Nuclear magnetic resonance relaxation times for human lung cancer and lung tissues

International Nuclear Information System (INIS)

Matsuura, Yoshifumi; Shioya, Sumie; Kurita, Daisaku; Ohta, Takashi; Haida, Munetaka; Ohta, Yasuyo; Suda, Syuichi; Fukuzaki, Minoru.

1994-01-01

We investigated the nuclear magnetic resonance (NMR) relaxation times, T 1 and T 2 , for lung cancer tissue, and other samples of lung tissue obtained from surgical specimens. The samples were nine squamous cell carcinomas, five necrotic squamous cell carcinomas, 15 adenocarcinomas, two benign mesotheliomas, and 13 fibrotic lungs. The relaxation times were measured with a 90 MHz NMR spectrometer and the results were correlated with histological changes. The values of T 1 and T 2 for squamous cell carcinoma and mesothelioma were significantly longer than those of adenocarcinoma and fibrotic lung tissue. There were no significant differences in values of T 1 and T 2 between adenocarcinoma and lung tissue. The values of T 1 and T 2 for benign mesothelioma were similar to those of squamous cell carcinoma, which suggested that increases in T 1 and T 2 are not specific to malignant tissues. (author)

The First Korean Case of Cutaneous Lung Tissue Heterotopia

Science.gov (United States)

Jeon, Ga Won; Han, Seong Woo; Jung, Ji Mi; Kang, Mi Seon

2010-01-01

Cutaneous lung tissue heterotopia is a very rare disorder where mature lung tissues develop in the skin. This is only the second known report of cutaneous lung tissue heterotopia, with the first by Singer et al. in 1998. A newborn infant had a hemangioma-like, freely movable mass connected to the anterior aspect of the sternal manubrium. Pathologic findings showed mature lung tissues with bronchi, bronchioles, and alveoli through the dermis and subcutis, and it was diagnosed as cutaneous lung tissue heterotopia. Cutaneous lung tissue heterotopia is hypervascular, so grossly it looks like a hemangioma. It can be differentiated from pulmonary sequestration, teratoma, bronchogenic cyst, and branchial cleft cyst by histology and the location of the mass. We describe the clinical, radiologic, and pathologic findings of a cutaneous lung tissue heterotopia, the first reported in Korea. PMID:20808688

SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Lindsay, WD; Berlind, CG; Gee, JC; Simone, CB

2015-01-01

Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Lindsay, WD [University of Pennsylvania, Philadelphia, PA (United States); Oncora Medical, LLC, Philadelphia, PA (United States); Berlind, CG [Georgia Institute of Technology, Atlanta, GA (Georgia); Oncora Medical, LLC, Philadelphia, PA (United States); Gee, JC; Simone, CB [University of Pennsylvania, Philadelphia, PA (United States)

2015-06-15

Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry.

Science.gov (United States)

Kami, Kenjiro; Fujimori, Tamaki; Sato, Hajime; Sato, Mutsuko; Yamamoto, Hiroyuki; Ohashi, Yoshiaki; Sugiyama, Naoyuki; Ishihama, Yasushi; Onozuka, Hiroko; Ochiai, Atsushi; Esumi, Hiroyasu; Soga, Tomoyoshi; Tomita, Masaru

2013-04-01

Metabolic microenvironment of tumor cells is influenced by oncogenic signaling and tissue-specific metabolic demands, blood supply, and enzyme expression. To elucidate tumor-specific metabolism, we compared the metabolomics of normal and tumor tissues surgically resected pairwise from nine lung and seven prostate cancer patients, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Phosphorylation levels of enzymes involved in central carbon metabolism were also quantified. Metabolomic profiles of lung and prostate tissues comprised 114 and 86 metabolites, respectively, and the profiles not only well distinguished tumor from normal tissues, but also squamous cell carcinoma from the other tumor types in lung cancer and poorly differentiated tumors from moderately differentiated tumors in prostate cancer. Concentrations of most amino acids, especially branched-chain amino acids, were significantly higher in tumor tissues, independent of organ type, but of essential amino acids were particularly higher in poorly differentiated than moderately differentiated prostate cancers. Organ-dependent differences were prominent at the levels of glycolytic and tricarboxylic acid cycle intermediates and associated energy status. Significantly high lactate concentrations and elevated activating phosphorylation levels of phosphofructokinase and pyruvate kinase in lung tumors confirmed hyperactive glycolysis. We highlighted the potential of CE-TOFMS-based metabolomics combined with phosphorylated enzyme analysis for understanding tissue-specific tumor microenvironments, which may lead to the development of more effective and specific anticancer therapeutics.

Lung involvement in systemic connective tissue diseases

Directory of Open Access Journals (Sweden)

Plavec Goran

2008-01-01

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

Tracking lung tissue motion and expansion/compression with inverse consistent image registration and spirometry.

Science.gov (United States)

Christensen, Gary E; Song, Joo Hyun; Lu, Wei; El Naqa, Issam; Low, Daniel A

2007-06-01

Breathing motion is one of the major limiting factors for reducing dose and irradiation of normal tissue for conventional conformal radiotherapy. This paper describes a relationship between tracking lung motion using spirometry data and image registration of consecutive CT image volumes collected from a multislice CT scanner over multiple breathing periods. Temporal CT sequences from 5 individuals were analyzed in this study. The couch was moved from 11 to 14 different positions to image the entire lung. At each couch position, 15 image volumes were collected over approximately 3 breathing periods. It is assumed that the expansion and contraction of lung tissue can be modeled as an elastic material. Furthermore, it is assumed that the deformation of the lung is small over one-fifth of a breathing period and therefore the motion of the lung can be adequately modeled using a small deformation linear elastic model. The small deformation inverse consistent linear elastic image registration algorithm is therefore well suited for this problem and was used to register consecutive image scans. The pointwise expansion and compression of lung tissue was measured by computing the Jacobian of the transformations used to register the images. The logarithm of the Jacobian was computed so that expansion and compression of the lung were scaled equally. The log-Jacobian was computed at each voxel in the volume to produce a map of the local expansion and compression of the lung during the breathing period. These log-Jacobian images demonstrate that the lung does not expand uniformly during the breathing period, but rather expands and contracts locally at different rates during inhalation and exhalation. The log-Jacobian numbers were averaged over a cross section of the lung to produce an estimate of the average expansion or compression from one time point to the next and compared to the air flow rate measured by spirometry. In four out of five individuals, the average log

Tracking lung tissue motion and expansion/compression with inverse consistent image registration and spirometry

International Nuclear Information System (INIS)

Christensen, Gary E.; Song, Joo Hyun; Lu, Wei; Naqa, Issam El; Low, Daniel A.

2007-01-01

Breathing motion is one of the major limiting factors for reducing dose and irradiation of normal tissue for conventional conformal radiotherapy. This paper describes a relationship between tracking lung motion using spirometry data and image registration of consecutive CT image volumes collected from a multislice CT scanner over multiple breathing periods. Temporal CT sequences from 5 individuals were analyzed in this study. The couch was moved from 11 to 14 different positions to image the entire lung. At each couch position, 15 image volumes were collected over approximately 3 breathing periods. It is assumed that the expansion and contraction of lung tissue can be modeled as an elastic material. Furthermore, it is assumed that the deformation of the lung is small over one-fifth of a breathing period and therefore the motion of the lung can be adequately modeled using a small deformation linear elastic model. The small deformation inverse consistent linear elastic image registration algorithm is therefore well suited for this problem and was used to register consecutive image scans. The pointwise expansion and compression of lung tissue was measured by computing the Jacobian of the transformations used to register the images. The logarithm of the Jacobian was computed so that expansion and compression of the lung were scaled equally. The log-Jacobian was computed at each voxel in the volume to produce a map of the local expansion and compression of the lung during the breathing period. These log-Jacobian images demonstrate that the lung does not expand uniformly during the breathing period, but rather expands and contracts locally at different rates during inhalation and exhalation. The log-Jacobian numbers were averaged over a cross section of the lung to produce an estimate of the average expansion or compression from one time point to the next and compared to the air flow rate measured by spirometry. In four out of five individuals, the average log

DNA Double-Strand Break Rejoining in Complex Normal Tissues

International Nuclear Information System (INIS)

Ruebe, Claudia E.; Dong, Xiaorong; Kuehne, Martin; Fricke, Andreas; Kaestner, Lars; Lipp, Peter; Ruebe, Christian

2008-01-01

Purpose: The clinical radiation responses of different organs vary widely and likely depend on the intrinsic radiosensitivities of their different cell populations. Double-strand breaks (DSBs) are the most deleterious form of DNA damage induced by ionizing radiation, and the cells' capacity to rejoin radiation-induced DSBs is known to affect their intrinsic radiosensitivity. To date, only little is known about the induction and processing of radiation-induced DSBs in complex normal tissues. Using an in vivo model with repair-proficient mice, the highly sensitive γH2AX immunofluorescence was established to investigate whether differences in DSB rejoining could account for the substantial differences in clinical radiosensitivity observed among normal tissues. Methods and Materials: After whole body irradiation of C57BL/6 mice (0.1, 0.5, 1.0, and 2.0 Gy), the formation and rejoining of DSBs was analyzed by enumerating γH2AX foci in various organs representative of both early-responding (small intestine) and late-responding (lung, brain, heart, kidney) tissues. Results: The linear dose correlation observed in all analyzed tissues indicated that γH2AX immunofluorescence allows for the accurate quantification of DSBs in complex organs. Strikingly, the various normal tissues exhibited identical kinetics for γH2AX foci loss, despite their clearly different clinical radiation responses. Conclusion: The identical kinetics of DSB rejoining measured in different organs suggest that tissue-specific differences in radiation responses are independent of DSB rejoining. This finding emphasizes the fundamental role of DSB repair in maintaining genomic integrity, thereby contributing to cellular viability and functionality and, thus, tissue homeostasis

[Expression of high mobility group box-1 in the lung tissue and serum of patients with pulmonary tuberculosis].

Science.gov (United States)

Yang, Xiao-min; Yang, Hua

2013-07-01

To explore the expression of high mobility group box-1 (HMGB1) in the lung tissue and serum of patients with pulmonary tuberculosis and to explore its relationship with tumor necrosis factor (TNF)-α and interleukin(IL)-1β. Sixty samples of lung tissues were obtained from patients with pulmonary tuberculosis who had underwent pneumonectomy in Department of Chest Surgery, First Affiliated Hospital of Zunyi Medical College from June 2010 to December 2011. At the same period, 40 normal lung samples were also obtained from patients with pulmonary contusion and lung cancer by surgical resections as the control group. The mRNA expressions of HMGB1 was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the protein level of HMGB1 was measured by immunohistochemical staining of tissue microarrays in lung tissue. Blood samples were taken from 89 patients with active pulmonary tuberculosis (pulmonary tuberculosis group), including hematogenous disseminated pulmonary tuberculosis (type II) in 35 cases and secondary pulmonary tuberculosis (type III) in 54 cases, and 50 healthy volunteers (control group). Furthermore, the 54 patients with secondary pulmonary tuberculosis were divided into different subgroups according to cavity formation and the lung fields involved: patients without lung cavity (35 cases) vs those with lung cavity (19 cases), patients with involvement of pulmonary tuberculosis (69 ± 29) was significantly higher than that in normal lung tissue (22 ± 12) (t = 2.389, P pulmonary tuberculosis (786 ± 86) was significantly higher than that in normal lung tissue (202 ± 60) (t = 3.872, P pulmonary tuberculosis group were (5.0 ± 3.2) µg/L, (118 ± 77) ng/L and (33 ± 20) ng/L, respectively, which were significantly higher than those in the control group [(1.7 ± 1.0) µg/L, (40 ± 11) ng/L and (18 ± 12) ng/L, respectively], the respective t values being -0.928, 4.268 and 11.064, all P pulmonary tuberculosis, the serum concentration of HMGB

Mesenchymal Stem Cells From Bone Marrow, Adipose Tissue, and Lung Tissue Differentially Mitigate Lung and Distal Organ Damage in Experimental Acute Respiratory Distress Syndrome.

Science.gov (United States)

Silva, Johnatas D; Lopes-Pacheco, Miquéias; Paz, Ana H R; Cruz, Fernanda F; Melo, Elga B; de Oliveira, Milena V; Xisto, Débora G; Capelozzi, Vera L; Morales, Marcelo M; Pelosi, Paolo; Cirne-Lima, Elizabeth; Rocco, Patricia R M

2018-02-01

Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome. Animal study and primary cell culture. Laboratory investigation. Seventy-five Wistar rats. Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium). Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1β, keratinocyte-derived chemokine, transforming growth factor-β, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue

Mesenchymal Stem Cells Adopt Lung Cell Phenotype in Normal and Radiation-induced Lung Injury Conditions.

Science.gov (United States)

Maria, Ola M; Maria, Ahmed M; Ybarra, Norma; Jeyaseelan, Krishinima; Lee, Sangkyu; Perez, Jessica; Shalaby, Mostafa Y; Lehnert, Shirley; Faria, Sergio; Serban, Monica; Seuntjens, Jan; El Naqa, Issam

2016-04-01

Lung tissue exposure to ionizing irradiation can invariably occur during the treatment of a variety of cancers leading to increased risk of radiation-induced lung disease (RILD). Mesenchymal stem cells (MSCs) possess the potential to differentiate into epithelial cells. However, cell culture methods of primary type II pneumocytes are slow and cannot provide a sufficient number of cells to regenerate damaged lungs. Moreover, effects of ablative radiation doses on the ability of MSCs to differentiate in vitro into lung cells have not been investigated yet. Therefore, an in vitro coculture system was used, where MSCs were physically separated from dissociated lung tissue obtained from either healthy or high ablative doses of 16 or 20 Gy whole thorax irradiated rats. Around 10±5% and 20±3% of cocultured MSCs demonstrated a change into lung-specific Clara and type II pneumocyte cells when MSCs were cocultured with healthy lung tissue. Interestingly, in cocultures with irradiated lung biopsies, the percentage of MSCs changed into Clara and type II pneumocytes cells increased to 40±7% and 50±6% at 16 Gy irradiation dose and 30±5% and 40±8% at 20 Gy irradiation dose, respectively. These data suggest that MSCs to lung cell differentiation is possible without cell fusion. In addition, 16 and 20 Gy whole thorax irradiation doses that can cause varying levels of RILD, induced different percentages of MSCs to adopt lung cell phenotype compared with healthy lung tissue, providing encouraging outlook for RILD therapeutic intervention for ablative radiotherapy prescriptions.

Fabrication and characterization of scaffold from cadaver goat-lung tissue for skin tissue engineering applications

Energy Technology Data Exchange (ETDEWEB)

Gupta, Sweta K. [Department of Polymer and Process Engineering, Indian Institute of Technology, Roorkee (India); Dinda, Amit K. [Department of Pathology, All India Institute of Medical Sciences, New Delhi (India); Potdar, Pravin D. [Department of Molecular Medicine, Jaslok Hospital and Research Centre, Mumbai (India); Mishra, Narayan C., E-mail: mishrawise@gmail.com [Department of Polymer and Process Engineering, Indian Institute of Technology, Roorkee (India)

2013-10-15

The present study aims to fabricate scaffold from cadaver goat-lung tissue and evaluate it for skin tissue engineering applications. Decellularized goat-lung scaffold was fabricated by removing cells from cadaver goat-lung tissue enzymatically, to have cell-free 3D-architecture of natural extracellular matrix. DNA quantification assay and Hematoxylin and eosin staining confirmed the absence of cellular material in the decellularized lung-tissue. SEM analysis of decellularized scaffold shows the intrinsic porous structure of lung tissue with well-preserved pore-to-pore interconnectivity. FTIR analysis confirmed non-denaturation and well maintainance of collagenous protein structure of decellularized scaffold. MTT assay, SEM analysis and H and E staining of human skin-derived Mesenchymal Stem cell, seeded over the decellularized scaffold, confirms stem cell attachment, viability, biocompatibility and proliferation over the decellularized scaffold. Expression of Keratin18 gene, along with CD105, CD73 and CD44, by human skin-derived Mesenchymal Stem cells over decellularized scaffold signifies that the cells are viable, proliferating and migrating, and have maintained their critical cellular functions in the presence of scaffold. Thus, overall study proves the applicability of the goat-lung tissue derived decellularized scaffold for skin tissue engineering applications. - Highlights: • We successfully fabricated decellularized scaffold from cadaver goat-lung tissue. • Decellularized goat-lung scaffolds were found to be highly porous. • Skin derived MSC shows high cell viability and proliferation over the scaffold. • Phenotype of MSCs was well maintained over the scaffold. • The scaffold shows potential for applications in skin tissue engineering.

Fabrication and characterization of scaffold from cadaver goat-lung tissue for skin tissue engineering applications

International Nuclear Information System (INIS)

Gupta, Sweta K.; Dinda, Amit K.; Potdar, Pravin D.; Mishra, Narayan C.

2013-01-01

The present study aims to fabricate scaffold from cadaver goat-lung tissue and evaluate it for skin tissue engineering applications. Decellularized goat-lung scaffold was fabricated by removing cells from cadaver goat-lung tissue enzymatically, to have cell-free 3D-architecture of natural extracellular matrix. DNA quantification assay and Hematoxylin and eosin staining confirmed the absence of cellular material in the decellularized lung-tissue. SEM analysis of decellularized scaffold shows the intrinsic porous structure of lung tissue with well-preserved pore-to-pore interconnectivity. FTIR analysis confirmed non-denaturation and well maintainance of collagenous protein structure of decellularized scaffold. MTT assay, SEM analysis and H and E staining of human skin-derived Mesenchymal Stem cell, seeded over the decellularized scaffold, confirms stem cell attachment, viability, biocompatibility and proliferation over the decellularized scaffold. Expression of Keratin18 gene, along with CD105, CD73 and CD44, by human skin-derived Mesenchymal Stem cells over decellularized scaffold signifies that the cells are viable, proliferating and migrating, and have maintained their critical cellular functions in the presence of scaffold. Thus, overall study proves the applicability of the goat-lung tissue derived decellularized scaffold for skin tissue engineering applications. - Highlights: • We successfully fabricated decellularized scaffold from cadaver goat-lung tissue. • Decellularized goat-lung scaffolds were found to be highly porous. • Skin derived MSC shows high cell viability and proliferation over the scaffold. • Phenotype of MSCs was well maintained over the scaffold. • The scaffold shows potential for applications in skin tissue engineering

MRI of normal and pathological fetal lung development

International Nuclear Information System (INIS)

Kasprian, Gregor; Balassy, Csilla; Brugger, Peter C.; Prayer, Daniela

2006-01-01

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

MRI of normal and pathological fetal lung development

Energy Technology Data Exchange (ETDEWEB)

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

2006-02-15

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

Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

International Nuclear Information System (INIS)

Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

2013-01-01

Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The phantom study showed that

UPLC-MS method for quantification of pterostilbene and its application to comparative study of bioavailability and tissue distribution in normal and Lewis lung carcinoma bearing mice.

Science.gov (United States)

Deng, Li; Li, Yongzhi; Zhang, Xinshi; Chen, Bo; Deng, Yulin; Li, Yujuan

2015-10-10

A UPLC-MS method was developed for determination of pterostilbene (PTS) in plasma and tissues of mice. PTS was separated on Agilent Zorbax XDB-C18 column (50 × 2.1 mm, 1.8 μm) with gradient mobile phase at the flow rate of 0.2 ml/min. The detection was performed by negative ion electrospray ionization in multiple reaction monitoring mode. The linear calibration curve of PTS in mouse plasma and tissues ranged from 1.0 to 5000 and 0.50 to 500 ng/ml (r(2)>0.9979), respectively, with lowest limits of quantification (LLOQ) were between 0.5 and 2.0 ng/ml, respectively. The accuracy and precision of the assay were satisfactory. The validated method was applied to the study of bioavailability and tissue distribution of PTS in normal and Lewis lung carcinoma (LLC) bearing mice. The bioavailability of PTS (dose 14, 28 and 56 mg/kg) in normal mice were 11.9%, 13.9% and 26.4%, respectively; and the maximum level (82.1 ± 14.2 μg/g) was found in stomach (dose 28 mg/kg). The bioavailability, peak concentration (Cmax), time to peak concentration (Tmax) of PTS in LLC mice was increased compared with normal mice. The results indicated the UPLC-MS method is reliable and bioavailability and tissue distribution of PTS in normal and LLC mice were dramatically different. Copyright © 2015 Elsevier B.V. All rights reserved.

Estimation of gas and tissue lung volumes by MRI: functional approach of lung imaging.

Science.gov (United States)

Qanadli, S D; Orvoen-Frija, E; Lacombe, P; Di Paola, R; Bittoun, J; Frija, G

1999-01-01

The purpose of this work was to assess the accuracy of MRI for the determination of lung gas and tissue volumes. Fifteen healthy subjects underwent MRI of the thorax and pulmonary function tests [vital capacity (VC) and total lung capacity (TLC)] in the supine position. MR examinations were performed at inspiration and expiration. Lung volumes were measured by a previously validated technique on phantoms. Both individual and total lung volumes and capacities were calculated. MRI total vital capacity (VC(MRI)) was compared with spirometric vital capacity (VC(SP)). Capacities were correlated to lung volumes. Tissue volume (V(T)) was estimated as the difference between the total lung volume at full inspiration and the TLC. No significant difference was seen between VC(MRI) and VC(SP). Individual capacities were well correlated (r = 0.9) to static volume at full inspiration. The V(T) was estimated to be 836+/-393 ml. This preliminary study demonstrates that MRI can accurately estimate lung gas and tissue volumes. The proposed approach appears well suited for functional imaging of the lung.

A Comparative Study of Rat Lung Decellularization by Chemical Detergents for Lung Tissue Engineering

Directory of Open Access Journals (Sweden)

Hamid Tebyanian

2017-12-01

CONCLUSION: Decellularized lung tissue can be used in the laboratory to study various aspects of pulmonary biology and physiology and also, these results can be used in the continued improvement of engineered lung tissue.

Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

Directory of Open Access Journals (Sweden)

Xiaolin He

Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

Directory of Open Access Journals (Sweden)

Federica Novelli

Full Text Available Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons. Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations. Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor

Fabrication and characterization of scaffold from cadaver goat-lung tissue for skin tissue engineering applications.

Science.gov (United States)

Gupta, Sweta K; Dinda, Amit K; Potdar, Pravin D; Mishra, Narayan C

2013-10-01

The present study aims to fabricate scaffold from cadaver goat-lung tissue and evaluate it for skin tissue engineering applications. Decellularized goat-lung scaffold was fabricated by removing cells from cadaver goat-lung tissue enzymatically, to have cell-free 3D-architecture of natural extracellular matrix. DNA quantification assay and Hematoxylin and eosin staining confirmed the absence of cellular material in the decellularized lung-tissue. SEM analysis of decellularized scaffold shows the intrinsic porous structure of lung tissue with well-preserved pore-to-pore interconnectivity. FTIR analysis confirmed non-denaturation and well maintainance of collagenous protein structure of decellularized scaffold. MTT assay, SEM analysis and H&E staining of human skin-derived Mesenchymal Stem cell, seeded over the decellularized scaffold, confirms stem cell attachment, viability, biocompatibility and proliferation over the decellularized scaffold. Expression of Keratin18 gene, along with CD105, CD73 and CD44, by human skin-derived Mesenchymal Stem cells over decellularized scaffold signifies that the cells are viable, proliferating and migrating, and have maintained their critical cellular functions in the presence of scaffold. Thus, overall study proves the applicability of the goat-lung tissue derived decellularized scaffold for skin tissue engineering applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Protein signature of lung cancer tissues.

Directory of Open Access Journals (Sweden)

Michael R Mehan

Full Text Available Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan to compare protein expression signatures of non small-cell lung cancer (NSCLC tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment.

Over-expression of thymosin β4 in granulomatous lung tissue with active pulmonary tuberculosis.

Science.gov (United States)

Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun; Yoo, Young-Bin; Chun, Bong-Kwon; Oak, Chul-Ho; Cha, Hee-Jae

2014-05-01

Recent studies have shown that thymosin β4 (Tβ4) stimulates angiogenesis by inducing vascular endothelial growth factor (VEGF) expression and stabilizing hypoxia inducible factor-1α (HIF-1α) protein. Pulmonary tuberculosis (TB), a type of granulomatous disease, is accompanied by intense angiogenesis and VEGF levels have been reported to be elevated in serum or tissue inflamed by pulmonary tuberculosis. We investigated the expression of Tβ4 in granulomatous lung tissues at various stages of active pulmonary tuberculosis, and we also examined the expression patterns of VEGF and HIF-1α to compare their Tβ4 expression patterns in patients' tissues and in the tissue microarray of TB patients. Tβ4 was highly expressed in both granulomas and surrounding lymphocytes in nascent granulomatous lung tissue, but was expressed only surrounding tissues of necrotic or caseous necrotic regions. The expression pattern of HIF-1α was similar to that of Tβ4. VEGF was expressed in both granulomas and blood vessels surrounding granulomas. The expression pattern of VEGF co-localized with CD31 (platelet endothelial cell adhesion molecule, PECAM-1), a blood endothelial cell marker, and partially co-localized with Tβ4. However, the expression of Tβ4 did not co-localize with alveolar macrophages. Stained alveolar macrophages were present surrounding regions of granuloma highly expressing Tβ4. We also analyzed mRNA expression in the sputum of 10 normal and 19 pulmonary TB patients. Expression of Tβ4 was significantly higher in patients with pulmonary tuberculosis than in normal controls. These data suggest that Tβ4 is highly expressed in granulomatous lung tissue with active pulmonary TB and is associated with HIF-1α- and VEGF-mediated inflammation and angiogenesis. Furthermore, the expression of Tβ4 in the sputum of pulmonary tuberculosis patients can be used as a potential marker for diagnosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of lung tissue particles among silicosis cases

Directory of Open Access Journals (Sweden)

B Case

2005-10-01

Full Text Available Background and Aims:Lung tissue samples of several miners, millers, sandblaster, welders andconstruction workers with historical exposure to mineral particles were analyzed. These subjectshad significant respiratory exposure to silica particles and demanded compensation foroccupational lung diseases.Method: Lung tissue samples were observed under an Electron microscope with 10000Xmagnification. Mineral particles were sized and analyzed by EDS detector based on X-rayspectrophotometry.Results: The results have indicated that the lung particle burden of the subjects was closelyrelated to their occupational history. The highest level of mineral silica particles were found in thelungs of miners and sandblasters. The highest concentration of metallic particles was found in thelungs of welders and miners in ferric mining industry. Severity of lung fibrosis was directlyrelated to the lung free silica concentration. However, no association was found between particlediameter and severity of fibrosis. In addition, lung particle burden of silicotic cases with lungcancer contained a much higher concentration of metallic particles and asbestos fibres that thelung of those subject with silicosis only.Conclusion: Although workers in mining and construction may be predominantly exposed tosilica particles including quartz, the role of other mineral particles including asbestos fibres,metallic fibres and other minerals should be taken into account in the genesis of occupational lungdisease in particular lung cancer. Lung tissue sample analysis can provide valuable informationto assess the legal and compensation cases.

Proteomic Analysis of Lung Tissue in a Rat Acute Lung Injury Model: Identification of PRDX1 as a Promoter of Inflammation

Directory of Open Access Journals (Sweden)

Dongdong Liu

2014-01-01

Full Text Available Acute respiratory distress syndrome (ARDS remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes of Pseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS challenge in airway epithelial cells in vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6, interleukin-8 (IL-8, and tumor necrosis factor-α (TNF-α, whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI.

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

Directory of Open Access Journals (Sweden)

Johnny eKao

2015-06-01

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

SU-F-R-31: Identification of Robust Normal Lung CT Texture Features for the Prediction of Radiation-Induced Lung Disease

Energy Technology Data Exchange (ETDEWEB)

Choi, W; Riyahi, S; Lu, W [University of Maryland School of Medicine, Baltimore, MD (United States)

2016-06-15

Purpose: Normal lung CT texture features have been used for the prediction of radiation-induced lung disease (radiation pneumonitis and radiation fibrosis). For these features to be clinically useful, they need to be relatively invariant (robust) to tumor size and not correlated with normal lung volume. Methods: The free-breathing CTs of 14 lung SBRT patients were studied. Different sizes of GTVs were simulated with spheres placed at the upper lobe and lower lobe respectively in the normal lung (contralateral to tumor). 27 texture features (9 from intensity histogram, 8 from grey-level co-occurrence matrix [GLCM] and 10 from grey-level run-length matrix [GLRM]) were extracted from [normal lung-GTV]. To measure the variability of a feature F, the relative difference D=|Fref -Fsim|/Fref*100% was calculated, where Fref was for the entire normal lung and Fsim was for [normal lung-GTV]. A feature was considered as robust if the largest non-outlier (Q3+1.5*IQR) D was less than 5%, and considered as not correlated with normal lung volume when their Pearson correlation was lower than 0.50. Results: Only 11 features were robust. All first-order intensity-histogram features (mean, max, etc.) were robust, while most higher-order features (skewness, kurtosis, etc.) were unrobust. Only two of the GLCM and four of the GLRM features were robust. Larger GTV resulted greater feature variation, this was particularly true for unrobust features. All robust features were not correlated with normal lung volume while three unrobust features showed high correlation. Excessive variations were observed in two low grey-level run features and were later identified to be from one patient with local lung diseases (atelectasis) in the normal lung. There was no dependence on GTV location. Conclusion: We identified 11 robust normal lung CT texture features that can be further examined for the prediction of radiation-induced lung disease. Interestingly, low grey-level run features identified normal

The expression of Egfl7 in human normal tissues and epithelial tumors.

Science.gov (United States)

Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

2013-04-23

To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease.

Science.gov (United States)

Pragman, Alexa A; Lyu, Tianmeng; Baller, Joshua A; Gould, Trevor J; Kelly, Rosemary F; Reilly, Cavan S; Isaacson, Richard E; Wendt, Chris H

2018-01-09

Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection. Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R. Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue. This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that

Histopathology of lung disease in the connective tissue diseases.

Science.gov (United States)

Vivero, Marina; Padera, Robert F

2015-05-01

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

Early and late effects of prenatal corticosteroid treatment on the microRNA profiles of lung tissue in rats

Science.gov (United States)

YU, HONG-REN; LI, SUNG-CHOU; TSENG, WAN-NING; TAIN, YOU-LIN; CHEN, CHIH-CHENG; SHEEN, JIUNN-MING; TIAO, MAO-MENG; KUO, HO-CHANG; HUANG, CHAO-CHENG; HSIEH, KAI-SHENG; HUANG, LI-TUNG

2016-01-01

Glucocorticoids have been administered to mothers at risk of premature delivery to induce maturation of preterm fetal lungs and prevent the development of respiratory distress syndrome. Micro (mi)RNAs serve various crucial functions in cell proliferation, differentiation and organ development; however, few studies have demonstrated an association between miRNAs and lung development. The aim of the present study was to investigate alterations in the miRNA profiles of rat lung tissue following prenatal glucocorticoid therapy for fetal lung development. The differences in miRNA expression profiles were compared between postnatal days 7 (D7) and 120 (D120) rat lung tissues, followed by validation using reverse transcription-quantitative polymerase chain reaction. The miRNA profiles of rat lung tissues following prenatal dexamethasone (DEX) therapy were also investigated. miRNAs with 2-fold changes were selected for further analysis. At D120, 6 upregulated and 6 downregulated miRNAs were detected, compared with D7. Among these differentially expressed miRNAs, miR-101-3p and miR-99b-5p were associated with the lowest and highest expressions of miRNA at D7, respectively. A limited impact on the miRNA profiles of rat lung tissues was observed following prenatal DEX treatment, which may help to further clarify the mechanisms underlying normal lung development. However, the results of the present study cannot entirely elucidate the effects of prenatal DEX treatment on the lung development of premature infants, and further studies investigating the impact of prenatal corticosteroids on fetal lung miRNA profiles are required. PMID:26997989

Aerosol lung inhalation scintigraphy in normal subjects

Energy Technology Data Exchange (ETDEWEB)

Sui, Osamu; Shimazu, Hideki

1985-03-01

We previously reported basic and clinical evaluation of aerosol lung inhalation scintigraphy with /sup 99m/Tc-millimicrosphere albumin (milli MISA) and concluded aerosol inhalation scintigraphy with /sup 99m/Tc-milli MISA was useful for routine examination. But central airway deposit of aerosol particles was found in not only the patients with chronic obstructive pulmonary disease (COPD) but also normal subjects. So we performed aerosol inhalation scintigraphy in normal subjects and evaluated their scintigrams. The subjects had normal values of FEVsub(1.0)% (more than 70%) in lung function tests, no abnormal findings in chest X-ray films and no symptoms and signs. The findings of aerosol inhalation scintigrams in them were classified into 3 patterns; type I: homogeneous distribution without central airway deposit, type II: homogeneous distribution with central airway deposit, type III: inhomogeneous distribution. These patterns were compared with lung function tests. There was no significant correlation between type I and type II in lung function tests. Type III was different from type I and type II in inhomogeneous distribution. This finding showed no correlation with %VC, FEVsub(1.0)%, MMF, V radical50 and V radical50/V radical25, but good correlation with V radical25 in a maximum forced expiratory flow-volume curve. Flow-volume curve is one of the sensitive methods in early detection of COPD, so inhomogeneous distribution of type III is considered to be due to small airway dysfunction.

Connective tissue diseases, multimorbidity and the ageing lung.

Science.gov (United States)

Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

2016-05-01

Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients. Copyright ©ERS 2016.

Production of decellularized porcine lung scaffolds for use in tissue engineering.

Science.gov (United States)

Balestrini, Jenna L; Gard, Ashley L; Liu, Angela; Leiby, Katherine L; Schwan, Jonas; Kunkemoeller, Britta; Calle, Elizabeth A; Sivarapatna, Amogh; Lin, Tylee; Dimitrievska, Sashka; Cambpell, Stuart G; Niklason, Laura E

2015-12-01

There is a growing body of work dedicated to producing acellular lung scaffolds for use in regenerative medicine by decellularizing donor lungs of various species. These scaffolds typically undergo substantial matrix damage due to the harsh conditions required to remove cellular material (e.g., high pH, strong detergents), lengthy processing times, or pre-existing tissue contamination from microbial colonization. In this work, a new decellularization technique is described that maintains the global tissue architecture, key matrix components, mechanical composition and cell-seeding potential of lung tissue while effectively removing resident cellular material. Acellular lung scaffolds were produced from native porcine lungs using a combination of Triton X-100 and sodium deoxycholate (SDC) at low concentrations in 24 hours. We assessed the effect of matrix decellularization by measuring residual DNA, biochemical composition, mechanical characteristics, tissue architecture, and recellularization capacity.

Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity.

Science.gov (United States)

Monceau, Virginie; Pasinetti, Nadia; Schupp, Charlotte; Pouzoulet, Fred; Opolon, Paule; Vozenin, Marie-Catherine

2010-11-01

The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibrogenic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardiomyocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibrogenic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibrogenic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established

Detection of EGFR and COX-2 Expression by Immunohistochemical Method on a Tissue Microarray Section in Lung Cancer and Biological Significance

Directory of Open Access Journals (Sweden)

Xinyun WANG

2010-02-01

Full Text Available Background and objective Epidermal growth factor receptor (EGFR and cyclooxygenase-2 (COX-2, which can regulate growth, invasion and metastasis of tumor through relevant signaling pathway, have been detected in a variety of solid tumors. The aim of this study is to investigate the biological significance of EGFR and COX-2 expression in lung cancer and the relationship between them. Methods The expression of EGFR and COX-2 was detected in 89 primary lung cancer tissues, 12 premaliganant lesions, 12 lymph node metastases, and 10 normal lung tissues as the control by immunohistochemical method on a tissue microarray section. Results EGFR protein was detectable in 59.6%, 41.7%, and 66.7% of primary lung cancer tissues, premalignant lesions and lymph node metastases, respectively; COX-2 protein was detectable in 52.8%, 41.7%, and 66.7% of primary lung cancer tissues, premalignant lesions and lymph node metastases, respectively, which were significantly higher than those of the control (P 0.05. COX-2 expression was related to gross type (P < 0.05. A highly positive correlation was observed between EGFR and COX-2 expression (P < 0.01. Conclusion Overexpression of EGFR and COX-2 may play an important role in the tumorgenesis, progression and malignancy of lung cancer. Detection of EGFR and COX-2 expression might be helpful to diagnosis and prognosis of lung cancer.

[The role of disequilibrium of expression of matrix metalloproteinase-2/9 and their tissue inhibitors in pathogenesis of hyperoxia-induced acute lung injury in mice].

Science.gov (United States)

Zhang, Xiang-feng; Zhu, Guang-fa; Liu, Shuang; Foda, Hussein D

2008-10-01

To investigate the role of matrix metalloproteinase-2/9 (MMP-2/9) and their tissue inhibitors (TIMP-1/2) in pathogenesis of acute lung injury (ALI) induced by hyperoxia. Seventy-two C57BL/6 mice were randomly divided into normal control group, hyperoxia for 24 hours group, hyperoxia for 48 hours group, and hyperoxia for 72 hours group, with 18 mice in each group. The mice in hyperoxia groups were exposed to >98% oxygen in sealed cages, and the normal control group were placed outside of the cage to breathe room air. At the end of the exposure time the animals were euthanized, the right lung was removed and phosphate buffer solution (PBS) was used to lavage the lung through the endotracheal catheter. The wet/dry weight ratio, broncho-alveolar lavage fluid (BALF) protein content and the volume of pleural fluid were measured, the severity of lung injury was assessed; the expression of MMP-2/9 and TIMP-1/2 mRNA in lung tissue at 24, 48 and 72 hours of hyperoxia were assessed by reverse transcript-polymerase chain reaction (RT-PCR); the amount of MMP-2/9 and TIMP-1/2 protein in lung tissue were measured by enzyme-linked immunosorbent assay (ELISA). Hyperoxia caused ALI as evidenced by the increase in lung wet/dry weight ratio, BALF protein content and the volume of pleural fluid as compared with the normal control group (P<0.05 or P<0.01). RT-PCR study showed increased expression of MMP-2/9 and TIMP-1 mRNA in lung tissues (P<0.05 or P<0.01), and ELISA assay also demonstrated upregulation of MMP-2/9 and an increase in TIMP-1 amount in BALF compared with their normal control group (P<0.05 or P<0.01). The ratios of both MMP-2 mRNA/TIMP-2 mRNA and MMP-2 protein/TIMP-2 protein were all increased in hyperoxia groups as compared with their normal control group (all P<0.01). Hyperoxia causes ALI in mice, and disturbance of MMP-2/TIMP-2 balance plays an important role in the development of hyperoxia-induced ALI in mice.

Measurement of asbestos bodies in lung tissue of autopsy cases diagnosed with primary lung cancer

International Nuclear Information System (INIS)

Idei, Yuka; Kamada, Satoe; Matsumoto, Shoji; Ohnishi, Kazuo; Kitazawa, Riko; Kitazawa, Sohei

2007-01-01

To investigate the relation between asbestos-related lung cancer and the concentration of asbestos bodies in lung tissue, we analyzed the concentration in 24 autopsy cases diagnosed with primary lung cancer, with regard to the gender, age, histological type of lung cancer and occupation of each case. The asbestos bodies were measured according to Kohyama's method. Positive cases (more than 5,000 bodies per 1 g of dry lung tissue) were further analyzed for asbestosis and pleural plaques by chest X-ray and chest CT. Two cases exhibited more than 5,000 bodies, five cases between 1,000 and 5,000, and seventeen cases less than 1,000. The occupation of the two positive cases was not informative: one demonstrated neither asbestosis nor pleural plaques, and the other showed only pleural plaques. Although the number of cases of asbestos-related lung cancer is minimal among all lung cancer cases, the number of the former may exceed that of mesothelioma patients. Not only physicians but also radiologists, surgeons and pathologists need to collaborate in the diagnosis of asbestos-related lung cancer. (author)

CT Densitometry of the Lung in Healthy Nonsmokers with Normal Pulmonary Function

Energy Technology Data Exchange (ETDEWEB)

Oh, Tack Sun; Chae, Eun Jin; Seo, Joon Beom; Jung, Young Ju; Oh, Yeon Mok; Lee, Sang Do [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

2012-09-15

To investigate the upper normal limit of low attenuation area in healthy nonsmokers. A total of 36 nonsmokers with normal pulmonary function test underwent a CT scan. Six thresholds (-980 --930 HU) on inspiration CT and two thresholds (-950 and -910 HU) on expiration CT were used for obtaining low attenuation area. The mean lung density was obtained on both inspiration CT and expiration CT. Descriptive statistics of low attenuation area and the mean lung density, evaluation of difference of low attenuation area and the mean lung density in both sex and age groups, analysis of the relationship between demographic information and CT parameters were performed. Upper normal limit for low attenuation area was 12.96% on inspiration CT (-950 HU) and 9.48% on expiration CT (-910 HU). Upper normal limit for the mean lung density was -837.58 HU on inspiration CT and 686.82 HU on expiration CT. Low attenuation area and the mean lung density showed no significant differences in both sex and age groups. Body mass index (BMI) was negatively correlated with low attenuation area on inspiration CT (-950 HU, r = -0.398, p = 0.016) and positively correlated with the mean lung density on inspiration CT (r 0.539, p = 0.001) and expiration CT (r = 0.432, p = 0.009). Age and body surface area were not correlated with low attenuation area or the mean lung density. Low attenuation area on CT densitometry of the lung could be found in healthy nonsmokers with normal pulmonary function, and showed negative association with BMI. Reference values, such as range and upper normal limit for low attenuation area in healthy subjects could be helpful in quantitative analysis and follow up of early emphysema, using CT densitometry of the lung.

Effects of lung elasticity on the sound propagation in the lung

International Nuclear Information System (INIS)

Yoneda, Takahiro; Wada, Shigeo; Nakamura, Masanori; Horii, Noriaki; Mizushima, Koichiro

2011-01-01

Sound propagation in the lung was simulated for gaining insight into its acoustic properties. A thorax model consisting of lung parenchyma, thoracic bones, trachea and other tissues was made from human CT images. Acoustic nature of the lung parenchyma and bones was expressed with the Biot model of poroelastic material, whereas trachea and tissues were modeled with gas and an elastic material. A point sound source of white noises was placed in the first bifurcation of trachea. The sound propagation in the thorax model was simulated in a frequency domain. The results demonstrated the significant attenuation of sound especially in frequencies larger than 1,000 Hz. Simulations with a stiffened lung demonstrated suppression of the sound attenuation for higher frequencies observed in the normal lung. These results indicate that the normal lung has the nature of a low-pass filter, and stiffening helps the sound at higher frequencies to propagate without attenuations. (author)

[Effect of oxidative stress-associated damage to the lung tissue caused by different body mass index in the rat models].

Science.gov (United States)

Li, X Y; Zhang, X J; Zhao, J H; Xu, J Y

2016-12-12

Objective: To investigate the influence of different diets on serum protein expression levels of 4-hydroxynonenal (4-HNE), thioredoxin (Trx), thioredoxin reductase (TrxR) and the activities of Trx and TrxR, and to explore the effect of damage to the lung tissue and the underlying mechanisms of different body mass index caused by different diets in the rat models . Method: Healthy clean male SD rats were randomly divided into normal group, emaciation group and fat group, which were raised by different diets for 6 months.Then the rats were sacrificed and the serum and lung tissue were prepared. The levels of 4-HNE, Trx and TrxR in peripheral blood were quantitatively analyzed by enzyme-linked immunosorbent assay(ELISA), and the activities of Trx and TrxR were measured by chemical methods. Results: Compared with the normal group, the lung tissue had more apparent emphysema in the emaciation and the fat groups under light microscope, and more inflammatory cell infiltration in alveolar septum was observed in the fat group.The levels of 4-HNE in the fat group[(24.7±8.7)mg/L]was significantly higher than that in the normal group[(15.4±4.7)mg/L, P 0.05)in the levels of 4-HNE between the emaciation and the normal groups. The levels of TrxR in the emaciation group[(7.7±1.4)μg/ml]was significantly higher than that in the normal and the fat groups[(6.2±1.1), (4.9±1.4)μg/ml, all P 0.05). The activity of Trx in the emaciation group[(32.4±8.5)×10 -3 A ·min -1 ·mg -1 ]was significantly higher than that in the normal group[(19.6±3.3)×10 -3 A ·min -1 ·mg -1 ]and the fat group[(11.3±7.5)×10 -3 A ·min -1 ·mg -1 , all P 0.05). Conclusion: Both high BMI and low BMI can affect the oxidative stress of the body, resulting in increased oxidants and decreased antioxidants, and can cause damage to the lung tissue in the rat models.

The relationship among human papilloma virus infection, survivin, and p53 gene in lung squamous carcinoma tissue

International Nuclear Information System (INIS)

Yue-Hua Wang; De-jie Chen; Tie-Nan Yi

2010-01-01

To study the relationship between the infection of human papillomavirus (HPV) type 16, type 18, the expression of survivin, and the mutation of p53 gene in lung squamous carcinoma tissue for the research of pathogenesis of lung carcinoma.This study was carried out at the Laboratory of Molecular Biology, Xiangfan Central Hospital of Hubei Province, China from September 2008 to May 2010. Forty-five specimens of lung squamous carcinoma tissue confirmed by histopathology were the excisional specimens taken by the Thoracic Surgery of Xiangfan Central Hospital. Normal tissue, closely adjacent to the fresh carcinoma specimens, was used as the control group for p53 gene mutation analysis. Sixteen surgical excisional specimens of benign lung disease were used as a control group of non-carcinomatous diseases. Human papillomavirus DNA were detected by polymerase chain reaction (PCR), and we used the PCR-single-strand conformation polymorphism-ethidium bromide (PCR-SSCP-EB) method to detect the mutations of the p53 gene. The expression of the survivin gene was detected by immunohistochemistry methods. Approximately 68.9% of 45 lung squamous carcinoma tissue had p53 gene mutations. The mutation rate of exon 5-8 p53 were 15.6%, 17.8%, 15.6% and 20%. Approximately 42.2% of lung squamous cell carcinoma samples were shown to be positive for HPV DNA expression and 62.2% were positive for survivin expression. There was an inverse correlation between the presence of HPV infections and mutations of p53 gene; and the mutations of p53 gene and expression of survivin had a positive relationship. Mutation of p53 gene and HPV infection may facilitate each other in the generation of lung squamous cell carcinoma. Abnormal expression of the survivin gene may take part in the onset and progression of lung squamous cell carcinoma (Author).

Absorbed dose calculation of the energy deposition close to bone, lung and soft tissue interfaces in molecular radiotherapy

International Nuclear Information System (INIS)

Fernandez, M.; Lassman, M.

2015-01-01

Full text of publication follows. Aim: for voxel-based dosimetry in molecular radiotherapy (MRT) based on tabulated voxel S-values these values are usually obtained only for soft tissue. In order to study the changes in the dose deposition patterns at interfaces between different materials we have performed Monte Carlo simulations. Methods: the deposited energy patterns were obtained using the Monte-Carlo radiation code MCNPX v2.7 for Lu 177 (medium-energy) and Y 90 (high-energy). The following interfaces were studied: soft tissue-bone and soft tissue-lungs. For this purpose a volume of soft tissue homogeneously filled with Lu 177 or Y 90 was simulated at the interface to 3 different volumes containing no activity: soft tissue, lungs and bone. The emission was considered to be isotropic. The dimensions were chosen to ensure that the energy deposited by all generated particles was scored. The materials were defined as recommended by ICPR46; the decay schemes of Eckerman and Endo were used. With these data the absorbed dose patterns normalized to the maximum absorbed dose in the source region (soft tissue) were calculated. Results: the absorbed dose fractions in the boundary with soft tissue, bone and lungs are 50%, 47% and 57%, respectively, for Lu 177 and 50%, 47% and 51% for Y 90 . The distances to the interface at which the absorbed fractions are at 0.1% are 1.0, 0.6 and 3.0 mm for Lu 177 and 7.0, 4.0 and 24 mm for Y 90 , for soft tissue, bone and lungs respectively. Conclusions: in MRT, the changes in the absorbed doses at interfaces between soft tissue and bone/lungs need to be considered for isotopes emitting high energy particles. (authors)

Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

Science.gov (United States)

Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

2014-01-01

The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

Production of decellularized porcine lung scaffolds for use in tissue engineering†

Science.gov (United States)

Balestrini, Jenna L.; Gard, Ashley L.; Liu, Angela; Leiby, Katherine L.; Schwan, Jonas; Kunkemoeller, Britta; Calle, Elizabeth A.; Sivarapatna, Amogh; Lin, Tylee; Dimitrievska, Sashka; Cambpella, Stuart G.; Niklason, Laura E.

2015-01-01

There is a growing body of work dedicated to producing acellular lung scaffolds for use in regenerative medicine by decellularizing donor lungs of various species. These scaffolds typically undergo substantial matrix damage due to the harsh conditions required to remove cellular material (e.g., high pH, strong detergents), lengthy processing times, or pre-existing tissue contamination from microbial colonization. In this work, a new decellularization technique is described that maintains the global tissue architecture, key matrix components, mechanical composition and cell-seeding potential of lung tissue while effectively removing resident cellular material. Acellular lung scaffolds were produced from native porcine lungs using a combination of Triton X-100 and sodium deoxycholate (SDC) at low concentrations in 24 hours. We assessed the effect of matrix decellularization by measuring residual PMID:26426090

[Normal lung volumes in patients with idiopathic pulmonary fibrosis and emphysema].

Science.gov (United States)

Casas, Juan Pablo; Abbona, Horacio; Robles, Adriana; López, Ana María

2008-01-01

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

Do Tumors in the Lung Deform During Normal Respiration? An Image Registration Investigation

International Nuclear Information System (INIS)

Wu Jianzhou; Lei Peng; Shekhar, Raj; Li Huiling; Suntharalingam, Mohan; D'Souza, Warren D.

2009-01-01

Purpose: The purpose of this study was to investigate whether lung tumors may be described adequately using a rigid body assumption or whether they deform during normal respiration. Methods and Materials: Thirty patients with early stage non-small-cell lung cancer underwent four-dimensional (4D) computed tomography (CT) simulation. The gross tumor volume (GTV) was delineated on the 4D CT images. Image registration was performed in the vicinity of the GTV. The volume of interest for registration was the GTV and minimal volume of surrounding non-GTV tissue. Three types of registration were performed: translation only, translation + rotation, and deformable. The GTV contour from end-inhale was mapped to end-exhale using the registration-derived transformation field. The results were evaluated using three metrics: overlap index (OI), root-mean-squared distance (RMS), and Hausdorff distance (HD). Results: After translation only image registration, on average OI increased by 21.3%, RMS and HD reduced by 1.2 mm and 2.0 mm, respectively. The succeeding increases in OI after translation + rotation and deformable registration were 1.1% and 1.4% respectively. The succeeding reductions in RMS were 0.1 mm and 0.2 mm respectively. No reduction in HD was observed after translation + rotation and deformable image registration compared with translation only registration. The difference in the results from the three registration scenarios was independent of GTV size and motion amplitude. Conclusions: The primary effect of normal respiration on lung tumors was the translation of tumors. Rotation and deformation of lung tumors was determined to be minimal.

Neutron RBE for normal tissues

International Nuclear Information System (INIS)

Field, S.B.; Hornsey, S.

1979-01-01

RBE for various normal tissues is considered as a function of neutron dose per fraction. Results from a variety of centres are reviewed. It is shown that RBE is dependent on neutron energy and is tissue dependent, but is not specially high for the more critical tissues or for damage occurring late after irradiation. (author)

Accumulation of DNA Double-Strand Breaks in Normal Tissues After Fractionated Irradiation

International Nuclear Information System (INIS)

Ruebe, Claudia E.; Fricke, Andreas; Wendorf, Juliane; Stuetzel, Annika; Kuehne, Martin; Ong, Mei Fang; Lipp, Peter; Ruebe, Christian

2010-01-01

Purpose: There is increasing evidence that genetic factors regulating the recognition and/or repair of DNA double-strand breaks (DSBs) are responsible for differences in radiosensitivity among patients. Genetically defined DSB repair capacities are supposed to determine patients' individual susceptibility to develop adverse normal tissue reactions after radiotherapy. In a preclinical murine model, we analyzed the impact of different DSB repair capacities on the cumulative DNA damage in normal tissues during the course of fractionated irradiation. Material and Methods: Different strains of mice with defined genetic backgrounds (SCID -/- homozygous, ATM -/- homozygous, ATM +/- heterozygous, and ATM +/+ wild-type mice) were subjected to single (2 Gy) or fractionated irradiation (5 x 2 Gy). By enumerating γH2AX foci, the formation and rejoining of DSBs were analyzed in organs representative of both early-responding (small intestine) and late-responding tissues (lung, kidney, and heart). Results: In repair-deficient SCID -/- and ATM -/- homozygous mice, large proportions of radiation-induced DSBs remained unrepaired after each fraction, leading to the pronounced accumulation of residual DNA damage after fractionated irradiation, similarly visible in early- and late-responding tissues. The slight DSB repair impairment of ATM +/- heterozygous mice was not detectable after single-dose irradiation but resulted in a significant increase in unrepaired DSBs during the fractionated irradiation scheme. Conclusions: Radiation-induced DSBs accumulate similarly in acute- and late-responding tissues during fractionated irradiation, whereas the whole extent of residual DNA damage depends decisively on the underlying genetically defined DSB repair capacity. Moreover, our data indicate that even minor impairments in DSB repair lead to exceeding DNA damage accumulation during fractionated irradiation and thus may have a significant impact on normal tissue responses in clinical

Elastin Cables Define the Axial Connective Tissue System in the Murine Lung.

Science.gov (United States)

Wagner, Willi; Bennett, Robert D; Ackermann, Maximilian; Ysasi, Alexandra B; Belle, Janeil; Valenzuela, Cristian D; Pabst, Andreas; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

2015-11-01

The axial connective tissue system is a fiber continuum of the lung that maintains alveolar surface area during changes in lung volume. Although the molecular anatomy of the axial system remains undefined, the fiber continuum of the lung is central to contemporary models of lung micromechanics and alveolar regeneration. To provide a detailed molecular structure of the axial connective tissue system, we examined the extracellular matrix of murine lungs. The lungs were decellularized using a 24 hr detergent treatment protocol. Systematic evaluation of the decellularized lungs demonstrated no residual cellular debris; morphometry demonstrated a mean 39 ± 7% reduction in lung dimensions. Scanning electron microscopy (SEM) demonstrated an intact structural hierarchy within the decellularized lung. Light, fluorescence, and SEM of precision-cut lung slices demonstrated that alveolar duct structure was defined by a cable line element encased in basement membrane. The cable line element arose in the distal airways, passed through septal tips and inserted into neighboring blood vessels and visceral pleura. The ropelike appearance, collagenase resistance and anti-elastin immunostaining indicated that the cable was an elastin macromolecule. Our results indicate that the helical line element of the axial connective tissue system is composed of an elastin cable that not only defines the structure of the alveolar duct, but also integrates the axial connective tissue system into visceral pleura and peripheral blood vessels. © 2015 Wiley Periodicals, Inc.

Calculation of microplanar beam dose profiles in a tissue/lung/tissue phantom

International Nuclear Information System (INIS)

Company, F.Z.; Allen, B.J.

1998-01-01

Recent advances in synchrotron generated x-ray beams with a high fluence rate permit investigation of the application of an array of closely spaced, parallel or converging microplanar beams in radiotherapy. The proposed technique takes advantage of the hypothesized repair mechanism of capillary cells between alternate microbeam zones, which regenerates the lethally irradiated endothelial cells. The lateral and depth doses of 100 keV microplanar beams are investigated for different beam dimensions and spacings in a tissue, lung and tissue/lung/tissue phantom. The EGS4 Monte Carlo code is used to calculate dose profiles at different depths and bundles of beams (up to 20x20cm square cross section). The maximum dose on the beam axis (peak) and the minimum interbeam dose (valley) are compared at different depths, bundles, heights, widths and beam spacings. (author)

[The effects of postconditioning with propofol on Toll-like receptor 4 expression in the lung tissue of rat with acute lung injury].

Science.gov (United States)

Li, Guo-Fu; Tong, Xin; Luan, Ting; Zang, Bin

2012-10-01

To investigate the effect of postconditioning with propofol on Toll-like receptor 4 (TLR4) expression in the lung tissue in lipopolysaccharide (LPS)-induced acute lung injury (ALI) rats. Thirty Sprague-Dawley (SD) rats were randomly assigned to control group, ALI group, and propofol postcondition group (each n=10). The model of ALI was reproduced by intravenous injection of LPS (8 mg/kg for 30 minutes) into the rats, equivalent normal saline was injected into the rats of control group. The rats were postconditioned with propofol injected intravenously by 20 mg/kg bolus dose and then continuously by 40 mg×kg(-1)×h(-1) with a constant speed for 1 hour. The rats were sacrificed 6 hours after drug injection. Lung wet/dry weight (W/D) ratio and lung permeability index (LPI) was taken. Tumor necrosis factor-α (TNF-α) level in bronchoalveolar lavage fluid (BALF) was detected using enzyme linked immunosorbent assay (ELISA) method and TLR4 mRNA expression in lung tissue was assessed by reverse transcription-polymerase chain reaction (RT-PCR). The lung W/D ratio, LPI, TLR4 mRNA and TNF-α in BALF were all increased in ALI group compared with control group [lung W/D ratio: 5.30±0.28 vs. 4.21±0.14, LPI (×10(-3)): 8.7±2.2 vs. 3.3±2.0, TLR4 mRNA: 2.451±0.028 vs. 0.998±0.021, TNF-α: 643.46±62.31 ng/L vs. 120.43±12.65 ng/L, all Pwaterfall-like inflammatory reaction.

Measurement of histamine release from human lung tissue ex vivo by microdialysis technique

DEFF Research Database (Denmark)

Nissen, Dan; Petersen, Lars Jelstrup; Nolte, H

1998-01-01

OBJECTIVE AND DESIGN: Currently no method is available for measurement of mediator release from intact human lung. In this study, a microdialysis technique was used to measure histamine release from mast cells in human lung tissue ex vivo. MATERIAL: Microdialysis fibers of 216 microm were inserted...... responses were observed but data could be reproduced within individual donors. Monocyte chemoattractant protein-1, a potent basophil secretagogue, did not induce histamine release in lung tissue which indicated mast cells to be the histamine source. Substance P did not release histamine in the lung tissue....... CONCLUSIONS: The microdialysis technique allowed measurements of histamine release from mast cells in intact lung ex vivo. The method may prove useful since a number of experiments can be performed in a few hours in intact lung tissue without any dispersion or enzymatic treatment....

Modulation of the ρ/rock pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity

International Nuclear Information System (INIS)

Monceau, V.; Pasinetti, N.; Schupp, C.; Pouzoulet, F.; Opolon, P.; Vozenin, M.C.

2010-01-01

The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibro-genic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardio-myocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibro-genic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibro-genic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of

The role of high airway pressure and dynamic strain on ventilator-induced lung injury in a heterogeneous acute lung injury model.

Science.gov (United States)

Jain, Sumeet V; Kollisch-Singule, Michaela; Satalin, Joshua; Searles, Quinn; Dombert, Luke; Abdel-Razek, Osama; Yepuri, Natesh; Leonard, Antony; Gruessner, Angelika; Andrews, Penny; Fazal, Fabeha; Meng, Qinghe; Wang, Guirong; Gatto, Louis A; Habashi, Nader M; Nieman, Gary F

2017-12-01

Acute respiratory distress syndrome causes a heterogeneous lung injury with normal and acutely injured lung tissue in the same lung. Improperly adjusted mechanical ventilation can exacerbate ARDS causing a secondary ventilator-induced lung injury (VILI). We hypothesized that a peak airway pressure of 40 cmH 2 O (static strain) alone would not cause additional injury in either the normal or acutely injured lung tissue unless combined with high tidal volume (dynamic strain). Pigs were anesthetized, and heterogeneous acute lung injury (ALI) was created by Tween instillation via a bronchoscope to both diaphragmatic lung lobes. Tissue in all other lobes was normal. Airway pressure release ventilation was used to precisely regulate time and pressure at both inspiration and expiration. Animals were separated into two groups: (1) over-distension + high dynamic strain (OD + H DS , n = 6) and (2) over-distension + low dynamic strain (OD + L DS , n = 6). OD was caused by setting the inspiratory pressure at 40 cmH 2 O and dynamic strain was modified by changing the expiratory duration, which varied the tidal volume. Animals were ventilated for 6 h recording hemodynamics, lung function, and inflammatory mediators followed by an extensive necropsy. In normal tissue (N T ), OD + L DS caused minimal histologic damage and a significant reduction in BALF total protein (p < 0.05) and MMP-9 activity (p < 0.05), as compared with OD + H DS . In acutely injured tissue (ALI T ), OD + L DS resulted in reduced histologic injury and pulmonary edema (p < 0.05), as compared with OD + H DS . Both N T and ALI T are resistant to VILI caused by OD alone, but when combined with a H DS , significant tissue injury develops.

[Elevated expression of endothelin 2 in lung tissues of asthmatic rats after exposed to cigarette smoke and its mechanism].

Science.gov (United States)

Han, Fangfang; Zhu, Shuyang; Chen, Bi; Li, Jingjing

2017-08-01

Objective To study the effect of cigarette smoke exposure on the expression of endothelin 2 (ET-2) in bronchial epithelium of asthmatic rats. Methods Asthma models were established through intraperitoneal injection of 1 mL chicken ovalbumin (OVA)/Al(OH) 3 mixture (asthma model group, n=6); based on the asthma models, exposure to smoking gas lasted four weeks with 10 cigarettes per day (smoke-exposed asthma group, n=6); based on the smoke-exposed asthma models, the rats were treated with intraperitoneal injection of dexamethasone 2 mg/(kg.d), intragastric administration of ET receptor inhibitor bosentan 100 mg/(kg.d) and combined use, respectively named dexamethasone treated group, bosentan treated group, and dexamethasone-bosentan treated group, 6 rats in every group. What's more, other 6 rats were only subjected to intraperitoneal injection of 1 mL normal saline as normal controls; in addition to the injection of saline, cigarette smoke control group (n=6) was set up by the exposure to smoking gas for four weeks with 10 cigarettes per day. Bronchoalveolar lavage fluid (BALF) was collected from the upper lobe of the left lung for cell counting and classification. Pathological changes of the right upper lung lobe tissues were observed by HE staining. In other lung tissues, the expression of JNK1/2 was detected by Western blotting; ET-2 was tested by Western blotting and immunohistochemistry; thiobarbituric acid reactive substances (TBARS) assay and trace enzyme standard method were used to measure malondialdehyde (MDA) and glutathione (GSH), respectively. Results Compared with normal control group, the number of airway inflammation cells increased in the BALF, and the expressions of ET-2, JNK1/2, MDA and GSH increased in the lung tissues of cigarette smoke control group, asthma model group and cigarette smoke-exposed asthma group. Compared with cigarette smoke-exposed asthma group, the number of airway inflammation cells decreased in the BALF, and the expressions of

Effects of tracheal occlusion with retinoic acid administration on normal lung development.

Science.gov (United States)

Delabaere, Amélie; Marceau, Geoffroy; Coste, Karen; Blanchon, Loïc; Déchelotte, Pierre-Jean; Blanc, Pierre; Sapin, Vincent; Gallot, Denis

2017-05-01

Tracheal occlusion (TO) is an investigational therapy for severe congenital diaphragmatic hernia that decreases pulmonary hypoplasia, but sustained TO also induces deficient surfactant synthesis. Intramuscular maternal administration of retinoic acid (RA) in a surgical rabbit model of congenital diaphragmatic hernia showed a beneficial effect on lung maturation. We evaluated the potential of RA delivery into the trachea and studied the combined effects of TO and RA on normal lung development. Experiments were performed on normal rabbit fetuses. Liposomes and capric triglyceride (Miglyol ® ), alone and with RA, were administered in the trachea just before TO (d26). Lung morphology and surfactant production were studied at term (d30). Tracheal occlusion increased lung weight and enhanced alveolar development but increased apoptotic activity and decreased surfactant expression. Tracheal injection of RA improved surfactant production to levels of normal controls. We established the potential of liposome and Miglyol as RA vehicle for delivering this bioactive molecule in the fetal airways. Tracheal RA injection seems to oppose the effects of TO in fetuses with normal lungs. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Analysis of lung tissue using ion beams

International Nuclear Information System (INIS)

Alvarez, J.L.; Barrera, R.; Miranda, J.

2002-01-01

In this work a comparative study is presented of the contents of metals in lung tissue from healthy patients and with lung cancer, by means of two analytical techniques: Particle Induced X-ray Emission (PIXE) and Rutherford Backscattering Spectrometry (RBS). The samples of cancerous tissue were taken from 26 autopsies made to individuals died in the National Institute of Respiratory Disease (INER), 22 of cancer and 4 of other non-cancer biopsies. When analyzing the entirety of the samples, in the cancerous tissues, there were increments in the concentrations of S (4%), K (635%), Co (85%) and Cu (13%). Likewise, there were deficiencies in the concentrations of Cl (59%), Ca (6%), Fe (26%) and Zn (7%). Only in the cancerous tissues there were appearances of P, Ca, Ti, V, Cr, Mn, Ni, Br and Sr. The tissue samples were classified according to cancer types (adenocarcinomas, epidermoides and of small cell carcinoma), personal habits (smokers and alcoholic), genetic predisposition and residence place. There was a remarkable decrease in the concentration of Ca and a marked increment in the Cu in the epidermoide tissue samples with regard to those of adenocarcinoma or of small cells cancer. Also, decrements were detected in K and increments of Fe, Co and Cu in the sample belonging to people that resided in Mexico City with regard to those that resided in the State of Mexico

Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

International Nuclear Information System (INIS)

Rangel, M.P.; Sá, V.K. de; Martins, V.; Martins, J.R.M.; Parra, E.R.; Mendes, A.; Andrade, P.C.; Reis, R.M.; Longatto-Filho, A.; Oliveira, C.Z.; Takagaki, T.; Carraro, D.M.; Nader, H.B.; Capelozzi, V.L.

2015-01-01

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology

Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

Energy Technology Data Exchange (ETDEWEB)

Rangel, M.P.; Sá, V.K. de; Martins, V. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Martins, J.R.M. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Disciplina de Endocrinologia e Metabolismo, Laboratório de Endocrinologia Molecular e Translacional-LEMT, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Parra, E.R. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mendes, A. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Andrade, P.C. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Reis, R.M. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Longatto-Filho, A. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Laboratório de Investigação Médica (LIM 14), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Oliveira, C.Z. [Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Takagaki, T. [Divisão de Pneumologia, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carraro, D.M. [Centro Internacional de Pesquisa/CIPE, AC Camargo Cancer Center, São Paulo, SP (Brazil); Nader, H.B. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Capelozzi, V.L. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

2015-05-08

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.

Tumor and normal tissue motion in the thorax during respiration: Analysis of volumetric and positional variations using 4D CT

International Nuclear Information System (INIS)

Weiss, Elisabeth; Wijesooriya, Krishni; Dill, S. Vaughn; Keall, Paul J.

2007-01-01

Purpose: To investigate temporospatial variations of tumor and normal tissue during respiration in lung cancer patients. Methods and Materials: In 14 patients, gross tumor volume (GTV) and normal tissue structures were manually contoured on four-dimensional computed tomography (4D-CT) scans. Structures were evaluated for volume changes, centroid (center of mass) motion, and phase dependence of variations relative to inspiration. Only volumetrically complete structures were used for analysis (lung in 2, heart in 8, all other structures in >10 patients). Results: During respiration, the magnitude of contoured volumes varied up to 62.5% for GTVs, 25.5% for lungs, and 12.6% for hearts. The range of maximum three-dimensional centroid movement for individual patients was 1.3-24.0 mm for GTV, 2.4-7.9 mm for heart, 5.2-12.0 mm for lungs, 0.3-5.5 mm for skin markers, 2.9-10.0 mm for trachea, and 6.6-21.7 mm for diaphragm. During respiration, the centroid positions of normal structures varied relative to the centroid position of the respective GTV by 1.5-8.1 mm for heart, 2.9-9.3 mm for lungs, 1.2-9.2 mm for skin markers, 0.9-7.1 mm for trachea, and 2.7-16.4 mm for diaphragm. Conclusion: Using 4D-CT, volumetric changes, positional alterations as well as changes in the position of contoured structures relative to the GTV were observed with large variations between individual patients. Although the interpretation of 4D-CT data has considerable uncertainty because of 4D-CT artifacts, observer variations, and the limited acquisition time, the findings might have a significant impact on treatment planning

Esophageal involvement and interstitial lung disease in mixed connective tissue disease.

Science.gov (United States)

Fagundes, M N; Caleiro, M T C; Navarro-Rodriguez, T; Baldi, B G; Kavakama, J; Salge, J M; Kairalla, R; Carvalho, C R R

2009-06-01

Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa's classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; pmotor dysfunction (90% vs. 35%; pesophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

Frequency and number of ultrasound lung rockets (B-lines) using a regionally based lung ultrasound examination named vet BLUE (veterinary bedside lung ultrasound exam) in dogs with radiographically normal lung findings.

Science.gov (United States)

Lisciandro, Gregory R; Fosgate, Geoffrey T; Fulton, Robert M

2014-01-01

Lung ultrasound is superior to lung auscultation and supine chest radiography for many respiratory conditions in human patients. Ultrasound diagnoses are based on easily learned patterns of sonographic findings and artifacts in standardized images. By applying the wet lung (ultrasound lung rockets or B-lines, representing interstitial edema) versus dry lung (A-lines with a glide sign) concept many respiratory conditions can be diagnosed or excluded. The ultrasound probe can be used as a visual stethoscope for the evaluation of human lungs because dry artifacts (A-lines with a glide sign) predominate over wet artifacts (ultrasound lung rockets or B-lines). However, the frequency and number of wet lung ultrasound artifacts in dogs with radiographically normal lungs is unknown. Thus, the primary objective was to determine the baseline frequency and number of ultrasound lung rockets in dogs without clinical signs of respiratory disease and with radiographically normal lung findings using an 8-view novel regionally based lung ultrasound examination called Vet BLUE. Frequency of ultrasound lung rockets were statistically compared based on signalment, body condition score, investigator, and reasons for radiography. Ten left-sided heart failure dogs were similarly enrolled. Overall frequency of ultrasound lung rockets was 11% (95% confidence interval, 6-19%) in dogs without respiratory disease versus 100% (95% confidence interval, 74-100%) in those with left-sided heart failure. The low frequency and number of ultrasound lung rockets observed in dogs without respiratory disease and with radiographically normal lungs suggests that Vet BLUE will be clinically useful for the identification of canine respiratory conditions. © 2014 American College of Veterinary Radiology.

CT quantification of lung and airways in normal Korean subjects

Energy Technology Data Exchange (ETDEWEB)

Kim, Song Soo; Lee, Jeong Eun; Shin, Hye Soo [Dept. of Radiology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon (Korea, Republic of); Jin, Gong Yong; Li, Yuan Zhe [Dept. of Radiology, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju (Korea, Republic of)

2017-08-01

To measure and compare the quantitative parameters of the lungs and airways in Korean never-smokers and current or former smokers (“ever-smokers”). Never-smokers (n = 119) and ever-smokers (n = 45) who had normal spirometry and visually normal chest computed tomography (CT) results were retrospectively enrolled in this study. For quantitative CT analyses, the low attenuation area (LAA) of LAA{sub I-950}, LAA{sub E-856}, CT attenuation value at the 15th percentile, mean lung attenuation (MLA), bronchial wall thickness of inner perimeter of a 10 mm diameter airway (Pi10), total lung capacity (TLC{sub CT}), and functional residual capacity (FRC{sub CT}) were calculated based on inspiratory and expiratory CT images. To compare the results between groups according to age, sex, and smoking history, independent t test, one way ANOVA, correlation test, and simple and multiple regression analyses were performed. The values of attenuation parameters and volume on inspiratory and expiratory quantitative computed tomography (QCT) were significantly different between males and females (p < 0.001). The MLA and the 15th percentile value on inspiratory QCT were significantly lower in the ever-smoker group than in the never-smoker group (p < 0.05). On expiratory QCT, all lung attenuation parameters were significantly different according to the age range (p < 0.05). Pi10 in ever-smokers was significantly correlated with forced expiratory volume in 1 second/forced vital capacity (r = −0.455, p = 0.003). In simple and multivariate regression analyses, TLC{sub CT}, FRC{sub CT}, and age showed significant associations with lung attenuation (p < 0.05), and only TLC{sub CT} was significantly associated with inspiratory Pi10. In Korean subjects with normal spirometry and visually normal chest CT, there may be significant differences in QCT parameters according to sex, age, and smoking history.

CT quantification of lung and airways in normal Korean subjects

International Nuclear Information System (INIS)

Kim, Song Soo; Lee, Jeong Eun; Shin, Hye Soo; Jin, Gong Yong; Li, Yuan Zhe

2017-01-01

To measure and compare the quantitative parameters of the lungs and airways in Korean never-smokers and current or former smokers (“ever-smokers”). Never-smokers (n = 119) and ever-smokers (n = 45) who had normal spirometry and visually normal chest computed tomography (CT) results were retrospectively enrolled in this study. For quantitative CT analyses, the low attenuation area (LAA) of LAA_I_-_9_5_0, LAA_E_-_8_5_6, CT attenuation value at the 15th percentile, mean lung attenuation (MLA), bronchial wall thickness of inner perimeter of a 10 mm diameter airway (Pi10), total lung capacity (TLC_C_T), and functional residual capacity (FRC_C_T) were calculated based on inspiratory and expiratory CT images. To compare the results between groups according to age, sex, and smoking history, independent t test, one way ANOVA, correlation test, and simple and multiple regression analyses were performed. The values of attenuation parameters and volume on inspiratory and expiratory quantitative computed tomography (QCT) were significantly different between males and females (p < 0.001). The MLA and the 15th percentile value on inspiratory QCT were significantly lower in the ever-smoker group than in the never-smoker group (p < 0.05). On expiratory QCT, all lung attenuation parameters were significantly different according to the age range (p < 0.05). Pi10 in ever-smokers was significantly correlated with forced expiratory volume in 1 second/forced vital capacity (r = −0.455, p = 0.003). In simple and multivariate regression analyses, TLC_C_T, FRC_C_T, and age showed significant associations with lung attenuation (p < 0.05), and only TLC_C_T was significantly associated with inspiratory Pi10. In Korean subjects with normal spirometry and visually normal chest CT, there may be significant differences in QCT parameters according to sex, age, and smoking history

Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

Energy Technology Data Exchange (ETDEWEB)

Warren, Samantha, E-mail: Samantha.warren@oncology.ox.ac.uk [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Partridge, Mike [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Carrington, Rhys [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hurt, Chris [Wales Cancer Trials Unit, School of Medicine, Heath Park, Cardiff (United Kingdom); Crosby, Thomas [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hawkins, Maria A. [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom)

2014-10-01

Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

Changes in the rate of proliferation in normal tissues after irradiation

International Nuclear Information System (INIS)

Denekamp, J.

1975-01-01

In tissues where reproductive cell death is known to cause the functional tissue damage (e.g., intestine and skin), repopulation becomes important only after the death of the radiation-damaged cells. Since these tissues have a fairly rapid turnover, this can occur within a short period of time and can assist in the healing of tissues during fractionated therapy. However, in tissues which express their damage late, such as the lung, it is very unlikely that repopulation will be stimulated before cell death is manifested and this does not occur during the period over which fractionated radiotherapy is administered. Although repopulation may be of no importance in these tissues, e.g., lungs and kidneys, there appears to be some other ''repair'' process which requires additional radiation dose to be administered to achieve the same endpoint if the overall time is increased

Uncovering growth-suppressive MicroRNAs in lung cancer

DEFF Research Database (Denmark)

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

2009-01-01

PURPOSE: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth-suppressive miRNAs in lung cancer. EXPERIMENTAL DESIGN: miRNA arrays were done on normal lung tissues...... and adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each......-malignant human lung tissue bank. RESULTS: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung...

Radiation-induced hypoxia may perpetuate late normal tissue injury

International Nuclear Information System (INIS)

Vujaskovic, Zeljko; Anscher, Mitchell S.; Feng, Q.-F.; Rabbani, Zahid N.; Amin, Khalid; Samulski, Thaddeus S.; Dewhirst, Mark W.; Haroon, Zishan A.

2001-01-01

Purpose: The purpose of this study was to determine whether or not hypoxia develops in rat lung tissue after radiation. Methods and Materials: Fisher-344 rats were irradiated to the right hemithorax using a single dose of 28 Gy. Pulmonary function was assessed by measuring the changes in respiratory rate every 2 weeks, for 6 months after irradiation. The hypoxia marker was administered 3 h before euthanasia. The tissues were harvested at 6 weeks and 6 months after irradiation and processed for immunohistochemistry. Results: A moderate hypoxia was detected in the rat lungs at 6 weeks after irradiation, before the onset of functional or histopathologic changes. The more severe hypoxia, that developed at the later time points (6 months) after irradiation, was associated with a significant increase in macrophage activity, collagen deposition, lung fibrosis, and elevation in the respiratory rate. Immunohistochemistry studies revealed an increase in TGF-β, VEGF, and CD-31 endothelial cell marker, suggesting a hypoxia-mediated activation of the profibrinogenic and proangiogenic pathways. Conclusion: A new paradigm of radiation-induced lung injury should consider postradiation hypoxia to be an important contributing factor mediating a continuous production of a number of inflammatory and fibrogenic cytokines

CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.

Directory of Open Access Journals (Sweden)

Mariam El-Ashmawy

Full Text Available Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs. In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF = 1.3, and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients.

Signs of Gas Trapping in Normal Lung Density Regions in Smokers.

Science.gov (United States)

Bodduluri, Sandeep; Reinhardt, Joseph M; Hoffman, Eric A; Newell, John D; Nath, Hrudaya; Dransfield, Mark T; Bhatt, Surya P

2017-12-01

A substantial proportion of subjects without overt airflow obstruction have significant respiratory morbidity and structural abnormalities as visualized by computed tomography. Whether regions of the lung that appear normal using traditional computed tomography criteria have mild disease is not known. To identify subthreshold structural disease in normal-appearing lung regions in smokers. We analyzed 8,034 subjects with complete inspiratory and expiratory computed tomographic data participating in the COPDGene Study, including 103 lifetime nonsmokers. The ratio of the mean lung density at end expiration (E) to end inspiration (I) was calculated in lung regions with normal density (ND) by traditional thresholds for mild emphysema (-910 Hounsfield units) and gas trapping (-856 Hounsfield units) to derive the ND-E/I ratio. Multivariable regression analysis was used to measure the associations between ND-E/I, lung function, and respiratory morbidity. The ND-E/I ratio was greater in smokers than in nonsmokers, and it progressively increased from mild to severe chronic obstructive pulmonary disease severity. A proportion of 26.3% of smokers without airflow obstruction had ND-E/I greater than the 90th percentile of normal. ND-E/I was independently associated with FEV 1 (adjusted β = -0.020; 95% confidence interval [CI], -0.032 to -0.007; P = 0.001), St. George's Respiratory Questionnaire scores (adjusted β = 0.952; 95% CI, 0.529 to 1.374; P smokers without airflow obstruction, and it is associated with respiratory morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

Oxygen delivery in irradiated normal tissue

Energy Technology Data Exchange (ETDEWEB)

Kiani, M.F.; Ansari, R. [Univ. of Tennessee Health Science Center, Memphis, TN (United States). School of Biomedical Engineering; Gaber, M.W. [St. Jude Children' s Research Hospital, Memphis, TN (United States)

2003-03-01

Ionizing radiation exposure significantly alters the structure and function of microvascular networks, which regulate delivery of oxygen to tissue. In this study we use a hamster cremaster muscle model to study changes in microvascular network parameters and use a mathematical model to study the effects of these observed structural and microhemodynamic changes in microvascular networks on oxygen delivery to the tissue. Our experimental observations indicate that in microvascular networks while some parameters are significantly affected by irradiation (e.g. red blood cell (RBC) transit time), others remain at the control level (e.g. RBC path length) up to 180 days post-irradiation. The results from our mathematical model indicate that tissue oxygenation patterns are significantly different in irradiated normal tissue as compared to age-matched controls and the differences are apparent as early as 3 days post irradiation. However, oxygen delivery to irradiated tissue was not found to be significantly different from age matched controls at any time between 7 days to 6 months post-irradiation. These findings indicate that microvascular late effects in irradiated normal tissue may be due to factors other than compromised tissue oxygenation. (author)

Normal expiratory flow rate and lung volumes in patients with combined emphysema and interstitial lung disease: a case series and literature review.

Science.gov (United States)

Heathcote, Karen L; Cockcroft, Donald W; Fladeland, Derek A; Fenton, Mark E

2011-01-01

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

Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors

Directory of Open Access Journals (Sweden)

Erickson-Miller Connie L

2012-09-01

Full Text Available Abstract Background Numerous efficacious chemotherapy regimens may cause thrombocytopenia. Thrombopoietin receptor (TPO-R agonists, such as eltrombopag, represent a novel approach for the treatment of chemotherapy-induced thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte precursors, although little is known about its expression on other tissues. Methods Breast, lung, and ovarian tumor samples were analyzed for MPL expression by microarray and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR, and for TPO-R protein expression by immunohistochemistry (IHC. Cell line proliferation assays were used to analyze the in vitro effect of eltrombopag on breast, lung, and ovarian tumor cell proliferation. The lung carcinoma cell lines were also analyzed for TPO-R protein expression by Western blot. Results MPL mRNA was not detectable in 118 breast tumors and was detectable at only very low levels in 48% of 29 lung tumors studied by microarray analysis. By qRT-PCR, low but detectable levels of MPL mRNA were detectable in some normal (14-43% and malignant (3-17% breast, lung, and ovarian tissues. A comparison of MPL to EPOR, ERBB2, and IGF1R mRNA demonstrates that MPL mRNA levels were far lower than those of EPOR and ERBB2 mRNA in the same tissues. IHC analysis showed negligible TPO-R protein expression in tumor tissues, confirming mRNA analysis. Culture of breast, lung, and ovarian carcinoma cell lines showed no increase, and in fact, showed a decrease in proliferation following incubation with eltrombopag. Western blot analyses revealed no detectable TPO-R protein expression in the lung carcinoma cell lines. Conclusions Multiple analyses of breast, lung, and ovarian tumor samples and/or cell lines show no evidence of MPL mRNA or TPO-R protein expression. Eltrombopag does not stimulate growth of breast, lung, or ovarian tumor cell lines at doses likely to exert their actions on megakaryocytes and

Low tidal volume and high positive end-expiratory pressure mechanical ventilation results in increased inflammation and ventilator-associated lung injury in normal lungs.

Science.gov (United States)

Hong, Caron M; Xu, Da-Zhong; Lu, Qi; Cheng, Yunhui; Pisarenko, Vadim; Doucet, Danielle; Brown, Margaret; Aisner, Seena; Zhang, Chunxiang; Deitch, Edwin A; Delphin, Ellise

2010-06-01

Protective mechanical ventilation with low tidal volume (Vt) and low plateau pressure reduces mortality and decreases the length of mechanical ventilation in patients with acute respiratory distress syndrome. Mechanical ventilation that will protect normal lungs during major surgical procedures of long duration may improve postoperative outcomes. We performed an animal study comparing 3 ventilation strategies used in the operating room in normal lungs. We compared the effects on pulmonary mechanics, inflammatory mediators, and lung tissue injury. Female pigs were randomized into 3 groups. Group H-Vt/3 (n = 6) was ventilated with a Vt of 15 mL/kg predicted body weight (PBW)/positive end-expiratory pressure (PEEP) of 3 cm H(2)O, group L-Vt/3 (n = 6) with a Vt of 6 mL/kg PBW/PEEP of 3 cm H(2)O, and group L-Vt/10 (n = 6) with a Vt of 6 mL/kg PBW/PEEP of 10 cm H(2)O, for 8 hours. Hemodynamics, airway mechanics, arterial blood gases, and inflammatory markers were monitored. Bronchoalveolar lavage (BAL) was analyzed for inflammatory markers and protein concentration. The right lower lobe was assayed for mRNA of specific cytokines. The right lower lobe and right upper lobe were evaluated histologically. In contrast to groups H-Vt/3 and L-Vt/3, group L-Vt/10 exhibited a 6-fold increase in inflammatory mediators in BAL (P ventilation with high PEEP resulted in increased production of inflammatory markers. Low PEEP resulted in lower levels of inflammatory markers. High Vt/low PEEP resulted in less histologic lung injury.

Three dimensional conformal radiation therapy may improve the therapeutic ratio of radiation therapy after pneumonectomy for lung cancer

Energy Technology Data Exchange (ETDEWEB)

Trouette, R; Causse, N; Elkhadri, M; Caudry, M; Maire, J P; Houlard, J P; Racaldini, L; Demeaux, H

1995-12-01

Three dimensional conformal radiation therapy would allow to decrease the normal tissue dose while maintaining the same target dose as standard treatment. To evaluate the feasibility of normal tissue dose reduction for ten patients with pneumonectomy for lung cancer, we determined the dose distribution to the normal tissue with 3-dimensional conformal radiation therapy (3-DCRT) and conventional treatment planning (CTP). Dose-volume histograms for target and normal tissue (lung, heart) were used for comparison of the different treatment planning. The mean percentages of lung and heart volumes which received 40 Gy with 3-DCRT were respectively 63% and 37% of the mean percentage of lung and volumes which received the same dose with CTP. These preliminary results suggest that conformal therapy may improve the therapeutic ratio by reducing risk to normal tissue.

Lung Cancer Signature Biomarkers: tissue specific semantic similarity based clustering of Digital Differential Display (DDD data

Directory of Open Access Journals (Sweden)

Srivastava Mousami

2012-11-01

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

TH-E-BRF-07: Raman Spectroscopy for Radiation Treatment Response Assessment in a Lung Metastases Mouse Model

Energy Technology Data Exchange (ETDEWEB)

Devpura, S; Barton, K; Brown, S; Siddiqui, F; Chetty, I [Henry Ford Health System, Detroit, MI (United States); Sethi, S [Karmanos Cancer Center, Detroit, MI (United States); Klein, M [Children' s Hospital of Michigan, Detroit, MI (United States)

2014-06-15

Purpose: Raman spectroscopy is an optical spectroscopic method used to probe chemical information about a target tissue. Our goal was to investigate whether Raman spectroscopy is able to distinguish lung tumors from normal lung tissue and whether this technique can identify the molecular changes induced by radiation. Methods: 4T1 mouse breast cancer cells were implanted subcutaneously into the flanks of 6 Balb/C female mice. Four additional mice were used as “normal lung” controls. After 14 days, 3 mice bearing tumors received 6Gy to the left lung with 6MV photons and the other three were treated as “unirradiated tumor” controls. At a 24-hour time point, lungs were excised and the specimens were sectioned using a cryostat; alternating sections were either stained with hematoxylin and eosin (H and E) for evaluation by a pathologist or unstained for Raman measurements. 240 total Raman spectra were collected; 84 from normal lung controls; 63 from unirradiated tumors and 64 from tumors irradiated with 6Gy in a single fraction. Raman spectra were also collected from normal lung tissues of mice with unirradiated tumors. Principal component analysis (PCA) and discriminant function analysis (DFA) were performed to analyze the data. Results: Raman bands assignable to DNA/RNA showed prominent contributions in tumor tissues while Raman bands associated with hemoglobin showed strong contributions in normal lung tissue. PCA/DFA analysis identified normal lung tissue and tumor with 100% and 98.4% accuracy, respectively, relative to pathologic scoring. Additionally, normal lung tissues from unirradiated mice bearing tumors were classified as normal with 100% accuracy. In a model consisting of unirradiated and irradiated tumors identification accuracy was 79.4% and 93.8% respectively, relative to pathologic assessment. Conclusion: Initial results demonstrate the promise for Raman spectroscopy in the diagnosis normal vs. lung metastases as well as the assessment of

TH-E-BRF-07: Raman Spectroscopy for Radiation Treatment Response Assessment in a Lung Metastases Mouse Model

International Nuclear Information System (INIS)

Devpura, S; Barton, K; Brown, S; Siddiqui, F; Chetty, I; Sethi, S; Klein, M

2014-01-01

Purpose: Raman spectroscopy is an optical spectroscopic method used to probe chemical information about a target tissue. Our goal was to investigate whether Raman spectroscopy is able to distinguish lung tumors from normal lung tissue and whether this technique can identify the molecular changes induced by radiation. Methods: 4T1 mouse breast cancer cells were implanted subcutaneously into the flanks of 6 Balb/C female mice. Four additional mice were used as “normal lung” controls. After 14 days, 3 mice bearing tumors received 6Gy to the left lung with 6MV photons and the other three were treated as “unirradiated tumor” controls. At a 24-hour time point, lungs were excised and the specimens were sectioned using a cryostat; alternating sections were either stained with hematoxylin and eosin (H and E) for evaluation by a pathologist or unstained for Raman measurements. 240 total Raman spectra were collected; 84 from normal lung controls; 63 from unirradiated tumors and 64 from tumors irradiated with 6Gy in a single fraction. Raman spectra were also collected from normal lung tissues of mice with unirradiated tumors. Principal component analysis (PCA) and discriminant function analysis (DFA) were performed to analyze the data. Results: Raman bands assignable to DNA/RNA showed prominent contributions in tumor tissues while Raman bands associated with hemoglobin showed strong contributions in normal lung tissue. PCA/DFA analysis identified normal lung tissue and tumor with 100% and 98.4% accuracy, respectively, relative to pathologic scoring. Additionally, normal lung tissues from unirradiated mice bearing tumors were classified as normal with 100% accuracy. In a model consisting of unirradiated and irradiated tumors identification accuracy was 79.4% and 93.8% respectively, relative to pathologic assessment. Conclusion: Initial results demonstrate the promise for Raman spectroscopy in the diagnosis normal vs. lung metastases as well as the assessment of

Epidermal growth factor receptor in primary human lung cancer

International Nuclear Information System (INIS)

Yu Xueyan; Hu Guoqiang; Tian Keli; Wang Mingyun

1996-01-01

Cell membranes were prepared from 12 human lung cancers for the study of the expression of epidermal growth factor receptors (EGFR). EGFR concentration was estimated by ligand binding studies using 125 I-radiolabeled EGF. The dissociation constants of the high affinity sites were identical, 1.48 nmol and 1.1 nmol in cancer and normal lung tissues, the EGFR contents were higher in lung cancer tissues (range: 2.25 to 19.39 pmol·g -1 membrane protein) than that in normal tissues from the same patients (range: 0.72 to 7.43 pmol·g -1 membrane protein). These results suggest that EGF and its receptor may play a role in the regulatory mechanisms in the control of lung cellular growth and tumor promotion

Radiogenomics: predicting clinical normal tissue radiosensitivity

DEFF Research Database (Denmark)

Alsner, Jan

2006-01-01

Studies on the genetic basis of normal tissue radiosensitivity, or  'radiogenomics', aims at predicting clinical radiosensitivity and optimize treatment from individual genetic profiles. Several studies have now reported links between variations in certain genes related to the biological response...... to radiation injury and risk of normal tissue morbidity in cancer patients treated with radiotherapy. However, after these initial association studies including few genes, we are still far from being able to predict clinical radiosensitivity on an individual level. Recent data from our own studies on risk...

Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis

Science.gov (United States)

Heinrichs, M. Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D.; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A.; Blumberg, Henry M.; Vashakidze, Sergo

2017-01-01

ABSTRACT Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass-like (n = 3 patients), or consolidative (n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R = −0.66, P = 0.04) and acid-fast bacilli (R = −0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. PMID:28373198

Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis.

Science.gov (United States)

Kempker, Russell R; Heinrichs, M Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A; Blumberg, Henry M; Vashakidze, Sergo

2017-06-01

Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary ( n = 6 patients), mass-like ( n = 3 patients), or consolidative ( n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis ( R = -0.66, P = 0.04) and acid-fast bacilli ( R = -0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. Copyright © 2017 American Society for Microbiology.

Diffusion-weighted MR imaging of the normal fetal lung

International Nuclear Information System (INIS)

Balassy, Csilla; Kasprian, Gregor; Weber, Michael; Hoermann, Marcus; Bankier, Alexander; Herold, Christian J.; Prayer, Daniela; Brugger, Peter C.; Csapo, Bence; Bammer, Roland

2008-01-01

To quantify apparent diffusion coefficient (ADC) changes in fetuses with normal lungs and to determine whether ADC can be used in the assessment of fetal lung development. In 53 pregnancies (20-37th weeks of gestation), we measured ADC on diffusion-weighted imaging (DWI) in the apical, middle, and basal thirds of the right lung. ADCs were correlated with gestational age. Differences between the ADCs were assessed. Fetal lung volumes were measured on T2-weighted sequences and correlated with ADCs and with age. ADCs were 2.13 ± 0.44 μm 2 /ms (mean ± SD) in the apex, 1.99 ± 0.42 μm 2 /ms (mean ± SD) in the middle third, and 1.91 ± 0.41 μm 2 /ms (mean ± SD) in the lung base. Neither the individual ADC values nor average ADC values showed a significant correlation with gestational age or with lung volumes. Average ADCs decreased significantly from the lung apex toward the base. Individual ADCs showed little absolute change and heterogeneity. Lung volumes increased significantly during gestation. We have not been able to identify a pattern of changes in the ADC values that correlate with lung maturation. Furthermore, the individual, gravity-related ADC changes are subject to substantial variability and show nonuniform behavior. ADC can therefore not be used as an indicator of lung maturity. (orig.)

Diffusion-weighted MR imaging of the normal fetal lung

Energy Technology Data Exchange (ETDEWEB)

Balassy, Csilla; Kasprian, Gregor; Weber, Michael; Hoermann, Marcus; Bankier, Alexander; Herold, Christian J.; Prayer, Daniela [Medical University of Vienna, Department of Radiology, Vienna (Austria); Brugger, Peter C. [Medical University of Vienna, Center of Anatomy and Cell Biology, Vienna (Austria); Csapo, Bence [Medical University of Vienna, Department of Obstetrics and Gyneocology, Vienna (Austria); Bammer, Roland [University of Stanford, Department of Radiology, Stanford, CA (United States)

2008-04-15

To quantify apparent diffusion coefficient (ADC) changes in fetuses with normal lungs and to determine whether ADC can be used in the assessment of fetal lung development. In 53 pregnancies (20-37th weeks of gestation), we measured ADC on diffusion-weighted imaging (DWI) in the apical, middle, and basal thirds of the right lung. ADCs were correlated with gestational age. Differences between the ADCs were assessed. Fetal lung volumes were measured on T2-weighted sequences and correlated with ADCs and with age. ADCs were 2.13 {+-} 0.44 {mu}m{sup 2}/ms (mean {+-} SD) in the apex, 1.99 {+-} 0.42 {mu}m{sup 2}/ms (mean {+-} SD) in the middle third, and 1.91 {+-} 0.41 {mu}m{sup 2}/ms (mean {+-} SD) in the lung base. Neither the individual ADC values nor average ADC values showed a significant correlation with gestational age or with lung volumes. Average ADCs decreased significantly from the lung apex toward the base. Individual ADCs showed little absolute change and heterogeneity. Lung volumes increased significantly during gestation. We have not been able to identify a pattern of changes in the ADC values that correlate with lung maturation. Furthermore, the individual, gravity-related ADC changes are subject to substantial variability and show nonuniform behavior. ADC can therefore not be used as an indicator of lung maturity. (orig.)

Automating the expert consensus paradigm for robust lung tissue classification

Science.gov (United States)

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

2012-03-01

Clinicians confirm the efficacy of dynamic multidisciplinary interactions in diagnosing Lung disease/wellness from CT scans. However, routine clinical practice cannot readily accomodate such interactions. Current schemes for automating lung tissue classification are based on a single elusive disease differentiating metric; this undermines their reliability in routine diagnosis. We propose a computational workflow that uses a collection (#: 15) of probability density functions (pdf)-based similarity metrics to automatically cluster pattern-specific (#patterns: 5) volumes of interest (#VOI: 976) extracted from the lung CT scans of 14 patients. The resultant clusters are refined for intra-partition compactness and subsequently aggregated into a super cluster using a cluster ensemble technique. The super clusters were validated against the consensus agreement of four clinical experts. The aggregations correlated strongly with expert consensus. By effectively mimicking the expertise of physicians, the proposed workflow could make automation of lung tissue classification a clinical reality.

Data-driven classification of ventilated lung tissues using electrical impedance tomography

International Nuclear Information System (INIS)

Gómez-Laberge, Camille; Hogan, Matthew J; Elke, Gunnar; Weiler, Norbert; Frerichs, Inéz; Adler, Andy

2011-01-01

Current methods for identifying ventilated lung regions utilizing electrical impedance tomography images rely on dividing the image into arbitrary regions of interest (ROI), manually delineating ROI, or forming ROI with pixels whose signal properties surpass an arbitrary threshold. In this paper, we propose a novel application of a data-driven classification method to identify ventilated lung ROI based on forming k clusters from pixels with correlated signals. A standard first-order model for lung mechanics is then applied to determine which ROI correspond to ventilated lung tissue. We applied the method in an experimental study of 16 mechanically ventilated swine in the supine position, which underwent changes in positive end-expiratory pressure (PEEP) and fraction of inspired oxygen (F I O 2 ). In each stage of the experimental protocol, the method performed best with k = 4 and consistently identified 3 lung tissue ROI and 1 boundary tissue ROI in 15 of the 16 subjects. When testing for changes from baseline in lung position, tidal volume, and respiratory system compliance, we found that PEEP displaced the ventilated lung region dorsally by 2 cm, decreased tidal volume by 1.3%, and increased the respiratory system compliance time constant by 0.3 s. F I O 2 decreased tidal volume by 0.7%. All effects were tested at p < 0.05 with n = 16. These findings suggest that the proposed ROI detection method is robust and sensitive to ventilation dynamics in the experimental setting

Estimation of Lung Ventilation

Science.gov (United States)

Ding, Kai; Cao, Kunlin; Du, Kaifang; Amelon, Ryan; Christensen, Gary E.; Raghavan, Madhavan; Reinhardt, Joseph M.

Since the primary function of the lung is gas exchange, ventilation can be interpreted as an index of lung function in addition to perfusion. Injury and disease processes can alter lung function on a global and/or a local level. MDCT can be used to acquire multiple static breath-hold CT images of the lung taken at different lung volumes, or with proper respiratory control, 4DCT images of the lung reconstructed at different respiratory phases. Image registration can be applied to this data to estimate a deformation field that transforms the lung from one volume configuration to the other. This deformation field can be analyzed to estimate local lung tissue expansion, calculate voxel-by-voxel intensity change, and make biomechanical measurements. The physiologic significance of the registration-based measures of respiratory function can be established by comparing to more conventional measurements, such as nuclear medicine or contrast wash-in/wash-out studies with CT or MR. An important emerging application of these methods is the detection of pulmonary function change in subjects undergoing radiation therapy (RT) for lung cancer. During RT, treatment is commonly limited to sub-therapeutic doses due to unintended toxicity to normal lung tissue. Measurement of pulmonary function may be useful as a planning tool during RT planning, may be useful for tracking the progression of toxicity to nearby normal tissue during RT, and can be used to evaluate the effectiveness of a treatment post-therapy. This chapter reviews the basic measures to estimate regional ventilation from image registration of CT images, the comparison of them to the existing golden standard and the application in radiation therapy.

T2 relaxation time in MR imaging of normal and abnormal lung parenchyma

International Nuclear Information System (INIS)

Mayo, J.R.; McKay, A.; Mueller, N.L.

1990-01-01

To measure the T2 relaxation times of normal and abnormal lung parenchyma and to evaluate the influence of field strength and lung inflation on T2. Five healthy volunteers and five patients with diffuse lung disease were imaged at 0.15 and 1.5 T. Excised normal pig lung was imaged at 0.15 and 1.5 T and analyzed in a spectrometer at 2.0 T. Single-echo (Hahn) pulse sequences (TR, 2,000 msec; TE, 20, 40, 60, 80, and 100 msec) were compared with multiecho trains (Carr-Purcell-Meiboom-Gill [CPMG] at 0.15 T (TR, 2,000 msec; TE, 20-40-60... 240 msec) and 2.0 T (TR, 2,000 msec; TE, 1, 2, 3,..., 10msec). T2 relaxation times calculated from single-echo sequences showed considerable variation between 0.15 and 2.0 T. T2 also changed with lung inflation. However, the T2 measurements on CPMG sequences did not change significantly (P > .05) with field strength and were only minimally affected by lung inflation. The mean ± SD T2 values for normal lung were 99 ± 8 and for abnormal lung were 84 ± 17. Lung parenchyma T2 measurements obtained with the use of conventional single-echo pulse sequences are variable and inaccurate because of inflation and field strength dependent magnetic susceptibility effects that lead to rapid nonrecoverable dephasing. The results indicate that multiecho sequences with appropriately short echo spacings yield more reproducible determinations of T2, which are independent of field strength and less dependent on lung inflation

Expression of Apoptosis Inducing-Ligands, TRAIL and Fas-L in Hydatid Cyst Germinal Layer and Normal Tissue

Directory of Open Access Journals (Sweden)

Adel Spotin

2012-04-01

Full Text Available Background & objectives: Hydaticosis is a zoonotic helminthic disease of human and other intermediated hosts in which larval stages of the tapeworm Echinococcus granulosu transfect human. The liver and lung are the host tissues for the hydatid cyst . It is unknown which mechanisms are involved in infertility of the cyst and suppression of the fertile cyst. This study was aimed to evaluate the expression of the apoptosis inducing-ligands such as TRAIL and Fas-L in germinal layer of the cyst and human normal tissue surrounding the cyst that is one of the unknown host innate immunity mechanisms against the hydatid cyst.   Methods: In this study, four isolated hydatid cysts were used which had been diagnosed in patients by radiography and parasitological examination in Mashhad Ghaem hospital. Furthermore, the germinal layer of the cyst and accompanied normal peripheral tissues were separated by scalpel in sterile conditions. After homogenization, expression of TRAIL and Fas-L genes were studied by semi-quantitive RT-PCR method.   Results: The TRAIL and Fas-L showed significant higher level expression in germinal layer of infertile cyst than the fertile cyst and host normal tissues.   Conclusion: The host tissue-induced apoptosis of germinal layer of the fertile cysts is probably one of the infertility mechanism in patients with hydaticosis

Lung tissue remodeling in the acute respiratory distress syndrome

Directory of Open Access Journals (Sweden)

Souza Alba Barros de

2003-01-01

Full Text Available Acute respiratory distress syndrome (ARDS is characterized by diffuse alveolar damage, and evolves progressively with three phases: exsudative, fibroproliferative, and fibrotic. In the exudative phase, there are interstitial and alveolar edemas with hyaline membrane. The fibropro­liferative phase is characterized by exudate organization and fibroelastogenesis. There is proliferation of type II pneumocytes to cover the damaged epithelial surface, followed by differentiation into type I pneumocytes. The fibroproliferative phase starts early, and its severity is related to the patient?s prognosis. The alterations observed in the phenotype of the pulmonary parenchyma cells steer the tissue remodeling towards either progressive fibrosis or the restoration of normal alveolar architecture. The fibrotic phase is characterized by abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. The deposition of proteoglycans in the extracellular matrix of ARDS patients needs better study. The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. This review article will analyze the ECM organization in ARDS, the different pulmonary parenchyma remodeling mechanisms, and the role of cytokines in the regulation of the different matrix components during the remodeling process.

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

Directory of Open Access Journals (Sweden)

Karen L Heathcote

2011-01-01

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

Options and pitfalls of normal tissues complication probability models

International Nuclear Information System (INIS)

Dorr, Wolfgang

2011-01-01

Full text: Technological improvements in the physical administration of radiotherapy have led to increasing conformation of the treatment volume (TV) with the planning target volume (PTV) and of the irradiated volume (IV) with the TV. In this process of improvement of the physical quality of radiotherapy, the total volumes of organs at risk exposed to significant doses have significantly decreased, resulting in increased inhomogeneities in the dose distributions within these organs. This has resulted in a need to identify and quantify volume effects in different normal tissues. Today, irradiated volume today must be considered a 6t h 'R' of radiotherapy, in addition to the 5 'Rs' defined by Withers and Steel in the mid/end 1980 s. The current status of knowledge of these volume effects has recently been summarized for many organs and tissues by the QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) initiative [Int. J. Radiat. Oncol. BioI. Phys. 76 (3) Suppl., 2010]. However, the concept of using dose-volume histogram parameters as a basis for dose constraints, even without applying any models for normal tissue complication probabilities (NTCP), is based on (some) assumptions that are not met in clinical routine treatment planning. First, and most important, dose-volume histogram (DVH) parameters are usually derived from a single, 'snap-shot' CT-scan, without considering physiological (urinary bladder, intestine) or radiation induced (edema, patient weight loss) changes during radiotherapy. Also, individual variations, or different institutional strategies of delineating organs at risk are rarely considered. Moreover, the reduction of the 3-dimentional dose distribution into a '2dimensl' DVH parameter implies that the localization of the dose within an organ is irrelevant-there are ample examples that this assumption is not justified. Routinely used dose constraints also do not take into account that the residual function of an organ may be

A hybrid electron and photon IMRT planning technique that lowers normal tissue integral patient dose using standard hardware.

Science.gov (United States)

Rosca, Florin

2012-06-01

To present a mixed electron and photon IMRT planning technique using electron beams with an energy range of 6-22 MeV and standard hardware that minimizes integral dose to patients for targets as deep as 7.5 cm. Ten brain cases, two lung, a thyroid, an abdominal, and a parotid case were planned using two planning techniques: a photon-only IMRT (IMRT) versus a mixed modality treatment (E+IMRT) that includes an enface electron beam and a photon IMRT portion that ensures a uniform target coverage. The electron beam is delivered using a regular cutout placed in an electron cone. The electron energy was chosen to provide a good trade-off between minimizing integral dose and generating a uniform, deliverable plan. The authors choose electron energies that cover the deepest part of PTV with the 65%-70% isodose line. The normal tissue integral dose, the dose for ring structures around the PTV, and the volumes of the 75%, 50%, and 25% isosurfaces were used to compare the dose distributions generated by the two planning techniques. The normal tissue integral dose was lowered by about 20% by the E+IMRT plans compared to the photon-only IMRT ones for most studied cases. With the exception of lungs, the dose reduction associated to the E+IMRT plans was more pronounced further away from the target. The average dose ratio delivered to the 0-2 cm and the 2-4 cm ring structures for brain patients for the two planning techniques were 89.6% and 70.8%, respectively. The enhanced dose sparing away from the target for the brain patients can also be observed in the ratio of the 75%, 50%, and 25% isodose line volumes for the two techniques, which decreases from 85.5% to 72.6% and further to 65.1%, respectively. For lungs, the lateral electron beams used in the E+IMRT plans were perpendicular to the mostly anterior/posterior photon beams, generating much more conformal plans. The authors proved that even using the existing electron delivery hardware, a mixed electron/photon planning

DNA-repair, cell killing and normal tissue damage

International Nuclear Information System (INIS)

Dahm-Daphi, J.; Dikomey, E.; Brammer, I.

1998-01-01

Background: Side effects of radiotherapy in normal tissue is determined by a variety of factors of which cellular and genetic contributions are described here. Material and methods: Review. Results: Normal tissue damage after irradiation is largely due to loss of cellular proliferative capacity. This can be due to mitotic cell death, apoptosis, or terminal differentiation. Dead or differentiated cells release cytokines which additionally modulate the tissue response. DNA damage, in particular non-reparable or misrepaired double-strand breaks are considered the basic lesion leading to G1-arrest and ultimately to cell inactivation. Conclusion: Evidence for genetic bases of normal tissue response, cell killing and DNA-repair capacity is presented. However, a direct link of all 3 endpoints has not yet been proved directly. (orig.) [de

Optical measurement of isolated canine lung filtration coefficients at normal hematocrits.

Science.gov (United States)

Klaesner, J W; Pou, N A; Parker, R E; Finney, C; Roselli, R J

1997-12-01

In this study, lung filtration coefficient (Kfc) values were measured in eight isolated canine lung preparations at normal hematocrit values using three methods: gravimetric, blood-corrected gravimetric, and optical. The lungs were kept in zone 3 conditions and subjected to an average venous pressure increase of 10.24 +/- 0.27 (SE) cmH2O. The resulting Kfc (ml . min-1 . cmH2O-1 . 100 g dry lung wt-1) measured with the gravimetric technique was 0.420 +/- 0.017, which was statistically different from the Kfc measured by the blood-corrected gravimetric method (0.273 +/- 0.018) or the product of the reflection coefficient (sigmaf) and Kfc measured optically (0. 272 +/- 0.018). The optical method involved the use of a Cellco filter cartridge to separate red blood cells from plasma, which allowed measurement of the concentration of the tracer in plasma at normal hematocrits (34 +/- 1.5). The permeability-surface area product was measured using radioactive multiple indicator-dilution methods before, during, and after venous pressure elevations. Results showed that the surface area of the lung did not change significantly during the measurement of Kfc. These studies suggest that sigmafKfc can be measured optically at normal hematocrits, that this measurement is not influenced by blood volume changes that occur during the measurement, and that the optical sigmafKfc agrees with the Kfc obtained via the blood-corrected gravimetric method.

Association Between RT-Induced Changes in Lung Tissue Density and Global Lung Function

International Nuclear Information System (INIS)

Ma Jinli; Zhang Junan; Zhou Sumin; Hubbs, Jessica L.; Foltz, Rodney J.; Hollis, Donna R.; Light, Kim L.; Wong, Terence Z.; Kelsey, Christopher R.; Marks, Lawrence B.

2009-01-01

Purpose: To assess the association between radiotherapy (RT)-induced changes in computed tomography (CT)-defined lung tissue density and pulmonary function tests (PFTs). Methods and Materials: Patients undergoing incidental partial lung RT were prospectively assessed for global (PFTs) and regional (CT and single photon emission CT [SPECT]) lung function before and, serially, after RT. The percent reductions in the PFT and the average changes in lung density were compared (Pearson correlations) in the overall group and subgroups stratified according to various clinical factors. Comparisons were also made between the CT- and SPECT-based computations using the Mann-Whitney U test. Results: Between 1991 and 2004, 343 patients were enrolled in this study. Of these, 111 patients had a total of 203 concurrent post-RT evaluations of changes in lung density and PFTs available for the analyses, and 81 patients had a total of 141 concurrent post-RT SPECT images. The average increases in lung density were related to the percent reductions in the PFTs, albeit with modest correlation coefficients (range, 0.20-0.43). The analyses also indicated that the association between lung density and PFT changes is essentially equivalent to the corresponding association with SPECT-defined lung perfusion. Conclusion: We found a weak quantitative association between the degree of increase in lung density as defined by CT and the percent reduction in the PFTs.

HU deviation in lung and bone tissues: Characterization and a corrective strategy.

Science.gov (United States)

Ai, Hua A; Meier, Joseph G; Wendt, Richard E

2018-05-01

study, the HU difference was as much as -136.7 ± 8.2 HU (or -7.6% ± 0.5% of the attenuation coefficient, AC) in the spine region, and up to 37.6 ± 1.6 HU (or 17.3% ± 0.8% of AC) in the lung region between scenarios that simulated normal and obese patients. Our HU correction method reduced the HU deviations to 8.5 ± 9.1 HU (or 0.5% ± 0.5%) for bone and to -6.4 ± 1.7 HU (or -3.0% ± 0.8%) for lung. The HU differences in the soft tissue materials before and after the correction were insignificant. Visual improvement of the tissue contrast was also achieved in the data of the simulated obese patient. The effect of a patient's size on the HU values of lung and bone tissues can be significant. The accuracy of those HU values was substantially improved by the correction method that was developed for and employed in this study. © 2018 American Association of Physicists in Medicine.

Normal tissue dose-effect models in biological dose optimisation

International Nuclear Information System (INIS)

Alber, M.

2008-01-01

Sophisticated radiotherapy techniques like intensity modulated radiotherapy with photons and protons rely on numerical dose optimisation. The evaluation of normal tissue dose distributions that deviate significantly from the common clinical routine and also the mathematical expression of desirable properties of a dose distribution is difficult. In essence, a dose evaluation model for normal tissues has to express the tissue specific volume effect. A formalism of local dose effect measures is presented, which can be applied to serial and parallel responding tissues as well as target volumes and physical dose penalties. These models allow a transparent description of the volume effect and an efficient control over the optimum dose distribution. They can be linked to normal tissue complication probability models and the equivalent uniform dose concept. In clinical applications, they provide a means to standardize normal tissue doses in the face of inevitable anatomical differences between patients and a vastly increased freedom to shape the dose, without being overly limiting like sets of dose-volume constraints. (orig.)

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-03-15

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

Lung sound intensity in patients with emphysema and in normal subjects at standardised airflows.

Science.gov (United States)

Schreur, H J; Sterk, P J; Vanderschoot, J; van Klink, H C; van Vollenhoven, E; Dijkman, J H

1992-01-01

BACKGROUND: A common auscultatory finding in pulmonary emphysema is a reduction of lung sounds. This might be due to a reduction in the generation of sounds due to the accompanying airflow limitation or to poor transmission of sounds due to destruction of parenchyma. Lung sound intensity was investigated in normal and emphysematous subjects in relation to airflow. METHODS: Eight normal men (45-63 years, FEV1 79-126% predicted) and nine men with severe emphysema (50-70 years, FEV1 14-63% predicted) participated in the study. Emphysema was diagnosed according to pulmonary history, results of lung function tests, and radiographic criteria. All subjects underwent phonopneumography during standardised breathing manoeuvres between 0.5 and 2 1 below total lung capacity with inspiratory and expiratory target airflows of 2 and 1 l/s respectively during 50 seconds. The synchronous measurements included airflow at the mouth and lung volume changes, and lung sounds at four locations on the right chest wall. For each microphone airflow dependent power spectra were computed by using fast Fourier transformation. Lung sound intensity was expressed as log power (in dB) at 200 Hz at inspiratory flow rates of 1 and 2 l/s and at an expiratory flow rate of 1 l/s. RESULTS: Lung sound intensity was well repeatable on two separate days, the intraclass correlation coefficient ranging from 0.77 to 0.94 between the four microphones. The intensity was strongly influenced by microphone location and airflow. There was, however, no significant difference in lung sound intensity at any flow rate between the normal and the emphysema group. CONCLUSION: Airflow standardised lung sound intensity does not differ between normal and emphysematous subjects. This suggests that the auscultatory finding of diminished breath sounds during the regular physical examination in patients with emphysema is due predominantly to airflow limitation. Images PMID:1440459

Radiation-induced normal tissue damage: implications for radiotherapy

International Nuclear Information System (INIS)

Prasanna, Pataje G.

2014-01-01

Radiotherapy is an important treatment modality for many malignancies, either alone or as a part of combined modality treatment. However, despite technological advances in physical treatment delivery, patients suffer adverse effects from radiation therapy due to normal tissue damage. These side effects may be acute, occurring during or within weeks after therapy, or intermediate to late, occurring months to years after therapy. Minimizing normal tissue damage from radiotherapy will allow enhancement of tumor killing and improve tumor control and patients quality of life. Understanding mechanisms through which radiation toxicity develops in normal tissue will facilitate the development of next generation radiation effect modulators. Translation of these agents to the clinic will also require an understanding of the impact of these protectors and mitigators on tumor radiation response. In addition, normal tissues vary in radiobiologically important ways, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response. Therefore, successful development of radiation modulators may require multiple approaches to address organ/site-specific needs. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects. Further, an understanding of mechanisms of normal tissue damage will allow development of predictive biomarkers; however harmonization of such assays is critical. This is a necessary step towards patient-specific treatment customization. Examples of important adverse effects of radiotherapy either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors for improving therapeutic outcome will be highlighted. (author)

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

Directory of Open Access Journals (Sweden)

Lizhi NIU

2010-07-01

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

Telomere length in normal and neoplastic canine tissues.

Science.gov (United States)

Cadile, Casey D; Kitchell, Barbara E; Newman, Rebecca G; Biller, Barbara J; Hetler, Elizabeth R

2007-12-01

To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues. 57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs. Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois. Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length. Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human anti-telomerase strategies.

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

Directory of Open Access Journals (Sweden)

O'Hanlon LD

2014-02-01

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

Pathologic evaluation of normal and perfused term placental tissue

DEFF Research Database (Denmark)

Maroun, Lisa Leth; Mathiesen, Line; Hedegaard, Morten

2014-01-01

This study reports for the 1st time the incidence and interobserver variation of morphologic findings in a series of 34 term placentas from pregnancies with normal outcome used for perfusion studies. Histologic evaluation of placental tissue is challenging, especially when it comes to defining...... "normal tissue" versus "pathologic lesions." A scoring system for registration of abnormal morphologic findings was developed. Light microscopic examination was performed independently by 2 pathologists, and interobserver variation was analyzed. Findings in normal and perfused tissue were compared...... and selected findings were tested against success parameters from the perfusions. Finally, the criteria for frequent lesions with fair to poor interobserver variation in the nonperfused tissue were revised and reanalyzed. In the perfused tissue, the perfusion artefact "trophoblastic vacuolization," which...

Reduced generation of lung tissue-resident memory T cells during infancy.

Science.gov (United States)

Zens, Kyra D; Chen, Jun Kui; Guyer, Rebecca S; Wu, Felix L; Cvetkovski, Filip; Miron, Michelle; Farber, Donna L

2017-10-02

Infants suffer disproportionately from respiratory infections and generate reduced vaccine responses compared with adults, although the underlying mechanisms remain unclear. In adult mice, lung-localized, tissue-resident memory T cells (TRMs) mediate optimal protection to respiratory pathogens, and we hypothesized that reduced protection in infancy could be due to impaired establishment of lung TRM. Using an infant mouse model, we demonstrate generation of lung-homing, virus-specific T effectors after influenza infection or live-attenuated vaccination, similar to adults. However, infection during infancy generated markedly fewer lung TRMs, and heterosubtypic protection was reduced compared with adults. Impaired TRM establishment was infant-T cell intrinsic, and infant effectors displayed distinct transcriptional profiles enriched for T-bet-regulated genes. Notably, mouse and human infant T cells exhibited increased T-bet expression after activation, and reduction of T-bet levels in infant mice enhanced lung TRM establishment. Our findings reveal that infant T cells are intrinsically programmed for short-term responses, and targeting key regulators could promote long-term, tissue-targeted protection at this critical life stage. © 2017 Zens et al.

Measurement of lung tissue dynamics in artificially ventilated rats with optical coherence tomography

Directory of Open Access Journals (Sweden)

Schnabel Christian

2017-09-01

Full Text Available Diseases of lung tissue and the airways become a major task for medical care and health care systems in modern industrial countries in the future. Suitable treatment methods and strategies for lung support and artificial ventilation are of dare need. Besides the obvious importance as life-saving intervention, the effects of usually used over-pressure ventilation onto the sensitive alveolar tissue are insufficiently understood. Therefore, it is of great interest to characterize lung tissue during artificial ventilation at the alveolar level. Those measurements can be used to link micromechanics of alveolar structures to mechanical properties of the whole lung like compliance and resistance measured at the ventilator device. This can be done only in animal experiments due to the fact that imaging techniques used in human diagnostics like CT or MRT fail to resolve alveolar tissue structures. The disadvantage of high-resolution techniques like optical coherence tomography (OCT or intravital microscopy (IVM is the need of a surgical access to the lung due to the limitation in penetration depth of these techniques. Furthermore, imaging dynamic processes with high-resolution imaging techniques during uninterrupted artificial ventilation is a challenging task. In this study, we present a measurement setup for combined imaging of conventional pressure-controlled ventilated rats and the visualization of volume changes of alveolar structures during one cycle of breath. A custom-made OCT system in combination with a triggered scanning algorithm was used to acquire time-resolved 3D OCT image data. Furthermore, this system was combined with a self-adapting autofocus function for intravital microscopy to track the lung surface keeping the tissue in focal plane. The combination of new dynamic measurement modes for OCT and IVM allows new insights into alveolar tissue and will promote the understanding of mechanical behavior during artificial ventilation.

Interstitial lung disease associated with connective tissue diseases

International Nuclear Information System (INIS)

Medina, Yimy F; Restrepo, Jose Felix; Iglesias, Antonio; Ojeda, Paulina; Matiz, Carlos

2007-01-01

An interstitial lung disease (ILD) belongs to a group of diffuse parenchyma lung diseases it should be differentiated from other pathologies among those are idiopathic and ILD associated to connective tissue diseases (CTD) New concepts have been developed in the last years and they have been classified in seven defined subgroups. It has been described the association of each one of these subgroups with CTD. Natural history and other aspects of its treatment is not known completely .For complete diagnose it is required clinical, image and histopathologic approaches. The biopsy lung plays an essential role. It is important to promote and to stimulate the subclasification of each subgroup with the purpose of knowing their natural history directing the treatment and to improve their outcome

Distribution of latex particles in lung and lymph node tissues of rats and dogs

International Nuclear Information System (INIS)

Mueller, H.L; Muggenburg, B.A.; Gillett, N.A.; Guilmette, R.A.

1988-01-01

The distribution of fluorescent poly sytrene microspheres in different lung compartments, with differing particle numbers within individual lung and lymph node cells was examined In methacrylate-embedded tissue slices. Rat tissues were analyzed at 1, 7 and 13 days after particle instillation, dog tissues at 7 and 13 days. A much higher fraction of particles was seen in the lung interstitium and in lung-associated lymph nodes in dogs than in rats. Particle concentrations in TBLN cells were generally very low in both species, but were high in free alveolar cells after high particle numbers were instilled, and increased from 1 to 13 days, suggesting that alveolar cells with few particles were cleared faster than those wth high ingested particle numbers. (author)

Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

Energy Technology Data Exchange (ETDEWEB)

Salama, Samir A., E-mail: salama.3@buckeyemail.osu.edu [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751 (Egypt); Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Omar, Hany A. [Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514 (Egypt); Maghrabi, Ibrahim A. [Department of Clinical Pharmacy, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); AlSaeed, Mohammed S. [Department of Surgery, College of Medicine, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); EL-Tarras, Adel E. [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia)

2014-01-01

Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron

Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

International Nuclear Information System (INIS)

Salama, Samir A.; Omar, Hany A.; Maghrabi, Ibrahim A.; AlSaeed, Mohammed S.; EL-Tarras, Adel E.

2014-01-01

Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron

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 proposed model, we simulate the non-linear elastic response of twelve representative volume elements (RVEs) of lung parenchyma with micrometric dimensions, whose geometry is obtained from micrometric computed-tomography reconstructions of murine lungs. We show that the proposed micromechanical model accurately captures the RVEs response not only for isotropic

Biochemical and morphological changes in rat lung tissue under the influence of external ionizing radiation

International Nuclear Information System (INIS)

Uzlenkova, N.Je.; Mamotyuk, Je.M.; Gusakova, V.A.; Kononenko, O.K.

2006-01-01

Single external x-ray exposure at minimum and mean lethal doses was established to cause a long activation of biochemical processes in the connective tissue of the rat lungs. Morphological and ultrastructure changes in the tissue of the lungs at early terms after x-ray and gamma-radiation exposure were due to development of destructive and degenerative reactions. The long-term changes were characterized by growth of connective tissue and formation of areas of fibrous changes in the structure of the lungs

Telomerase in lung cancer diagnostics

International Nuclear Information System (INIS)

Kovkarova, E.; Stefanovski, T.; Dimov, A.; Naumovski, J.

2003-01-01

Background. Telomerase is a ribonucleoprotein that looks after the telomeric cap of the linear chromosomes maintaining its length. It is over expressed in tumour tissues, but not in normal somatic cells. Therefore the aim of this study was to determine the telomerase activity in lung cancer patients as novel marker for lung cancer detection evaluating the influence of tissue/cell obtaining technique. Material and methods. Using the TRAP (telomeric repeat amplification protocol), telomerase activity was determined in material obtained from bronchobiopsy (60 lung cancer patients compared with 20 controls) and washings from transthoracic fine needle aspiration biopsy performed in 10 patients with peripheral lung tumours. Results. Telomerase activity was detected in 75% of the lung cancer bronchobyopsies, and in 100% in transthoracic needle washings. Conclusions. Measurement of telomerase activity can contribute in fulfilling the diagnosis of lung masses and nodules suspected for lung cancer. (author)

Significant reduction of normal tissue dose by proton radiotherapy compared with three-dimensional conformal or intensity-modulated radiation therapy in Stage I or Stage III non-small-cell lung cancer

International Nuclear Information System (INIS)

Chang, Joe Y.; Zhang Xiaodong; Wang Xiaochun; Kang Yixiu; Riley, Beverly C.; Bilton, Stephen C.; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.

2006-01-01

Purpose: To compare dose-volume histograms (DVH) in patients with non-small-cell lung cancer (NSCLC) treated by photon or proton radiotherapy. Methods and Materials: Dose-volume histograms were compared between photon, including three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and proton plans at doses of 66 Gy, 87.5 Gy in Stage I (n = 10) and 60-63 Gy, and 74 Gy in Stage III (n 15). Results: For Stage I, the mean total lung V5, V10, and V20 were 31.8%, 24.6%, and 15.8%, respectively, for photon 3D-CRT with 66 Gy, whereas they were 13.4%, 12.3%, and 10.9%, respectively, with proton with dose escalation to 87.5 cobalt Gray equivalents (CGE) (p = 0.002). For Stage III, the mean total lung V5, V10, and V20 were 54.1%, 46.9%, and 34.8%, respectively, for photon 3D-CRT with 63 Gy, whereas they were 39.7%, 36.6%, and 31.6%, respectively, for proton with dose escalation to 74 CGE (p = 0.002). In all cases, the doses to lung, spinal cord, heart, esophagus, and integral dose were lower with proton therapy even compared with IMRT. Conclusions: Proton treatment appears to reduce dose to normal tissues significantly, even with dose escalation, compared with standard-dose photon therapy, either 3D-CRT or IMRT

Autofluorescence Imaging and Spectroscopy of Human Lung Cancer

Directory of Open Access Journals (Sweden)

Mengyan Wang

2016-12-01

Full Text Available Lung cancer is one of the most common cancers, with high mortality rate worldwide. Autofluorescence imaging and spectroscopy is a non-invasive, label-free, real-time technique for cancer detection. In this study, lung tissue sections excised from patients were detected by laser scan confocal microscopy and spectroscopy. The autofluorescence images demonstrated the cellular morphology and tissue structure, as well as the pathology of stained images. Based on the spectra study, it was found that the majority of the patients showed discriminating fluorescence in tumor tissues from normal tissues. Therefore, autofluorescence imaging and spectroscopy may be a potential method for aiding the diagnosis of lung cancer.

HOXA9 inhibits migration of lung cancer cells and its hypermethylation is associated with recurrence in non-small cell lung cancer.

Science.gov (United States)

Hwang, Jung-Ah; Lee, Bo Bin; Kim, Yujin; Hong, Seung-Hyun; Kim, Young-Ho; Han, Joungho; Shim, Young Mog; Yoon, Chae-Yeong; Lee, Yeon-Su; Kim, Duk-Hwan

2015-06-01

This study was aimed at understanding the clinicopathological significance of HOXA9 hypermethylation in non-small cell lung cancer (NSCLC). HOXA9 hypermethylation was characterized in six lung cancer cell lines, and its clinicopathological significance was analyzed using methylation-specific PCR in 271 formalin-fixed paraffin-embedded tissues and 27 fresh-frozen tumor and matched normal tissues from 298 NSCLC patients, and Ki-67 expression was analyzed using immunohistochemistry. The promoter region of HOXA9 was highly methylated in six lung cancer cell lines, but not in normal bronchial epithelial cells. The loss of expression was restored by treatment of the cells with a demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC). Transient transfection of HOXA9 into H23 lung cancer cells resulted in the inhibition of cell migration but not proliferation. Conversely, sequence-specific siRNA-mediated knockdown of HOXA9 enhanced cell migration. The mRNA levels of HOXA9 in 27 fresh-frozen tumor tissues were significantly lower than in matched normal tissues (Precurrence-free survival (hazard ratio=3.98, 95% confidence interval = 1.07-17.09, P=0.01) in never-smokers, after adjusting for age, sex, tumor size, adjuvant therapy, pathologic stage, and histology. In conclusion, the present study suggests that HOXA9 inhibits migration of lung cancer cells and its hypermethylation is an independent prognostic factor for recurrence-free survival in never-smokers with NSCLC. © 2014 Wiley Periodicals, Inc.

Developing a reference of normal lung sounds in healthy Peruvian children.

Science.gov (United States)

Ellington, Laura E; Emmanouilidou, Dimitra; Elhilali, Mounya; Gilman, Robert H; Tielsch, James M; Chavez, Miguel A; Marin-Concha, Julio; Figueroa, Dante; West, James; Checkley, William

2014-10-01

Lung auscultation has long been a standard of care for the diagnosis of respiratory diseases. Recent advances in electronic auscultation and signal processing have yet to find clinical acceptance; however, computerized lung sound analysis may be ideal for pediatric populations in settings, where skilled healthcare providers are commonly unavailable. We described features of normal lung sounds in young children using a novel signal processing approach to lay a foundation for identifying pathologic respiratory sounds. 186 healthy children with normal pulmonary exams and without respiratory complaints were enrolled at a tertiary care hospital in Lima, Peru. Lung sounds were recorded at eight thoracic sites using a digital stethoscope. 151 (81%) of the recordings were eligible for further analysis. Heavy-crying segments were automatically rejected and features extracted from spectral and temporal signal representations contributed to profiling of lung sounds. Mean age, height, and weight among study participants were 2.2 years (SD 1.4), 84.7 cm (SD 13.2), and 12.0 kg (SD 3.6), respectively; and, 47% were boys. We identified ten distinct spectral and spectro-temporal signal parameters and most demonstrated linear relationships with age, height, and weight, while no differences with genders were noted. Older children had a faster decaying spectrum than younger ones. Features like spectral peak width, lower-frequency Mel-frequency cepstral coefficients, and spectro-temporal modulations also showed variations with recording site. Lung sound extracted features varied significantly with child characteristics and lung site. A comparison with adult studies revealed differences in the extracted features for children. While sound-reduction techniques will improve analysis, we offer a novel, reproducible tool for sound analysis in real-world environments.

Transarterial Embolization of Anomalous Systemic Arterial Supply to Normal Basal Segments of the Lung

Energy Technology Data Exchange (ETDEWEB)

Jiang, Sen, E-mail: jasfly77@vip.163.com; Yu, Dong; Jie, Bing [Tongji University School of Medicine, Department of Radiology, Shanghai Pulmonary Hospital (China)

2016-09-15

PurposeTo evaluate transarterial embolization (TAE) for the management of anomalous systemic arterial (ASA) supply to normal basal segments of the lung.MethodsThirteen patients with ASA supply to normal basal segments of the lung underwent TAE. All patients presented with hemoptysis and had complete-type anomalies on pre-TAE or post-TAE computed tomography (CT). The anomaly was unilateral in all patients; 11 lesions were located in the left lung and 2 in the right. All patients underwent embolization with coils (n = 10) or a vascular plug (n = 3). Procedural success, clinical efficacy, and complications were assessed. Mean post-TAE CT and clinical follow-up was 25.4 and 42.1 months, respectively.ResultsTechnical success was achieved in 100 % of cases. Several changes were noted on follow-up CT: complete obstruction of the ASA in all cases, normal (n = 11) or decreased (n = 2) density of the affected lung parenchyma, reduction of the primary enlarged inferior pulmonary vein in all cases, and pulmonary infarction and thickening of the corresponding bronchial artery (n = 4). The main complication was pulmonary infarction in four cases.ConclusionTAE is a safe, effective, and minimally invasive therapeutic option for patients with ASA supply to normal basal segments of the lung.

THE PRESENCE OF ENDOGENOUS PYROGEN IN NORMAL RABBIT TISSUES.

Science.gov (United States)

SNELL, E S; ATKINS, E

1965-06-01

Saline extracts of homogenized, uninfected, rabbit tissues produced febrile responses when injected intravenously into rabbits. Extracts of muscle, lung, and heart evoked fevers that were similar to those induced by leucocyte pyrogen; extracts of spleen, liver, and kidney caused more sustained fevers. The minimal pyrogenic dose appeared to be between 1.5 and 3 gm wet weight of tissue. Evidence is presented that neither Gram-negative bacterial endotoxin nor polymorphonuclear leucocytes (circulating or sequestered in the tissues) can be implicated as the source of pyrogen in tissue extracts. It seems likely, therefore, that a pyrogenic material of truly endogenous origin is widely distributed in tissues. Tissue pyrogen appears to be a large molecule which is relatively resistant to treatment with acid but not with alkali. Possible pathological roles for this endogenous agent (or agents) are briefly indicated.

Metal concentrations in homing pigeon lung tissue as a biomonitor of atmospheric pollution.

Science.gov (United States)

Cui, Jia; Halbrook, Richard S; Zang, Shuying; Han, Shuang; Li, Xinyu

2018-03-01

Atmospheric pollution in urban areas is a major worldwide concern with potential adverse impacts on wildlife and humans. Biomonitoring can provide direct evidence of the bioavailability and bioaccumulation of toxic metals in the environment that is not available with mechanical air monitoring. The current study continues our evaluation of the usefulness of homing pigeon lung tissue as a biomonitor of atmospheric pollution. Homing pigeons (1-2, 5-6, and 9-10+ year old (yo)) collected from Guangzhou during 2015 were necropsied and concentrations of cadmium (Cd), lead (Pb), and mercury (Hg) were measured in lung tissue. Lung Cd and Pb concentrations were significantly greater in 9-10+-year-old pigeons compared with those in other age groups, indicating their bioavailability and bioaccumulation. Lung Pb and Cd concentrations measured in 5-yo pigeons collected from Guangzhou during 2015 were significantly lower than concentrations reported in 5-yo homing pigeons collected from Guangzhou during 2011 and correlated with concentrations measured using mechanical air monitoring. In addition to temporal differences, spatial differences in concentrations of Cd, Pb, and Hg reported in ambient air samples and in pigeon lung tissues collected from Beijing and Guangzhou are discussed.

Histological changes in lung tissues related with sub-chronic exposure to ambient urban levels of PM2.5 in Córdoba, Argentina

Science.gov (United States)

Tavera Busso, Iván; Vera, Anahí; Mateos, Ana Carolina; Amarillo, Ana Carolina; Carreras, Hebe

2017-10-01

Concentration of fine particulate matter (PM2.5) is one of the most important environmental parameters to estimate health impacts attributable to air pollution. Despite the fact there are many studies regarding PM2.5 effects on human health, most of them were performed under conditions that do not simulate the natural particles interaction with the organism. In the present paper, we studied the effects of mammals' sub-chronic exposure to PM2.5 on the lower respiratory tract, addressing realistic exposure conditions to normal urban air. Thus, we exposed Wistar rats under controlled settings to the same normal urban air, with and without particles. Next, we analyzed chemical composition of PM2.5 and lungs samples, performed a histologic examination and run the comet assay to assess genotoxic effects. We found a strong agreement between lung tissues and PM2.5 elemental composition suggesting that metals found in lungs came from the particles inhaled. Histological analysis showed a mild to moderate infiltration, with a reduction of alveoli lumen and increment of alveolar macrophages and periodic acid-Schiff (PAS) (+) cells in treated animals. We also observed an increase in the number of nuclei with comets, mostly comets type 3, with a high DNA fragmentation as well. These results provide strong evidence that sub-chronic exposure to low particle levels, even below the 24 h WHO standard, can cause injuries in lungs tissues and DNA damage, as well.

Ectopic Intrathoracic Hepatic Tissue and Accessory Lung Lobe Aplasia in a Dog.

Science.gov (United States)

Lande, Rachel; Dvorak, Laura; Gardiner, David W; Bahr, Anne

2015-01-01

A 6 yr old male Yorkshire terrier was presented for an ~6 yr history of progressive cough and dyspnea. Thoracic radiographs revealed a 6 cm diameter mass within the right caudal thorax. Thoracic ultrasound identified an intrathoracic mass ultrasonographically consistent with liver tissue and a chronic diaphragmatic hernia was suspected. Exploratory laparotomy was performed, but no evidence of a diaphragmatic hernia was identified. Thoracic exploration identified abnormal lung parenchyma. The accessory lung lobe was removed using a stapling devise near its base. The consolidated mass had the gross appearance of liver and was histologically identified as ectopic hepatic tissue. Ectopic hepatic tissue, unlike ectopic splenic and pancreatic tissue, is rare and generally has a subdiaphragmatic distribution. This solitary case report demonstrates that ectopic intrathoracic hepatic tissue should be considered a differential diagnosis for a caudal mediastinal mass.

Developing a Reference of Normal Lung Sounds in Healthy Peruvian Children

Science.gov (United States)

Ellington, Laura E.; Emmanouilidou, Dimitra; Elhilali, Mounya; Gilman, Robert H.; Tielsch, James M.; Chavez, Miguel A.; Marin-Concha, Julio; Figueroa, Dante; West, James

2018-01-01

Purpose Lung auscultation has long been a standard of care for the diagnosis of respiratory diseases. Recent advances in electronic auscultation and signal processing have yet to find clinical acceptance; however, computerized lung sound analysis may be ideal for pediatric populations in settings, where skilled healthcare providers are commonly unavailable. We described features of normal lung sounds in young children using a novel signal processing approach to lay a foundation for identifying pathologic respiratory sounds. Methods 186 healthy children with normal pulmonary exams and without respiratory complaints were enrolled at a tertiary care hospital in Lima, Peru. Lung sounds were recorded at eight thoracic sites using a digital stethoscope. 151 (81 %) of the recordings were eligible for further analysis. Heavy-crying segments were automatically rejected and features extracted from spectral and temporal signal representations contributed to profiling of lung sounds. Results Mean age, height, and weight among study participants were 2.2 years (SD 1.4), 84.7 cm (SD 13.2), and 12.0 kg (SD 3.6), respectively; and, 47 % were boys. We identified ten distinct spectral and spectro-temporal signal parameters and most demonstrated linear relationships with age, height, and weight, while no differences with genders were noted. Older children had a faster decaying spectrum than younger ones. Features like spectral peak width, lower-frequency Mel-frequency cepstral coefficients, and spectro-temporal modulations also showed variations with recording site. Conclusions Lung sound extracted features varied significantly with child characteristics and lung site. A comparison with adult studies revealed differences in the extracted features for children. While sound-reduction techniques will improve analysis, we offer a novel, reproducible tool for sound analysis in real-world environments. PMID:24943262

Radiobiology in clinical radiation therapy - Part III: Normal tissue damage

International Nuclear Information System (INIS)

Travis, Elizabeth L.

1996-01-01

Objective: This is the third part of a course designed for residents in radiation oncology preparing for their boards. This part of the course will focus on the mechanisms underlying damage in normal tissues. Although conventional wisdom long held that killing and depletion of a critical cell(s) in a tissue was responsible for the later expression of damage, histopathologic changes in normal tissue can now be explained and better understood in terms of the new molecular biology. The concept that depletion of a single cell type is responsible for the observed histopathologic changes in normal tissues has been replaced by the hypothesis that damage results from the interaction of many different cell systems, including epithelial, endothelial, macrophages and fibroblasts, via the production of specific autocrine, paracrine and endocrine growth factors. A portion of this course will discuss the clinical and experimental data on the production and interaction of those cytokines and cell systems considered to be critical to tissue damage. It had long been suggested that interindividual differences in radiation-induced normal tissue damage was genetically regulated, at least in part. Both clinical and experimental data supported this hypothesis but it is the recent advances in human and mouse molecular genetics which have provided the tools to dissect out the genetic component of normal tissue damage. These data will be presented and related to the potential to develop genetic markers to identify sensitive individuals. The impact on clinical outcome of the ability to identify prospectively sensitive patients will be discussed. Clinically it is well-accepted that the volume of tissue irradiated is a critical factor in determining tissue damage. A profusion of mathematical models for estimating dose-volume relationships in a number of organs have been published recently despite the fact that little data are available to support these models. This course will review the

Positioning effects on lung ventilation in older normal subjects: a technegas study

International Nuclear Information System (INIS)

Krieg, S.; McCarren, B.; Alison, J.; Cowell, S.F.; Leiper, C.; Bankstown-Lidcombe Hospital, Sydney, NSW; El Zein, H.

2002-01-01

Full text: While the effects of positioning on the distribution of ventilation in the lungs of younger subjects has been relatively well investigated, this is not so in the older age group. Known age-associated changes in the respiratory system are proposed to alter the distribution of ventilation in the lungs of older people. The aim of the present study was therefore to determine the effects of positioning on the distribution of ventilation in the lungs of older normal subjects. The distribution of ventilation in upright sitting and right side lying was measured in ten subjects using Technegas lung ventilation during tidal breathing. In the upright sitting position ventilation was preferentially distributed to the middle and basal regions (dependent regions). Right side lying ventilation was preferentially distributed to the right lung (dependent region). These results suggest that preferential distribution of ventilation to the dependent lung regions in older subjects is mainly due to the gravity-dependent gradient in pleural pressure. It is proposed that this distribution may partly result from loss of elasticity in the lungs with ageing. Predominantly, the distribution of ventilation in the lungs of older normal subjects in our study is similar to that previously described in younger subjects (Amis et al., 1984, Kaneko et al, 1966, Milic-Emili et al, 1966. This suggests that a similar pleural pressure gradient may exist in the lungs of older and younger subjects. This is an important implication as the majority of patients that physiotherapists treat with cardiopulmonary dysfunction are in the older age group. Further research is required to determine the effects of positioning on the distribution of ventilation in older patients with cardiopulmonary dysfunction to enable direct clinical implications to be made. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

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

International Nuclear Information System (INIS)

Kapp, Karin Sigrid; Zurl, Brigitte; Stranzl, Heidi; Winkler, Peter

2010-01-01

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

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

Directory of Open Access Journals (Sweden)

Eman Magdy

2015-01-01

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

Multivariate Normal Tissue Complication Probability Modeling of Heart Valve Dysfunction in Hodgkin Lymphoma Survivors

International Nuclear Information System (INIS)

Cella, Laura; Liuzzi, Raffaele; Conson, Manuel; D’Avino, Vittoria; Salvatore, Marco; Pacelli, Roberto

2013-01-01

Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced asymptomatic heart valvular defects (RVD). Methods and Materials: Fifty-six patients treated with sequential chemoradiation therapy for Hodgkin lymphoma (HL) were retrospectively reviewed for RVD events. Clinical information along with whole heart, cardiac chambers, and lung dose distribution parameters was collected, and the correlations to RVD were analyzed by means of Spearman's rank correlation coefficient (Rs). For the selection of the model order and parameters for NTCP modeling, a multivariate logistic regression method using resampling techniques (bootstrapping) was applied. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: When we analyzed the whole heart, a 3-variable NTCP model including the maximum dose, whole heart volume, and lung volume was shown to be the optimal predictive model for RVD (Rs = 0.573, P<.001, AUC = 0.83). When we analyzed the cardiac chambers individually, for the left atrium and for the left ventricle, an NTCP model based on 3 variables including the percentage volume exceeding 30 Gy (V30), cardiac chamber volume, and lung volume was selected as the most predictive model (Rs = 0.539, P<.001, AUC = 0.83; and Rs = 0.557, P<.001, AUC = 0.82, respectively). The NTCP values increase as heart maximum dose or cardiac chambers V30 increase. They also increase with larger volumes of the heart or cardiac chambers and decrease when lung volume is larger. Conclusions: We propose logistic NTCP models for RVD considering not only heart irradiation dose but also the combined effects of lung and heart volumes. Our study establishes the statistical evidence of the indirect effect of lung size on radio-induced heart toxicity

Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

DEFF Research Database (Denmark)

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

1993-01-01

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

A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection.

Science.gov (United States)

Braian, Clara; Svensson, Mattias; Brighenti, Susanna; Lerm, Maria; Parasa, Venkata R

2015-10-05

Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M. tuberculosis). The 3D tissue model consists of tissue-specific epithelial cells and fibroblasts, which are cultured in a matrix of collagen on top of a porous membrane. Upon air exposure, the epithelial cells stratify and secrete mucus at the apical side. By introducing human primary macrophages infected with M. tuberculosis to the tissue model, we have shown that immune cells migrate into the infected-tissue and form early stages of TB granuloma. These structures recapitulate the distinct feature of human TB, the granuloma, which is fundamentally different or not commonly observed in widely used experimental animal models. This organotypic culture method enables the 3D visualization and robust quantitative analysis that provides pivotal information on spatial and temporal features of host cell-pathogen interactions. Taken together, the lung tissue model provides a physiologically relevant tissue micro-environment for studies on TB. Thus, the lung tissue model has potential implications for both basic mechanistic and applied studies. Importantly, the model allows addition or manipulation of individual cell types, which thereby widens its use for modelling a variety of infectious diseases that affect the lungs.

Classification of normal and abnormal images of lung cancer

Science.gov (United States)

Bhatnagar, Divyesh; Tiwari, Amit Kumar; Vijayarajan, V.; Krishnamoorthy, A.

2017-11-01

To find the exact symptoms of lung cancer is difficult, because of the formation of the most cancers tissues, wherein large structure of tissues is intersect in a different way. This problem can be evaluated with the help of digital images. In this strategy images will be examined with basic operation of PCA Algorithm. In this paper, GLCM method is used for pre-processing of the snap shots and function extraction system and to test the level of diseases of a patient in its premature stage get to know it is regular or unusual. With the help of result stage of cancer will be evaluated. With the help of dataset and result survival rate of cancer patient can be estimated. Result is based totally on the precise and wrong arrangement of the patterns of tissues.

WE-AB-207B-05: Correlation of Normal Lung Density Changes with Dose After Stereotactic Body Radiotherapy (SBRT) for Early Stage Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Wu, Q; Devpura, S; Feghali, K; Liu, C; Ajlouni, M; Movsas, B; Chetty, I [Henry Ford Health System, Detroit, MI (United States)

2016-06-15

Purpose: To investigate correlation of normal lung CT density changes with dose accuracy and outcome after SBRT for patients with early stage lung cancer. Methods: Dose distributions for patients originally planned and treated using a 1-D pencil beam-based (PB-1D) dose algorithm were retrospectively recomputed using algorithms: 3-D pencil beam (PB-3D), and model-based Methods: AAA, Acuros XB (AXB), and Monte Carlo (MC). Prescription dose was 12 Gy × 4 fractions. Planning CT images were rigidly registered to the followup CT datasets at 6–9 months after treatment. Corresponding dose distributions were mapped from the planning to followup CT images. Following the method of Palma et al .(1–2), Hounsfield Unit (HU) changes in lung density in individual, 5 Gy, dose bins from 5–45 Gy were assessed in the peri-tumor region, defined as a uniform, 3 cm expansion around the ITV(1). Results: There is a 10–15% displacement of the high dose region (40–45 Gy) with the model-based algorithms, relative to the PB method, due to the electron scattering of dose away from the tumor into normal lung tissue (Fig.1). Consequently, the high-dose lung region falls within the 40–45 Gy dose range, causing an increase in HU change in this region, as predicted by model-based algorithms (Fig.2). The patient with the highest HU change (∼110) had mild radiation pneumonitis, and the patient with HU change of ∼80–90 had shortness of breath. No evidence of pneumonitis was observed for the 3 patients with smaller CT density changes (<50 HU). Changes in CT densities, and dose-response correlation, as computed with model-based algorithms, are in excellent agreement with the findings of Palma et al. (1–2). Conclusion: Dose computed with PB (1D or 3D) algorithms was poorly correlated with clinically relevant CT density changes, as opposed to model-based algorithms. A larger cohort of patients is needed to confirm these results. This work was supported in part by a grant from Varian

High-resolution computed tomography of the lungs: the borderlands of normality

International Nuclear Information System (INIS)

Dalal, P.U.; Hansell, D.M.

2006-01-01

High-resolution computed tomography (HRCT) is now widely used in the assessment of airways and diffuse lung disease. Considerable literature on pathologic correlation has increased the understanding of the signs of disease seen on HRCT. However, neither the significance of subtle individual signs nor the spectrum of HRCT appearances in healthy lungs is well documented. HRCT signs that cause diagnostic uncertainty and the spectrum of findings that exist between definite normality and definite abnormality are discussed. (orig.)

The role of zinc supplementation in the inhibition of tissue damage caused by exposure to electromagnetic field in rat lung and liver tissues.

Science.gov (United States)

Baltaci, A K; Mogulkoc, R; Salbacak, A; Celik, I; Sivrikaya, A

2012-01-01

The objective of the present study was to examine the effects of zinc supplementation on the oxidant damage in lung and liver tissues in rats exposed to a 50-Hz frequency magnetic field for 5 minutes every other day over a period of 6 months. The study included 24 adult male Sprague-Dawley rats, which were divided into the three groups in equal numbers: Group 1, the control group (G1); Group 2, the group exposed to an electromagnetic field (G2); and Group 3, the group, which was exposed to an EMF and supplemented with zinc (G3). At the end of the 6-month procedures, the animals were decapitated to collect lung and liver tissue samples, in which MDA was analyzed using the "TBARS method (nmol/g/protein)", GSH by the "biuret method (mg/g/protein)" and zinc levels by atomic emission (µg/dl). MDA levels in lung and liver tissues in G2 were higher than those in G1 and G3, and the levels in G3 were higher than those in G1 (pelectromagnetic field caused cellular damage in lung and liver tissues and zinc supplementation inhibited the inflicted cellular damage. Another important result of this study that needs emphasis was that exposure to an electromagnetic field led to a significant decrease in zinc levels in lung and liver tissues (Tab. 3, Ref. 23).

Oxidative DNA damage in lung tissue from patients with COPD is clustered in functionally significant sequences

Directory of Open Access Journals (Sweden)

Viktor M Pastukh

2011-03-01

Full Text Available Viktor M Pastukh1, Li Zhang2, Mykhaylo V Ruchko1, Olena Gorodnya1, Gina C Bardwell1, Rubin M Tuder2, Mark N Gillespie11Department of Pharmacology and Center for Lung Biology, University of South Alabama College of Medicine, Mobile, AL, USA; 2Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado at Denver, Aurora, CO, USAAbstract: Lung tissue from COPD patients displays oxidative DNA damage. The present study determined whether oxidative DNA damage was randomly distributed or whether it was localized in specific sequences in either the nuclear or mitochondrial genomes. The DNA damage-specific histone, gamma-H2AX, was detected immunohistochemically in alveolar wall cells in lung tissue from COPD patients but not control subjects. A PCR-based method was used to search for oxidized purine base products in selected 200 bp sequences in promoters and coding regions of the VEGF, TGF-β1, HO-1, Egr1, and β-actin genes while quantitative Southern blot analysis was used to detect oxidative damage to the mitochondrial genome in lung tissue from control subjects and COPD patients. Among the nuclear genes examined, oxidative damage was detected in only 1 sequence in lung tissue from COPD patients: the hypoxic response element (HRE of the VEGF promoter. The content of VEGF mRNA also was reduced in COPD lung tissue. Mitochondrial DNA content was unaltered in COPD lung tissue, but there was a substantial increase in mitochondrial DNA strand breaks and/or abasic sites. These findings show that oxidative DNA damage in COPD lungs is prominent in the HRE of the VEGF promoter and in the mitochondrial genome and raise the intriguing possibility that genome and sequence-specific oxidative DNA damage could contribute to transcriptional dysregulation and cell fate decisions in COPD.Keywords: DNA damage, VEGF hypoxic response element, mtDNA, COPD

A morphological study of bronchi and lung tissues in long-term survived dogs

OpenAIRE

松本, 伸

1984-01-01

Morphological changes of the bronchus and lung tissue of ten adult dogs were examined at various intervals after sleeve resection of the left upper lobe was performed in combination with bronchoplasty and pulmonary artery angioplasty. Postoperative changes in the bronchus and pulmonary artery were investigated by bronchoscopy and pulmonary angiography 8 months to 14 months after the operation. The dogs were sacrificed 9 months to 32 months after the operation, and the bronchus and lung tissue...

Differential action on cancer and normal tissue by adrenochrome monoaminoguanidine methanesulfonate and cytochrome C combined with radiotherapy

International Nuclear Information System (INIS)

Nakatsugawa, S.; Sugahara, T.

1994-01-01

The possibility that radioprotective effects on potent natural killer (NK) cells by adrenochrome monoaminoguanidine methanesulfonate (AMM) + cytochrome C during radiotherapy (RT) for lung cancer might result in the radiosensitization of human lung cancer cells in vivo is examined. Human lung cancer xenografts in the right hind legs of KSN mice (10 weeks old) were locally irradiated with 20 Gy of X ray. AMM (10 mg/kg/day) and/or cytochrome C (CCC) (5 mg/kg/day) were given intraperitoneally immediately before or after RT, followed by daily administration for 4 days. Natural killer activities of host splenocytes were also tested with the standard 51 Cr releasing assay with YAC-1 cells as target cells. In a clinical study, 65 patients with lung cancer were treated with more than 50 Gy of RT with or without combination with AMM + CCC, OK-432 or AMM + CCC + OK-432. Before and after RT, lymphocyte subsets in the peripheral blood were examined with dichromatic analysis using an Ortho Spectrum IIIFCM system and fluorescent MABs. In this study, the change in the absolute number of each subset was investigated. AMM + cytochrome C augumented NK activity in KSN nude mice, protected potent NK cells in patients with lung cancer against RT and sensitized the human lung cancer xenografts to RT. AMM + cytochrome C may have potential as a differential modulator of radiosensitivity of normal tissues and of tumors. 8 refs., 2 figs., 1 tab

Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma

DEFF Research Database (Denmark)

Daugaard, Iben; Dominguez, Diana; Kjeldsen, Tina E

2016-01-01

-adjacent normal lung tissue from four lung adenocarcinoma (LAC) patients using DNA methylation microarrays and identified 74 differentially methylated regions (DMRs). Eighteen DMRs were selected for validation in a cohort comprising primary tumors from 52 LAC patients and tumor-adjacent normal lung tissue from 32...... patients by methylation-sensitive high resolution melting (MS-HRM) analysis. Significant increases in methylation were confirmed for 15 DMRs associated with the genes and genomic regions: OSR1, SIM1, GHSR, OTX2, LOC648987, HIST1H3E, HIST1H3G/HIST1H2BI, HIST1H2AJ/HIST1H2BM, HOXD10, HOXD3, HOXB3/HOXB4, HOXA3...

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

Immunolocalization of transforming growth factor alpha in normal human tissues

DEFF Research Database (Denmark)

Christensen, M E; Poulsen, Steen Seier

1996-01-01

anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

Progress in Tissue Specimens Alternative for the Driver Genes Testing of Non-small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Yan SUN

2015-06-01

Full Text Available Target treatment based on driver genes in advanced non-small cell lung cancer is very important currently. Tumor tissues is the gold standard for driver genes testing. However, most of patients could not get the gene information for lack of enough tissues. To explore the tissue specimens alternatives is a hot spot in clinical work. This report reviews the tissue specimen alternatives of driver gene testing in non-small cell lung cancer.

Usefulness of normal saline for sealing the needle track after CT-guided lung biopsy

International Nuclear Information System (INIS)

Li, Y.; Du, Y.; Luo, T.Y.; Yang, H.F.; Yu, J.H.; Xu, X.X.; Zheng, H.J.; Li, B.

2015-01-01

Aim: To determine whether the use of normal saline for sealing the needle track can reduce the incidence of pneumothorax and chest tube placement after computed tomography (CT)-guided lung biopsy. Materials and methods: A prospective, randomised, controlled trial enrolling 322 patients was conducted. All patients were randomly assigned to one of two groups: those in whom the needle track was not sealed with normal saline (n=161, Group A) and those who did receive normal saline (n=161, Group B). CT-guided biopsy was performed with coaxial technique. Normal saline, which ranged from 1–3 ml, was injected while the trocar needle was being withdrawn. Patient characteristics, lesion, and procedure variables were analysed as potential risk variables for occurrence of pneumothorax and chest tube placement. Results: The incidence of pneumothorax was 26.1% in Group A and 6.2% in Group B (p<0.001). Nine patients in Group A and one patient in Group B required chest tube placement (p=0.010). Using multiple logistic regression analysis, smaller lesion size, greater needle–pleural angle, longer lesion–pleural distance, presence of emphysema, and no sealing the needle track with normal saline were significantly associated with an increased risk of pneumothorax, and that the latter three factors were also associated with an increased risk of pneumothorax requiring chest tube placement. Conlusion: Normal saline for sealing the needle track significantly reduces the incidence of pneumothorax and prevents subsequent chest tube placement after CT-guided lung biopsy. - Highlights: • Normal saline is an effective sealant for use in lung biopsy. • This technique reduced the incidence of pneumothorax and chest tube placement. • This technique should be recommended for CT-guided lung biopsy.

Radiation therapy and late reactions in normal tissues

International Nuclear Information System (INIS)

Aoyama, Takashi; Kuroda, Yasumasa

1998-01-01

Recent developments in cancer therapy have made us increasingly aware that the quality of life of a patient is as valuable as other benefits received from therapy. This awareness leads to an emphasis on organ and/or function preservation in the course of therapy. In line with this new thinking, greater consideration is placed on radiation therapy as an appropriate modality of cancer therapy. Possible complications in normal tissues, especially those of late reaction type after the therapy must be overcome. This review, therefore, focuses on recent progress of studies on mechanisms of the complications of the late reaction type. An observation of a clinical case concerning a late reaction of spinal cord (radiation myelopathy) and surveys of experimental studies on the mechanisms of late reactions (including radiation pneumonitis and lung fibrosis, and radiation response of vascular endothelial cells) provide a hypothesis that apoptosis through the pathway starting with radiation-induced sphingomyelin hydrolysis may play an important role in causing a variety of late reactions. This insight is based on the fact that radiation also activates protein kinase C which appears to block apoptosis. The mechanisms of late reactions, therefore, may involve a balance between radiation-induced apoptotic death and its down regulation by suppressor mechanisms through protein kinase C. (author)

Method to characterize inorganic particulates in lung tissue biopsies using field emission scanning electron microscopy

Science.gov (United States)

Lowers, Heather; Breit, George N.; Strand, Matthew; Pillers, Renee M.; Meeker, Gregory P.; Todorov, Todor I.; Plumlee, Geoffrey S.; Wolf, Ruth E.; Robinson, Maura; Parr, Jane; Miller, Robert J.; Groshong, Steve; Green, Francis; Rose, Cecile

2018-01-01

Humans accumulate large numbers of inorganic particles in their lungs over a lifetime. Whether this causes or contributes to debilitating disease over a normal lifespan depends on the type and concentration of the particles. We developed and tested a protocol for in situ characterization of the types and distribution of inorganic particles in biopsied lung tissue from three human groups using field emission scanning electron microscopy (FE-SEM) combined with energy dispersive spectroscopy (EDS). Many distinct particle types were recognized among the 13 000 particles analyzed. Silica, feldspars, clays, titanium dioxides, iron oxides and phosphates were the most common constituents in all samples. Particles were classified into three general groups: endogenous, which form naturally in the body; exogenic particles, natural earth materials; and anthropogenic particles, attributed to industrial sources. These in situ results were compared with those using conventional sodium hypochlorite tissue digestion and particle filtration. With the exception of clays and phosphates, the relative abundances of most common particle types were similar in both approaches. Nonetheless, the digestion/filtration method was determined to alter the texture and relative abundances of some particle types. SEM/EDS analysis of digestion filters could be automated in contrast to the more time intensive in situ analyses.

Immunological risk stratification of the bronchiolitis obliterans syndrome after lung transplantation

NARCIS (Netherlands)

Kwakkel - van Erp, J.M.

2011-01-01

The development of chronic allograft rejection after lung transplantation (LTx) is the most common cause of poor long-term survival in lung transplant recipients. This rejection leads to obliteration of the bronchioli. Since this obliteration has a patchy distribution and normal lung tissue obtained

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

Science.gov (United States)

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

2016-05-01

ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. © 2016 Federation of European Biochemical Societies.

Measurement of human normal tissue and tumour responses

International Nuclear Information System (INIS)

Ross, G.; Yarnold, J.R.

1988-01-01

The scarcity of quantitative measures of normal tissue damage and tumour response in patients undergoing radiotherapy is an obstacle to the clinical evaluation of new treatment strategies. Retrospective studies of complications in critical normal tissues taught important lessons in the past concerning the potential dangers of hypofractionation. However, it is unethical to use serious complications as planned end-points in prospective studies. This paper reviews the desirable characteristics of clinical end-points required to compare alternative treatments employing radiotherapy, with emphasis on simple scales applied by clinicians or even the patients themselves

Extravascular transport in normal and tumor tissues.

Science.gov (United States)

Jain, R K; Gerlowski, L E

1986-01-01

The transport characteristics of the normal and tumor tissue extravascular space provide the basis for the determination of the optimal dosage and schedule regimes of various pharmacological agents in detection and treatment of cancer. In order for the drug to reach the cellular space where most therapeutic action takes place, several transport steps must first occur: (1) tissue perfusion; (2) permeation across the capillary wall; (3) transport through interstitial space; and (4) transport across the cell membrane. Any of these steps including intracellular events such as metabolism can be the rate-limiting step to uptake of the drug, and these rate-limiting steps may be different in normal and tumor tissues. This review examines these transport limitations, first from an experimental point of view and then from a modeling point of view. Various types of experimental tumor models which have been used in animals to represent human tumors are discussed. Then, mathematical models of extravascular transport are discussed from the prespective of two approaches: compartmental and distributed. Compartmental models lump one or more sections of a tissue or body into a "compartment" to describe the time course of disposition of a substance. These models contain "effective" parameters which represent the entire compartment. Distributed models consider the structural and morphological aspects of the tissue to determine the transport properties of that tissue. These distributed models describe both the temporal and spatial distribution of a substance in tissues. Each of these modeling techniques is described in detail with applications for cancer detection and treatment in mind.

Computer modeling the boron compound factor in normal brain tissue

International Nuclear Information System (INIS)

Gavin, P.R.; Huiskamp, R.; Wheeler, F.J.; Griebenow, M.L.

1993-01-01

The macroscopic distribution of borocaptate sodium (Na 2 B 12 H 11 SH or BSH) in normal tissues has been determined and can be accurately predicted from the blood concentration. The compound para-borono-phenylalanine (p-BPA) has also been studied in dogs and normal tissue distribution has been determined. The total physical dose required to reach a biological isoeffect appears to increase directly as the proportion of boron capture dose increases. This effect, together with knowledge of the macrodistribution, led to estimates of the influence of the microdistribution of the BSH compound. This paper reports a computer model that was used to predict the compound factor for BSH and p-BPA and, hence, the equivalent radiation in normal tissues. The compound factor would need to be calculated for other compounds with different distributions. This information is needed to design appropriate normal tissue tolerance studies for different organ systems and/or different boron compounds

A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

Directory of Open Access Journals (Sweden)

Thorsten Schlomm

2013-03-01

Full Text Available We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA levels (14 and 17 individuals, respectively were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs. Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b, which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.

Differentiating cancerous from normal breast tissue by redox imaging

Science.gov (United States)

Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

2015-02-01

Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (pcancerous tissues than in the normal ones (pcancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

Over, and Underexpression of Endothelin 1 and TGF-Beta Family Ligands and Receptors in Lung Tissue of Broilers with Pulmonary Hypertension

Science.gov (United States)

Dominguez-Avila, Norma; Ruiz-Castañeda, Gabriel; González-Ramírez, Javier; Fernandez-Jaramillo, Nora; Escoto, Jorge; Sánchez-Muñoz, Fausto; Marquez-Velasco, Ricardo; Bojalil, Rafael; Espinosa-Cervantes, Román; Sánchez, Fausto

2013-01-01

Transforming growth factor beta (TGFβ) is a family of genes that play a key role in mediating tissue remodeling in various forms of acute and chronic lung disease. In order to assess their role on pulmonary hypertension in broilers, we determined mRNA expression of genes of the TGFβ family and endothelin 1 in lung samples from 4-week-old chickens raised either under normal or cold temperature conditions. Both in control and cold-treated groups of broilers, endothelin 1 mRNA expression levels in lungs from ascitic chickens were higher than levels from healthy birds (P 0.05). BAMBI mRNA gene expression was lowest in birds with ascites only in the control group as compared with the values from healthy birds (P < 0.05). PMID:24286074

T lymphocytes and normal tissue responses to radiation

International Nuclear Information System (INIS)

Schaue, Dörthe; McBride, William H.

2012-01-01

There is compelling evidence that lymphocytes are a recurring feature in radiation damaged normal tissues, but assessing their functional significance has proven difficult. Contradictory roles have been postulated in both tissue pathogenesis and protection, although these are not necessarily mutually exclusive as the immune system can display what may seem to be opposing faces at any one time. While the exact role of T lymphocytes in irradiated normal tissue responses may still be obscure, their accumulation after tissue damage suggests they may be critical targets for radiotherapeutic intervention and worthy of further study. This is accentuated by recent findings that pathologically damaged “self,” such as occurs after exposure to ionizing radiation, can generate danger signals with the ability to activate pathways similar to those that activate adoptive immunity to pathogens. In addition, the demonstration of T cell subsets with their recognition radars tuned to “self” moieties has revolutionized our ideas on how all immune responses are controlled and regulated. New concepts of autoimmunity have resulted based on the dissociation of immune functions between different subsets of immune cells. It is becoming axiomatic that the immune system has the power to regulate radiation-induced tissue damage, from failure of regeneration to fibrosis, to acute and chronic late effects, and even to carcinogenesis. Our understanding of the interplay between T lymphocytes and radiation-damaged tissue may still be rudimentary but this is a good time to re-examine their potential roles, their radiobiological and microenvironmental influences, and the possibilities for therapeutic manipulation. This review will discuss the yin and yang of T cell responses within the context of radiation exposures, how they might drive or protect against normal tissue side effects and what we may be able do about it.

Role of endothelium in radiation-induced normal tissue damages

International Nuclear Information System (INIS)

Milliat, F.

2007-05-01

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

Losartan Attenuates Degradation of Aorta and Lung Tissue Micromechanics in a Mouse Model of Severe Marfan Syndrome.

Science.gov (United States)

Lee, Jia-Jye; Galatioto, Josephine; Rao, Satish; Ramirez, Francesco; Costa, Kevin D

2016-10-01

Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue due to mutations in the fibrillin-1 gene (FBN1). This study aimed at characterizing microelastic properties of the ascending aortic wall and lung parenchyma tissues from wild type (WT) and age-matched Fbn1 hypomorphic mice (Fbn1(mgR/mgR) mice) to identify tissue-specific biomechanical effects of aging and disease in MFS. Atomic force microscopy was used to indent lung parenchyma and aortic wall tissues, using Hybrid Eshelby Decomposition analysis to extract layer-specific properties of the intima and media. The intima stiffened with age and was not different between WT and Fbn1(mgR/mgR) tissues, whereas the media layer of MFS aortas showed progressive structural and mechanical degradation with a modulus that was 50% softer than WT by 3.5 months of age. Similarly, MFS mice displayed progressive structural and mechanical deterioration of lung tissue, which was over 85% softer than WT by 3.5 months of age. Chronic treatment with the angiotensin type I receptor antagonist, losartan, attenuated the aorta and lung tissue degradation, resulting in structural and mechanical properties not significantly different from age-matched WT controls. By revealing micromechanical softening of elastin-rich aorta and lung tissues with disease progression in fibrillin-1 deficient mice, our findings support the use of losartan as a prophylactic treatment that may abrogate the life-threatening symptoms of MFS.

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.)

Oxidative damage induced by cigarette smoke exposure in mice: impact on lung tissue and diaphragm muscle,

Directory of Open Access Journals (Sweden)

Samanta Portão de Carlos

2014-08-01

Full Text Available OBJECTIVE: To evaluate oxidative damage (lipid oxidation, protein oxidation, thiobarbituric acid-reactive substances [TBARS], and carbonylation and inflammation (expression of phosphorylated AMP-activated protein kinase and mammalian target of rapamycin [p-AMPK and p-mTOR, respectively] in the lung parenchyma and diaphragm muscles of male C57BL-6 mice exposed to cigarette smoke (CS for 7, 15, 30, 45, or 60 days. METHODS: Thirty-six male C57BL-6 mice were divided into six groups (n = 6/group: a control group; and five groups exposed to CS for 7, 15, 30, 45, and 60 days, respectively. RESULTS: Compared with control mice, CS-exposed mice presented lower body weights at 30 days. In CS-exposed mice (compared with control mice, the greatest differences (increases in TBARS levels were observed on day 7 in diaphragm-muscle, compared with day 45 in lung tissue; the greatest differences (increases in carbonyl levels were observed on day 7 in both tissue types; and sulfhydryl levels were lower, in both tissue types, at all time points. In lung tissue and diaphragm muscle, p-AMPK expression exhibited behavior similar to that of TBARS. Expression of p-mTOR was higher than the control value on days 7 and 15 in lung tissue, as it was on day 45 in diaphragm muscle. CONCLUSION: Our data demonstrate that CS exposure produces oxidative damage, not only in lung tissue but also (primarily in muscle tissue, having an additional effect on respiratory muscle, as is frequently observed in smokers with COPD.

Characterization and optimization of the RA-3 experimental dosimetry for normal sheep lung radio-tolerance study

International Nuclear Information System (INIS)

Soto, M.S.; Gonzalez, S.J.; Thorp, Silvia I.; Pozzi, Emiliano; Gadan, M.; Miller, Marcelo; Farias, R.

2009-01-01

In the spirit of the novel technique proposed by the University of Pavia group (Italy) to irradiate an isolated organ using BNCT, the Comision Nacional de Energia Atomica (CNEA) in collaboration with the Fundacion Favaloro has initiated a project that aims to investigate the feasibility of BNCT for ex-situ treatment of diffuse metastatic disease in the lungs. The present work was carried out in the framework of the undergoing experimental study of the radio tolerance of normal sheep lung. With the purpose of characterizing and optimizing the resulting experimental dosimetry in normal lung subjected to neutron irradiation in the BNCT facility of the RA-3 reactor (CNEA), we have performed a series of experiments to find the optimum configuration of the container-lung system deriving a dose distribution preferentially uniform throughout the organ. Once the optimal set-up was established, we measured the total gamma dose rate and estimated the irradiation time compatible with the maximum tolerable dose of normal lung resulting from previous studies in rats. This estimation was performed using RBE, CBE and tolerance dose values derived from radiobiological studies with BNCT. In parallel with the experimental characterization, we built two different computational models of the container-lung system to perform Monte Carlo simulation with MCNP and Treatment Planning System NCTPlan. (author)

DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing.

Science.gov (United States)

Rübe, Claudia E; Grudzenski, Saskia; Kühne, Martin; Dong, Xiaorong; Rief, Nicole; Löbrich, Markus; Rübe, Christian

2008-10-15

Radiotherapy is an effective cancer treatment, but a few patients suffer severe radiation toxicities in neighboring normal tissues. There is increasing evidence that the variable susceptibility to radiation toxicities is caused by the individual genetic predisposition, by subtle mutations, or polymorphisms in genes involved in cellular responses to ionizing radiation. Double-strand breaks (DSB) are the most deleterious form of radiation-induced DNA damage, and DSB repair deficiencies lead to pronounced radiosensitivity. Using a preclinical mouse model, the highly sensitive gammaH2AX-foci approach was tested to verify even subtle, genetically determined DSB repair deficiencies known to be associated with increased normal tissue radiosensitivity. By enumerating gammaH2AX-foci in blood lymphocytes and normal tissues (brain, lung, heart, and intestine), the induction and repair of DSBs after irradiation with therapeutic doses (0.1-2 Gy) was investigated in repair-proficient and repair-deficient mouse strains in vivo and blood samples irradiated ex vivo. gammaH2AX-foci analysis allowed to verify the different DSB repair deficiencies; even slight impairments caused by single polymorphisms were detected similarly in both blood lymphocytes and solid tissues, indicating that DSB repair measured in lymphocytes is valid for different and complex organs. Moreover, gammaH2AX-foci analysis of blood samples irradiated ex vivo was found to reflect repair kinetics measured in vivo and, thus, give reliable information about the individual DSB repair capacity. gammaH2AX analysis of blood and tissue samples allows to detect even minor genetically defined DSB repair deficiencies, affecting normal tissue radiosensitivity. Future studies will have to evaluate the clinical potential to identify patients more susceptible to radiation toxicities before radiotherapy.

Human normal tissue reactions in radiotherapy

International Nuclear Information System (INIS)

Taniike, Keiko

1990-01-01

Acute and late normal tissue reactions in radiotherapy have not been considered to be major problems with conventional fractionation. But they may cause certain problems when newer schedules such as hyperfractionation or accelerated fractionation are used. In opposing parallel radiotherapy, the dose fractionation of skin or subcutaneous connective tissue are different between in one portal and two portals daily. So we examined acute skin erythema and late connective tissue fibrosis in the two groups (one and two portals) of the patients with uterus cancer. Acute skin erythema and late connective tissue fibrosis were slightly stronger in case of one portal daily. In relation to the anatomical site of skin, acute skin erythema was stronger at the buttocks than the lower abdomen, but late fibrosis was reverse to that. So the degree of acute skin erythema did not predict the degree of late connective tissue fibrosis. The number of Time Dose Fractionation Factor could roughly estimate the degree of erythema and fibrosis. Late fibrosis in 36 fractions increased with an increase of abdominal thickness, but acute erythema did not. (author)

Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells

DEFF Research Database (Denmark)

Rolandsson, Sara; Andersson Sjöland, Annika; Brune, Jan C

2014-01-01

BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported. This st......BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported...

Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

Science.gov (United States)

Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

2015-10-10

Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Copyright © 2015 Elsevier B.V. All rights reserved.

Rapid detection of Mannheimia haemolytica in lung tissues of sheep and from bacterial culture

Directory of Open Access Journals (Sweden)

Jyoti Kumar

2015-09-01

Full Text Available Aim: This study was aimed to detect Mannheimia haemolytica in lung tissues of sheep and from a bacterial culture. Introduction: M. haemolytica is one of the most important and well-established etiological agents of pneumonia in sheep and other ruminants throughout the world. Accurate diagnosis of M. haemolytica primarily relies on bacteriological examination, biochemical characteristics and, biotyping and serotyping of the isolates. In an effort to facilitate rapid M. haemolytica detection, polymerase chain reaction assay targeting Pasteurella haemolytica serotype-1 specific antigens (PHSSA, Rpt2 and 12S ribosomal RNA (rRNA genes were used to detect M. haemolytica directly from lung tissues and from bacterial culture. Materials and Methods: A total of 12 archived lung tissues from sheep that died of pneumonia on an organized farm were used. A multiplex polymerase chain reaction (mPCR based on two-amplicons targeted PHSSA and Rpt2 genes of M. haemolytica were used for identification of M. haemolytica isolates in culture from the lung samples. All the 12 lung tissue samples were tested for the presence M. haemolytica by PHSSA and Rpt2 genes based PCR and its confirmation by sequencing of the amplicons. Results: All the 12 lung tissue samples tested for the presence of PHSSA and Rpt2 genes of M. haemolytica by mPCR were found to be positive. Amplification of 12S rRNA gene fragment as internal amplification control was obtained with each mPCR reaction performed from DNA extracted directly from lung tissue samples. All the M. haemolytica were also positive for mPCR. No amplified DNA bands were observed for negative control reactions. All the three nucleotide sequences were deposited in NCBI GenBank (Accession No. KJ534629, KJ534630 and KJ534631. Sequencing of the amplified products revealed the identity of 99-100%, with published sequence of PHSSA and Rpt2 genes of M. haemolytica available in the NCBI database. Sheep specific mitochondrial 12S r

Depth-dose evaluation for lung and pancreas cancer treatment by BNCT using an epithermal neutron beam

International Nuclear Information System (INIS)

Matsumoto, Tetsuo; Fukushima, Yuji

2000-01-01

The depth-dose distributions were evaluated for possible treatment of both lung and pancreas cancers using an epithermal neutron beam. The MCNP calculations showed that physical dose in tumors were 6 and 7 Gy/h, respectively, for lung and pancreas, attaining an epithermal neutron flux of 5x10 8 ncm -2 s -1 . The boron concentrations were assumed at 100 ppm and 30 ppm, respectively, for lung and pancreas tumors and normal tissues contains 1/10 tumor concentrations. The dose ratios of tumor to normal tissue were 2.5 and 2.4, respectively, for lung and pancreas. The dose evaluation suggests that BNCT could be applied for both lung and pancreas cancer treatment. (author)

Volume-controlled histographic analysis of pulmonary parenchyma in normal and diffuse parenchymal lung disease: a pilot study

International Nuclear Information System (INIS)

Park, Hyo Yong; Lee, Jongmin; Kim, Jong Seob; Won, Chyl Ho; Kang, Duk Sik; Kim, Myoung Nam

2000-01-01

To evaluate the clinical usefulness of a home-made histographic analysis system using a lung volume controller. Our study involved ten healthy volunteers, ten emphysema patients, and two idiopathic pulmonary fibrosis (IPF) patients. Using a home-made lung volume controller, images were obtained in the upper, middle, and lower lung zones at 70%, 50%, and 20% of vital capacity. Electron beam tomography was used and scanning parameters were single slice mode, 10-mm slice thickness, 0.4-second scan time, and 35-cm field of view. Usinga home-made semi-automated program, pulmonary parenchyma was isolated and a histogrm then obtained. Seven histographic parameters, namely mean density (MD), density at maximal frequency (DMF), maximal ascending gradient (MAG),maximal ascending gradient density (MAGD), maximal sescending gradient (MDG), maximal descending gradient density (MDGD), and full width at half maximum (FWHM) were derived from the histogram. We compared normal controls with abnormal groups including emphysema and IPF patients at the same respiration levels. A normal histographic zone with ± 1 standard deviation was obtained. Histographic curves of normal controls shifted toward the high density level, and the width of the normal zone increased as the level of inspiration decreased. In ten normal controls, MD, DMF, MAG, MAGD, MDG, MDGD, and FWHM readings at a 70% inspiration level were lower than those at 20% (p less than0.05). At the same level of inspiration, histograms of emphysema patients were locatedat a lower density area than those of normal controls. As inspiration status decreased, histograms of emphysema patients showed diminished shift compared with those of normal controls. At 50% and 20% inspiration levels, the MD, DMF, and MAGD readings of emphysema patients were significantly lower than those of normal controls (p less than 0.05). Compared with those of normal controls, histogrms of the two IPF patients obtained at three inspiration levels were

Volume-controlled histographic analysis of pulmonary parenchyma in normal and diffuse parenchymal lung disease: a pilot study

Energy Technology Data Exchange (ETDEWEB)

Park, Hyo Yong; Lee, Jongmin; Kim, Jong Seob; Won, Chyl Ho; Kang, Duk Sik [School of Medicine, Kyungpook National University, Taegu (Korea, Republic of); Kim, Myoung Nam [The University of Iowa (United States)

2000-06-01

To evaluate the clinical usefulness of a home-made histographic analysis system using a lung volume controller. Our study involved ten healthy volunteers, ten emphysema patients, and two idiopathic pulmonary fibrosis (IPF) patients. Using a home-made lung volume controller, images were obtained in the upper, middle, and lower lung zones at 70%, 50%, and 20% of vital capacity. Electron beam tomography was used and scanning parameters were single slice mode, 10-mm slice thickness, 0.4-second scan time, and 35-cm field of view. Usinga home-made semi-automated program, pulmonary parenchyma was isolated and a histogrm then obtained. Seven histographic parameters, namely mean density (MD), density at maximal frequency (DMF), maximal ascending gradient (MAG),maximal ascending gradient density (MAGD), maximal sescending gradient (MDG), maximal descending gradient density (MDGD), and full width at half maximum (FWHM) were derived from the histogram. We compared normal controls with abnormal groups including emphysema and IPF patients at the same respiration levels. A normal histographic zone with {+-} 1 standard deviation was obtained. Histographic curves of normal controls shifted toward the high density level, and the width of the normal zone increased as the level of inspiration decreased. In ten normal controls, MD, DMF, MAG, MAGD, MDG, MDGD, and FWHM readings at a 70% inspiration level were lower than those at 20% (p less than0.05). At the same level of inspiration, histograms of emphysema patients were locatedat a lower density area than those of normal controls. As inspiration status decreased, histograms of emphysema patients showed diminished shift compared with those of normal controls. At 50% and 20% inspiration levels, the MD, DMF, and MAGD readings of emphysema patients were significantly lower than those of normal controls (p less than 0.05). Compared with those of normal controls, histogrms of the two IPF patients obtained at three inspiration levels were

Analytical formulae in fractionated irradiation of normal tissue

International Nuclear Information System (INIS)

Kozubek, S.

1982-01-01

The new conception of the modeling of the cell tissue kinetics after fractionated irradiation is proposed. The formulae given earlier are compared with experimental data on various normal tissues and further adjustments are considered. The tissues are shown to exhibit several general patterns of behaviour. The repopulation, if it takes place, seems to start after some time, independently of fractionation in first approximation and can be treated as simple autogenesis. The results are compared with the commonly used NSD conception and the well-known Cohen cell tissue kinetic model

Development of an experimental model of brain tissue heterotopia in the lung

Science.gov (United States)

Quemelo, Paulo Roberto Veiga; Sbragia, Lourenço; Peres, Luiz Cesar

2007-01-01

Summary The presence of heterotopic brain tissue in the lung is a rare abnormality. The cases reported thus far are usually associated with neural tube defects (NTD). As there are no reports of experimental models of NTD that present this abnormality, the objective of the present study was to develop a surgical method of brain tissue heterotopia in the lung. We used 24 pregnant Swiss mice divided into two groups of 12 animals each, denoted 17GD and 18GD according to the gestational day (GD) when caesarean section was performed to collect the fetuses. Surgery was performed on the 15th GD, one fetus was removed by hysterectomy and its brain tissue was cut into small fragments and implanted in the lung of its litter mates. Thirty-four live fetuses were obtained from the 17GD group. Of these, eight (23.5%) were used as control (C), eight (23.5%) were sham operated (S) and 18 (52.9%) were used for pulmonary brain tissue implantation (PBI). Thirty live fetuses were obtained from the females of the 18GD group. Of these, eight (26.6%) were C, eight (26.6%) S and 14 (46.6%) were used for PBI. Histological examination of the fetal trunks showed implantation of GFAP-positive brain tissue in 85% of the fetuses of the 17GD group and in 100% of those of the 18GD group, with no significant difference between groups for any of the parameters analysed. The experimental model proved to be efficient and of relatively simple execution, showing complete integration of the brain tissue with pulmonary and pleural tissue and thus representing a model that will permit the study of different aspects of cell implantation and interaction. PMID:17877535

Epithermal neutron beam adoption for lung and pancreatic cancer treatment by boron neutron capture therapy

International Nuclear Information System (INIS)

Matsumoto, Tetsuo; Fukushima, Yuji

2001-01-01

The depth-dose distributions were evaluated for possible treatment of both lung and pancreatic cancers using an epithermal neutron beam. The Monte Carlo Neutron Photon (MCNP) calculations showed that physical dose in tumors were 6 and 7 Gy/h, respectively, for lung and pancreas, attaining an epithermal neutron flux of 5 x 10 8 ncm -2 s -1 . The boron concentrations were assumed at 100 ppm and 30 ppm, respectively, for lung and pancreas tumors and normal tissues contains 1/10 tumor concentrations. The dose ratios of tumor to normal tissue were 2.5 and 2.4, respectively, for lung and pancreas. The dose evaluation suggests that BNCT using an epithermal neutron beam could be applied for both lung and pancreatic cancer treatment. (author)

Deep neural network convolution (NNC) for three-class classification of diffuse lung disease opacities in high-resolution CT (HRCT): consolidation, ground-glass opacity (GGO), and normal opacity

Science.gov (United States)

Hashimoto, Noriaki; Suzuki, Kenji; Liu, Junchi; Hirano, Yasushi; MacMahon, Heber; Kido, Shoji

2018-02-01

Consolidation and ground-glass opacity (GGO) are two major types of opacities associated with diffuse lung diseases. Accurate detection and classification of such opacities are crucially important in the diagnosis of lung diseases, but the process is subjective, and suffers from interobserver variability. Our study purpose was to develop a deep neural network convolution (NNC) system for distinguishing among consolidation, GGO, and normal lung tissue in high-resolution CT (HRCT). We developed ensemble of two deep NNC models, each of which was composed of neural network regression (NNR) with an input layer, a convolution layer, a fully-connected hidden layer, and a fully-connected output layer followed by a thresholding layer. The output layer of each NNC provided a map for the likelihood of being each corresponding lung opacity of interest. The two NNC models in the ensemble were connected in a class-selection layer. We trained our NNC ensemble with pairs of input 2D axial slices and "teaching" probability maps for the corresponding lung opacity, which were obtained by combining three radiologists' annotations. We randomly selected 10 and 40 slices from HRCT scans of 172 patients for each class as a training and test set, respectively. Our NNC ensemble achieved an area under the receiver-operating-characteristic (ROC) curve (AUC) of 0.981 and 0.958 in distinction of consolidation and GGO, respectively, from normal opacity, yielding a classification accuracy of 93.3% among 3 classes. Thus, our deep-NNC-based system for classifying diffuse lung diseases achieved high accuracies for classification of consolidation, GGO, and normal opacity.

Mouse genetic approaches applied to the normal tissue radiation response

International Nuclear Information System (INIS)

Haston, Christina K.

2012-01-01

The varying responses of inbred mouse models to radiation exposure present a unique opportunity to dissect the genetic basis of radiation sensitivity and tissue injury. Such studies are complementary to human association studies as they permit both the analysis of clinical features of disease, and of specific variants associated with its presentation, in a controlled environment. Herein I review how animal models are studied to identify specific genetic variants influencing predisposition to radiation-induced traits. Among these radiation-induced responses are documented strain differences in repair of DNA damage and in extent of tissue injury (in the lung, skin, and intestine) which form the base for genetic investigations. For example, radiation-induced DNA damage is consistently greater in tissues from BALB/cJ mice, than the levels in C57BL/6J mice, suggesting there may be an inherent DNA damage level per strain. Regarding tissue injury, strain specific inflammatory and fibrotic phenotypes have been documented for principally, C57BL/6 C3H and A/J mice but a correlation among responses such that knowledge of the radiation injury in one tissue informs of the response in another is not evident. Strategies to identify genetic differences contributing to a trait based on inbred strain differences, which include linkage analysis and the evaluation of recombinant congenic (RC) strains, are presented, with a focus on the lung response to irradiation which is the only radiation-induced tissue injury mapped to date. Such approaches are needed to reveal genetic differences in susceptibility to radiation injury, and also to provide a context for the effects of specific genetic variation uncovered in anticipated clinical association studies. In summary, mouse models can be studied to uncover heritable variation predisposing to specific radiation responses, and such variations may point to pathways of importance to phenotype development in the clinic.

Comparative study of radiosensitivity of normal and regenerating tissues

International Nuclear Information System (INIS)

Samokhvalova, H.S.; Popova, M.F.

1983-01-01

A comparative study of radiosensitivity of cells of normal and regenerating tissues of bone marrow and spleen has demonstrated that single exposure to X-rays produces a lesser damaging effect on regenerating tissues than on normal ones. The data obtained indicate that the increase in radioresistance of the organism during active regeneration of the haemopoietic organs is due not merely to the increase in the dividing cell pool of these organs but also to qualitative changes in their functional state

Effects of pions on normal tissues

International Nuclear Information System (INIS)

Tokita, N.

1981-01-01

Verification of the uniform biological effectiveness of pion beams of various dimensions produced at LAMPF has been made using cultured mammalian cells and mouse jejunum. Normal tissue radiobiology studies at LAMPF are reviewed with regard to biological beam characterization for the therapy program and the current status of acute and late effect studies on rodents

Diurnal levels of immunoreactive erythropoietin in normal subjects and subjects with chronic lung disease

Energy Technology Data Exchange (ETDEWEB)

Miller, M.E.; Garcia, J.F.; Cohen, R.A.; Cronkite, E.P.; Moccia, G.; Acevedo, J.

1981-10-01

Serum levels of immunoreactive erythropoietin (Ep) were measured in 48 normal male and female volunteers, ages 20-60 years, to establish a control value for Ep of 18.5 +/- 5.0 (mean +/- SD) mU/ml. Levels of the hormone were also measured sequentially over a 24 h period of time in an additional 17 normal volunteers with no diurnal variation. Diurnal levels of immunoreactive Ep were also measured in 30 subjects, with chronic lung disease. These patients, in contrast to normal subjects exhibited a diurnal variation in the level of immunoreactive Ep with peak levels occurring at midnight. The only variable measured which correlated with the serum immunoreactive Ep level in subjects with chronic lung disease was the level of carboxyhaemoglobin (P less than 0.02).

Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation.

Science.gov (United States)

Solleti, Siva Kumar; Srisuma, Sorachai; Bhattacharya, Soumyaroop; Rangel-Moreno, Javier; Bijli, Kaiser M; Randall, Troy D; Rahman, Arshad; Mariani, Thomas J

2016-07-01

Serine proteinase inhibitor, clade E, member 2 (SERPINE2), is a cell- and extracellular matrix-associated inhibitor of thrombin. Although SERPINE2 is a candidate susceptibility gene for chronic obstructive pulmonary disease, the physiologic role of this protease inhibitor in lung development and homeostasis is unknown. We observed spontaneous monocytic-cell infiltration in the lungs of Serpine2-deficient (SE2(-/-)) mice, beginning at or before the time of lung maturity, which resulted in lesions that resembled bronchus-associated lymphoid tissue (BALT). The initiation of lymphocyte accumulation in the lungs of SE2(-/-) mice involved the excessive expression of chemokines, cytokines, and adhesion molecules that are essential for BALT induction, organization, and maintenance. BALT-like lesion formation in the lungs of SE2(-/-) mice was also associated with a significant increase in the activation of thrombin, a recognized target of SE2, and excess stimulation of NF-κB, a major regulator of chemokine expression and inflammation. Finally, systemic delivery of thrombin rapidly stimulated lung chemokine expression in vivo These data uncover a novel mechanism whereby loss of serine protease inhibition leads to lung lymphocyte accumulation.-Solleti, S. K., Srisuma, S., Bhattacharya, S., Rangel-Moreno, J., Bijli, K. M., Randall, T. D., Rahman, A., Mariani, T. J. Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation. © FASEB.

SU-D-18A-04: Quantifying the Ability of Tumor Tracking to Spare Normal Tissue

Energy Technology Data Exchange (ETDEWEB)

Burger, A; Buzurovic, I; Hurwitz, M; Williams, C; Lewis, J [Brigham and Women' s Hospital, Dana-Farber Cancer Center, Harvard Medical Sc, Boston, MA (United States); Mishra, P [Varian Medical Systems, Palo Alto, CA (United States); Seco, J [Mass General Hospital, Harvard Medical, Boston, MA (United States)

2014-06-01

Purpose: Tumor tracking allows for smaller tissue volumes to be treated, potentially reducing normal tissue damage. However, tumor tracking is a more complex treatment and has little benefit in some scenarios. Here we quantify the benefit of tumor tracking for a range of patients by estimating the dose of radiation to organs at risk and the normal tissue complication probability (NTCP) for both standard and tracking treatment plans. This comparison is performed using both patient 4DCT data and extended Cardiac-Torso (XCAT) digital phantoms. Methods: We use 4DCT data for 10 patients. Additionally, we generate digital phantoms with motion derived from measured patient long tumor trajectories to compare standard and tracking treatment plans. The standard treatment is based on the average intensity projection (AIP) of 4DCT images taken over a breath cycle. The tracking treatment is based on doses calculated on images representing the anatomy at each time point. It is assumed that there are no errors in tracking the target. The NTCP values are calculated based on RTOG guidelines. Results: The mean reduction in the mean dose delivered was 5.5% to the lungs (from 7.3 Gy to 6.9 Gy) and 4.0% to the heart (from 12.5 Gy to 12.0 Gy). The mean reduction in the max dose delivered was 13% to the spinal cord (from 27.6 Gy to 24.0 Gy), 2.5% to the carina (from 31.7 Gy to 30.9 Gy), and 15% to the esophagus (from 69.6 Gy to 58.9 Gy). The mean reduction in the probability of 2nd degree radiation pneumonitis (RP) was 8.7% (3.1% to 2.8%) and the mean reduction in the effective volume was 6.8% (10.8% to 10.2%). Conclusions: Tumor tracking has the potential to reduce irradiation of organs at risk, and consequentially reduce the normal tissue complication probability. The benefits vary based on the clinical scenario. This study is supported by Varian Medical Systems, Inc.

Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia.

Science.gov (United States)

Wang, Yaping; Zhao, Zhen; Zhu, Zhiyong; Li, Pingying; Li, Xiaolin; Xue, Xiaohong; Duo, Jie; Ma, Yingcai

2018-02-17

The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues. Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α). Increased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α. Acute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.

Registration-based assessment of regional lung function via volumetric CT images of normal subjects vs. severe asthmatics

Science.gov (United States)

Choi, Sanghun; Hoffman, Eric A.; Wenzel, Sally E.; Tawhai, Merryn H.; Yin, Youbing; Castro, Mario

2013-01-01

The purpose of this work was to explore the use of image registration-derived variables associated with computed tomographic (CT) imaging of the lung acquired at multiple volumes. As an evaluation of the utility of such an imaging approach, we explored two groups at the extremes of population ranging from normal subjects to severe asthmatics. A mass-preserving image registration technique was employed to match CT images at total lung capacity (TLC) and functional residual capacity (FRC) for assessment of regional air volume change and lung deformation between the two states. Fourteen normal subjects and thirty severe asthmatics were analyzed via image registration-derived metrics together with their pulmonary function test (PFT) and CT-based air-trapping. Relative to the normal group, the severely asthmatic group demonstrated reduced air volume change (consistent with air trapping) and more isotropic deformation in the basal lung regions while demonstrating increased air volume change associated with increased anisotropic deformation in the apical lung regions. These differences were found despite the fact that both PFT-derived TLC and FRC in the two groups were nearly 100% of predicted values. Data suggest that reduced basal-lung air volume change in severe asthmatics was compensated by increased apical-lung air volume change and that relative increase in apical-lung air volume change in severe asthmatics was accompanied by enhanced anisotropic deformation. These data suggest that CT-based deformation, assessed via inspiration vs. expiration scans, provides a tool for distinguishing differences in lung mechanics when applied to the extreme ends of a population range. PMID:23743399

Resolvin D1 prevents smoking-induced emphysema and promotes lung tissue regeneration.

Science.gov (United States)

Kim, Kang-Hyun; Park, Tai Sun; Kim, You-Sun; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

2016-01-01

Emphysema is an irreversible disease that is characterized by destruction of lung tissue as a result of inflammation caused by smoking. Resolvin D1 (RvD1), derived from docosahexaenoic acid, is a novel lipid that resolves inflammation. The present study tested whether RvD1 prevents smoking-induced emphysema and promotes lung tissue regeneration. C57BL/6 mice, 8 weeks of age, were randomly divided into four groups: control, RvD1 only, smoking only, and smoking with RvD1 administration. Four different protocols were used to induce emphysema and administer RvD1: mice were exposed to smoking for 4 weeks with poly(I:C) or to smoking only for 24 weeks, and RvD1 was injected within the smoking exposure period to prevent regeneration or after completion of smoking exposure to assess regeneration. The mean linear intercept and inflammation scores were measured in the lung tissue, and inflammatory cells and cytokines were measured in the bronchoalveolar lavage fluid. Measurements of mean linear intercept showed that RvD1 significantly attenuated smoking-induced lung destruction in all emphysema models. RvD1 also reduced smoking-induced inflammatory cell infiltration, which causes the structural derangements observed in emphysema. In the 4-week prevention model, RvD1 reduced the smoking-induced increase in eosinophils and interleukin-6 in the bronchoalveolar lavage fluid. In the 24-week prevention model, RvD1 also reduced the increased neutrophils and total cell counts induced by smoking. RvD1 attenuated smoking-induced emphysema in vivo by reducing inflammation and promoting tissue regeneration. This result suggests that RvD1 may be useful in the prevention and treatment of emphysema.

SPECT/CT of lung nodules using 111In-DOTA-c(RGDfK) in a mouse lung carcinogenesis model.

Science.gov (United States)

Hayakawa, Takuya; Mutoh, Michihiro; Imai, Toshio; Tsuta, Koji; Yanaka, Akinori; Fujii, Hirofumi; Yoshimoto, Mitsuyoshi

2013-08-01

Lung cancer is one of the leading causes of cancer-related deaths worldwide, including Japan. Although computed tomography (CT) can detect small lung lesions such as those appearing as ground glass opacity, it cannot differentiate between malignant and non-malignant lesions. Previously, we have shown that single photon emission computed tomography (SPECT) imaging using (111)In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-cyclo-(Arg-Gly-Asp-D-Phe-Lys) (DOTA-c(RGDfK)), an imaging probe of αvβ3 integrin, is useful for the early detection of pancreatic cancer in a hamster pancreatic carcinogenesis model. In this study, we aimed to assess the usefulness of SPECT/CT with (111)In-DOTA-c(RGDfK) for the evaluation of the malignancy of lung cancer. Lung tumors were induced by a single intraperitoneal injection (250 mg/kg) of urethane in male A/J mice. Twenty-six weeks after the urethane treatment, SPECT was performed an hour after injection of (111)In-DOTA-c(RGDfK). Following this, the radioactivity ratios of tumor to normal lung tissue were measured by autoradiography (ARG) in the excised lung samples. We also examined the expression of αvβ3 integrin in mouse and human lung samples. Urethane treatment induced 5 hyperplasias, 41 adenomas and 12 adenocarcinomas in the lungs of 8 A/J mice. SPECT with (111)In-DOTA-c(RGDfK) could clearly visualize lung nodules, though we failed to detect small lung nodules like adenoma and hyperplasias (adenocarcinoma: 66.7%, adenoma: 33.6%, hyperplasia: 0.0%). ARG analysis revealed significant uptake of (111)In-DOTA-c(RGDfK) in all the lesions. Moreover, tumor to normal lung tissue ratios increased along with the progression of carcinogenesis. Histopathological examination using human lung tissue samples revealed clear up-regulation of αvβ3 integrin in well-differentiated adenocarcinoma (Noguchi type B and C) rather than atypical adenomatous hyperplasia. Although there are some limitations in evaluating the malignancy of

SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

International Nuclear Information System (INIS)

Yaparpalvi, R; Mynampati, D; Kuo, H; Garg, M; Tome, W; Kalnicki, S

2016-01-01

Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performed using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V_2_0 and V_5 to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm"3. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V_2_0 (+3.1%) and V_5 (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose overestimates attributable to algorithm

SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

Energy Technology Data Exchange (ETDEWEB)

Yaparpalvi, R; Mynampati, D; Kuo, H; Garg, M; Tome, W; Kalnicki, S [Montefiore Medical Center, Bronx, NY (United States)

2016-06-15

Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performed using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V{sub 20} and V{sub 5} to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm{sup 3}. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V{sub 20} (+3.1%) and V{sub 5} (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose overestimates

Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice

Science.gov (United States)

Chai, Y; Calaf, G M; Zhou, H; Ghandhi, S A; Elliston, C D; Wen, G; Nohmi, T; Amundson, S A; Hei, T K

2013-01-01

Background: Although radiation-induced bystander effects have been confirmed using a variety of endpoints, the mechanism(s) underlying these effects are not well understood, especially for in vivo study. Methods: A 1-cm2 area (1 cm × 1 cm) in the lower abdominal region of gpt delta transgenic mice was irradiated with 5 Gy of 300 keV X-rays, and changes in out-of-field lung and liver were observed. Results: Compared with sham-treated controls, the Spi− mutation frequency increased 2.4-fold in non-targeted lung tissues at 24 h after partial body irradiation (PBIR). Consistent with dramatic Cyclooxygenase 2 (COX-2) induction in the non-targeted bronchial epithelial cells, increasing levels of prostaglandin, together with 8-hydroxydeoxyguanosine, in the out-of-field lung tissues were observed after PBIR. In addition, DNA double-strand breaks and apoptosis were induced in bystander lung tissues after PBIR. Conclusion: The PBIR induces DNA damage and mutagenesis in non-targeted lung tissues, especially in bronchial epithelial cells, and COX-2 has an essential role in bystander mutagenesis. PMID:23321513

Critical transition in tissue homeostasis accompanies murine lung senescence.

Directory of Open Access Journals (Sweden)

Carla L Calvi

Full Text Available BACKGROUND: Respiratory dysfunction is a major contributor to morbidity and mortality in aged populations. The susceptibility to pulmonary insults is attributed to "low pulmonary reserve", ostensibly reflecting a combination of age-related musculoskeletal, immunologic and intrinsic pulmonary dysfunction. METHODS/PRINCIPAL FINDINGS: Using a murine model of the aging lung, senescent DBA/2 mice, we correlated a longitudinal survey of airspace size and injury measures with a transcriptome from the aging lung at 2, 4, 8, 12, 16 and 20 months of age. Morphometric analysis demonstrated a nonlinear pattern of airspace caliber enlargement with a critical transition occurring between 8 and 12 months of age marked by an initial increase in oxidative stress, cell death and elastase activation which is soon followed by inflammatory cell infiltration, immune complex deposition and the onset of airspace enlargement. The temporally correlative transcriptome showed exuberant induction of immunoglobulin genes coincident with airspace enlargement. Immunohistochemistry, ELISA analysis and flow cytometry demonstrated increased immunoglobulin deposition in the lung associated with a contemporaneous increase in activated B-cells expressing high levels of TLR4 (toll receptor 4 and CD86 and macrophages during midlife. These midlife changes culminate in progressive airspace enlargement during late life stages. CONCLUSION/SIGNIFICANCE: Our findings establish that a tissue-specific aging program is evident during a presenescent interval which involves early oxidative stress, cell death and elastase activation, followed by B lymphocyte and macrophage expansion/activation. This sequence heralds the progression to overt airspace enlargement in the aged lung. These signature events, during middle age, indicate that early stages of the aging immune system may have important correlates in the maintenance of tissue morphology. We further show that time-course analyses of aging

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)

Proteoglycan changes in the extracellular matrix of lung tissue from patients with pulmonary emphysema

NARCIS (Netherlands)

van Straaten, JFM; Coers, W; Noordhoek, JA; Flipsen, JTM; Kauffman, HF; Timens, W; Postma, DS

To characterize the changes in the extracellular matrix in smoking-related pulmonary emphysema, we undertook immunohistochemical studies in lung tissues from controls (n = 7), from patients with mild (n = 11) and severe (n = 8) emphysema, and from patients with lung fibrosis (n = 6). We studied

β class II tubulin predominates in normal and tumor breast tissues

International Nuclear Information System (INIS)

Dozier, James H; Hiser, Laree; Davis, Jennifer A; Thomas, Nancy Stubbs; Tucci, Michelle A; Benghuzzi, Hamed A; Frankfurter, Anthony; Correia, John J; Lobert, Sharon

2003-01-01

Antimitotic chemotherapeutic agents target tubulin, the major protein in mitotic spindles. Tubulin isotype composition is thought to be both diagnostic of tumor progression and a determinant of the cellular response to chemotherapy. This implies that there is a difference in isotype composition between normal and tumor tissues. To determine whether such a difference occurs in breast tissues, total tubulin was fractionated from lysates of paired normal and tumor breast tissues, and the amounts of β-tubulin classes I + IV, II, and III were measured by competitive enzyme-linked immunosorbent assay (ELISA). Only primary tumor tissues, before chemotherapy, were examined. Her2/neu protein amplification occurs in about 30% of breast tumors and is considered a marker for poor prognosis. To gain insight into whether tubulin isotype levels might be correlated with prognosis, ELISAs were used to quantify Her2/neu protein levels in these tissues. β-Tubulin isotype distributions in normal and tumor breast tissues were similar. The most abundant β-tubulin isotypes in these tissues were β-tubulin classes II and I + IV. Her2/neu levels in tumor tissues were 5–30-fold those in normal tissues, although there was no correlation between the Her2/neu biomarker and tubulin isotype levels. These results suggest that tubulin isotype levels, alone or in combination with Her2/neu protein levels, might not be diagnostic of tumorigenesis in breast cancer. However, the presence of a broad distribution of these tubulin isotypes (for example, 40–75% β-tubulin class II) in breast tissue, in conjunction with other factors, might still be relevant to disease progression and cellular response to antimitotic drugs

Iso-effect tables for tolerance of irradiated normal human tissues

International Nuclear Information System (INIS)

Cohen, L.; Creditor, M.

1983-01-01

Available literature on a radiation injury to human tissues (lung, brain, kidney and intestine) was surveyed. A parameter search program (RAD3) was used to derive best-fitting cell kinetic parameters, on the assumption that radiation injury arises from depletion of parenchymal cells in the irradiated organs. From these parameters iso-effect tables were constructed for a wide range of treatment schedules, including daily treatment as well as fractionation at longer intervals, for each tissue. The tables provide a set of limiting doses, above which the risk of radiation injury becomes substantial. Tolerance limits and dose-time-factors were substantially different in the four tissues. It is concluded that computed iso-effect tables provide a more reliable guide to treatment than conventional time-dose equations

Late effects of normal tissues (lent) scoring system: the soma scale

International Nuclear Information System (INIS)

Mornex, F.; Pavy, J.J.; Denekamp, J.

1997-01-01

Radiation tolerance of normal tissues remains the limiting factor for delivering tumoricidal dose. The late toxicity of normal tissues is the most critical element of an irradiation: somatic, functional and structural alterations occur during the actual treatment itself, but late effects manifest months to years after acute effects heal, and may progress with time. The optimal therapeutic ratio ultimately requires not only complete tumor clearance, but also minimal residual injury to surrounding vital normal tissues. The disparity between the intensity of acute and late effects and the inability to predict the eventual manifestation of late normal tissue injury has made radiation oncologists recognize the importance of careful patient follow-up. There is so far no uniform toxicity scoring system to compare several clinical studies in the absence of a 'common toxicity language'. This justifies the need to establish a precise evaluation system for the analysis of late effects of radiation on normal tissues. The SOMA/LENT scoring system results from an international collaboration. European Organization Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group (RTOG) have created subcommittees with the aim of addressing the question of standardized toxic effects criteria. This effort appeared as a necessity to standardize and improve the data recording, to then describe and evaluate uniform toxicity at regular time intervals. The current proposed scale is not yet validated, and should be used cautiously. (authors)

Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

Directory of Open Access Journals (Sweden)

Tozeren Aydin

2006-11-01

Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

The significance of PIWI family expression in human lung embryogenesis and non-small cell lung cancer.

Science.gov (United States)

Navarro, Alfons; Tejero, Rut; Viñolas, Nuria; Cordeiro, Anna; Marrades, Ramon M; Fuster, Dolors; Caritg, Oriol; Moises, Jorge; Muñoz, Carmen; Molins, Laureano; Ramirez, Josep; Monzo, Mariano

2015-10-13

The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recently believed to be limited to germinal stem cells. We have studied the expression of PIWI genes during human lung embryogenesis and in paired tumor and normal tissue prospectively collected from 71 resected non-small-cell lung cancer patients. The mRNA expression analysis showed that PIWIL1 was highly expressed in 7-week embryos and downregulated during the subsequent weeks of development. PIWIL1 was expressed in 11 of the tumor samples but in none of the normal tissue samples. These results were validated by immunohistochemistry, showing faint cytoplasmic reactivity in the PIWIL1-positive samples. Interestingly, the patients expressing PIWIL1 had a shorter time to relapse (TTR) (p = 0.006) and overall survival (OS) (p = 0.0076) than those without PIWIL1 expression. PIWIL2 and 4 were downregulated in tumor tissue in comparison to the normal tissue (p < 0.001) and the patients with lower levels of PIWIL4 had shorter TTR (p = 0.048) and OS (p = 0.033). In the multivariate analysis, PIWIL1 expression emerged as an independent prognostic marker. Using 5-Aza-dC treatment and bisulfite sequencing, we observed that PIWIL1 expression could be regulated in part by methylation. Finally, an in silico study identified a stem-cell expression signature associated with PIWIL1 expression.

Histological evaluation of lung cancer with T2-weighted magnetic resonance images

International Nuclear Information System (INIS)

Ohta, Takashi; Matsuura, Yoshifumi; Shioya, Sumie; Ohta, Yasuyo

1995-01-01

We investigated the differences in signal intensity of lung cancer tissue and non-cancerous lung tissues on T 2 -weighted magnetic resonance (MR) images. MR images were obtained from patients with squamous cell carcinoma (n=6), adenocarcinoma (n=5), small cell carcinoma (n=5), and large cell carcinoma (n=1). To compare the MR signal intensity between tissues, we calculated the signal intensity ratios for tumor/skeletal muscle and lung/skeletal muscle. The MR signal intensity for each tissue was measured with a densitometer and T 2 -weighted MR images with a similar window and a center. The value of the signal intensity ratio for squamous cell carcinoma (3.26±0.76) was greater than those for adenocarcinoma (1.99±0.50, p<0.05), small cell carcinoma (2.35±0.60), large cell carcinoma (2.46), and non-cancerous lung tissues (1.70±0.68, p<0.02). The values of the MR signal intensity ratio for non-cancerous lung tissues were 2.00 for a collapsed lung, 0.93 for a fibrotic lung, and 2.18 for a fibrotic lung with obstructive pneumonia. The results suggest that the MR signal intensity ratio for pathologic tissues/normal skeletal muscle can be a useful indicator for qualitative and quantitative MR imaging diagnosis. (author)

The expression of GST isoenzymes and p53 in non-small cell lung cancer.

Directory of Open Access Journals (Sweden)

MĂźzeyyen Ozhavzali

2010-06-01

Full Text Available This study investigated the immunohistochemical staining characteristics of glutathione-S-transferase alpha, pi, mu, theta and p53 in non-small cell lung carcinoma and normal lung tissue from 50 patients. The relationships between expressions of the Glutathione-S-transferase isoenzymes and some clinicopathological features were also examined. Expression of glutathione-S-transferase pi, mu, alpha, theta and p53 was assessed by immunohistochemistry for primary lung carcinomas of 50 patients from the Sanitarium Education and Research Hospital, Ankara lung cancer collection. The relationships between expression of the glutathione-S-transferase isoenzymes, p53 in normal and tumor tissue by Student T test and the clinicopathological data were also examined by Spearman Rank tests. When the normal and tumor tissue of these cases were compared according to their staining intensity and percentage of positive staining, glutathione-S-transferase alpha, pi, mu, theta expressions in tumor cells was significantly higher than normal cells (p<0.05. There was no significant difference in the expression of p53 between normal and tumor cells (p>0.05. When the immunohistochemical results of glutathione-S-transferase isoenzymes and p53 were correlated with the clinical parameters, there were no significant associations between glutathione-S-transferases and p53 expressions and tumor stage, tumor grade and smoking status (p>0.05.

Comparison of effective atomic numbers of the cancerous and normal kidney tissue

International Nuclear Information System (INIS)

Manjunatha, H.C.

2015-01-01

The effective atomic number (Z eff ) and electron density (N e ) of normal kidney and cancerous kidney have been computed for total and partial photon interactions by computing the molecular, atomic, and electronic cross section in the wide energy range of 1 keV-100 GeV using WinXCOM. The mean Z eff and N e of normal kidney and cancerous kidney in the various energy ranges and for total and partial photon interactions are tabulated. The variation of effective N e with energy is shown graphically for all photon interactions. In addition to this computer tomography (CT), numbers of normal kidney and cancerous kidney for photon interaction and energy absorption is also computed. The role of Z eff in the dual-energy dividing radiography is also discussed. The values of Z eff and N e for cancerous kidney are higher than normal kidney. This is due to the levels of elements K, Ca, Fe, Ni, and Se are lower and those of the elements Ti, Co, Zn, As, and Cd are higher in the cancer tissue of kidney than those observed in the normal tissue. The soft tissue and cancerous tissue are very similar, but their atomic number differs. The cancerous tissue exhibits a higher Z eff than the normal tissue. This fact helps in the dual-energy dividing radiography which enables to improve the diagnosis of the kidney cancer. Hence, the computed values may be useful in the diagnosis of the kidney cancer. CT numbers for normal kidney are higher than cancerous kidney. (author)

Intensity-Modulated Proton Therapy Further Reduces Normal Tissue Exposure During Definitive Therapy for Locally Advanced Distal Esophageal Tumors: A Dosimetric Study

Energy Technology Data Exchange (ETDEWEB)

Welsh, James, E-mail: jwelsh@mdanderson.org [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Gomez, Daniel; Palmer, Matthew B.; Riley, Beverly A.; Mayankkumar, Amin V.; Komaki, Ritsuko [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Dong, Lei; Zhu, X. Ronald [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Likhacheva, Anna; Liao, Zhongxing [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Cox, James D. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

2011-12-01

Purpose: We have previously found that {<=} 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Patients and Methods: Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Results: Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p < .0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p {<=} .0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p < .001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p {<=} .02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p < .0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p {<=} .005), heart (p {<=} .003), and liver (p {<=} .04). Conclusions: Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for

Response of rat lung tissue to short-term hyperoxia: a proteomic approach.

Science.gov (United States)

Spelten, Oliver; Wetsch, Wolfgang A; Wrettos, Georg; Kalenka, Armin; Hinkelbein, Jochen

2013-11-01

An inspiratory oxygen fraction of 1.0 is often required to avoid hypoxia both in many pre- and in-hospital situations. On the other hand, hyperoxia may lead to deleterious consequences (cell growth inhibition, inflammation, and apoptosis) for numerous tissues including the lung. Whereas clinical effects of hyperoxic lung injury are well known, its impact on the expression of lung proteins has not yet been evaluated sufficiently. The aim of this study was to analyze time-dependent alterations of protein expression in rat lung tissue after short-term normobaric hyperoxia (NH). After approval of the local ethics committee for animal research, N = 36 Wistar rats were randomized into six different groups: three groups with NH with exposure to 100 % oxygen for 3 h and three groups with normobaric normoxia (NN) with exposure to room air (21 % oxygen). After the end of the experiments, lungs were removed immediately (NH0 and NN0), after 3 days (NH3 and NN3) and after 7 days (NH7 and NN7). Lung lysates were analyzed by two-dimensional gel electrophoresis (2D-GE) followed by peptide mass fingerprinting using mass spectrometry. Statistical analysis was performed with Delta 2D (DECODON GmbH, Greifswald, Germany; ANOVA, Bonferroni correction, p pO2 was significantly higher in NH-groups compared to NN-groups (581 ± 28 vs. 98 ± 12 mmHg; p < 0.01), all other physiological parameters did not differ. Expression of 14 proteins were significantly altered: two proteins were up-regulated and 12 proteins were down-regulated. Even though NH was comparatively short termed, significant alterations in lung protein expression could be demonstrated up to 7 days after hyperoxia. The identified proteins indicate an association with cell growth inhibition, regulation of apoptosis, and approval of structural cell integrity.

CD4 T Cell Epitope Specificity and Cytokine Potential Are Preserved as Cells Transition from the Lung Vasculature to Lung Tissue following Influenza Virus Infection.

Science.gov (United States)

DiPiazza, Anthony; Laniewski, Nathan; Rattan, Ajitanuj; Topham, David J; Miller, Jim; Sant, Andrea J

2018-07-01

Pulmonary CD4 T cells are critical in respiratory virus control, both by delivering direct effector function and through coordinating responses of other immune cells. Recent studies have shown that following influenza virus infection, virus-specific CD4 T cells are partitioned between pulmonary vasculature and lung tissue. However, very little is known about the peptide specificity or functional differences of CD4 T cells within these two compartments. Using a mouse model of influenza virus infection in conjunction with intravascular labeling in vivo , the cell surface phenotype, epitope specificity, and functional potential of the endogenous polyclonal CD4 T cell response was examined by tracking nine independent CD4 T cell epitope specificities. These studies revealed that tissue-localized CD4 cells were globally distinct from vascular cells in expression of markers associated with transendothelial migration, residency, and micropositioning. Despite these differences, there was little evidence for remodeling of the viral epitope specificity or cytokine potential as cells transition from vasculature to the highly inflamed lung tissue. Our studies also distinguished cells in the pulmonary vasculature from peripheral circulating CD4 T cells, providing support for the concept that the pulmonary vasculature does not simply reflect circulating cells that are trapped within the narrow confines of capillary vessels but rather is enriched in transitional cells primed in the draining lymph node that have specialized potential to enter the lung tissue. IMPORTANCE CD4 T cells convey a multitude of functions in immunity to influenza, including those delivered in the lymph node and others conveyed by CD4 T cells that leave the lymph node, enter the blood, and extravasate into the lung tissue. Here, we show that the transition of recently primed CD4 cells detected in the lung vasculature undergo profound changes in expression of markers associated with tissue localization as

5-Aza-2'-deoxycytidine protects against emphysema in mice via suppressing p16Ink4a expression in lung tissue

Directory of Open Access Journals (Sweden)

He ZH

2017-10-01

Full Text Available Zhi-Hui He,1 Yan Chen,2 Ping Chen,2 Sheng-Dong He,2 Hui-Hui Zeng,2 Ji-Ru Ye,2 Da Liu,2 Jun Cao3 1Intensive Care Unit, 2Department of Respiratory Medicine, Second Xiangya Hospital, Central South University, Changsha, 3Department of Respiratory Medicine, Hunan Provincial People’s Hospital, Changsha, China Background: There is a growing realization that COPD, or at least emphysema, involves several processes presenting in aging and cellular senescence. Endothelial progenitor cells (EPCs contribute to neovascularization and play an important role in the development of COPD. The gene for p16Ink4a is a major dominant senescence one. The aim of the present study was to observe changes in lung function, histomorphology of lung tissue, and expression of p16Ink4a in lung tissue and bone marrow-derived EPCs in emphysematous mice induced by cigarette-smoke extract (CSE, and further to search for a potential candidate agent protecting against emphysema induced by CSE. Materials and methods: An animal emphysema model was induced by intraperitoneal injection of CSE. 5-Aza-2'-deoxycytidine (5-Aza-CdR was administered to the emphysematous mice. Lung function and histomorphology of lung tissue were measured. The p16Ink4a protein and mRNA in EPCs and lung tissues were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction, respectively. Results: CSE induced emphysema with increased p16Ink4a expression in lung tissue and bone marrow-derived EPCs. 5-Aza-CdR partly protected against emphysema, especially in the lung-morphology profile, and partly protest against the overexpression of p16Ink4a in EPCs and lung tissue induced by CSE. Conclusion: 5-Aza-CdR partly protected against emphysema in mice via suppressing p16Ink4a expression in EPCs and lung tissue. Keywords: 5-Aza-2'-deoxycytidine, cigarette smoke, emphysema, endothelial progenitor cells, p16Ink4a

Therapy-induced effects in normal tissue; Therapieinduzierte Effekte am Normalgewebe

Energy Technology Data Exchange (ETDEWEB)

Kaick, G. van; Delorme, S. [Deutsches Krebsforschungszentrum (DKFZ), Abteilung E010 - Radiologie, Heidelberg (Germany)

2008-09-15

More than 50% of cancer patients survive for more than 5 years, owing to modern and effective treatment. Therefore, long-term sequelae of treatment are more frequently seen than in the past. Such effects on normal tissue may both mimic and obscure tumor recurrences. Besides the direct consequences of surgery, tissue damage due to radiation or chemotherapy frequently cause problems in differential diagnosis. Among the numerous sequelae of radiotherapy, the most prominent are disturbance of the blood-brain barrier, radiation pneumonitis, osteodystrophy and osteoradionecrosis, fatty changes of bone marrow, or increased radiodensity of breast parenchyma. Chemotherapy may cause, e.g., diffuse abnormalities of white matter, pneumonitis and lung fibrosis, cardiomyopathy, or diffuse and patchy changes in bone marrow signals in MRI. The most devastating long-term complications are secondary cancers and leukemia induced by both radiotherapy and chemotherapy. (orig.) [German] Mehr als 50% der Tumorpatienten ueberleben dank moderner Therapie laenger als 5 Jahre, sodass die Spaetfolgen am gesunden Gewebe haeufiger und genauer erfasst werden. Diese koennen Tumorrezidive sowohl verschleiern als auch vortaeuschen. Neben den unmittelbaren Folgen operativer Eingriffe sind Auswirkungen der Chemo- und Strahlentherapie ein haeufiges differenzialdiagnostisches Problem. Wichtige Folgen einer Strahlentherapie sind z. B. Blut-Hirn-Schranken-Stoerungen, Strahlenpneumonitis, Osteodystrophie und -radionekrose, Verfettung des blutbildenden Knochenmarks oder Parenchymverdichtungen der Brust. Chemotherapie kann u. a. zur Leukenzephalopathie, Pneumonitis und Lungenfibrose, Kardiomyopathie sowie zu diffusen und fleckfoermigen Signalaenderungen des Knochenmarks in der MRT fuehren. Die schwerstwiegende Spaetkomplikation ist die Induktion solider Zweittumoren und Leukaemien sowohl nach Strahlen- als auch Chemotherapie. (orig.)

MRI characterization of brown adipose tissue in obese and normal-weight children

Energy Technology Data Exchange (ETDEWEB)

Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Schoeneman, Samantha E. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Zhang, Huiyuan [John H. Stroger, Jr. Hospital of Cook County, Collaborative Research Unit, Chicago, IL (United States); Kwon, Soyang [Ann and Robert H. Lurie Children' s Hospital of Chicago, Stanley Manne Children' s Research Institute, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States); Josefson, Jami L. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Endocrinology, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States)

2015-10-15

Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

MRI characterization of brown adipose tissue in obese and normal-weight children

International Nuclear Information System (INIS)

Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M.; Schoeneman, Samantha E.; Zhang, Huiyuan; Kwon, Soyang; Josefson, Jami L.

2015-01-01

Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

Radiosensitization effects of nicotinamide on malignant and normal mouse tissue

International Nuclear Information System (INIS)

Jonsson, G.G.; Kjellen, E.; Pero, R.W.; Cameron, R.

1985-01-01

Inhibitors of the chromatin-associated enzyme adenosine diphosphate ribosyltransferase have been found to inhibit DNA strand rejoining and to potentiate lethality of DNA-damaging agents both in vivo and in vitro. The authors have in this work examined the radiosensitizing potential of one such inhibitor, nicotinamide, on tumor tissue by using transplanted C3H mouse mammary adenocarcinomas and on normal tissue in a tail-stunting experiment using BALB/cA mice. The data indicate a radiosensitizing effect of nicotinamide on tumor cells as well as on normal tissue. The data indicate a possible role of adenosine diphosphate ribosyltransferase inhibitors as a sensitizing agent in the radiotherapy of malignant tumors

Distribution and mRNA Expression of BAMBI in Non-small-cell Lung Cancer

Directory of Open Access Journals (Sweden)

Shen MIAO

2009-03-01

Full Text Available Background and objective BAMBI structure is similar with that of the receptor Ⅰof TGF-β, it broadly participates in the control of TGF-β signaling. The aim of this study is to investigate the expression and its significance of BAMBI in non-small cell lung cancer (NSCLC and explore the relation between BAMBI and clinical and pathological factors of NSCLC. Methods Sixty-three cases with NSCLC and adjacent normal tissue specimens were used for immunohistochemical assay. Thirty-one fresh lung cancer tissue specimens and surrounding normal lung tissue specimens was preserved for RT-PCR in -70 ℃ after quick-frozen in liquid nitrogen immediately. Results The level of BAMBI mRNA in cancer tissues was higher than that in the corresponding adjacent tissues (0.358±0.135 vs 0.249±0.129, with the difference being statistically significant (P =0.003. BAMBI protein expressed mainly in the membrane and the cytoplasm close to the membrane, its expression in the cancer tissue was higher than that in the adjacent tissues, the difference was significant (P <0.01. Expression of BAMBI in the cancer tissue was higher than that in the adjacent tissues, and the expression of BAMBI in adenocarcinoma of lung is higher than that in squamous carcinoma. Conclusion The expressions of BAMBI significantly increase in NSCLC. It might be a common affair in carcinogenesis of NSCLC.

Scribble is required for normal epithelial cell–cell contacts and lumen morphogenesis in the mammalian lung

Science.gov (United States)

Yates, Laura L.; Schnatwinkel, Carsten; Hazelwood, Lee; Chessum, Lauren; Paudyal, Anju; Hilton, Helen; Romero, M. Rosario; Wilde, Jonathan; Bogani, Debora; Sanderson, Jeremy; Formstone, Caroline; Murdoch, Jennifer N.; Niswander, Lee A.; Greenfield, Andy; Dean, Charlotte H.

2013-01-01

During lung development, proper epithelial cell arrangements are critical for the formation of an arborized network of tubes. Each tube requires a lumen, the diameter of which must be tightly regulated to enable optimal lung function. Lung branching and lumen morphogenesis require close epithelial cell–cell contacts that are maintained as a result of adherens junctions, tight junctions and by intact apical–basal (A/B) polarity. However, the molecular mechanisms that maintain epithelial cohesion and lumen diameter in the mammalian lung are unknown. Here we show that Scribble, a protein implicated in planar cell polarity (PCP) signalling, is necessary for normal lung morphogenesis. Lungs of the Scrib mouse mutant Circletail (Crc) are abnormally shaped with fewer airways, and these airways often lack a visible, ‘open’ lumen. Mechanistically we show that Scrib genetically interacts with the core PCP gene Vangl2 in the developing lung and that the distribution of PCP pathway proteins and Rho mediated cytoskeletal modification is perturbed in ScribCrc/Crc lungs. However A/B polarity, which is disrupted in Drosophila Scrib mutants, is largely unaffected. Notably, we find that Scrib mediates functions not attributed to other PCP proteins in the lung. Specifically, Scrib localises to both adherens and tight junctions of lung epithelia and knockdown of Scrib in lung explants and organotypic cultures leads to reduced cohesion of lung epithelial cells. Live imaging of Scrib knockdown lungs shows that Scrib does not affect bud bifurcation, as previously shown for the PCP protein Celsr1, but is required to maintain epithelial cohesion. To understand the mechanism leading to reduced cell–cell association, we show that Scrib associates with β-catenin in embryonic lung and the sub-cellular distribution of adherens and tight junction proteins is perturbed in mutant lung epithelia. Our data reveal that Scrib is required for normal lung epithelial organisation and lumen

Influence of industrial dust of uranium ore on rats' lung tissue

International Nuclear Information System (INIS)

Jumasheva, R.T.

2010-01-01

Under the conditions of radiotoxic influence of uranium ore dust (UOD), the respiratory organs are the main system specifically responsible for adaptation to this factor. At the same time, there are not sufficient studies regarding the morphological aspects of structural lung distortions due to inhalational influence by UOD. To identify the nature of morphological changes in the animals' lung tissue at the cellular and subcellular levels under the influence of industrial dust of uranium ore in a dose of 50 MPC. Experimental studies were conducted on 80 white rats (tom) with a body mass of 120-180 g. The experimental animals were subjected to chronic inhalation of UOD in a dose of 50 MPC (107.75 mg/m 3 ). The animals that were kept in similar chambers but that were not exposed to UOD served as control animals. Material from the animals for research was withdrawn in 3, 7, 30 and 60 days after the beginning of the experiment. The animals were withdrawn from the experiment by decapitation after a brief ether anesthesia. The lung tissue was subjected to conventional histological processing. Sections were stained with haematoxylin and eosin according to van Gieson's method. For electronic microscopic examination the lung tissue slices were fixed and embedded by conventional methods. Obtained blocks were used to prepare ultrathin sections. An impact of UOD in a dose of 50 MPC was accompanied by the development of acute focal serous inflammation in the wall of the small bronchi and lung parenchyma in the early stages of the experiment (3-7 days), pneumonic foci of fibrosis, and the development of marked sclerotic changes in the peribronchial lymphoid tissue by the 30-th day. By the 60-th day, an increase of sclerotic changes in the bronchial wall accompanied by inhibition of the reaction on the part of interstitial macrophages and bronchus associated lymphoid tissue were reported. These indicate the intense course of the compensatory processes. Conducted electron

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

International Nuclear Information System (INIS)

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

2010-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Min Yugang; Santhanam, Anand; Ruddy, Bari H [University of Central Florida, FL (United States); Neelakkantan, Harini; Meeks, Sanford L [M D Anderson Cancer Center Orlando, FL (United States); Kupelian, Patrick A, E-mail: anand.santhanam@orlandohealth.co [Department of Radiation Oncology, University of California, Los Angeles, CA (United States)

2010-09-07

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

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

Science.gov (United States)

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

2010-09-07

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

Influence of Manufacturing Processes on the Performance of Phantom Lungs

International Nuclear Information System (INIS)

Traub, Richard J.

2008-01-01

Chest counting is an important tool for estimating the radiation dose to individuals who have inhaled radioactive materials. Chest counting systems are calibrated by counting the activity in the lungs of phantoms where the activity in the phantom lungs is known. In the United States a commonly used calibration phantom was developed at the Lawrence Livermore National Laboratory and is referred to as the Livermore Torso Phantom. An important feature of this phantom is that the phantom lungs can be interchanged so that the counting system can be challenged by different combinations of radionuclides and activity. Phantom lungs are made from lung tissue substitutes whose constituents are foaming plastics and various adjuvants selected to make the lung tissue substitute similar to normal healthy lung tissue. Some of the properties of phantom lungs cannot be readily controlled by phantom lung manufacturers. Some, such as density, are a complex function of the manufacturing process, while others, such as elemental composition of the bulk plastic are controlled by the plastics manufacturer without input, or knowledge of the phantom manufacturer. Despite the fact that some of these items cannot be controlled, they can be measured and accounted for. This report describes how manufacturing processes can influence the performance of phantom lungs. It is proposed that a metric that describes the brightness of the lung be employed by the phantom lung manufacturer to determine how well the phantom lung approximates the characteristics of a human lung. For many purposes, the linear attenuation of the lung tissue substitute is an appropriate surrogate for the brightness

Preliminary Examination of X-ray Scattering from Human Tissues

International Nuclear Information System (INIS)

Desouky, O.S.; Wilkinson, S.; Hall, C.; Rogers, K.; Round, A.

2008-01-01

Small Angle x-ray scattering (SAXS) and wide angle x-ray scattering (WAXS) patterns have been recorded from different human soft tissues using x-ray synchrotron radiation.Pathological breast, normal kidney and lung tissues show SAXS peaks at q-values equal to 0.291 nm -1 and 0.481 nm -1 (d 21.6 nm and d =13. nm) which are the 3 r d and 5 t h order of the well known axial D-spacing of collagen fibrils. The diffraction is particularly intense in the meridional direction indicating some febrile alignment. In contrast, the normal tissue of brain, liver and heart shows diffuse scatter.The wide-angle coherent scattering from normal human tissues of brain, liver, heart, lung, and kidney is typical of that for amorphous materials. The scatter of the healthy adipose breast tissue shows a sharp peak at momentum transfer 1.24 nm -1 (d= 0.417 nm). The data of the other tissues appears to consist of a broad scattering peak. The two scattering regimes succeed in differentiating between the two major components of breast tissue, collagen and adipose tissue. The results of this study suggest that the soft tissues may have scattering patterns that are characteristics for the particular tissue types and tissue disease state. These results indicate that it may be possible use the coherent scattering as a diagnostic tool

Fetal lung development on MRI. Normal course and impairment due to premature rupture of membranes

International Nuclear Information System (INIS)

Kasprian, G.; Zentrum fuer Anatomie und Zellbiologie der Medizinischen Universitaet Wien; Brugger, P.C.; Helmer, H.; Langer, M.; Balassy, C.; Prayer, D.

2006-01-01

A well-organized interplay between many molecular factors as well as mechanical forces influence fetal lung development. At the end of this complex process a sufficiently sized and structurally mature organ should ensure the postnatal survival of the newborn. Besides prenatal ultrasonography, magnetic resonance imaging (MRI) can now be used to investigate normal and pathological human lung growth in utero. Oligohydramnios, due to premature rupture of membranes (PROM), is an important risk factor for compromised fetal lung growth. In these situations MR volumetry can be used to measure the size of the fetal lung quite accurately. Together with the evaluation of lung signal intensities on T2-weighted sequences, fetuses with pulmonary hypoplasia can be readily detected. (orig.) [de

Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

International Nuclear Information System (INIS)

Bentzen, Soeren M.

1997-01-01

A critical appraisal is given of the possible benefit from a reliable pre-treatment knowledge of individual normal-tissue sensitivity to radiotherapy. The considerations are in part, but not exclusively, based on the recent experience with in vitro colony-forming assays of the surviving fraction at 2 Gy, the SF 2 . Three strategies are reviewed: (1) to screen for rare cases with extreme radiosensitivity, so-called over-reactors, and treat these with reduced total dose, (2) to identify the sensitive tail of the distribution of 'normal' radiosensitivities, refer these patients to other treatment, and to escalate the dose to the remaining patients, or (3) to individualize dose prescriptions based on individual radiosensitivity, i.e. treating to isoeffect rather than to a specific dose-fractionation schedule. It is shown that these strategies will have a small, if any, impact on routine radiotherapy. Screening for over-reactors is hampered by the low prevalence of these among otherwise un-selected patients that leads to a low positive predictive value of in vitro radiosensitivity assays. It is argued, that this problem may persist even if the noise on current assays could be reduced to (the unrealistic value of) zero, simply because of the large biological variation in SF 2 . Removing the sensitive tail of the patient population, will only have a minor effect on the dose that could be delivered to the remaining patients, because of the sigmoid shape of empirical dose-response relationships. Finally, individualizing dose prescriptions based exclusively on information from a normal-tissue radiosensitivity assay, leads to a nearly symmetrical distribution of dose-changes that would produce a very small gain, or even a loss, of tumor control probability if implemented in the clinic. From a theoretical point of view, other strategies could be devised and some of these are considered in this review. Right now the most promising clinical use of in vitro radiosensitivity

Transpulmonary pressures and lung mechanics with glossopharyngeal insufflation and exsufflation beyond normal lung volumes in competitive breath-hold divers.

Science.gov (United States)

Loring, Stephen H; O'Donnell, Carl R; Butler, James P; Lindholm, Peter; Jacobson, Francine; Ferrigno, Massimo

2007-03-01

Throughout life, most mammals breathe between maximal and minimal lung volumes determined by respiratory mechanics and muscle strength. In contrast, competitive breath-hold divers exceed these limits when they employ glossopharyngeal insufflation (GI) before a dive to increase lung gas volume (providing additional oxygen and intrapulmonary gas to prevent dangerous chest compression at depths recently greater than 100 m) and glossopharyngeal exsufflation (GE) during descent to draw air from compressed lungs into the pharynx for middle ear pressure equalization. To explore the mechanical effects of these maneuvers on the respiratory system, we measured lung volumes by helium dilution with spirometry and computed tomography and estimated transpulmonary pressures using an esophageal balloon after GI and GE in four competitive breath-hold divers. Maximal lung volume was increased after GI by 0.13-2.84 liters, resulting in volumes 1.5-7.9 SD above predicted values. The amount of gas in the lungs after GI increased by 0.59-4.16 liters, largely due to elevated intrapulmonary pressures of 52-109 cmH(2)O. The transpulmonary pressures increased after GI to values ranging from 43 to 80 cmH(2)O, 1.6-2.9 times the expected values at total lung capacity. After GE, lung volumes were reduced by 0.09-0.44 liters, and the corresponding transpulmonary pressures decreased to -15 to -31 cmH(2)O, suggesting closure of intrapulmonary airways. We conclude that the lungs of some healthy individuals are able to withstand repeated inflation to transpulmonary pressures far greater than those to which they would normally be exposed.

Differential N-glycan patterns identified in lung adenocarcinoma by N-glycan profiling of formalin-fixed paraffin-embedded (FFPE) tissue sections.

Science.gov (United States)

Wang, Xiaoning; Deng, Zaian; Huang, Chuncui; Zhu, Tong; Lou, Jiatao; Wang, Lin; Li, Yan

2018-02-10

N-glycan profiling is a powerful approach for analyzing the functional relationship between N-glycosylation and cancer. Current methods rely on either serum or fresh tissue samples; however, N-glycan patterns may differ between serum and tissue, as the proteins of serum originate from a variety of tissues. Furthermore, fresh tissue samples are difficult to ship and store. Here, we used a profiling method based on formalin-fixed paraffin-embedded (FFPE) tissue sections from lung adenocarcinoma patients. We found that our method was highly reproducible. We identified 58 N-glycan compositions from lung adenocarcinoma FFPE samples, 51 of which were further used for MS n -based structure prediction. We show that high mannose type N-glycans are upregulated, while sialylated N-glycans are downregulated in our FFPE lung adenocarcinoma samples, compared to the control samples. Our receiver operating characteristic (ROC) curve analysis shows that high mannose type and sialylated N-glycans are useful discriminators to distinguish between lung adenocarcinoma and control tissue. Together, our results indicate that expression levels of specific N-glycans correlate well with lung adenocarcinoma, and strongly suggest that our FFPE-based method will be useful for N-glycan profiling of cancer tissues. Glycosylation is one of the most important post-translational protein modifications, and is associated with several physiopathological processes, including carcinogenesis. In this study, we tested the feasibility of using formalin-fixed paraffin-embedded (FFPE) tissue sections to identify changes in N-glycan patterns and identified the differentially expressed N-glycans of lung adenocarcinoma. Our study shows that the FFPE-based N-glycan profiling method is useful for clinical diagnosis as well as identification of potential biomarkers, and our data expand current knowledge of differential N-glycan patterns of lung adenocarcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Methodologies and tools for proton beam design for lung tumors

International Nuclear Information System (INIS)

Moyers, Michael F.; Miller, Daniel W.; Bush, David A.; Slater, Jerry D.

2001-01-01

Purpose: Proton beams can potentially increase the dose delivered to lung tumors without increasing the dose to critical normal tissues because protons can be stopped before encountering the normal tissues. This potential can only be realized if tissue motion and planning uncertainties are correctly included during planning. This study evaluated several planning strategies to determine which method best provides adequate tumor coverage, minimal normal tissue irradiation, and simplicity of use. Methods and Materials: Proton beam treatment plans were generated using one or more of three different planning strategies. These strategies included designing apertures and boluses to the PTV, apertures to the PTV and boluses to the CTV, and aperture and bolus to the CTV. Results: The planning target volume as specified in ICRU Report 50 can be used only to design the lateral margins of beams, because the distal and proximal margins resulting from CT number uncertainty, beam range uncertainty, tissue motions, and setup uncertainties, are different than the lateral margins resulting from these same factors. The best strategy for target coverage with the planning tools available overirradiated some normal tissues unnecessarily. The available tools also made the planning of lung tumors difficult. Conclusions: This study demonstrated that inclusion of target motion and setup uncertainties into a plan should be performed in the beam design step instead of creating new targets. New computerized treatment planning system tools suggested by this study will ease planning, facilitate abandonment of the PTV concept, improve conformance of the dose distribution to the target, and improve conformal avoidance of critical normal tissues

4-D segmentation and normalization of 3He MR images for intrasubject assessment of ventilated lung volumes

Science.gov (United States)

Contrella, Benjamin; Tustison, Nicholas J.; Altes, Talissa A.; Avants, Brian B.; Mugler, John P., III; de Lange, Eduard E.

2012-03-01

Although 3He MRI permits compelling visualization of the pulmonary air spaces, quantitation of absolute ventilation is difficult due to confounds such as field inhomogeneity and relative intensity differences between image acquisition; the latter complicating longitudinal investigations of ventilation variation with respiratory alterations. To address these potential difficulties, we present a 4-D segmentation and normalization approach for intra-subject quantitative analysis of lung hyperpolarized 3He MRI. After normalization, which combines bias correction and relative intensity scaling between longitudinal data, partitioning of the lung volume time series is performed by iterating between modeling of the combined intensity histogram as a Gaussian mixture model and modulating the spatial heterogeneity tissue class assignments through Markov random field modeling. Evaluation of the algorithm was retrospectively applied to a cohort of 10 asthmatics between 19-25 years old in which spirometry and 3He MR ventilation images were acquired both before and after respiratory exacerbation by a bronchoconstricting agent (methacholine). Acquisition was repeated under the same conditions from 7 to 467 days (mean +/- standard deviation: 185 +/- 37.2) later. Several techniques were evaluated for matching intensities between the pre and post-methacholine images with the 95th percentile value histogram matching demonstrating superior correlations with spirometry measures. Subsequent analysis evaluated segmentation parameters for assessing ventilation change in this cohort. Current findings also support previous research that areas of poor ventilation in response to bronchoconstriction are relatively consistent over time.

Identification of Gene Biomarkers for Distinguishing Small-Cell Lung Cancer from Non-Small-Cell Lung Cancer Using a Network-Based Approach

Directory of Open Access Journals (Sweden)

Fei Long

2015-01-01

Full Text Available Lung cancer consists of two main subtypes: small-cell lung cancer (SCLC and non-small-cell lung cancer (NSCLC that are classified according to their physiological phenotypes. In this study, we have developed a network-based approach to identify molecular biomarkers that can distinguish SCLC from NSCLC. By identifying positive and negative coexpression gene pairs in normal lung tissues, SCLC, or NSCLC samples and using functional association information from the STRING network, we first construct a lung cancer-specific gene association network. From the network, we obtain gene modules in which genes are highly functionally associated with each other and are either positively or negatively coexpressed in the three conditions. Then, we identify gene modules that not only are differentially expressed between cancer and normal samples, but also show distinctive expression patterns between SCLC and NSCLC. Finally, we select genes inside those modules with discriminating coexpression patterns between the two lung cancer subtypes and predict them as candidate biomarkers that are of diagnostic use.

Exploiting unsupervised and supervised classification for segmentation of the pathological lung in CT

International Nuclear Information System (INIS)

Korfiatis, P; Costaridou, L; Kalogeropoulou, C; Petsas, T; Daoussis, D; Adonopoulos, A

2009-01-01

Delineation of lung fields in presence of diffuse lung diseases (DLPDs), such as interstitial pneumonias (IP), challenges segmentation algorithms. To deal with IP patterns affecting the lung border an automated image texture classification scheme is proposed. The proposed segmentation scheme is based on supervised texture classification between lung tissue (normal and abnormal) and surrounding tissue (pleura and thoracic wall) in the lung border region. This region is coarsely defined around an initial estimate of lung border, provided by means of Markov Radom Field modeling and morphological operations. Subsequently, a support vector machine classifier was trained to distinguish between the above two classes of tissue, using textural feature of gray scale and wavelet domains. 17 patients diagnosed with IP, secondary to connective tissue diseases were examined. Segmentation performance in terms of overlap was 0.924±0.021, and for shape differentiation mean, rms and maximum distance were 1.663±0.816, 2.334±1.574 and 8.0515±6.549 mm, respectively. An accurate, automated scheme is proposed for segmenting abnormal lung fields in HRC affected by IP

Exploiting unsupervised and supervised classification for segmentation of the pathological lung in CT

Science.gov (United States)

Korfiatis, P.; Kalogeropoulou, C.; Daoussis, D.; Petsas, T.; Adonopoulos, A.; Costaridou, L.

2009-07-01

Delineation of lung fields in presence of diffuse lung diseases (DLPDs), such as interstitial pneumonias (IP), challenges segmentation algorithms. To deal with IP patterns affecting the lung border an automated image texture classification scheme is proposed. The proposed segmentation scheme is based on supervised texture classification between lung tissue (normal and abnormal) and surrounding tissue (pleura and thoracic wall) in the lung border region. This region is coarsely defined around an initial estimate of lung border, provided by means of Markov Radom Field modeling and morphological operations. Subsequently, a support vector machine classifier was trained to distinguish between the above two classes of tissue, using textural feature of gray scale and wavelet domains. 17 patients diagnosed with IP, secondary to connective tissue diseases were examined. Segmentation performance in terms of overlap was 0.924±0.021, and for shape differentiation mean, rms and maximum distance were 1.663±0.816, 2.334±1.574 and 8.0515±6.549 mm, respectively. An accurate, automated scheme is proposed for segmenting abnormal lung fields in HRC affected by IP

Decellularized Rat Lung Scaffolds Using Sodium Lauryl Ether Sulfate for Tissue Engineering.

Science.gov (United States)

Ma, Jinhui; Ju, Zhihai; Yu, Jie; Qiao, Yeru; Hou, Chenwei; Wang, Chen; Hei, Feilong

Perfusion decellularization with detergents is effective to maintain the architecture and proteins of extracellular matrix (ECM) for use in the field of lung tissue engineering (LTE). However, it is unclear which detergent is ideal to produce an acellular lung scaffold. In this study, we obtained two decellularized rat lung scaffolds using a novel detergent sodium lauryl ether sulfate (SLES) and a conventional detergent sodium dodecyl sulfate (SDS). Both decellularized lung scaffolds were assessed by histology, immunohistochemistry, scanning electron microscopy, DNA quantification, sulfated glycosaminoglycans (GAGs) quantification and western blot. Subsequently, the scaffolds were implanted subcutaneously in rats for 6 weeks and were evaluated via hematoxylin and eosin staining and Masson staining. Results indicated that SLES was effective to remove cells; moreover, lungs decellularized with SLES showed better preservation of sulfated GAGs, lung architecture, and ECM proteins than SDS. After 6 weeks, SLES scaffolds demonstrated a significantly greater potential for cell infiltration and blood vessel formation compared with SDS scaffolds. Taken together, we conclude that SLES is a promising detergent to produce an acellular scaffold using LTE for eventual transplantation.

Injurious mechanical ventilation in the normal lung causes a progressive pathologic change in dynamic alveolar mechanics

OpenAIRE

Pavone, Lucio A; Albert, Scott; Carney, David; Gatto, Louis A; Halter, Jeffrey M; Nieman, Gary F

2007-01-01

Introduction Acute respiratory distress syndrome causes a heterogeneous lung injury, and without protective mechanical ventilation a secondary ventilator-induced lung injury can occur. To ventilate noncompliant lung regions, high inflation pressures are required to 'pop open' the injured alveoli. The temporal impact, however, of these elevated pressures on normal alveolar mechanics (that is, the dynamic change in alveolar size and shape during ventilation) is unknown. In the present study we ...

Synthetic Secoisolariciresinol Diglucoside (LGM2605 Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage

Directory of Open Access Journals (Sweden)

Anastasia Velalopoulou

2017-11-01

Full Text Available Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS, pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung.

Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon

International Nuclear Information System (INIS)

Shapiro, S.D.; Endicott, S.K.; Province, M.A.; Pierce, J.A.; Campbell, E.J.

1991-01-01

Normal structure and function of the lung parenchyma depend upon elastic fibers. Amorphous elastin is biochemically stable in vitro, and may provide a metabolically stable structural framework for the lung parenchyma. To test the metabolic stability of elastin in the normal human lung parenchyma, we have (a) estimated the time elapsed since the synthesis of the protein through measurement of aspartic acid racemization and (b) modeled the elastin turnover through measurement of the prevalence of nuclear weapons-related 14 C. Elastin purified by a new technique from normal lung parenchyma was hydrolyzed; then the prevalences of D-aspartate and 14 C were measured by gas chromatography and accelerator-mass spectrometry, respectively. D-aspartate increased linearly with age; Kasp (1.76 x 10 - 3 yr - 1 ) was similar to that previously found for extraordinarily stable human tissues, indicating that the age of lung parenchymal elastin corresponded with the age of the subject. Radiocarbon prevalence data also were consistent with extraordinary metabolic stability of elastin; the calculated mean carbon residence time in elastin was 74 yr (95% confidence limits, 40-174 yr). These results indicate that airspace enlargement characteristic of 'aging lung' is not associated with appreciable new synthesis of lung parenchymal elastin. The present study provides the first tissue-specific evaluation of turnover of an extracellular matrix component in humans and underscores the potential importance of elastin for maintenance of normal lung structure. Most importantly, the present work provides a foundation for strategies to directly evaluate extracellular matrix injury and repair in diseases of lung (especially pulmonary emphysema), vascular tissue, and skin

Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

DEFF Research Database (Denmark)

Skjøt-Arkil, Helene; Clausen, Rikke E; Nguyen, Quoc Hai Trieu

2012-01-01

Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part...... are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases....

MMP-10 Is Overexpressed, Proteolytically Active, and a Potential Target for Therapeutic Intervention in Human Lung Carcinomas

Directory of Open Access Journals (Sweden)

Jason H. Gill

2004-11-01

Full Text Available Matrix metalloproteinase (MMP-mediated degradation of the extracellular matrix is a major factor for tumor development and expansion. This study analysed MMP-10 protein expression and activity in human lung tumors of various grade, stage, and type to address the relationship between MMP-10 and tumor characteristics and to evaluate MMP-10 as a therapeutic target in non small cell lung carcinoma (NSCLC. Unlike the majority of MMPs, MMP-10 was located in the tumor mass as opposed to tumor stroma. MMP-10 protein was observed at low levels in normal human lung tissues and at significantly higher levels in all types of NSCLC. No correlation was observed between MMP-10 protein expression and tumor type, stage, or lymph node invasion. To discriminate between active and inactive forms of MMP-10 in samples of human NSCLC, we have developed an ex vivo fluorescent assay. Measurable MMP-10 activity was detected in 42 of 50 specimens of lung cancer and only 2 of 10 specimens of histologically normal lung tissue. No relationship was observed between MMP-10 activity levels and clinicopathologic characteristics. Our results suggest that MMP-10 is expressed and active at high levels in human NSCLC compared to normal lung tissues, and, as such, is a potential target for the development of novel therapeutics for lung cancer treatment.

β2-Microglobulin participates in development of lung emphysema by inducing lung epithelial cell senescence.

Science.gov (United States)

Gao, Na; Wang, Ying; Zheng, Chun-Ming; Gao, Yan-Li; Li, Hui; Li, Yan; Fu, Ting-Ting; Xu, Li-Li; Wang, Wei; Ying, Sun; Huang, Kewu

2017-05-01

β 2 -Microglobulin (β 2 M), the light chain of the major histocompatibility complex class I (MHC I), has been identified as a proaging factor and is involved in the pathogenesis of neurodegenerative disorders by driving cognitive and regenerative impairments. However, little attention has focused on the effect of β 2 M in the development of lung emphysema. Here, we found that concentrations of β 2 M in plasma were significantly elevated in patients with lung emphysema than those in normal control subjects (1.89 ± 0.12 vs. 1.42 ± 0.06 mg/l, P lung tissue of emphysema (39.90 ± 1.97 vs. 23.94 ± 2.11%, P lung emphysema through induction of lung epithelial cell senescence and inhibition. Copyright © 2017 the American Physiological Society.

Clinical significance of preoperative serum albumin level for prognosis in surgically resected patients with non-small cell lung cancer: Comparative study of normal lung, emphysema, and pulmonary fibrosis.

Science.gov (United States)

Miura, Kentaro; Hamanaka, Kazutoshi; Koizumi, Tomonobu; Kitaguchi, Yoshiaki; Terada, Yukihiro; Nakamura, Daisuke; Kumeda, Hirotaka; Agatsuma, Hiroyuki; Hyogotani, Akira; Kawakami, Satoshi; Yoshizawa, Akihiko; Asaka, Shiho; Ito, Ken-Ichi

2017-09-01

This study was performed to clarify whether preoperative serum albumin level is related to the prognosis of non-small cell lung cancer patients undergoing surgical resection, and the relationships between serum albumin level and clinicopathological characteristics of lung cancer patients with emphysema or pulmonary fibrosis. We retrospectively evaluated 556 patients that underwent surgical resection for non-small cell lung cancer. The correlation between preoperative serum albumin level and survival was evaluated. Patients were divided into three groups according to the findings on chest high-resolution computed tomography (normal lung, emphysema, and pulmonary fibrosis), and the relationships between serum albumin level and clinicopathological characteristics, including prognosis, were evaluated. The cut-off value of serum albumin level was set at 4.2g/dL. Patients with low albumin levels (albumin emphysema group (n=48) and pulmonary fibrosis group (n=45) were significantly lower than that in the normal lung group (n=463) (p=0.009 and pulmonary fibrosis groups, but not in the emphysema group. Preoperative serum albumin level was an important prognostic factor for overall survival and recurrence-free survival in patients with resected non-small cell lung cancer. Divided into normal lung, emphysema, and pulmonary fibrosis groups, serum albumin level showed no influence only in patients in the emphysema group. Copyright © 2017 Elsevier B.V. All rights reserved.

A Protocol for the Comprehensive Flow Cytometric Analysis of Immune Cells in Normal and Inflamed Murine Non-Lymphoid Tissues

Science.gov (United States)

Yu, Yen-Rei A.; O’Koren, Emily G.; Hotten, Danielle F.; Kan, Matthew J.; Kopin, David; Nelson, Erik R.; Que, Loretta; Gunn, Michael D.

2016-01-01

Flow cytometry is used extensively to examine immune cells in non-lymphoid tissues. However, a method of flow cytometric analysis that is both comprehensive and widely applicable has not been described. We developed a protocol for the flow cytometric analysis of non-lymphoid tissues, including methods of tissue preparation, a 10-fluorochrome panel for cell staining, and a standardized gating strategy, that allows the simultaneous identification and quantification of all major immune cell types in a variety of normal and inflamed non-lymphoid tissues. We demonstrate that our basic protocol minimizes cell loss, reliably distinguishes macrophages from dendritic cells (DC), and identifies all major granulocytic and mononuclear phagocytic cell types. This protocol is able to accurately quantify 11 distinct immune cell types, including T cells, B cells, NK cells, neutrophils, eosinophils, inflammatory monocytes, resident monocytes, alveolar macrophages, resident/interstitial macrophages, CD11b- DC, and CD11b+ DC, in normal lung, heart, liver, kidney, intestine, skin, eyes, and mammary gland. We also characterized the expression patterns of several commonly used myeloid and macrophage markers. This basic protocol can be expanded to identify additional cell types such as mast cells, basophils, and plasmacytoid DC, or perform detailed phenotyping of specific cell types. In examining models of primary and metastatic mammary tumors, this protocol allowed the identification of several distinct tumor associated macrophage phenotypes, the appearance of which was highly specific to individual tumor cell lines. This protocol provides a valuable tool to examine immune cell repertoires and follow immune responses in a wide variety of tissues and experimental conditions. PMID:26938654

Real-time soft tissue motion estimation for lung tumors during radiotherapy delivery.

Science.gov (United States)

Rottmann, Joerg; Keall, Paul; Berbeco, Ross

2013-09-01

To provide real-time lung tumor motion estimation during radiotherapy treatment delivery without the need for implanted fiducial markers or additional imaging dose to the patient. 2D radiographs from the therapy beam's-eye-view (BEV) perspective are captured at a frame rate of 12.8 Hz with a frame grabber allowing direct RAM access to the image buffer. An in-house developed real-time soft tissue localization algorithm is utilized to calculate soft tissue displacement from these images in real-time. The system is tested with a Varian TX linear accelerator and an AS-1000 amorphous silicon electronic portal imaging device operating at a resolution of 512 × 384 pixels. The accuracy of the motion estimation is verified with a dynamic motion phantom. Clinical accuracy was tested on lung SBRT images acquired at 2 fps. Real-time lung tumor motion estimation from BEV images without fiducial markers is successfully demonstrated. For the phantom study, a mean tracking error real-time markerless lung tumor motion estimation from BEV images alone. The described system can operate at a frame rate of 12.8 Hz and does not require prior knowledge to establish traceable landmarks for tracking on the fly. The authors show that the geometric accuracy is similar to (or better than) previously published markerless algorithms not operating in real-time.

Longitudinal micro-CT as an outcome measure of interstitial lung disease in TNF-transgenic mice.

Directory of Open Access Journals (Sweden)

Richard D Bell

Full Text Available Rheumatoid arthritis associated interstitial lung disease (RA-ILD is a debilitating condition with poor survival prognosis. High resolution computed tomography (CT is a common clinical tool to diagnose RA-ILD, and is increasingly being adopted in pre-clinical studies. However, murine models recapitulating RA-ILD are lacking, and CT outcomes for inflammatory lung disease have yet to be formally validated. To address this, we validate μCT outcomes for ILD in the tumor necrosis factor transgenic (TNF-Tg mouse model of RA.Cross sectional μCT was performed on cohorts of male TNF-Tg mice and their WT littermates at 3, 4, 5.5 and 12 months of age (n = 4-6. Lung μCT outcomes measures were determined by segmentation of the μCT datasets to generate Aerated and Tissue volumes. After each scan, lungs were obtained for histopathology and 3 sections stained with hematoxylin and eosin. Automated histomorphometry was performed to quantify the tissue area (nuclei, cytoplasm, and extracellular matrix and aerated area (white space within the tissue sections. Spearman's correlation coefficients were used to evaluate the extent of association between μCT imaging and histopathology endpoints.TNF-Tg mice had significantly greater tissue volume, total lung volume and mean intensity at all timepoints compared to age matched WT littermates. Histomorphometry also demonstrated a significant increase in tissue area at 3, 4, and 5.5 months of age in TNF-Tg mice. Lung tissue volume was correlated with lung tissue area (ρ = 0.81, p<0.0001, and normalize lung aerated volume was correlated with normalized lung air area (ρ = 0.73, p<0.0001.We have validated in vivo μCT as a quantitative biomarker of ILD in mice. Further, development of longitudinal measures is critical for dissecting pathologic progression of ILD, and μCT is a useful non-invasive method to study lung inflammation in the TNF-Tg mouse model.

Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

Science.gov (United States)

Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

2014-04-16

The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

Normal tissue complication probability (NTCP), the clinician,s perspective

International Nuclear Information System (INIS)

Yeoh, E.K.

2011-01-01

Full text: 3D radiation treatment planning has enabled dose distributions to be related to the volume of normal tissues irradiated. The dose volume histograms thus derived have been utilized to set NTCP dose constraints to facilitate optimization of treatment planning. However, it is not widely appreciated that a number of important variables other than DYH's which determine NTCP in the individual patient. These variables will be discussed under the headings of patient and treatment related as well as tumour related factors. Patient related factors include age, co-morbidities such as connective tissue disease and diabetes mellitus, previous tissue/organ damage, tissue architectural organization (parallel or serial), regional tissue/organ and individual tissue/organ radiosensitivities as well as the development of severe acute toxicity. Treatment related variables which need to be considered include dose per fraction (if not the conventional 1.8012.00 Gy/fraction, particularly for IMRT), number of fractions and total dose, dose rate (particularly if combined with brachytherapy) and concurrent chemotherapy or other biological dose modifiers. Tumour related factors which impact on NTCP include infiltration of normal tissue/organ usually at presentation leading to compromised function but also with recurrent disease after radiation therapy as well as variable tumour radiosensitivities between and within tumour types. Whilst evaluation of DYH data is a useful guide in the choice of treatment plan, the current state of knowledge requires the clinician to make an educated judgement based on a consideration of the other factors.

Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

Science.gov (United States)

Li, Li; Xie, Wengming; Li, Hui

2012-12-01

The thyroid is one of the main endocrine glands of human body, which plays a crucial role in the body's metabolism. Thyroid cancer mortality ranks only second to ovarian cancer in endocrine cancer. Routine diagnostic methods of thyroid diseases in present clinic exist misdiagnosis and missed diagnosis to varying degrees. Those lead to miss the best period of cancer treatment--early. Photoacoustic spectroscopy technology is a new tool, which provides an effective and noninvasive way for biomedical materials research, being highly sensitive and without sample pretreatment. In this paper, we use photoacoustic spectroscopy technology (PAST) to detect the absorption spectrum between normal and malignant thyroid tissues. The result shows that the photoacoustic spectroscopy technology (PAST) could differentiate malignant thyroid tissue from normal thyroid tissue very well. This technique combined with routine diagnostic methods has the potential to increase the diagnostic accuracy in clinical thyroid cancer diagnosis.

Investigating the bioavailability of graphene quantum dots in lung tissues via Fourier transform infrared spectroscopy.

Science.gov (United States)

Tabish, Tanveer A; Lin, Liangxu; Ali, Muhammad; Jabeen, Farhat; Ali, Muhammad; Iqbal, Rehana; Horsell, David W; Winyard, Paul G; Zhang, Shaowei

2018-06-06

Biomolecular fractions affect the fate and behaviour of quantum dots (QDs) in living systems but how the interactions between biomolecules and QDs affect the bioavailability of QDs is a major knowledge gap in risk assessment analysis. The transport of QDs after release into a living organism is a complex process. The majority accumulate in the lungs where they can directly affect the inhalation process and lung architecture. Here, we investigate the bioavailability of graphene quantum dots (GQDs) to the lungs of rats by measuring the alterations in macromolecular fractions via Fourier transform infrared spectroscopy (FTIR). GQDs were intravenously injected into the rats in a dose-dependent manner (low (5 mg kg -1 ) and high (15 mg kg -1 ) doses of GQDs per body weight of rat) for 7 days. The lung tissues were isolated, processed and haematoxylin-eosin stained for histological analysis to identify cell death. Key biochemical differences were identified by spectral signatures: pronounced changes in cholesterol were found in two cases of low and high doses; a change in phosphorylation profile of substrate proteins in the tissues was observed in low dose at 24 h. This is the first time biomolecules have been measured in biological tissue using FTIR to investigate the biocompatibility of foreign material. We found that highly accurate toxicological changes can be investigated with FTIR measurements of tissue sections. As a result, FTIR could form the basis of a non-invasive pre-diagnostic tool for predicting the toxicity of GQDs.

Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3 as a novel lung cancer-related gene

International Nuclear Information System (INIS)

Wu, Mingsong; Tu, Tao; Huang, Yunchao; Cao, Yi

2013-01-01

To understand the carcinogenesis caused by accumulated genetic and epigenetic alterations and seek novel biomarkers for various cancers, studying differentially expressed genes between cancerous and normal tissues is crucial. In the study, two cDNA libraries of lung cancer were constructed and screened for identification of differentially expressed genes. Two cDNA libraries of differentially expressed genes were constructed using lung adenocarcinoma tissue and adjacent nonmalignant lung tissue by suppression subtractive hybridization. The data of the cDNA libraries were then analyzed and compared using bioinformatics analysis. Levels of mRNA and protein were measured by quantitative real-time polymerase chain reaction (q-RT-PCR) and western blot respectively, as well as expression and localization of proteins were determined by immunostaining. Gene functions were investigated using proliferation and migration assays after gene silencing and gene over-expression. Two libraries of differentially expressed genes were obtained. The forward-subtracted library (FSL) and the reverse-subtracted library (RSL) contained 177 and 59 genes, respectively. Bioinformatic analysis demonstrated that these genes were involved in a wide range of cellular functions. The vast majority of these genes were newly identified to be abnormally expressed in lung cancer. In the first stage of the screening for 16 genes, we compared lung cancer tissues with their adjacent non-malignant tissues at the mRNA level, and found six genes (ERGIC3, DDR1, HSP90B1, SDC1, RPSA, and LPCAT1) from the FSL were significantly up-regulated while two genes (GPX3 and TIMP3) from the RSL were significantly down-regulated (P < 0.05). The ERGIC3 protein was also over-expressed in lung cancer tissues and cultured cells, and expression of ERGIC3 was correlated with the differentiated degree and histological type of lung cancer. The up-regulation of ERGIC3 could promote cellular migration and proliferation in vitro. The

Multiplex zymography captures stage-specific activity profiles of cathepsins K, L, and S in human breast, lung, and cervical cancer.

Science.gov (United States)

Chen, Binbin; Platt, Manu O

2011-07-14

Cathepsins K, L, and S are cysteine proteases upregulated in cancer and proteolyze extracellular matrix to facilitate metastasis, but difficulty distinguishing specific cathepsin activity in complex tissue extracts confounds scientific studies and employing them for use in clinical diagnoses. Here, we have developed multiplex cathepsin zymography to profile cathepsins K, L, and S activity in 10 μg human breast, lung, and cervical tumors by exploiting unique electrophoretic mobility and renaturation properties. Frozen breast, lung, and cervix cancer tissue lysates and normal organ tissue lysates from the same human patients were obtained (28 breast tissues, 23 lung tissues, and 23 cervix tissues), minced and homogenized prior to loading for cathepsin gelatin zymography to determine enzymatic activity. Cleared bands of cathepsin activity were identified and validated in tumor extracts and detected organ- and stage-specific differences in activity. Cathepsin K was unique compared to cathepsins L and S. It was significantly higher for all cancers even at the earliest stage tested (stage I for lung and cervix (n = 6, p zymography, yielded 100% sensitivity and specificity for 20 breast tissue samples tested (10 normal; 10 tumor) in part due to the consistent absence of cathepsin K in normal breast tissue across all patients. To summarize, this sensitive assay provides quantitative outputs of cathepsins K, L, and S activities from mere micrograms of tissue and has potential use as a supplement to histological methods of clinical diagnoses of biopsied human tissue.

The Use of 4DCT to Reduce Lung Dose: A Dosimetric Analysis

International Nuclear Information System (INIS)

Khan, Fazal; Bell, Glenn; Antony, Jacob; Palmer, Matt; Balter, Peter; Bucci, Kara; Chapman, Melissa Jane

2009-01-01

Dosimetric studies on respiratory movement suggest several advantages toward the use of 4-dimensional computed tomography (4DCT) in radiation treatment planning. 4DCT is a method to obtain a series of CT scans each representing a different respiratory phase. The use of 4DCT has provided substantial information on tumor movement in the lung, allowing for the creation of custom planning margins explicitly including respiratory motion. These custom motion margins may result in an increase in the amount of normal lung in the field; however, it is believed less normal lung is irradiated than if generic motion margins were used. Clinical data regarding dose to normal lung by using 4DCT remain rather limited. Thus, a study presenting figures on the change in normal lung dose between planned free breathing CT and 4DCT cases would be useful to the dosimetry community. We have generated plans comparing fast spiral CT and 4DCT in regard to tumor coverage and the resulting dose to normal lung for the clinical target volume (CTV) and planning target volume (PTV) expansions used at our institution. These data were analyzed for free breathing and 4D plans of 6 lung cancer patients using intensity modulated radiation therapy (IMRT). We compared doses to normal lung tissue between free breathing and 4DCT plans.

Expression of Nitric Oxide Synthase Isoenzyme in Lung Tissue of Smokers with and without Chronic Obstructive Pulmonary Disease

Directory of Open Access Journals (Sweden)

Wen-Ting Jiang

2015-01-01

Full Text Available Background: It has been demonstrated that only 10%-20% cigarette smokers finally suffer chronic obstructive pulmonary disease (COPD. The underlying mechanism of development remains uncertain so far. Nitric oxide (NO has been found to be closely associated with the pathogenesis of COPD, the alteration of NO synthase (NOS expression need to be revealed. The study aimed to investigate the alterations of NOS isoforms expressions between smokers with and without COPD, which might be helpful for identifying the susceptibility of smokers developing into COPD. Methods: Peripheral lung tissues were obtained from 10 nonsmoker control subjects, 15 non-COPD smokers, and 15 smokers with COPD. Neuronal NOS (nNOS, inducible NOS (iNOS, and endothelial NOS (eNOS mRNA and protein levels were measured in each sample by using real-time polymerase chain reaction and Western blotting. Results: INOS mRNA was significantly increased in patients with COPD compared with nonsmokers and smokers with normal lung function (P < 0.001, P = 0.001, respectively. iNOS protein was also higher in COPD patients than nonsmokers and smokers with normal lung function (P < 0.01 and P = 0.01, respectively. However, expressions of nNOS and eNOS did not differ among nonsmokers, smokers with and without COPD. Furthermore, there was a negative correlation between iNOS protein level and lung function parameters forced expiratory volume in 1 s (FEV 1 (% predicted (r = −0.549, P = 0.001 and FEV 1 /forced vital capacity (%, r = −0.535, P = 0.001. Conclusions: The expression of iNOS significantly increased in smokers with COPD compared with that in nonsmokers or smokers without COPD. The results suggest that iNOS might be involved in the pathogenesis of COPD, and may be a potential marker to identify the smokers who have more liability to suffer COPD.

Metallic artifact mitigation and organ-constrained tissue assignment for Monte Carlo calculations of permanent implant lung brachytherapy

Energy Technology Data Exchange (ETDEWEB)

Sutherland, J. G. H.; Miksys, N.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca [Carleton Laboratory for Radiotherapy Physics, Department of Physics, Carleton University, Ottawa, Ontario K1S 5B6 (Canada); Furutani, K. M. [Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905 (United States)

2014-01-15

Purpose: To investigate methods of generating accurate patient-specific computational phantoms for the Monte Carlo calculation of lung brachytherapy patient dose distributions. Methods: Four metallic artifact mitigation methods are applied to six lung brachytherapy patient computed tomography (CT) images: simple threshold replacement (STR) identifies high CT values in the vicinity of the seeds and replaces them with estimated true values; fan beam virtual sinogram replaces artifact-affected values in a virtual sinogram and performs a filtered back-projection to generate a corrected image; 3D median filter replaces voxel values that differ from the median value in a region of interest surrounding the voxel and then applies a second filter to reduce noise; and a combination of fan beam virtual sinogram and STR. Computational phantoms are generated from artifact-corrected and uncorrected images using several tissue assignment schemes: both lung-contour constrained and unconstrained global schemes are considered. Voxel mass densities are assigned based on voxel CT number or using the nominal tissue mass densities. Dose distributions are calculated using the EGSnrc user-code BrachyDose for{sup 125}I, {sup 103}Pd, and {sup 131}Cs seeds and are compared directly as well as through dose volume histograms and dose metrics for target volumes surrounding surgical sutures. Results: Metallic artifact mitigation techniques vary in ability to reduce artifacts while preserving tissue detail. Notably, images corrected with the fan beam virtual sinogram have reduced artifacts but residual artifacts near sources remain requiring additional use of STR; the 3D median filter removes artifacts but simultaneously removes detail in lung and bone. Doses vary considerably between computational phantoms with the largest differences arising from artifact-affected voxels assigned to bone in the vicinity of the seeds. Consequently, when metallic artifact reduction and constrained tissue

Statistical validation of normal tissue complication probability models

NARCIS (Netherlands)

Xu, Cheng-Jian; van der Schaaf, Arjen; van t Veld, Aart; Langendijk, Johannes A.; Schilstra, Cornelis

2012-01-01

PURPOSE: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: A penalized regression method, LASSO (least absolute shrinkage

18FDG uptake associated with CT density on PET/CT in lungs with and without chronic interstitial lung diseases

International Nuclear Information System (INIS)

Inoue, Kentaro; Okada, Ken; Taki, Yasuyuki; Goto, Ryoi; Kinomura, Shigeo; Fukuda, Hiroshi

2009-01-01

The dependent-density of computed tomography (CT) images of positron emission tomography (PET)/CT is sometimes difficult to distinguish from chronic interstitial lung disease (ILD) when it accompanies increased 18 F-fluorodeoxy-D-glucose ( 18 FDG) uptake. Though the possible utility of 18 FDG-PET for the diagnosis of active ILD has been reported, the clinical relevance of mild lung 18 FDG uptake in ILD cases without signs and symptoms suggesting acute progression has not been described. This study aimed to test relationships between 18 FDG uptake and lung density on CT using PET/CT in patients with normal lung as well as clinically stable chronic ILD. Thirty-six patients with normal lungs (controls) and 28 patients with chronic ILD (ILD cases) without acute exacerbation were retrospectively selected from 18 FDG PET/CT scans performed in examination of malignant neoplasms. Elliptical regions of interest (ROIs) were placed on the lung. The relationships between CT density and 18 FDG uptake between the control and ILD cases were tested. The CT density and 18 FDG uptake had a linear correlation in both the controls and the ILD cases without a difference in their regression slopes, and they were overlapped between the controls and the ILD cases with higher mean values in the ILD cases. Lung 18 FDG uptake was considered to reflect a gravity-dependent tissue density in the normal lung. Though the lung 18 FDG uptake as well as the CT density tended to be higher in chronic ILD patients, it may be difficult to distinguish them in normal dependent regions from those related to chronic ILD in some cases. (author)

Iso-effect tables and therapeutic ratios for epidermoid cancer and normal tissue stroma

International Nuclear Information System (INIS)

Cohen, L.; Creditor, M.

1983-01-01

Available literature on radiation injury to normal tissue stroma and ablation of epidermoid carcinoma was surveyed. Computer programs (RAD3 and RAD1) were then used to derive cell kinetic parameters and generate iso-effect tables for the relevant tissues. The two tables provide a set of limiting doses for tolerance of normal connective tissue (16% risk of injury) and for ablation of epidermoid cancer (16% risk of recurrence) covering a wide range of treatment schedules. Calculating the ratios of normal tissue tolerance to tumor control doses for each treatment scheme provides an array of therapeutic ratios, from which appropriate treatment schemes can be selected

Cyclophosphamide for connective tissue disease-associated interstitial lung disease.

Science.gov (United States)

Barnes, Hayley; Holland, Anne E; Westall, Glen P; Goh, Nicole Sl; Glaspole, Ian N

2018-01-03

Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death. ILD is now the major cause of death amongst individuals with systemic sclerosis.Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses. However this comes with potential toxicities, including nausea, haemorrhagic cystitis, bladder cancer, bone marrow suppression, increased risk of opportunistic infections, and haematological and solid organ malignancies.Decision-making in the treatment of individuals with CTD-ILD is difficult; the clinician needs to identify those who will develop progressive disease, and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy, for which only relatively limited data on efficacy can be found. Similarly, it is not clear whether histological subtype, disease duration, or disease extent can be used to predict treatment responsiveness. To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD. We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to May 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. We included randomised controlled parallel-group trials that compared cyclophosphamide in any form, used individually or concomitantly with other immunomodulating therapies, versus non

Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

Science.gov (United States)

Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.

1998-01-01

The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

Evaluation of normal tissue responses to high-LET radiations

International Nuclear Information System (INIS)

Halnan, K.E.

1979-01-01

Clinical results presented have been analysed to evaluate normal tissue responses to high-LET radiations. Damage to brain, spinal cord, gut, skin, connective tissue and bone has occurred. A high RBE is probable for brain and possible for spinal cord and gut but other reasons for damage are also discussed. A net gain seems likely. Random controlled trials are advocated. (author)

Multiple fields may offer better esophagus sparing without increased probability of lung toxicity in optimized IMRT of lung tumors

International Nuclear Information System (INIS)

Chapet, Olivier; Fraass, Benedick A.; Haken, Randall K. ten

2006-01-01

Purpose: To evaluate whether increasing numbers of intensity-modulated radiation therapy (IMRT) fields enhance lung-tumor dose without additional predicted toxicity for difficult planning geometries. Methods and Materials: Data from 8 previous three dimensional conformal radiation therapy (3D-CRT) patients with tumors located in various regions of each lung, but with planning target volumes (PTVs) overlapping part of the esophagus, were used as input. Four optimized-beamlet IMRT plans (1 plan that used the 3D-CRT beam arrangement and 3 plans with 3, 5, or 7 axial, but predominantly one-sided, fields) were compared. For IMRT, the equivalent uniform dose (EUD) in the whole PTV was optimized simultaneously with that in a reduced PTV exclusive of the esophagus. Normal-tissue complication probability-based costlets were used for the esophagus, heart, and lung. Results: Overall, IMRT plans (optimized by use of EUD to judiciously allow relaxed PTV dose homogeneity) result in better minimum PTV isodose surface coverage and better average EUD values than does conformal planning; dose generally increases with the number of fields. Even 7-field plans do not significantly alter normal-lung mean-dose values or lung volumes that receive more than 13, 20, or 30 Gy. Conclusion: Optimized many-field IMRT plans can lead to escalated lung-tumor dose in the special case of esophagus overlapping PTV, without unacceptable alteration in the dose distribution to normal lung

86Rb Distribution in the Lung of the Rabbit with Pneumothorax

International Nuclear Information System (INIS)

Huh, Kap To

1972-01-01

86 Rb uptake of some organs and tissues, eg. both lungs, both renal cortices. small intestine, liver and skeletal muscle were studied in the control and the rabbit subjected to pneumothorax. 86 Rb in the form of chloride mixed with physiological saline was intravenously injected. The doses were 100 μc for a rabbit. The rabbits were sacrificed at intervals of 10, 20, 40, and 60 seconds after the injection of 86 Rb, by the injection of saturated KCI solution. After scarification, the organ and tissue sample were quickly removed. 86 Rb uptake in gm of the organs and tissues were measured. On the basis of uptake value, administered doses and body weight, % dose/gm tissues per 200 gm body weight was calculated. Followings were the results: 1. Pneumothorax resulted in a marked elevation in 86 Rb uptake value of collapsed lung and returned to normal level lately. 2. Contralateral lung of pneumothorax also showed marked elevation in 86 Rb uptake value and recovered to normal level. 3. Initial 86 Rb uptake value of liver, small intestine of the rabbit with pneumothorax showed some elevation as compared to control, but that of late stage were similar with control. 4. Local blood flow determination by means of 86 Rb uptake were inadequate in the collapsed lung of pneumothorax. 5. It was suggested that the mechanism for the initial elevation of 86 Rb uptake value in each organs and tissue were different from each other.

Overexpression of K-p21Ras play a prominent role in lung cancer

Science.gov (United States)

Zhang, Peng-bo; Zhou, Xin-liang; Yang, Ju-lun

2018-06-01

The proto-oncogene ras product, p21Ras, has been found overexpression in many human tumors. However, the subtypes of overexpressed p21Ras still remain unclear. The purpose of this study was to investigate overexpressed isoforms of p21Ras and their roles in the progress of lung cancer. Method: The expression of total p21Ras in normal lung tissues and lung cancers was determined by immunohistochemically staining with monoclonal antibody (Mab) KGHR-1 which could recognize and broad spectrum reaction with the (K/H/N) ras protein. Then, the isoforms of p21Ras was examined by specific Mab for each p21Ras subtypes. Results: Low expression of total p21Ras was found in 26.67% (8/30) of normal lung tissues, and 81.31% (87/107) of adenocarcinoma harbored overexpressed total p21Ras. Besides, 70.00% (35/50) of squamous cell carcinoma were detected overexpressed total p21Ras. In addition, 122 lung cancer tissues from overexpression of total p21Ras protein were selected to detect the expression of each subtype. And all the 122 lung cancer tissues were K-p21Ras overexpression. Moreover, there was a statistical significance difference between the expression level of total p21Ras and differentiation, and the same results were observed between the expression level of total p21Ras and lymph node metastasis (P0.05). Conclusions: Overexpression of K-p21Ras plays a prominent role in the progress of lung cancer and it is suggested that the p21Ras could serve as a promising treatment target in lung cancer.

MRI appearance of radiation-induced changes of normal cervical tissues

International Nuclear Information System (INIS)

Noemayr, A.; Lell, M.; Bautz, W.; Sweeney, R.; Lukas, P.

2001-01-01

Irradiation causes specific MRI changes in anatomic morphology and signal intensity. To avoid misinterpretation, it is important to consider the potential radiation changes of normal tissue in MRI. The aim of this study was to describe the detected radiation effects on normal cervical tissues in MRI. Pretreatment and posttreatment MRI of 52 patients with primary neck tumors were evaluated retrospectively. The MR imaging was performed before initiating radiotherapy and at the end of the treatment period. Patients underwent follow-up studies within 24 months after the end of irradiation. Edema was the main radiation-induced effect. It was detected in the epiglottis, larynx, pharynx wall, retro- and parapharyngeal space, salivary glands, muscles, and subcutaneous tissue. In some cases the bone marrow of the mandible showed edema, due to osteonecrosis. We additionally detected fluid accumulation in the mastoid cells. Radiation caused volume reduction of the parotid gland, thickening of the pharynx wall, and fatty degeneration of bone marrow. Magnetic resonance imaging is an excellent method of depicting radiation-induced changes of normal tissue. Especially T2-weighted sequences allow the detection of even slight edema. It is important to be aware of the most common radiation-induced changes in MRI and to take them into account when assessing an examination. (orig.)

Investigation of normal tissue complication probabilities in prostate and partial breast irradiation radiotherapy techniques

International Nuclear Information System (INIS)

Bezak, E.; Takam, R.; Bensaleh, S.; Yeoh, E.; Marcu, L.

2011-01-01

Full text: Normal- Tissue-Complication Probabilities of rectum, bladder and urethra following various radiation techniques for prostate cancer were evaluated using the relative-seriality and Lyman models. NTCPs of lungs, heart and skin, their dependence on sourceposition, balloon-deformation were also investigated for HDR mammosite brachytherapy. The prostate treatment techniques included external three dimentional conformal-radiotherapy, Low-Dose-Rate brachytherapy (1-125), High-Dose-Rate brachytherapy (Ir-I92). Dose- Volume-Histograms of critical structures for prostate and breast radiotherapy, retrieved from corresponding treatment planning systems, were converted to Biological Effective Dose (BEffD)-based and Equivalent Dose(Deq)-based DVHs to account for differences in radiation delivery and fractionation schedule. Literature-based model parameters were used to calculate NTCPs. Hypofractionated 3D-CRT (2.75 Gy/fraction, total dose 55 Gy) NTCPs of rectum, bladder and urethra were less than those for standard fractionated 4-field 3D-CRT (2-Gy/fraction, 64 Gy) and dose-escalated 4- and 5-field 3D-CRT (74 Gy). Rectal and bladder NTCPs (5.2% and 6.6%) following the dose-escalated 4-field 3D-CRT (74 Gy) were the highest among analyzed techniques. The average NTCP for rectum and urethra were 0.6% and 24.7% for LDRBT and 0.5% and 11.2% for HDR-BT. For Mammosite, NTCP was estimated to be 0.1 %, 0.1 %, 1.2% and 3.5% for skin desquamation, erythema, telangiectasia and fibrosis respectively (the source positioned at the balloon centre). A 4 mm Mammosite-balloon deformation leads to overdosing of PTV regions by ∼40%, resulting in excessive skin dose and increased NTCP. Conclusions Prostate brachytherapy resulted in NTCPs lower compared to external beam techniques. Mammosite-brachytherapy resulted in no heart/lung complications regardless of balloon deformation. However, 4 mm deformation caused 0.6% increase in tissue fibrosis NTCP.

Matrix metalloproteinases in lung biology

Directory of Open Access Journals (Sweden)

Parks William C

2000-12-01

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

Real-time soft tissue motion estimation for lung tumors during radiotherapy delivery

International Nuclear Information System (INIS)

Rottmann, Joerg; Berbeco, Ross; Keall, Paul

2013-01-01

Purpose: To provide real-time lung tumor motion estimation during radiotherapy treatment delivery without the need for implanted fiducial markers or additional imaging dose to the patient.Methods: 2D radiographs from the therapy beam's-eye-view (BEV) perspective are captured at a frame rate of 12.8 Hz with a frame grabber allowing direct RAM access to the image buffer. An in-house developed real-time soft tissue localization algorithm is utilized to calculate soft tissue displacement from these images in real-time. The system is tested with a Varian TX linear accelerator and an AS-1000 amorphous silicon electronic portal imaging device operating at a resolution of 512 × 384 pixels. The accuracy of the motion estimation is verified with a dynamic motion phantom. Clinical accuracy was tested on lung SBRT images acquired at 2 fps.Results: Real-time lung tumor motion estimation from BEV images without fiducial markers is successfully demonstrated. For the phantom study, a mean tracking error <1.0 mm [root mean square (rms) error of 0.3 mm] was observed. The tracking rms accuracy on BEV images from a lung SBRT patient (≈20 mm tumor motion range) is 1.0 mm.Conclusions: The authors demonstrate for the first time real-time markerless lung tumor motion estimation from BEV images alone. The described system can operate at a frame rate of 12.8 Hz and does not require prior knowledge to establish traceable landmarks for tracking on the fly. The authors show that the geometric accuracy is similar to (or better than) previously published markerless algorithms not operating in real-time

Real-time soft tissue motion estimation for lung tumors during radiotherapy delivery

Energy Technology Data Exchange (ETDEWEB)

Rottmann, Joerg; Berbeco, Ross [Brigham and Women' s Hospital, Dana Farber-Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States); Keall, Paul [Radiation Physics Laboratory, Sydney Medical School, University of Sydney, Sydney NSW 2006 (Australia)

2013-09-15

Purpose: To provide real-time lung tumor motion estimation during radiotherapy treatment delivery without the need for implanted fiducial markers or additional imaging dose to the patient.Methods: 2D radiographs from the therapy beam's-eye-view (BEV) perspective are captured at a frame rate of 12.8 Hz with a frame grabber allowing direct RAM access to the image buffer. An in-house developed real-time soft tissue localization algorithm is utilized to calculate soft tissue displacement from these images in real-time. The system is tested with a Varian TX linear accelerator and an AS-1000 amorphous silicon electronic portal imaging device operating at a resolution of 512 × 384 pixels. The accuracy of the motion estimation is verified with a dynamic motion phantom. Clinical accuracy was tested on lung SBRT images acquired at 2 fps.Results: Real-time lung tumor motion estimation from BEV images without fiducial markers is successfully demonstrated. For the phantom study, a mean tracking error <1.0 mm [root mean square (rms) error of 0.3 mm] was observed. The tracking rms accuracy on BEV images from a lung SBRT patient (≈20 mm tumor motion range) is 1.0 mm.Conclusions: The authors demonstrate for the first time real-time markerless lung tumor motion estimation from BEV images alone. The described system can operate at a frame rate of 12.8 Hz and does not require prior knowledge to establish traceable landmarks for tracking on the fly. The authors show that the geometric accuracy is similar to (or better than) previously published markerless algorithms not operating in real-time.

Diagnostic significance of gallium lung uptake in patients with normal chest radiographs

International Nuclear Information System (INIS)

MacMahon, H.; Bekerman, C.

1978-01-01

Nine patients were encountered with normal chest radiographs, but diffuse bilateral lung uptake of 67 Ga-citrate. They were divided into three groups. The first consisted of 6 patients who had lymphoma or leukemia and had had multiple cycles of chemotherapy. Here, abnormal uptake may have resulted from a toxic effect of the drugs or from a low-grade, subclinical infectious process. The 2 patients in the second group were drug addicts and a subradiographic interstitial inflammatory reaction was probably responsible for abnormal uptake. The last patient had diffuse uptake of 67 Ga-citrate throughout the lungs two weeks before lymphomatous infiltrates became radiographically visible

Time evolution of regional CT density changes in normal lung after IMRT for NSCLC

International Nuclear Information System (INIS)

Bernchou, Uffe; Schytte, Tine; Bertelsen, Anders; Bentzen, Søren M.; Hansen, Olfred; Brink, Carsten

2013-01-01

Purpose: This study investigates the clinical radiobiology of radiation induced lung disease in terms of regional computed tomography (CT) density changes following intensity modulated radiotherapy (IMRT) for non-small-cell lung cancer (NSCLC). Methods: A total of 387 follow-up CT scans in 131 NSCLC patients receiving IMRT to a prescribed dose of 60 or 66 Gy in 2 Gy fractions were analyzed. The dose-dependent temporal evolution of the density change was analyzed using a two-component model, a superposition of an early, transient component and a late, persistent component. Results: The CT density of healthy lung tissue was observed to increase significantly (p 12 months. Conclusions: The radiobiology of lung injury may be analyzed in terms of CT density change. The initial transient change in density is consistent with radiation pneumonitis, while the subsequent stabilization of the density is consistent with pulmonary fibrosis

Raman spectroscopy of normal oral buccal mucosa tissues: study on intact and incised biopsies

Science.gov (United States)

Deshmukh, Atul; Singh, S. P.; Chaturvedi, Pankaj; Krishna, C. Murali

2011-12-01

Oral squamous cell carcinoma is one of among the top 10 malignancies. Optical spectroscopy, including Raman, is being actively pursued as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant, and malignant oral ex vivo tissues. Spectral features showed predominance of lipids and proteins in normal and cancer conditions, respectively, which were attributed to membrane lipids and surface proteins. In view of recent developments in deep tissue Raman spectroscopy, we have recorded Raman spectra from superior and inferior surfaces of 10 normal oral tissues on intact, as well as incised, biopsies after separation of epithelium from connective tissue. Spectral variations and similarities among different groups were explored by unsupervised (principal component analysis) and supervised (linear discriminant analysis, factorial discriminant analysis) methodologies. Clusters of spectra from superior and inferior surfaces of intact tissues show a high overlap; whereas spectra from separated epithelium and connective tissue sections yielded clear clusters, though they also overlap on clusters of intact tissues. Spectra of all four groups of normal tissues gave exclusive clusters when tested against malignant spectra. Thus, this study demonstrates that spectra recorded from the superior surface of an intact tissue may have contributions from deeper layers but has no bearing from the classification of a malignant tissues point of view.

Classification of 27 Tumor-Associated Antigens by Histochemical Analysis of 36 Freshly Resected Lung Cancer Tissues

Directory of Open Access Journals (Sweden)

Gene Kurosawa

2016-11-01

Full Text Available In previous studies, we identified 29 tumor-associated antigens (TAAs and isolated 488 human monoclonal antibodies (mAbs that specifically bind to one of the 29 TAAs. In the present study, we performed histochemical analysis of 36 freshly resected lung cancer tissues by using 60 mAbs against 27 TAAs. Comparison of the staining patterns of tumor cells, bronchial epithelial cells, and normal pulmonary alveolus cells and interalveolar septum allowed us to determine the type and location of cells that express target molecules, as well as the degree of expression. The patterns were classified into 7 categories. While multiple Abs were used against certain TAAs, the differences observed among them should be derived from differences in the binding activity and/or the epitope. Thus, such data indicate the versatility of respective clones as anti-cancer drugs. Although the information obtained was limited to the lung and bronchial tube, bronchial epithelial cells represent normal growing cells, and therefore, the data are informative. The results indicate that 9 of the 27 TAAs are suitable targets for therapeutic Abs. These 9 Ags include EGFR, HER2, TfR, and integrin α6β4. Based on our findings, a pharmaceutical company has started to develop anti-cancer drugs by using Abs to TfR and integrin α6β4. HGFR, PTP-LAR, CD147, CDCP1, and integrin αvβ3 are also appropriate targets for therapeutic purposes.

Isolation of Blastomyces dermatitidis yeast from lung tissue during murine infection for in vivo transcriptional profiling.

Science.gov (United States)

Marty, Amber J; Wüthrich, Marcel; Carmen, John C; Sullivan, Thomas D; Klein, Bruce S; Cuomo, Christina A; Gauthier, Gregory M

2013-07-01

Blastomyces dermatitidis belongs to a group of thermally dimorphic fungi that grow as sporulating mold in the soil and convert to pathogenic yeast in the lung following inhalation of spores. Knowledge about the molecular events important for fungal adaptation and survival in the host remains limited. The development of high-throughput analytic tools such as RNA sequencing (RNA-Seq) has potential to provide novel insight on fungal pathogenesis especially if applied in vivo during infection. However, in vivo transcriptional profiling is hindered by the low abundance of fungal cells relative to mammalian tissue and difficulty in isolating fungal cells from the tissues they infect. For the purpose of obtaining B. dermatitidis RNA for in vivo transcriptional analysis by RNA-Seq, we developed a simple technique for isolating yeast from murine lung tissue. Using a two-step approach of filtration and centrifugation following lysis of murine lung cells, 91% of yeast cells causing infection were isolated from lung tissue. B. dermatitidis recovered from the lung yielded high-quality RNA with minimal murine contamination and was suitable for RNA-Seq. Approximately 87% of the sequencing reads obtained from the recovered yeast aligned with the B. dermatitidis genome. This was similar to 93% alignment for yeast grown in vitro. The use of near-freezing temperature along with short ex vivo time minimized transcriptional changes that would have otherwise occurred with higher temperature or longer processing time. In conclusion, we have developed a technique that recovers the majority of yeast causing pulmonary infection and yields high-quality fungal RNA with minimal contamination by mammalian RNA. Copyright © 2013 Elsevier Inc. All rights reserved.

Normal spectrum of pulmonary parametric response map to differentiate lung collapsibility: distribution of densitometric classifications in healthy adult volunteers

International Nuclear Information System (INIS)

Silva, Mario; Nemec, Stefan F.; Dufresne, Valerie; Occhipinti, Mariaelena; Heidinger, Benedikt H.; Bankier, Alexander A.; Chamberlain, Ryan

2016-01-01

Pulmonary parametric response map (PRM) was proposed for quantitative densitometric phenotypization of chronic obstructive pulmonary disease. However, little is known about this technique in healthy subjects. The purpose of this study was to describe the normal spectrum of densitometric classification of pulmonary PRM in a group of healthy adults. 15 healthy volunteers underwent spirometrically monitored chest CT at total lung capacity (TLC) and functional residual capacity (FRC). The paired CT scans were analyzed by PRM for voxel-by-voxel characterization of lung parenchyma according to 4 densitometric classifications: normal lung (TLC ≥ -950 HU, FRC ≥ -856 HU); expiratory low attenuation area (LAA) (TLC ≥ -950 HU, FRC < -856 HU); dual LAA (TLC<-950 HU, FRC < -856 HU); uncharacterized (TLC < -950 HU, FRC ≥ -856 HU). PRM spectrum was 78 % ± 10 % normal lung, 20 % ± 8 % expiratory LAA, and 1 % ± 1 % dual LAA. PRM was similar between genders, there was moderate correlation between dual LAA and spirometrically assessed TLC (R = 0.531; p = 0.042), and between expiratory LAA and Vol Exp/Insp ratio (R = -0.572; p = 0.026). PRM reflects the predominance of normal lung parenchyma in a group of healthy volunteers. However, PRM also confirms the presence of physiological expiratory LAA seemingly related to air trapping and a minimal amount of dual LAA likely reflecting emphysema. (orig.)

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

Directory of Open Access Journals (Sweden)

Juan Pablo Casas

2008-08-01

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

Abnormalities in lung volumes and airflow in children with newly diagnosed connective tissue disease.

Science.gov (United States)

Peradzyńska, Joanna; Krenke, Katarzyna; Szylling, Anna; Kołodziejczyk, Beata; Gazda, Agnieszka; Rutkowska-Sak, Lidia; Kulus, Marek

2016-01-01

Connective tissue diseases (CTDs) of childhood are rare inflammatory disorders, involving various organs and tissues including respiratory system. Pulmonary involvement in patients with CTDs is uncommon but may cause functional impairment. Data on prevalence and type of lung function abnormalities in children with CTDs are scarce. Thus, the aim of this study was to asses pulmonary functional status in children with newly diagnosed CTD and follow the results after two years of the disease course. There were 98 children (mean age: 13 ± 3; 76 girls), treated in Department of Pediatric Rheumatology, Institute of Rheumatology, Warsaw and 80 aged-matched, healthy controls (mean age 12.7 ± 2.4; 50 girls) included into the study. Study procedures included medical history, physical examination, chest radiograph and PFT (spirometry and whole body-plethysmography). Then, the assessment of PFT was performed after 24 months. FEV₁, FEV₁/FVC and MEF50 were significantly lower in CTD as compared to control group, there was no difference in FVC and TLC. The proportion of patients with abnormal lung function was significantly higher in the study group, 41 (42%) vs 9 (11%). 24-months observation didn't reveal progression in lung function impairment. Lung function impairment is relatively common in children with CTDs. Although restrictive ventilatory pattern is considered typical feature of lung involvement in CTDs, airflow limitation could also be an initial abnormality.

Tumor and normal tissue responses to fractioned non-uniform dose delivery

Energy Technology Data Exchange (ETDEWEB)

Kaellman, P; Aegren, A; Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

1996-08-01

The volume dependence of the radiation response of a tumor is straight forward to quantify because it depends primarily on the eradication of all its clonogenic cells. A tumor therefore has a parallel organization as any surviving clonogen in principle can repopulate the tumor. The difficulty with the response of the tumor is instead to know the density and sensitivity distribution of the most resistant clonogenic cells. The increase in the 50% tumor control dose and the decrease in the maximum normalized slope of the dose response relation, {gamma}, in presence of small compartments of resistant tumor cells have therefore been quantified to describe their influence on the dose response relation. Injury to normal tissue is a much more complex and gradual process. It depends on earlier effects induced long before depletion of the differentiated and clonogenic cells that in addition may have a complex structural and functional organization. The volume dependence of the dose response relation of normal tissues is therefore described here by the relative seriality, s, of the infrastructure of the organ. The model can also be generalized to describe the response of heterogeneous tissues to non uniform dose distributions. The new model is compared with clinical and experimental data on normal tissue response, and shows good agreement both with regard to the shape of dose response relation and the volume dependence of the isoeffect dose. The response of tumors and normal tissues are quantified for arbitrary dose fractionations using the linear quadratic cell survival parameters {alpha} and {beta}. The parameters of the dose response relation are derived both for a constant dose per fraction and a constant number of dose fractions, thus in the latter case accounting also for non uniform dose delivery. (author). 26 refs, 4 figs.

High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

International Nuclear Information System (INIS)

Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

2012-01-01

Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

Dosimetric precision requirements and quantities for characterizing the response of tumors and normal tissues

Energy Technology Data Exchange (ETDEWEB)

Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

1996-08-01

Based on simple radiobiological models the effect of the distribution of absorbed dose in therapy beams on the radiation response of tumor and normal tissue volumes are investigated. Under the assumption that the dose variation in the treated volume is small it is shown that the response of the tissue to radiation is determined mainly by the mean dose to the tumor or normal tissue volume in question. Quantitative expressions are also given for the increased probability of normal tissue complications and the decreased probability of tumor control as a function of increasing dose variations around the mean dose level to these tissues. When the dose variations are large the minimum tumor dose (to cm{sup 3} size volumes) will generally be better related to tumor control and the highest dose to significant portions of normal tissue correlates best to complications. In order not to lose more than one out of 20 curable patients (95% of highest possible treatment outcome) the required accuracy in the dose distribution delivered to the target volume should be 2.5% (1{sigma}) for a mean dose response gradient {gamma} in the range 2 - 3. For more steeply responding tumors and normal tissues even stricter requirements may be desirable. (author). 15 refs, 6 figs.

Evidence for tankyrases as antineoplastic targets in lung cancer

International Nuclear Information System (INIS)

Busch, Alexander M; Johnson, Kevin C; Stan, Radu V; Sanglikar, Aarti; Ahmed, Yashi; Dmitrovsky, Ethan; Freemantle, Sarah J

2013-01-01

New pharmacologic targets are urgently needed to treat or prevent lung cancer, the most common cause of cancer death for men and women. This study identified one such target. This is the canonical Wnt signaling pathway, which is deregulated in cancers, including those lacking adenomatous polyposis coli or β-catenin mutations. Two poly-ADP-ribose polymerase (PARP) enzymes regulate canonical Wnt activity: tankyrase (TNKS) 1 and TNKS2. These enzymes poly-ADP-ribosylate (PARsylate) and destabilize axin, a key component of the β-catenin phosphorylation complex. This study used comprehensive gene profiles to uncover deregulation of the Wnt pathway in murine transgenic and human lung cancers, relative to normal lung. Antineoplastic consequences of genetic and pharmacologic targeting of TNKS in murine and human lung cancer cell lines were explored, and validated in vivo in mice by implantation of murine transgenic lung cancer cells engineered with reduced TNKS expression relative to controls. Microarray analyses comparing Wnt pathway members in malignant versus normal tissues of a murine transgenic cyclin E lung cancer model revealed deregulation of Wnt pathway components, including TNKS1 and TNKS2. Real-time PCR assays independently confirmed these results in paired normal-malignant murine and human lung tissues. Individual treatments of a panel of human and murine lung cancer cell lines with the TNKS inhibitors XAV939 and IWR-1 dose-dependently repressed cell growth and increased cellular axin 1 and tankyrase levels. These inhibitors also repressed expression of a Wnt-responsive luciferase construct, implicating the Wnt pathway in conferring these antineoplastic effects. Individual or combined knockdown of TNKS1 and TNKS2 with siRNAs or shRNAs reduced lung cancer cell growth, stabilized axin, and repressed tumor formation in murine xenograft and syngeneic lung cancer models. Findings reported here uncovered deregulation of specific components of the Wnt pathway in both

Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

Science.gov (United States)

Yang, Tao; Liu, Shan; Zheng, Tian-Hui; Tao, Yan-Yan; Liu, Cheng-Hai

2015-05-26

Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis. To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY. Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats. A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (Pdistribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (Pdistribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Intermittent Fluorescence Oscillations in Lipid Droplets in a Live Normal and Lung Cancer Cell: Time-Resolved Confocal Microscopy.

Science.gov (United States)

Chowdhury, Rajdeep; Amin, Md Asif; Bhattacharyya, Kankan

2015-08-27

Intermittent structural oscillation in the lipid droplets of live lung cells is monitored using time-resolved confocal microscopy. Significant differences are observed between the lung cancer cell (A549) and normal (nonmalignant) lung cell (WI38). For this study, the lipid droplets are covalently labeled with a fluorescent dye, coumarin maleimide (7-diethylamino-3-(4-maleimido-phenyl)-4-methylcoumarin, CPM). The number of lipid droplets in the cancer cell is found to be ∼20-fold higher than that in the normal (nonmalignant) cell. The fluctuation in the fluorescence intensity of the dye (CPM) is attributed to the red-ox processes and periodic formation/rupture of the S-CPM bond. The amount of reactive oxygen species (ROS) is much higher in a cancer cell. This is manifested in faster oscillations (0.9 ± 0.3 s) in cancer cells compared to that in the normal cells (2.8 ± 0.7 s). Solvation dynamics in the lipid droplets of cancer cells is slower compared to that in the normal cell.

Combining deep learning and coherent anti-Stokes Raman scattering imaging for automated differential diagnosis of lung cancer

Science.gov (United States)

Weng, Sheng; Xu, Xiaoyun; Li, Jiasong; Wong, Stephen T. C.

2017-10-01

Lung cancer is the most prevalent type of cancer and the leading cause of cancer-related deaths worldwide. Coherent anti-Stokes Raman scattering (CARS) is capable of providing cellular-level images and resolving pathologically related features on human lung tissues. However, conventional means of analyzing CARS images requires extensive image processing, feature engineering, and human intervention. This study demonstrates the feasibility of applying a deep learning algorithm to automatically differentiate normal and cancerous lung tissue images acquired by CARS. We leverage the features learned by pretrained deep neural networks and retrain the model using CARS images as the input. We achieve 89.2% accuracy in classifying normal, small-cell carcinoma, adenocarcinoma, and squamous cell carcinoma lung images. This computational method is a step toward on-the-spot diagnosis of lung cancer and can be further strengthened by the efforts aimed at miniaturizing the CARS technique for fiber-based microendoscopic imaging.

Optical redox imaging indices discriminate human breast cancer from normal tissues

Science.gov (United States)

Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

2016-01-01

Abstract. Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (predox ratio Fp/(NADH + Fp) was ∼27% higher in the cancerous tissues (predox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients. PMID:27896360

Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma.

Science.gov (United States)

de Castro, Ligia Lins; Xisto, Debora Gonçalves; Kitoko, Jamil Zola; Cruz, Fernanda Ferreira; Olsen, Priscilla Christina; Redondo, Patricia Albuquerque Garcia; Ferreira, Tatiana Paula Teixeira; Weiss, Daniel Jay; Martins, Marco Aurélio; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo

2017-06-24

Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Most current drugs focus on controlling the inflammatory process, but are unable to revert the changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) are effective at reducing inflammation and tissue remodeling; nevertheless, no study has evaluated the therapeutic effects of extracellular vesicles (EVs) obtained from human adipose tissue-derived MSCs (AD-MSC) on established airway remodeling in experimental allergic asthma. C57BL/6 female mice were sensitized and challenged with ovalbumin (OVA). Control (CTRL) animals received saline solution using the same protocol. One day after the last challenge, each group received saline, 10 5 human AD-MSCs, or EVs (released by 10 5  AD-MSCs). Seven days after treatment, animals were anesthetized for lung function assessment and subsequently euthanized. Bronchoalveolar lavage fluid (BALF), lungs, thymus, and mediastinal lymph nodes were harvested for analysis of inflammation. Collagen fiber content of airways and lung parenchyma were also evaluated. In OVA animals, AD-MSCs and EVs acted differently on static lung elastance and on BALF regulatory T cells, CD3 + CD4 + T cells, and pro-inflammatory mediators (interleukin [IL]-4, IL-5, IL-13, and eotaxin), but similarly reduced eosinophils in lung tissue, collagen fiber content in airways and lung parenchyma, levels of transforming growth factor-β in lung tissue, and CD3 + CD4 + T cell counts in the thymus. No significant changes were observed in total cell count or percentage of CD3 + CD4 + T cells in the mediastinal lymph nodes. In this immunocompetent mouse model of allergic asthma, human AD-MSCs and EVs effectively reduced eosinophil counts in lung tissue and BALF and modulated airway remodeling, but their effects on T cells differed in lung and thymus. EVs may hold promise for asthma; however, further studies are required to elucidate the different

Correlation between matrix metalloproteinase-9 and vascular endothelial growth factor expression in lung adenocarcinoma.

Science.gov (United States)

Wen, Y L; Li, L

2015-12-29

The aim of this study was to investigate the correlation between the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) and clinicopathological features of lung adenocarcinoma. The expression of MMP-9 and VEGF was evaluated by immunohistochemistry of 30 samples from lung adenocarcinoma patients and 12 paratumoral (normal) tissue samples. In addition, the change in VEGF or MMP-9 expression after MMP-9 or VEGF blockade, respectively, was measured using western blot in lung adenocarcinoma A549 cells. High expression of MMP-9 was found in 63.3% of adenocarcinoma tissues versus 16.7% in normal tissues (P correlation was identified between MMP-9 and VEGF expression (correlation coefficient = 0.7094, P < 0.001), and their mutual overexpression was associated with clinical staging and lymph node status (P < 0.05). In addition, an decrease in VEGF protein expression was observed after MMP-9 blockade by an MMP-9-specific monoclonal antibody. Similarly, a decrease in MMP-9 protein expression was found after VEGF blockade by a VEGF-specific monoclonal antibody. In conclusion, VEGF and MMP-9 are overexpressed in lung adenocarcinoma tissues, and they have a synergistic effect on the invasion and metastasis of adenocarcinoma.

Validation of SCT Methylation as a Hallmark Biomarker for Lung Cancers.

Science.gov (United States)

Zhang, Yu-An; Ma, Xiaotu; Sathe, Adwait; Fujimoto, Junya; Wistuba, Ignacio; Lam, Stephen; Yatabe, Yasushi; Wang, Yi-Wei; Stastny, Victor; Gao, Boning; Larsen, Jill E; Girard, Luc; Liu, Xiaoyun; Song, Kai; Behrens, Carmen; Kalhor, Neda; Xie, Yang; Zhang, Michael Q; Minna, John D; Gazdar, Adi F

2016-03-01

The human secretin gene (SCT) encodes secretin, a hormone with limited tissue distribution. Analysis of the 450k methylation array data in The Cancer Genome Atlas (TCGA) indicated that the SCT promoter region is differentially hypermethylated in lung cancer. Our purpose was to validate SCT methylation as a potential biomarker for lung cancer. We analyzed data from TCGA and developed and applied SCT-specific bisulfite DNA sequencing and quantitative methylation-specific polymerase chain reaction assays. The analyses of TCGA 450K data for 801 samples showed that SCT hypermethylation has an area under the curve (AUC) value greater than 0.98 that can be used to distinguish lung adenocarcinomas or squamous cell carcinomas from nonmalignant lung tissue. Bisulfite sequencing of lung cancer cell lines and normal blood cells allowed us to confirm that SCT methylation is highly discriminative. By applying a quantitative methylation-specific polymerase chain reaction assay, we found that SCT hypermethylation is frequently detected in all major subtypes of malignant non-small cell lung cancer (AUC = 0.92, n = 108) and small cell lung cancer (AUC = 0.93, n = 40) but is less frequent in lung carcinoids (AUC = 0.54, n = 20). SCT hypermethylation appeared in samples of lung carcinoma in situ during multistage pathogenesis and increased in invasive samples. Further analyses of TCGA 450k data showed that SCT hypermethylation is highly discriminative in most other types of malignant tumors but less frequent in low-grade malignant tumors. The only normal tissue with a high level of methylation was the placenta. Our findings demonstrated that SCT methylation is a highly discriminative biomarker for lung and other malignant tumors, is less frequent in low-grade malignant tumors (including lung carcinoids), and appears at the carcinoma in situ stage. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Morphologic alterations in normal and neoplastic tissues following hyperthermia treatment

International Nuclear Information System (INIS)

Badylak, S.F.; Babbs, C.F.

1984-01-01

The sequential morphologic alterations in normal skeletal muscle in rats, Walker 256 tumors in rats, and transmissible venereal tumors (TVT) in dogs following microwave-induced hyperthermia (43 0 C and 45 0 for 20 minutes) were studied by light and electron microscopy. Normal muscle and Walker 256 tumors showed vascular damage at 5 minutes post-heating (PH), followed by suppuration and thrombosis at 6 and 48 hours PH, and by regeneration and repair at 7 days PH. Endothelial damage and parenchymal degeneration were present 5 minutes PH. Progressive ischemic injury occurred for at least 48 hours PH. Two hyperthermia treatments, separated by a 30 or 60 minute cooling interval, were applied to rats implanted with Walker 256 tumors. Increased selective heating of tumor tissue versus surrounding normal tissue, and increased intratumoral temperatures were found during the second hyperthermia treatment. Canine TVTs were resistant to hyperthermia damage. These results characterized the sequential morphologic alterations following hyperthermia treatment and showed that: 1) vascular damage contributed to the immediate and latent cytotoxic effects of hyperthermia, 2) selective heating occurred in the neoplastic tissue disrupted by prior heat treatment, and 3) not all neoplasms are responsive to hyperthermia treatment

The cryoablation of lung tissue using liquid nitrogen in gel and in the ex vivo pig lung.

Science.gov (United States)

Nomori, Hiroaki; Yamazaki, Ikuo; Kondo, Toshiya; Kanno, Masaya

2017-02-01

To examine the efficiency of cryoablation using liquid nitrogen in lung tissue, we measured the size and temperature distribution of the frozen area (iceball) in gel and in the ex vivo pig lungs. Cryoprobes with diameters of 2.4 and 3.4 mm (2.4D and 3.4D, respectively) were used. Three temperature sensors were positioned at the surface of the cryoprobe and at distances of 0.5 and 1.5 cm from the cryoprobe. The ex vivo pig lungs were perfused with 37 °C saline and inflated using ventilator to simulate in vivo lung conditions. In gel, the 2.4D and 3.4D probes made iceballs of 3.9 ± 0.1 and 4.8 ± 0.3 cm in diameter, respectively, and the temperature at 1.5 cm from those probes reached -32 ± 8 and -53 ± 5 °C, respectively. In the pig lung, the 2.4D and 3.4D probes made iceballs of 5.2 ± 0.1 and 5.5 ± 0.4 cm in diameter, respectively, and the temperature at 1.5 cm from these probes reached -49 ± 5 and -58 ± 3 °C, respectively. Liquid nitrogen cryoablation using both 2.4D and 3.4D probes made iceballs that were of sufficient size, and effective temperatures were reached in both gel and the ex vivo pig lung.

A mast cell secretagogue, compound 48/80, prevents the accumulation of hyaluronan in lung tissue injured by ionizing irradiation

International Nuclear Information System (INIS)

Nilsson, K.; Bjermer, L.; Hellstroem, S.H.; Henriksson, R.; Haellgren, R.

1990-01-01

Irradiation with a single dose of 30 Grey on the basal regions of the lungs of Sprague-Dawley rats induced a peribronchial and alveolar inflammation. Infiltration of mast cells in the edematous alveolar interstitial tissue and also in the peribronchial tissue were characteristic features of the lesion. The appearance of mast cells was already seen 4 wk after irradiation and by weeks 6 to 8 there was a heavy infiltration. The staining properties suggested that they were connective tissue-type mast cells. The infiltration of mast cells was paralleled by an accumulation of hyaluronan (hyaluronic acid) in the alveolar interstitial tissue 6 and 8 wk after irradiation. The recovery of hyaluronan (HA) during bronchoalveolar lavage (BAL) of the lungs also increased at this time. Treatment with a mast cell secretagogue, compound 48/80, induced a distinct reduction of granulated mast cells in the alveolar tissue. Regular treatment with compound 48/80 from the time of irradiation considerably reduced the HA recovery during BAL and the HA accumulation in the interstitial tissue but did not affect the interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. By contrast, an accumulation of HA in the alveolar interstitial space was induced when compound 48/80 was given not until mast cell infiltration of the lung had started. The effects of compound 48/80 indicate that the connective tissue response after lung irradiation is dependent on whether or not mast cell degranulation is induced before or after the mast cell infiltration of the alveolar tissue

Forcing lateral electron disequilibrium to spare lung tissue: a novel technique for stereotactic body radiation therapy of lung cancer

International Nuclear Information System (INIS)

Disher, Brandon; Hajdok, George; Gaede, Stewart; Mulligan, Matthew; Battista, Jerry J

2013-01-01

Stereotactic body radiation therapy (SBRT) has quickly become a preferred treatment option for early-stage lung cancer patients who are ineligible for surgery. This technique uses tightly conformed megavoltage (MV) x-ray beams to irradiate a tumour with ablative doses in only a few treatment fractions. Small high energy x-ray fields can cause lateral electron disequilibrium (LED) to occur within low density media, which can reduce tumour dose. These dose effects may be challenging to predict using analytic dose calculation algorithms, especially at higher beam energies. As a result, previous authors have suggested using low energy photons ( 5 × 5 cm 2 ) for lung cancer patients to avoid the negative dosimetric effects of LED. In this work, we propose a new form of SBRT, described as LED-optimized SBRT (LED-SBRT), which utilizes radiotherapy (RT) parameters designed to cause LED to advantage. It will be shown that LED-SBRT creates enhanced dose gradients at the tumour/lung interface, which can be used to manipulate tumour dose, and/or normal lung dose. To demonstrate the potential benefits of LED-SBRT, the DOSXYZnrc (National Research Council of Canada, Ottawa, ON) Monte Carlo (MC) software was used to calculate dose within a cylindrical phantom and a typical lung patient. 6 MV or 18 MV x-ray fields were focused onto a small tumour volume (diameter ∼1 cm). For the phantom, square fields of 1 × 1 cm 2 , 3 × 3 cm 2 , or 5 × 5 cm 2 were applied. However, in the patient, 3 × 1 cm 2 , 3 × 2 cm 2 , 3 × 2.5 cm 2 , or 3 × 3 cm 2 field sizes were used in simulations to assure target coverage in the superior–inferior direction. To mimic a 180° SBRT arc in the (symmetric) phantom, a single beam profile was calculated, rotated, and beams were summed at 1° segments to accumulate an arc dose distribution. For the patient, a 360° arc was modelled with 36 equally weighted (and spaced) fields focused on the tumour centre. A planning target volume (PTV) was generated

Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation

International Nuclear Information System (INIS)

Hanley, J.; Debois, M.M.; Raben, A.; Mageras, G.S.; Lutz, W.R.; Mychalczak, B.; Schwartz, L.H.; Gloeggler, P.J.; Leibel, S.A.; Fuks, Z.; Kutcher, G.J.

1996-01-01

Purpose/Objective: Lung tumors are subject to movement due to respiratory motion. Conventionally, a margin is applied to the clinical target volume (CTV) to account for this and other treatment uncertainties. The purpose of this study is to evaluate the dosimetric benefits of a deep inspiration breath-hold (DIBH) technique which has two distinct features - deep inspiration which reduces lung density and breath-hold which immobilizes lung tumors. Both properties can potentially reduce the mass of normal lung tissue in the high dose region, thus improving the possibility of dose escalation. Methods and Materials: To study the efficacy of the DIBH technique, CT scans are acquired for each patient under 4 respiration conditions: free-breathing; DIBH; shallow inspiration breath-hold; shallow expiration breath-hold. The free-breathing and DIBH scans are used to generate treatment plans for comparison of standard and DIBH techniques, while the shallow inspiration and expiration scans provide information on the maximum extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry and slow vital capacity maneuvers. For the treatment plan comparison free-breathing and DIBH planning target volumes (PTVs) are constructed consisting of the CTV plus a margin for setup error and lung tumor motion. For both plans the margin for setup error is the same while the margin for lung tumor motion differs. The margin for organ motion in free-breathing is determined by the maximum tumor excursions in the shallow inspiration and expiration CT scans. For the DIBH, tumor motion is reduced to the extent to which DIBH can be maintained and the margin for any residual tumor motion is determined from repeat fluoroscopic movies, acquired with the patient monitored using spirometry. Three-dimensional treatment plans, generated using apertures based on the free-breathing and DIBH PTVs, are

Analysis of factors causing signal loss in the measurement of lung tissue water by nuclear magnetic resonance

International Nuclear Information System (INIS)

Fukuzaki, Minoru; Shioya, Sumie; Haida, Munetaka

1997-01-01

The water content of lung, brain, and muscle tissue was measured by nuclear magnetic resonance (NMR) and compared with gravimetric determinations. The NMR signal intensity of water was measured by a single 90 degree pulse and by a spin-echo sequence. The absolute water content was determined by the difference in the sample's weight before and after desiccation. The NMR detectable water in each tissue was expressed as a percentage of the signal intensity for an equal weight of distilled water. Using the single pulse measurement, 67% of the gravimetrically-measured water was detected in collapsed lung samples (consisting of about 47% retained air), in contrast to 96% for brain and 98% for muscle. For degassed lung samples, the NMR detectability of water increased to 87% with the single pulse measurement and to 90% with the spin-echo measurement, but the values remained significantly less than those of brain or muscle. Factors that caused the NMR signal loss of 33% in collapsed lung samples were: air-tissue interfaces (20%), microscopic field inhomogeneity (3%), and a water component with an extremely short magnetization decay time constant (10%). (author)

Overexpression of microRNA miR-30a or miR-191 in A549 lung cancer or BEAS-2B normal lung cell lines does not alter phenotype.

Directory of Open Access Journals (Sweden)

Santosh Kumar Patnaik

Full Text Available BACKGROUND: MicroRNAs (miRNAs are small, noncoding RNAs (ribonucleic acids that regulate translation. Several miRNAs have been shown to be altered in whole cancer tissue compared to normal tissue when quantified by microarray. Based on previous such evidence of differential expression, we chose to study the functional significance of miRNAs miR-30a and -191 alterations in human lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: The functional significance of miRNAs miR-30a and -191 was studied by creating stable transfectants of the lung adenocarcinoma cell line A549 and the immortalized bronchial epithelial cell line BEAS-2B with modest overexpression of miR-30a or -191 using a lentiviral system. When compared to the corresponding controls, both cell lines overexpressing miR-30a or -191 do not demonstrate any significant changes in cell cycle distribution, cell proliferation, adherent colony formation, soft agar colony formation, xenograft formation in a subcutaneous SCID mouse model, and drug sensitivity to doxorubicin and cisplatin. There is a modest increase in cell migration in cell lines overexpressing miR-30a compared to their controls. CONCLUSIONS/SIGNIFICANCE: Overexpression of miR-30a or -191 does not lead to an alteration in cell cycle, proliferation, xenograft formation, and chemosensitivity of A549 and BEAS-2B cell lines. Using microarray data from whole tumors to select specific miRNAs for functional study may be a suboptimal strategy.

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

Science.gov (United States)

Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

2015-07-01

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

Does Three-Dimensional External Beam Partial Breast Irradiation Spare Lung Tissue Compared With Standard Whole Breast Irradiation?

International Nuclear Information System (INIS)

Jain, Anudh K.; Vallow, Laura A.; Gale, Ashley A.; Buskirk, Steven J.

2009-01-01

Purpose: To determine whether three-dimensional conformal partial breast irradiation (3D-PBI) spares lung tissue compared with whole breast irradiation (WBI) and to include the biologically equivalent dose (BED) to account for differences in fractionation. Methods and Materials: Radiotherapy treatment plans were devised for WBI and 3D-PBI for 25 consecutive patients randomized on the NSABP B-39/RTOG 0413 protocol at Mayo Clinic in Jacksonville, Florida. WBI plans were for 50 Gy in 25 fractions, and 3D-PBI plans were for 38.5 Gy in 10 fractions. Volume of ipsilateral lung receiving 2.5, 5, 10, and 20 Gy was recorded for each plan. The linear quadratic equation was used to calculate the corresponding dose delivered in 10 fractions and volume of ipsilateral lung receiving these doses was recorded for PBI plans. Ipsilateral mean lung dose was recorded for each plan and converted to BED. Results: There was a significant decrease in volume of lung receiving 20 Gy with PBI (median, 4.4% vs. 7.5%; p 3 vs 4.85 Gy 3 , p = 0.07). PBI plans exposed more lung to 2.5 and 5 Gy. Conclusions: 3D-PBI exposes greater volumes of lung tissue to low doses of radiation and spares the amount of lung receiving higher doses when compared with WBI.

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

Science.gov (United States)

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

2006-01-01

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

Comparison of plantar pressure on normal -footed vs. high arch-footed badminton players in two-way lunge

Directory of Open Access Journals (Sweden)

parvane bazipoor

2017-03-01

Full Text Available Background: Compared to the individuals with a normal arch structure, those with high or low arch can be at an increased risk of overuse injuries. The risk of overuse injury among athletes is high due, in part, to the repeated loading of the lower extremities. The current study aimed to determine if foot type (high-arched or normal results in differences in plantar pressure during two badminton-specific movements (right-reverse lunge and right-lateral lunge. Methods: Twenty badminton players (10 with normal feet and 10 with higharched feet completed five trials in both right-reverse and right-lateral lunge, while in-shoe pressure data were collected at 100 Hz. The peak pressure and mean pressure were analyzed among the subjects for five major anatomical regions of the foot, using the independent t test in SPSS version 20. The foot type was determined by the foot posture index (FPI (α<0.05. Results: Results showed that the plantar pressure characteristics of normal and high-arched feet were different; such that in high-arched feet, as compared to normal subjects, there were significantly fewer pressure strikes in the medial (P=0.010 and lateral (P=0.002 mid-foot in right-reverse lunge and this was significantly higher in forefoot (P=0.003 and toes (P=0.010. However, the peak (P=0.157 and mean (P=0.104 pressure in the heel was higher but not significant. In the right- lateral lunge, we found statistically lower peak pressure stroke for the lateral mid-foot (P=0.010 and forefoot (P=0.011; however, the mean pressure was lower in the lateral (P=0.010 and medial (P=0.040 mid-foot and forefoot (P=0.120, although it was not significant in the forefoot. Conclusion: Results showed that the medial longitudinal arch of the foot might cause pressure differences in the feet among the players with normal and higharched feet. As the results demonstrated, in high-arched feet, there are some regions where plantar pressure is higher and some where it is lower

Protective ventilation reduces Pseudomonas aeruginosa growth in lung tissue in a porcine pneumonia model.

Science.gov (United States)

Sperber, Jesper; Nyberg, Axel; Lipcsey, Miklos; Melhus, Åsa; Larsson, Anders; Sjölin, Jan; Castegren, Markus

2017-08-31

Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury. A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H 2 O and a tidal volume of 6 ml x kg -1 . The control group (n = 10) had an end expiratory pressure of 5 cm H 2 O and a tidal volume of 10 ml x kg -1 . 10 11 colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements. The protective group displayed lower numbers of Pseudomonas aeruginosa (p protective group was unchanged (p protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.

Gene Expression Profiling in Lung Tissues from Rat Exposed to Lunar Dust Particles

Science.gov (United States)

Zhang, Ye; Lam, Chiu-Wing; Zalesak, Selina M.; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Scully, Robert R.; Williams, Kyle; Wu, Honglu; James, John T.

2014-01-01

The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (gene expression changes in lung tissues from rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, and 3 months after the last inhalation exposure. The total RNAs were isolated from lung tissues after being lavaged. The Agilent Rat GE v3 microarray was used to profile global gene expression (44K). The genes with significant expression changes are identified and the gene expression data were further analyzed using various statistical tools.

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

DEFF Research Database (Denmark)

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

2011-01-01

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

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

Radiation-induced changes in production of prostaglandins Fsub(2α), E, and thromboxane B2 in guinea pig parenchymal lung tissues

International Nuclear Information System (INIS)

Steel, L.K.; Catravas, G.N.

1982-01-01

At 1 hour to 4 days after unilateral exposure of guinea pigs to a single dose (0.5, 1.5, or 3.0 Gy) of gamma-radiation, changes were detected in prostaglandin and thromboxane concentrations in parenchymal lung tissues. At 1-3 hours after exposure, tissue levels of PGFsub(2α), PGE, and thromboxane B 2 were significantly elevated in animals receiving 3.0 Gy, with the magnitude of alteration revealing a radiation dose effect. By 24 hours, tissue prostaglandin and thromboxane levels returned to near control values. Lung tissue synthesis of prostaglandins in response to H-1 receptor stimulation by the exogenous addition of histamine revealed similar radiation dose effects. The carboxylic acid ionophore A23187, exogenously applied to lung tissues, revealed a transient peak of increased sensitivity to ionophore stimulation for TxB 2 synthesis at 24 hours and for PGFsub(2α) at 72 hours post-irradiation. The data suggest that significant alterations in prostaglandin and thromboxane concentrations in parenchymal lung tissues occur following irradiation, in a dose-dependent manner, and that altered responsiveness to H-1 receptor stimulation and divalent cation transport also occur

Mass Preserving Registration for lung CT

DEFF Research Database (Denmark)

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

2009-01-01

intensities due to differences in inspiration level, we propose to adjust the intensity of lung tissue according to the local expansion or compression. An image registration method without intensity adjustment is compared to the proposed method. Both approaches are evaluated on a set of 10 pairs of expiration...... and inspiration CT scans of children with cystic fibrosis lung disease. The proposed method with mass preserving adjustment results in significantly better alignment of the vessel trees. Analysis of local volume change for regions with trapped air compared to normally ventilated regions revealed larger...

Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo

International Nuclear Information System (INIS)

Ostrau, Christian; Huelsenbeck, Johannes; Herzog, Melanie; Schad, Arno; Torzewski, Michael; Lackner, Karl J.; Fritz, Gerhard

2009-01-01

Background and purpose: HMG-CoA-reductase inhibitors (statins) are widely used lipid-lowering drugs. Moreover, they have pleiotropic effects on cellular stress responses, proliferation and apoptosis in vitro. Here, we investigated whether lovastatin attenuates acute and subchronic ionizing radiation-induced normal tissue toxicity in vivo. Materials and methods: Four hours to 24 h after total body irradiation (6 Gy) of Balb/c mice, acute pro-inflammatory and pro-fibrotic responses were analyzed. To comprise subchronic radiation toxicity, mice were irradiated twice with 2.5 Gy and analyses were performed 3 weeks after the first radiation treatment. Molecular markers of inflammation and fibrosis as well as organ toxicities were measured. Results: Lovastatin attenuated IR-induced activation of NF-κB, mRNA expression of cell adhesion molecules and mRNA expression of pro-inflammatory and pro-fibrotic marker genes (i.e. TNFα, IL-6, TGFβ, CTGF, and type I and type III collagen) in a tissue- and time-dependent manner. γH2AX phosphorylation stimulated by IR was not affected by lovastatin, indicating that the statin has no major impact on the induction of DNA damage in vivo. Radiation-induced thrombopenia was significantly alleviated by lovastatin. Conclusions: Lovastatin inhibits both acute and subchronic IR-induced pro-inflammatory and pro-fibrotic responses and cell death in normal tissue in vivo. Therefore, lovastatin might be useful for selectively attenuating acute and subchronic normal tissue damage caused by radiotherapy.

Modification of the biologic dose to normal tissue by daily fraction

Energy Technology Data Exchange (ETDEWEB)

Wollin, M; Kagan, A R [Southern California Permanente Medical Group, Los Angeles Calif. (USA). Dep. of Radiation Therapy

1976-12-01

A method to predict normal tissue injury is proposed that includes high daily doses and unusual times successfully by calculating a new value called BIR (Biologic Index of Reaction). BIR and NSD were calculated for various normal tissue reactions. With the aid of statistical correlation techniques it is found that the BIR model is better than the NSD model in predicting radiation myelopathy and vocal edema and as good as NSD IN PREDICTING RIB FRACTURE/ Neither model predicts pericardial effusion. In no case were the results of BIR inferior to those of NSD.

Lung cancer and angiogenesis imaging using synchrotron radiation

International Nuclear Information System (INIS)

Liu Xiaoxia; Zhao Jun; Xu, Lisa X; Sun Jianqi; Gu Xiang; Liu Ping; Xiao Tiqiao

2010-01-01

Early detection of lung cancer is the key to a cure, but a difficult task using conventional x-ray imaging. In the present study, synchrotron radiation in-line phase-contrast imaging was used to study lung cancer. Lewis lung cancer and 4T1 breast tumor metastasis in the lung were imaged, and the differences were clearly shown in comparison to normal lung tissue. The effect of the object-detector distance and the energy level on the phase-contrast difference was investigated and found to be in good agreement with the theory of in-line phase-contrast imaging. Moreover, 3D image reconstruction of lung tumor angiogenesis was obtained for the first time using a contrast agent, demonstrating the feasibility of micro-angiography with synchrotron radiation for imaging tumor angiogenesis deep inside the body.

Rapid clearance of xanthines from airway and pulmonary tissues

International Nuclear Information System (INIS)

Kroell, F.K.; Karlsson, J.A.; Nilsson, E.; Ryrfeldt, A.; Persson, C.G.

1990-01-01

The airway and pulmonary fate of two antiasthma xanthines was examined in a guinea pig perfused lung preparation where the airway mechanics and airway microvascular perfusion are maintained at near normal values. 14C-theophylline or 14C-enprofylline was infused for 10, 30, and 300 s into the pulmonary artery of the guinea pig isolated lung. The radioactivity increased rapidly (within 10 s) in tracheobronchial as well as in lung tissue, confirming that the large airway microcirculation was well supplied also by the perfusion. The effluent concentrations of total 3H and 14C radioactivity at the onset, during, and after intrapulmonary infusion of 14C-labeled xanthines and 3H-sucrose were closely associated, suggesting that the xanthines, like sucrose, largely distributed in extracellular fluid and were not taken up by the tissues. No metabolites of enprofylline or theophylline could be detected in the lung tissue or lung effluent, suggesting that xanthines are not biotransformed by the guinea pig lung. After intratracheal instillation of 14C-theophylline, the peak radioactivity in the lung effluent appeared in the second 15-s fraction after instillation, and after 10 and 60 min, 68.1 +/- 4.7% and 86.9 +/- 8.4%, respectively, of the given dose had appeared in the lung effluent. The present data suggest a mainly extracellular distribution and a rapid clearance of xanthines from the lung and airway tissues. The rapid disappearance of topical theophylline may explain the lack of success of inhalation therapy with this drug

Differential expression patterns of housekeeping genes increase diagnostic and prognostic value in lung cancer

Directory of Open Access Journals (Sweden)

Yu-Chun Chang

2018-05-01

Full Text Available Background Using DNA microarrays, we previously identified 451 genes expressed in 19 different human tissues. Although ubiquitously expressed, the variable expression patterns of these “housekeeping genes” (HKGs could separate one normal human tissue type from another. Current focus on identifying “specific disease markers” is problematic as single gene expression in a given sample represents the specific cellular states of the sample at the time of collection. In this study, we examine the diagnostic and prognostic potential of the variable expressions of HKGs in lung cancers. Methods Microarray and RNA-seq data for normal lungs, lung adenocarcinomas (AD, squamous cell carcinomas of the lung (SQCLC, and small cell carcinomas of the lung (SCLC were collected from online databases. Using 374 of 451 HKGs, differentially expressed genes between pairs of sample types were determined via two-sided, homoscedastic t-test. Principal component analysis and hierarchical clustering classified normal lung and lung cancers subtypes according to relative gene expression variations. We used uni- and multi-variate cox-regressions to identify significant predictors of overall survival in AD patients. Classifying genes were selected using a set of training samples and then validated using an independent test set. Gene Ontology was examined by PANTHER. Results This study showed that the differential expression patterns of 242, 245, and 99 HKGs were able to distinguish normal lung from AD, SCLC, and SQCLC, respectively. From these, 70 HKGs were common across the three lung cancer subtypes. These HKGs have low expression variation compared to current lung cancer markers (e.g., EGFR, KRAS and were involved in the most common biological processes (e.g., metabolism, stress response. In addition, the expression pattern of 106 HKGs alone was a significant classifier of AD versus SQCLC. We further highlighted that a panel of 13 HKGs was an independent predictor of

Differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance

Directory of Open Access Journals (Sweden)

Ben-Zhou Feng

2016-04-01

Full Text Available Objective: To study the differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance. Methods: Preeclampsia placenta tissue and normal placenta tissue were collected and GPR30 expression levels were detected; human umbilical vein endothelial cells were cultured and processed with GRP30 inhibitor and GRP30 agonist combined with hypoxia-reoxygenation respectively, and cell apoptosis as well as pro-angiogenesis molecule and apoptosis molecule contents were detected. Results: mRNA content and protein content of GRP30 in preeclampsia placenta tissue were significantly lower than those in normal placenta tissue; apoptosis rate of G15 group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of H/R group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of G1 group was significantly lower than that of H/R group, VEGF and bFGF contents in supernatant were significantly higher than those of H/R group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly lower than those of H/R group. Conclusions: Low expression of GPR30 in placenta tissue is closely associated with the occurrence of preeclampsia, enhancing GPR function can reduce endothelial cell apoptosis and increase the contents of pro-angiogenesis factors, and it has endothelial protection effect.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L. [Dept.of Radiation Oncology, Henry Ford Health System, Detroit (United States)

2014-09-15

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

International Nuclear Information System (INIS)

Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L.

2014-01-01

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

Improved correction for the tissue fraction effect in lung PET/CT imaging

International Nuclear Information System (INIS)

Holman, Beverley F; Cuplov, Vesna; Millner, Lynn; Hutton, Brian F; Groves, Ashley M; Thielemans, Kris; Maher, Toby M

2015-01-01

Recently, there has been an increased interest in imaging different pulmonary disorders using PET techniques. Previous work has shown, for static PET/CT, that air content in the lung influences reconstructed image values and that it is vital to correct for this ‘tissue fraction effect’ (TFE). In this paper, we extend this work to include the blood component and also investigate the TFE in dynamic imaging. CT imaging and PET kinetic modelling are used to determine fractional air and blood voxel volumes in six patients with idiopathic pulmonary fibrosis. These values are used to illustrate best and worst case scenarios when interpreting images without correcting for the TFE. In addition, the fractional volumes were used to determine correction factors for the SUV and the kinetic parameters. These were then applied to the patient images. The kinetic parameters K 1 and K i along with the static parameter SUV were all found to be affected by the TFE with both air and blood providing a significant contribution to the errors. Without corrections, errors range from 34–80% in the best case and 29–96% in the worst case. In the patient data, without correcting for the TFE, regions of high density (fibrosis) appeared to have a higher uptake than lower density (normal appearing tissue), however this was reversed after air and blood correction. The proposed correction methods are vital for quantitative and relative accuracy. Without these corrections, images may be misinterpreted. (paper)

Improved correction for the tissue fraction effect in lung PET/CT imaging

Science.gov (United States)

Holman, Beverley F.; Cuplov, Vesna; Millner, Lynn; Hutton, Brian F.; Maher, Toby M.; Groves, Ashley M.; Thielemans, Kris

2015-09-01

Recently, there has been an increased interest in imaging different pulmonary disorders using PET techniques. Previous work has shown, for static PET/CT, that air content in the lung influences reconstructed image values and that it is vital to correct for this ‘tissue fraction effect’ (TFE). In this paper, we extend this work to include the blood component and also investigate the TFE in dynamic imaging. CT imaging and PET kinetic modelling are used to determine fractional air and blood voxel volumes in six patients with idiopathic pulmonary fibrosis. These values are used to illustrate best and worst case scenarios when interpreting images without correcting for the TFE. In addition, the fractional volumes were used to determine correction factors for the SUV and the kinetic parameters. These were then applied to the patient images. The kinetic parameters K1 and Ki along with the static parameter SUV were all found to be affected by the TFE with both air and blood providing a significant contribution to the errors. Without corrections, errors range from 34-80% in the best case and 29-96% in the worst case. In the patient data, without correcting for the TFE, regions of high density (fibrosis) appeared to have a higher uptake than lower density (normal appearing tissue), however this was reversed after air and blood correction. The proposed correction methods are vital for quantitative and relative accuracy. Without these corrections, images may be misinterpreted.

Andrographolide protects against radiation-induced lung injury in mice

International Nuclear Information System (INIS)

Kang Yahui; Wang Jinfeng; Zhang Qu; Huang Guanhong; Ma Jianxin; Yang Baixia; He Xiangfeng; Wang Zhongming

2014-01-01

Objective: To investigate the protective effect of andrographolide against radiation-induced lung injury (RILI) in C57BL/6 mice. Methods: Eighty C57BL mice were randomly divided into four groups: un-irradiated and normal saline-treated group (n = 20, control group), un-irradiated and andrographolide-treated group (n = 20, drug group), radiation plus normal saline-treated group (n = 20, radiation group) and radiation plus andrographolide-treated group (n = 20, treatment group). Before radiation, the mice in drug group and treatment group were administered daily via gavage with andrographolide (20 mg·kg -1 ·d -1 )) for 30 d, while the same volume of normal saline solution was given daily in the control and radiation groups. The model of RILI in C57BL mice was established by irradiating whole mouse chest with a single dose of 15 Gy of 6 MV X-rays. The pathological changes of the lung stained with HE/Masson were observed with a light microscope. The transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) in serum were examined by enzyme-linked immunosorbent assay. The activities of malondialdehyde (MDA) and superoxide dismutase (SOD) and the content of hydroxyproline in lung tissues were examined by corresponding kits. Results: Compared with radiation group, there was an obvious amelioration in pathological injury of lung tissue in the treatment group. The lung coefficient, the activities of lung tissue MDA, the content of Hyp, the serum content of hydroxide free radical, and the serum levels of TGF-β1 and TNF-α in the treatment group were significantly lower than those in radiation group at 24 th week, (t lung coefficient = 1.60, t MDA = 7.06, t Hyp = 17.44, t TGF-β1 = 16.67, t TNF-α = 14.03, P < 0.05), while slightly higher than those in control group. The activity of SOD was significantly higher in the treatment group than that in radiation group (t = 60.81, P < 0.05), while lower than those in control group and drug group. There were no

Expression and Its Clinical Significance of SLC22A18 in Non-small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Ming LEI

2012-01-01

Full Text Available Background and objective It has been proven that multidrug resistance (MDR is the main cause of chemotherapy failure in lung cancer. Research on emergence mechanisms of MDR has great clinical significance in improving the curative efficiency of lung cancer chemotherapy. Proteins encoded by the SLC22A18 gene, which is similar to the transmembrane transporter, may influence the sensitivity of chemotherapeutics as well as the metabolism and growth of cells. In addition, these proteins probably have some effect on the development of lung cancer MDR. The aim of the present study is to investigate the expression of SLC22A18 protein in non-small cell lung cancer (NSCLC as well as in corresponding normal lung tissue. Furthermore, the relationship between SLC22A18 expression and pathological grade and TNM stage is analyzed. Methods The expression of SLC22A18 was detected by EnVinsion in 96 cases with NSCLC and in corresponding normal lung tissue. Statistical analysis was performed using SPSS 17.0 statistical software. Results SLC22A18 was mainly located in cell membrane and cytoplasm. The expression level of SLC22A18 in NSCLC was significantly higher than that in normal tissue (P<0.01. The positive rates in squamous cell lung cancer and lung adenocarcinoma were 68% and 78.2%, respectively (P<0.05. Moreover, the higher expression of SLC22A18 was associated with lower histological grade and later TNM stage (P<0.05. Conclusion SLC22A18 protein is overexpressed in NSCLC, and its expression is correlated with pathological grade and TNM stage. These findings provide the experimental basis for investigating the role of tumor and chemoresistance.

Three-dimensional simultaneous optical coherence tomography and confocal fluorescence microscopy for investigation of lung tissue.

Science.gov (United States)

Gaertner, Maria; Cimalla, Peter; Meissner, Sven; Kuebler, Wolfgang M; Koch, Edmund

2012-07-01

Although several strategies exist for a minimal-invasive treatment of patients with lung failure, the mortality rate of acute respiratory distress syndrome still reaches 30% at minimum. This striking number indicates the necessity of understanding lung dynamics on an alveolar level. To investigate the dynamical behavior on a microscale, we used three-dimensional geometrical and functional imaging to observe tissue parameters including alveolar size and length of embedded elastic fibers during ventilation. We established a combined optical coherence tomography (OCT) and confocal fluorescence microscopy system that is able to monitor the distension of alveolar tissue and elastin fibers simultaneously within three dimensions. The OCT system can laterally resolve a 4.9 μm line pair feature and has an approximately 11 μm full-width-half-maximum axial resolution in air. confocal fluorescence microscopy visualizes molecular properties of the tissue with a resolution of 0.75 μm (laterally), and 5.9 μm (axially) via fluorescence detection of the dye sulforhodamine B specifically binding to elastin. For system evaluation, we used a mouse model in situ to perform lung distension by application of different constant pressure values within the physiological regime. Our method enables the investigation of alveolar dynamics by helping to reveal basic processes emerging during artificial ventilation and breathing.

Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis.

Directory of Open Access Journals (Sweden)

Yu-Zhe Song

Full Text Available The X-ray repair cross-complementing group 3 (XRCC3 protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs with corresponding 95% confidence intervals (CIs were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539 polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31-3.01, P = 0.001. A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97-1.68, P = 0.08. In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49-3.89, p = 0.0003 and breast irradiation (OR = 1.41, 95%CI: 1.02-1.95, p = 0.04, whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26-0.86, P = 0.01. Well-designed large-scale clinical studies are required to further validate our results.

Comparison of Tissue Stiffness Using Shear Wave Elastography in Men with Normal Testicular Tissue, Testicular Microlithiasis and Testicular Cancer

DEFF Research Database (Denmark)

Pedersen, Malene Roland; Møller, Henrik; Osther, Palle Jørn Sloth

2017-01-01

Objectives: To compare elastography measurements in men with normal testicular tissue, testicular microlithiasis and testicular cancer. Methods: A total of 248 consecutive patients were included. All men provided written informed consent. Testicular stiffness was assessed using shear wave...... elastography (SWE). Three SWE velocity measurements were assessed in each testicle. The patients were divided into three groups; men with normal testicular tissue (n=130), men with testicular microlithiasis (n=99) and men with testicular cancer (n=19). Results: We found a higher mean velocity in the group...... of patients with testicular cancer (1.92 m/s (95% CI 1.82-2.03)) compared to both the group with normal tissue (0.76 m/s (95% CI: 0.75-0.78)) (ptesticular microlithiasis 0.79 m/s (95% CI: 0.77-0.81) (ptesticular microlithiasis increased stiffness...

Normal-tissue radioprotection by overexpression of the copper-zinc and manganese superoxide dismutase genes

Energy Technology Data Exchange (ETDEWEB)

Veldwijk, Marlon R. [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Pharmacology of Cancer Treatment (G402), German Cancer Research Center, Heidelberg (Germany); Herskind, Carsten; Wenz, Frederik [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Sellner, Leopold; Zeller, W. Jens [Pharmacology of Cancer Treatment (G402), German Cancer Research Center, Heidelberg (Germany); Radujkovic, Aleksandar [Dept. of Internal Medicine V, Univ. of Heidelberg (Germany); Laufs, Stephanie [Dept. of Experimental Surgery, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Molecular Oncology of Solid Tumors (G360), German Cancer Research Center, Heidelberg (Germany); Fruehauf, Stefan [Center for Tumor Diagnostic and Therapy, Paracelsus-Klinik, Osnabrueck (Germany)

2009-08-15

Background and Purpose: Protection of normal tissue against radiation-induced damage may increase the therapeutic ratio of radiotherapy. A promising strategy for testing this approach is gene therapy-mediated overexpression of the copper-zinc (CuZnSOD) or manganese superoxide dismutase (MnSOD) using recombinant adeno-associated viral (rAAV2) vectors. The purpose of this study was to test the modulating effects of the SOD genes on human primary lung fibroblasts (HPLF) after irradiation. Material and Methods: HPLF were transduced with rAAV2 vectors containing cDNA for the CuZnSOD, MnSOD or a control gene. The cells were irradiated (1-6 Gy), and gene transfer efficiency, apoptosis, protein expression/activity, and radiosensitivity measured by the colony-forming assay determined. Results: After transduction, 90.0% {+-} 6.4% of the cells expressed the transgene. A significant fivefold overexpression of both SOD was confirmed by an SOD activity assay (control: 21.1 {+-} 12.6, CuZnSOD: 95.1 {+-} 17.1, MnSOD: 108.5 {+-} 36.0 U SOD/mg protein) and immunohistochemistry. CuZnSOD and MnSOD overexpression resulted in a significant radioprotection of HPLF compared to controls (surviving fraction [SF] ratio SOD/control > 1): CuZnSOD: 1.18-fold (95% confidence interval [CI]: 1.06-1.32; p = 0.005), MnSOD: 1.23-fold (95% CI: 1.07-1.43; p = 0.01). Conclusion: Overexpression of CuZnSOD and MnSOD in HPLF mediated an increase in clonogenic survival after irradiation compared to controls. In previous works, a lack of radioprotection in SOD-overexpressing tumor cells was observed. Therefore, the present results suggest that rAAV2 vectors are promising tools for the delivery of radioprotective genes in normal tissue. (orig.)

Age-dependent accumulation of heavy metals in liver, kidney and lung tissues of homing pigeons in Beijing, China.

Science.gov (United States)

Cui, Jia; Wu, Bin; Halbrook, Richard S; Zang, Shuying

2013-12-01

Biomonitoring provides direct evidence of the bioavailability and accumulation of toxic elements in the environment. In the current study, 1-2, 5-6, and 9-10+ year old homing pigeons collected from the Haidian District of Beijing during 2011 were necropsied and concentrations of cadmium, lead, and mercury were measured in liver, lung, and kidney tissue. At necropsy, gray/black discoloration of the margins of the lungs was observed in 98 % of the pigeons. There were no significant differences in metal concentrations as a function of gender. Cadmium concentrations in all tissues and Pb concentrations in the lung tissues were significantly greater in 9-10+ year old pigeons compared to other age groups indicating that Cd and Pb were bioavailable. Mercury concentrations were not significantly different among age groups. Cadmium concentrations in kidney and lung tissues of 9-10+ year old pigeons were similar to or exceeded concentrations of Cd reported in pigeons from another high traffic urban area and most wild avian species from Korea suggesting that Cd in this region of Beijing may be of concern. Homing pigeons provide valuable exposure and bioaccumulation data not readily available from air monitoring alone, thus providing information regarding potential health effects in wildlife and humans in urban areas. As environmental quality standards are implemented in China, homing pigeons will serve as a valuable bio-monitor of the efficacy of these actions.

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

International Nuclear Information System (INIS)

Bertelsen, Anders; Schytte, Tine; Bentzen, Soren M.; Hansen, Olfred; Nielsen, Morten; Brink, Carsten

2011-01-01

Background: Density changes of healthy lung tissue during radiotherapy as observed by Cone Beam CT (CBCT) might be an early indicator of patient specific lung toxicity. This study investigates the time course of CBCT density changes and tests for a possible correlation with locally delivered dose. Methods: A total of 665 CBCTs in 65 lung cancer patients treated with IMRT/VMAT to 60 or 66 Gy in 2 Gy fractions were analyzed. For each patient, CBCT lung density changes during the treatment course were related to the locally delivered dose. Results: A dose response is observed for the patient population at the end of the treatment course. However, the observed dose response is highly variable among patients. Density changes at 10th and 20th fraction are clearly correlated to those observed at the end of the treatment course. Conclusions: CBCT density changes in healthy lung tissue during radiotherapy correlate with the locally delivered dose and can be detected relatively early during the treatment. If these density changes are correlated to subsequent clinical toxicity this assay could form the basis for biological adaptive radiotherapy.

SU-F-T-187: Quantifying Normal Tissue Sparing with 4D Robust Optimization of Intensity Modulated Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Newpower, M; Ge, S; Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: To report an approach to quantify the normal tissue sparing for 4D robustly-optimized versus PTV-optimized IMPT plans. Methods: We generated two sets of 90 DVHs from a patient’s 10-phase 4D CT set; one by conventional PTV-based optimization done in the Eclipse treatment planning system, and the other by an in-house robust optimization algorithm. The 90 DVHs were created for the following scenarios in each of the ten phases of the 4DCT: ± 5mm shift along x, y, z; ± 3.5% range uncertainty and a nominal scenario. A Matlab function written by Gay and Niemierko was modified to calculate EUD for each DVH for the following structures: esophagus, heart, ipsilateral lung and spinal cord. An F-test determined whether or not the variances of each structure’s DVHs were statistically different. Then a t-test determined if the average EUDs for each optimization algorithm were statistically significantly different. Results: T-test results showed each structure had a statistically significant difference in average EUD when comparing robust optimization versus PTV-based optimization. Under robust optimization all structures except the spinal cord received lower EUDs than PTV-based optimization. Using robust optimization the average EUDs decreased 1.45% for the esophagus, 1.54% for the heart and 5.45% for the ipsilateral lung. The average EUD to the spinal cord increased 24.86% but was still well below tolerance. Conclusion: This work has helped quantify a qualitative relationship noted earlier in our work: that robust optimization leads to plans with greater normal tissue sparing compared to PTV-based optimization. Except in the case of the spinal cord all structures received a lower EUD under robust optimization and these results are statistically significant. While the average EUD to the spinal cord increased to 25.06 Gy under robust optimization it is still well under the TD50 value of 66.5 Gy from Emami et al. Supported in part by the NCI U19 CA021239.

Estimation of lung volume and pulmonary blood volume from radioisotopic images

International Nuclear Information System (INIS)

Kanazawa, Minoru

1989-01-01

Lung volume and pulmonary blood volume in man were estimated from the radioisotopic image using single photon emission computed tomography (SPECT). Six healthy volunteers were studied in a supine position with normal and altered lung volumes by applying continuous negative body-surface pressure (CNP) and by positive end-expiratory pressure (PEEP). 99m Tc labeled human serum albumin was administered as an aerosol to image the lungs. The CNP caused the diaphragm to be lowered and it increased the mean lung tissue volume obtained by SPECT from 3.09±0.49 l for baseline to 3.67±0.62 l for 10 cmH 2 O (p 2 O (p 2 O), respectively. The PEEP also increased the lung tissue volume to 3.68±0.68 l for 10 cmH 2 O as compared with the baseline (p 2 O PEEP. The lung tissue volume obtained by SPECT showed a positive correlation with functional residual capacity measured by the He dilution method (r=0.91, p 99m Tc-labeled red blood cells. The L/H ratio decreased after either the CNP or PEEP, suggesting a decrease in the blood volume per unit lung volume. However, it was suggested that the total pulmonary blood volume increased slightly either on the CNP (+7.4% for 10 cmH 2 O, p 2 O,p<0.05) when we extrapolated the L/H ratio to the whole lungs by multiplying the lung tissue volume obtained by SPECT. We concluded that SPECT could offer access to the estimation of lung volume and pulmonary blood volume in vivo. (author)

Monte Carlo calculations of lung dose in ORNL phantom for boron neutron capture therapy

International Nuclear Information System (INIS)

Krstic, D.; Markovic, V.M.; Jovanovic, Z.; Milenkovic, B.; Nikezic, D.; Atanackovic, J.

2014-01-01

Monte Carlo simulations were performed to evaluate dose for possible treatment of cancers by boron neutron capture therapy (BNCT). The computational model of male Oak Ridge National Laboratory (ORNL) phantom was used to simulate tumours in the lung. Calculations have been performed by means of the MCNP5/X code. In this simulation, two opposite neutron beams were considered, in order to obtain uniform neutron flux distribution inside the lung. The obtained results indicate that the lung cancer could be treated by BNCT under the assumptions of calculations. The difference in evaluated dose in cancer and normal lung tissue suggests that BNCT could be applied for the treatment of cancers. The difference in exposure of cancer and healthy tissue can be observed, so the healthy tissue can be spared from damage. An absorbed dose ratio of metastatic tissue-to-the healthy tissue was ∼5. Absorbed dose to all other organs was low when compared with the lung dose. Absorbed dose depth distribution shows that BNC therapy can be very useful in the treatments for tumour. The ratio of the tumour absorbed dose and irradiated healthy tissue absorbed dose was also ∼5. It was seen that an elliptical neutron field was better irradiation choice. (authors)

68Ga-DOTATOC PET/CT and somatostatin receptor (sst1-sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax

International Nuclear Information System (INIS)

Boy, Christian; Poeppel, Thorsten D.; Jentzen, Walter; Brandau, Wolfgang; Bockisch, Andreas; Heusner, Till A.; Antoch, Gerald; Redmann-Bischofs, Anja; Unger, Nicole; Mann, Klaus; Petersenn, Stephan

2011-01-01

By targeting somatostatin receptors (sst) radiopeptides have been established for both diagnosis and therapy. For physiologically normal human tissues the study provides a normative database of maximum standardized uptake value (SUV max ) and sst mRNA. A total of 120 patients were subjected to diagnostic 68 Ga-DOTATOC positron emission tomography (PET)/CT (age range 19-83 years). SUV max values were measured in physiologically normal tissues defined by normal morphology, absence of surgical intervention and absence of metastatic spread during clinical follow-up. Expression of sst subtypes (sst1-sst5) was measured independently in pooled adult normal human tissue by real-time reverse transcriptase polymerase chain reaction (RT-PCR). SUV max revealed a region-specific pattern (e.g., mean ± SD, spleen 31.1 ± 10.9, kidney 16.9 ± 5.3, liver 12.8 ± 3.6, stomach 7.0 ± 3.1, head of pancreas 6.2 ± 2.3, small bowel 4.8 ± 1.8, thyroid 4.7 ± 2.2, bone 3.9 ± 1.3, large bowel 2.9 ± 0.8, muscle 2.1 ± 0.5, parotid gland 1.9 ± 0.6, axillary lymph node 0.8 ± 0.3 and lung 0.7 ± 0.3). SUV max was age independent. Gender differences were evident within the thyroid (female/male: 3.7 ± 1.6/5.5 ± 2.4, p max values exclusively correlated with sst2 expression (r = 0.846, p max with the expression of the other four subtypes. In normal human tissues 68 Ga-DOTATOC imaging has been related to the expression of sst2 at the level of mRNA. The novel normative database may improve diagnostics, monitoring and therapy of sst-expressing tumours or inflammation on a molecular basis. (orig.)

EXSPRESSION OF MDR-GENES AND MONORESISTANCE GENES IN NON-SMALL-CELL LUNG CANCER

Directory of Open Access Journals (Sweden)

E. L. Yumov

2014-01-01

Full Text Available We studied the expression of multidrug resistance genes (MDR and monoresistance genes in normal bronchial tissue and tumor tissue of the non-small cell lung cancer (NSCLC after neoadjuvant chemotherapy (NACT (vinorelbine-carboplatine. The study included 30 patients with NSCLC (Т2–4N0–3M0. Normal bronchial tissue, normal lung tissue and tumor tissue collected during surgery following neoadjuvant chemotherapy (NACT served as a material of the study. The expression levels of MDR genes (ABCB1, ABCB2, ABCC1, ABCC2, ABCС5, ABCG1, ABCG2, GSTP and MVP, and monoresistance genes (BRCA1, ERCC1, RRM1, TOP1, TOP2A, TUBB3 and TYMS were estimated by quantitative reverse transcriptase PCR (RT-qPCR. The expression levels of some MDR genes and monoresistance genes (АВСВ1, АВСВ2, ABCG1, ERCC1, GSTP1 and MVP were significantly higher in the bronchi than in tumor tissue. The expression of ABCG1, ABCG2 and ERCC1 genes was higher in patients with T1-2 cancer than in patients with T3-4 cancer. Patients with adenocarcinoma had higher expression of BRCA1, MVP and ABCB1 genes than patients with squamous cell lung cancer. A tendency towards reduction in the expression level of MDR-genes and monoresistance genes was observed in patients with partial tumor regression compared to that observed in patients with stable disease. These findings were consistent with the previous data on reduction in the MDR-gene expression after chemotherapy with a good response in breast cancer patients.

Overexpression and small molecule-triggered downregulation of CIP2A in lung cancer.

Directory of Open Access Journals (Sweden)

Liang Ma

Full Text Available Lung cancer is the leading cause of cancer deaths worldwide, with a five-year overall survival rate of only 15%. Cancerous inhibitor of PP2A (CIP2A is a human oncoprotein inhibiting PP2A in many human malignancies. However, whether CIP2A can be a new drug target for lung cancer is largely unclear.Normal and malignant lung tissues were derived from 60 lung cancer patients from southern China. RT-PCR, Western blotting and immunohistochemistry were used to evaluate the expression of CIP2A. We found that among the 60 patients, CIP2A was undetectable or very low in paratumor normal tissues, but was dramatically elevated in tumor samples in 38 (63.3% patients. CIP2A overexpression was associated with cigarette smoking. Silencing CIP2A by siRNA inhibited the proliferation and clonogenic activity of lung cancer cells. Intriguingly, we found a natural compound, rabdocoetsin B which is extracted from a Traditional Chinese Medicinal herb Rabdosia coetsa, could induce down-regulation of CIP2A and inactivation of Akt pathway, and inhibit proliferation and induce apoptosis in a variety of lung cancer cells.Our findings strongly indicate that CIP2A could be an effective target for lung cancer drug development, and the therapeutic potentials of CIP2A-targeting agents warrant further investigation.

Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis.

Science.gov (United States)

Tominaga, Masaki; Okamoto, Masaki; Kawayama, Tomotaka; Matsuoka, Masanobu; Kaieda, Shinjiro; Sakazaki, Yuki; Kinoshita, Takashi; Mori, Daisuke; Inoue, Akira; Hoshino, Tomoaki

2017-09-01

Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Trace elemental correlation study in malignant and normal breast tissue by PIXE technique

International Nuclear Information System (INIS)

Raju, G.J. Naga; Sarita, P.; Kumar, M. Ravi; Murty, G.A.V. Ramana; Reddy, B. Seetharami; Lakshminarayana, S.; Vijayan, V.; Lakshmi, P.V.B. Rama; Gavarasana, Satyanarayana; Reddy, S. Bhuloka

2006-01-01

Particle induced X-ray emission technique was used to study the variations in trace elemental concentrations between normal and malignant human breast tissue specimens and to understand the effects of altered homeostasis of these elements in the etiology of breast cancer. A 3 MeV proton beam was used to excite the biological samples of normal and malignant breast tissues. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb and Sr were identified and their relative concentrations were estimated. Almost all the elements were found to be elevated (p < 0.05, Wilcoxon signed-ranks test) in the cancerous tissues when compared with normal tissues. The excess levels of trace elements observed in the cancerous breast tissues could either be a cause or a consequence of breast cancer. Regarding their role in the initiation or promotion of breast cancer, one possible interpretation is that the elevated levels of Cu, Fe and Cr could have led to the formation of free radicals or other reactive oxygen species (ROS) that adversely affect DNA thereby causing breast cancer, which is mainly attributed to genetic abnormalities. Moreover, since Cu and Fe are required for angiogenesis, elevated concentrations of these elements are likely to promote breast cancer by increasing the blood supply for tumor growth. On the other hand elevated concentrations of elements in breast cancer tissues might also be a consequence of the cancer. This can be understood in terms of the biochemical and histological differences between normal and cancerous breast tissues. Tumors, characterized by unregulated multiplication of cells, need an ever-increasing supply of essential nutrients including trace elements. This probably results in an increased vascularity of malignant tissues, which in turn leads to enhancement of elemental concentrations in tumors

The components of somatostatin and ghrelin systems are altered in neuroendocrine lung carcinoids and associated to clinical-histological features.

Science.gov (United States)

Herrera-Martínez, Aura D; Gahete, Manuel D; Sánchez-Sánchez, Rafael; Salas, Rosa Ortega; Serrano-Blanch, Raquel; Salvatierra, Ángel; Hofland, Leo J; Luque, Raúl M; Gálvez-Moreno, María A; Castaño, Justo P

2017-07-01

Lung carcinoids (LCs) are rare tumors that comprise 1-5% of lung malignancies but represent 20-30% of neuroendocrine tumors. Their incidence is progressively increasing and a better characterization of these tumors is required. Alterations in somatostatin (SST)/cortistatin (CORT) and ghrelin systems have been associated to development/progression of various endocrine-related cancers, wherein they may become useful diagnostic, prognostic and therapeutic biomarkers. We aimed to evaluate the expression levels of ghrelin and SST/CORT system components in LCs, as well as to explore their putative relationship with histological/clinical characteristics. An observational retrospective study was performed; 75 LC patients with clinical/histological characteristics were included. Samples from 46 patients were processed to isolate mRNA from tumor and adjacent non-tumor region, and the expression levels of SST/CORT and ghrelin systems components, determined by quantitative-PCR, were compared to those of 7 normal lung tissues. Patient cohort was characterized by mean age 53±15 years, 48% males, 34% with tobacco exposure; 71.4/28.6% typical/atypical carcinoids, 21.7% incidental tumors, 4.3% functioning tumors, 17.7% with metastasis. SST/CORT and ghrelin system components were expressed at variable levels in a high proportion of tumors, as well as in adjacent non-tumor tissues, while a lower proportion of normal lung samples also expressed these molecules. A gradation was observed from normal non-neoplastic lung tissues, non-tumor adjacent tissue and LCs, being SST, sst4, sst5, GHS-R1a and GHS-R1b overexpressed in tumor tissue compared to normal tissue. Importantly, several SST/CORT and ghrelin system components displayed significant correlations with relevant clinical parameters, such as necrosis, peritumoral and vascular invasion, or metastasis. Altogether, these data reveal a prominent, widespread expression of key SST/CORT/ghrelin system components in LCs, where they display

iASPP is over-expressed in human non-small cell lung cancer and regulates the proliferation of lung cancer cells through a p53 associated pathway

International Nuclear Information System (INIS)

Chen, Jinfeng; Xie, Fei; Zhang, Lijian; Jiang, Wen G

2010-01-01

iASPP is a key inhibitor of tumour suppressor p53 and is found to be up-regulated in certain malignant conditions. The present study investigated the expression of iASPP in clinical lung cancer, a leading cancer type in the world, and the biological impact of this molecule on lung cancer cells. iASPP protein levels in lung cancer tissues were evaluated using an immunohistochemical method. In vitro, iASPP gene expression was suppressed with a lentvirus-mediated shRNA method and the biological impact after knocking down iASSP on lung cancer cell lines was investigated in connection with the p53 expression status. We showed here that the expression of iASPP was significantly higher in lung cancer tissues compared with the adjacent normal tissues. iASPP shRNA treatment resulted in a down-regulation of iASPP in lung cancer cells. There was a subsequent reduction of cell proliferation of the two lung tumour cell lines A459 and 95D both of which had wild-type p53 expression. In contrast, reduction of iASPP in H1229 cells, a cell with little p53 expression, had no impact on its growth rate. iASPP regulates the proliferation and motility of lung cancer cells. This effect is intimately associated with the p53 pathway. Together with the pattern of the over-expression in clinical lung cancers, it is concluded that iASPP plays an pivotal role in the progression of lung cancer and is a potential target for lung cancer therapy

SU-E-T-168: Evaluation of Normal Tissue Damage in Head and Neck Cancer Treatments

International Nuclear Information System (INIS)

Ai, H; Zhang, H

2014-01-01

Purpose: To evaluate normal tissue toxicity in patients with head and neck cancer by calculating average survival fraction (SF) and equivalent uniform dose (EUD) for normal tissue cells. Methods: 20 patients with head and neck cancer were included in this study. IMRT plans were generated using EclipseTM treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The average SF for three different normal tissue cells of each concerned structure can be calculated from dose spectrum acquired from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant that represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Finally, EUDs for three types of normal tissue of each structure were calculated from average SF. Results: The EUDs of the brainstem, spinal cord, parotid glands, brachial plexus and etc were calculated. Our analysis indicated that the brainstem can absorb as much as 14.3% of prescription dose to the tumor if the cell line is radiosensitive. In addition, as much as 16.1% and 18.3% of prescription dose were absorbed by the brainstem for moderately radiosensitive and radio-resistant cells, respectively. For the spinal cord, the EUDs reached up to 27.6%, 35.0% and 42.9% of prescribed dose for the three types of radiosensitivities respectively. Three types of normal cells for parotid glands can get up to 65.6%, 71.2% and 78.4% of prescription dose, respectively. The maximum EUDs of brachial plexsus were calculated as 75.4%, 76.4% and 76.7% of prescription for three types of normal cell lines. Conclusion: The results indicated that EUD can be used to quantify and evaluate the radiation damage to surrounding normal tissues. Large variation of normal tissue EUDs may come from variation of target volumes and radiation beam orientations among the patients

Adipose Tissues Characteristics of Normal, Obesity, and Type 2 Diabetes in Uygurs Population

Directory of Open Access Journals (Sweden)

Jun Zhang

2015-01-01

Full Text Available Our results showed that, at the same BMI level, Uygurs have greater WHR values, abdominal visceral fat content, and diabetes risks than Kazaks. In addition, values of HDL-C in Uygur subjects were lower than those in Kazak subjects, and values of creatinine, uric acid, diastolic blood pressure, blood glucose, and fructosamine in Uygur male subjects were lower than those in Kazak male subjects. In contrast, systolic blood pressure values in Uygur subjects were greater than those in Kazak subjects, and blood glucose values were greater in Uygur female subjects than in Kazak female subjects. Additionally, in Uygurs, visceral adipose tissue expression levels of TBX1 and TCF21 were greater in obesity group than in normal and T2DM groups and lower in T2DM group than in normal group (P<0.01. The visceral adipose tissue expression levels of APN in normal group was greater than those in obesity and T2DM groups, and visceral adipose tissue expression levels of TNF-α and MCP-1 in normal group were lower than those in obesity and T2DM groups (P<0.01. In conclusion, T2DM in Uygurs was mainly associated with not only distribution of adipose tissue in body, but also change in metabolic activity and adipocytokines secretion of adipose tissue.