br [Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Fontes, Aparecida M., E-mail: aparecidamfontes@usp.br [Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

    2016-07-15

    The discovery that the regenerative properties of bone marrow multipotent mesenchymal stromal cells (BM-MSCs) could collaterally favor neoplastic progression has led to a great interest in the function of these cells in tumors. However, the effect of BM-MSCs on colonization, a rate-limiting step of the metastatic cascade, is unknown. In this study, we investigated the effect of BM-MSCs on metastatic outgrowth of B16-F10 melanoma cells. In in vitro experiments, direct co-culture assays demonstrated that BM-MSCs stimulated the proliferation of B16-F10 cells in a dose-dependent manner. For in vivo experiments, luciferase-expressing B16-F10 cells were injected through tail vein and mice were subsequently treated with four systemic injections of BM-MSCs. In vivo bioluminescent imaging during 16 days demonstrated that BM-MSCs enhanced the colonization of lungs by B16-F10 cells, which correlated with a 2-fold increase in the number of metastatic foci. Flow cytometry analysis of lungs demonstrated that although mice harboring B16-F10 metastases displayed more endothelial cells, CD4 T and CD8 T lymphocytes in the lungs in comparison to metastases-free mice, BM-MSCs did not alter the number of these cells. Interestingly, BM-MSCs inoculation resulted in a 2-fold increase in the number of CD11b{sup +} myeloid cells in the lungs of melanoma-bearing animals, a cell population previously described to organize “premetastatic niches” in experimental models. These findings indicate that BM-MSCs provide support to B16-F10 cells to overcome the constraints that limit metastatic outgrowth and that these effects might involve the interplay between BM-MSCs, CD11b{sup +} myeloid cells and tumor cells. - Highlights: • BM-MSCs enhanced B16-F10 proliferation in a dose-dependent manner in vitro. • BM-MSCs facilitated lung colonization by B16-F10 melanoma cells. • BM-MSCs administration did not alter the number of endothelial cells and T lymphocytes in the lungs. • BM-MSCs enhanced

  16. 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 ...

  17. MRI features of meningeal metastasis from lung cancer

    International Nuclear Information System (INIS)

    Luo Xuemao; Long Wansheng; Jin Zhifa; Hu Maoqing; Mai Xuyu

    2009-01-01

    Objective: To investigate the pathway and MRI findings of meningeal metastasis original from lung cancer. Methods: 44 cases with cerebro-spinal meningeal metastasis original from lung cancer proven by clinical and pathology were retrospectively reviewed. All cases undergone plain MRI scan and Gd-DTPA enhanced MRI scan on brain and/or spine. Results: MRI plain scan indicated 28 cases with brain metastases, 3 cases with meningeal nodosity or irregularly patchy abnormal signal, 1 case with nodule in left cavernous sinus, 10 cases with abnormal signal in spine, 2 cases with abnormal signal in spinal dura mater. 34 cases with cerebro meningeal metastases were found in MRI enhancement scan. Among them, 11 cases displayed cerebral dura mater-arachnoid enhancement, 17 cases revealed cerebral pia mater-arachnoid enhancement and 6 cases with mixed typed enhancement. Osteoclasia in skull was found in 4 cases, spinal metastasis was revealed in 17 cases, and patchy abnormal enhancement in spinal dura mater was showed in 12 cases. Conclusion: Hematogenous metastasis is a main route of meningeal metastasis caused by lung cancer and enhanced MRI scan is of important diagnostic value. (authors)

  18. Lung Cancer Screening

    Science.gov (United States)

    ... factors increase or decrease the risk of lung cancer. Lung cancer is a disease in which malignant (cancer) ... following PDQ summaries for more information about lung cancer: Lung Cancer Prevention Non-Small Cell Lung Cancer Treatment ...

  19. Diffuse cavitary lung lesions

    Energy Technology Data Exchange (ETDEWEB)

    Grunzke, Mindy; Garrington, Timothy [University of Colorado Denver, Department of Pediatrics, Aurora, CO (United States); The Children' s Hospital, Rick Wilson Center for Cancer and Blood Disorders, Aurora, CO (United States); Hayes, Kari [The Children' s Hospital, Pediatric Radiology, Aurora, CO (United States); Bourland, Wendy [Children' s Hospital at St. Francis, Warren Clinic, Inc., Tulsa, OK (United States)

    2010-02-15

    An 11-year-old girl presented with a 2-month history of progressively worsening cough, daily fevers, and weight loss. A chest radiograph revealed multiple cystic cavitary lung lesions. An extensive infectious work-up was negative. Chest CT verified multiple cavitary lung lesions bilaterally, and [F-18]2-fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) positron emission tomography with CT (PET/CT) showed increased uptake in the lung lesions as well as regional lymph nodes. Subsequent biopsy of an involved lymph node confirmed classical Hodgkin lymphoma, nodular sclerosis type. This case represents an unusual presentation for a child with Hodgkin lymphoma and demonstrates a role for {sup 18}F-FDG PET/CT in evaluating a child with cavitary lung lesions. (orig.)

  20. Diffuse cavitary lung lesions

    International Nuclear Information System (INIS)

    Grunzke, Mindy; Garrington, Timothy; Hayes, Kari; Bourland, Wendy

    2010-01-01

    An 11-year-old girl presented with a 2-month history of progressively worsening cough, daily fevers, and weight loss. A chest radiograph revealed multiple cystic cavitary lung lesions. An extensive infectious work-up was negative. Chest CT verified multiple cavitary lung lesions bilaterally, and [F-18]2-fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography with CT (PET/CT) showed increased uptake in the lung lesions as well as regional lymph nodes. Subsequent biopsy of an involved lymph node confirmed classical Hodgkin lymphoma, nodular sclerosis type. This case represents an unusual presentation for a child with Hodgkin lymphoma and demonstrates a role for 18 F-FDG PET/CT in evaluating a child with cavitary lung lesions. (orig.)

  1. Physiological Interaction of Heart and Lung in Thoracic Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ghobadi, Ghazaleh; Veen, Sonja van der [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Bartelds, Beatrijs [Center for Congenital Heart Disease, Beatrix Children Hospital, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Boer, Rudolf A. de [Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Dickinson, Michael G. [Center for Congenital Heart Disease, Beatrix Children Hospital, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Jong, Johan R. de [Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Faber, Hette; Niemantsverdriet, Maarten [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Brandenburg, Sytze [Kernfysisch Versneller Instituut, University of Groningen, Groningen (Netherlands); Berger, Rolf M.F. [Center for Congenital Heart Disease, Beatrix Children Hospital, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Coppes, Robert P. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Luijk, Peter van, E-mail: p.van.luijk@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

    2012-12-01

    Introduction: The risk of early radiation-induced lung toxicity (RILT) limits the dose and efficacy of radiation therapy of thoracic tumors. In addition to lung dose, coirradiation of the heart is a known risk factor in the development RILT. The aim of this study was to identify the underlying physiology of the interaction between lung and heart in thoracic irradiation. Methods and Materials: Rat hearts, lungs, or both were irradiated to 20 Gy using high-precision proton beams. Cardiopulmonary performance was assessed using breathing rate measurements and F{sup 18}-fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG-PET) scans biweekly and left- and right-sided cardiac hemodynamic measurements and histopathology analysis at 8 weeks postirradiation. Results: Two to 12 weeks after heart irradiation, a pronounced defect in the uptake of {sup 18}F-FDG in the left ventricle (LV) was observed. At 8 weeks postirradiation, this coincided with LV perivascular fibrosis, an increase in LV end-diastolic pressure, and pulmonary edema in the shielded lungs. Lung irradiation alone not only increased pulmonary artery pressure and perivascular edema but also induced an increased LV relaxation time. Combined irradiation of lung and heart induced pronounced increases in LV end-diastolic pressure and relaxation time, in addition to an increase in right ventricle end-diastolic pressure, indicative of biventricular diastolic dysfunction. Moreover, enhanced pulmonary edema, inflammation and fibrosis were also observed. Conclusions: Both lung and heart irradiation cause cardiac and pulmonary toxicity via different mechanisms. Thus, when combined, the loss of cardiopulmonary performance is intensified further, explaining the deleterious effects of heart and lung coirradiation. Our findings show for the first time the physiological mechanism underlying the development of a multiorgan complication, RILT. Reduction of dose to either of these organs offers new opportunities to

  2. WCK 5107 (Zidebactam) and WCK 5153 Are Novel Inhibitors of PBP2 Showing Potent "β-Lactam Enhancer" Activity against Pseudomonas aeruginosa, Including Multidrug-Resistant Metallo-β-Lactamase-Producing High-Risk Clones.

    Science.gov (United States)

    Moya, Bartolome; Barcelo, Isabel M; Bhagwat, Sachin; Patel, Mahesh; Bou, German; Papp-Wallace, Krisztina M; Bonomo, Robert A; Oliver, Antonio

    2017-06-01

    Zidebactam and WCK 5153 are novel β-lactam enhancers that are bicyclo-acyl hydrazides (BCH), derivatives of the diazabicyclooctane (DBO) scaffold, targeted for the treatment of serious infections caused by highly drug-resistant Gram-negative pathogens. In this study, we determined the penicillin-binding protein (PBP) inhibition profiles and the antimicrobial activities of zidebactam and WCK 5153 against Pseudomonas aeruginosa , including multidrug-resistant (MDR) metallo-β-lactamase (MBL)-producing high-risk clones. MIC determinations and time-kill assays were conducted for zidebactam, WCK 5153, and antipseudomonal β-lactams using wild-type PAO1, MexAB-OprM-hyperproducing ( mexR ), porin-deficient ( oprD ), and AmpC-hyperproducing ( dacB ) derivatives of PAO1, and MBL-expressing clinical strains ST175 ( bla VIM-2 ) and ST111 ( bla VIM-1 ). Furthermore, steady-state kinetics was used to assess the inhibitory potential of these compounds against the purified VIM-2 MBL. Zidebactam and WCK 5153 showed specific PBP2 inhibition and did not inhibit VIM-2 (apparent K i [ K i app ] > 100 μM). MICs for zidebactam and WCK 5153 ranged from 2 to 32 μg/ml (amdinocillin MICs > 32 μg/ml). Time-kill assays revealed bactericidal activity of zidebactam and WCK 5153. LIVE-DEAD staining further supported the bactericidal activity of both compounds, showing spheroplast formation. Fixed concentrations (4 or 8 μg/ml) of zidebactam and WCK 5153 restored susceptibility to all of the tested β-lactams for each of the P. aeruginosa mutant strains. Likewise, antipseudomonal β-lactams (CLSI breakpoints), in combination with 4 or 8 μg/ml of zidebactam or WCK 5153, resulted in enhanced killing. Certain combinations determined full bacterial eradication, even with MDR MBL-producing high-risk clones. β-Lactam-WCK enhancer combinations represent a promising β-lactam "enhancer-based" approach to treat MDR P. aeruginosa infections, bypassing the need for MBL inhibition. Copyright © 2017

  3. Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

    International Nuclear Information System (INIS)

    Yang, Heekyoung; Yoon, Su Jin; Jin, Juyoun; Choi, Seung Ho; Seol, Ho Jun; Lee, Jung-Il

    2011-01-01

    Research highlights: → The most important therapeutic tool in brain metastasis is radiation therapy. → Radiosensitivity of cancer cells was enhanced with treatment of Chk1 inhibitor. → Depletion of Chk1 in cancer cells showed an enhancement of sensitivity to radiation. → Chk1 can be a good target for enhancement of radiosensitivity. -- Abstract: The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity.

  4. Pulmonary Perfusion Changes as Assessed by Contrast-Enhanced Dual-Energy Computed Tomography after Endoscopic Lung Volume Reduction by Coils.

    Science.gov (United States)

    Lador, Frédéric; Hachulla, Anne-Lise; Hohn, Olivia; Plojoux, Jérôme; Ronot, Maxime; Montet, Xavier; Soccal, Paola M

    2016-01-01

    Endoscopic lung volume reduction by coils (LVRC) is a recent treatment approach for severe emphysema. Furthermore, dual-energy computed tomography (DECT) now offers a combined assessment of lung morphology and pulmonary perfusion. The aim of our study was to assess the impact of LVRC on pulmonary perfusion with DECT. Seventeen patients (64.8 ± 6.7 years) underwent LVRC. DECT was performed prior to and after LVRC. For each patient, lung volumes and emphysema quantification were automatically calculated. Then, 6 regions of interest (ROIs) on the iodine perfusion map were drawn in the anterior, mid, and posterior right and left lungs at 4 defined levels. The ROI values were averaged to obtain lung perfusion as assessed by the lung's iodine concentration (CLung, μg·cm-3). The CLung values were normalized using the left atrial iodine concentration (CLA) to take into account differences between successive DECT scans. The 6-min walk distance (6MWD) improved significantly after the procedure (p = 0.0002). No lung volume changes were observed between successive DECT scans for any of the patients (p = 0.32), attesting the same suspended inspiration. After LVRC, the emphysema index was significantly reduced in the treated lung (p = 0.0014). Lung perfusion increased significantly adjacent to the treated areas (CLung/CLA from 3.4 ± 1.7 to 5.6 ± 2.2, p < 0.001) and in the ipsilateral untreated areas (from 4.1 ± 1.4 to 6.6 ± 1.7, p < 0.001), corresponding to a mean 65 and 61% increase in perfusion, respectively. No significant difference was observed in the contralateral upper and lower areas (from 4.4 ± 1.9 to 4.8 ± 2.1, p = 0.273, and from 4.9 ± 2.0 to 5.2 ± 1.7, p = 0.412, respectively). A significant correlation between increased 6MWD and increased perfusion was found (p = 0.0027, R2 = 0.3850). Quantitative analysis based on DECT acquisition revealed that LVRC results in a significant increase in perfusion in the coil-free areas adjacent to the treated ones, as

  5. LncRNA MEG3 enhances cisplatin sensitivity in non-small cell lung cancer by regulating miR-21-5p/SOX7 axis

    Directory of Open Access Journals (Sweden)

    Wang P

    2017-10-01

    Full Text Available Pei Wang,* Dong Chen,* Hongbing Ma, Yong LiDepartment of Cardiothoracic Surgery, Huaihe Hospital of Henan University, Kaifeng, People’s Republic of China *These authors contributed equally to this work Background: Long noncoding RNAs (lncRNAs have been revealed to play essential role in drug resistance of multiple cancers. LncRNA MEG3 was previously reported to be associated with cisplatin (DDP resistance in non-small cell lung cancer (NSCLC cells. However, the molecular mechanism of MEG3 affecting DDP resistance in NSCLC remains to be further illustrated. In this study, we attempted to discuss whether MEG3 also could function as a competing endogenous RNA to regulate DDP resistance in NSCLC.Materials and methods: The expression of MEG3, miR-21-5p, and sex-determining region Y-box 7 (SOX7 in NSCLC tissues or cells was examined by quantitative real-time polymerase chain reaction (qRT-PCR. 3-(4,5-Dimethylthazol-2-yl-2,5-diphenyltetrazolium bromide (MTT, flow cytometry, and caspase-3 activity analysis were applied to assess the DDP sensitivity of NSCLC cells. The interaction between MEG3, miR-21-5p, and SOX7 was explored by luciferase reporter assay, RNA immunoprecipitation (RIP assay, qRT-PCR, and Western blot. Mouse NSCLC transplanted tumor was established to verify the functional role of MEG3 in DDP resistance in vivo.Results: MEG3 was downregulated in DDP-resistant NSCLC cells. Overexpression of MEG3 enhanced DDP sensitivity of NSCLC cells in vitro. MEG3 directly interacted with miR-21-5p and suppressed its expression. miR-21-5p significantly abolished the effects of MEG3 on DDP resistance via modulating cell proliferation and apoptosis. SOX7 was identified as a direct target of miR-21-5p and MEG3 positively regulated SOX7 expression by suppressing miR-21-5p. Moreover, MEG3 knockdown-induced pro-proliferative and anti-apoptotic effects were reversed in DDP-resistant NSCLC cells by upregulating SOX7. Furthermore, upregulation of MEG3 induced

  6. Predicting tumor hypoxia in non-small cell lung cancer by combining CT, FDG PET and dynamic contrast-enhanced CT.

    Science.gov (United States)

    Even, Aniek J G; Reymen, Bart; La Fontaine, Matthew D; Das, Marco; Jochems, Arthur; Mottaghy, Felix M; Belderbos, José S A; De Ruysscher, Dirk; Lambin, Philippe; van Elmpt, Wouter

    2017-11-01

    Most solid tumors contain inadequately oxygenated (i.e., hypoxic) regions, which tend to be more aggressive and treatment resistant. Hypoxia PET allows visualization of hypoxia and may enable treatment adaptation. However, hypoxia PET imaging is expensive, time-consuming and not widely available. We aimed to predict hypoxia levels in non-small cell lung cancer (NSCLC) using more easily available imaging modalities: FDG-PET/CT and dynamic contrast-enhanced CT (DCE-CT). For 34 NSCLC patients, included in two clinical trials, hypoxia HX4-PET/CT, planning FDG-PET/CT and DCE-CT scans were acquired before radiotherapy. Scans were non-rigidly registered to the planning CT. Tumor blood flow (BF) and blood volume (BV) were calculated by kinetic analysis of DCE-CT images. Within the gross tumor volume, independent clusters, i.e., supervoxels, were created based on FDG-PET/CT. For each supervoxel, tumor-to-background ratios (TBR) were calculated (median SUV/aorta SUV mean ) for HX4-PET/CT and supervoxel features (median, SD, entropy) for the other modalities. Two random forest models (cross-validated: 10 folds, five repeats) were trained to predict the hypoxia TBR; one based on CT, FDG, BF and BV, and one with only CT and FDG features. Patients were split in a training (trial NCT01024829) and independent test set (trial NCT01210378). For each patient, predicted, and observed hypoxic volumes (HV) (TBR > 1.2) were compared. Fifteen patients (3291 supervoxels) were used for training and 19 patients (1502 supervoxels) for testing. The model with all features (RMSE training: 0.19 ± 0.01, test: 0.27) outperformed the model with only CT and FDG-PET features (RMSE training: 0.20 ± 0.01, test: 0.29). All tumors of the test set were correctly classified as normoxic or hypoxic (HV > 1 cm 3 ) by the best performing model. We created a data-driven methodology to predict hypoxia levels and hypoxia spatial patterns using CT, FDG-PET and DCE-CT features in NSCLC. The

  7. Nanodiamonds-mediated doxorubicin nuclear delivery to inhibit lung metastasis of breast cancer.

    Science.gov (United States)

    Xiao, Jisheng; Duan, Xiaopin; Yin, Qi; Zhang, Zhiwen; Yu, Haijun; Li, Yaping

    2013-12-01

    Lung metastasis is one of the greatest challenges for breast cancer treatment. Here, a nanodiamonds (NDs)-mediated doxorubicin (DOX) delivery system was first designed to inhibit the lung metastasis of breast cancer effectively. DOX was non-covalently bound to NDs via physical adsorption in an aqueous solution, then DSPE-PEG 2K was coated to the NDs-DOX complex (NDX) to increase the dispersibility and prolong the circulation time. DSPE-PEG 2K coating NDX (DNX) displayed high drug loading and excellent ability to deliver DOX to the nucleus, thereby significantly enhancing cytotoxicity and inducing cell apoptosis. Furthermore, DNX showed good histocompatibility and could improve drug accumulation in lung, as a result, markedly inhibited the lung metastasis of breast cancer. The high anti-metastasis efficacy with the decreased systemic toxicity suggested that DNX could be a promising drug delivery system for the therapy of lung metastasis of breast cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice.

    Science.gov (United States)

    Hwang, S-K; Jin, H; Kwon, J T; Chang, S-H; Kim, T H; Cho, C-S; Lee, K H; Young, M R; Colburn, N H; Beck, G R; Yang, H-S; Cho, M-H

    2007-09-01

    The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the re-emergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor in the future.

  9. The contribution of DNA apurinic/apyrimidinic endonuclease genotype and smoking habit to Taiwan lung cancer risk.

    Science.gov (United States)

    Chen, Wei-Chun; Tsai, Chia-Wen; Hsia, Te-Chun; Chang, Wen-Shin; Lin, Liang-Yi; Liang, Shinn-Jye; Tu, Chih-Yen; Cheng, Wei-Erh; Chen, Hung-Jen; Wang, Shu-Ming; Bau, da-Tian

    2013-06-01

    To evaluate the association and interaction of genotypic polymorphism the gene for DNA-apurinic/apyrimidinic endonuclease (APEX1) with personal smoking habit and lung cancer risk in Taiwan, the polymorphic variants of APEX1, Asp(148)Glu (rs1130409), were analyzed in association with lung cancer risk, and their joint effect with personal smoking habits on lung cancer susceptibility was discussed. In this hospital-based case-control study, 358 patients with lung cancer and 716 cancer-free controls, frequency-matched by age and sex, were recruited and genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The results showed that the percentages of TT, TG and GG APEX1 Asp(148)Glu genotypes were not significantly different at 43.0%, 41.1% and 15.9% in the lung cancer patient group and 39.9%, 46.1% and 14.0% in non-cancer control group, respectively. We further analyzed the genetic-lifestyle effects on lung cancer risk and found the contribution of APEX1 Asp(148)Glu genotypes to lung cancer susceptibility was neither enhanced in the cigarette smokers nor in the non-smokers (p=0.3550 and 0.8019, respectively). Our results provide evidence that the non-synonymous polymorphism of APEX1 Asp(148)Glu may not be directly associated with lung cancer risk, nor enhance the effects of smoking habit on lung cancer development.

  10. Lung abscess

    International Nuclear Information System (INIS)

    Ha, H.K.; Kang, M.W.; Park, J.M.; Yang, W.J.; Shinn, K.S.; Bahk, Y.W.

    1993-01-01

    Lung abscess was successfully treated with percutaneous drainage in 5 of 6 patients. Complete abscess resolution occurred in 4 patients, partial resolution in one, and no response in one. The duration of drainage ranged from 7 to 18 days (mean 15.5 days) in successful cases. The failure of drainage in one neurologicall impaired patient was attributed to persistent aspiration. In 2 patients, concurrent pleural empyema was also cured. CT provided the anatomic details necessary for choosing the puncture site and avoiding puncture of the lung parenchyma. Percutaneous catheter drainage is a safe and effective method for treating lung abscess. (orig.)

  11. Curcumin enhances the mitomycin C-induced cytotoxicity via downregulation of MKK1/2-ERK1/2-mediated Rad51 expression in non-small cell lung cancer cells

    International Nuclear Information System (INIS)

    Ko, Jen-Chung; Tsai, Min-Shao; Weng, Shao-Hsing; Kuo, Ya-Hsun; Chiu, Yu-Fan; Lin, Yun-Wei

    2011-01-01

    Curcumin (diferuloylmethane), a major active component of turmeric (Curcuma longa), has been reported to suppress the proliferation of a wide variety of tumor cells. Rad51 is a key protein in the homologous recombination (HR) pathway of DNA double-strand break repair, and HR represents a novel target for cancer therapy. A high expression of Rad51 has been reported in chemo- or radio-resistant carcinomas. Therefore, in the current study, we will examine whether curcumin could enhance the effects of mitomycin C (MMC), a DNA interstrand cross-linking agent, to induce cytotoxicity by decreasing Rad51 expression. Exposure of two human non-small lung cancer (NSCLC) cell lines (A549 and H1975) to curcumin could suppress MMC-induced MKK1/2-ERK1/2 signal activation and Rad51 protein expression. Enhancement of ERK1/2 activation by constitutively active MKK1/2 (MKK1/2-CA) increased Rad51 protein levels in curcumin and MMC co-treated human lung cells. Moreover, the synergistic cytotoxic effect induced by curcumin combined with MMC was decreased by MKK1-CA-mediated enhancement of ERK1/2 activation by a significant degree. In contrast, MKK1/2 inhibitor, U0126 was shown to augment the cytotoxicity of curcumin and MMC through downregulation of ERK1/2 activation and Rad51 expression. Depletion of endogenous Rad51 expression by siRad51 RNA transfection significantly enhanced MMC and/or curcumin induced cell death and cell growth inhibition. In contrast, an overexpression of Rad51 protected lung cancer cells from synergistic cytotoxic effects induced by curcumin and MMC. We concluded that Rad51 inhibition may be an additional action mechanism for enhancing the chemosensitization of MMC by curcumin in NSCLC. - Highlights: → Curcumin downregulates MKK-ERK-mediated Rad51 expression. → Curcumin enhances mitomycin C-induced cytotoxicity. → Rad51 protects cells from cytotoxic effects induced by curcumin and mitomycin C. → Rad51 inhibition enhances the chemosensitization of

  12. CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway

    Directory of Open Access Journals (Sweden)

    Ruijie Zhang

    2017-09-01

    Full Text Available Background/Aims: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1 is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. Methods: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression by using real-time time PCR and Western blotting. Other methods, including CNTN-1 overexpression in A549 cells and CNTN-1 knockdown in A549/DDP cells, were also used to investigate the role of CNTN-1 in mediating the EMT phenotype and thr resulting cisplatin resistance and malignant progression of cancer cells in vitro and in vivo. Results: A549/DDP cells exhibited an EMT phenotype and aggravated malignant behaviors. CNTN-1 knockdown in A549/DDP cells partly reversed the EMT phenotype, increased drug sensitivity, and attenuated the malignant progression whereas CNTN-1 overexpression in A549 cells resulted in the opposite trend. Furthermore, the PI3K/Akt pathway was involved in the effects of CNTN-1 on EMT progression in A549/DDP cells, verified by the xenograft mouse model. Conclusion: CNTN-1 promotes cisplatin resistance in human cisplatin-resistant lung adenocarcinoma through inducing the EMT process by activating the PI3K/Akt signaling pathway. CNTN-1 may be a potential therapeutic target to reverse chemoresistance in cisplatin-resistant lung adenocarcinoma.

  13. Lung cancer

    Science.gov (United States)

    ... causing chemicals such as uranium, beryllium, vinyl chloride, nickel chromates, coal products, mustard gas, chloromethyl ethers, gasoline, and diesel exhaust Exposure to radon gas Family history of lung cancer ...

  14. Lung surgery

    Science.gov (United States)

    ... are thoracotomy and video-assisted thoracoscopic surgery (VATS). Robotic surgery may also be used. Lung surgery using ... Center-Shreveport, Shreveport, LA. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, ...

  15. Pseudo tumors of the lung after lung volume reduction surgery.

    Science.gov (United States)

    Oey, Inger F; Jeyapalan, Kanagaratnam; Entwisle, James J; Waller, David A

    2004-03-01

    We describe 2 patients who underwent lung volume reduction surgery, who postoperatively had computed tomographic scans that showed symptomatic mass lesions suggestive of malignancy and an inhaled foreign body. Investigations excluded these conditions with the remaining likely diagnosis of pseudotumor secondary to buttressing material. These potential sequelae of lung volume reduction surgery should be recognized in follow-up investigations.

  16. Unexpandable lung.

    Science.gov (United States)

    Pereyra, Marco F; Ferreiro, Lucía; Valdés, Luis

    2013-02-01

    Unexpandable lung is a mechanical complication by which the lung does not expand to the chest wall, impeding a normal apposition between the two pleural layers. The main mechanism involved is the restriction of the visceral pleura due to the formation of a fibrous layer along this pleural membrane. This happens because of the presence of an active pleural disease (lung entrapment), which can be resolved if proper therapeutic measures are taken, or a remote disease (trapped lung), in which an irreversible fibrous pleural layer has been formed. The clinical suspicion arises with the presence of post-thoracocentesis hydropneumothorax or a pleural effusion that cannot be drained due to the appearance of thoracic pain. The diagnosis is based on the analysis of the pleural liquid, the determination of pleural pressures as we drain the effusion and on air-contrast chest CT. As both represent the continuity of one same process, the results will depend on the time at which these procedures are done. If, when given a lung that is becoming entrapped, the necessary therapeutic measures are not taken, the final result will be a trapped lung. In this instance, most patients are asymptomatic or have mild exertional dyspnea and therefore they do not require treatment. Nevertheless, in cases of incapacitating dyspnea, it may be necessary to use pleural decortication in order to resolve the symptoms. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

  17. Inflammatory response and abscopal effects in the lungs after abdominal irradiation

    International Nuclear Information System (INIS)

    Van Der Meeren, A.; Monti, P.; Squiban, C.; Wysocki, J.; Vandamme, M.; Griffiths, N.

    2003-01-01

    Abscopal effects can be defined as biological effects observed in a tissue outside of the field of irradiation. Elucidating such mechanisms might help in the understanding of the radiation-induced multi organ failure. However, the mechanisms involved are still poorly understood. In the present study, C57BL6/J mice were irradiated in the abdominal region using an ORION accelerator, at the dose of 15 Gy. Inflammatory response was evaluated by measuring with ELISA, TNF-α, IL-6 and KC in the plasma of irradiated mice as well as in the jejunum and in the lungs. In addition, immunohistochemistry was used to determine PECAM-1 expression in the lungs. Results show the radiation-induced increase in the concentrations of IL-6 and KC measured in the plasma 3 and 6 days after exposure, although TNF-α remained undetectable. In the jejunum, KC content was greatly enhanced in irradiated animals, but IL-6 and TNF-α enhancements were only moderate. KC was also increased in the lungs of irradiated animals as compared to sham irradiated mice. In addition, PECAM-1 expression on lung endothelial cells was enhanced 3 and 6 days post-exposure. Our results show that the lungs, outside of the field of irradiation, show an inflammatory response with enhanced chemokine production and adhesion molecule expression on endothelial cells. This effect could be mediated through the release and circulation of inflammatory mediators in the blood and possibly in the lymphatic system

  18. Inflammatory response and abscopal effects in the lungs after abdominal irradiation

    International Nuclear Information System (INIS)

    Van Der Meeren, A.; Monti, P.; Squiban, C.; Wysocki, J.; Vandamme, M.; Griffiths, N.

    2003-01-01

    Abscopal effects can be defined as biological effects observed in a tissue outside of the field of irradiation. Elucidating such mechanisms might help in the understanding of the radiation-induced multi organ failure. However, the mechanisms involved are still poorly understood. In the present study, C57BL6/J mice were irradiated in the abdominal region using an ORION accelerator, at the dose of 15 Gy. Inflammatory response was evaluated by measuring with ELISA TNF-α , IL-6 and KC in the plasma of irradiated mice as well as in the jejunum and in the lungs. In addition, immunohistochemistry was used to determine PECAM-1 expression in the lungs. Results show the radiation-induced increase Three and 6 days after exposure in the concentrations of IL-6 and KC measured in the plasma, although TNF-α remained undetectable. In the jejunum, KC content was greatly enhanced in irradiated animals, but IL-6 and TNF-α enhancements were only moderate. KC was also increased in the lungs of irradiated animals as compared to sham irradiated mice. In addition, PECAM-1 expression on lung endothelial cells was enhanced 3 and 6 days post-exposure. Our results show that the lungs, outside of the field of irradiation, show an inflammatory response with enhanced chemokine production and adhesion molecule expression on endothelial cells. This effect could be mediated through the release and circulation of inflammatory mediators in the blood and possibly in the lymphatic fluid

  19. Win, Place, or Show?

    DEFF Research Database (Denmark)

    Blomkvist, Katarina; Kappen, Philip; Zander, Ivo

    2014-01-01

    This paper investigates the sources of technological growth of the multinational corporation. We conceptualize and shed empirical light on whether foreign investment strategies based on advanced greenfield subsidiaries, acquired subsidiaries, or a combination of both increase the likelihood...... strategies based on foreign acquisitions, as opposed to investment strategies based on greenfield establishments only. To the extent that MNC managers seek to enhance technological and strategic renewal through the expansion of foreign operations, the findings suggest that foreign investment strategies...

  20. Netrin-1 regulates fibrocyte accumulation in the decellularized fibrotic scleroderma lung microenvironment and in bleomycin induced pulmonary fibrosis

    Science.gov (United States)

    Sun, Huanxing; Zhu, Yangyang; Pan, Hongyi; Chen, Xiaosong; Balestrini, Jenna L.; Lam, TuKiet T.; Kanyo, Jean E.; Eichmann, Anne; Gulati, Mridu; Fares, Wassim H.; Bai, Hanwen; Feghali-Bostwick, Carol A.; Gan, Ye; Peng, Xueyan; Moore, Meagan W.; White, Eric S.; Sava, Parid; Gonzalez, Anjelica L.; Cheng, Yuwei; Niklason, Laura E.; Herzog, Erica L.

    2017-01-01

    Objectives Fibrocytes are collagen-producing leukocytes that accumulate in Scleroderma-associated interstitial lung disease (SSc-ILD) via unknown mechanisms. The extracellular matrix (ECM) influences cellular phenotypes. However, a relationship between the lung ECM and fibrocytes in Scleroderma has not been explored. This study uses a novel translational platform based on decellularized human lungs to determine whether the scleroderma lung ECM controls fibrocyte development from peripheral blood mononuclear cells. Methods Decellularized scaffolds prepared from healthy and fibrotic Scleroderma lung explants underwent biomechanical evaluation using tensile testing and biochemical analysis using proteomics. Cells from healthy and SSc-ILD subjects were cultured on these scaffolds, and CD45+Pro-ColIα1+ cells meeting criteria for fibrocytes were quantified. The contribution of Netrin-1 to fibrosis was assessed using neutralizing antibodies in this system and via the inhalational administration of bleomycin to Netrin-1+/− mice. Results Compared to control lung scaffold, SSc-ILD lung scaffolds showed aberrant anatomy, enhanced stiffness, and abnormal extracellular matrix composition. Culture of control cells in Scleroderma scaffolds increased Pro-ColIα1+ production, which was stimulated by enhanced stiffness and abnormal ECM composition. SSc-ILD cells demonstrated increased Pro-ColIα1 responsiveness to Scleroderma lung scaffolds, but not enhanced stiffness. Enhanced Netrin-1 expression was seen on CD14lo SSc-ILD cells and antibody mediated Netrin-1 neutralization attenuated CD45+Pro-ColIα1+ detection in all settings. Netrin-1+/− mice were protected from bleomycin induced lung fibrosis and fibrocyte accumulation. Conclusion Factors present in Scleroderma lung matrices regulate fibrocyte accumulation via a Netrin-1-dependent pathway. Netrin-1 regulates bleomycin induced murine pulmonary fibrosis. Netrin-1 might be a novel therapeutic target in SSc-ILD. PMID:26749424

  1. A Community-acquired Lung Abscess Attributable to Streptococcus pneumoniae which Extended Directly into the Chest Wall.

    Science.gov (United States)

    Ko, Yuki; Tobino, Kazunori; Yasuda, Yuichiro; Sueyasu, Takuto; Nishizawa, Saori; Yoshimine, Kouhei; Munechika, Miyuki; Asaji, Mina; Yamaji, Yoshikazu; Tsuruno, Kosuke; Miyajima, Hiroyuki; Mukasa, Yosuke; Ebi, Noriyuki

    We herein report the case of 75-year-old Japanese female with a community-acquired lung abscess attributable to Streptococcus pneumoniae (S. penumoniae) which extended into the chest wall. The patient was admitted to our hospital with a painful mass on the left anterior chest wall. A contrast-enhanced chest computed tomography scan showed a lung abscess in the left upper lobe which extended into the chest wall. Surgical debridement of the chest wall abscess and percutaneous transthoracic tube drainage of the lung abscess were performed. A culture of the drainage specimen yielded S. pneumoniae. The patient showed a remarkable improvement after the initiation of intravenous antibiotic therapy.

  2. Tomato PYR/PYL/RCAR abscisic acid receptors show high expression in root, differential sensitivity to the abscisic acid agonist quinabactin, and the capability to enhance plant drought resistance.

    Science.gov (United States)

    González-Guzmán, Miguel; Rodríguez, Lesia; Lorenzo-Orts, Laura; Pons, Clara; Sarrión-Perdigones, Alejandro; Fernández, Maria A; Peirats-Llobet, Marta; Forment, Javier; Moreno-Alvero, Maria; Cutler, Sean R; Albert, Armando; Granell, Antonio; Rodríguez, Pedro L

    2014-08-01

    Abscisic acid (ABA) plays a crucial role in the plant's response to both biotic and abiotic stress. Sustainable production of food faces several key challenges, particularly the generation of new varieties with improved water use efficiency and drought tolerance. Different studies have shown the potential applications of Arabidopsis PYR/PYL/RCAR ABA receptors to enhance plant drought resistance. Consequently the functional characterization of orthologous genes in crops holds promise for agriculture. The full set of tomato (Solanum lycopersicum) PYR/PYL/RCAR ABA receptors have been identified here. From the 15 putative tomato ABA receptors, 14 of them could be grouped in three subfamilies that correlated well with corresponding Arabidopsis subfamilies. High levels of expression of PYR/PYL/RCAR genes was found in tomato root, and some genes showed predominant expression in leaf and fruit tissues. Functional characterization of tomato receptors was performed through interaction assays with Arabidopsis and tomato clade A protein phosphatase type 2Cs (PP2Cs) as well as phosphatase inhibition studies. Tomato receptors were able to inhibit the activity of clade A PP2Cs differentially in an ABA-dependent manner, and at least three receptors were sensitive to the ABA agonist quinabactin, which inhibited tomato seed germination. Indeed, the chemical activation of ABA signalling induced by quinabactin was able to activate stress-responsive genes. Both dimeric and monomeric tomato receptors were functional in Arabidopsis plant cells, but only overexpression of monomeric-type receptors conferred enhanced drought resistance. In summary, gene expression analyses, and chemical and transgenic approaches revealed distinct properties of tomato PYR/PYL/RCAR ABA receptors that might have biotechnological implications. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  3. Show-Bix &

    DEFF Research Database (Denmark)

    2014-01-01

    The anti-reenactment 'Show-Bix &' consists of 5 dias projectors, a dial phone, quintophonic sound, and interactive elements. A responsive interface will enable the Dias projectors to show copies of original dias slides from the Show-Bix piece ”March på Stedet”, 265 images in total. The copies are...

  4. Polymeric Nano-Encapsulation of Curcumin Enhances its Anti-Cancer Activity in Breast (MDA-MB231) and Lung (A549) Cancer Cells Through Reduction in Expression of HIF-1α and Nuclear p65 (Rel A).

    Science.gov (United States)

    Khan, Mohammed N; Haggag, Yusuf A; Lane, Majella E; McCarron, Paul A; Tambuwala, Murtaza M

    2018-02-14

    The anti-cancer potential of curcumin, a natural NFκβ inhibitor, has been reported extensively in breast, lung and other cancers. In vitro and in vivo studies indicate that the therapeutic efficacy of curcumin is enhanced when formulated in a nanoparticulate carrier. However, the mechanism of action of curcumin at the molecular level in the hypoxic tumour micro-environment is not fully understood. Hence, the aim of our study was to investigate the mechanism of action of curcumin formulated as nanoparticles in in vitro models of breast and lung cancer under an hypoxic microenvironment. Biodegradable poly(lactic-co-glycolic acid) PLGA nanoparticles (NP), loaded with curcumin (cur-PLGA-NP), were fabricated using a solvent evaporation technique to overcome solubility issues and to facilitate intracellular curcumin delivery. Cytotoxicity of free curcumin and cur-PLGA-NP was evaluated in MDA-MB-231 and A549 cell lines using migration, invasion and colony formation assays. All treatments were performed under an hypoxic micro-environment and whole cell lysates from controls and test groups were used to determine the expression of HIF-1α and p65 levels using ELISA assays. A ten-fold increase in solubility, three-fold increase in anti-cancer activity and a significant reduction in the levels of cellular HIF-1α and nuclear p65 (Rel A) were observed for cur-PLGA-NP, when compared to free curcumin. Our findings indicate that curcumin can effectively lower the elevated levels of HIF-1α and nuclear p65 (Rel A) in breast and lung cancer cells under an hypoxic tumour micro-environment when delivered in nanoparticulate form. This applied means of colloidal delivery could explain the improved anti-cancer efficacy of curcumin and has further potential applications in enhancing the activity of anti-cancer agents of low solubility. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Size effects of latex nanomaterials on lung inflammation in mice

    International Nuclear Information System (INIS)

    Inoue, Ken-ichiro; Takano, Hirohisa; Yanagisawa, Rie; Koike, Eiko; Shimada, Akinori

    2009-01-01

    Effects of nano-sized materials (nanomaterials) on sensitive population have not been well elucidated. This study examined the effects of pulmonary exposure to (latex) nanomaterials on lung inflammation related to lipopolysaccharide (LPS) or allergen in mice, especially in terms of their size-dependency. In protocol 1, ICR male mice were divided into 8 experimental groups that intratracheally received a single exposure to vehicle, latex nanomaterials (250 μg/animal) with three sizes (25, 50, and 100 nm), LPS (75 μg/animal), or LPS plus latex nanomaterials. In protocol 2, ICR male mice were divided into 8 experimental groups that intratracheally received repeated exposure to vehicle, latex nanomaterials (100 μg/animal), allergen (ovalbumin: OVA; 1 μg/animal), or allergen plus latex nanomaterials. In protocol 1, latex nanomaterials with all sizes exacerbated lung inflammation elicited by LPS, showing an overall trend of amplified lung expressions of proinflammatory cytokines. Furthermore, LPS plus nanomaterials, especially with size less than 50 nm, significantly elevated circulatory levels of fibrinogen, macrophage chemoattractant protein-1, and keratinocyte-derived chemoattractant, and von Willebrand factor as compared with LPS alone. The enhancement tended overall to be greater with the smaller nanomaterials than with the larger ones. In protocol 2, latex nanomaterials with all sizes did not significantly enhance the pathophysiology of allergic asthma, characterized by eosinophilic lung inflammation and Igs production, although latex nanomaterials with less than 50 nm significantly induced/enhanced neutrophilic lung inflammation. These results suggest that latex nanomaterials differentially affect two types of (innate and adaptive immunity-dominant) lung inflammation

  6. Lung function

    International Nuclear Information System (INIS)

    Sorichter, S.

    2009-01-01

    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 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 max , P 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.) [de

  7. Radon exposure and lung cancer

    International Nuclear Information System (INIS)

    Planinic, J.; Vukovic, B.; Faj, Z.; Radolic, V.; Suveljak, B.

    2003-01-01

    Although studies of radon exposure have established that Rn decay products are a cause of lung cancer among miners, the lung cancer risk to the general population from indoor radon remains unclear and controversial. Our epidemiological investigation of indoor radon influence on lung cancer incidence was carried out for 201 patients from the Osijek town. Ecological method was applied by using the town map with square fields of 1 km 2 and the town was divided into 24 fields. Multiple regression study for the lung cancer rate on field, average indoor radon exposure and smoking showed a positive linear double regression for the mentioned variables. Case-control study showed that patients, diseased of lung cancer, dwelt in homes with significantly higher radon concentrations, by comparison to the average indoor radon level of control sample. (author)

  8. Open lung biopsy

    Science.gov (United States)

    Biopsy - open lung ... An open lung biopsy is done in the hospital using general anesthesia . This means you will be asleep and ... The open lung biopsy is done to evaluate lung problems seen on x-ray or CT scan .

  9. Lung Cancer: Glossary

    Science.gov (United States)

    ... professional support team today. Learn More . Find more lung cancer resources. Learn More Donate Today! What is Lung ... to Give How Your Support Helps Events Lung Cancer Awareness © Lung Cancer Alliance. The information presented in this website ...

  10. Lung Cancer Prevention

    Science.gov (United States)

    ... Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer ... following PDQ summaries for more information about lung cancer: Lung Cancer Screening Non-Small Cell Lung Cancer Treatment ...

  11. 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 ...

  12. [Lung scintigraphy].

    Science.gov (United States)

    Schümichen, Carl; Schmidt, Matthias; Krause, Thomas

    2018-06-01

    The S1 guideline for lung scintigraphy has been updated and extended in order to emphasize the advantages oft the method in detecting acute pulmonary embolism (PE) in the periphery oft the lung (subsegmental PE), in underlying subacute and chronic pulmonary disorders, as well as in detecting chronic LE (CTEPH). Method of choice is ventilation / perfusion (V/P) SPECT or V/P SPECT/CT with even higher specificity. Because of its high sensitivity, a threshold (V/P mismatch in at least one segment or two subsegments) is introduced to avoid overtreatment. In case of a change in the therapeutic approach (observation only instead of anticoaculation) the threshold can be omitted. New data concerning the clinical and therapeutical impact of subsegmental PE are included, the chapters open questions have been extented. Other indications for V/P SPECT (secondary diagnoses, abnormalities in pulmonary perfusion, prediction of postoperative lung function) are presented with new data. Schattauer GmbH.

  13. Effect of grain boundary layer strain on the magnetic and transport properties of (100-x) La0.7Ca0.3MnO3/(x) BaTiO3 composites showing enhanced magnetoresistance

    International Nuclear Information System (INIS)

    Bose, Esa; Taran, S.; Karmakar, S.; Chaudhuri, B.K.; Pal, S.; Sun, C.P.; Yang, H.D.

    2007-01-01

    A ferromagnetic/ferroelectric composite system, viz. (100-x)La 0.7 Ca 0.3 MnO 3 [LCMO]/(x) BaTiO 3 [BTO] (with x=0.0%, 1.0%, 5.0%, 7.5%, 10.0% and 15.0%, in wt%) has been synthesized and the temperature-dependent DC magnetization M(T), resistivity ρ(T), magnetoresistance (MR), and thermoelectric power S(T) have been studied. Both metal-insulator transition temperature (T MI ) and the corresponding Curie temperature (T C ) decrease whereas peak resistivity at T MI increases as x is enhanced from 0.0% to 10.0%. For x>10.0%, this trend of variation is reversed. A maximum three-fold increase of magnetoresistance (MR) is observed (for sample with x=10.0%) due to the addition of ferroelectric (non-magnetic) perovskite BTO (compared to the mother compound LCMO). Interestingly, thermoelectric power S(T) shows a pronounced depression (dip) near the magnetic transition region for the composite samples. The above results have been analyzed considering strain induced by the LCMO/BTO grain boundary layer (BL)

  14. Lung radiopharmaceuticals

    International Nuclear Information System (INIS)

    Gonzalez, B.M.

    1994-01-01

    Indication or main clinical use of Lung radiopharmaceuticals is presented and clasification of radiopharmaceuticals as ventilation and perfusion studies. Perfusion radiopharmaceuticals, main controls for administration quality acceptance. Clearence after blood administration and main clinical applications. Ventilation radiopharmaceuticals, gases and aerosols, characteristics of a ideal radioaerosol, techniques of good inhalation procedure, clinical applications. Comparison of several radiopharmaceuticals reflering to retention time as 50% administered dose, percent administered dose at 6 hours post inhalation, blood activity at 30 and 60 minutes post inhalation, initial lung absorbed dose, cumulated activity.Kinetic description of two radiopharmaceuticals, 99mTcDTPA and 99mTc-PYP

  15. What Are the Lungs?

    Science.gov (United States)

    ... and the muscles that enable breathing. The Respiratory System Figure A shows the location of the respiratory ... buildup in the lung tissues. These sensors are thought to trigger rapid, shallow breathing. Sensors in your ... is a complex process. If injury, disease, or other factors affect any ...

  16. Talking with TV shows

    DEFF Research Database (Denmark)

    Sandvik, Kjetil; Laursen, Ditte

    2014-01-01

    User interaction with radio and television programmes is not a new thing. However, with new cross-media production concepts such as X Factor and Voice, this is changing dramatically. The second-screen logic of these productions encourages viewers, along with TV’s traditional one-way communication...... mode, to communicate on interactive (dialogue-enabling) devices such as laptops, smartphones and tablets. Using the TV show Voice as our example, this article shows how the technological and situational set-up of the production invites viewers to engage in new ways of interaction and communication...

  17. Lung Transplant

    Science.gov (United States)

    ... Severity of the recipient's lung disease Recipient's overall health Likelihood that the transplant will be successful Immediately before ... will begin within days of your surgery. Your health care team will likely work with you to design an exercise program that's right for you. Your doctor may ...

  18. 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...

  19. Talk Show Science.

    Science.gov (United States)

    Moore, Mitzi Ruth

    1992-01-01

    Proposes having students perform skits in which they play the roles of the science concepts they are trying to understand. Provides the dialog for a skit in which hot and cold gas molecules are interviewed on a talk show to study how these properties affect wind, rain, and other weather phenomena. (MDH)

  20. Obesity in show cats.

    Science.gov (United States)

    Corbee, R J

    2014-12-01

    Obesity is an important disease with a high prevalence in cats. Because obesity is related to several other diseases, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain cat breeds has been suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, 268 cats of 22 different breeds investigated by determining their body condition score (BCS) on a nine-point scale by inspection and palpation, at two different cat shows. Overall, 45.5% of the show cats had a BCS > 5, and 4.5% of the show cats had a BCS > 7. There were significant differences between breeds, which could be related to the breed standards. Most overweight and obese cats were in the neutered group. It warrants firm discussions with breeders and cat show judges to come to different interpretations of the standards in order to prevent overweight conditions in certain breeds from being the standard of beauty. Neutering predisposes for obesity and requires early nutritional intervention to prevent obese conditions. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

  1. Honored Teacher Shows Commitment.

    Science.gov (United States)

    Ratte, Kathy

    1987-01-01

    Part of the acceptance speech of the 1985 National Council for the Social Studies Teacher of the Year, this article describes the censorship experience of this honored social studies teacher. The incident involved the showing of a videotape version of the feature film entitled "The Seduction of Joe Tynan." (JDH)

  2. Ischemia postconditioning and mesenchymal stem cells engraftment synergistically attenuate ischemia reperfusion-induced lung injury in rats.

    Science.gov (United States)

    Chen, Shuchen; Chen, Liangwan; Wu, Xiaonan; Lin, Jiangbo; Fang, Jun; Chen, Xiangqi; Wei, Shijin; Xu, Jianxin; Gao, Qin; Kang, Mingqiang

    2012-11-01

    It has been reported that ischemic postconditioning (IPO) or mesenchymal stem cell (MSC) engraftment could protect organs from ischemia/reperfusion (I/R) injury. We investigated the synergetic effects of combined treatment on lung injury induced by I/R. Adult Sprague-Dawley rats were randomly assigned to one of the following groups: sham-operated control, I/R, IPO, MSC engraftment, and IPO plus MSC engraftment. Lung injury was assessed by arterial blood gas analysis, the wet/dry lung weight ratio, superoxide dismutase level, malondialdehyde content, myeloperoxidase activity, and tissue histologic changes. Cytokine expression was detected using real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. Cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end assay and annexin V staining. MSC engraftment or IPO alone markedly attenuated the lung wet/dry weight ratio, malondialdehyde and myeloperoxidase production, and lung pathologic injury and enhanced arterial partial oxygen pressure, superoxide dismutase content, inhibited pro-inflammatory cytokine levels, and decreased cell apoptosis in lung tissue, compared with the I/R group. In contrast, IPO pretreatment enhanced the protective effects of MSC on I/R-induced lung injury compared with treatment alone. Moreover, in the combined treatment group, the number of MSC engraftments in the lung tissue was increased, associated with enhanced survival of MSCs compared with MSC treatment alone. Additional investigation showed that IPO treatment increased expression of vascular endothelial growth factor and stromal cell-derived factor-1 in I/R lung tissue. IPO might contribute to the homing and survival of transplanted MSCs and enhance their therapeutic effects through improvement of the microenvironment of I/R injury. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. The energy show

    International Nuclear Information System (INIS)

    1988-01-01

    The Energy Show is a new look at the problems of world energy, where our supplies come from, now and in the future. The programme looks at how we need energy to maintain our standards of living. Energy supply is shown as the complicated set of problems it is - that Fossil Fuels are both raw materials and energy sources, that some 'alternatives' so readily suggested as practical options are in reality a long way from being effective. (author)

  4. The environmental pollutant and carcinogen 3-nitrobenzanthrone induces cytochrome P450 1A1 and NAD(P)H:quinone oxidoreductase in rat lung and kidney, thereby enhancing its own genotoxicity

    International Nuclear Information System (INIS)

    Stiborova, Marie; Dracinska, Helena; Mizerovska, Jana; Frei, Eva; Schmeiser, Heinz H.; Hudecek, Jiri; Hodek, Petr; Phillips, David H.; Arlt, Volker M.

    2008-01-01

    3-Nitrobenzanthrone (3-NBA) is a carcinogen occurring in diesel exhaust and air pollution. Using the 32 P-postlabelling method, we found that 3-NBA and its human metabolite, 3-aminobenzanthrone (3-ABA), are activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and kidney. Each compound generated identical five DNA adducts. We have demonstrated the importance of pulmonary and renal NAD(P)H:quinone oxidoreductase (NQO1) to reduce 3-NBA to species that are further activated by N,O-acetyltransferases and sulfotransferases. Cytochrome P450 (CYP) 1A1 is the essential enzyme for oxidative activation of 3-ABA in microsomes of both organs, while cyclooxygenase plays a minor role. 3-NBA was also investigated for its ability to induce NQO1 and CYP1A1 in lungs and kidneys, and for the influence of such induction on DNA adduct formation by 3-NBA and 3-ABA. When cytosols from rats treated i.p. with 40 mg/kg bw of 3-NBA were incubated with 3-NBA, DNA adduct formation was up to 2.1-fold higher than in incubations with cytosols from control animals. This increase corresponded to an increase in protein level and enzymatic activity of NQO1. Incubations of 3-ABA with microsomes of 3-NBA-treated rats led to up to a fivefold increase in DNA adduct formation relative to controls. The stimulation of DNA adduct formation correlated with the potential of 3-NBA to induce protein expression and activity of CYP1A1. These results demonstrate that 3-NBA is capable to induce NQO1 and CYP1A1 in lungs and kidney of rats thereby enhancing its own genotoxic and carcinogenic potential

  5. Microbiome overview in swine lungs.

    Directory of Open Access Journals (Sweden)

    Franciele Maboni Siqueira

    Full Text Available Mycoplasma hyopneumoniae is the etiologic agent of swine enzootic pneumonia. However other mycoplasma species and secondary bacteria are found as inhabitants of the swine respiratory tract, which can be also related to disease. In the present study we have performed a total DNA metagenomic analysis from the lungs of pigs kept in a field condition, with suggestive signals of enzootic pneumonia and without any infection signals to evaluate the bacteria variability of the lungs microbiota. Libraries from metagenomic DNA were prepared and sequenced using total DNA shotgun metagenomic pyrosequencing. The metagenomic distribution showed a great abundance of bacteria. The most common microbial families identified from pneumonic swine's lungs were Mycoplasmataceae, Flavobacteriaceae and Pasteurellaceae, whereas in the carrier swine's lungs the most common families were Mycoplasmataceae, Bradyrhizobiaceae and Flavobacteriaceae. Analysis of community composition in both samples confirmed the high prevalence of M. hyopneumoniae. Moreover, the carrier lungs had more diverse family population, which should be related to the lungs normal flora. In summary, we provide a wide view of the bacterial population from lungs with signals of enzootic pneumonia and lungs without signals of enzootic pneumonia in a field situation. These bacteria patterns provide information that may be important for the establishment of disease control measures and to give insights for further studies.

  6. LOXL4 knockdown enhances tumor growth and lung metastasis through collagen-dependent extracellular matrix changes in triple-negative breast cancer.

    Science.gov (United States)

    Choi, Sul Ki; Kim, Hoe Suk; Jin, Tiefeng; Moon, Woo Kyung

    2017-02-14

    Lysyl oxidase (LOX) family genes catalyze collagen cross-link formation. To determine the effects of lysyl oxidase-like 4 (LOXL4) expression on breast tumor formation and metastasis, we evaluated primary tumor growth and lung metastasis in mice injected with LOXL4-knockdown MDA-MB-231 triple-negative human breast cancer cells. In addition, we analyzed overall survival in breast cancer patients based on LOXL4 expression using a public online database. In the mouse xenograft model, LOXL4 knockdown increased primary tumor growth and lung colonization as well as collagen I and IV, lysine hydroxylase 1 and 2, and prolyl 4-hydroxylase subunit alpha 1 and 2 levels. Second harmonic generation imaging revealed that LOXL4 knockdown resulted in the thickening of collagen bundles within tumors. In addition, weak LOXL4 expression was associated with poor overall survival in breast cancer patients from the BreastMark dataset, and this association was strongest in triple-negative breast cancer patients. These results demonstrate that weak LOXL4 expression leads to remodeling of the extracellular matrix through induction of collagen synthesis, deposition, and structural changes. These alterations in turn promote tumor growth and metastasis and are associated with poor clinical outcomes in triple-negative breast cancer.

  7. Epidemiology, aetiology, diagnosis and screening of lung cancer

    International Nuclear Information System (INIS)

    Berzinec, P.

    2006-01-01

    Lung cancer is the leading cause of cancer death globally. Smoking causes about 90 % of all lung cancer cases. Passive, i.e. involuntary smoking has been confirmed to enhance the risk of lung cancer in exposed people. Individual susceptibility is one of important factors in lung cancer formation. New knowledge in epidemiology and aetiology of lung cancer gives new possibilities in diagnostic and screening of this disease. Results of large randomised trials aimed at new technologies in lung cancer screening will be available in a few years. (author)

  8. Spleen-lung interface as diagnostic information

    International Nuclear Information System (INIS)

    DeLuca, S.A.; Kolodny, G.M.

    1975-01-01

    Left anterior, lateral, and posterior views on 50 consecutive /sup 99m/Tc-sulfur colloid lung scans were examined. Normal patients had continuity of activity between the left lung and the spleen on all three views. Patients with subphrenic abscess or large left pleural effusions showed no continuity between lung and spleen activity on any view, while other abnormalities, most commonly cardiomegaly, accounted for lack of lung-spleen continuity on the anterior view only. It is suggested that in all combined /sup 99m/Tc-sulfur colloid lung studies, the left side be examined as well as the right for abnormalities adjacent to the left diaphragm. (auth)

  9. Current lung water measurement methods in man

    International Nuclear Information System (INIS)

    Basset, G.; Moreau, F.; Marsac, J.; Capitini, R.; Botter, F.

    1979-01-01

    Two kinds of tracer method are used to estimate the lung water pools differing by the tracer intake and the sector observed. Airborne intake gives an estimate of the tissues irrigated by the lung and bronchial circulation, whereas vascular intake only shows the sectors perfused by the lung flow. Either of these methods is suitable for a general or regional analysis. In general methods the tracer is followed at the lung exit on expired air for the first method, on peripheral arterial blood for the second. Regional methods imply partial or whole-lung external detection systems [fr

  10. Showing Value (Editorial

    Directory of Open Access Journals (Sweden)

    Denise Koufogiannakis

    2009-06-01

    Full Text Available When Su Cleyle and I first decided to start Evidence Based Library and Information Practice, one of the things we agreed upon immediately was that the journal be open access. We knew that a major obstacle to librarians using the research literature was that they did not have access to the research literature. Although Su and I are both academic librarians who can access a wide variety of library and information literature from our institutions, we belong to a profession where not everyone has equal access to the research in our field. Without such access to our own body of literature, how can we ever hope for practitioners to use research evidence in their decision making? It would have been contradictory to the principles of evidence based library and information practice to do otherwise.One of the specific groups we thought could use such an open access venue for discovering research literature was school librarians. School librarians are often isolated and lacking access to the research literature that may help them prove to stakeholders the importance of their libraries and their role within schools. Certainly, school libraries have been in decline and the use of evidence to show value is needed. As Ken Haycock noted in his 2003 report, The Crisis in Canada’s School Libraries: The Case for Reform and Reinvestment, “Across the country, teacher-librarians are losing their jobs or being reassigned. Collections are becoming depleted owing to budget cuts. Some principals believe that in the age of the Internet and the classroom workstation, the school library is an artifact” (9. Within this context, school librarians are looking to our research literature for evidence of the impact that school library programs have on learning outcomes and student success. They are integrating that evidence into their practice, and reflecting upon what can be improved locally. They are focusing on students and showing the impact of school libraries and

  11. The bisphosphonate zoledronic acid effectively targets lung cancer cells by inhibition of protein prenylation

    International Nuclear Information System (INIS)

    Xie, Fan; Li, Pengcheng; Gong, Jianhua; Zhang, Jiahong; Ma, Jingping

    2015-01-01

    Aberrant activation of oncoproteins such as members of the Ras family is common in human lung cancers. The proper function of Ras largely depends on a post-translational modification termed prenylation. Bisphosphonates have been shown to inhibit prenylation in cancer cells. In this study, we show that zoledronic acid, a third generation bisphosphonate, is effective in targeting lung cancer cells. This is achieved by the induction of apoptosis and inhibition of proliferation, through suppressing the activation of downstream Ras and EGFR signalling by zoledronic acid. The combination of zoledronic acid and paclitaxel or cisplatin (commonly used chemotherapeutic drugs for lung cancer) augmented the activity of either drug alone in in vitro lung cancer cellular system and in vivo lung xenograft mouse model. Importantly, zoledronic acid inhibits protein prenylation as shown by the increased levels of unprenylated Ras and Rap1A. In addition, the effects of zoledronic acid were reversed in the presence of geranylgeraniol and farnesol, further confirming that mechanism of zoledroinc acid's action in lung cancer cells is through prenylation inhibition. Since zoledronic acid is already available for clinic use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of lung cancer. - Highlights: • Zoledronic acid (ZA) is effectively against lung cancer cells in vitro and in vivo. • ZA acts on lung cancer cells through inhibition of protein prenylation. • ZA suppresses global downstream phosphorylation of Ras signalling. • ZA enhances the effects of chemotherapeutic drugs in lung cancer cells.

  12. The bisphosphonate zoledronic acid effectively targets lung cancer cells by inhibition of protein prenylation

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Fan [Department of Respiratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China); Li, Pengcheng [Department of Oncology, Wuhan Union Hospital Affiliated to Huazhong University of Science and Technology, Wuhan (China); Gong, Jianhua; Zhang, Jiahong [Department of Respiratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China); Ma, Jingping, E-mail: mjpjzhospital@hotmail.com [Department of Respiratory Medicine, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Jingzhou (China)

    2015-11-27

    Aberrant activation of oncoproteins such as members of the Ras family is common in human lung cancers. The proper function of Ras largely depends on a post-translational modification termed prenylation. Bisphosphonates have been shown to inhibit prenylation in cancer cells. In this study, we show that zoledronic acid, a third generation bisphosphonate, is effective in targeting lung cancer cells. This is achieved by the induction of apoptosis and inhibition of proliferation, through suppressing the activation of downstream Ras and EGFR signalling by zoledronic acid. The combination of zoledronic acid and paclitaxel or cisplatin (commonly used chemotherapeutic drugs for lung cancer) augmented the activity of either drug alone in in vitro lung cancer cellular system and in vivo lung xenograft mouse model. Importantly, zoledronic acid inhibits protein prenylation as shown by the increased levels of unprenylated Ras and Rap1A. In addition, the effects of zoledronic acid were reversed in the presence of geranylgeraniol and farnesol, further confirming that mechanism of zoledroinc acid's action in lung cancer cells is through prenylation inhibition. Since zoledronic acid is already available for clinic use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of lung cancer. - Highlights: • Zoledronic acid (ZA) is effectively against lung cancer cells in vitro and in vivo. • ZA acts on lung cancer cells through inhibition of protein prenylation. • ZA suppresses global downstream phosphorylation of Ras signalling. • ZA enhances the effects of chemotherapeutic drugs in lung cancer cells.

  13. The lungs

    International Nuclear Information System (INIS)

    Macey, D.J.; Marshall, R.

    1982-01-01

    Currently emission tomography of the lungs is only practical for perfusion images with sup(99m)Tc microaggregates and ventilation images with sup(81m)Kr. The following topics are touched on: the rotating gamma camera single photon ECT system, spatial resolution and linearity, resolution in phantom studies, area and volume studies, quantitation studies, with particular reference to the authors' experience of perfusion and ventilation in investigations of pulmonary embolism. (U.K.)

  14. Hyperlucent lung

    International Nuclear Information System (INIS)

    Jimenez-Gutierrez, Florana; Soto-Quiros, Manuel E.

    2007-01-01

    Unilateral hyperlucent lung is also known as Swyer-James Syndrome, Macleod Syndrome or lobular or unilateral emphysema. It is an uncommon disease characterized by lung or unilateral lobe hiperlucency associated to an air trapping upon expiration. As regards to etiology, this syndrome is considered to be an acquired disease that appears secondary to respiratory infections during the early years of life, probably bronchiolitis and/ or viral pneumonia. The clinical presentation varies among patients. Some of them are asymptomatic, others present a history of recurrent episodes of pulmonary infections from early years of life or present effort dyspnea. The diagnosis is usually made accidentally by a chest radiograph in a child with history of respiratory infections or in an adult during a routine chest x- ray in an asymptomatic person. It is important to differentiate this syndrome from other causes of unilateral pulmonary hiperlucency on conventional chest x-rays. Few cases of Swyer-James Syndrome in children have been reported, it is presented the clinical case of a patient who had a parainfluenza 3 bronchopneumonia when he was a month and eighteen days of age. The differential diagnosis of this syndrome should be done with other thoracic entities that diminish the radiological pulmonary unilateral density. A case of a child who is the bearer of hyperlucent lung is described. (author) [es

  15. Short-Course Treatment With Gefitinib Enhances Curative Potential of Radiation Therapy in a Mouse Model of Human Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Bokobza, Sivan M.; Jiang, Yanyan; Weber, Anika M.; Devery, Aoife M.; Ryan, Anderson J.

    2014-01-01

    Purpose: To evaluate the combination of radiation and an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in preclinical models of human non-small cell lung cancer. Methods and Materials: Sensitivity to an EGFR TKI (gefitinib) or radiation was assessed using proliferation assays and clonogenic survival assays. Effects on receptor signal transduction pathways (pEGFR, pAKT, pMAPK) and apoptosis (percentage of cleaved PARP Poly (ADP-ribose) polymerase (PARP)) were assessed by Western blotting. Radiation-induced DNA damage was assessed by γH2AX immunofluorescence. Established (≥100 mm 3 ) EGFR-mutated (HCC287) or EGFR wild-type (A549) subcutaneous xenografts were treated with radiation (10 Gy, day 1) or gefitinib (50 mg/kg, orally, on days 1-3) or both. Results: In non-small cell lung cancer (NSCLC) cell lines with activating EGFR mutations (PC9 or HCC827), gefitinib treatment markedly reduced pEGFR, pAKT, and pMAPK levels and was associated with an increase in cleaved PARP but not in γH2AX foci. Radiation treatment increased the mean number of γH2AX foci per cell but did not significantly affect EGFR signaling. In contrast, NSCLC cell lines with EGFR T790M (H1975) or wild-type EGFR (A549) were insensitive to gefitinib treatment. The combination of gefitinib and radiation treatment in cell culture produced additive cell killing with no evidence of synergy. In xenograft models, a short course of gefitinib (3 days) did not significantly increase the activity of radiation treatment in wild-type EGFR (A549) tumors (P=.27), whereas this combination markedly increased the activity of radiation (P<.001) or gefitinib alone (P=.002) in EGFR-mutated HCC827 tumors, producing sustained tumor regressions. Conclusions: Gefitinib treatment increases clonogenic cell killing by radiation but only in cell lines sensitive to gefitinib alone. Our data suggest additive rather than synergistic interactions between gefitinib and radiation and that a

  16. [Study on characteristics of pharmacological effects of traditional Chinese medicines distributing along lung meridian based on medicinal property combination].

    Science.gov (United States)

    Gu, Hao; Zhang, Yan-Ling; Wang, Yun; Qiao, Yan-Jiang

    2014-07-01

    Medicinal properties are the basic attribute of traditional Chinese medicines (TCM), while the medicinal property theory is the core theoretical foundation of TCM formula combination. In this particle, authors studied the characteristics of pharmacological effects of property combination of traditional Chinese medicines distributing along meridians, with the aim to introduce the medicinal property combination regularity into the design and optimization process of compound TCMs, and bring the medicinal property theory into full play in guiding the formula combination. In this paper, TCMs distributing along "the lung meridian" was taken for example. The medicinal property combinations of TCMs distributing along "the lung meridian" recorded in Pharmacopeia (2010) was collected and processed. Besides, Chinese journal full-text database (CNKI) was used to collect all of pharmacological study literatures concerning the above TCMs that have been published since 1980. The pharmacological information was also supplemented by reference to Science of Chinese Materia Medica and Clinical Science of Chinese Materia Medica. TCMs distributing along the lung meridian with different properties and tastes showed significant differences in pharmacological effects. For example, mild-sweet-lung medicines could lower blood sugar levels, decrease anoxia and enhance immunity; Mild-bitter-lung medicines showed anti-bacterial, anti-hypertension, anti-oxidation effects; Hot-sweet-lung medicines showed antibechic and anti-bacterial effects. And Hot-bitter-lung medicines showed phlegm eliminating and anti-inflammatory effects. Meanwhile, TCMs distributing along the lung meridian had similar pharmacological characteristics, such as anti-bacterial and anti-inflammatory effects, which is consistent with lung's feature in susceptibility to exogenous pathogenic factors. In this study, authors discovered pharmacological characteristics of different TCMs distributing along the lung meridian, which

  17. Seawater immersion aggravates burn-associated lung injury and inflammatory and oxidative-stress responses.

    Science.gov (United States)

    Ma, Jun; Wang, Ying; Wu, Qi; Chen, Xiaowei; Wang, Jiahan; Yang, Lei

    2017-08-01

    With the increasing frequency of marine development activities and local wars at sea, the incidence of scald burns in marine accidents or wars has been increasing yearly. Various studies have indicated that immersion in seawater has a systemic impact on some organs of animals or humans with burn. Thus, for burn/scald injuries after immersion in seawater, it is desirable to study the effects and mechanisms of action on important organs. In the present study, we aimed to investigate the effect of immersion in seawater on lung injury, inflammatory and oxidative-stress responses in scalded rats. The structural damage to lungs was detected by hematoxylin and eosin staining and the results showed that seawater immersion aggravated structural lung injury in scalded rats. The expression of HMGB1 in lung tissues was detected by immunohistochemical analysis and the results showed that seawater immersion increased HMGB1 expression in lung tissues of scalded rats. Apoptosis in lung tissues was detected by terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) staining and the results showed that seawater immersion increased apoptosis rate in lung tissues of scalded rats. In addition, the expression levels of TNF-α, IL-6, IL-8, SOD, and MDA in serum were analyzed by enzyme-linked immunosorbent assays (ELISAs) and the results showed that seawater immersion induced secretion of proinflammatory factors (TNF-α, IL-6, and IL-8), increased MDA protein level, and suppressed SOD activity in the serum of scalded rats. Furthermore, measurement of plasma volume and pH showed that seawater immersion decreased plasma volume and pH value. Overall, the results indicated that all effects induced by immersion in seawater in scalded rats are more pronounced than those induced by freshwater. In conclusion, seawater immersion may aggravate lung injury and enhance inflammatory and oxidative-stress responses after burn. Copyright © 2017 Elsevier Ltd and ISBI. All rights

  18. Intracrainal metastases of lung cancer -CT and histopathologic correlation-

    International Nuclear Information System (INIS)

    Park, Hyun Ju; Kim, Myung Soon; Kang, Myung Jae

    1991-01-01

    The authors retrospectively analyzed high resolution (HR) CT scans of the brain in 23 patients with surgically proved primary lung cancer and intracranial metastatic lesions from April 1986 to March 1990. The purpose of this study was to evaluate the relationship between histopathologic types of primary lung cancer and HRCT findings of brain. The results were as follows: The locations of metastatic lesion were intraaxial in 93% and extraaxial in 7%. In the intraaxial lesions, most were in the supratentorial area (83%) and the remainer in the infratentorial area (10%). Among the supratentorial lesions, the parietal lobe was the most commonly involved (33%), while the second most common location was frontal lobe (22%). The HRCT showed multiple lesions in 52% and solitary lesions in 48%. All cell types except for squamous cell carcinoma showed the same incidence in multiplicity, and the squamous cell carcinoma showed slightly more multiple lesions rather than solitary ones. The degree of peritumoral edema was none in 4%, mild in 25%, moderate in 46%, and severe in 25%. All cell types except for squamous cell carcinoma in general showed a moderate degree of edema, and the squamous cell carcinoma mainly showed mild and severe edema. Precontrast CT scans showed mixed density in 52%, isodensity in 24%, low density in 19%, and high density in 5%. All cell types except for large cell carcinoma showed mixed density, the large cell carcinoma showed a low density unlike the others. Hemorrhages were seen in 24% and noted in all cell types except for large cell carcinoma. Postcontrast CT scans showed ring enhancement in 64%, nodular enhancement in 20%, and inhomogeneous enhancement in 16%. All cell types except for small cell carcinoma generally showed ring enhancement, and the small cell carcinoma showed a variable degree of enhancement

  19. Computed tomography in opportunistic lung infections

    International Nuclear Information System (INIS)

    Hartelius, H.

    1988-01-01

    Chest radiography in two teenage boys, one with Wiscott-Aldrich's syndrome and one with acute lymphatic leucemia in remission showed increased interstitial pattern. In both computed tomography (CT) of the lungs showed heavy interstitial pneumonia, rather different in appearance but in both cases equal to the CT findings in opportunistic lung infections known from immunoincompetent patients with for instance pneumocystis carinii and/or cytomegalo virus infections. In both patients the CT findings led to lung biopsy establishing the etiologic agent. (orig.)

  20. RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer.

    Science.gov (United States)

    Rao, Shuan; Sigl, Verena; Wimmer, Reiner Alois; Novatchkova, Maria; Jais, Alexander; Wagner, Gabriel; Handschuh, Stephan; Uribesalgo, Iris; Hagelkruys, Astrid; Kozieradzki, Ivona; Tortola, Luigi; Nitsch, Roberto; Cronin, Shane J; Orthofer, Michael; Branstetter, Daniel; Canon, Jude; Rossi, John; D'Arcangelo, Manolo; Botling, Johan; Micke, Patrick; Fleur, Linnea La; Edlund, Karolina; Bergqvist, Michael; Ekman, Simon; Lendl, Thomas; Popper, Helmut; Takayanagi, Hiroshi; Kenner, Lukas; Hirsch, Fred R; Dougall, William; Penninger, Josef M

    2017-10-15

    Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas G12D in mouse lung epithelial cells markedly impairs the progression of KRas G12D -driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas G12D -driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer. © 2017 Rao et al.; Published by Cold Spring Harbor Laboratory Press.

  1. Hedgehog Pathway Inhibition Radiosensitizes Non-Small Cell Lung Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Aftab, Blake T. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M.; Wong, John [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Rudin, Charles M. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hales, Russell K., E-mail: rhales1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2013-05-01

    Purpose: Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials: We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of Kras{sup G12D}-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results: In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radiosensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions: Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer.

  2. Unevenness on aerosol inhalation lung images and lung function

    International Nuclear Information System (INIS)

    Teshima, Takeo; Isawa, Toyoharu; Hirano, Tomio; Ebina, Akio; Shiraishi, Koichiro; Konno, Kiyoshi

    1985-01-01

    The unevenness or inhomogeneity of aerosol deposition patterns on radioaerosol inhalation lung images has been interpreted rather qualitatively in the clinical practice. We have reported our approach to quantitatively analyze the radioactive count distribution on radioaerosol inhalation lung images in relation to the actual lung function data. We have defined multiple indexes to express the shape and the unevenness of the count distribution of the lung images. To reduce as much as possible the number of indexes to be used in the regression functions, the method of selection of variables was introduced to the multiple regression analysis. Because some variables showed greater coefficients of simple correlation, while others did not, multicollinearity of variables had to be taken into consideration. For this reason, we chose a principal components regression analysis. The multiple regression function for each item of pulmonary function data thus established from analysis of 67 subjects appeared usable as a predictor of the actual lung function: for example, % VC (vital capacity) could be estimated by using four indexes out of the multiple ones with a coefficient of multiple correlation (R) of 0.753, and FEVsub(1.0) % (forced expiratory volume in one second divided by forced expiratory volume), by 7 indexes with R = 0.921. Pulmonary function data regarding lung volumes and lung mechanics were estimated more accurately with greater R's than those for lung diffusion, but even in the latter the prediction was still statistically significant at p less than 0.01. We believe the multiple regression functions thus obtained are useful for estimating not only the overall but also the regional function of the lungs. (author)

  3. Metastatic tumors of lungs

    International Nuclear Information System (INIS)

    Rozenshtraukh, L.C.; Rybakova, N.I.; Vinner, M.G.

    1987-01-01

    Roentgenologic semiotics of lung metastases and their complications, as well as peculiarities of lung metastases of separate localization tumours are presented. Definition table for primary tumour by roentgenologic aspect of lung metastases is given

  4. How Lungs Work

    Science.gov (United States)

    ... Diseases > How Lungs Work How Lungs Work The Respiratory System Your lungs are part of the respiratory system, ... your sense of smell. The Parts of the Respiratory System and How They Work Airways SINUSES are hollow ...

  5. Protecting Your Lungs

    Science.gov (United States)

    ... lung capacity. Specific breathing exercises can also help improve your lung function if you have certain lung diseases, like COPD. Exercise and breathing techniques are also great for improving your mood and helping you relax. Public Health and Your ...

  6. Bone-marrow-derived mesenchymal stem cells inhibit gastric aspiration lung injury and inflammation in rats.

    Science.gov (United States)

    Zhou, Jing; Jiang, Liyan; Long, Xuan; Fu, Cuiping; Wang, Xiangdong; Wu, Xiaodan; Liu, Zilong; Zhu, Fen; Shi, Jindong; Li, Shanqun

    2016-09-01

    Gastric aspiration lung injury is one of the most common clinical events. This study investigated the effects of bone-marrow-derived mesenchymal stem cells (BMSCs) on combined acid plus small non-acidified particle (CASP)-induced aspiration lung injury. Enhanced green fluorescent protein (EGFP(+) ) or EGFP(-) BMSCs or 15d-PGJ2 were injected via the tail vein into rats immediately after CASP-induced aspiration lung injury. Pathological changes in lung tissues, blood gas analysis, the wet/dry weight ratio (W/D) of the lung, levels of total proteins and number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) were determined. The cytokine levels were measured using ELISA. Protein expression was determined by Western blot. Bone-marrow-derived mesenchymal stem cells treatment significantly reduced alveolar oedema, exudation and lung inflammation; increased the arterial partial pressure of oxygen; and decreased the W/D of the lung, the levels of total proteins and the number of total cells and neutrophils in BALF in the rats with CASP-induced lung injury. Bone-marrow-derived mesenchymal stem cells treatment decreased the levels of tumour necrosis factor-α and Cytokine-induced neutrophil chemoattractant (CINC)-1 and the expression of p-p65 and increased the levels of interleukin-10 and 15d-PGJ2 and the expression of peroxisome proliferator-activated receptor (PPAR)-γ in the lung tissue in CASP-induced rats. Tumour necrosis factor-α stimulated BMSCs to secrete 15d-PGJ2 . A tracking experiment showed that EGFP(+) BMSCs were able to migrate to local lung tissues. Treatment with 15d-PGJ2 also significantly inhibited CASP-induced lung inflammation and the production of pro-inflammatory cytokines. Our results show that BMSCs can protect lung tissues from gastric aspiration injury and inhibit lung inflammation in rats. A beneficial effect might be achieved through BMSC-derived 15d-PGJ2 activation of the PPAR-γ receptor, reducing the production of

  7. The effects of collagen-rich extracellular matrix on the intracellular delivery of glycol chitosan nanoparticles in human lung fibroblasts.

    Science.gov (United States)

    Yhee, Ji Young; Yoon, Hong Yeol; Kim, Hyunjoon; Jeon, Sangmin; Hergert, Polla; Im, Jintaek; Panyam, Jayanth; Kim, Kwangmeyung; Nho, Richard Seonghun

    2017-01-01

    Recent progress in nanomedicine has shown a strong possibility of targeted therapy for obstinate chronic lung diseases including idiopathic pulmonary fibrosis (IPF). IPF is a fatal lung disease characterized by persistent fibrotic fibroblasts in response to type I collagen-rich extracellular matrix. As a pathological microenvironment is important in understanding the biological behavior of nanoparticles, in vitro cellular uptake of glycol chitosan nanoparticles (CNPs) in human lung fibroblasts was comparatively studied in the presence or absence of type I collagen matrix. Primary human lung fibroblasts from non-IPF and IPF patients (n=6/group) showed significantly increased cellular uptake of CNPs (>33.6-78.1 times) when they were cultured on collagen matrix. To elucidate the underlying mechanism of enhanced cellular delivery of CNPs in lung fibroblasts on collagen, cells were pretreated with chlorpromazine, genistein, and amiloride to inhibit clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis, respectively. Amiloride pretreatment remarkably reduced the cellular uptake of CNPs, suggesting that lung fibroblasts mainly utilize the macropinocytosis-dependent mechanism when interacted with collagen. In addition, the internalization of CNPs was predominantly suppressed by a phosphoinositide 3-kinase (PI3K) inhibitor in IPF fibroblasts, indicating that enhanced PI3K activity associated with late-stage macropinocytosis can be particularly important for the enhanced cellular delivery of CNPs in IPF fibroblasts. Our study strongly supports the concept that a pathological microenvironment which surrounds lung fibroblasts has a significant impact on the intracellular delivery of nanoparticles. Based on the property of enhanced intracellular delivery of CNPs when fibroblasts are made to interact with a collagen-rich matrix, we suggest that CNPs may have great potential as a drug-carrier system for targeting fibrotic lung fibroblasts.

  8. The Murine Lung Microbiome Changes During Lung Inflammation and Intranasal Vancomycin Treatment

    Science.gov (United States)

    Barfod, Kenneth Klingenberg; Vrankx, Katleen; Mirsepasi-Lauridsen, Hengameh Chloé; Hansen, Jitka Stilund; Hougaard, Karin Sørig; Larsen, Søren Thor; Ouwenhand, Arthur C.; Krogfelt, Karen Angeliki

    2015-01-01

    Most microbiome research related to airway diseases has focused on the gut microbiome. This is despite advances in culture independent microbial identification techniques revealing that even healthy lungs possess a unique dynamic microbiome. This conceptual change raises the question; if lung diseases could be causally linked to local dysbiosis of the local lung microbiota. Here, we manipulate the murine lung and gut microbiome, in order to show that the lung microbiota can be changed experimentally. We have used four different approaches: lung inflammation by exposure to carbon nano-tube particles, oral probiotics and oral or intranasal exposure to the antibiotic vancomycin. Bacterial DNA was extracted from broncho-alveolar and nasal lavage fluids, caecum samples and compared by DGGE. Our results show that: the lung microbiota is sex dependent and not just a reflection of the gut microbiota, and that induced inflammation can change lung microbiota. This change is not transferred to offspring. Oral probiotics in adult mice do not change lung microbiome detectible by DGGE. Nasal vancomycin can change the lung microbiome preferentially, while oral exposure does not. These observations should be considered in future studies of the causal relationship between lung microbiota and lung diseases. PMID:26668669

  9. Technology and outcomes assessment in lung transplantation.

    Science.gov (United States)

    Yusen, Roger D

    2009-01-15

    Lung transplantation offers the hope of prolonged survival and significant improvement in quality of life to patients that have advanced lung diseases. However, the medical literature lacks strong positive evidence and shows conflicting information regarding survival and quality of life outcomes related to lung transplantation. Decisions about the use of lung transplantation require an assessment of trade-offs: do the potential health and quality of life benefits outweigh the potential risks and harms? No amount of theoretical reasoning can resolve this question; empiric data are needed. Rational analyses of these trade-offs require valid measurements of the benefits and harms to the patients in all relevant domains that affect survival and quality of life. Lung transplant systems and registries mainly focus outcomes assessment on patient survival on the waiting list and after transplantation. Improved analytic approaches allow comparisons of the survival effects of lung transplantation versus continued waiting. Lung transplant entities do not routinely collect quality of life data. However, the medical community and the public want to know how lung transplantation affects quality of life. Given the huge stakes for the patients, the providers, and the healthcare systems, key stakeholders need to further support quality of life assessment in patients with advanced lung disease that enter into the lung transplant systems. Studies of lung transplantation and its related technologies should assess patients with tools that integrate both survival and quality of life information. Higher quality information obtained will lead to improved knowledge and more informed decision making.

  10. Kinetics of badminton lunges in four directions.

    Science.gov (United States)

    Hong, Youlian; Wang, Shao Jun; Lam, Wing Kai; Cheung, Jason Tak Man

    2014-02-01

    The lunge is the most fundamental skill in badminton competitions. Fifteen university-level male badminton players performed lunge maneuvers in four directions, namely, right-forward, left-forward, right-backward, and left-backward, while wearing two different brands of badminton shoes. The test compared the kinetics of badminton shoes in performing typical lunge maneuvers. A force plate and an insole measurement system measured the ground reaction forces and plantar pressures. These measurements were compared across all lunge maneuvers. The left-forward lunge generated significantly higher first vertical impact force (2.34 ± 0.52 BW) than that of the right-backward (2.06 ± 0.60 BW) and left-backward lunges (1.78 ± 0.44 BW); higher second vertical impact force (2.44 ± 0.51 BW) than that of the left-backward lunge (2.07 ± 0.38 BW); and higher maximum anterior-posterior shear force (1.48 ± 0.36 BW) than that of the left-backward lunge (1.18 ± 0.38 BW). Compared with other lunge directions, the left-forward lunge showed higher mean maximum vertical impact anterior-posterior shear forces and their respective maximum loading rates, and the plantar pressure at the total foot and heel regions. Therefore, the left-forward lunge is a critical maneuver for badminton biomechanics and related footwear research because of the high loading magnitude generated during heel impact.

  11. Lung PET scan

    Science.gov (United States)

    ... Chest PET scan; Lung positron emission tomography; PET - chest; PET - lung; PET - tumor imaging; ... Grainger & Allison's Diagnostic Radiology: A Textbook of Medical Imaging . 6th ed. Philadelphia, ...

  12. Extravascular Lung Water and Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    Ritesh Maharaj

    2012-01-01

    Full Text Available Acute lung injury carries a high burden of morbidity and mortality and is characterised by nonhydrostatic pulmonary oedema. The aim of this paper is to highlight the role of accurate quantification of extravascular lung water in diagnosis, management, and prognosis in “acute lung injury” and “acute respiratory distress syndrome”. Several studies have verified the accuracy of both the single and the double transpulmonary thermal indicator techniques. Both experimental and clinical studies were searched in PUBMED using the term “extravascular lung water” and “acute lung injury”. Extravascular lung water measurement offers information not otherwise available by other methods such as chest radiography, arterial blood gas, and chest auscultation at the bedside. Recent data have highlighted the role of extravascular lung water in response to treatment to guide fluid therapy and ventilator strategies. The quantification of extravascular lung water may predict mortality and multiorgan dysfunction. The limitations of the dilution method are also discussed.

  13. Histochemical alterations in one lung ventilation.

    Science.gov (United States)

    Yin, Kingsley; Gribbin, Elizabeth; Emanuel, Steven; Orndorff, Rebecca; Walker, Jean; Weese, James; Fallahnejad, Manucher

    2007-01-01

    One lung ventilation is a commonly performed surgical procedure. Although there have been several reports showing that one-lung ventilation can cause pathophysiological alterations such as pulmonary hypoxic vasoconstriction and intrapulmonary shunting, there have been virtually no reports on the effects of one-lung ventilation on lung histology. Yorkshire pigs (11-17 kg) were anesthetized, a tracheotomy performed and a tracheal tube inserted. The chest was opened and one lung ventilation (OLV), was induced by clamping of the right main bronchus. OLV was continued for 60 min before the clamp was removed and two lung ventilation (TLV) started. TLV was continued for 30 to 60 min. Blood and lung biopsies were taken immediately before OLV, 30 min and 60 min of OLV and after restoration of TLV. Histological analyses revealed that the non-ventilated lung was totally collapsed during OLV. On reventilation, there was clear evidence of vascular congestion and alveolar wall thickening at 30 min after TLV. At 60 min of TLV, there was still vascular congestion. Serum nitrite levels (as an index of nitric oxide production) showed steady decline over the course of the experimental period, reaching a significantly low level on reventilation (compared with baseline levels before OLV). Lung MPO activity (marker of neutrophil sequestration) and serum TNFalpha levels were not raised during the entire experimental period. These results suggest that there was lung vascular injury after OLV, which was associated with reduced levels of nitric oxide production and not associated with an inflammatory response.

  14. Antitumor activity of ZD6126, a novel vascular-targeting agent, is enhanced when combined with ZD1839, an epidermal growth factor receptor tyrosine kinase inhibitor, and potentiates the effects of radiation in a human non-small cell lung cancer xenograft model.

    Science.gov (United States)

    Raben, David; Bianco, Cataldo; Damiano, Vincenzo; Bianco, Roberto; Melisi, Davide; Mignogna, Chiara; D'Armiento, Francesco Paolo; Cionini, Luca; Bianco, A Raffaele; Tortora, Giampaolo; Ciardiello, Fortunato; Bunn, Paul

    2004-08-01

    Targeting the tumor vasculature may offer an alternative or complementary therapeutic approach to targeting growth factor signaling in lung cancer. The aim of these studies was to evaluate the antitumor effects in vivo of the combination of ZD6126, a tumor-selective vascular-targeting agent; ZD1839 (gefitinib, Iressa), an epidermal growth factor receptor tyrosine kinase inhibitor; and ionizing radiation in the treatment of non-small cell lung cancer xenograft model. Athymic nude mice with established flank A549 human non-small cell lung cancer xenograft model xenografts were treated with fractionated radiation therapy, ZD6126, ZD1839, or combinations of each treatment. ZD6126 (150 mg/kg) was given i.p. the day after each course of radiation. Animals treated with ZD1839 received 100 mg/kg per dose per animal, 5 or 7 days/wk for 2 weeks. Immunohistochemistry was done to evaluate the effects on tumor growth using an anti-Ki67 monoclonal antibody. Effects on tumor-induced vascularization were quantified using an anti-factor VIII-related antigen monoclonal antibody. ZD6126 attenuated the growth of human A549 flank xenografts compared with untreated animals. Marked antitumor effects were observed when animals were treated with a combination of ZD6126 and fractionated radiation therapy with protracted tumor regression. ZD6126 + ZD1839 resulted in a greater tumor growth delay than either agent alone. Similar additive effects were seen with ZD1839 + fractionated radiation. Finally, the addition of ZD6126 to ZD1839 and radiation therapy seemed to further improve tumor growth control, with a significant tumor growth delay compared with animals treated with single agent or with double combinations. Immunohistochemistry showed that ZD1839 induced a marked reduction in A549 tumor cell proliferation. Both ZD1839 and ZD6126 treatment substantially reduced tumor-induced angiogenesis. ZD6126 caused marked vessel destruction through loss of endothelial cells and thrombosis

  15. Cooperative Enhancement of Radiosensitivity After Combined Treatment of 17-(Allylamino)-17-Demethoxygeldanamycin and Celecoxib in Human Lung and Colon Cancer Cell Lines

    Science.gov (United States)

    Kim, Young-Mee

    2012-01-01

    We investigated whether the combined treatment of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an inhibitor of heat-shock protein 90 (hsp90), and celecoxib, an inhibitor of cyclooxygenase-2, can cooperatively enhance the radiosensitivity of various human cancer cells. Combined treatment with 17-AAG and celecoxib, at clinically relevant concentrations, cooperatively induced radiosensitization in all tested cancer cells, but not in normal cells. Cooperative radiosensitization by the drug combination was also shown in a human tumor xenograft system. We found that ataxia-telangiectasia and rad3-related (ATR) and ataxia-telangiectasia mutated (ATM) are novel client proteins of hsp90. Combined treatment with 17-AAG and celecoxib cooperatively induced downregulation of ATR and ATM. In conclusion, combined treatment with 17-AAG and celecoxib at clinically relevant concentrations may significantly enhance the therapeutic efficacy of ionizing radiation. PMID:21830942

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

    Science.gov (United States)

    Kim, Carla F

    2017-06-30

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

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

    Directory of Open Access Journals (Sweden)

    Carla F. Kim

    2017-06-01

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

  18. Analysis of ring enhancement in the cranial computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Huh, Seung Jae; Chung, Yong In; Chang, Kee Hyun [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    1980-12-15

    A total of 83 cases with ring enhancement in the cranial computed tomography were radiologically analyzed to determine the specific CT findings of the primary and metastatic brain tumor, inflammatory disease, resolving hematoma, and cerebral infarction. The brief results are as follows. Glioblastoma multiform show a characteristic thick or thin irregular ring enhancement with significant mass effect and surrounding edema. Most of the metastatic tumors also show irregular thick or thin walled ring enhancement with significant surrounding edema. Tumoral hemorrhage was observed in the metastatic melanoma, breast cancer, and lung cancer. The brain abscess usually show characteristic thin regular and smooth ring enhancement with moderate peripheral edema. The parasitic cysts also show thin regular ring enhancement with different degree of surrounding edema. Ring enhancement in resolving hematomas and cerebral infarctions usually occurs about 10-30 days after the onset of symptoms, which shows thin and regular ring pattern without significant surrounding edema.

  19. Analysis of ring enhancement in the cranial computed tomography

    International Nuclear Information System (INIS)

    Huh, Seung Jae; Chung, Yong In; Chang, Kee Hyun

    1980-01-01

    A total of 83 cases with ring enhancement in the cranial computed tomography were radiologically analyzed to determine the specific CT findings of the primary and metastatic brain tumor, inflammatory disease, resolving hematoma, and cerebral infarction. The brief results are as follows. Glioblastoma multiform show a characteristic thick or thin irregular ring enhancement with significant mass effect and surrounding edema. Most of the metastatic tumors also show irregular thick or thin walled ring enhancement with significant surrounding edema. Tumoral hemorrhage was observed in the metastatic melanoma, breast cancer, and lung cancer. The brain abscess usually show characteristic thin regular and smooth ring enhancement with moderate peripheral edema. The parasitic cysts also show thin regular ring enhancement with different degree of surrounding edema. Ring enhancement in resolving hematomas and cerebral infarctions usually occurs about 10-30 days after the onset of symptoms, which shows thin and regular ring pattern without significant surrounding edema

  20. Staging of Lung Cancer

    Science.gov (United States)

    ... LUNG CANCER MINI-SERIES #2 Staging of Lung Cancer Once your lung cancer is diagnosed, staging tells you and your health care provider about ... at it under a microscope. The stages of lung cancer are listed as I, II, III, and IV ...

  1. Lung needle biopsy

    Science.gov (United States)

    ... if you have certain lung diseases such as emphysema. Usually, a collapsed lung after a biopsy does not need treatment. But ... any type Bullae (enlarged alveoli that occur with emphysema) Cor pulmonale (condition ... of the lung High blood pressure in the lung arteries Severe ...

  2. Two cases with giant lung abscess originating in the irradiated lung field following the concurrent chemo-radiotherapy of lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Takeshi; Inui, Hiroyuki; Yukawa, Susumu; Nomoto, Hiroshi (Wakayama Medical Coll. (Japan)); Minakata, Yoshiaki; Yamagata, Toshiyuki

    1992-05-01

    Two patients with giant lung abscess originating in the irradiated lung field are reported. Lung abscesses occurred during the term of leukopenia following the concurrent chemo-radiotherapy of lung cancer. Both patients were diagnosed as small cell lung cancer, and were treated concurrently with chemotherapy (Cisplatin + Etoposide) and radiotherapy (total 40-50 Gy). Case 1 was a 59 years old male. Seven weeks after the first irradiation, a giant lung abscess was caused by methicillin resistant staphylococcus aureus (MRSA) originated in the lung field with radiation pneumonitis, and giant bronchial fistula was formed, that showed the specific bronchofiberscopic findings. Case 2 was a 67 years old male. Twelve weeks after the first irradiation, a giant lung abscess was caused by pseudomonas aeruginosa originated in the irradiated lung field following the formation of a pneumatocele. MRSA and pseudomonas aeruginosa are important as cause of hospital infection, and both can cause lung abscess. However, in our cases, lung abscess were formed just in the irradiated lung field and rapidly enlarged. These clinical findings suggested that myelosuppression and radiation injury of lung tissue might cause such giant lung abscess. (author).

  3. Two cases with giant lung abscess originating in the irradiated lung field following the concurrent chemo-radiotherapy of lung cancer

    International Nuclear Information System (INIS)

    Ikeda, Takeshi; Inui, Hiroyuki; Yukawa, Susumu; Nomoto, Hiroshi; Minakata, Yoshiaki; Yamagata, Toshiyuki.

    1992-01-01

    Two patients with giant lung abscess originating in the irradiated lung field are reported. Lung abscesses occurred during the term of leukopenia following the concurrent chemo-radiotherapy of lung cancer. Both patients were diagnosed as small cell lung cancer, and were treated concurrently with chemotherapy (Cisplatin + Etoposide) and radiotherapy (total 40-50 Gy). Case 1 was a 59 years old male. Seven weeks after the first irradiation, a giant lung abscess was caused by methicillin resistant staphylococcus aureus (MRSA) originated in the lung field with radiation pneumonitis, and giant bronchial fistula was formed, that showed the specific bronchofiberscopic findings. Case 2 was a 67 years old male. Twelve weeks after the first irradiation, a giant lung abscess was caused by pseudomonas aeruginosa originated in the irradiated lung field following the formation of a pneumatocele. MRSA and pseudomonas aeruginosa are important as cause of hospital infection, and both can cause lung abscess. However, in our cases, lung abscess were formed just in the irradiated lung field and rapidly enlarged. These clinical findings suggested that myelosuppression and radiation injury of lung tissue might cause such giant lung abscess. (author)

  4. Enhanced anticancer effects of Scutellaria barbata D. Don in combination with traditional Chinese medicine components on non-small cell lung cancer cells.

    Science.gov (United States)

    Wang, Qian; Acharya, Narayan; Liu, Zhongwei; Zhou, Xianmei; Cromie, Meghan; Zhu, Jia; Gao, Weimin

    2018-05-10

    Experience-based herbal medicine as a complementary to modern western medicine has triggered an array of studies in quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used to treat different types of cancers, but its molecular mechanism of action is not clearly understood. In this study, we attempted to elucidate the mode of action of a traditional Chinese medicine prescription with a total of 14 components, named Lian-Jia-San-Jie-Fang (LJSJF, in Chinese), where SB works as the "principle" against non-small cell lung cancer (NSCLC) cells. Four different NSCLC cell lines (A549, H460, H1650, and H1975) were used. Cytotoxicity, in vitro tumorigenicity, gene expression, and protein expression were analyzed by MTT assay, soft agar assay, real-time PCR, and Western blots, respectively. Among the 14 components in LJSJF, SB was the only one to possess cytotoxic effects at its pharmacologically relevant doses. Additionally, we observed synergistically dose-dependent cytotoxic effects of SB in combination with other LJSJF components. After SB or LJSJF treatment, significant reductions in colony number and/or size were observed in A549 and H460; a notable dose-dependent decrease in EGFR was observed in A549, H460, and H1650; significant downregulation in EGFR and its downstream signaling targets mTOR and p38MAPK were also observed in A549 and H460; and p53 and p21 were significantly increased while survivin, cyclin D1, and MDM2 were significantly decreased in A549. Additionally, p53, p21, and Mettl7b were decreased, but p73 was increased in H460. Neither EGFR nor p53 was changed in H1975. Therefore, SB or LJSJF may induce cytotoxic effects by regulating multiple and/or distinct apoptotic pathways in different NSCLC cells. LJSJF exerts more pronounced cytotoxic effects against NSCLC cells than SB does by synergistically regulating the underlining molecular mechanisms including EGFR and/or p53 signaling pathways. Copyright © 2018 Elsevier B.V. All

  5. Pathogenic mechanism in lung fibrosis

    International Nuclear Information System (INIS)

    Witschi, H.; Haschek, W.M.; Meyer, K.R.; Ullrich, R.L.; Dalbey, W.E.

    1979-01-01

    The purpose of the study was to examine whether an interaction between two agents causing alveolar epithelial damage would produce lung fibrosis. In mouse lung, intraperitoneal injection of the antioxidant butylated hydroxytoluene causes diffuse alveolar type I cell necrosis, followed by proliferation of type II alveolar cells. In animals exposed to 70% O 2 or 100-200 rad x rays during the phase of type II cell proliferation following BHT, diffuse interstitial lung fibrosis developed within 2 weeks. Quantitative analysis of the lungs for hydroxyproline showed that the interaction between BHT and O 2 or x rays was synergistic. If exposure to O 2 or x rays was delayed until epithelial recovery was complete, no fibrosis was seen. Abnormally high levels of lung collagen persisted up to 6 months after one single treatment with BHT and 100 rad x rays. A commonly seen form of chronic lung damage may thus be caused by an acute interaction between a bloodborne agent which damages the alveolar cell and a toxic inhalant or x rays, provided a critically ordered sequence of exposure is observed

  6. Bacterial lung abscess

    International Nuclear Information System (INIS)

    Groskin, S.A.; Panicek, D.M.; Ewing, D.K.; Rivera, F.; Math, K.; Teixeira, J.; Heitzman, E.R.

    1987-01-01

    A retrospective review of patients with bacterial lung abscess was carried out. Demographic, clinical, and radiographical features of this patient group are compared with similar data from patients with empyema and/or cavitated lung carcinoma; differential diagnostic points are stressed. The entity of radiographically occult lung abscess is discussed. Complications associated with bacterial lung abscess are discussed. Current therapeutic options and treatment philosophy for patients with bacterial lung abscess are noted

  7. New estimates for human lung dimensions

    International Nuclear Information System (INIS)

    Kennedy, Christine; Sidavasan, Sivalal; Kramer, Gary

    2008-01-01

    Full text: The currently used lung dimensions in dosimetry were originally estimated in the 1940s from Army recruits. This study provides new estimates of lung dimensions based on images acquired from a sample from the general population (varying age and sex). Building accurate models, called phantoms, of the human lung requires that the spatial dimensions (length, width, and depth) be quantified, in addition to volume. Errors in dose estimates may result from improperly sized lungs as the counting efficiency of externally mounted detectors (e.g., in a lung counter) is dependent on the position of internally deposited radioactive material (i.e., the size of the lung). This study investigates the spatial dimensions of human lungs. Lung phantoms have previously been made in one of two sizes. The Lawrence Livermore National Laboratory Torso Phantom (LLNL) has deep, short lungs whose dimensions do not comply well with the data published in Report 23 (Reference Man) issued by the International Commission on Radiological Protection (ICRP). The Japanese Atomic Energy Research Institute Torso Phantom(JAERI), has longer, shallower lungs that also deviate from the ICRP values. However, careful examination of the ICRP recommended values shows that they are soft. In fact, they have been dropped from the ICRP's Report 89 which updates Report 23. Literature surveys have revealed a wealth of information on lung volume, but very little data on the spatial dimensions of human lungs. Better lung phantoms need to be constructed to more accurately represent a person so that dose estimates may be quantified more accurately in view of the new, lower, dose limits for occupationally exposed workers and the general public. Retrospective chest images of 60 patients who underwent imaging of the chest- lungs as part of their healthy persons occupational screening for lung disease were chosen. The chosen normal lung images represent the general population). Ages, gender and weight of the

  8. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

    Science.gov (United States)

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y; Fong, Guo-Hua; Sakmar, Thomas P; Rafii, Shahin; Ding, Bi-Sen

    2016-02-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.

  9. Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis.

    Science.gov (United States)

    Kida, Taiki; Ayabe, Shinya; Omori, Keisuke; Nakamura, Tatsuro; Maehara, Toko; Aritake, Kosuke; Urade, Yoshihiro; Murata, Takahisa

    2016-01-01

    Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Compared with H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition in lungs 14 days after the bleomycin injection. The enhanced fibrotic response was accompanied by an increased mRNA expression of inflammatory mediators, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and cyclooxygenase-2 on day 3. H-PGDS deficiency also increased vascular permeability on day 3 and infiltration of neutrophils and macrophages in lungs on day 3 and 7. Immunostaining showed that the neutrophils and macrophages expressed H-PGDS, and its mRNA expression was increased on day 3and 7 in WT lungs. These observations suggest that H-PGDS-derived PGD2 plays a protective role in bleomycin-induced lung inflammation and pulmonary fibrosis.

  10. Role of macrophages and oxygen radicals in IgA induced lung injury in the rat

    International Nuclear Information System (INIS)

    Johnson, K.J.; Ward, P.A.; Kunkel, R.G.; Wilson, B.S.

    1986-01-01

    Acute lung injury in the rat has been induced by the instillation of affinity-purified mouse monoclonal IgA antibody with specific reactivity to dinitrophenol (DNP) coupled to albumin. This model of lung injury requires an intact complement system but not neutrophils, and evidence suggests that pulmonary macrophages are the critical effector cell. Macrophages retrievable from the lungs of the IgA immune complex treated rats are considerably increased in number as compared to control animals which received only the antibody. In addition these cells show evidence of activation in vivo with greater spontaneous generation of the superoxide anion (O 2 - ) as well as significantly enhanced O 2 - response in the presence of a second stimulus. Inhibition studies in vivo suggest that the lung injury is mediated by oxygen radical generation by the pulmonary macrophages. Pretreatment of rats with superoxide dismutase (SOD), catalase, the iron chelator deferoxamine or the hydroxyl radical scavenger dimethyl sulfoxide (DMSO) all markedly suppressed the development of the lung injury. In summary, these studies suggest that IgA immune complex injury in the rat lung is mediated by oxygen radical formation from pulmonary macrophages

  11. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis

    Science.gov (United States)

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y.; Fong, Guo-Hua; Sakmar, Thomas P.; Rafii, Shahin; Ding, Bi-Sen

    2016-01-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin–dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladaptbed hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis. PMID:26779814

  12. [Development of the lung cancer diagnostic system].

    Science.gov (United States)

    Lv, You-Jiang; Yu, Shou-Yi

    2009-07-01

    To develop a lung cancer diagnosis system. A retrospective analysis was conducted in 1883 patients with primary lung cancer or benign pulmonary diseases (pneumonia, tuberculosis, or pneumonia pseudotumor). SPSS11.5 software was used for data processing. For the relevant factors, a non-factor Logistic regression analysis was used followed by establishment of the regression model. Microsoft Visual Studio 2005 system development platform and VB.Net corresponding language were used to develop the lung cancer diagnosis system. The non-factor multi-factor regression model showed a goodness-of-fit (R2) of the model of 0.806, with a diagnostic accuracy for benign lung diseases of 92.8%, a diagnostic accuracy for lung cancer of 89.0%, and an overall accuracy of 90.8%. The model system for early clinical diagnosis of lung cancer has been established.

  13. Lung Cancer—Patient Version

    Science.gov (United States)

    The two main types of lung cancer are non-small cell lung cancer and small cell lung cancer. Smoking causes most lung cancers, but nonsmokers can also develop lung cancer. Start here to find information on lung cancer treatment, causes and prevention, screening, research, and statistics on lung cancer.

  14. Netrin-1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin-Induced Pulmonary Fibrosis.

    Science.gov (United States)

    Sun, Huanxing; Zhu, Yangyang; Pan, Hongyi; Chen, Xiaosong; Balestrini, Jenna L; Lam, TuKiet T; Kanyo, Jean E; Eichmann, Anne; Gulati, Mridu; Fares, Wassim H; Bai, Hanwen; Feghali-Bostwick, Carol A; Gan, Ye; Peng, Xueyan; Moore, Meagan W; White, Eric S; Sava, Parid; Gonzalez, Anjelica L; Cheng, Yuwei; Niklason, Laura E; Herzog, Erica L

    2016-05-01

    Fibrocytes are collagen-producing leukocytes that accumulate in patients with systemic sclerosis (SSc; scleroderma)-related interstitial lung disease (ILD) via unknown mechanisms that have been associated with altered expression of neuroimmune proteins. The extracellular matrix (ECM) influences cellular phenotypes. However, a relationship between the lung ECM and fibrocytes in SSc has not been explored. The aim of this study was to use a novel translational platform based on decellularized human lungs to determine whether the lung ECM of patients with scleroderma controls the development of fibrocytes from peripheral blood mononuclear cells. We performed biomechanical evaluation of decellularized scaffolds prepared from lung explants from healthy control subjects and patients with scleroderma, using tensile testing and biochemical and proteomic analysis. Cells obtained from healthy controls and patients with SSc-related ILD were cultured on these scaffolds, and CD45+pro-ColIα1+ cells meeting the criteria for fibrocytes were quantified. The contribution of the neuromolecule netrin-1 to fibrosis was assessed using neutralizing antibodies in this system and by administering bleomycin via inhalation to netrin-1(+/-) mice. Compared with control lung scaffolds, lung scaffolds from patients with SSc-related ILD showed aberrant anatomy, enhanced stiffness, and abnormal ECM composition. Culture of control cells in lung scaffolds from patients with SSc-related ILD increased production of pro-ColIα1+ cells, which was stimulated by enhanced stiffness and abnormal ECM composition. Cells from patients with SSc-related ILD demonstrated increased pro-ColIα1 responsiveness to lung scaffolds from scleroderma patients but not enhanced stiffness. Enhanced detection of netrin-1-expressing CD14(low) cells in patients with SSc-related ILD was observed, and antibody-mediated netrin-1 neutralization attenuated detection of CD45+pro-ColIα1+ cells in all settings. Netrin-1(+/-) mice were

  15. Estrogen Signaling in Lung Cancer: An Opportunity for Novel Therapy

    International Nuclear Information System (INIS)

    Baik, Christina S.; Eaton, Keith D.

    2012-01-01

    Lung cancer is the leading cause of cancer death in U.S. and represents a major public health burden. Epidemiologic data have suggested that lung cancer in women may possess different biological characteristics compared to men, as evidenced by a higher proportion of never-smokers among women with lung cancer. Emerging data indicate that female hormones such as estrogen and progesterone play a significant role in lung carcinogenesis. It has been reported that estrogen and progesterone receptors are expressed in lung cancer cell lines as well as in patient-derived tumors. Hormone related risk factors such as hormone replacement therapy have been implicated in lung carcinogenesis and several preclinical studies show activity of anti-estrogen therapy in lung cancer. In this review, we summarize the emerging evidence for the role of reproductive hormones in lung cancer and implications for lung cancer therapy

  16. Positron emission tomography of the lung

    International Nuclear Information System (INIS)

    Wollmer, P.

    1984-01-01

    Positron emission tomography enables the distribution of positron emitting isotopes to be imaged in a transverse plane through the body and the regional concentration of the isotope to be measured quantitatively. This thesis reports some applications of positron emission tomography to studies of pulmonary pathophysiology. Measurements in lung phantoms showed that regional lung density could be measured from a transmission tomogram obtained with an external source of positron emitting isotope. The regional, fractional blood volume was measured after labelling the blood with carbon-11-monoxide. Regional extravascular lung density (lung tissue and interstitial water per unit thoracic volume) was obtained by subtracting fractional blood volume from lung density. Measurements in normal subjects revealed large regional variations in lung density and fractional blood volume in the supine posture. Extravascular lung density showed a more uniform distribution. The technique has been used to study patients with chronic interstitial pulmonary oedema, pulmonary sarcoidosis and fibrosis, pulmonary arterial hypertension and patients with intracardiac, left-to-right shunt. Tomographic measurements of pulmonary tissue concentration of radionuclides are difficult, since corrections for the blood content and the inflation of the lung must be applied. A simultaneous measurement of lung density and fractional blood volume allows such corrections to be made and the extravascular tracer concentration to be calculated. This has been applied to measurements of the tissue penetration of carbon-11-labelled erythromycin in patients with lobar pneumonia. (author)

  17. Waiting narratives of lung transplant candidates.

    Science.gov (United States)

    Yelle, Maria T; Stevens, Patricia E; Lanuza, Dorothy M

    2013-01-01

    Before 2005, time accrued on the lung transplant waiting list counted towards who was next in line for a donor lung. Then in 2005 the lung allocation scoring system was implemented, which meant the higher the illness severity scores, the higher the priority on the transplant list. Little is known of the lung transplant candidates who were listed before 2005 and were caught in the transition when the lung allocation scoring system was implemented. A narrative analysis was conducted to explore the illness narratives of seven lung transplant candidates between 2006 and 2007. Arthur Kleinman's concept of illness narratives was used as a conceptual framework for this study to give voice to the illness narratives of lung transplant candidates. Results of this study illustrate that lung transplant candidates expressed a need to tell their personal story of waiting and to be heard. Recommendation from this study calls for healthcare providers to create the time to enable illness narratives of the suffering of waiting to be told. Narrative skills of listening to stories of emotional suffering would enhance how healthcare providers could attend to patients' stories and hear what is most meaningful in their lives.

  18. Waiting Narratives of Lung Transplant Candidates

    Directory of Open Access Journals (Sweden)

    Maria T. Yelle

    2013-01-01

    Full Text Available Before 2005, time accrued on the lung transplant waiting list counted towards who was next in line for a donor lung. Then in 2005 the lung allocation scoring system was implemented, which meant the higher the illness severity scores, the higher the priority on the transplant list. Little is known of the lung transplant candidates who were listed before 2005 and were caught in the transition when the lung allocation scoring system was implemented. A narrative analysis was conducted to explore the illness narratives of seven lung transplant candidates between 2006 and 2007. Arthur Kleinman’s concept of illness narratives was used as a conceptual framework for this study to give voice to the illness narratives of lung transplant candidates. Results of this study illustrate that lung transplant candidates expressed a need to tell their personal story of waiting and to be heard. Recommendation from this study calls for healthcare providers to create the time to enable illness narratives of the suffering of waiting to be told. Narrative skills of listening to stories of emotional suffering would enhance how healthcare providers could attend to patients’ stories and hear what is most meaningful in their lives.

  19. Intracerebral metastasis showing restricted diffusion: Correlation with histopathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Duygulu, G. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Ovali, G. Yilmaz [Radiology Department, Celal Bayar University Medicine School, Manisa (Turkey)], E-mail: gulgun.yilmaz@bayar.edu.tr; Calli, C.; Kitis, O.; Yuenten, N. [Radiology Department, Ege University Medicine School, Izmir (Turkey); Akalin, T. [Pathology Department, Ege University Medicine School, Izmir (Turkey); Islekel, S. [Neurosurgery Department, Ege University Medicine School, Izmir (Turkey)

    2010-04-15

    Objective: We aimed to detect the frequency of restricted diffusion in intracerebral metastases and to find whether there is correlation between the primary tumor pathology and diffusion-weighted MR imaging (DWI) findings of these metastases. Material and methods: 87 patients with intracerebral metastases were examined with routine MR imaging and DWI. 11 hemorrhagic metastatic lesions were excluded. The routine MR imaging included three plans before and after contrast enhancement. The DWI was performed with spin-echo EPI sequence with three b values (0, 500 and 1000), and ADC maps were calculated. 76 patients with metastases were grouped according to primary tumor histology and the ratios of restricted diffusion were calculated according to these groups. ADCmin values were measured within the solid components of the tumors and the ratio of metastases with restricted diffusion to that which do not show restricted diffusion were calculated. Fisher's exact and Mann-Whitney U tests were used for the statistical analysis. Results: Restricted diffusion was observed in a total of 15 metastatic lesions (19, 7%). Primary malignancy was lung carcinoma in 10 of these cases (66, 6%) (5 small cell carcinoma, 5 non-small cell carcinoma), and breast carcinoma in three cases (20%). Colon carcinoma and testicular teratocarcinoma were the other two primary tumors in which restricted diffusion in metastasis was detected. There was no statistical significant difference between the primary pathology groups which showed restricted diffusion (p > 0.05). ADCmin values of solid components of the metastasis with restricted diffusion and other metastasis without restricted diffusion also showed no significant statistical difference (0.72 {+-} 0.16 x 10{sup -3} mm{sup 2}/s and 0.78 {+-} 21 x 10{sup -3} mm{sup 2}/s respectively) (p = 0.325). Conclusion: Detection of restricted diffusion on DWI in intracerebral metastasis is not rare, particularly if the primary tumor is lung or breast

  20. Planimetric determination of lung volume

    International Nuclear Information System (INIS)

    Bieber, M.; Maurer, H.J.

    1984-01-01

    The total volume of the lungs was determined by digital planimetry in 102 patients with emphysema and 33 normal controls aged between 30 and 79 years. The results were compared with the findings obtained from spirometric measurements. Mean values showed a significant relationship to age, body size and body surface. Planimetrically determined lung volume did not show a linear relationship with age, but increased after 60 years. Beyong 60 years, spirometric findings were lower because of an increase in the number of patients with emphysema. The results have shown that digital planimetry is a useful addition to spirometry. (orig.) [de

  1. Application of serum SELDI proteomic patterns in diagnosis of lung cancer

    International Nuclear Information System (INIS)

    Yang, Shuan-ying; Xiao, Xue-yuan; Zhang, Wang-gang; Zhang, Li-juan; Zhang, Wei; Zhou, Bin; Chen, Guoan; He, Da-cheng

    2005-01-01

    Currently, no satisfactory biomarkers are available to screen for lung cancer. Surface-Enhanced Laser Desorption/ionization Time-of- Flight Mass Spectrometry ProteinChip system (SELDI-TOF-MS) is one of the currently used techniques to identify biomarkers for cancers. The aim of this study is to explore the application of serum SELDI proteomic patterns to distinguish lung cancer patients from healthy individuals. A total of 208 serum samples, including 158 lung cancer patients and 50 healthy individuals, were randomly divided into a training set (including 11 sera from patients with stages I/II lung cancer, 63 from patients with stages III/IV lung cancer and 20 from healthy controls) and a blinded test set (including 43 sera from patients with stages I/II lung cancer, 41 from patients with stages III/IV lung cancer and 30 from healthy controls). All samples were analyzed by SELDI technology. The spectra were generated on weak cation exchange (WCX2) chips, and protein peaks clustering and classification analyses were made using Ciphergen Biomarker Wizard and Biomarker Pattern software, respectively. We additionally determined Cyfra21-1 and NSE in the 208 serum samples included in this study using an electrochemiluminescent immunoassay. Five protein peaks at 11493, 6429, 8245, 5335 and 2538 Da were automatically chosen as a biomarker pattern in the training set. When the SELDI marker pattern was tested with the blinded test set, it yielded a sensitivity of 86.9%, a specificity of 80.0% and a positive predictive value of 92.4%. The sensitivities provided by Cyfra21-1 and NSE used individually or in combination were significantly lower than that of the SELDI marker pattern (P < 0.005 or 0.05, respectively). Based on the results of the test set, we found that the SELDI marker pattern showed a sensitivity of 91.4% in the detection of non-small cell lung cancers (NSCLC), which was significantly higher than that in the detection of small cell lung cancers (P < 0.05); The

  2. Antineoplastic and immunomodulatory effect of polyphenolic components of Achyranthes aspera (PCA) extract on urethane induced lung cancer in vivo.

    Science.gov (United States)

    Narayan, Chandradeo; Kumar, Arvind

    2014-01-01

    Polyphenolic compounds of Achyranthes aspera (PCA) extract is evaluated for anti-cancerous and cytokine based immunomodulatory effects. The PCA extract contains known components of phenolic acid and flavonoids such as mixture of quinic acid, chlorogenic acid, kaempferol, quercetin and chrysin along with many unknown components. PCA has been orally feed to urethane (ethyl carbamate) primed lung cancerous mice at a dosage of 100 mg/kg body weight for 30 consecutive days. 100 mg powder of A. aspera contains 2.4 mg phenolic acid and 1.1 mg flavonoid (2:1 ratio). Enhanced activities and expression of antioxidant enzymes GST, GR, CAT, SOD, while down regulated expression and activation of LDH enzymes in PCA feed urethane primed lung cancerous tissues as compared to PCA non-feed urethane primed lung cancerous tissues were observed. PCA feed urethane primed lung tissues showed down regulated expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α along with TFs, NF-κB and Stat3 while the expression of pro-apoptotic proteins Bax and p53 were enhanced in PCA feed urethane primed lung tissues. FTIR and CD spectroscopy data revealed that PCA resisted the urethane mediated conformational changes of DNA which is evident by the shift in guanine and thymine bands in FTIR from 1,708 to 1,711 cm(-1) and 1,675 to 1,671 cm(-1), respectively in PCA feed urethane primed lung cancerous tissues DNA in comparison to urethane primed lung cancerous tissues DNA. The present study suggests that PCA components have synergistic anti-cancerous and cytokine based immunomodulatory role and DNA conformation restoring effects. However, more research is required to show the effects of each component separately and in combination for effective therapeutic use to cure and prevent lung cancer including other cancers.

  3. Longitudinal follow-up study of smoking-induced emphysema progression in low-dose CT screening of lung cancer

    Science.gov (United States)

    Suzuki, H.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, Masahiro; Moriyama, N.

    2014-03-01

    Chronic obstructive pulmonary disease is a major public health problem that is predicted to be third leading cause of death in 2030. Although spirometry is traditionally used to quantify emphysema progression, it is difficult to detect the loss of pulmonary function by emphysema in early stage, and to assess the susceptibility to smoking. This study presents quantification method of smoking-induced emphysema progression based on annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in lung cancer screening. The method consists of three steps. First, lung lobes are segmented using extracted interlobar fissures by enhancement filter based on fourdimensional curvature. Second, LAV of each lung lobe is segmented. Finally, smoking-induced emphysema progression is assessed by statistical analysis of the annual changes represented by linear regression of LAV percentage in each lung lobe. This method was applied to 140 participants in lung cancer CT screening for six years. The results showed that LAV progressions of nonsmokers, past smokers, and current smokers are different in terms of pack-year and smoking cessation duration. This study demonstrates effectiveness in diagnosis and prognosis of early emphysema in lung cancer CT screening.

  4. Domiciliary humidification improves lung mucociliary clearance in patients with bronchiectasis.

    Science.gov (United States)

    Hasani, A; Chapman, T H; McCool, D; Smith, R E; Dilworth, J P; Agnew, J E

    2008-01-01

    Inspired air humidification has been reported to show some benefit in bronchiectatic patients. We have investigated the possibility that one effect might be to enhance mucociliary clearance. Such enhancement might, if it occurs, help to lessen the risks of recurrent infective episodes. Using a radioaerosol technique, we measured lung mucociliary clearance before and after 7 days of domiciliary humidification. Patients inhaled high flow saturated air at 37 degrees C via a patient-operated humidification nasal inhalation system for 3 h per day. We assessed tracheobronchial mucociliary clearance from the retention of (99m)Tc-labelled polystyrene tracer particles monitored for 6 h, with a follow-up 24-h reading. Ten out of 14 initially recruited patients (age 37-75 years; seven females) completed the study (two withdrew after their initial screening and two prior to the initial clearance test). Seven patients studied were non-smokers; three were ex-smokers (1-9 pack-years). Initial tracer radioaerosol distribution was closely similar between pre- and post-treatment. Following humidification, lung mucociliary clearance significantly improved, the area under the tracheobronchial retention curve decreased from 319 +/- 50 to 271 +/- 46%h (p humidification treatment improved lung mucociliary clearance in our bronchiectatic patients. Given this finding plus increasing laboratory and clinical interest in humidification mechanisms and effects, we believe further clinical trials of humidification therapy are desirable, coupled with analysis of humidification effects on mucus properties and transport.

  5. Transgenic alfalfa plants co-expressing glutathione S-transferase (GST) and human CYP2E1 show enhanced resistance to mixed contaminates of heavy metals and organic pollutants

    International Nuclear Information System (INIS)

    Zhang, Yuanyuan; Liu, Junhong

    2011-01-01

    Transgenic alfalfa plants simultaneously expressing human CYP2E1 and glutathione S-transferase (GST) were generated from hypocotyl segments by the use of an Agrobacterium transformation system for the phytoremediation of the mixed contaminated soil with heavy metals and organic pollutants. The transgenic alfalfa plants were screened by a combination of kanamycin resistance, PCR, GST and CYP2E1 activity and Western blot analysis. The capabilities of mixed contaminants (heavy metals-organic compounds) resistance of pKHCG transgenic alfalfa plants became markedly increased compared with the transgenic alfalfa plants expressing single gene (GST or CYP2E1) and the non-transgenic control plants. The pKHCG alfalfa plants exhibited strong resistance towards the mixtures of cadmium (Cd) and trichloroethylene (TCE) that were metabolized by the introduced GST and CYP2E1 in combination. Our results show that the pKHCG transgenic alfalfa plants have good potential for phytoremediation because they have cross-tolerance towards the complex contaminants of heavy metals and organic pollutants. Therefore, these transgenic alfalfa plants co-expressing GST and human P450 CDNAs may have a great potential for phytoremediation of mixed environmental contaminants.

  6. Transgenic alfalfa plants co-expressing glutathione S-transferase (GST) and human CYP2E1 show enhanced resistance to mixed contaminates of heavy metals and organic pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuanyuan [Department of Pharmaceutics, Qingdao University of Science and Technology, 53 Zhengzhou Road, P.O. Box 70, Qingdao 266042 (China); Liu, Junhong, E-mail: liujh@qust.edu.cn [Department of Pharmaceutics, Qingdao University of Science and Technology, 53 Zhengzhou Road, P.O. Box 70, Qingdao 266042 (China)

    2011-05-15

    Transgenic alfalfa plants simultaneously expressing human CYP2E1 and glutathione S-transferase (GST) were generated from hypocotyl segments by the use of an Agrobacterium transformation system for the phytoremediation of the mixed contaminated soil with heavy metals and organic pollutants. The transgenic alfalfa plants were screened by a combination of kanamycin resistance, PCR, GST and CYP2E1 activity and Western blot analysis. The capabilities of mixed contaminants (heavy metals-organic compounds) resistance of pKHCG transgenic alfalfa plants became markedly increased compared with the transgenic alfalfa plants expressing single gene (GST or CYP2E1) and the non-transgenic control plants. The pKHCG alfalfa plants exhibited strong resistance towards the mixtures of cadmium (Cd) and trichloroethylene (TCE) that were metabolized by the introduced GST and CYP2E1 in combination. Our results show that the pKHCG transgenic alfalfa plants have good potential for phytoremediation because they have cross-tolerance towards the complex contaminants of heavy metals and organic pollutants. Therefore, these transgenic alfalfa plants co-expressing GST and human P450 CDNAs may have a great potential for phytoremediation of mixed environmental contaminants.

  7. Lung growth and development.

    Science.gov (United States)

    Joshi, Suchita; Kotecha, Sailesh

    2007-12-01

    Human lung growth starts as a primitive lung bud in early embryonic life and undergoes several morphological stages which continue into postnatal life. Each stage of lung growth is a result of complex and tightly regulated events governed by physical, environmental, hormonal and genetic factors. Fetal lung liquid and fetal breathing movements are by far the most important determinants of lung growth. Although timing of the stages of lung growth in animals do not mimic that of human, numerous animal studies, mainly on sheep and rat, have given us a better understanding of the regulators of lung growth. Insight into the genetic basis of lung growth has helped us understand and improve management of complex life threatening congenital abnormalities such as congenital diaphragmatic hernia and pulmonary hypoplasia. Although advances in perinatal medicine have improved survival of preterm infants, premature birth is perhaps still the most important factor for adverse lung growth.

  8. Epidemiology of Lung Cancer

    Science.gov (United States)

    Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

    2013-01-01

    Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

  9. Epithelioid lung haenangioendiothelioma

    International Nuclear Information System (INIS)

    Finozzi, V.; Andrade, E.; Campos, N.; Pizarrosa, C.

    2000-01-01

    The first national case of epithelioid lung haenangioendiothelioma concerned a 60 years old woman. Clinical picture and TC diagnosis showed a vascularized tumor producing persistent haenoptoic expectoration.It is necessary to be acquainted with it for the purpose of a differentiated diagnosis. It is a tumor with specific immunohistochemical markers against factor V III.Treatment consisted of surgical resection. Concerning its classification it is situated at the limit between benign and malignant, prognosis is usually good, but evolution is slow, extending for over 20 years

  10. Lichen Secondary Metabolite, Physciosporin, Inhibits Lung Cancer Cell Motility

    Science.gov (United States)

    Yang, Yi; Park, So-Yeon; Nguyen, Thanh Thi; Yu, Young Hyun; Nguyen, Tru Van; Sun, Eun Gene; Udeni, Jayalal; Jeong, Min-Hye; Pereira, Iris; Moon, Cheol; Ha, Hyung-Ho; Kim, Kyung Keun; Hur, Jae-Seoun; Kim, Hangun

    2015-01-01

    Lichens produce various unique chemicals that can be used for pharmaceutical purposes. To screen for novel lichen secondary metabolites showing inhibitory activity against lung cancer cell motility, we tested acetone extracts of 13 lichen samples collected in Chile. Physciosporin, isolated from Pseudocyphellaria coriacea (Hook f. & Taylor) D.J. Galloway & P. James, was identified as an effective compound and showed significant inhibitory activity in migration and invasion assays against human lung cancer cells. Physciosporin treatment reduced both protein and mRNA levels of N-cadherin with concomitant decreases in the levels of epithelial-mesenchymal transition markers such as snail and twist. Physciosporin also suppressed KITENIN (KAI1 C-terminal interacting tetraspanin)-mediated AP-1 activity in both the absence and presence of epidermal growth factor stimulation. Quantitative real-time PCR analysis showed that the expression of the metastasis suppressor gene, KAI1, was increased while that of the metastasis enhancer gene, KITENIN, was dramatically decreased by physciosporin. Particularly, the activity of 3’-untranslated region of KITENIN was decreased by physciosporin. Moreover, Cdc42 and Rac1 activities were decreased by physciosporin. These results demonstrated that the lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility through novel mechanisms of action. PMID:26371759

  11. Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury.

    Science.gov (United States)

    Rotta, A T; Gunnarsson, B; Fuhrman, B P; Hernan, L J; Steinhorn, D M

    2001-11-01

    To determine the impact of different protective and nonprotective mechanical ventilation strategies on the degree of pulmonary inflammation, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury. A prospective, randomized, controlled, in vivo animal laboratory study. Animal research facility of a health sciences university. Forty-six New Zealand White rabbits. Mature rabbits were instrumented with a tracheostomy and vascular catheters. Lavage-injured rabbits were randomized to receive conventional ventilation with either a) low peak end-expiratory pressure (PEEP; tidal volume of 10 mL/kg, PEEP of 2 cm H2O); b) high PEEP (tidal volume of 10 mL/kg, PEEP of 10 cm H2O); c) low tidal volume with PEEP above Pflex (open lung strategy, tidal volume of 6 mL/kg, PEEP set 2 cm H2O > Pflex); or d) high-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. Lung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total protein, elastase activity, tumor necrosis factor-alpha, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded. Animals that received a lung protective strategy (open lung or high-frequency oscillatory ventilation) exhibited more favorable oxygenation and lung mechanics compared with the low PEEP and high PEEP groups. Animals ventilated by a lung protective strategy also showed attenuation of inflammation (reduced tracheal fluid protein, tracheal fluid elastase, tracheal fluid tumor necrosis factor-alpha, and pulmonary leukostasis). Animals treated with high-frequency oscillatory ventilation had attenuated oxidative injury to the lung and greater hemodynamic stability compared with the other experimental groups. Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and

  12. Cross-sectional changes in lung volume measured by electrical impedance tomography are representative for the whole lung in ventilated preterm infants

    NARCIS (Netherlands)

    van der Burg, Pauline S.; Miedema, Martijn; de Jongh, Frans H.; Frerichs, Inez; van Kaam, Anton H.

    2014-01-01

    Electrical impedance tomography measures lung volume in a cross-sectional slice of the lung. Whether these cross-sectional volume changes are representative of the whole lung has only been investigated in adults, showing conflicting results. This study aimed to compare cross-sectional and whole lung

  13. Polymorphism in cytochrome P450 1A2 and their interaction with risk factors in determining risk of squamous cell lung carcinoma in men.

    Science.gov (United States)

    Singh, Arvind P; Pant, Mohan C; Ruwali, Munindra; Shah, Parag P; Prasad, Rajendra; Mathur, Neeraj; Parmar, Devendra

    The present case-control study was carried out to investigate the association of functionally important polymorphisms of cytochrome P450 1A2 (CYP1A2) involved in the metabolic activation of tobacco derived procarcinogens with squamous cell carcinoma (SCC) of lung in North Indian men. The study consisted of 200 male cases with SCC of lung and an equal number of age and sex matched healthy controls. Our data showed that variant genotype of CYP1A2*1D and CYP1A2*1F were significantly associated with increased susceptibility to SCC of lung. Likewise, GSTM1 null genotype was found to be over represented in patients when compared to controls. Haplotype analysis revealed that haplotype, G-Tdel-T-C was significantly associated with risk to SCC of lung. Moreover, a significant increase in the risk to SCC of lung in the cases carrying combination of variant genotype of CYP1A2 with either CYP1A1 or GSTM1 have shown that gene-gene interactions may play an important role in squamous cell lung cancer risk. Our data also revealed that smokers or tobacco chewers carrying variant alleles of either CYP1A2*1D or CYP1A2*1F were at increased risk to SCC of lung, further demonstrating that CYP1A2 genotypes interact with environmental risk factors in enhancing the risk to squamous cell lung carcinoma.

  14. Genetics Home Reference: lung cancer

    Science.gov (United States)

    ... Share: Email Facebook Twitter Home Health Conditions Lung cancer Lung cancer Printable PDF Open All Close All Enable Javascript ... cancer, childhood Additional NIH Resources (3 links) National Cancer Institute: Lung Cancer Overview National Cancer Institute: Lung Cancer Prevention ...

  15. Radiation Therapy for Lung Cancer

    Science.gov (United States)

    ... is almost always due to smoking. TREATING LUNG CANCER Lung cancer treatment depends on several factors, including the ... org TARGETING CANCER CARE Radiation Therapy for Lung Cancer Lung cancer is the second most common cancer in ...

  16. Dosimetric verification of small fields in the lung using lung-equivalent polymer gel and Monte Carlo simulation

    Directory of Open Access Journals (Sweden)

    Nahideh Gharehaghaji

    2018-01-01

    Conclusion: Our study showed that the dose reduction with small fields in the lung was very high. Thus, inaccurate prediction of absorbed dose inside the lung and also lung/soft-tissue interfaces with small photon beams may lead to critical consequences for treatment outcome.

  17. Lungs and Respiratory System

    Science.gov (United States)

    ... Videos for Educators Search English Español Lungs and Respiratory System KidsHealth / For Parents / Lungs and Respiratory System ... ll have taken at least 600 million breaths. Respiratory System Basics All of this breathing couldn't ...

  18. Childhood Interstitial Lung Disease

    Science.gov (United States)

    ... rule out conditions such as asthma , cystic fibrosis , acid reflux, heart disease, neuromuscular disease, and immune deficiency. Various ... a lung infection. Acid-blocking medicines can prevent acid reflux, which can lead to aspiration. Lung Transplant A ...

  19. Interstitial Lung Disease

    Science.gov (United States)

    ... propranolol (Inderal, Innopran), may harm lung tissue. Some antibiotics. Nitrofurantoin (Macrobid, Macrodantin, others) and ethambutol (Myambutol) can cause lung damage. Anti-inflammatory drugs. Certain anti-inflammatory drugs, such as rituximab ( ...

  20. Eosinophilic Lung Disorders

    Science.gov (United States)

    ... problems characterized by having an increased number of eosinophils (white blood cells) in the lungs. These white ... category of pneumonias that feature increased numbers of eosinophils in the lung tissue. Pneumonia is an inflammatory ...

  1. Psychopaths Show Enhanced Amygdala Activation during Fear Conditioning

    OpenAIRE

    Schultz, Douglas H.; Balderston, Nicholas L.; Baskin-Sommers, Arielle R.; Larson, Christine L.; Helmstetter, Fred J.

    2016-01-01

    Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into “primary” and “secondary” psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional “fearlessness,” while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental d...

  2. Hepatocyte growth factor, a determinant of airspace homeostasis in the murine lung.

    Directory of Open Access Journals (Sweden)

    Carla Calvi

    Full Text Available The alveolar compartment, the fundamental gas exchange unit in the lung, is critical for tissue oxygenation and viability. We explored hepatocyte growth factor (HGF, a pleiotrophic cytokine that promotes epithelial proliferation, morphogenesis, migration, and resistance to apoptosis, as a candidate mediator of alveolar formation and regeneration. Mice deficient in the expression of the HGF receptor Met in lung epithelial cells demonstrated impaired airspace formation marked by a reduction in alveolar epithelial cell abundance and survival, truncation of the pulmonary vascular bed, and enhanced oxidative stress. Administration of recombinant HGF to tight-skin mice, an established genetic emphysema model, attenuated airspace enlargement and reduced oxidative stress. Repair in the TSK/+ mouse was punctuated by enhanced akt and stat3 activation. HGF treatment of an alveolar epithelial cell line not only induced proliferation and scattering of the cells but also conferred protection against staurosporine-induced apoptosis, properties critical for alveolar septation. HGF promoted cell survival was attenuated by akt inhibition. Primary alveolar epithelial cells treated with HGF showed improved survival and enhanced antioxidant production. In conclusion, using both loss-of-function and gain-of-function maneuvers, we show that HGF signaling is necessary for alveolar homeostasis in the developing lung and that augmentation of HGF signaling can improve airspace morphology in murine emphysema. Our studies converge on prosurvival signaling and antioxidant protection as critical pathways in HGF-mediated airspace maintenance or repair. These findings support the exploration of HGF signaling enhancement for diseases of the airspace.

  3. Lung nodules after whole lung radiation

    International Nuclear Information System (INIS)

    Cohen, M.D.; Mirkin, D.L.; Provisor, A.; Hornback, N.B.; Smith, J.A.; Slabaugh, R.D.

    1983-01-01

    It is essential to recognize radiation pneumonitis after whole lung irradiation, or nodular changes in response to chemotherapy, so that such conditions are not mistaken for tumor metastases, causing grave error in patient management and the possibility of further lung damage

  4. Lung perfusion scintigraphy by SPECT

    International Nuclear Information System (INIS)

    Hirayama, Takanobu

    1990-01-01

    The initial study reports the characteristic performance using lung segmental phantom filled in Tc-99m pertechnetate. To evaluate the segmental defect in lung perfusion scintigraphy, we applied Bull's-eye analysis in addition to planar image set. Bull's-eye analysis especially facilitated the interpretation in both middle and lower lobes. Subsequently, to evolute the clinical application of Bull's-eye analysis, pulmonary scintigraphy was performed on 10 normal subjects and 60 patients with several pulmonary diseases. Of interest, Bull's-eye analysis, however, encouraged the interpretation in both lower lobes. To calculate the extention and severity of perfusion defect, the present study describes Bull's-eye analysis. Quantitative scoring showed higher in patients with lung cancer than those with pulmonary tuberculosis. The present study focus that Bull's-eye analysis can be useful for evaluating perfusion in patients with a couple of pulmonary diseases. (author)

  5. Lung cancer in pregnancy.

    Science.gov (United States)

    Holzmann, Kornelia; Kropfmüller, Roland; Schinko, Herwig; Bogner, Stephan; Fellner, Franz; Arzt, Wolfgang; Lamprecht, Bernd

    2015-08-01

    In the 26th week of gestation, a 29-year-old pregnant office employee was referred to the pulmonary department of Linz General Hospital (AKH) under the suspicion of tuberculosis. She complained of a cough with intermittent hemoptysis and pain in the thoracic spine from which she had been suffering the past 9 weeks. A plain chest X-ray showed a dense infiltrate on the right side and multiple smaller shadows in both lungs. Laboratory testing revealed anemia, leukocytosis, and an increase of C-reactive protein. All tests for tuberculosis were negative.A bronchoscopy was performed and biopsies were taken from the right upper and middle lobe. The histopathological examination found cells of an adenocarcinoma. A magnetic resonance imaging (MRI) revealed a large tumor and surrounding atelectasis were seen in the right upper and middle lobe, as well as multiple intrapulmonary metastases in both lungs. In addition, not only metastases in the thoracic spine (level Th2/3) but also at other osseous locations and multiple cerebral metastases were detected. The patient received one cycle of chemotherapy consisting of docetaxel and carboplatin (AUC5) in the 27th week of gestation. Additional radiotherapy was applied to the involved thoracic spine. Due to positive epidermal growth factor receptor mutation, therapy with gefitinib 250 mg/day was started 2 days after a Caesarean section (preceded by treatment for fetal lung maturation). A healthy girl was delivered in the 30th week of pregnancy. Staging with computed tomography (CT) after delivery revealed an unstable fracture of Th2 with compression of the spinal cord. Neurosurgery was performed, consisting of a ventral corporectomy of Th1-2 followed by an anterior and posterior osteosynthesis for stabilization. The patient was discharged without neurological deficits within 1 week. Subsequent treatment with gefitinib improved the performance status of the patient, and CT scans of the chest and an MRI of the brain showed the size of

  6. Lung release of HIPDM: A new index of lung dysfunction for clinical and experimental studies

    International Nuclear Information System (INIS)

    Pistolesi, M.; Miniati, M.; Ghelarducci, L.

    1985-01-01

    Lung uptake, metabolism and release of amines has been experimentally documented. The authors studied in rabbit and man the lung kinetics of radioiodinated N-N-N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1, 3-propanediamine (HIPDM). In rabbits, after i.v. injection, 95% of HIPDM is kept within the lungs and is then released with a mean time (t-bar) of several hours as assessed both in vivo, by gamma camera external counting (n=5; t-bar=7.0 hrs), and in vitro by measuring activity in lung homogenates at various times after injection (n=56; t-bar=7.6 hrs). In 10 healthy non smoking subjects t-bar was 6.4 +- 1 hrs, whereas it was 12.1 +- 2 hrs in 10 asymptomatic smokers with normal pulmonary function tests. Preliminary clinical studies showed that HIPDM lung release is delayed in non smoking patients with primary pulmonary hypertension (n=4; t-bar=11.5 +- 2 hrs) and to a greater extent in adult respiratory distress syndrome (n=4; t-bar=25.8 +- 5hrs), whereas it was not significantly affected in cardiogenic pulmonary edema (n=4; t-bar=8.8 +- 2 hrs). Hence, both smoke exposure and injury to the lung microcirculation may impair HIPDM lung kinetics. HIPDM external counting may therefore provide a new index of lung dysfunction in man. Rabbit can be used as a model to evaluate HIPDM lung kinetics in experimentally induced lung injury

  7. Lung scintigraphy; Centellograma pulmonar

    Energy Technology Data Exchange (ETDEWEB)

    Dalenz, Roberto

    1994-12-31

    A review of lung scintigraphy, perfusion scintigraphy with SPECT, lung ventilation SPECT, blood pool SPECT. The procedure of lung perfusion studies, radiopharmaceutical, administration and clinical applications, imaging processing .Results encountered and evaluation criteria after Biello and Pioped. Recommendations and general considerations have been studied about relation of this radiopharmaceutical with other pathologies.

  8. American Lung Association

    Science.gov (United States)

    ... see if you should get screened. Learn more EDUCATION ADVOCACY RESEARCH Our vision is a world free of lung disease The American Lung Association is ... by lung disease. Help us continue to deliver education, advocacy and research to those who need it. $250 $100 $50 Your best gift Donate now Learn More ... nonprofit software

  9. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

    2015-07-01

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  10. Long noncoding RNA HOTAIR, a hypoxia-inducible factor-1α activated driver of malignancy, enhances hypoxic cancer cell proliferation, migration, and invasion in non-small cell lung cancer.

    Science.gov (United States)

    Zhou, Chunxia; Ye, Lincai; Jiang, Chuan; Bai, Jie; Chi, Yongbin; Zhang, Haibo

    2015-12-01

    Despite the fact that great advances have been made in the management of non-small cell lung cancer (NSCLC), the prognosis of advanced NSCLC remains very poor. HOX transcript antisense intergenic RNA (HOTAIR) has been identified as an oncogenic long noncoding RNA (lncRNA) that is involved in the progression of a variety of carcinomas and acts as a negative prognostic biomarker. Yet, little is known about the effect of HOTAIR in the hypoxic microenvironment of NSCLC. The expression and promoter activity of HOTAIR were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase reporter assay. The function of the hypoxia-inducible factor-1α (HIF-1α) binding site to hypoxia-responsive elements (HREs) in the HOTAIR promoter region was tested by luciferase reporter assay with nucleotide substitutions. The binding of HIF-1α to the HOTAIR promoter in vivo was confirmed by chromatin immunoprecipitation assay (CHIP) and electrophoretic mobility shift assay (EMSA). The effect of HIF-1α suppression by small interference RNA or YC-1 on HOTAIR expression was also determined. In the present study, we demonstrated that HOTAIR was upregulated by hypoxia in NSCLC cells. HOTAIR is a direct target of HIF-1α through interaction with putative HREs in the upstream region of HOTAIR in NSCLC cells. Furthermore, HIF-1α knockdown or inhibition could prevent HOTAIR upregulation under hypoxic conditions. Under hypoxic conditions, HOTAIR enhanced cancer cell proliferation, migration, and invasion. These data suggested that suppression of HOTAIR upon hypoxia of NSCLC could be a novel therapeutic strategy.

  11. Dynamic Contrast-Enhanced Perfusion Area-Detector CT: Preliminary Comparison of Diagnostic Performance for N Stage Assessment With FDG PET/CT in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Ohno, Yoshiharu; Fujisawa, Yasuko; Sugihara, Naoki; Kishida, Yuji; Seki, Shinichiro; Koyama, Hisanobu; Yoshikawa, Takeshi

    2017-11-01

    The objective of our study was to directly compare the capability of dynamic first-pass contrast-enhanced (CE) perfusion area-detector CT (ADCT) and FDG PET/CT for differentiation of metastatic from nonmetastatic lymph nodes and assessment of N stage in patients with non-small cell lung carcinoma (NSCLC). Seventy-seven consecutive patients, 45 men (mean age ± SD, 70.4 ± 5.9 years) and 32 women (71.2 ± 7.7 years), underwent dynamic first-pass CE-perfusion ADCT at two or three different positions for covering the entire thorax, FDG PET/CT, surgical treatment, and pathologic examination. From all ADCT data for each of the subjects, a whole-chest perfusion map was computationally generated using the dual- and single-input maximum slope and Patlak plot methods. For quantitative N stage assessment, perfusion parameters and the maximum standardized uptake value (SUV max ) for each lymph node were determined by measuring the relevant ROI. ROC curve analyses were performed for comparing the diagnostic capability of each of the methods on a per-node basis. N stages evaluated by each of the indexes were then statistically compared with the final pathologic diagnosis by means of chi-square and kappa statistics. The area under the ROC curve (A z ) values of systemic arterial perfusion (A z = 0.89), permeability surface (A z = 0.78), and SUV max (A z = 0.85) were significantly larger than the A z values of total perfusion (A z = 0.70, p Dynamic first-pass CE-perfusion ADCT is as useful as FDG PET/CT for the differentiation of metastatic from nonmetastatic lymph nodes and assessment of N stage in patients with NSCLC.

  12. Attenuated Escherichia coli strains expressing the colonization factor antigen I (CFA/I) and a detoxified heat-labile enterotoxin (LThK63) enhance clearance of ETEC from the lungs of mice and protect mice from intestinal ETEC colonization and LT-induced fluid accumulation.

    Science.gov (United States)

    Byrd, Wyatt; Boedeker, Edgar C

    2013-03-15

    Although enterotoxigenic Escherichia coli (ETEC) infections are important causes of infantile and traveler's diarrhea there is no licensed vaccine available for those at-risk. Our goal is to develop a safe, live attenuated ETEC vaccine. We used an attenuated E. coli strain (O157:H7, Δ-intimin, Stx1-neg, Stx2-neg) as a vector (ZCR533) to prepare two vaccine strains, one strain expressing colonization factor antigen I (ZCR533-CFA/I) and one strain expressing CFA/I and a detoxified heat-labile enterotoxin (ZCR533-CFA/I+LThK63) to deliver ETEC antigens to mucosal sites in BALB/c mice. Following intranasal and intragastric immunization with the vaccine strains, serum IgG and IgA antibodies were measured to the CFA/I antigen, however, only serum IgG antibodies were detected to the heat-labile enterotoxin. Intranasal administration of the vaccine strains induced respiratory and intestinal antibody responses to the CFA/I and LT antigens, while intragastric administration induced only intestinal antibody responses with no respiratory antibodies detected to the CFA/I and LT antigens. Mice immunized intranasally with the vaccine strains showed enhanced clearance of wild-type (wt) ETEC bacteria from the lungs. Mice immunized intranasally and intragastrically with the vaccine strains were protected from intestinal colonization following oral challenge with ETEC wt bacteria. Mice immunized intragastrically with the ZCR533-CFA/I+LThK63 vaccine strain had less fluid accumulate in their intestine following challenge with ETEC wt bacteria or with purified LT as compared to the sham mice indicating that the immunized mice were protected from LT-induced intestinal fluid accumulation. Thus, mice intragastrically immunized with the ZCR533-CFA/I+LThK63 vaccine strain were able to effectively neutralize the activity of the LT enterotoxin. However, no difference in intestinal fluid accumulation was detected in the mice immunized intranasally with the vaccine strain as compared to the sham

  13. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E

    2011-01-01

    A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time...... of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patient's clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs......, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report....

  14. Whole lung lavage with intermittent double lung ventilation. A modified technique for managing pulmonary alveolar proteinosis

    International Nuclear Information System (INIS)

    Ahmed, Raees; Iqbal, Mobeen; Kashef, Sayed H.; Almomatten, Mohammed I.

    2005-01-01

    Whole lung lavage is still the most effective treatment for pulmonary alveolar proteinosis. We report a 21-year-old male diagnosed with pulmonary alveolar proteinosis by open lung biopsy and who underwent whole lung lavage with a modified technique. He showed significant improvement in clinical and functional parameters. The technique of intermittent double lung ventilation during lavage procedure keeps the oxygen saturation in acceptable limits in patients at risk for severe hypoxemia and allows the procedure to be completed in a single setting. (author)

  15. Table incremental slow injection CE-CT in lung cancer

    International Nuclear Information System (INIS)

    Yoshida, Shoji; Maeda, Tomoho; Morita, Masaru

    1988-01-01

    The purpose of this study is to evaluate tumor enhancement in lung cancer under the table incremental study with slow injection of contrast media. The early serial 8 sliced images during the slow injection (1.5 ml/sec) of contrant media were obtained. Following the early images, delayed 8 same sliced images were taken in 2 minutes later. Chacteristic enhanced patterns of the primary cancer and metastatic mediastinal lymphnode were recognized in this study. Enhancement of the primary lesion was classified in 4 patterns, irregular geographic pattern, heterogeneous pattern, homogeneous pattern and rim-enhanced pattern. In mediastinal metastatic lymphadenopathy, three enhanced patterns were obtained, heterogeneous, homogeneous and ring enhanced pattern. Some characteristic enhancement patterns according to the histopathological finding of the lung cancer were obtained. With using this incremental slow injection CE-CT, precise information about the relationship between lung cancer and adjacent mediastinal structure, and obvious staining patterns of the tumor and mediastinal lymphnode were recognized. (author)

  16. European Lung Foundation: from local to global

    Directory of Open Access Journals (Sweden)

    Pippa Powell

    2016-09-01

    To show how patient- and public-focussed initiatives and activities can be adapted and modified to be effective in local, national and international settings, and to provide specific examples of these from the European Lung Foundation.

  17. Lung structure and function relation in systemic sclerosis: Application of lung densitometry

    Energy Technology Data Exchange (ETDEWEB)

    Ninaber, Maarten K., E-mail: m.k.ninaber@lumc.nl [Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Stolk, Jan; Smit, Jasper; Le Roy, Ernest J. [Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Kroft, Lucia J.M. [Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Els Bakker, M. [Division of Image Processing, Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Vries Bouwstra, Jeska K. de; Schouffoer, Anne A. [Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Staring, Marius; Stoel, Berend C. [Division of Image Processing, Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands)

    2015-05-15

    Highlights: • A quantitative CT parameter of lung parenchyma in systemic sclerosis is presented. • We examine the optimal percentage threshold for the percentile density. • The 85th percentile density threshold correlated significantly with lung function. • A lung structure–function relation is confirmed. • We report applicability of Perc85 in progression mapping of interstitial lung disease. - Abstract: Introduction: Interstitial lung disease occurs frequently in patients with systemic sclerosis (SSc). Quantitative computed tomography (CT) densitometry using the percentile density method may provide a sensitive assessment of lung structure for monitoring parenchymal damage. Therefore, we aimed to evaluate the optimal percentile density score in SSc by quantitative CT densitometry, against pulmonary function. Material and methods: We investigated 41 SSc patients by chest CT scan, spirometry and gas transfer tests. Lung volumes and the nth percentile density (between 1 and 99%) of the entire lungs were calculated from CT histograms. The nth percentile density is defined as the threshold value of densities expressed in Hounsfield units. A prerequisite for an optimal percentage was its correlation with baseline DLCO %predicted. Two patients showed distinct changes in lung function 2 years after baseline. We obtained CT scans from these patients and performed progression analysis. Results: Regression analysis for the relation between DLCO %predicted and the nth percentile density was optimal at 85% (Perc85). There was significant agreement between Perc85 and DLCO %predicted (R = −0.49, P = 0.001) and FVC %predicted (R = −0.64, P < 0.001). Two patients showed a marked change in Perc85 over a 2 year period, but the localization of change differed clearly. Conclusions: We identified Perc85 as optimal lung density parameter, which correlated significantly with DLCO and FVC, confirming a lung parenchymal structure–function relation in SSc. This provides

  18. Lung structure and function relation in systemic sclerosis: Application of lung densitometry

    International Nuclear Information System (INIS)

    Ninaber, Maarten K.; Stolk, Jan; Smit, Jasper; Le Roy, Ernest J.; Kroft, Lucia J.M.; Els Bakker, M.; Vries Bouwstra, Jeska K. de; Schouffoer, Anne A.; Staring, Marius; Stoel, Berend C.

    2015-01-01

    Highlights: • A quantitative CT parameter of lung parenchyma in systemic sclerosis is presented. • We examine the optimal percentage threshold for the percentile density. • The 85th percentile density threshold correlated significantly with lung function. • A lung structure–function relation is confirmed. • We report applicability of Perc85 in progression mapping of interstitial lung disease. - Abstract: Introduction: Interstitial lung disease occurs frequently in patients with systemic sclerosis (SSc). Quantitative computed tomography (CT) densitometry using the percentile density method may provide a sensitive assessment of lung structure for monitoring parenchymal damage. Therefore, we aimed to evaluate the optimal percentile density score in SSc by quantitative CT densitometry, against pulmonary function. Material and methods: We investigated 41 SSc patients by chest CT scan, spirometry and gas transfer tests. Lung volumes and the nth percentile density (between 1 and 99%) of the entire lungs were calculated from CT histograms. The nth percentile density is defined as the threshold value of densities expressed in Hounsfield units. A prerequisite for an optimal percentage was its correlation with baseline DLCO %predicted. Two patients showed distinct changes in lung function 2 years after baseline. We obtained CT scans from these patients and performed progression analysis. Results: Regression analysis for the relation between DLCO %predicted and the nth percentile density was optimal at 85% (Perc85). There was significant agreement between Perc85 and DLCO %predicted (R = −0.49, P = 0.001) and FVC %predicted (R = −0.64, P < 0.001). Two patients showed a marked change in Perc85 over a 2 year period, but the localization of change differed clearly. Conclusions: We identified Perc85 as optimal lung density parameter, which correlated significantly with DLCO and FVC, confirming a lung parenchymal structure–function relation in SSc. This provides

  19. 67Ga lung scan

    International Nuclear Information System (INIS)

    Niden, A.H.; Mishkin, F.S.; Khurana, M.M.L.; Pick, R.

    1977-01-01

    Twenty-three patients with clinical signs of pulmonary embolic disease and lung infiltrates were studied to determine the value of gallium citrate 67 Ga lung scan in differentiating embolic from inflammatory lung disease. In 11 patients without angiographically proved embolism, only seven had corresponding ventilation-perfusion defects compatible with inflammatory disease. In seven of these 11 patients, the 67 Ga concentration indicated inflammatory disease. In the 12 patients with angiographically proved embolic disease, six had corresponding ventilation-perfusion defects compatible with inflammatory disease. None had an accumulation of 67 Ga in the area of pulmonary infiltrate. Thus, ventilation-perfusion lung scans are of limited value when lung infiltrates are present. In contrast, the accumulation of 67 Ga in the lung indicates an inflammatory process. Gallium imaging can help select those patients with lung infiltrates who need angiography

  20. Congenital cystic lung malformations

    International Nuclear Information System (INIS)

    Stoever, B.; Scheer, I.; Bassir, C.; Chaoui, R.; Henrich, W.; Schwabe, M.; Wauer, R.

    2006-01-01

    Purpose: The aim of the study concerning congenital cystic lung malformations was to evaluate prenatal diagnoses postnatally to determine prognostic factors as well as to define optimized perinatal management. Materials and Methods: The study is based on 45 prenatal ultrasound examinations depicting fetal cystic lung lesions. 32 of the mothers had follow-up examinations. 5 pregnancies were terminated due to CCAM and additional malformations. Complete regression of the lesions was seen prenatally in 8 cases and postnatally in 5 children. Results: Surgical intervention due to respiratory insufficiency was necessary in 4 neonates. According to the imaging results, CCAM was present in 4 cases and sequestration in 7 patients. No correlation between the imaging findings and the surgical results was found in 3 children: One child suffered from rhadomyoid dysplasia, and in the case of the second child, a left-sided hernia of the diaphragm and additional sequestration were detected. The third child showed AV malformation. The cystic lesions of the 14 children operated upon were proven histologically. The degree of accuracy in the present study was high. Conclusion: Precise perinatal management is warranted in order to determine according to the clinical relevance surgical intervention and to prevent complications after the first year of life. This is performed during the neonatal period for respiratory insufficient neonates and within the first year of life for clinically stable children. (orig.)

  1. Micromechanical model of lung parenchyma hyperelasticity

    Science.gov (United States)

    Concha, Felipe; Sarabia-Vallejos, Mauricio; Hurtado, Daniel E.

    2018-03-01

    Mechanics plays a key role in respiratory physiology, as lung tissue cyclically deforms to bring air in and out the lung, a life-long process necessary for respiration. The study of regional mechanisms of deformation in lung parenchyma has received great attention to date due to its clinical relevance, as local overstretching and stress concentration in lung tissue is currently associated to pathological conditions such as lung injury during mechanical ventilation therapy. This mechanical approach to lung physiology has motivated the development of constitutive models to better understand the relation between stress and deformation in the lung. While material models proposed to date have been key in the development of whole-lung simulations, either they do not directly relate microstructural properties of alveolar tissue with coarse-scale behavior, or they require a high computational effort when based on real alveolar geometries. Furthermore, most models proposed to date have not been thoroughly validated for anisotropic deformation states, which are commonly found in normal lungs in-vivo. In this work, we develop a novel micromechanical model of lung parenchyma hyperelasticity using the framework of finite-deformation homogenization. To this end, we consider a tetrakaidecahedron unit cell with incompressible Neo-Hookean structural elements that account for the alveolar wall tissue responsible for the elastic response, and derive expressions for its effective coarse-scale behavior that directly depend on the alveolar wall elasticity, reference porosity, and two other geometrical coefficients. To validate the propose