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Sample records for assessing lung carcinogenic

  1. Exposure Assessment Suggests Exposure to Lung Cancer Carcinogens in a Painter Working in an Automobile Bumper Shop

    Science.gov (United States)

    Kim, Boowook; Yoon, Jin-Ha; Choi, Byung-Soon; Shin, Yong Chul

    2013-01-01

    A 46-year-old man who had worked as a bumper spray painter in an automobile body shop for 15 years developed lung cancer. The patient was a nonsmoker with no family history of lung cancer. To determine whether the cancer was related to his work environment, we assessed the level of exposure to carcinogens during spray painting, sanding, and heat treatment. The results showed that spray painting with yellow paint increased the concentration of hexavalent chromium in the air to as much as 118.33 μg/m3. Analysis of the paint bulk materials showed that hexavalent chromium was mostly found in the form of lead chromate. Interestingly, strontium chromate was also detected, and the concentration of strontium chromate increased in line with the brightness of the yellow color. Some paints contained about 1% crystalline silica in the form of quartz. PMID:24422178

  2. Exposure Assessment Suggests Exposure to Lung Cancer Carcinogens in a Painter Working in an Automobile Bumper Shop

    Directory of Open Access Journals (Sweden)

    Boowook Kim

    2013-12-01

    Full Text Available A 46-year-old man who had worked as a bumper spray painter in an automobile body shop for 15 years developed lung cancer. The patient was a nonsmoker with no family history of lung cancer. To determine whether the cancer was related to his work environment, we assessed the level of exposure to carcinogens during spray painting, sanding, and heat treatment. The results showed that spray painting with yellow paint increased the concentration of hexavalent chromium in the air to as much as 118.33 μg/m3. Analysis of the paint bulk materials showed that hexavalent chromium was mostly found in the form of lead chromate. Interestingly, strontium chromate was also detected, and the concentration of strontium chromate increased in line with the brightness of the yellow color. Some paints contained about 1% crystalline silica in the form of quartz.

  3. Metformin prevents tobacco carcinogen-induced lung tumorigenesis

    Science.gov (United States)

    Memmott, Regan M.; Mercado, Jose R.; Maier, Colleen R.; Kawabata, Shigeru; Fox, Stephen D.; Dennis, Phillip A.

    2011-01-01

    Activation of the mTOR pathway is an important and early event in tobacco carcinogen-induced lung tumorigenesis, and therapies that target mTOR could be effective in the prevention or treatment of lung cancer. The biguanide metformin, which is widely prescribed for the treatment of type II diabetes, might be a good candidate for lung cancer chemoprevention because it activates AMPK, which can inhibit the mTOR pathway. To test this, A/J mice were treated with oral metformin after exposure to the tobacco carcinogen NNK. Metformin reduced lung tumor burden by up to 53% at steady-state plasma concentrations that are achievable in humans. mTOR was inhibited in lung tumors but only modestly. To test whether intraperitoneal administration of metformin might improve mTOR inhibition, we injected mice and assessed biomarkers in liver and lung tissues. Plasma levels of metformin were significantly higher after injection than oral administration. In liver tissue, metformin activated AMPK and inhibited mTOR. In lung tissue, metformin did not activate AMPK but inhibited phosphorylation of IGF-IR/IR, Akt, ERK, and mTOR. This suggested that metformin indirectly inhibited mTOR in lung tissue by decreasing activation of IGF-1R/IR and Akt upstream of mTOR. Based on these data, we repeated the NNK-induced lung tumorigenesis study using intraperitoneal administration of metformin. Metformin decreased tumor burden by 72%, which correlated with decreased cellular proliferation and marked inhibition of mTOR in tumors. These studies show that metformin prevents tobacco carcinogen-induced lung tumorigenesis, and support clinical testing of metformin as a chemopreventive agent. PMID:20810672

  4. Risk assessment of carcinogens in food.

    Science.gov (United States)

    Barlow, Susan; Schlatter, Josef

    2010-03-01

    Approaches for the risk assessment of carcinogens in food have evolved as scientific knowledge has advanced. Early methods allowed little more than hazard identification and an indication of carcinogenic potency. Evaluation of the modes of action of carcinogens and their broad division into genotoxic and epigenetic (non-genotoxic, non-DNA reactive) carcinogens have played an increasing role in determining the approach followed and provide possibilities for more detailed risk characterisation, including provision of quantitative estimates of risk. Reliance on experimental animal data for the majority of risk assessments and the fact that human exposures to dietary carcinogens are often orders of magnitude below doses used in experimental studies has provided a fertile ground for discussion and diverging views on the most appropriate way to offer risk assessment advice. Approaches used by national and international bodies differ, with some offering numerical estimates of potential risks to human health, while others express considerable reservations about the validity of quantitative approaches requiring extrapolation of dose-response data below the observed range and instead offer qualitative advice. Recognising that qualitative advice alone does not provide risk managers with information on which to prioritise the need for risk management actions, a "margin of exposure" approach for substances that are both genotoxic and carcinogenic has been developed, which is now being used by the World Health Organization and the European Food Safety Authority. This review describes the evolution of risk assessment advice on carcinogens and discusses examples of ways in which carcinogens in food have been assessed in Europe.

  5. Comparison of exposure assessment methods for occupational carcinogens in a multi-centre lung cancer case-control study

    NARCIS (Netherlands)

    Peters, Susan; Vermeulen, Roel; Cassidy, Adrian; 't Mannetje, Andrea; van Tongeren, Martie; Boffetta, Paolo; Straif, Kurt; Kromhout, Hans

    Objectives Retrospective exposure assessment remains a problematic aspect of population-based case-control studies. Different methods have been developed, including case-by-case expert assessment and job-exposure matrices (JEM). The present analyses compare exposure prevalence and risk estimates

  6. Comparison of exposure assessment methods for occupational carcinogens in a multi-centre lung cancer case-control study.

    Science.gov (United States)

    Peters, Susan; Vermeulen, Roel; Cassidy, Adrian; Mannetje, Andrea 't; van Tongeren, Martie; Boffetta, Paolo; Straif, Kurt; Kromhout, Hans

    2011-02-01

    Retrospective exposure assessment remains a problematic aspect of population-based case-control studies. Different methods have been developed, including case-by-case expert assessment and job-exposure matrices (JEM). The present analyses compare exposure prevalence and risk estimates derived by different exposure assessment methods. In the context of a case-control study conducted in seven European countries, exposure was estimated for asbestos, diesel motor emissions (DME) and crystalline silica, using three different assessment methods. First, experts assigned exposures to all reported jobs on a case-by-case basis. Second, a population-specific JEM (PSJEM) was developed using the expert assessments of controls only, and re-applied to all study subjects. Third, an independent general population JEM (GPJEM) was created by occupational exposure experts not involved in the original study, and applied to study subjects. Results from these methods were compared. There was poor to fair agreement in assigned exposure between expert assessment and the GPJEM (kappas: asbestos 0.17; DME 0.48; silica 0.38). Exposure prevalence was significantly heterogeneous (psilica diminished. It has been previously advocated that the expert assessment approach to assign exposures based on detailed questionnaire responses provides more accurate exposure estimates than JEM-based results. However, current results demonstrated little, if any, advantage of case-by-case assessment when compared to a JEM approach.

  7. Chemoprevention with Acetylsalicylic Acid, Vitamin D and Calcium Reduces Risk of Carcinogen-induced Lung Tumors

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, J

    2013-01-01

    Background/Aim: Research has shown that chemoprevention may be effective against the development of lung cancer. The purpose of the present study was to evaluate the effect of oral chemoprevention in a mouse model of tobacco carcinogen-induced lung tumor.......Background/Aim: Research has shown that chemoprevention may be effective against the development of lung cancer. The purpose of the present study was to evaluate the effect of oral chemoprevention in a mouse model of tobacco carcinogen-induced lung tumor....

  8. [Environmental carcinogenic agents and cancer prevention: risk assessment and management].

    Science.gov (United States)

    Tsugane, Shoichiro

    2013-11-01

    Many agents in our environment have been established as being carcinogenic, and in most cases, the carcinogenic properties of these agents were identified because of high-dose occupational or accidental exposure. Risk characterization, taking into account the dose-response relationship, and exposure assessment are essential for risk assessment and subsequent cancer prevention. Based on scientific risk assessment, risk management should be conducted practically by considering the economic, social, political, and other technical issues and by balancing the risks and benefits. Asbestos and environmental tobacco smoke are typical examples of established carcinogenic agents in the general environment, contributing to low-dose exposure. Further epidemiological studies are required to investigate the carcinogenicity of low-dose exposure to known carcinogenic agents such as arsenic and cadmium through dietary intake, radiation via medical and natural exposure, and air pollution due to diesel exhaust. In contrast, occupational chemical exposure to 1,2-dichloropropane and/or dichloromethane, whose carcinogenicity had not been established, was suggested to cause cholangiocarcinoma among workers involved in offset color proof-printing only after a rare situation of high-dose exposure was unveiled. Continuous monitoring of unusual cancer occurrences in target populations such as workers in occupational and regional settings as well as exposure reduction to suspected carcinogenic agents to levels as low as reasonably achievable is essential for reducing the risk of cancer due to environmental carcinogens.

  9. Genetic modifiers of carcinogen DNA adducts in target lung and peripheral blood mononuclear cells.

    Science.gov (United States)

    Lee, Mi-Sun; Su, Li; Mark, Eugene J; Wain, John C; Christiani, David C

    2010-12-01

    Measurement of carcinogen DNA adducts in blood has been used as a surrogate for the target lung tissue. We aimed to examine whether genetic polymorphisms in several metabolic pathway genes modify the relation between DNA adducts in target lung and blood. One hundred and thirty-five early-stage lung cancer patients from the Massachusetts General Hospital were studied. DNA adducts were measured by the (32)P-postlabeling assay in lung and blood mononuclear cells (MNCs) in a subset of 53 who had paired blood samples. Single-nucleotide polymorphisms (SNPs) were assessed in genes involved in phase II (GSTs, NAT2, EPHX and NQO1), DNA repair (ERCC1, ERCC2 and XRCC1) and DNA methylation (MTHFR C677T and A1298C) pathways. There was a significant correlation between DNA adduct levels in lung and blood within the different genotypes, with one exception. Significant modifications in adducts were found by variants in genes for phase II metabolism [NAT2 (1.51 for rapid versus 0.76 for slow, P = 0.022)], DNA repair [ERCC1 C118T (P = 0.014), ERCC2 (P = 0.003) and XRCC1 (P = 0.025)] and MTHFR [C677T (P = 0.005) and A1298C (P = 0.005)]. The relation between DNA adducts in blood MNCs and target lung tissue was significantly modified by the single-nucleotide polymorphisms in the three main pathways. Despite the relatively small sample size, our results suggest that genetic factors may need to be considered when assessing the association of DNA adducts using surrogate tissue in studies of lung cancer. Further studies are needed to better understand their role and the mechanisms.

  10. MTHFR Polymorphisms, Folate Intake, and Carcinogen DNA Adducts in the Lung

    OpenAIRE

    Lee, Mi-Sun; Asomaning, Kofi; Su, Li; Wain, John C.; Mark, Eugene J.; Christiani, David C.

    2012-01-01

    The methylenetetrahydrofolate reductase (MTHFR) genes and folate in one-carbon metabolism are essential for DNA methylation and synthesis. However, their role in carcinogen DNA damage in target lung tissue, a dosimeter for cancer risk, is not known. Our study aimed to investigate the association between genetic and nutritional one-carbon metabolism factors and DNA adducts in target lung. Data on 135 lung cancer cases from the Massachusetts General Hospital were studied. Genotyping was complet...

  11. The role of the Akt/mTOR pathway in tobacco-carcinogen induced lung tumorigenesis

    Science.gov (United States)

    Memmott, Regan M.; Dennis, Phillip A.

    2009-01-01

    Lung cancer is the leading cause of cancer-related death in the United States, and 85–90% of lung cancer cases are associated with tobacco use. Tobacco components promote lung tumorigenesis through genotoxic effects, as well as through biochemical modulation of signaling pathways such as the Akt/mTOR pathway that regulate cell proliferation and survival. This review will describe cell surface receptors and other upstream components required for tobacco-carcinogen induced activation of Akt and mTOR. Preclinical studies demonstrate that inhibitors of the Akt/mTOR pathway inhibit tumor formation in mouse models of carcinogen-induced lung tumorigenesis. Some of these inhibitors will be highlighted, and their clinical potential for the treatment and prevention of lung cancer will be discussed. PMID:20028747

  12. Isoform-Specific Effects of Wild-Type Ras Genes on Carcinogen-Induced Lung Tumorigenesis in Mice.

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    Jamie D Weyandt

    Full Text Available The gene KRAS is commonly mutated in lung cancer to encode a constitutively active and oncogenic protein that is well established to initiate and maintain lung tumorigenesis. However, the remaining wild-type KRAS protein, or the other family members HRAS and NRAS, can still be activated in the presence of oncogenic KRAS. Moreover, loss of any one of these three genes has been shown to increase the sensitivity of mice to the carcinogen urethane, which induces Kras mutation-positive early lung lesions. To determine the contribution of progressively disrupting Hras and Nras genes on urethane lung tumorigenesis, mice with different combinations of wild-type and null alleles of Hras and Nras were exposed with urethane and tumor burden was assessed. As previously reported, loss of one allele of Hras increased the sensitivity of mice to this carcinogen, and this effect was further exacerbated by the loss of the second Hras allele. However, loss of one or both alleles of Nras failed to alter tumor burden, either in the absence or presence of Hras, after exposure to urethane. Additionally, no obvious difference between lung lesions in mice with wild-type versus null alleles was detected, suggesting that wild-type Ras proteins may exert a tumor suppressive effects at the time of initiation, although other interpretations are certainly possible. In summary, these data suggest that in some genetic backgrounds inactivation of different wild-type Ras genes can have different effects on urethane-induced lung tumorigenesis.

  13. Isoform-Specific Effects of Wild-Type Ras Genes on Carcinogen-Induced Lung Tumorigenesis in Mice.

    Science.gov (United States)

    Weyandt, Jamie D; Carney, John M; Pavlisko, Elizabeth N; Xu, MengMeng; Counter, Christopher M

    2016-01-01

    The gene KRAS is commonly mutated in lung cancer to encode a constitutively active and oncogenic protein that is well established to initiate and maintain lung tumorigenesis. However, the remaining wild-type KRAS protein, or the other family members HRAS and NRAS, can still be activated in the presence of oncogenic KRAS. Moreover, loss of any one of these three genes has been shown to increase the sensitivity of mice to the carcinogen urethane, which induces Kras mutation-positive early lung lesions. To determine the contribution of progressively disrupting Hras and Nras genes on urethane lung tumorigenesis, mice with different combinations of wild-type and null alleles of Hras and Nras were exposed with urethane and tumor burden was assessed. As previously reported, loss of one allele of Hras increased the sensitivity of mice to this carcinogen, and this effect was further exacerbated by the loss of the second Hras allele. However, loss of one or both alleles of Nras failed to alter tumor burden, either in the absence or presence of Hras, after exposure to urethane. Additionally, no obvious difference between lung lesions in mice with wild-type versus null alleles was detected, suggesting that wild-type Ras proteins may exert a tumor suppressive effects at the time of initiation, although other interpretations are certainly possible. In summary, these data suggest that in some genetic backgrounds inactivation of different wild-type Ras genes can have different effects on urethane-induced lung tumorigenesis.

  14. Leisure time activities related to carcinogen exposure and lung cancer risk in never smokers. A case-control study

    Energy Technology Data Exchange (ETDEWEB)

    Ruano-Ravina, Alberto, E-mail: alberto.ruano@usc.es [Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela (Spain); CIBER de Epidemiología y Salud Pública CIBERESP, Barcelona (Spain); García-Lavandeira, José Antonio [Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela (Spain); Department of Preventive Medicine, A Coruña University Hospital Complex, Coruña (Spain); Torres-Durán, María [Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela (Spain); Service of Neumology, University Hospital Complex of Vigo, Vigo (Spain); Prini-Guadalupe, Luciana [Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela (Spain); Parente-Lamelas, Isaura [Service of Neumology, Ourense Hospital Complex, Ourense (Spain); Leiro-Fernández, Virginia [Service of Neumology, University Hospital Complex of Vigo, Vigo (Spain); Montero-Martínez, Carmen [Service of Neumology, University Hospital Complex of A Coruña, Coruña (Spain); González-Barcala, Francisco Javier; Golpe-Gómez, Antonio [Service of Neumology, Santiago de Compostela University Clinic Hospital, Santiago de Compostela (Spain); Martínez, Cristina [National Institute of Silicosis, University Hospital of Asturias, Oviedo, Asturias (Spain); Castro-Añón, Olalla [Service of Neumology, Hospital Lucus Augusti, Lugo (Spain); Mejuto-Martí, María José [Service of Neumology, Hospital Arquitecto Marcide, Ferrol (Spain); and others

    2014-07-15

    We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjusted also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78–2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93–5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer. - Highlights: • Some leisure time activities are associated with the exposure to carcinogenic substances. • These activities are model-making, painting (artistic or not), furniture refinishing or wood working. • Few studies have assessed lung cancer risk due to these hobbies and none in never-smokers. • Leisure activities related to exposure to carcinogenic substances present higher lung cancer risk. • The risk is higher when these activities are performed for more than 10 years.

  15. Environmental Carcinogen Releases and Lung Cancer Mortality in Rural-Urban Areas of the United States

    Science.gov (United States)

    Luo, Juhua; Hendryx, Michael

    2011-01-01

    Purpose: Environmental hazards are unevenly distributed across communities and populations; however, little is known about the distribution of environmental carcinogenic pollutants and lung cancer risk across populations defined by race, sex, and rural-urban setting. Methods: We used the Toxics Release Inventory (TRI) database to conduct an…

  16. Systematic network assessment of the carcinogenic activities of cadmium.

    Science.gov (United States)

    Chen, Peizhan; Duan, Xiaohua; Li, Mian; Huang, Chao; Li, Jingquan; Chu, Ruiai; Ying, Hao; Song, Haiyun; Jia, Xudong; Ba, Qian; Wang, Hui

    2016-11-01

    Cadmium has been defined as type I carcinogen for humans, but the underlying mechanisms of its carcinogenic activity and its influence on protein-protein interactions in cells are not fully elucidated. The aim of the current study was to evaluate, systematically, the carcinogenic activity of cadmium with systems biology approaches. From a literature search of 209 studies that performed with cellular models, 208 proteins influenced by cadmium exposure were identified. All of these were assessed by Western blotting and were recognized as key nodes in network analyses. The protein-protein functional interaction networks were constructed with NetBox software and visualized with Cytoscape software. These cadmium-rewired genes were used to construct a scale-free, highly connected biological protein interaction network with 850 nodes and 8770 edges. Of the network, nine key modules were identified and 60 key signaling pathways, including the estrogen, RAS, PI3K-Akt, NF-κB, HIF-1α, Jak-STAT, and TGF-β signaling pathways, were significantly enriched. With breast cancer, colorectal and prostate cancer cellular models, we validated the key node genes in the network that had been previously reported or inferred form the network by Western blotting methods, including STAT3, JNK, p38, SMAD2/3, P65, AKT1, and HIF-1α. These results suggested the established network was robust and provided a systematic view of the carcinogenic activities of cadmium in human. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. AKT1E¹⁷K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer.

    Science.gov (United States)

    Malanga, Donatella; Belmonte, Stefania; Colelli, Fabiana; Scarfò, Marzia; De Marco, Carmela; Oliveira, Duarte Mendes; Mirante, Teresa; Camastra, Caterina; Gagliardi, Monica; Rizzuto, Antonia; Mignogna, Chiara; Paciello, Orlando; Papparella, Serenella; Fagman, Henrik; Viglietto, Giuseppe

    2016-01-01

    The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6-2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26) locus (R26-AKT1E17K mice) we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype.

  18. MTHFR polymorphisms, folate intake and carcinogen DNA adducts in the lung.

    Science.gov (United States)

    Lee, Mi-Sun; Asomaning, Kofi; Su, Li; Wain, John C; Mark, Eugene J; Christiani, David C

    2012-09-01

    The methylenetetrahydrofolate reductase (MTHFR) genes and folate in one-carbon metabolism are essential for DNA methylation and synthesis. However, their role in carcinogen DNA damage in target lung tissue, a dosimeter for cancer risk, is not known. Our study aimed to investigate the association between genetic and nutritional one-carbon metabolism factors and DNA adducts in target lung. Data on 135 lung cancer cases from the Massachusetts General Hospital were studied. Genotyping was completed for MTHFR C677T (rs1801133) and A1298C (rs1801131). Information on dietary intake for one-carbon related micronutrients, folate and other B vitamin was derived from a validated food frequency questionnaire. DNA adducts in lung were measured by (32) P-postlabeling. After adjusting for potential confounders, DNA adduct levels in lung significantly increased by 69.2% [95% confidence interval (CI), 5.5% to 171.5%] for the MTHFR 1298AC+CC genotype. The high risk group, combining the A1298C (AC+CC) plus C677T (CT+TT) genotypes, had significantly enhanced levels of lung adducts by 210.7% (95% CI, 21.4% to 695.2%) in contrast to the A1298C (AA) plus C677T (CC) genotypes. Elevation of DNA adduct was pronounced-111.3% (95% CI, -3.0 to 360.5%) among 1298AC+CC patients, who consumed the lowest level of folate intake as compared to 1298AA individuals with highest tertile of intake. These results indicate that DNA adducts levels are influenced by MTHFR polymorphisms and low folate consumption, suggesting an important role of genetic and nutritional factors in protecting DNA damage from lung carcinogen in at-risk populations. Copyright © 2011 UICC.

  19. Effects of watercress consumption on metabolism of a tobacco-specific lung carcinogen in smokers.

    Science.gov (United States)

    Hecht, S S; Chung, F L; Richie, J P; Akerkar, S A; Borukhova, A; Skowronski, L; Carmella, S G

    1995-12-01

    Epidemiological studies indicate that vegetable consumption protects against lung cancer in humans, but the protective constituents have not been identified. Phenethyl isothiocyanate (PEITC), which is release upon chewing of watercress (nasturtium officinale), is a chemopreventive agent against lung cancer induced by the tobacco-specific lung carcinogen 4- (methylnitrosamino)-1-(3-pyridyl-1-butanone (NNK) in rats and mice. PEITC inhibits the carcinogenicity of NNK by inhibiting its metabolic activation and thereby increasing the levels of detoxified metabolites excreted in urine. In this study, our goal was to determine whether watercress consumption would modify NNK metabolism in smokers. Eleven smokers maintained constant smoking habits and avoided cruciferous vegetables and other sources of isothiocyanates throughout the study. They donated 24-h urine samples on 3 consecutive days (baseline period). One to 3 days later, they consumed 2 ounces (56.8 g) of watercress at each meal for 3 days and donated 24-h urine samples on each of these days (watercress consumption period). One and 2 weeks later, they again donated 24-h urine samples on 2-3 consecutive days (follow-up periods). The samples were analyzed for two metabolites of NNK; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and [4-methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-omega-D-glucosiduro nic acid (NNAL- Gluc). NNAL-Gluc is believed to be a detoxification product of NNK. The urine samples were also analyzed for PEITC-NAC, a metabolite of PEITC. Minimum exposure to PEITC during the watercress consumption period averaged 19-38 mg/day. Seven of the 11 subjects had increased levels of urinary NNAL plus NNAL-Gluc on days 2 and 3 of the watercress consumption period, compared to the baseline period. Overall, the increase in urinary NNAL plus NNAL-Gluc in this period was significant [mean +/- SD 0.924 +/- 1.12 nmol/24 h (33.5%); P < 0.01]. Urinary levels of NNAl plus NNAL-Gluc returned to near baseline

  20. AKT1E¹⁷K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Donatella Malanga

    Full Text Available The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6-2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26 locus (R26-AKT1E17K mice we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype.

  1. AKT1E17K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer

    Science.gov (United States)

    Malanga, Donatella; Belmonte, Stefania; Colelli, Fabiana; Scarfò, Marzia; De Marco, Carmela; Oliveira, Duarte Mendes; Mirante, Teresa; Camastra, Caterina; Gagliardi, Monica; Rizzuto, Antonia; Mignogna, Chiara; Paciello, Orlando; Papparella, Serenella; Fagman, Henrik; Viglietto, Giuseppe

    2016-01-01

    The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6–2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26) locus (R26-AKT1E17K mice) we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype. PMID:26859676

  2. Medical follow-up of workers exposed to lung carcinogens: French evidence-based and pragmatic recommendations

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    Fleur Delva

    2017-02-01

    Full Text Available Abstract Background The aim of this work was to establish recommendations for the medical follow-up of workers currently or previously exposed to lung carcinogens. Methods A critical synthesis of the literature was conducted. Occupational lung carcinogenic substances were listed and classified according to their level of lung cancer risk. A targeted screening protocol was defined. Results A clinical trial, National Lung Screnning Trial (NLST, showed the efficacy of chest CAT scan (CT screening for populations of smokers aged 55–74 years with over 30 pack-years of exposure who had stopped smoking for less than 15 years. To propose screening in accordance with NLST criteria, and to account for occupational risk factors, screening among smokers and former smokers needs to consider the types of occupational exposure for which the risk level is at least equivalent to the risk of the subjects included in the NLST. The working group proposes an algorithm that estimates the relative risk of each occupational lung carcinogen, taking into account exposure to tobacco, based on available data from the literature. Conclusion Given the lack of data on bronchopulmonary cancer (BPC screening in occupationally exposed workers, the working group proposed implementing a screening experiment for bronchopulmonary cancer in subjects occupationally exposed or having been occupationally exposed to lung carcinogens who are confirmed as having high risk factors for BPC. A specific algorithm is proposed to determine the level of risk of BPC, taking into account the different occupational lung carcinogens and tobacco smoking at the individual level.

  3. Environmentally prevalent polycyclic aromatic hydrocarbons can elicit co-carcinogenic properties in an in vitro murine lung epithelial cell model.

    Science.gov (United States)

    Bauer, Alison K; Velmurugan, Kalpana; Plöttner, Sabine; Siegrist, Katelyn J; Romo, Deedee; Welge, Peter; Brüning, Thomas; Xiong, Ka-Na; Käfferlein, Heiko U

    2017-11-23

    Low molecular weight (LMW) polycyclic aromatic hydrocarbons (PAH) are the most abundant PAHs environmentally, occupationally, and are in cigarette smoke; however, little is known about their carcinogenic potential. We hypothesized that LMW PAHs act as co-carcinogens in the presence of a known carcinogen (benzo[a]pyrene (B[a]P)) in a mouse non-tumorigenic type II cell line (C10 cells). Gap junctions are commonly suppressed and inflammation induced during tumor promotion, while DNA-adduct formation is observed during the initiation stage of cancer. We used these endpoints together as markers of carcinogenicity in these lung adenocarcinoma progenitor cells. LMW PAHs (1-methylanthracene and fluoranthene, 1-10 µM total in a 1:1 ratio) were used based on previous studies as well as B[a]P (0-3 µM) as the classic carcinogen; non-cytotoxic doses were used. B[a]P-induced inhibition of gap junctional intercellular communication (GJIC) was observed at low doses and further reduced in the presence of the LMW PAH mixture (P carcinogenic potential. Future studies will further address the mechanisms of co-carcinogenesis driving these responses.

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

    OpenAIRE

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

    2016-01-01

    Background Tobacco smoking is the main cause of lung cancer, but it is not the sole causal factor. Significant proportions of workers are smokers and exposed to occupational lung carcinogens. This study aims to systematically review the statistical interaction between occupational lung carcinogens and tobacco smoking, in particular asbestos, crystalline silica and diesel engine exhaust emissions. Methods Articles were identified using Scopus, PubMed, and Web of Science, and were limited to th...

  5. Assessment of carcinogenic health risk for population living in monocities and rural settelements

    Directory of Open Access Journals (Sweden)

    V.M. Boev

    2017-06-01

    Full Text Available Our research goal was to perform assessment of carcinogenic health risk for population living in monocities and rural settlements in Orenburg region including both total and individual carcinogenic risk assessment. We assessed carcinogenic health risks for population living in cities with industrial enterprises as economic bases (Novotroitsk and Mednogorsk and rural settlements (Oktyabrskiy, Ilekskiy, and Tyul'ganskiy districts in Orenburg region. Exposure assessment was based on the data obtained via laboratory research of environmental objects over 2005–2013 (1,265 atmospheric air samples and 1,897 drinking water samples. We determined total carcinogenic risks for population on each territory under multi-environment impacts exerted by chemicals; a share of each chemical in risk formation was also identified. The results we obtained allow us to make a conclusion that monocities' areas are unfavorable in terms of carcinogenic effects on population health. We detected priority carcinogens for each territory in order to work out practical recommendations on lowering carcinogenic risks and on possibility of delayed effects evolvement. Carcinogenic risk caused by chemicals contained in drinking water both in monocities and rural settlements was considered to be acceptable; however, it was 1.5-2 times higher for monocities population. Overall, chromium took the leading role among carcinogens in monocities air; benzene and arsenic occupied the same place in rural settlements air. Chromium, benzpyrene, and arsenic were priority carcinogens contained in drinking water in rural settlements. Our research proves the necessity to work our practical recommendations on lowering carcinogenic risks and on possibility of delayed effects evolvement on regional level.

  6. Polycyclic Aromatic Hydrocarbons In Edible Mushrooms from Niger Delta, Nigeria: Carcinogenic and Non-Carcinogenic Health Risk Assessment

    Science.gov (United States)

    Igbiri, Sorbari; Udowelle, Nnaemeka Arinze; Ekhator, Osazuwa Clinton; Asomugha, Rose Ngozi; Igweze, Zelinjo Nkeiruka; Orisakwe, Orish Ebere

    2017-01-01

    In the oil-rich Niger Delta, hydrocarbon pollution and oil spillages, gas flaring and sundry anthropogenic activities constitute sources of polycyclic aromatic hydrocarbons (PAHs), with food contamination playing a major role in human exposure. In this study we assessed PAH levels in wild and cultivated edible mushroom species consumed by the general population from the oil producing Niger Delta, Nigeria. The concentrations of USEPA-16 PAHs were determined by gas chromatography and carcinogenic and non-carcinogenic health risks were calculated. The concentrations of USEPA-16 PAHs ranged from 0.02 mg/kg – 3.37 mg/kg. The dietary intake of carcinogenic and non-carcinogenic USEPA-16 PAHs (Naphthalene, Acenaphthylene, Acenaphthene, Anthracene, Phenanthrene, Flourene, Flouranthene, Pyrene, Benzo[a]Anthracene, Chrysene, Benzo[a]Pyrene, Benzo[b]Flouranthene, Benzo[K]Flouranthene, Benzo[g, h, i]Perylene, Dibenz[a, h]Anthracene and Ideno[1,2,3-cd]Pyrene) for adults, adolescents and seniors ranged from 0.00 – 0.05 mg/kg/day, 0.00 – 0.06 mg/kg/day and 0.00 – 0.07 mg/kg/day. The BaPeq ranged from 0.02 – 2.76 with margin of exposure MOE values of BaP ranging from 3,500,000 to 700,000, 3,500,000 and 3,500,000 to 7,000,000 for adults, adolescents and seniors indicating very insignificant health risk. The incremental lifetime cancer risk was within the safe range of 1.56x10-8 – 1.73x10-6 with the highest calculated risk found for wild Pleurotus ostreatus mushroom species from the study area. PMID:28345827

  7. Polycyclic Aromatic Hydrocarbons In Edible Mushrooms from Niger Delta, Nigeria: Carcinogenic and Non-Carcinogenic Health Risk Assessment

    Science.gov (United States)

    Igbiri, Sorbari; Udowelle, Nnaemeka Arinze; Ekhator, Osazuwa Clinton; Asomugha, Rose Ngozi; Igweze, Zelinjo Nkeiruka; Orisakwe, Orish Ebere

    2017-02-01

    In the oil-rich Niger Delta, hydrocarbon pollution and oil spillages, gas flaring and sundry anthropogenic activities constitute sources of polycyclic aromatic hydrocarbons (PAHs), with food contamination playing a major role in human exposure. In this study we assessed PAH levels in wild and cultivated edible mushroom species consumed by the general population from the oil producing Niger Delta, Nigeria. The concentrations of USEPA-16 PAHs were determined by gas chromatography and carcinogenic and non-carcinogenic health risks were calculated. The concentrations of USEPA-16 PAHs ranged from 0.02 mg/kg – 3.37 mg/kg. The dietary intake of carcinogenic and non-carcinogenic USEPA-16 PAHs (Naphthalene, Acenaphthylene, Acenaphthene, Anthracene, Phenanthrene, Flourene, Flouranthene, Pyrene, Benzo[a]Anthracene, Chrysene, Benzo[a]Pyrene, Benzo[b]Flouranthene, Benzo[K]Flouranthene, Benzo[g,h,i] Perylene, Dibenz[a,h]Anthracene and Ideno[1,2,3-cd]Pyrene) for adults, adolescents and seniors ranged from 0.00 – 0.05 mg/kg/day, 0.00 – 0.06 mg/kg/day and 0.00 – 0.07 mg/kg/day. The BaPeq ranged from 0.02 – 2.76 with margin of exposure MOE values of BaP ranging from 3,500,000 to 700,000, 3,500,000 and 3,500,000 to 7,000,000 for adults, adolescents and seniors indicating very insignificant health risk. The incremental lifetime cancer risk was within the safe range of 1.56x10-8 – 1.73x10-6 with the highest calculated risk found for wild Pleurotus ostreatus mushroom species from the study area. Creative Commons Attribution License

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-01

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

  9. Chemopreventive Effects of the p53-Modulating Agents CP-31398 and Prima-1 in Tobacco Carcinogen-Induced Lung Tumorigenesis in A/J Mice

    Directory of Open Access Journals (Sweden)

    Chinthalapally V. Rao

    2013-09-01

    Full Text Available Lung cancer is the leading cause of cancer deaths worldwide. Expression of the p53 tumor suppressor protein is frequently altered in tobacco-associated lung cancers. We studied chemopreventive effects of p53-modulating agents, namely, CP-31398 and Prima-1, on 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK-induced lung adenoma and adenocarcinoma formation in female A/J mice. Seven-week-old mice were treated with a single dose of NNK (10 µmol/mouse by intraperitoneal injection and, 3 weeks later, were randomized to mice fed a control diet or experimental diets containing 50 or 100 ppm CP-31398 or 150 or 300 ppm Prima-1 for either 17 weeks (10 mice/group or 34 weeks (15 mice/group to assess the efficacy against lung adenoma and adenocarcinoma. Dietary feeding of 50 or 100 ppm CP-31398 significantly suppressed (P < .0001 lung adenocarcinoma by 64% and 73%, respectively, after 17 weeks and by 47% and 56%, respectively, after 34 weeks. Similarly, 150 or 300 ppm Prima-1 significantly suppressed (P < .0001 lung adenocarcinoma formation by 56% and 62%, respectively, after 17 weeks and 39% and 56%, respectively, after 34 weeks. Importantly, these results suggest that both p53 modulators cause a delay in the progression of adenoma to adenocarcinoma. Immunohistochemical analysis of lung tumors from mice exposed to p53-modulating agents showed a significantly reduced tumor cell proliferation and increased accumulation of wild-type p53 in the nucleus. An increase in p21- and apoptotic-positive cells was also observed in lung tumors of mice exposed to p53-modulating agents. These results support a chemopreventive role of p53-modulating agents in tobacco carcinogen-induced lung adenocarcinoma formation.

  10. Exposure assessment for a nested case-control study of lung cancer among European asphalt workers.

    NARCIS (Netherlands)

    Agostini, M.; Ferro, G.; Olsson, A.; Burstyn, I.; de Vocht, F.; Hansen, J.; Funch Lassen, C.; Johansen, C.; Kjaerheim, K.; Langard, S.; Stucker, I.; Ahrens, W.; Behrens, T.; Lindbohm, M-J.; Heikkila, P.; Heederik, D.; Portengen, L.; Shaham, J.; Boffetta, P.; Kromhout, H.

    2010-01-01

    OBJECTIVE: Development of a method for retrospective assessment of exposure to bitumen fume, bitumen condensate, organic vapour, polycyclic aromatic hydrocarbons, and co-exposures to known or suspected lung carcinogens for a nested case-control study of lung cancer mortality among European asphalt

  11. Assessment of chronic toxicity and carcinogenicity in an accelerated cancer bioassay in rats of Nifurtimox, an antitrypanosomiasis drug.

    Science.gov (United States)

    Iatropoulos, M J; Wang, C X; von Keutz, E; Williams, G M

    2006-07-01

    The chronic toxicity and carcinogenicity of Nifurtimox (NFX), a 5-nitrofuran derivative used in the treatment of American trypanosomiasis, were studied in male and female Wistar rats in an accelerated cancer bioassay (ACB). The ACB is a mechanistic initiation/promotion chronic toxicity and carcinogenicity bioassay designed to assess potential carcinogenic activity of a test substance in critical organs and tissues of rodents in which human carcinogens are active. The organs studied were liver, lungs, urinary bladder (UB), mammary gland (MG), bone marrow, spleen, kidneys, colon, stomach and any grossly observed lesions. NFX is a genotoxin which has been reported previously to exert a variable degree of carcinogenic activity in rat liver, kidney, UB and MG. The present study was undertaken to assess whether NFX has initiating activity in these four named target sites. In the initiation phase, groups of 20 Wistar rats were given NFX daily in the diet at 0.2% for the first 12 weeks of the study to assess initiating activity, followed by promoters (PROs) for four organs for an additional 24 weeks. NFX was compared to the following known initiators (INs) for each of these four tissues: diethylnitrosamine (DEN) for liver and kidney, N-butyl-N(4-hydroxybutyl)nitrosamine (BBN) for UB and 7,12-dimethylbenz(a)anthracene (DMBA) for MG. PROs included phenobarbital (PB) for liver and kidney, nitrilotriacetic acid (NTA) for UB, and diethylstilbestrol (DES) for MG. NFX was also administered continuously without PROs for 40 weeks. At the end of dosing (40 weeks) and at the end of recovery (52 weeks), animals were sacrificed and subjected to complete gross and histopathological examinations, along with evaluations of body weight gain over time and terminal body weights. Mortality was highest with DEN+PB (group 6) (40%), followed by BBN+NTA (group 7) (15%) and NFX+DES (group 5) and DMBA+DES (group 8) (10% each). The same groups also showed significant reductions in body weight gain

  12. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yan; Choksi, Swati; Liu, Zheng-Gang, E-mail: zgliu@helix.nih.gov [Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-12-04

    Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80{sup +} macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206{sup +} TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer.

  13. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2013-12-01

    Full Text Available Tumor-associated macrophages (TAMs promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA blocks occurrence of tumor associated macrophages (TAMs in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA, a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80+ macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206+ TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer.

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

    Directory of Open Access Journals (Sweden)

    Mohamad El Zoghbi

    2017-02-01

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

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

    Science.gov (United States)

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

    2017-02-02

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

  16. Inter-rater agreement in the assessment of exposure to carcinogens in the offshore petroleum industry.

    Science.gov (United States)

    Steinsvåg, Kjersti; Bråtveit, Magne; Moen, Bente E; Kromhout, Hans

    2007-09-01

    To evaluate the reliability of an expert team assessing exposure to carcinogens in the offshore petroleum industry and to study how the information provided influenced the agreement among raters. Eight experts individually assessed the likelihood of exposure for combinations of 17 carcinogens, 27 job categories and four time periods (1970-1979, 1980-1989, 1990-1999 and 2000-2005). Each rater assessed 1836 combinations based on summary documents on carcinogenic agents, which included descriptions of sources of exposure and products, descriptions of work processes carried out within the different job categories, and monitoring data. Inter-rater agreement was calculated using Cohen's kappa index and single and average score intraclass correlation coefficients (ICC) (ICC(2,1) and ICC(2,8), respectively). Differences in inter-rater agreement for time periods, raters, International Agency for Research on Cancer groups and the amount of information provided were consequently studied. Overall, 18% of the combinations were denoted as possible exposure, and 14% scored probable exposure. Stratified by the 17 carcinogenic agents, the probable exposure prevalence ranged from 3.8% for refractory ceramic fibres to 30% for crude oil. Overall mean kappa was 0.42 (ICC(2,1) = 0.62 and ICC(2,8) = 0.93). Providing limited quantitative measurement data was associated with less agreement than for equally well described carcinogens without sampling data. The overall kappa and single-score ICC indicate that the raters agree on exposure estimates well above the chance level. The levels of inter-rater agreement were higher than in other comparable studies. The average score ICC indicates reliable mean estimates and implies that sufficient raters were involved. The raters seemed to have enough documentation on which to base their estimates, but provision of limited monitoring data leads to more incongruence among raters. Having real exposure data, with the inherent variability of such data

  17. Association of carcinogenic polycyclic aromatic hydrocarbon emissions and smoking with lung cancer mortality rates on a global scale.

    Science.gov (United States)

    Motorykin, Oleksii; Matzke, Melissa M; Waters, Katrina M; Massey Simonich, Staci L

    2013-04-02

    The objective of this research was to investigate the relationship between lung cancer mortality rates, carcinogenic polycyclic aromatic hydrocarbon (PAH) emissions, and smoking on a global scale, as well as for different socioeconomic country groups. The estimated lung cancer deaths per 100,000 people (ED100000) and age standardized lung cancer death rate per 100,000 people (ASDR100000) in 2004 were regressed on PAH emissions in benzo[a]pyrene equivalence (BaPeq), smoking prevalence, cigarette price, gross domestic product per capita, percentage of people with diabetes, and average body mass index using simple and multiple linear regression for 136 countries. Using stepwise multiple linear regression, a statistically significant positive linear relationship was found between loge(ED100000) and loge(BaPeq) emissions for high (p-value emissions for the combination of upper-middle and high (p-value emissions in the U.S., Canada, Australia, France, Germany, Brazil, South Africa, Poland, Mexico, and Malaysia could reduce ED100000, while reducing smoking prevalence in Democratic People's Republic of Korea, Nepal, Mongolia, Cambodia, and Bangladesh could significantly reduce the ED100000 and ASDR100000.

  18. Expert assessment of exposure to carcinogens in Norway's offshore petroleum industry.

    Science.gov (United States)

    Steinsvåg, Kjersti; Bråtveit, Magne; Moen, Bente; Austgulen, Li V-Torill; Hollund, Bjørg Eli; Haaland, Inger Margrethe; Naerheim, Jakob; Svendsen, Kristin; Kromhout, Hans

    2008-03-01

    This study presents and evaluates an expert group's assessment of exposure to carcinogens for defined job categories in Norway's offshore petroleum industry, 1970-2005, to provide exposure information for a planned cohort study on cancer. Three university and five industry experts in occupational hygiene individually assessed the likelihood of exposure to 1836 combinations of carcinogens (n=17), job categories (n=27) and time periods (n=4). In subsequent plenary discussions, the experts agreed on exposed combinations. Agreement between the individual and the panel assessments was calculated by Cohen's kappa index. Using the panel assessment as reference, sensitivity and specificity were estimated. The eight experts assessed 63% of the 1836 combinations in plenary, resulting in 265 (14%) convened exposed combinations. Chlorinated hydrocarbons, benzene and inhalation of mineral oils had the highest number of exposed job categories (n=14, 9 and 10, respectively). The job categories classified as exposed to the highest numbers of carcinogens were the mechanics (n=10), derrick workers (n=6) and process technicians (n=5). The agreement between the experts' individual assessments and the panel assessment was kappa=0.53-0.74. The sensitivity was 0.55-0.86 and specificity 0.91-0.97. For these parameters, there were no apparent differences between the university experts and the industry experts. The resulting 265 of 1836 possible exposure combinations convened as "exposed" by expert assessment is presented in this study. The experts' individual ratings highly agreed with the succeeding panel assessment. Correlation was found between years of experience of the raters and agreement with the panel. The university experts and the industry experts' assessments had no apparent differences. Further validation of the exposure assessment is suggested, such as by new sampling data or observational studies.

  19. A Novel Approach: Chemical Relational Databases, and the Role of the ISSCAN Database on Assessing Chemical Carcinogenity

    Science.gov (United States)

    Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as "look-up-tables" of existing data, and most often did no...

  20. Inter‐rater agreement in the assessment of exposure to carcinogens in the offshore petroleum industry

    Science.gov (United States)

    Steinsvåg, Kjersti; Bråtveit, Magne; Moen, Bente E; Kromhout, Hans

    2007-01-01

    Objectives To evaluate the reliability of an expert team assessing exposure to carcinogens in the offshore petroleum industry and to study how the information provided influenced the agreement among raters. Methods Eight experts individually assessed the likelihood of exposure for combinations of 17 carcinogens, 27 job categories and four time periods (1970–1979, 1980–1989, 1990–1999 and 2000–2005). Each rater assessed 1836 combinations based on summary documents on carcinogenic agents, which included descriptions of sources of exposure and products, descriptions of work processes carried out within the different job categories, and monitoring data. Inter‐rater agreement was calculated using Cohen's kappa index and single and average score intraclass correlation coefficients (ICC) (ICC(2,1) and ICC(2,8), respectively). Differences in inter‐rater agreement for time periods, raters, International Agency for Research on Cancer groups and the amount of information provided were consequently studied. Results Overall, 18% of the combinations were denoted as possible exposure, and 14% scored probable exposure. Stratified by the 17 carcinogenic agents, the probable exposure prevalence ranged from 3.8% for refractory ceramic fibres to 30% for crude oil. Overall mean kappa was 0.42 (ICC(2,1) = 0.62 and ICC(2,8) = 0.93). Providing limited quantitative measurement data was associated with less agreement than for equally well described carcinogens without sampling data. Conclusion The overall κ and single‐score ICC indicate that the raters agree on exposure estimates well above the chance level. The levels of inter‐rater agreement were higher than in other comparable studies. The average score ICC indicates reliable mean estimates and implies that sufficient raters were involved. The raters seemed to have enough documentation on which to base their estimates, but provision of limited monitoring data leads to more incongruence among raters. Having real

  1. Comparative risk assessment of carcinogens in alcoholic beverages using the margin of exposure approach.

    Science.gov (United States)

    Lachenmeier, Dirk W; Przybylski, Maria C; Rehm, Jürgen

    2012-09-15

    Alcoholic beverages have been classified as carcinogenic to humans. As alcoholic beverages are multicomponent mixtures containing several carcinogenic compounds, a quantitative approach is necessary to compare the risks. Fifteen known and suspected human carcinogens (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, lead, 4-methylimidazole, N-nitrosodimethylamine, ochratoxin A and safrole) occurring in alcoholic beverages were identified based on monograph reviews by the International Agency for Research on Cancer. The margin of exposure (MOE) approach was used for comparative risk assessment. MOE compares a toxicological threshold with the exposure. MOEs above 10,000 are judged as low priority for risk management action. MOEs were calculated for different drinking scenarios (low risk and heavy drinking) and different levels of contamination for four beverage groups (beer, wine, spirits and unrecorded alcohol). The lowest MOEs were found for ethanol (3.1 for low risk and 0.8 for heavy drinking). Inorganic lead and arsenic have average MOEs between 10 and 300, followed by acetaldehyde, cadmium and ethyl carbamate between 1,000 and 10,000. All other compounds had average MOEs above 10,000 independent of beverage type. Ethanol was identified as the most important carcinogen in alcoholic beverages, with clear dose response. Some other compounds (lead, arsenic, ethyl carbamate, acetaldehyde) may pose risks below thresholds normally tolerated for food contaminants, but from a cost-effectiveness point of view, the focus should be on reducing alcohol consumption in general rather than on mitigative measures for some contaminants that contribute only to a limited extent (if at all) to the total health risk. Copyright © 2012 UICC.

  2. Visual anatomical lung CT scan assessment of lung recruitability.

    Science.gov (United States)

    Chiumello, Davide; Marino, Antonella; Brioni, Matteo; Menga, Federica; Cigada, Irene; Lazzerini, Marco; Andrisani, Maria C; Biondetti, Pietro; Cesana, Bruno; Gattinoni, Luciano

    2013-01-01

    The computation of lung recruitability in acute respiratory distress syndrome (ARDS) is advocated to set positive end-expiratory pressure (PEEP) for preventing lung collapse. The quantitative lung CT scan, obtained by manual image processing, is the reference method but it is time consuming. The aim of this study was to evaluate the accuracy of a visual anatomical analysis compared with a quantitative lung CT scan analysis in assessing lung recruitability. Fifty sets of two complete lung CT scans of ALI/ARDS patients computing lung recruitment were analyzed. Lung recruitability computed at an airway pressure of 5 and 45 cm H(2)O was defined as the percentage decrease in the collapsed/consolidated lung parenchyma assessed by two expert radiologists using a visual anatomical analysis and as the decrease in not aerated lung regions using a quantitative analysis computed by dedicated software. Lung recruitability was 11.3 % (interquartile range 7.39-16.41) and 15.5 % (interquartile range 8.18-21.43) with the visual anatomical and quantitative analysis, respectively. In the Bland-Altman analysis, the bias and agreement bands between the visual anatomical and quantitative analysis were -2.9 % (-11.8 to +5.9 %). The ROC curve showed that the optimal cutoff values for the visual anatomical analysis in predicting high versus low lung recruitability was 8.9 % (area under the ROC curve 0.9248, 95 % CI 0.8550-0.9946). Considering this cutoff, the sensitivity, specificity, and diagnostic accuracy were 0.96, 0.76, and 0.86, respectively. Visual anatomical analysis can classify patients into those with high and low lung recruitability allowing more intensivists to get access to lung recruitability assessment.

  3. Is phenylbutazone a genotoxic carcinogen? A weight-of-evidence assessment.

    Science.gov (United States)

    Combes, Robert D

    2013-07-01

    Published in silico, in vitro, in vivo laboratory animal and human data, together with information on biotransformation and data from structure-activity analyses with two decision-tree systems (ACToR and Toxtree), have been used in a weight-of-evidence (WoE) assessment to determine whether phenylbutazone (PBZ) is a genotoxic or a non-genotoxic carcinogen. This was undertaken to facilitate the risk assessment of human exposure to this veterinary drug via the consumption of horsemeat from treated animals. Despite problems with data interpretation at all tiers of the database, it was concluded that PBZ behaves like a genotoxic carcinogen with a threshold dose. This conclusion is based mainly on the results of a definitive rodent bioassay, and on the following observations: a) that PBZ has weak in vitro activity only at high concentrations in some genotoxicity assays, accompanied by high levels of cytotoxicity; b) that it (and a major metabolite) is able to cause sister chromatid exchanges in vivo in rodents; and c) that it can induce cytogenetic effects in vivo in humans. It also takes into account the known and predicted activities of the parent drug, some of its metabolites and two structural analogues, and, importantly, several of the drug's other biochemical effects that are unrelated to toxicity. However, this conclusion is not fully supported by all the evidence, and much of the information is based on old papers. Therefore, more studies are required to establish whether the concentration thresholds seen in vitro would translate to dose thresholds for carcinogenicity, such that a safe dose-level could be defined for the purposes of assessing risk. It was disappointing that a WoE approach to evaluating all of the available hazard data, as is increasingly being advocated to improve the hazard identification paradigm, was unable to provide definitive answers in this case, particularly in view of the large numbers of animals that had been used to provide much of the

  4. Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation.

    Science.gov (United States)

    Aizawa, Koichi; Liu, Chun; Tang, Sanyuan; Veeramachaneni, Sudipta; Hu, Kang-Quan; Smith, Donald E; Wang, Xiang-Dong

    2016-09-01

    Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carcinoma (HCC). In the present study, we investigated whether the tobacco carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lesions in both lungs and livers of ferrets with or without lycopene intervention. Male ferrets (6 groups, n = 8-10) were treated either with NNK (50 mg/kg BW, i.p., once a month for four consecutive months) or saline with or without dietary lycopene supplementation (2.2 and 6.6 mg/kg BW/day, respectively) for 26 weeks. Results demonstrate that NNK exposure results in higher incidences of lung tumors, HCC and steatohepatitis (which is characterized by severe inflammatory cell infiltration with concurrent fat accumulation in liver, hepatocellular ballooning degeneration and increased NF-κB expression), as well as elevations in bilirubin and AST levels in ferrets. Lycopene supplementation at two doses prevented NNK-induced expressions of α7 nicotinic acetylcholine receptor in the lung and NF-κB and CYP2E1 in the liver and attenuated the NNK-induced mortality and pathological lesions in both the lungs and livers of ferrets. The present study provided strong experimental evidence that the tobacco carcinogen NNK can induce both HCC and steatohepatitis in the ferrets and can be a useful model for studying tobacco carcinogen-associated NAFLD and liver cancer. Furthermore, lycopene could provide potential benefits against smoke carcinogen-induced pulmonary and hepatic injury. © 2016 UICC.

  5. The in vivo rodent test systems for assessment of carcinogenic potential

    DEFF Research Database (Denmark)

    van der Laan, Jan-Willem; Spindler, Per

    2002-01-01

    mouse models, the RasH2 and Tg.AC transgenic mouse models, and the neonatal mouse model. The "ICH Guideline S1B on Testing for Carcinogenicity of Pharmaceuticals" advocates that carcinogenicity testing of pharmaceuticals, when needed, might be carried out choosing one 2-year rodent carcinogenicity study...... (rat) plus one other study that supplements the 2-year study and providing additional information that is not readily available from the 2-year study: either (1) a short- or medium-term in vivo rodent test system or (2) a 2-year carcinogenicity study in a second rodent species (mouse). Another topic...

  6. Genetic Susceptibility of Lung Cancer Associated With Common Variants in the 3 ' Untranslated Regions of the Adenosine Triphosphate-Binding Cassette B1 (ABCB1) and ABCC1 Candidate Transporter Genes for Carcinogen Export

    NARCIS (Netherlands)

    Wang, Haijian; Jin, Guangfu; Wang, Haifeng; Liu, Gaifen; Qian, Ji; Jin, Li; Wei, Qingyi; Shen, Hongbing; Huang, Wei; Lu, Daru

    2009-01-01

    BACKGROUND: Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK) is a well defined carcinogen that can induce lung cancer. Genetic polymorphisms in its disposition pathways could modify the risk of developing lung cancer. The authors of this report previously catalogued

  7. SHORT COMMUNICATION CARCINOGENIC POTENCY OF ...

    African Journals Online (AJOL)

    were used to compute the carcinogenic risk potency of the PAHs relative to benzo(a)pyrene (reference carcinogen). .... The health risk assessment methodology provided the basis for estimation of ..... IRIS, Integrated Risk Information System.

  8. Evaluation of the carcinogenicity of gallium arsenide.

    Science.gov (United States)

    Bomhard, Ernst M; Gelbke, Heinz-Peter; Schenk, Hermann; Williams, Gary M; Cohen, Samuel M

    2013-05-01

    Gallium arsenide (GaAs) is an important semiconductor material. In 2-year inhalation studies, GaAs increased the incidence of lung tumors in female rats, but not in male rats or male and female mice. Alveolar proteinosis followed by chronic active inflammation was the predominant non-neoplastic pulmonary findings. IARC classified GaAs as carcinogenic to humans (group 1) based on the assumption that As and Ga ions are bioavailable. The European Chemical Agency Risk Assessment Committee concluded that GaAs should be classified into Carcinogenicity Category 1B (presumed to have carcinogenic potential for humans; ECHA). We evaluate whether these classifications are justified. Physico-chemical properties of GaAs particles and the degree of mechanical treatment are critical in this evaluation. The available data on mode of action (MOA), genotoxicity and bioavailability do not support the contribution of As or Ga ions to the lung tumors in female rats. Most toxicological studies utilized small particles produced by strong mechanical treatment, destroying the crystalline structure. The resulting amorphous GaAs is not relevant to crystalline GaAs at production and processing sites. The likely tumorigenic MOA is lung toxicity related to particulate-induced inflammation and increased proliferation. It is concluded that there is no evidence for a primary carcinogenic effect of GaAs.

  9. MULTIFACTORIAL ASSESSMENT OF POSTMORTEM LUNG DONOR

    Directory of Open Access Journals (Sweden)

    M. S. Khubutiya

    2013-01-01

    Full Text Available The appropriate evaluation and the development of special measures to protect donor lungs are important factors for successful lung transplantation. Aim. To develop and determine the effectiveness of the protocol of morpho- functional assessment of potential lung donor. Methods and results. During the period from May, 2011 to May, 2012, 37 donors with diagnoses of brain death were surveyed. 5 bilateral lung transplantations were performed only in 2 cases donors have been evaluated as «ideal». In the majority of recipients early postoperative period was evaluated as satisfactory. Conclusion. Designed multivariate algorithm of donor with brain death assess- ment, effectively implemented through the selection of donors for lung transplantation with satisfactory results in the early postoperative period. However, compliance with ideal criteria will not allow to effectively provide care for patients with terminal lung disease under conditions of continuous growth of «waiting list». 

  10. Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

    NARCIS (Netherlands)

    Kuempel, Eileen D; Jaurand, Marie-Claude; Møller, Peter; Morimoto, Yasuo; Kobayashi, Norihiro; Pinkerton, Kent E; Sargent, Linda M; Vermeulen, Roel C H|info:eu-repo/dai/nl/216532620; Fubini, Bice; Kane, Agnes B

    2017-01-01

    In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the

  11. Prioritising action on occupational carcinogens in Europe: a socioeconomic and health impact assessment.

    Science.gov (United States)

    Cherrie, J W; Hutchings, S; Gorman Ng, M; Mistry, R; Corden, C; Lamb, J; Sánchez Jiménez, A; Shafrir, A; Sobey, M; van Tongeren, M; Rushton, L

    2017-07-11

    Work-related cancer is an important public health issue with a large financial impact on society. The key European legislative instrument is the Carcinogens and Mutagens Directive (2004/37/EC). In preparation for updating the Directive, the European Commission commissioned a study to provide a socioeconomic, health and environmental impact assessment. The evaluation was undertaken for 25 preselected hazardous substances or mixtures. Estimates were made of the number of cases of cancer attributable to workplace exposure, both currently and in the future, with and without any regulatory interventions, and these data were used to estimate the financial health costs and benefits. It was estimated that if no action is taken there will be >700 000 attributable cancer deaths over the next 60 years for the substances assessed. However, there are only seven substances where the data suggest a clear benefit in terms of avoided cancer cases from introducing a binding limit at the levels considered. Overall, the costs of the proposed interventions were very high (up to [euro ]34 000 million) and the associated monetised health benefits were mostly less than the compliance costs. The strongest cases for the introduction of a limit value are for: respirable crystalline silica, hexavalent chromium, and hardwood dust.

  12. A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment.

    Science.gov (United States)

    Williams, Gary M; Aardema, Marilyn; Acquavella, John; Berry, Sir Colin; Brusick, David; Burns, Michele M; de Camargo, Joao Lauro Viana; Garabrant, David; Greim, Helmut A; Kier, Larry D; Kirkland, David J; Marsh, Gary; Solomon, Keith R; Sorahan, Tom; Roberts, Ashley; Weed, Douglas L

    2016-09-01

    The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies. Two of the Panels (animal bioassay and genetic toxicology) also provided a critique of the IARC position with respect to conclusions made in these areas. The incidences of neoplasms in the animal bioassays were found not to be associated with glyphosate exposure on the basis that they lacked statistical strength, were inconsistent across studies, lacked dose-response relationships, were not associated with preneoplasia, and/or were not plausible from a mechanistic perspective. The overall weight of evidence from the genetic toxicology data supports a conclusion that glyphosate (including GBFs and AMPA) does not pose a genotoxic hazard and therefore, should not be considered support for the classification of glyphosate as a genotoxic carcinogen. The assessment of the epidemiological data found that the data do not support a causal relationship between glyphosate exposure and non-Hodgkin's lymphoma while the data were judged to be too sparse to assess a potential relationship between glyphosate exposure and multiple myeloma. As a result, following the review of the totality of the evidence, the Panels concluded that the data do not support IARC's conclusion that glyphosate is a "probable human carcinogen" and, consistent with previous regulatory assessments, further concluded that glyphosate is unlikely to pose a carcinogenic risk to humans.

  13. Carcinogenicity of syncrudes relative to natural petroleum as assessed by repetative mouse skin application

    Energy Technology Data Exchange (ETDEWEB)

    Holland, J.M.; Whitaker, M.S.; Wesley, J.W.

    1978-01-01

    The relative carcinogenicities of coal and shale derived liquid crudes was compared with a composite blend of natural petroleum using discontinuous exposure of mouse skin. All of the syncrudes were carcinogenic while the natural crude composite was negative following three times weekly application of 50% w/v solutions for 22 wks followed by a 22 wk observation period. In addition to eliciting progressive squamous carcinomas the syncrudes were also capable of inducing persistent ulcerative dermatitis. This inflammatory or necrotizing potential appeared to be inversely proportional to the carcinogenicity of the material. A measure of the relative solubility of the materials in mouse skin was obtained by quantitation of native fluorescence in frozen sections of skin. There appeared to be a general, although non-quantitative association between fluorescence intensity in sebaceous glands and carcinogenicity in epidermal cells, however it will be necessary to examine a greater number of samples to establish such a correlation.

  14. The mouse carcinogenicity study is no longer a scientifically justifiable core data requirement for the safety assessment of pesticides.

    Science.gov (United States)

    Billington, Richard; Lewis, Richard W; Mehta, Jyotigna M; Dewhurst, Ian

    2010-01-01

    Regulatory tests investigating pesticide carcinogenicity potential routinely comprise a battery of in vitro and in vivo genotoxicity studies and two cancer bioassays, one in rats and one in mice. The genotoxicity testing strategy essentially ensures that genotoxic compounds are eliminated, and any carcinogens identified in subsequent lifetime studies are probably nongenotoxic in character. Assessment of 202 pesticide evaluations from the European Union review programme under Directive 91/414/EEC indicated that the mouse carcinogenicity study contributed little or nothing to either derivation of an acceptable daily intake (ADI) for assessment of chronic risk to humans, or hazard classification for labelling purposes. From a pesticide approval perspective, the mouse study did not influence a single outcome. From a risk assessment perspective, the ADI for just one pesticide was based on tumours in mice and this would have barely changed if the mouse data had not been available. In total, only 10 (5%) pesticide ADIs were based solely on the mouse carcinogenicity study and even in these few cases, a similar value would have been identified from other studies if the mouse study had not been available. For pesticides with treatment-related tumours only in mice, just three, or 1.5%, were classified as carcinogens and all were in the lowest category, Category 3 (R40). For pesticides with treatment-related tumours in mice and rats, the mouse data were probably the main, if not the only, cause for another three cases of R40 classification. Absence of the mouse studies would not have influenced assignment of the higher, Category 2 (R45), cancer classification for any substance with treatment-related tumours in both species as all decisions for these substances were limited to Category 3 or 'unclassified' outcomes. Over 100,000 mice were used to test these pesticides. This review shows that the mouse carcinogenicity studies did not provide significant information over and above

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

    Science.gov (United States)

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

    2016-08-10

    Both gingerol and capsaicin are agonists of TRPV1, which can negatively control tumor progression. This study observed the long-term effects of oral administration of 6-gingerol alone or in combination with capsaicin for 20 weeks in a urethane-induced lung carcinogenic model. We showed that lung carcinoma incidence and multiplicity were 70% and 21.2 ± 3.6, respectively, in the control versus 100% and 35.6 ± 5.2 in the capsaicin group (P gingerol group (P gingerol and capsaicin reversed the cancer-promoting effect of capsaicin (carcinoma incidence of 100% versus 20% and multiplicity of 35.6 ± 5.2 versus 4.7 ± 2.3; P gingerol promoted TRPV1 level and drastically decreased the levels of EGFR, NF-κB, and cyclin D1 that favored reduced lung epithelial proliferation and EMT (P < 0.01). This study provides valuable information for the long-term consumption of chili-pepper-rich diets to decrease the risk of cancer development.

  16. Urine cotinine underestimates exposure to the tobacco-derived lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in passive compared to active smokers

    Science.gov (United States)

    Benowitz, Neal; Goniewicz, Maciej Lukasz; Eisner, Mark D.; Lazcano-Ponce, Eduardo; Zielinska-Danch, Wioleta; Koszowski, Bartosz; Sobczak, Andrzej; Havel, Christopher; Jacob, Peyton

    2010-01-01

    Objectives Cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are widely used biomarkers for tobacco-derived nicotine and the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively. The discrepancy between cotinine levels in relation to disease risk comparing active vs. passive smoking suggests a non-linear tobacco smoke dose-response and/or that cotinine is not providing an accurate measure of exposure to tobacco smoke toxic constituents from secondhand smoke. Methods Cotinine and NNAL were measured in urine of 373 active smokers and 228 passive smokers. Results Average cotinine levels were 1,155 (IQR 703-2,715) for active smokers and 1.82 (0.45-7.33) ng/mg creatinine for passive smokers. Average NNAL levels were 183 (103-393) and 5.19 (2.04-11.6) pg/mg creatinine, respectively. NNAL/cotinine ratio in urine was significantly higher for passive smokers when compared to active smokers (2.85×103 vs. 0.16×103, p<0.0001). Conclusions Passive smoking is associated with a much higher ratio of NNAL/cotinine in the urine compared to active smoking. Impact Cotinine measurement leads to an underestimation of exposure to the carcinogen NNK from second-hand smoke when compared with active smoking. PMID:20805316

  17. A novel approach: chemical relational databases, and the role of the ISSCAN database on assessing chemical carcinogenicity.

    Science.gov (United States)

    Benigni, Romualdo; Bossa, Cecilia; Richard, Ann M; Yang, Chihae

    2008-01-01

    Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as "look-up-tables" of existing data, and most often did not contain chemical structures. Concepts and technologies originated from the structure-activity relationships science have provided powerful tools to create new types of databases, where the effective linkage of chemical toxicity with chemical structure can facilitate and greatly enhance data gathering and hypothesis generation, by permitting: a) exploration across both chemical and biological domains; and b) structure-searchability through the data. This paper reviews the main public databases, together with the progress in the field of chemical relational databases, and presents the ISSCAN database on experimental chemical carcinogens.

  18. [Evaluation of carcinogenic risk assessment of metallurgic copper production based on mortality studies and predictive risk values].

    Science.gov (United States)

    Russkikh, K Iu; Adrianovskiĭ, V I; Kuz'mina, E A

    2014-01-01

    Comparative evaluation covered carcinogenic jeopardy at metallurgic copper production through studies of the workers' mortality with malignancies and calculation of individual carcinogenic risks. Findings are that the individual carcinogenic risks calucations correspond to the data obtained in epidemiologic study of the mortality with malignancies and could be used for evaluation of carcinogenic jeopardy.

  19. Combining transcriptomics and PBPK modeling indicates a primary role of hypoxia and altered circadian signaling in dichloromethane carcinogenicity in mouse lung and liver.

    Science.gov (United States)

    Andersen, Melvin E; Black, Michael B; Campbell, Jerry L; Pendse, Salil N; Clewell, Harvey J; Pottenger, Lynn H; Bus, James S; Dodd, Darol E; Kemp, Daniel C; McMullen, Patrick D

    2017-10-01

    Dichloromethane (DCM) is a lung and liver carcinogen in mice at inhalation exposures≥2000ppm. The modes of action (MOA) of these responses have been attributed to formation of genotoxic, reactive metabolite(s). Here, we examined gene expression in lung and liver from female B6C3F1 mice exposed to 0, 100, 500, 2000, 3000 and 4000ppm DCM for 90days. We also simulated dose measures - rates of DCM oxidation to carbon monoxide (CO) in lung and liver and expected blood carboxyhemoglobin (HbCO) time courses with a PBPK model inclusive of both conjugation and oxidation pathways. Expression of large numbers of genes was altered at 100ppm with maximal changes in the numbers occurring by 500 or 2000ppm. Most changes in genes common to the two tissues were related to cellular metabolism and circadian clock. At the lower concentrations, the changes in metabolism-related genes were discordant - up in liver and down in lung. These processes included organelle biogenesis, TCA cycle, and respiratory electron transport. Changes in circadian cycle genes - primarily transcription factors - showed strong concentration-related response at higher concentrations (Arntl, Npas2, and Clock were down-regulated; Cry2, Wee1, Bhlhe40, Per3, Nr1d1, Nr1d2 and Dbp) were up-regulated with similar directionality in both tissues. Overall, persistently elevated HbCO from DCM oxidation appears to cause extended periods of hypoxia, leading to altered circadian coupling to cellular metabolism. The dose response for altered circadian processes correlates with the cancer outcome. We found no evidence of changes in genes indicative of responses to cytotoxic, DNA-reactive metabolites. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Ultrasensitive High-Resolution Mass Spectrometric Analysis of a DNA Adduct of the Carcinogen Benzo[a]pyrene in Human Lung.

    Science.gov (United States)

    Villalta, Peter W; Hochalter, J Bradley; Hecht, Stephen S

    2017-12-05

    Benzo[a]pyrene (BaP), an archetypical polycyclic aromatic hydrocarbon, is classified as "carcinogenic to humans" and is ubiquitous in the environment, as evident by the measurable levels of BaP metabolites in virtually all human urine samples examined. BaP carcinogenicity is believed to occur mainly through its covalent modification of DNA, resulting in the formation of BPDE-N2-dG, an adduct formed between deoxyguanosine and a diol epoxide metabolite of BaP, with subsequent mutation of critical growth control genes. In spite of the liquid chromatography-mass spectrometry (LC-MS)-based detection of BPDE-N2-dG in BaP-treated rodents, and indirectly through high-performance liquid chromatography (HPLC)-fluorescence detection of BaP-7,8,9,10-tetraols released from human DNA upon acid hydrolysis, BPDE-N2-dG adducts have rarely if ever been observed directly in human samples using LC-MS techniques, even though sophisticated methodologies have been employed which should have had sufficient sensitivity. With this in mind, we developed a liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) methodology employing high-resolution/accurate mass analysis for detecting ultratrace levels of these adducts. These efforts are directly translatable to the development of sensitive detection of other small molecules using trap-based LC-ESI-MS/MS detection. The developed methodology had a limit of detection (LOD) of 1 amol of BPDE-N2-dG on-column, corresponding to 1 BPDE-N2-dG adduct per 1011 nucleotides (1 adduct per 10 human lung cells) using 40 μg of human lung DNA. To our knowledge, this is the most sensitive DNA adduct quantitation method yet reported, exceeding the sensitivity of the 32P-postlabeling assay (∼1 adduct per 1010 nucleotides). Twenty-nine human lung DNA samples resulted in 20 positive measurements above the LOD, with smoker and nonsmoker DNA containing 3.1 and 1.3 BPDE-N2-dG adducts per 1011 nucleotides, respectively.

  1. Report on carcinogens monograph on cumene.

    Science.gov (United States)

    2013-09-01

    The National Toxicology Program conducted a cancer evaluation on cumene for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for cumene in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to cumene. This monograph provides an assessment of the available scientific information on cumene, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that cumene be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found that cumene exposure caused lung tumors in male and female mice and liver tumors in female mice. Several proposed mechanisms of carcinogenesis support the relevance to humans of the lung and liver tumors observed in experimental animals. Specifically, there is evidence that humans and experimental animals metabolize cumene through similar metabolic pathways. In addition, mutations of the K-ras oncogene and p53 tumor-suppressor gene observed in cumene-induced lung tumors in mice, along with altered expression of many other genes, resemble molecular alterations found in human lung and other cancers.

  2. Assessment of chronic toxicity and carcinogenicity in rats of Wingstay 100, a rubber antioxidant/antiozonant.

    Science.gov (United States)

    Iatropoulos, M J; Williams, G M; Wang, C X; Brunnemann, K D; Leber, A P

    1997-08-01

    The chronic toxicity and carcinogenicity of Wingstay 100 (W 100), a rubber antioxidant/antiozonant, were studied in Fischer 344 (F 344) rats in two chronic studies. Earlier genetic studies indicated that the product had weak activity in a bacterial mutation assay, but lacked activity in chromosomal aberration assays. In an one year study, both genders of F 344 rats were exposed to 53, 310 or 1900 ppm in NIH-07 diet for 52 weeks, and sacrifices were made at 38, 52 and 64 weeks. No test substance related deaths occurred, although the high dose of 1900 ppm caused a decrease in body weight gain and food consumption in both genders. Red blood cell mean corpuscular volume was significantly increased at 38 weeks, accompanied by a significant decrease in mean corpuscular hemoglobin concentration. At 52 weeks, the red blood cell count and hemoglobin values were also significantly decreased in high dose animals of both genders. Total bilirubin and cholesterol were increased in high dose animals of 38 and 52-week sacrifices. During the 3 month recovery, hematology parameters, bilirubin and cholesterol returned to control values. Total protein was reduced in high dose animals of both genders, throughout the entire exposure and recovery periods. W 100 also produced increases in relative liver, spleen, heart and kidney weights in high dose animals. Both genders of all W 100 groups exhibited significant increases in urothelial cell proliferation (measured by PCNA) and adaptive hyperplasia. No regenerative hyperplasia, preneoplasia, or neoplasia were present. There was microscopic evidence of extramedullary erythropoiesis in the spleen and liver of high dose animals in both genders, otherwise no other pertinent microscopic finding was evident. In parallel, an accelerated bioassay (ABA) was conducted, which is a mechanistic initiation/promotion carcinogenicity study designed to assess tumor induction and promotion potential of a test substance in major organs of carcinogenesis. The

  3. Epidemiologic evidence for chloroprene carcinogenicity: review of study quality and its application to risk assessment.

    Science.gov (United States)

    Bukowski, John Arthur

    2009-09-01

    This article evaluates the quality and weight of evidence associated with epidemiologic studies of cancer among occupational cohorts exposed to chloroprene. The focus is on liver, lung, and lymphohematopoietic cancers, which had been increased in early studies. Literature searches identified eight morbidity/mortality studies covering seven chloroprene-exposed cohorts from six countries. These studies were summarized and their quality was assessed using the 10 criteria suggested by the U.S. Environmental Protection Agency. The limitations within this literature (primarily the early studies) included crude exposure assessment, incomplete follow-up, uncertain baseline rates, and uncontrolled confounding by factors such as smoking, drinking, and co-exposure to benzene and vinyl chloride. Four cohorts were studied by the same group of investigators, who reported no overall increased associations for any cancers. This four-cohort study was by far the most rigorous, having the most comprehensive exposure assessment and follow-up and the most detailed documentation. This study also contained the two largest cohorts, including an American cohort from Louisville, Kentucky, that ranked at or near the top for each of the 10 quality criteria. There was evidence of a strong healthy worker effect in the four-cohort study, which could have hidden small excess risks. Small increased risks were suggested by internal or company-specific analyses, but these were most likely caused by uncontrolled confounding and low baseline rates. Overall, the weight of evidence does not support any substantial link between chloroprene exposure and cancer, but inconsistencies and a lack of control for major confounders preclude drawing firmer conclusions.

  4. RADON AND CARCINOGENIC RISK IN MOSCOW

    Directory of Open Access Journals (Sweden)

    S. M. Golovanev

    2015-01-01

    Full Text Available Objective: comparative evaluation of carcinogenic risk inMoscowfrom radon in indoor and atmospheric pollutants.Materials and methods: the lung cancer incidence in Moscow; radiation-hygienic passport of the territory; .U.S. EPA estimated average age at all and radon induced deaths, years of life lost; Report of UNSCEAR 2006 and WHO handbook on indoor radon, 2009. Trend analysis of incidence; evaluation of the excess relative risk; assessment of ratio radon-induced population risk and published values оf total population carcinogenic risk from chemical carcinogens.Results: it is shown that the 304 cases of lung cancer per year (1. 85 10-3 on average from 2006 to 2011 (21280diseases for 70 years in addition to background level induced by radon; the differences in average trends of all lungcancer incidence in the districts can exceed 25%.Conclusion. The potential of risk reduction by measures of mitigation radon concentration exceeds 5 times the cost efficiency to reduce emissions from vehicles and can reduce cancer incidence, on average 236 cases per year; population risk 16520 cases over 70 years or save not less than 2832 person-years of life per year. The annual effect of reducing losses from not-survival of 12 years as a result of radon-induced lung cancer deaths exceeds 14160000 dollars. The evaluating of the carcinogenic risk from radon in accordance with the definition of population risk increases the predictive evaluation of the effectiveness of preventive measures more than twice.

  5. Prevalidation study of the BALB/c 3T3 cell transformation assay for assessment of carcinogenic potential of chemicals.

    Science.gov (United States)

    Tanaka, Noriho; Bohnenberger, Susanne; Kunkelmann, Thorsten; Munaro, Barbara; Ponti, Jessica; Poth, Albrecht; Sabbioni, Enrico; Sakai, Ayako; Salovaara, Susan; Sasaki, Kiyoshi; Thomas, B Claire; Umeda, Makoto

    2012-04-11

    The cell transformation assays (CTAs) have attracted attention within the field of alternative methods due to their potential to reduce the number of animal experiments in the field of carcinogenicity. The CTA using BALB/c 3T3 cells has proved to be able to respond to chemical carcinogens by inducing morphologically transformed foci. Although a considerable amount of data on the performance of the assay has been collected, a formal evaluation focusing particularly on reproducibility, and a standardised protocol were considered important. Therefore the European Centre for the Validation of Alternative Methods (ECVAM) decided to coordinate a prevalidation study of the BALB/c 3T3 CTA. Three different laboratories from Japan and Europe participated. In the study the following modules were assessed stepwise: test definition (Module 1) consisted of the standardisation of the protocol, the selection of the cell lineage, and the preparation of a photo catalogue on the transformed foci. The within-laboratory reproducibility (Module 2) and the transferability (Module 3) were assessed using non-coded and coded 3-methylcholanthrene. Then, five coded chemicals were tested for the assessment of between-laboratory reproducibility (Module 4). All three laboratories obtained positive results with benzo[a]pyrene, phenanthrene and o-toluidine HCl. 2-Acetylaminofluorene was positive in two laboratories and equivocal in one laboratory. Anthracene was negative in all three laboratories. The chemicals except phenanthrene, which is classified by IARC (http://monographs.iarc.fr) as group 3 "not classifiable as to its carcinogenicity to human", were correctly predicted as carcinogens. Further studies on phenanthrene will clarify this discrepancy. Thus, although only a few chemicals were tested, it can be seen that the predictive capacity of the BALB/c 3T3 CTA is satisfactory. On the basis of the outcome of this study, an improved protocol, incorporating some changes related to data

  6. Development of a cancer-based chronic inhalation reference value for hexavalent chromium based on a nonlinear-threshold carcinogenic assessment.

    Science.gov (United States)

    Haney, Joseph T; Erraguntla, Neeraja; Sielken, Robert L; Valdez-Flores, Ciriaco

    2012-12-01

    The carcinogenicity of hexavalent chromium(CrVI) is of significant interest to regulatory agencies for the protection of public health and to industry. Additionally, the mode of action (MOA) and conditions under which CrVI may induce carcinogenicity (e.g., reductive capacity considerations) have recently been the subject of significant scientific debate. Epidemiological data supported by data relevant to the carcinogenic MOA support considering nonlinear-threshold carcinogenic assessments for comparison to default linear low-dose extrapolation approaches. This study reviews epidemiological studies available in the scientific literature and conducts additional statistical dose-response analyses to identify potential carcinogenic thresholds and points of departure (PODs) in the context of supportive MOA information for a nonlinear-threshold inhalation carcinogenic assessment. Dosimetric adjustments and application of appropriate uncertainty factors (total UF of 30) to the selected cumulative exposure POD results in a cancer-based chronic inhalation reference value (ReV) of 0.24 μgCrVI/m(3). This chronic ReV is 300 times higher than the 1 in 100,000 excess cancer risk air concentration of 8E-04 μg/m(3) based on USEPA's unit risk factor. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. CPDB: Carcinogenic Potency Database.

    Science.gov (United States)

    Fitzpatrick, Roberta Bronson

    2008-01-01

    The Carcinogenic Potency Database reports analyses of animal cancer tests on 1,547 chemicals. These tests are used in support of cancer risk assessments for humans. Results are searchable and are made available via the National Library of Medicine's (NLM) TOXNET system. This column will provide background information on the database, as well as present search basics.

  8. Use of imaging in the follow-up of workers exposed to lung carcinogens: practices in occupational medicine and its determinants.

    Science.gov (United States)

    Verger, Pierre; Cabut, Sandrine; Viau, Alain; Souville, Marc; Pardon, Claire; Charrier, Danielle; De Labrusse, Benoît; Lehucher-Michel, Marie-Pascale; Arnaud, Sandrine

    2011-01-01

    We studied occupational physicians' (OPs) practices of referrals for imaging of workers occupationally exposed to lung/pleural carcinogens and the factors associated with them. This cross-sectional telephone survey of 379 OPs practicing in Southeastern France showed that 81% of them referred exposed patients for chest radiographs, 33.5% for computed tomography (CT), and 16.1% for neither. Making no referral was positively associated with believing cancer risks are lower in one's own geographic sector than elsewhere and negatively associated with keeping employee risk records up-to-date. Referrals for CT were positively associated with work at in-house occupational health services (OHS), and completing employee exposure histories often/always. Both the OHS type and factors that may shape OPs' awareness of cancer risks in their sector appear to influence imaging referral practices. Occupational physicians would benefit from guidelines clarifying benefits and risks associated with imaging in such patients. An effort to harmonize regulatory provisions and guidelines also appears necessary.

  9. Squamous cell carcinoma in association with dental implants: an assessment of previously hypothesized carcinogenic mechanisms and a case report.

    Science.gov (United States)

    Bhatavadekar, Neel B

    2012-12-01

    Although dental implants have seen tremendous clinical success over the past few decades, there are some worrying reports in literature describing squamous cell carcinoma (SCC) in close association with dental implants. This article also provides a critical assessment of the published literature relating to the presence of carcinoma in association with dental implants, analyzing the previously published and hypothesized carcinogenic responses to an implant, to try and come to a conclusion regarding the plausibility and clinical risk for cancer formation in association with dental implants. An unusual case of an SCC noted in close proximity to a dental implant is also presented. A systematic search was conducted using Medline (PubMed), Cochrane Database, and Google Scholar with the search terms "cancer," "squamous cell carcinoma," "dental implant," "SCC," "peri-implantitis," "oral cancer," and "implantology" and using multiple combinations using Boolean operators "or" and "and." The search was not limited to dental literature; orthopedic and biomedical literature was also included. The results were then hand screened to pick out the relevant articles. In total, 14 previous published reports were found, where 24 dental implants were reported to be associated with SCC. Not all the reported patients had a history of cancer, but contributory factors such as smoking were found. An analysis of the biological plausibility of previously proposed carcinogenic mechanisms, such as corrosion, metallic ion release, and particulate debris, did not support the etiologic role for dental implants in cancer development, and the standardized incidence ratio was found to be extremely low (0.00017). Peri-implantitis should be assessed cautiously in patients receiving implants who have a previous history of cancer. Dental implants are a safe treatment modality based on the published data, and any change in surgical protocol is not mandated.

  10. Assessment of the carcinogenic N-nitrosodiethanolamine in tobacco products and tobacco smoke.

    Science.gov (United States)

    Brunnemann, K D; Hoffmann, D

    1981-01-01

    A simple, reproducible gas chromatography-thermal energy analyzer (g.c.-TEA) method has been developed for the analysis of N-nitrosodiethanolamine (NDELA) in tobacco and tobacco smoke. The extract of tobacco or the trapped particulates of tobacco smoke are chromatographed on silica gel. The NDELA containing fractions are concentrated, silylated and analyzed with a modified g.c.-TEA system. [14C]NDELA serves as internal standard for the quantitative analysis. Experimental cigarettes made from tobaccos which were treated with the sucker growth inhibitor maleic hydrazidediethanolamine (MH-DELA) contained 115--420 p.p.b. of NDELA and their smoke contained 20--290 ng/cigarette, whereas hand-suckered tobacco and its smoke were free of NDELA. The tobacco of US smoking products contained 115--420 p.p.b. of NDELA and the mainstream smoke from such products yielded 10--68 ng/cigar or cigarette. NDELA levels in chewing tobacco ranged from 220--280 p.p.b. and in two commercial snuff products were 3,200 and 6,800 p.p.b. Although the five analyzed MH-DELA preparations contained between 0.6--1.9 p.p.m. NDELA it is evident that the major portion of NDELA in tobacco is formed from the DELA residue during the tobacco processing. Based on bioassay data from various laboratories which have shown that NDELA is a relatively strong carcinogen and based on the results of this study the use of MH-DELA for the cultivation of tobacco is questioned.

  11. Elimination Kinetics of the Tobacco-Specific Biomarker and Lung Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol

    Science.gov (United States)

    Goniewicz, Maciej L.; Havel, Christopher M.; Peng, Margaret Wilson; Jacob, Peyton; Dempsey, Delia; Yu, Lisa; Zielinska-Danch, Wioleta; Koszowski, Bartosz; Czogala, Jan; Sobczak, Andrzej; Benowitz, Neal L.

    2009-01-01

    4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is tobacco specific and has a longer half-life than other tobacco biomarkers studied thus far. An accurate measurement of the NNAL half-life is important for optimal use to assess exposure to tobacco smoke. We determined the half-life of NNAL in urine in eight daily smokers on a clinical research ward and in five occasional smokers in a real-life environment. Total NNAL in urine was monitored for 14 days in daily smokers after stopping smoking and for up to 60 days in occasional smokers. The average half-life for the terminal phase in the daily smoker group using a two-compartmental body model was 10.3 days (beta phase), and using a noncompartmental model, it was 9.1 days. In the occasional group, these values were 17.6 and 16.0 days, respectively. The alpha-phase half-lives were 14.3 and 27.8 hours for the two groups, respectively. The inter-subject coefficient of variation of the NNAL terminal half-life ranged from 14% to 30%, and the intra-subject coefficient of variation ranged from 3% to 18%. There was very good agreement between the plasma and urinary half-lives in two subjects with plasma analyses: 7.4 versus 7.9 days and 9.2 versus 10.7 days. Mean renal clearance of NNAL was 13 ± 2.3 mL/min. The terminal half-life of NNAL of 10 to 18 days indicates that this biomarker can be used to detect tobacco smoke exposure for 6 to 12 weeks after cessation of exposure and requires a similar time to assess the steady levels of NNAL after switching from one tobacco product to another. PMID:19959691

  12. Lung volume assessments in normal and surfactant depleted lungs: agreement between bedside techniques and CT imaging.

    Science.gov (United States)

    Albu, Gergely; Petak, Ferenc; Zand, Tristan; Hallbäck, Magnus; Wallin, Mats; Habre, Walid

    2014-01-01

    Bedside assessment of lung volume in clinical practice is crucial to adapt ventilation strategy. We compared bedside measures of lung volume by helium multiple-breath washout technique (EELVMBW,He) and effective lung volume based on capnodynamics (ELV) to those assessed from spiral chest CT scans (EELVCT) under different PEEP levels in control and surfactant-depleted lungs. Lung volume was assessed in anaesthetized mechanically ventilated rabbits successively by measuring i) ELV by analyzing CO2 elimination traces during the application of periods of 5 consecutive alterations in inspiratory/expiratory ratio (1:2 to 1.5:1), ii) measuring EELVMBW,He by using helium as a tracer gas, and iii) EELVCT from CT scan images by computing the normalized lung density. All measurements were performed at PEEP of 0, 3 and 9 cmH2O in random order under control condition and following surfactant depletion by whole lung lavage. Variables obtained with all techniques followed sensitively the lung volume changes with PEEP. Excellent correlation and close agreement was observed between EELVMBW,He and EELVCT (r = 0.93, p lungs, whereas this difference was not evidenced following surfactant depletion. These findings resulted in somewhat diminished but still significant correlations between ELV and EELVCT (r = 0.58, p Lung volume assessed with bedside techniques allow the monitoring of the changes in the lung aeration with PEEP both in normal lungs and in a model of acute lung injury. Under stable pulmonary haemodynamic condition, ELV allows continuous lung volume monitoring, whereas EELVMBW,He offers a more accurate estimation, but intermittently.

  13. Evaluation of a chemical risk assessment method of South Korea for chemicals classified as carcinogenic, mutagenic or reprotoxic (CMR).

    Science.gov (United States)

    Kim, Min-Uk; Byeon, Sang-Hoon

    2017-12-12

    Chemicals were used in various fields by the development of industry and science and technology. The Chemical Hazard Risk Management (CHARM) was developed to assess the risk of chemicals in South Korea. In this study, we were to evaluate the CHARM model developed for the effective management of workplace chemicals. We used 59 carcinogenic, mutagenic or reprotoxic (CMR) materials, which are both the work environment measurement result and the usage information among the manufacturer data. The CHARM model determines the risk to human health using the exposure level (based on working environment measurements or a combination of the quantity used and chemical physical properties (e.g., fugacity and volatility)), hazard (using occupational exposure limit (OEL) or Risk phrases (R-phrases)/Hazard statements (H-statements) from the Material Safety Data Sheet (MSDS)). The risk level was lower when using the results of the work environment measurement than when applying the chemical quantity and physical properties in the exposure level evaluation method. It was evaluated as grade 4 for the CMR material in the hazard class determination. The risk assessment method by R-phrases was evaluated more conservatively than the risk assessment method by OEL. And the risk assessment method by H-statements was evaluated more conservatively than the risk assessment method by R-phrases. The CHARM model was gradually conservatively assessed as it proceeded in the next step without quantitative information for individual workplaces. The CHARM is expected to help identify the risk if the hazards and exposure levels of chemicals were identified in individual workplaces. For CMR substances, although CHARM is highly evaluated for hazards, the risk is assessed to be low if exposure levels are assessed low. When evaluating the risk of highly hazardous chemicals such as CMR substances, we believe the model should be adapted to be more conservative and classify these as higher risk.

  14. The carcinogenicity of acrylamide.

    Science.gov (United States)

    Rice, Jerry M

    2005-02-07

    Acrylamide is carcinogenic to experimental mice and rats, causing tumors at multiple organ sites in both species when given in drinking water or by other means. In mice, acrylamide increases the incidence of alveologenic lung tumors and initiates skin tumors after dermal exposures. In two bioassays in rats, acrylamide administered in drinking water consistently induced peritesticular mesotheliomas, thyroid follicular cell tumors, and mammary gland tumors, as well as primary brain tumors when all such tumors were included in data analysis. In one of the rat bioassays, increased numbers of adrenal pheochromocytomas, adenomas of pituitary and clitoral glands, papillomas of the oral cavity, and adenocarcinomas of the uterus also occurred. In both humans and experimental animals, a significant fraction of ingested acrylamide is converted metabolically to the chemically reactive and genotoxic epoxide, glycidamide, which is likely to play an important role in the carcinogenicity of acrylamide. No studies on the carcinogenicity of glycidamide have been published, but bioassays of this compound are in progress. Epidemiologic studies of possible health effects from exposures to acrylamide have not produced consistent evidence of increased cancer risk, in either occupationally exposed workers or the general populations of several countries in which acrylamide is present in certain foods and beverages. A doubling of risk for pancreatic cancer was observed in the most highly exposed workers within the largest industrial cohort, but no consistent exposure-response relationships were identified. Retrospective re-analyses of previously conducted case-control studies of cancer incidence in several European populations have identified no causal relationship between consumption of foods or beverages that contain acrylamide and the incidence of cancers at various sites including kidney, large bowel, urinary bladder, oral cavity, pharynx, larynx, esophagus, breast, and ovary. These

  15. Animal carcinogenicity studies: 1. Poor human predictivity.

    Science.gov (United States)

    Knight, Andrew; Bailey, Jarrod; Balcombe, Jonathan

    2006-02-01

    The regulation of human exposure to potentially carcinogenic chemicals constitutes society's most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency's (EPA's) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or animal data also assessed by the World Health Organisation's International Agency for Research on Cancer (IARC), human carcinogenicity classifications were compatible with EPA classifications only for those 17 having at least limited human data (p = 0.5896). For those 111 primarily reliant on animal data, the EPA was much more likely than the IARC to assign carcinogenicity classifications indicative of greater human risk (p leading international authority on carcinogenicity assessments, and its significantly different human carcinogenicity classifications of identical chemicals indicate that: 1) in the absence of significant human data, the EPA is over-reliant on animal carcinogenicity data; 2) as a result, the EPA tends to over-predict carcinogenic risk; and 3) the true predictivity for human carcinogenicity of animal data is even poorer than is indicated by EPA figures alone. The EPA policy of erroneously assuming that tumours in animals are indicative of human carcinogenicity is implicated as a primary cause of these errors.

  16. The IARC Monographs on the carcinogenicity of crystalline silica.

    Science.gov (United States)

    Guha, Neela; Straif, Kurt; Benbrahim-Tallaa, Lamia

    2011-01-01

    Through extensive review of the published literature, two independent expert panels convened by the International Agency for Research on Cancer (IARC) Monographs Programme have classified crystalline silica as carcinogenic to humans while amorphous silica was not classifiable as to its carcinogenicity in humans. The panel remarked that crystalline silica in the form of quartz or cristobalite dust causes lung cancer in humans. We discuss the literature and rationale used to support the IARC evaluations of silica. A critical review, with a focus on lung tumors, was conducted of the pertinent literature on the carcinogenic effects of crystalline silica in humans and experimental animals as well as supportive mechanistic evidence. The strongest supportive evidence comes from pooled and meta-analyses that employed quantitative exposure assessment, focused on silicotics, accounted for potential confounding and demonstrated exposure-response trends. Consistency of the effect was observed despite some heterogeneity between individual studies. Tumor site concordance was observed with rodents and further supported by mechanistic data. Several million workers worldwide are exposed to crystalline silica. Silicosis and lung cancer in these workers are completely preventable diseases. The IARC evaluations are critical to supporting public health interventions to protect persons at high-risk.

  17. Carcinogenicity of acetaldehyde in alcoholic beverages: risk assessment outside ethanol metabolism.

    Science.gov (United States)

    Lachenmeier, Dirk W; Kanteres, Fotis; Rehm, Jürgen

    2009-04-01

    In addition to being produced in ethanol metabolism, acetaldehyde occurs naturally in alcoholic beverages. Limited epidemiological evidence points to acetaldehyde as an independent risk factor for cancer during alcohol consumption, in addition to the effects of ethanol. This study aims to estimate human exposure to acetaldehyde from alcoholic beverages and provide a quantitative risk assessment. The human dietary intake of acetaldehyde via alcoholic beverages was estimated based on World Health Organization (WHO) consumption data and literature on the acetaldehyde contents of different beverage groups (beer, wine, spirits and unrecorded alcohol). The risk assessment was conducted using the European Food Safety Authority's margin of exposure (MOE) approach with benchmark doses obtained from dose-response modelling of animal experiments. Life-time cancer risk was calculated using the T25 dose descriptor. The average exposure to acetaldehyde from alcoholic beverages was estimated at 0.112 mg/kg body weight/day. The MOE was calculated to be 498, and the life-time cancer risk at 7.6 in 10,000. Higher risk may exist for people exposed to high acetaldehyde contaminations, as we have found in certain unrecorded alcohol beverages in Guatemala and Russia, for which we have demonstrated possible exposure scenarios, with risks in the range of 1 in 1000. The life-time cancer risks for acetaldehyde from alcoholic beverages greatly exceed the usual limits for cancer risks from the environment set between 1 : 10,000 and 1 : 1,000,000. Alcohol consumption has thus been identified as a direct source of acetaldehyde exposure, which in conjunction with other sources (food flavourings, tobacco) results in a magnitude of risk requiring intervention. An initial public health measure could be to reduce the acetaldehyde content in alcoholic beverages as low as technologically possible, and to restrict its use as a food flavour additive.

  18. Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy

    Directory of Open Access Journals (Sweden)

    Pradyumna Kumar Mishra

    2015-12-01

    Full Text Available December 2014 marked the 30th year anniversary of Bhopal gas tragedy. This sudden and accidental leakage of deadly poisonous methyl isocyanate (MIC gas instigated research efforts to understand the nature, severity of health damage and sufferings of 570 000 ailing survivors of this tragedy. In a decade-long period, our systematic laboratory investigations coupled with long-term molecular surveillance studies have comprehensively demonstrated that the risk of developing an environmental associated aberrant disease phenotype, including cancer, involves complex interplay of genomic and epigenetic reprogramming. These findings poised us to translate this knowledge into an investigative framework of “molecular biodosimetry” in a strictly selected cohort of MIC exposed individuals. A pragmatic cancer risk-assessment strategy pursued in concert with a large-scale epidemiological study might unfold molecular underpinnings of host-susceptibility and exposureresponse relationship. The challenges are enormous, but we postulate that the study will be necessary to establish a direct initiation-promotion paradigm of environmental carcinogenesis. Given that mitochondrial retrograde signaling-induced epigenetic reprogramming is apparently linked to neoplasticity, a cutting-edge tailored approach by an expert pool of biomedical researchers will be fundamental to drive these strategies from planning to execution. Validating the epigenomic signatures will hopefully result in the development of biomarkers to better protect human lives in an overburdened ecosystem, such as India, which is continuously challenged to meet population demands. Besides, delineating the mechanistic links between MIC exposure and cancer morbidity, our investigative strategy might help to formulate suitable regulatory policies and measures to reduce the overall burden of occupational and environmental carcinogenesis.

  19. Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy.

    Science.gov (United States)

    Mishra, Pradyumna Kumar; Raghuram, Gorantla Venkata; Bunkar, Neha; Bhargava, Arpit; Khare, Naveen Kumar

    2015-01-01

    December 2014 marked the 30th year anniversary of Bhopal gas tragedy. This sudden and accidental leakage of deadly poisonous methyl isocyanate (MIC) gas instigated research efforts to understand the nature, severity of health damage and sufferings of 570 000 ailing survivors of this tragedy. In a decade-long period, our systematic laboratory investigations coupled with long-term molecular surveillance studies have comprehensively demonstrated that the risk of developing an environmental associated aberrant disease phenotype, including cancer, involves complex interplay of genomic and epigenetic reprogramming. These findings poised us to translate this knowledge into an investigative framework of "molecular biodosimetry" in a strictly selected cohort of MIC exposed individuals. A pragmatic cancer risk-assessment strategy pursued in concert with a large-scale epidemiological study might unfold molecular underpinnings of host-susceptibility and exposureresponse relationship. The challenges are enormous, but we postulate that the study will be necessary to establish a direct initiation-promotion paradigm of environmental carcinogenesis. Given that mitochondrial retrograde signaling-induced epigenetic reprogramming is apparently linked to neoplasticity, a cutting-edge tailored approach by an expert pool of biomedical researchers will be fundamental to drive these strategies from planning to execution. Validating the epigenomic signatures will hopefully result in the development of biomarkers to better protect human lives in an overburdened ecosystem, such as India, which is continuously challenged to meet population demands. Besides, delineating the mechanistic links between MIC exposure and cancer morbidity, our investigative strategy might help to formulate suitable regulatory policies and measures to reduce the overall burden of occupational and environmental carcinogenesis. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  20. Lung volume assessment in acute respiratory distress syndrome.

    Science.gov (United States)

    Chen, Lu; Brochard, Laurent

    2015-06-01

    Measurements of lung volumes allow evaluating the pathophysiogical severity of acute respiratory distress syndrome (ARDS) in terms of the degree of reduction in aerated lung volume, calculating strain, quantifying recruitment and/or hyperinflation, and gas volume distribution. We summarize the current techniques for lung volume assessment selected according to their possible usage in the ICU and discuss the recent findings obtained with implementation of these techniques in patients with ARDS. Computed tomography technique remains irreplaceable in terms of quantitative aeration of different lung regions, but the commonly used cut-offs for classification may be questioned with recent findings on nonpathological lungs. Monitoring end expiratory lung volume using nitrogen washout technique enhanced our understanding on lung volume change during positioning, pleural effusion drainage, intra-abdominal hypertension, and recruitment maneuver. Recent studies supported that tidal volume could not surrogate tidal strain, which needs measurement of functional residual capacity and which is correlated with pro-inflammatory lung response. Although lung volume measurements are still limited to research area of ARDS, recent progress in technology provides clinicians more opportunities to evaluate lung volumes noninvasively at the bedside and may facilitate individualization of ventilator settings based on the specific physiological understandings of a given patient.

  1. Bridging the etiologic and prognostic outlooks in individualized assessment of absolute risk of an illness: application in lung cancer.

    Science.gov (United States)

    Karp, Igor; Sylvestre, Marie-Pierre; Abrahamowicz, Michal; Leffondré, Karen; Siemiatycki, Jack

    2016-11-01

    Assessment of individual risk of illness is an important activity in preventive medicine. Development of risk-assessment models has heretofore relied predominantly on studies involving follow-up of cohort-type populations, while case-control studies have generally been considered unfit for this purpose. To present a method for individualized assessment of absolute risk of an illness (as illustrated by lung cancer) based on data from a 'non-nested' case-control study. We used data from a case-control study conducted in Montreal, Canada in 1996-2001. Individuals diagnosed with lung cancer (n = 920) and age- and sex-matched lung-cancer-free subjects (n = 1288) completed questionnaires documenting life-time cigarette-smoking history and occupational, medical, and family history. Unweighted and weighted logistic models were fitted. Model overfitting was assessed using bootstrap-based cross-validation and 'shrinkage.' The discriminating ability was assessed by the c-statistic, and the risk-stratifying performance was assessed by examination of the variability in risk estimates over hypothetical risk-profiles. In the logistic models, the logarithm of incidence-density of lung cancer was expressed as a function of age, sex, cigarette-smoking history, history of respiratory conditions and exposure to occupational carcinogens, and family history of lung cancer. The models entailed a minimal degree of overfitting ('shrinkage' factor: 0.97 for both unweighted and weighted models) and moderately high discriminating ability (c-statistic: 0.82 for the unweighted model and 0.66 for the weighted model). The method's risk-stratifying performance was quite high. The presented method allows for individualized assessment of risk of lung cancer and can be used for development of risk-assessment models for other illnesses.

  2. Physiologic assessment of the ex vivo donor lung for transplantation.

    Science.gov (United States)

    Yeung, Jonathan C; Cypel, Marcelo; Machuca, Tiago N; Koike, Terumoto; Cook, Douglas J; Bonato, Riccardo; Chen, Manyin; Sato, Masaaki; Waddell, Thomas K; Liu, Mingyao; Slutsky, Arthur S; Keshavjee, Shaf

    2012-10-01

    The evaluation of donor lungs by normothermic ex vivo acellular perfusion has improved the safety of organ utilization. However, this strategy requires a critical re-evaluation of the parameters used to assess lungs during ex vivo perfusion compared with those traditionally used to evaluate the donor lung in vivo. Using a porcine model, we studied the physiology of acellular lung perfusion with the aim of improving the accuracy of clinical ex vivo evaluation. Porcine lungs after 10 hours of brain death and 24 hours of cold ischemia and uninjured control lungs were perfused for 12 hours and then transplanted. PaO2, compliance, airway pressure and pulmonary vascular resistance were measured. Ventilation with 100% nitrogen and addition of red blood cells to the perfusate were used to clarify the physiologic disparities between in vivo blood perfusion and ex vivo acellular perfusion. During 12 hours of ex vivo perfusion, injured lungs developed edema with decreased compliance and increased airway pressure, but ex vivo PO2 remained stable. After transplantation, injured lungs demonstrated high vascular resistance and poor PaO2. A reduced effect of shunt on ex vivo lung perfusion PO2 was found to be attributable to the linearization of the relationship between oxygen content and PO2, which occurs with acellular perfusate. Ex vivo PO2 may not be the first indication of lung injury and, taken alone, may be misleading in assessing the ex vivo lung. Thus, evaluation of other physiologic parameters takes on greater importance. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Relevance of urinary 3-hydroxybenzo(a)pyrene and 1-hydroxypyrene to assess exposure to carcinogenic polycyclic aromatic hydrocarbon mixtures in metallurgy workers.

    Science.gov (United States)

    Barbeau, Damien; Persoons, Renaud; Marques, Marie; Hervé, Claire; Laffitte-Rigaud, Gilbert; Maitre, Anne

    2014-06-01

    In metallurgy, workers are exposed to mixtures of polycyclic aromatic hydrocarbons (PAHs) in which some compounds are carcinogenic. Biomonitoring of PAH exposure has been performed by measuring urinary 1-hydroxypyrene (1-OHP), a metabolite of pyrene which is not carcinogenic. This study investigated the use of 3-hydroxybenzo(a)pyrene (3-OHBaP), a metabolite of benzo(a)pyrene (BaP) which is the main carcinogenic component in PAHs, to improve carcinogen exposure assessment. We included 129 metallurgy workers routinely exposed to PAHs during working hours. Urinary samples were collected at three sampling times at the beginning and at the end of the working week for 1-OHP and 3-OHBaP analyses. Workers in anode production showed greater exposure to both biomarkers than those in cathode or silicon production, with respectively, 71, 40, and 30% of 3-OHBaP concentrations exceeding the value of 0.4 nmol mol(-1) creatinine. No difference was observed between the 3-OHBaP levels found at the end of the penultimate workday shift and those at the beginning of the last workday shift. Within these plants, the 1-OHP/3-OHBaP ratios varied greatly according to the workers' activity and emission sources. Using linear regression between these two metabolites, the 1-OHP level corresponding to the guidance value for 3-OHBaP ranged from 0.7 to 2.4 µmol mol(-1) creatinine, depending on the industrial sector. This study emphasizes the interest of monitoring urinary 3-OHBaP at the end of the last workday shift when working week exposure is relatively steady, and the irrelevance of a single guideline value for 1-OHP when assessing occupational health risk. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  4. Residual Volume and Total Lung Capacity to Assess Reversibility in Obstructive Lung Disease.

    Science.gov (United States)

    McCartney, Conor T; Weis, Melissa N; Ruppel, Gregg L; Nayak, Ravi P

    2016-11-01

    Reversibility of obstructive lung disease is traditionally defined by changes in FEV1 or FVC in response to bronchodilators. These may not fully reflect changes due to a reduction in hyperinflation or air-trapping, which have important clinical implications. To date, only a handful of studies have examined bronchodilators' effect on lung volumes. The authors sought to better characterize the response of residual volume and total lung capacity to bronchodilators. Responsiveness of residual volume and total lung capacity to bronchodilators was assessed with a retrospective analysis of pulmonary function tests of 965 subjects with obstructive lung disease as defined by the lower limit of normal based on National Health and Nutritional Examination Survey III prediction equations. A statistically significant number of subjects demonstrated response to bronchodilators in their residual volume independent of response defined by FEV1 or FVC, the American Thoracic Society and European Respiratory Society criteria. Reduced residual volume weakly correlated with response to FEV1 and to FVC. No statistically significant correlation was found between total lung capacity and either FEV1 or FVC. A significant number of subjects classified as being nonresponsive based on spirometry have reversible residual volumes. Subjects whose residual volumes improve in response to bronchodilators represent an important subgroup of those with obstructive lung disease. The identification of this subgroup better characterizes the heterogeneity of obstructive lung disease. The clinical importance of these findings is unclear but warrants further study. Copyright © 2016 by Daedalus Enterprises.

  5. Asbestos and metals as carcinogens.

    Science.gov (United States)

    Norseth, T

    1980-01-01

    Increased incidences of lung carcinoma and pleural mesothelioma in humans exposed to asbestos have been irrefutably established. Different forms of asbestos may have different tumorigenic activities, depending on surface properties, durability, and size of the fibers. A number of metals, such as nickel, chromium, and arsenic, are known to be carcinogenic to humans; for beryllium and cadmium the epidemiologic evidence is less extensive. All these metals also induce genetic toxicity in vitro. For chromium the molecular mechanism of metal tumorigenesis has been extensively investigated; the hexavalent form is generally a much more potent mutagen than is chromium (III). Solubility seems to be necessary for the genotoxicity of nickel. At present it cannot be concluded that all metals act by the same carcinogenic mechanism, even though direct modification of DNA seems to be the common experimental finding.

  6. Objective and Structured Assessment of Lung Ultrasound Competence

    DEFF Research Database (Denmark)

    Skaarup, Søren Helbo; Laursen, Christian B; Bjerrum, Anne Sofie

    2017-01-01

    . 5 elements were excluded. 2 new elements were proposed, 1 gained consensus. 2 elements were rephrased. We found that the lung ultrasound competence evaluation tool could differentiate between different levels of competence (p... and intermediate operators (p=0.005) but not between novices and intermediate (p=0.06). The assessment tool had a good inter-rater agreement; Pearson's R=0.85 (pevaluate operator competence in point-of-care lung ultrasound......RATIONALE: Point-of-care lung ultrasound imaging has substantial diagnostic value and is widely used in respiratory, emergency and critical care medicine. Like other ultrasound examinations, lung ultrasound is operator-dependent. The current recommendations for competence in lung ultrasound sets...

  7. Assessment of volume reduction effect after lung lobectomy for cancer.

    Science.gov (United States)

    Ueda, Kazuhiro; Murakami, Junichi; Sano, Fumiho; Hayashi, Masataro; Kobayashi, Taiga; Kunihiro, Yoshie; Hamano, Kimikazu

    2015-07-01

    Lung lobectomy results in an unexpected improvement of the remaining lung function in some patients with moderate-to-severe emphysema. Because the lung function is the main limiting factor for therapeutic decision making in patients with lung cancer, it may be advantageous to identify patients who may benefit from the volume reduction effect, particularly those with a poor functional reserve. We measured the regional distribution of the emphysematous lung and normal lung using quantitative computed tomography in 84 patients undergoing lung lobectomy for cancer between January 2010 and December 2012. The volume reduction effect was diagnosed using a combination of radiologic and spirometric parameters. Eight patients (10%) were favorably affected by the volume reduction effect. The forced expiratory volume in one second increased postoperatively in these eight patients, whereas the forced vital capacity was unchanged, thus resulting in an improvement of the airflow obstruction postoperatively. This improvement was not due to a compensatory expansion of the remaining lung but was associated with a relative decrease in the forced end-expiratory lung volume. According to a multivariate analysis, airflow obstruction and the forced end-expiratory lung volume were independent predictors of the volume reduction effect. A combined assessment using spirometry and quantitative computed tomography helped to characterize the respiratory dynamics underlying the volume reduction effect, thus leading to the identification of novel predictors of a volume reduction effect after lobectomy for cancer. Verification of our results by a large-scale prospective study may help to extend the indications for lobectomy in patients with oncologically resectable lung cancer who have a marginal pulmonary function. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Vegetables affect the expression of genes involved in carcinogenic and anticarcinogenic processes in the lungs of female C57BL/6 mice

    NARCIS (Netherlands)

    van Breda, S.G.J.; van Agen, E.; van Sanden, S.; Burzykowski, T.; Kleinjans, J.C.; van Delft, J.H.

    2005-01-01

    Worldwide, lung cancer is the most prevalent and lethal malignant disease. In addition to avoidance of the most predominant risk factor, i.e., tobacco use, consumption of high amounts of vegetables and fruits could be an effective means of preventing lung cancer. However, the molecular mechanisms

  9. Assessment of the mutagenic, recombinogenic, and carcinogenic potential of amphotericin B in somatic cells of Drosophila melanogaster.

    Science.gov (United States)

    Saturnino, Rosiane Soares; Machado, Nayane Moreira; Lopes, Jeyson Cesary; Nepomuceno, Júlio César

    2018-01-01

    Amphotericin B (AmB) is an antifungal antibiotic extracted from Streptomyces nodosus. Its fungicidal activity depends primarily on its binding to the sterol group that is present in fungal membranes. In view of the toxicity of this drug, the purpose of this study was to evaluate its mutagenic, carcinogenic, and recombinogenic activity, based on the wing somatic mutation and recombination test (SMART) and the epithelial tumor detection test (wts) applied to Drosophila melanogaster. Larvae were chronically treated with different concentrations of AmB (0.01, 0.02, and 0.04 mg/mL). The results revealed that AmB is a promutagen exhibiting increase in the number of spots on individuals from high bioactivation (HB) cross with a high level of cytochrome P450. The results also indicate that the main genotoxic event induced by AmB is recombinogenicity. Homologous recombination can act as a determinant at different stages of carcinogenesis. For verification of carcinogenic potential of this compound, larvae from the wts/mwh and wts/ORR, flr3 were treated with the same three AmB concentrations used in the SMART assay. The results did not provide evidence that AmB has carcinogenic potential in wts/mwh individuals. However, individuals from wts/ORR, flr3 developed tumors at the highest concentration tested.

  10. Assessment of the mutagenic, recombinogenic and carcinogenic potential of fipronil insecticide in somatic cells of Drosophila melanogaster.

    Science.gov (United States)

    de Morais, Cássio Resende; Bonetti, Ana Maria; Carvalho, Stephan Malfitano; de Rezende, Alexandre Azenha Alves; Araujo, Galber Rodrigues; Spanó, Mário Antônio

    2016-12-01

    Fipronil (FP) is an insecticide that belongs to the phenylpyrazole chemical family and is used to control pests by blocking GABA receptor at the entrance channel of the chlorine neurons. The aim of this study was to evaluate the mutagenic, recombinogenic and carcinogenic potential of FP. The mutagenic and recombinogenic effects were evaluated using the somatic mutation and recombination test (SMART) on wing cells of Drosophila melanogaster. Third instar larvae from standard (ST) and high bioactivation (HB) crosses were treated with different concentrations of FP (0.3, 0.7, 1.5 or 3.0 × 10-5 mM). The results showed mutagenic effects at all concentrations tested in the HB cross; and all concentrations tested in the ST cross, except at concentration of 0.7 × 10-5 mM. The carcinogenic effect of FP was assayed through the test for detection of epithelial tumor (warts) in D. melanogaster. Third instar larvae from wts/TM3 virgin females mated to mwh/mwh males were treated with different concentrations of FP (0.3, 0.7, 1.5 or 3.0 × 10-5 mM). All these concentrations induced a statistically significant increase in tumor frequency. In conclusion, FP proved to be mutagenic, recombinogenic and carcinogenic in somatic cells of D. melanogaster. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Environmental exposure to carcinogens in northwestern Cameroon ...

    African Journals Online (AJOL)

    Background: In developing countries, 6% of deaths are due to cancer but cancer prevention is not practiced. Humans can prevent themselves from a number of workplace and environmental carcinogens. Objectives: To assess exposure to carcinogens, risky behaviours and associated preventive methods. Methods: A ...

  12. [Assessment of nutritional status in patients with primary lung cancer].

    Science.gov (United States)

    Chermiti Ben Abdallah, Fatma; Ben Saïd, Hanène; Chamkhi, Najiba; Ferchichi, Marwa; Chtourou, Amel; Taktak, Sofia; Ben Kheder, Ali

    2013-10-01

    Lung cancer is the leading cause of cancer-related mortality worldwide. Malnutrition is a common problem among patients with cancer, affecting up to 85% of patients with certain cancers and represents a risk factor for poor prognosis. aim: evaluate nutritional status in patients with lung cancer before and during treatment using nutritional risk index. it's a prospective study conducted in pneumology IV department in Abderahman Mami hospital, from January to May 2011. 30 male patients with a lung cancer were included. Nutritional status was assessed before and during treatment based on anthropometric measures, biological markers and nutritional risk index (NRI). Mean age of patients was 58 ± 12 years, ranging from 19 to 82 years. 29 patients had non small cell lung cancer and one patient had small cell cancer. Malnutrition was noted in 14 patients (47%) before treatment according to the NRI. It was noted in 23 patients (77%) after three cycles of chemotherapy with severe malnutrition in 8 patients. Relationship between body mass index (BMI) and the NRI was linear, but NRI tends to evaluate more objectively risk of malnutrition in patients with lung cancer. Nutritional assessment in patient with lung cancer should be performed systematically, early and repeatedly. Several markers can be used such as BMI and NRI. Nutritional support will reduce morbidity and improve quality of life in patients with lung cancer.

  13. Particulate matter air pollution components and risk for lung cancer

    NARCIS (Netherlands)

    Raaschou-Nielsen, O.; Beelen, R.; Wang, M.; Hoek, G.|info:eu-repo/dai/nl/413650944; Andersen, Z. J.; Hoffmann, B.; Stafoggia, M.; Samoli, E.; Weinmayr, G.; Dimakopoulou, K.; Nieuwenhuijsen, M.; Xun, W. W.; Fischer, P.; Eriksen, K. T.; Sørensen, M.; Tjønneland, A.; Ricceri, F.; de Hoogh, K.; Key, T.; Eeftens, M.; Peeters, P. H.|info:eu-repo/dai/nl/074099655; Bueno-de-Mesquita, H. B.|info:eu-repo/dai/nl/06929528X; Meliefste, K.; Oftedal, B.; Schwarze, P. E.; Nafstad, P.; Galassi, C.; Migliore, E.; Ranzi, A.; Cesaroni, G.; Badaloni, C.; Forastiere, F.; Penell, J.; De Faire, U.; Korek, M.; Pedersen, N.; Östenson, C. G.; Pershagen, G.; Fratiglioni, L.; Concin, H.; Nagel, G.; Jaensch, A.; Ineichen, A.; Naccarati, A.; Katsoulis, M.; Trichpoulou, A.; Keuken, M.; Jedynska, A.; Kooter, I. M.; Kukkonen, J.; Brunekreef, B.|info:eu-repo/dai/nl/067548180; Sokhi, R. S.; Katsouyanni, K.; Vineis, P.

    2016-01-01

    Background: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. Methods: We used data from 14 cohort studies in eight European countries. We

  14. Weighted gene co-expression network analysis of pneumocytes under exposure to a carcinogenic dose of chloroprene.

    Science.gov (United States)

    Guo, Yinghua; Xing, Yonghua

    2016-04-15

    Occupational exposure to chloroprene via inhalation may lead to acute toxicity and chronic pulmonary diseases, including lung cancer. Currently, most research is focused on epidemiological studies of chloroprene production workers. The specific molecular mechanism of carcinogenesis by chloroprene in lung tissues still remains obscure, and specific candidate therapeutic targets for lung cancer are lacking. The present study identifies specific gene modules and valuable hubs associated with lung cancer. We downloaded the dataset GSE40795 from the Gene Expression Omnibus (GEO) and divided the dataset into the non-carcinogenic dose chloroprene exposed mice group and the carcinogenic dose chloroprene exposed mice group. With a systemic biological view, we discovered significantly altered gene modules between the two groups and identified hub genes in the carcinogenic dose exposed group using weighted co-expression network analysis (WGCNA). A total of 2434 differentially expressed genes were identified. Twelve gene modules with multiple biological activities were related to the carcinogenesis of chloroprene in lung tissue. Seven hub genes that were critical for the carcinogenesis of chloroprene in lung tissue were ultimately identified, including Cftr, Hip1, Tbl1x, Ephx1, Cbr3, Antxr2 and Ccnd2. They were implicated in inflammatory response, cell transformation, gene transcription regulation, phase II detoxification, angiogenesis, cell adhesion, motility and the cell cycle. The seven hub genes may become valuable candidates for risk assessment biomarkers and therapeutic targets in lung cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. FALLS-protocol: lung ultrasound in hemodynamic assessment of shock.

    Science.gov (United States)

    Lichtenstein, D

    2013-01-01

    The assessment of acute circulatory failure is a challenge in absence of solid gold standard. It is suggested that artifacts generated by lung ultrasound can be of help. The FALLS-protocol (Fluid Administration Limited by Lung Sonography) follows Weil's classification of shocks. Firstly, it searches for pericardial fluid, then right heart enlargment, lastly abolished lung sliding. In this setting, the diagnoses of pericardial tamponade, pulmonary embolism and tension pneumothorax, i.e. obstructive shock, can be schematically ruled out. Moreover, the search of diffuse lung rockets (i.e. multiple B-lines, a comet-tail artifact) is performed. Its absence excludes pulmonary edema, that in clinical practice is left cardiogenic shock (most cases). At this step, the patient (defined FALLS-responder) receives fluid therapy. He/she has usually a normal sonographic lung surface, an A-profile. Any clinical improvement suggests hypovolemic shock. The absence of improvement generates continuation of fluid therapy, eventually yielding fluid overload. This condition results in the change from A-profile to B-profile. Lung ultrasound has the advantage to demonstrate this interstitial syndrome at an early and infraclinical stage (FALLS-endpoint). The change from horizontal A-lines to vertical B-lines can be considered as a direct marker of volemia in this use. By elimination, this change indicates schematically distributive shock, while in current practice septic shock. The major limitation is the B-profile on admission generated by an initial lung disorder. FALLS-protocol, which can be associated with no drawback with traditional hemodynamic tools, uses a simple machine (without Doppler) and a suitable microconvex probe allowing for heart, lung and vein assessment.

  16. Prevalidation study of the Syrian hamster embryo (SHE) cell transformation assay at pH 6.7 for assessment of carcinogenic potential of chemicals.

    Science.gov (United States)

    Pant, Kamala; Bruce, Shannon W; Sly, Jamie E; Kunkelmann, Thorsten; Kunz-Bohnenberger, Susanne; Poth, Albrecht; Engelhardt, Günter; Schulz, Markus; Schwind, Karl-Rainer

    2012-04-11

    The Syrian hamster embryo (SHE) cell transformation assay (CTA) is an important in vitro method that is highly predictive of rodent carcinogenicity. It is a key method for reducing animal usage for carcinogenicity prediction. The SHE assay has been used for many years primarily to investigate and identify potential rodent carcinogens thereby reducing the number of 2-year bioassays performed in rodents. As for other assays with a long history of use, the SHE CTA has not undergone formal validation. To address this, the European Centre for the Validation of Alternative Methods (ECVAM) coordinated a prevalidation study. The aim of this study was to evaluate the within-laboratory reproducibility, test method transferability, and between-laboratory reproducibility and to develop a standardised state-of-the-art protocol for the SHE CTA at pH 6.7. Formal ECVAM principles for criteria on reproducibility (including the within-laboratory reproducibility, the transferability and the between-laboratories reproducibility) were applied. In addition to the assessment of reproducibility, this study helped define a standard protocol for use in developing an Organisation for Economic Co-operation and Development (OECD) test guideline for the SHE CTA. Six compounds were evaluated in this study: benzo(a)pyrene, 3-methylcholanthrene, o-toluidine HCl, 2,4-diaminotoluene, phthalic anhydride and anthracene. Results of this study demonstrate that a protocol is available that is transferable between laboratories, and that the SHE CTA at pH 6.7 is reproducible within- and between-laboratories. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Environmental carcinogenic polycyclic aromatic hydrocarbons in soil from Himalayas, India: Implications for spatial distribution, sources apportionment and risk assessment.

    Science.gov (United States)

    Devi, Ningombam Linthoingambi; Yadav, Ishwar Chandra; Shihua, Qi; Dan, Yang; Zhang, Gan; Raha, Priyankar

    2016-02-01

    The Indian Himalayan Region (IHR) is one of the important mountain ecosystems among the global mountain system which support wide variety of flora, fauna, human communities and cultural diversities. Surface soil samples (n = 69) collected from IHR were analysed for 16 priority polycyclic aromatic hydrocarbons (PAH) listed by USEPA. The ∑16PAH concentration in surface soil ranged from 15.3 to 4762 ngg(-1) (mean 458 ngg(-1)). The sum total of low molecular weight PAH (∑LMW-PAHs) (mean 74.0 ngg(-1)) were relatively lower than the high molecular weight PAH (∑HMW-PAHs) (mean 384 ngg(-1)). The concentration of eight carcinogenic PAHs (BaA, CHR, BbF, BkF, BaP, DahA, IcdP, BghiP) were detected high in mountain soil from IHR and ranged from 0.73 to 2729 ngg(-1) (mean 272 ngg(-1)). Based on spatial distribution map, high concentration of HMW- and LMW-PAHs were detected at GS1 site in Guwahati (615 and 4071 ngg(-1)), and lowest concentration of HMW-PAHs were found at IS6 in Itanagar (5.80 ngg(-1)) and LMW-PAHs at DS2 (17.3 ngg(-1)) in Dibrugarh. Total organic carbon (TOC) in mountain soil was poorly connected with ∑PAHs (r(2) = 0.072) and Car-PAHs (r(2) = 0.048), suggesting the little role of TOC in adsorption of PAHs. Isomeric ratio of PAHs showed the source of PAH contamination in IHR is mixed of petrogenic and pyrogenic origin and was affirmed by PAHs composition profile. These source apportionment results were further confirmed by principal component analysis (PCA). Eco-toxicological analysis showed the calculated TEQ for most carcinogenic PAH were 2-4 times more than the Dutch allowed limit, while TEQ of BaP was 25 times high, suggesting increasing trend of carcinogenicity of surface soil. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

    Science.gov (United States)

    Goodson, William H.; Lowe, Leroy; Carpenter, David O.; Gilbertson, Michael; Manaf Ali, Abdul; Lopez de Cerain Salsamendi, Adela; Lasfar, Ahmed; Carnero, Amancio; Azqueta, Amaya; Amedei, Amedeo; Charles, Amelia K.; Collins, Andrew R.; Ward, Andrew; Salzberg, Anna C.; Colacci, Anna Maria; Olsen, Ann-Karin; Berg, Arthur; Barclay, Barry J.; Zhou, Binhua P.; Blanco-Aparicio, Carmen; Baglole, Carolyn J.; Dong, Chenfang; Mondello, Chiara; Hsu, Chia-Wen; Naus, Christian C.; Yedjou, Clement; Curran, Colleen S.; Laird, Dale W.; Koch, Daniel C.; Carlin, Danielle J.; Felsher, Dean W.; Roy, Debasish; Brown, Dustin G.; Ratovitski, Edward; Ryan, Elizabeth P.; Corsini, Emanuela; Rojas, Emilio; Moon, Eun-Yi; Laconi, Ezio; Marongiu, Fabio; Al-Mulla, Fahd; Chiaradonna, Ferdinando; Darroudi, Firouz; Martin, Francis L.; Van Schooten, Frederik J.; Goldberg, Gary S.; Wagemaker, Gerard; Nangami, Gladys N.; Calaf, Gloria M.; Williams, Graeme P.; Wolf, Gregory T.; Koppen, Gudrun; Brunborg, Gunnar; Lyerly, H. Kim; Krishnan, Harini; Ab Hamid, Hasiah; Yasaei, Hemad; Sone, Hideko; Kondoh, Hiroshi; Salem, Hosni K.; Hsu, Hsue-Yin; Park, Hyun Ho; Koturbash, Igor; Miousse, Isabelle R.; Scovassi, A.Ivana; Klaunig, James E.; Vondráček, Jan; Raju, Jayadev; Roman, Jesse; Wise, John Pierce; Whitfield, Jonathan R.; Woodrick, Jordan; Christopher, Joseph A.; Ochieng, Josiah; Martinez-Leal, Juan Fernando; Weisz, Judith; Kravchenko, Julia; Sun, Jun; Prudhomme, Kalan R.; Narayanan, Kannan Badri; Cohen-Solal, Karine A.; Moorwood, Kim; Gonzalez, Laetitia; Soucek, Laura; Jian, Le; D’Abronzo, Leandro S.; Lin, Liang-Tzung; Li, Lin; Gulliver, Linda; McCawley, Lisa J.; Memeo, Lorenzo; Vermeulen, Louis; Leyns, Luc; Zhang, Luoping; Valverde, Mahara; Khatami, Mahin; Romano, Maria Fiammetta; Chapellier, Marion; Williams, Marc A.; Wade, Mark; Manjili, Masoud H.; Lleonart, Matilde E.; Xia, Menghang; Gonzalez Guzman, Michael J.; Karamouzis, Michalis V.; Kirsch-Volders, Micheline; Vaccari, Monica; Kuemmerle, Nancy B.; Singh, Neetu; Cruickshanks, Nichola; Kleinstreuer, Nicole; van Larebeke, Nik; Ahmed, Nuzhat; Ogunkua, Olugbemiga; Krishnakumar, P.K.; Vadgama, Pankaj; Marignani, Paola A.; Ghosh, Paramita M.; Ostrosky-Wegman, Patricia; Thompson, Patricia A.; Dent, Paul; Heneberg, Petr; Darbre, Philippa; Leung, Po Sing; Nangia-Makker, Pratima; Cheng, Qiang (Shawn); Robey, R.Brooks; Al-Temaimi, Rabeah; Roy, Rabindra; Andrade-Vieira, Rafaela; Sinha, Ranjeet K.; Mehta, Rekha; Vento, Renza; Di Fiore, Riccardo; Ponce-Cusi, Richard; Dornetshuber-Fleiss, Rita; Nahta, Rita; Castellino, Robert C.; Palorini, Roberta; Hamid, Roslida A.; Langie, Sabine A.S.; Eltom, Sakina E.; Brooks, Samira A.; Ryeom, Sandra; Wise, Sandra S.; Bay, Sarah N.; Harris, Shelley A.; Papagerakis, Silvana; Romano, Simona; Pavanello, Sofia; Eriksson, Staffan; Forte, Stefano; Casey, Stephanie C.; Luanpitpong, Sudjit; Lee, Tae-Jin; Otsuki, Takemi; Chen, Tao; Massfelder, Thierry; Sanderson, Thomas; Guarnieri, Tiziana; Hultman, Tove; Dormoy, Valérian; Odero-Marah, Valerie; Sabbisetti, Venkata; Maguer-Satta, Veronique; Rathmell, W.Kimryn; Engström, Wilhelm; Decker, William K.; Bisson, William H.; Rojanasakul, Yon; Luqmani, Yunus; Chen, Zhenbang; Hu, Zhiwei

    2015-01-01

    Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology. PMID:26106142

  19. Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study)

    Science.gov (United States)

    Perez-Saldivar, Maria Luisa; Ortega-Alvarez, Manuel Carlos; Fajardo-Gutierrez, Arturo; Bernaldez-Rios, Roberto; del Campo-Martinez, Maria de los Angeles; Medina-Sanson, Aurora; Palomo-Colli, Miguel Angel; Paredes-Aguilera, Rogelio; Martínez-Avalos, Armando; Borja-Aburto, Victor Hugo; Rodriguez-Rivera, Maria de Jesus; Vargas-Garcia, Victor Manuel; Zarco-Contreras, Jesus; Flores-Lujano, Janet; Mejia-Arangure, Juan Manuel

    2008-01-01

    Background Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL) in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring. Methods From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR) of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s). In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI) was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an expert's opinion. Results The

  20. Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study

    Directory of Open Access Journals (Sweden)

    Rodriguez-Rivera Maria

    2008-01-01

    Full Text Available Abstract Background Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring. Methods From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s. In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an

  1. Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

    DEFF Research Database (Denmark)

    Kuempel, Eileen D.; Jaurand, Marie-Claude; Møller, Peter

    2017-01-01

    : investigation of possible associations between in vitro and early-stage in vivo events that may be predictive of lung cancer or mesothelioma, and systematic analysis of dose–response relationships across materials, including evaluation of the influence of physico-chemical properties and experimental factors...

  2. Occupational exposure to silica and lung cancer risk in the Netherlands

    NARCIS (Netherlands)

    Preller, L.; Bosch, L.M.C. van den; Brandt, P.A. van den; Kauppinen, T.; Goldbohm, R.A.

    2010-01-01

    Objectives: The lung cancer carcinogenicity of crystalline silica dust remains the subject of discussion. Epidemiological evidence is based on occupational cohort studies and population-based case-control studies. The aim of this study was to assess associations between male lung cancer risk and

  3. [Script concordance test for knowledge assessment of lung cancer screening].

    Science.gov (United States)

    Couraud, S; Girard, P; Girard, N; Souquet, P-J; Coiffard, B; Charlin, B; Milleron, B

    2016-05-01

    Annual screening for lung cancer using low-dose CT-scans is associated with decreased mortality. A survey conducted in Rhône-Alpes area in France found that clinicians need education and information on this topic. Script concordance tests (SCT) are a tool for assessing clinical reasoning in situations of uncertainty. They have not previously been used in France in the context of continuing medical education. We created a questionnaire with 5 multiple-choice questions (MCQ) and two SCT scenarios. The questionnaire was sent to all clinicians and residents who are members of French-Speaking Respiratory Society or the French Young Pulmonologist Association. One hundred and ninety answers were analyzed. Seventy percent stated that decreasing mortality was the best criterion for assessing the effectiveness of a cancer screening policy, and 75% that low-dose CT scan was the best test to achieve this in lung cancer screening. Forty-five percent knew the eligibility criteria of the population, and 62% that low-dose CT scan should be performed annually. Participation in tumor boards and certification in oncology were significantly associated with a better score at MCQ and SCT. SCT and MCQ scores were significantly correlated (Spearman's Rho 0.339; P<0.0001). SCT are feasible by electronic survey and seem relevant. Improving knowledge of clinicians on lung cancer screening is still critical. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  4. Comparison between conventional and "clinical" assessment of experimental lung fibrosis

    Directory of Open Access Journals (Sweden)

    McClelland Grant B

    2008-04-01

    Full Text Available Abstract Background Idiopathic pulmonary fibrosis (IPF is a treatment resistant disease with poor prognosis. Numerous compounds have been demonstrated to efficiently prevent pulmonary fibrosis (PF in animal models but only a few were successful when given to animals with established fibrosis. Major concerns of current PF models are spontaneous resolution and high variability of fibrosis, and the lack of assessment methods that can allow to monitor the effect of drugs in individual animals over time. We used a model of experimental PF in rats and compare parameters obtained in living animals with conventional assessment tools that require removal of the lungs. Methods PF was induced in rats by adenoviral gene transfer of transforming growth factor-beta. Morphological and functional changes were assessed for up to 56 days by micro-CT, lung compliance (measured via a mechanical ventilator and VO2max and compared to histomorphometry and hydroxyproline content. Results Standard histological and collagen assessment confirmed the persistent fibrotic phenotype as described before. The histomorphological scores correlated both to radiological (r2 = 0.29, p 2 = 0.51, p 2max did not correlate with fibrosis. Conclusion The progression of pulmonary fibrosis can be reliably assessed and followed in living animals over time using invasive, non-terminal compliance measurements and micro-CT. This approach directly translates to the management of patients with IPF and allows to monitor therapeutic effects in drug intervention studies.

  5. Predictive Models for Carcinogenicity and Mutagenicity ...

    Science.gov (United States)

    Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendous cost (in time, money, animals) of rodent carcinogenicity bioassays. Both mutagenicity and carcinogenicity involve complex, cellular processes that are only partially understood. Advances in technologies and generation of new data will permit a much deeper understanding. In silico methods for predicting mutagenicity and rodent carcinogenicity based on chemical structural features, along with current mutagenicity and carcinogenicity data sets, have performed well for local prediction (i.e., within specific chemical classes), but are less successful for global prediction (i.e., for a broad range of chemicals). The predictivity of in silico methods can be improved by improving the quality of the data base and endpoints used for modelling. In particular, in vitro assays for clastogenicity need to be improved to reduce false positives (relative to rodent carcinogenicity) and to detect compounds that do not interact directly with DNA or have epigenetic activities. New assays emerging to complement or replace some of the standard assays include VitotoxTM, GreenScreenGC, and RadarScreen. The needs of industry and regulators to assess thousands of compounds necessitate the development of high-t

  6. Acute lung injury: effects of prone positioning on cephalocaudal distribution of lung inflation--CT assessment in dogs.

    Science.gov (United States)

    Lee, Hyun Ju; Im, Jung-Gi; Goo, Jin Mo; Kim, Young Il; Lee, Min Woo; Ryu, Ho-Geol; Bahk, Jae-Hyon; Yoo, Chul-Gyu

    2005-01-01

    To quantify cephalocaudal gradient of lung inflation in acute lung injury in a dog model in prone versus supine position. Experiments were performed in accordance with Guide for the Care and Use of Laboratory Animals, as approved by National Research Council (National Institutes of Health), and were approved by committee on care and use of animals in research at Seoul National University Hospital. After induction of acute lung injury with intravenous injection of oleic acid, dogs were randomized to be ventilated in either prone (n = 6) or supine (n = 6) position. Spiral computed tomography (CT) and hemodynamic measurement were performed sequentially on an hourly basis. Volume and mean attenuation of lung were measured quantitatively by using software to evaluate each CT section. Cephalocaudal gradient of mean lung attenuation, distribution of gas and tissue, and alveolar expansion were assessed. Functional residual capacity and net alveolar expansion of entire lung were measured. Statistical analysis was performed with Friedman, sign, and Mann-Whitney tests. Mean lung attenuation increased gradually from apex to base of lung in supine position. Thus, inflation gradient along cephalocaudal axis was found. Gas was located predominantly in upper lung, whereas tissue was dominant in lower lung in supine position. In supine group, cephalocaudal inflation gradient showed no significant change from baseline up to 4 hours. After prone positioning, cephalocaudal inflation gradient was reduced, and gas and tissue proportions became more uniform along cephalocaudal axis. In prone group, absolute values of cephalocaudal inflation gradient at time points of prone positioning for 1, 2, and 3 hours were significantly lower than baseline values (P lung was not altered significantly. Functional residual capacity was unchanged by prone positioning. In acute lung injury, prone positioning induced more uniform distribution of gas and tissue along cephalocaudal axis by reducing

  7. Food derived carcinogenic amnoimidazoazaarenes

    DEFF Research Database (Denmark)

    Frandsen, Henrik

    found to be multiple organ carcinogens. The aminoimidazoazaarenes are metabolically activated by hydroxylation of the exocyclic aminogroup to the N-hydroxyamino derivative. The resultant proximate mutagens often need further activation by phase II transferases for formation of reactive species that form...

  8. Evaluating Pesticides for Carcinogenic Potential

    Science.gov (United States)

    EPA reviews pesticides for potential carcinogenicity. Learn about EPA's guidelines for evaluating a chemical's potential carcinogenicity and updates to EPA's guidelines to reflect increased understanding of ways chemicals may cause cancer.

  9. Carcinogens in the Workplace: A Scientific, Political and Social Problem

    OpenAIRE

    Atherley, Gordon; Whiting, Robert

    1982-01-01

    Investigation, assessment, and management of carcinogenic risks are not only scientific but also political responsibilities. In Canada, this becomes cumbersome, since local, provincial and federal policies are involved. The process also involves workers and management. This article outlines Canadian legislative experience, the principles involved, the methods of risk assessment, and the classification of carcinogens in the workplace.

  10. 78 FR 44117 - Notice of a Public Comment Period on the Draft IRIS Carcinogenicity Assessment for Ethylene Oxide

    Science.gov (United States)

    2013-07-23

    ... policy or views. DATES: The 45-day public comment period on the draft Evaluation of the Inhalation... announcing a 45-day public comment period on the draft IRIS assessment titled, ``Evaluation of the Inhalation... public has been provided an opportunity to comment on a previous external review draft of the Evaluation...

  11. 78 FR 53138 - Notice of Extension of Public Comment Period on the Draft IRIS Carcinogenicity Assessment for...

    Science.gov (United States)

    2013-08-28

    ... the Ethylene Oxide Sterilization Association, Inc. The draft assessment was prepared by the National... Ethylene Oxide and Addition of Ethylene Oxide to October IRIS Bimonthly Meeting Agenda AGENCY..., and Addition of Ethylene Oxide to October IRIS Bimonthly Meeting Agenda. SUMMARY: EPA is announcing an...

  12. Research toward the development of a biologically based dose response assessment for inorganic arsenic carcinogenicity: a progress report.

    Science.gov (United States)

    Clewell, Harvey J; Thomas, Russell S; Gentry, P Robinan; Crump, Kenny S; Kenyon, Elaina M; El-Masri, Hisham A; Yager, Janice W

    2007-08-01

    Cancer risk assessments for inorganic arsenic have been based on human epidemiological data, assuming a linear dose response below the range of observation of tumors. Part of the reason for the continued use of the linear approach in arsenic risk assessments is the lack of an adequate biologically based dose response (BBDR) model that could provide a quantitative basis for an alternative nonlinear approach. This paper describes elements of an ongoing collaborative research effort between the CIIT Centers for Health Research, the U.S. Environmental Protection Agency, ENVIRON International, and EPRI to develop BBDR modeling approaches that could be used to inform a nonlinear cancer dose response assessment for inorganic arsenic. These efforts are focused on: (1) the refinement of physiologically based pharmacokinetic (PBPK) models of the kinetics of inorganic arsenic and its metabolites in the mouse and human; (2) the investigation of mathematical solutions for multi-stage cancer models involving multiple pathways of cell transformation; (3) the review and evaluation of the literature on the dose response for the genomic effects of arsenic; and (4) the collection of data on the dose response for genomic changes in the urinary bladder (a human target tissue for arsenic carcinogenesis) associated with in vivo drinking water exposures in the mouse as well as in vitro exposures of both mouse and human cells. An approach is proposed for conducting a biologically based margin of exposure risk assessment for inorganic arsenic using the in vitro dose response for the expression of genes associated with the obligatory precursor events for arsenic tumorigenesis.

  13. Risk assessment, and carcinogen mutagen for workers potentially exposed in the research laboratories of “Sapienza” University of Rome for Health Surveillance

    Directory of Open Access Journals (Sweden)

    Sabina Sernia

    2017-03-01

    Full Text Available The following work is meant to represent the evaluation of risk factors for the health of exposed workers, arising from the management of carcinogenic and mutagenic substances, through the use of algorithms. In some places of work as a research laboratory, it is more suitable a theoretical and practical methodology (algorithm which allows a "timely" exposure assessment. The methodology developed and used is able to determine the level of risk of exposure due to a single agent and / or to more agents. Results obtained by the algorithm, have shown an higher exposure to 1 for formaldehyde (Lcanc = 1.32, while for acrylamide results obtained shows a lower exposure to 1 (Lcanc = 0.528. Although the overall exposure level of studied workers higher value to 1 (Lcanc= 1.848, the Occupational Medicine Centre of "Sapienza" - University of Rome, in agreement with the position taken by the Italian Society of Occupational Medicine and Industrial Hygiene applies health surveillance even in the presence of potential health risk reducing it among the general protection measures the health and safety of workers.

  14. Low dose assessment of the carcinogenicity of furan in male F344/N Nctr rats in a 2-year gavage study.

    Science.gov (United States)

    Von Tungeln, Linda S; Walker, Nigel J; Olson, Greg R; Mendoza, Maria C B; Felton, Robert P; Thorn, Brett T; Marques, M Matilde; Pogribny, Igor P; Doerge, Daniel R; Beland, Frederick A

    2017-01-01

    Furan is a volatile organic chemical that is a contaminant in many common foods. Furan is hepatocarcinogenic in mice and rats; however, the risk to humans from dietary exposure to furan cannot be estimated accurately because the lowest tested dose of furan in a 2-year bioassay in rats gave nearly a 100% incidence of cholangiocarcinoma. To provide bioassay data that can be used in preparing risk assessments, the carcinogenicity of furan was determined in male F344/N Nctr rats administered 0, 0.02, 0.044, 0.092, 0.2, 0.44, 0.92, and 2 mg furan/kg body weight (BW) by gavage 5 days/week for 2 years. Exposure to furan was associated with the development of malignant mesothelioma on membranes surrounding the epididymis and on the testicular tunics, with the increase being significant at 2 mg furan/kg BW. There was also a dose-related increase in the incidence of mononuclear cell leukemia, with the increase in incidence being significant at 0.092, 0.2, 0.92, and 2 mg furan/kg BW. Dose-related non-neoplastic liver lesions included cholangiofibrosis, mixed cell foci, basophilic foci, biliary tract hyperplasia, oval cell hyperplasia, regenerative hyperplasia, and cytoplasmic vacuolization. The most sensitive non-neoplastic lesion was cholangiofibrosis, the frequency of which increased significantly at 0.2 mg furan/kg BW. Published by Elsevier Ltd.

  15. Assessment of the DNA Damage in Human Sperm and Lymphocytes Exposed to the Carcinogen Food Contaminant Furan with Comet Assay

    Directory of Open Access Journals (Sweden)

    Dilek Pandir

    2015-10-01

    Full Text Available ABSTRACTThe aim of this work was to assess the damage of DNA in human blood cell and spermin vitro under the influence of furan. These cells were administered 0-600 μM of furan at 37 and 32oC for 30 and 60 min, respectively. A significant increase in tail DNA%, tail length and moment indicating DNA damage was observed at increasing doses when compared to the controls. The treatment with 300 and 600 μM of furan showed a maximum increase of 86.74 ± 2.43 and 93.29 ± 8.68 compared to the control tail DNA% in lymphocytes. However, only 600 μM of furan showed a maximum increase of 94.71 ± 6.24 compared to the control tail DNA% in sperm. The results suggested that furan caused DNA damage in lymphocytes at increasing doses, but appeared to have not the same effect on human sperm at the low doses. Genotoxic activity had an impact on the risk assessment of furan formed on the food for human cells. Therefore, it would be important to further investigate these properties of furan as the food mutagen.

  16. The carcinogenicity of chromium

    OpenAIRE

    Norseth, Tor

    1981-01-01

    The carcinogenicity of chromium compounds is reviewed with specific attention to the gaps in knowledge for risk estimation and research needs. The most important problems at present are whether trivalent chromium compounds cause cancer, and whether there is a difference in cancer causing effects between the soluble and the slightly soluble hexavalent compounds in the practical exposure situation. Dose estimates for risk estimation based on epidemiological investigations are also lacking. Pres...

  17. Stair climbing in the functional assessment of lung resection candidates.

    Science.gov (United States)

    Koegelenberg, Coenraad F N; Diacon, Andreas H; Irani, Sarosh; Bolliger, Chris T

    2008-01-01

    Algorithms for the pre-operative evaluation of lung resection candidates with impaired lung function invariably include maximum oxygen uptake (VO(2)MAX) as a critical parameter of functional reserves, with a VO(2)MAX >or=20 ml/kg/min generally considered sufficient for pneumonectomy. Stair climbing is a low-cost alternative to assess exercise capacity. As stair climbing is not standardised, we aimed to compare the altitude reached and the speed of ascent with VO(2)MAX measured by cycle ergometry. We prospectively enrolled 44 pulmonary resection candidates (mean age: 47.6 +/- 12.5 years) with an FEV(1) speed of ascent were compared to VO(2)MAX. Forty-three patients reached a 20-metre elevation. Thirteen of them, as well as the patient who did not reach this height, had a VO(2)MAX speed of ascent and VO(2)MAX/kg (R(2) = 0.67), but not between altitude and VO(2)MAX/kg. All 24 patients with a speed >or=15 m/min had a VO(2)MAX >or=20 ml/kg/min. Thirty-nine of 40 patients with a speed >or=12 m/min had a VO(2)MAX >or=15 ml/kg/min. The average speed of ascent during stair climbing was an accurate semiquantitative predictor of VO(2)MAX/kg, whereas altitude was not. We were able to identify potential cut-off values for lobectomy or pneumonectomy. Pending validation with clinical endpoints, stair climbing may replace formal exercise testing at much lower costs in a large proportion of lung resection candidates. (c) 2008 S. Karger AG, Basel.

  18. Rater agreement of visual lameness assessment in horses during lungeing.

    Science.gov (United States)

    Hammarberg, M; Egenvall, A; Pfau, T; Rhodin, M

    2016-01-01

    Lungeing is an important part of lameness examinations as the circular path may accentuate low-grade lameness. Movement asymmetries related to the circular path, to compensatory movements and to pain make the lameness evaluation complex. Scientific studies have shown high inter-rater variation when assessing lameness during straight line movement. The aim was to estimate inter- and intra-rater agreement of equine veterinarians evaluating lameness from videos of sound and lame horses during lungeing and to investigate the influence of veterinarians' experience and the objective degree of movement asymmetry on rater agreement. Cross-sectional observational study. Video recordings and quantitative gait analysis with inertial sensors were performed in 23 riding horses of various breeds. The horses were examined at trot on a straight line and during lungeing on soft or hard surfaces in both directions. One video sequence was recorded per condition and the horses were classified as forelimb lame, hindlimb lame or sound from objective straight line symmetry measurements. Equine veterinarians (n = 86), including 43 with >5 years of orthopaedic experience, participated in a web-based survey and were asked to identify the lamest limb on 60 videos, including 10 repeats. The agreements between (inter-rater) and within (intra-rater) veterinarians were analysed with κ statistics (Fleiss, Cohen). Inter-rater agreement κ was 0.31 (0.38/0.25 for experienced/less experienced) and higher for forelimb (0.33) than for hindlimb lameness (0.11) or soundness (0.08) evaluation. Median intra-rater agreement κ was 0.57. Inter-rater agreement was poor for less experienced raters, and for all raters when evaluating hindlimb lameness. Since identification of the lame limb/limbs is a prerequisite for successful diagnosis, treatment and recovery, the high inter-rater variation when evaluating lameness on the lunge is likely to influence the accuracy and repeatability of lameness examinations

  19. MR assessment of fetal lung development using lung volumes and signal intensities

    Energy Technology Data Exchange (ETDEWEB)

    Keller, Thomas M.; Michel, Sven C.A.; Marincek, Borut [Institute of Diagnostic Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich (Switzerland); Rake, Annett; Wisser, Josef [Department of Obstetrics, University Hospital Zurich, Raemistrasse 100, 8091, Zurich (Switzerland); Seifert, Burkhardt [Department of Biostatistics, University of Zurich, Sumatrastrasse 30, 8006, Zurich (Switzerland); Kubik-Huch, Rahel A. [Institute of Diagnostic Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich (Switzerland); Institute of Radiology, Kantonsspital Baden, 5404, Baden (Switzerland)

    2004-06-01

    The purpose of this study was to evaluate the monitoring and diagnostic potential of MRI in fetal lung development and disease using lung volume and signal intensity changes through gestation. Thirty-five healthy fetuses (22-42 weeks) were examined on a 1.5- T MR system using sagittal T2w single-shot fast spin-echo imaging (TR indefinite, TE 90 ms, slice thickness/gap 3-5/0 mm, FOV 26-40 cm, NEX 0.5). Fetal body and lung were segmented manually and volumes calculated. Signal intensities (SI) of fetal lung and three reference values were measured on the section best displaying the lung. Regions of interests were defined by including the maximal organ area possible. The following SI ratios were generated: lung/liver, lung/amniotic fluid, lung/muscle, liver/fluid and liver/muscle. Volumes and ratios were correlated with gestational age. Data from seven fetuses with pulmonary pathology were compared with these normative values. Absolute lung volume varied from 12.3 to 143.5 cm{sup 3} in correlation with gestational age (P<0.001); lung volume relative to total body volume ranged from 1.6 to 5.0%, decreasing with gestational age (P=0.001). (orig.)

  20. Workshop on problem areas associated with developing carcinogen guidelines

    Energy Technology Data Exchange (ETDEWEB)

    1984-06-01

    A workshop was conducted to discuss problem areas associated with developing carcinogen guidelines. Session topics included (1) definition of a carcinogen for regulatory purposes; (2) potency; (3) risk assessment; (4) uncertainties; (5) de minimis quantity; and (6) legal and regulatory issues. Separate abstracts have been prepared for individual papers. (ACR)

  1. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis

    Science.gov (United States)

    Hu, Zhiwei; Brooks, Samira A.; Dormoy, Valérian; Hsu, Chia-Wen; Hsu, Hsue-Yin; Lin, Liang-Tzung; Massfelder, Thierry; Rathmell, W. Kimryn; Xia, Menghang; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Brown, Dustin G.; Prudhomme, Kalan R.; Colacci, Annamaria; Hamid, Roslida A.; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P.; Woodrick, Jordan; Scovassi, A. Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Lowe, Leroy; Jensen, Lasse; Bisson, William H.; Kleinstreuer, Nicole

    2015-01-01

    One of the important ‘hallmarks’ of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential. PMID:26106137

  2. Exercise capacity assessment in patients undergoing lung resection.

    Science.gov (United States)

    Bobbio, Antonio; Chetta, Alfredo; Internullo, Eveline; Ampollini, Luca; Carbognani, Paolo; Bettati, Stefano; Rusca, Michele; Olivieri, Dario

    2009-03-01

    The value is examined of preoperative functional assessment, including exercise capacity measurement by a cycloergometric maximal exercise test, in the prediction of postoperative cardio-pulmonary complication after lobar resection. In a prospective study over a 3-year period, all patients who were candidates for lung resection underwent preoperative functional evaluation by means of resting pulmonary function tests, measurement of the lung diffusing capacity for carbon monoxide and cardio-pulmonary exercise test. Patients who had had pneumonectomy or less than anatomical segmentectomy were excluded. The study population consisted of 73 patients. The postoperative morbidity and mortality record was collected. Sixty-four patients underwent lobectomy, five bilobectomy and four segmentectomy. Indication for surgery was NSCLC in 71 cases. Two postoperative deaths were recorded (2.7%). A pulmonary (n=19) and/or cardiac (n=17) complication was scored in 30 patients (41%). Mean preoperative FEV(1) and VO(2)max of patients who developed pulmonary complications were significantly lower (p=0.013 and p=0.043 respectively) than those of patients without pulmonary complications. Logistic regression analysis found FEV(1) to be an independent factor in pulmonary complication (p=0.002). With regard to pulmonary complication occurrence, the receiver operating characteristic curve showed an area of 0.69 with VO(2)max expressed in ml/kg min and of 0.62 when VO(2)max was expressed as a percentage of the predicted value. The widest point of the curve was found at a VO(2)max value of 18.7 ml/kg min. Six out of the 14 patients (43%) with a preoperative VO(2)max equal to or lower than 15 ml/kg min had a pulmonary complication. No functional preoperative identifiers were found for the 16 patients who presented with postoperative new onset atrial fibrillation. The mean preoperative value of carbon monoxide lung diffusing capacity was significantly lower (p=0.037) in the 30 patients who had

  3. Lung cancer and occupation in nonsmokers: a multicenter case-control study in Europe.

    Science.gov (United States)

    Zeka, Ariana; Mannetje, Andrea't; Zaridze, David; Szeszenia-Dabrowska, Neonila; Rudnai, Peter; Lissowska, Jolanta; Fabiánová, Eleonóra; Mates, Dana; Bencko, Vladimir; Navratilova, Marie; Cassidy, Adrian; Janout, Vladimir; Travier, Noemie; Fevotte, Joelle; Fletcher, Tony; Brennan, Paul; Boffetta, Paolo

    2006-11-01

    Tobacco smoking is the main cause for lung cancer worldwide, making it difficult to examine the carcinogenic role of other risk factors because of possible confounding by smoking. Therefore, the present study aimed to investigate the association between lung cancer and occupation independent of smoking. A case-control study of lung cancer was carried out between March 1998 and January 2002 in 16 centers from 7 European countries, including 223 never-smoking cases and 1039 controls. Information on lifestyle and occupation was obtained through detailed questionnaires. Job and industries were classified as entailing exposure to known or suspected carcinogens; in addition, expert assessment provided exposure estimates to specific agents. The odds ratio of lung cancer among women employed for more than 12 years in suspected high-risk occupations was 1.75 (95% confidence interval = 0.63-4.85). A comparable increase in risk was not detected for employment in established high-risk occupations or among men. Increased risk of lung cancer was suggested among individuals exposed to nonferrous metal dust and fumes, crystalline silica, and organic solvents. Occupations were found to play a limited role in lung cancer risk among never-smokers. Jobs entailing exposure to suspected lung carcinogens should receive priority in future studies among women. Nonferrous metal dust and fumes and silica may exert a carcinogenic effect independently from smoking.

  4. Assessment of Palliative Care in Lung Cancer in Turkey

    Science.gov (United States)

    Bülbül, Y.; Ozlu, T.; Arinc, S.; Ozyurek, B.A.; Gunbatar, H.; Senturk, A.; Bahadir, A.; Ozcelik, M.; Yilmaz, U.; Akbay, M.O.; Saglam, L.; Kilic, T.; Kirkil, G.; Ozcelik, N.; Tatar, D.; Baris, S.A.; Yavsan, D.M.; Sen, H.S.; Berk, S.; Acat, M.; Cakmak, G.; Yumuk, P.F.; Intepe, Y.S.; Toru, U.; Ayik, S.O.; Basyigit, I.; Ozkurt, S.; Mutlu, L.C.; Yasar, Z.A.; Esme, H.; Erol, M.M.; Oruc, O.; Erdoğan, Y.; Asker, S.; Ulas, A.; Erol, S.; Kerget, B.; Erbaycu, A.E.; Teke, T.; Beşiroğlu, M.; Can, H.; Dalli, A.; Talay, F.

    2017-01-01

    Objective To investigate the symptoms of lung cancer in Turkey and to evaluate approaches to alleviate these symptoms. Subjects and Methods This study included 1,245 lung cancer patients from 26 centers in Turkey. Demographic characteristics as well as information regarding the disease and treatments were obtained from medical records and patient interviews. Symptoms were evaluated using the Edmonton Symptom Assessment Scale (ESAS) and were graded on a scale between 0 and 10 points. Data were compared using the χ2, Student t, and Mann-Whitney U tests. Potential predictors of symptoms were analyzed using logistic regression analysis. Results The most common symptom was tiredness (n = 1,002; 82.1%), followed by dyspnea (n = 845; 69.3%), appetite loss (n = 801; 65.7%), pain (n = 798; 65.4%), drowsiness (n = 742; 60.8%), anxiety (n = 704; 57.7%), depression (n = 623; 51.1%), and nausea (n = 557; 45.5%). Of the 1,245 patients, 590 (48.4%) had difficulty in initiating or maintaining sleep. The symptoms were more severe in stages III and IV. Logistic regression analysis indicated a clear association between demographic characteristics and symptom distress, as well as between symptom distress (except nausea) and well-being. Overall, 804 (65.4%) patients used analgesics, 630 (51.5%) received treatment for dyspnea, 242 (19.8%) used enteral/parenteral nutrition, 132 (10.8%) used appetite stimulants, and 129 (10.6%) used anxiolytics/antidepressants. Of the 799 patients who received analgesics, 173 (21.7%) reported that their symptoms were under control, and also those on other various treatment modalities (dyspnea: 78/627 [12.4%], appetite stimulant: 25/132 [18.9%], and anxiolytics/antidepressants: 25/129 [19.4%]) reported that their symptoms were controlled. Conclusion In this study, the symptoms progressed and became more severe in the advanced stages of lung cancer, and palliative treatment was insufficient in most of the patients in Turkey. PMID:27780164

  5. Selection of appropriate tumour data sets for Benchmark Dose Modelling (BMD) and derivation of a Margin of Exposure (MoE) for substances that are genotoxic and carcinogenic: considerations of biological relevance of tumour type, data quality and uncertainty assessment.

    Science.gov (United States)

    Edler, Lutz; Hart, Andy; Greaves, Peter; Carthew, Philip; Coulet, Myriam; Boobis, Alan; Williams, Gary M; Smith, Benjamin

    2014-08-01

    This article addresses a number of concepts related to the selection and modelling of carcinogenicity data for the calculation of a Margin of Exposure. It follows up on the recommendations put forward by the International Life Sciences Institute - European branch in 2010 on the application of the Margin of Exposure (MoE) approach to substances in food that are genotoxic and carcinogenic. The aims are to provide practical guidance on the relevance of animal tumour data for human carcinogenic hazard assessment, appropriate selection of tumour data for Benchmark Dose Modelling, and approaches for dealing with the uncertainty associated with the selection of data for modelling and, consequently, the derived Point of Departure (PoD) used to calculate the MoE. Although the concepts outlined in this article are interrelated, the background expertise needed to address each topic varies. For instance, the expertise needed to make a judgement on biological relevance of a specific tumour type is clearly different to that needed to determine the statistical uncertainty around the data used for modelling a benchmark dose. As such, each topic is dealt with separately to allow those with specialised knowledge to target key areas of guidance and provide a more in-depth discussion on each subject for those new to the concept of the Margin of Exposure approach. Copyright © 2013 ILSI Europe. Published by Elsevier Ltd.. All rights reserved.

  6. Assessment of Carcinogenicity of di(2-ethylhexyl) phthalate in a short-term assay using Xpa(-/-) and Xpa(-/-)/p53(+/-) mice

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Bertram, Margareta; Aarup, V.

    2002-01-01

    the models. The only liver tumors in all models were adenomas in males with no statistically significantly increased incidence. For p-cresidine, the survival was decreased (p transgenic models. Statistically significantly increased incidences of nonneoplastic lesions were recorded in the liver......, urinary bladder, and nasal cavity in all models, and in kidneys in transgenic models. The only tumors with statistically significantly increased incidence were liver adenomas in transgenic models (XPA:1 vs 7; `XPA/p53': 0 vs 12; WT: 0 vs 5, p = 0.053) and urinary bladder carcinomas in XPA/p53 model (0 vs...... 7). The negative carcinogenic response to DEHP and the positive response to p-cresidine support the expected sensitivity to genotoxic carcinogens in these transgenic models....

  7. COMPACT and molecular structure in toxicity assessment: a prospective evaluation of 30 chemicals currently being tested for rodent carcinogenicity by the NCI/NTP.

    OpenAIRE

    Lewis, D F; Ioannides, C; Parke, D V

    1996-01-01

    A new series of 30 miscellaneous National Toxicology Program chemicals has been evaluated prospectively for carcinogenicity and overt toxicity by COMPACT (Computer Optimised Molecular Parametric Analysis for Chemical Toxicity. CYP1A and CYP2E1). Evaluations were also made by Hazardexpert, and for metal ion redox potentials; and these, together with COMPACT, were compared with results from the Ames test for mutagenicity in Salmonella, the micronucleus test, and 90-day subchronic rodent patholo...

  8. Prevalidation study of the Syrian hamster embryo (SHE) cell transformation assay at pH 7.0 for assessment of carcinogenic potential of chemicals.

    Science.gov (United States)

    Maire, Marie-Aline; Pant, Kamala; Poth, Albrecht; Schwind, Karl-Rainer; Rast, Claudine; Bruce, Shannon W; Sly, Jamie E; Kunz-Bohnenberger, Susanne; Kunkelmann, Thorsten; Engelhardt, Günter; Schulz, Markus; Vasseur, Paule

    2012-04-11

    The European Centre for the Validation of Alternative Methods (ECVAM) has organised an interlaboratory prevalidation study on the Syrian hamster embryo (SHE) cell transformation assay (CTA) at pH 7.0 for the detection of rodent carcinogens. The SHE CTA at pH 7.0 has been evaluated for its within-laboratory reproducibility, transferability and between-laboratory reproducibility. Four laboratories using the same basic protocol with minor modifications participated in this study and tested a series of six coded-chemicals: four rodent carcinogens (benzo(a)pyrene, 3-methylcholanthrene, 2,4-diaminotoluene and o-toluidine HCl) and two non-carcinogens (anthracene and phthalic anhydride). All the laboratories found the expected results with coded chemicals except for phthalic anhydride which resulted in a different call in only one laboratory. Based on the outcome of this study, it can be concluded that a standardised protocol is available that should be the basis for future use. This protocol and the assay system itself are transferable between laboratories and the SHE CTA at pH 7.0 is reproducible within- and between-laboratories. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Carcinogenic compounds in alcoholic beverages: an update.

    Science.gov (United States)

    Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

    2016-10-01

    The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

  10. Cannabis and tobacco smoke are not equally carcinogenic

    Directory of Open Access Journals (Sweden)

    Melamede Robert

    2005-10-01

    Full Text Available Abstract More people are using the cannabis plant as modern basic and clinical science reaffirms and extends its medicinal uses. Concomitantly, concern and opposition to smoked medicine has occurred, in part due to the known carcinogenic consequences of smoking tobacco. Are these reactions justified? While chemically very similar, there are fundamental differences in the pharmacological properties between cannabis and tobacco smoke. Cannabis smoke contains cannabinoids whereas tobacco smoke contains nicotine. Available scientific data, that examines the carcinogenic properties of inhaling smoke and its biological consequences, suggests reasons why tobacco smoke, but not cannabis smoke, may result in lung cancer.

  11. Inhalation carcinogenicity of dichloromethane in rats and mice.

    Science.gov (United States)

    Aiso, Shigetoshi; Take, Makoto; Kasai, Tatsuya; Senoh, Hideki; Umeda, Yumi; Matsumoto, Michiharu; Fukushima, Shoji

    2014-07-01

    The carcinogenicity of inhaled dichloromethane (DCM) was examined by exposing groups of 50 F344/DuCrj rats and 50 Crj: BDF1 mice of both sexes to 0, 1000, 2000, or 4000 ppm (w/w) DCM-containing aerosol for 2 years. Inhalation of DCM resulted in increased incidences of subcutis fibromas, mammary gland fibroadenoma, and peritoneum mesotheliomas in male rats; mammary gland fibroadenomas in female rats; and bronchiolar-alveolar adenomas and carcinomas in the lung and hepatocellular adenomas and carcinomas in male and female mice. These results clearly indicate that inhaled DCM is carcinogenic in F344/DuCrj (SPF) rats and Crj: BDF1 (SPF) mice.

  12. Cross-sectional Assessment of Daily Physical Activity in Chronic Obstructive Pulmonary Disease Lung Transplant Patients

    NARCIS (Netherlands)

    Bossenbrock, Linda; ten Thicken, Nick H. T.; van der Bij, Wim; Verschuuren, Erik A. M.; Koeter, Gerard H.; de Greef, Mathieu H. G.

    Background: information about daily physical activity of chronic obstructive pulmonary disease (COPD) lung transplant patients is relevant for evaluation of the functional recovery of physical capacity after lung transplantation. The objective of this study was to cross-sectionally assess daily

  13. Quantitative assessment of elemental carbon in the lungs of never smokers, cigarette smokers, and coal miners

    Energy Technology Data Exchange (ETDEWEB)

    Saxena, R.K.; McClure, M.E.; Hays, M.D.; Green, F.H.Y.; McPhee, L.J.; Vallyathan, V.; Gilmour, M.I. [US EPA, Research Triangle Park, NC (United States)

    2011-07-01

    Inhalation exposure to particulates such as cigarette smoke and coal dust is known to contribute to the development of chronic lung disease. The purpose of this study was to estimate the amount of elemental carbon (EC) deposits from autopsied lung samples from cigarette smokers, miners, and control subjects and explore the relationship between EC level, exposure history, and the extent of chronic lung disease. The samples comprised three subgroups representing never smokers (8), chronic cigarette smokers (26), and coal miners (6). Following the dissolution of lung tissue, the extracted EC residue was quantified using a thermal-optical transmission (TOT) carbon analyzer. Mean EC levels in the lungs of the control group were 56.68 +/- 24.86 (SD) g/g dry lung weight. Respective mean EC values in lung samples from the smokers and coal miners were 449.56 +/- 320.3 g/g and 6678.2 +/- 6162 g/g. These values were significantly higher than those obtained from the never-smoker group. EC levels in the lung and pack-years of cigarette smoking correlated significantly, as did EC levels and the severity of small airway disease. This study provides one of the first quantitative assessments of EC in human lungs from populations at high relative risk for the development of chronic lung disease.

  14. Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation.

    Science.gov (United States)

    Herceg, Zdenko; Lambert, Marie-Pierre; van Veldhoven, Karin; Demetriou, Christiana; Vineis, Paolo; Smith, Martyn T; Straif, Kurt; Wild, Christopher P

    2013-09-01

    Remarkable progress in the field of epigenetics has turned academic, medical and public attention to the potential applications of these new advances in medicine and various fields of biomedical research. The result is a broader appreciation of epigenetic phenomena in the a etiology of common human diseases, most notably cancer. These advances also represent an exciting opportunity to incorporate epigenetics and epigenomics into carcinogen identification and safety assessment. Current epigenetic studies, including major international sequencing projects, are expected to generate information for establishing the 'normal' epigenome of tissues and cell types as well as the physiological variability of the epigenome against which carcinogen exposure can be assessed. Recently, epigenetic events have emerged as key mechanisms in cancer development, and while our search of the Monograph Volume 100 revealed that epigenetics have played a modest role in evaluating human carcinogens by the International Agency for Research on Cancer (IARC) Monographs so far, epigenetic data might play a pivotal role in the future. Here, we review (i) the current status of incorporation of epigenetics in carcinogen evaluation in the IARC Monographs Programme, (ii) potential modes of action for epigenetic carcinogens, (iii) current in vivo and in vitro technologies to detect epigenetic carcinogens, (iv) genomic regions and epigenetic modifications and their biological consequences and (v) critical technological and biological issues in assessment of epigenetic carcinogens. We also discuss the issues related to opportunities and challenges in the application of epigenetic testing in carcinogen identification and evaluation. Although the application of epigenetic assays in carcinogen evaluation is still in its infancy, important data are being generated and valuable scientific resources are being established that should catalyse future applications of epigenetic testing.

  15. Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation

    Science.gov (United States)

    Herceg, Zdenko

    2013-01-01

    Remarkable progress in the field of epigenetics has turned academic, medical and public attention to the potential applications of these new advances in medicine and various fields of biomedical research. The result is a broader appreciation of epigenetic phenomena in the a etiology of common human diseases, most notably cancer. These advances also represent an exciting opportunity to incorporate epigenetics and epigenomics into carcinogen identification and safety assessment. Current epigenetic studies, including major international sequencing projects, are expected to generate information for establishing the ‘normal’ epigenome of tissues and cell types as well as the physiological variability of the epigenome against which carcinogen exposure can be assessed. Recently, epigenetic events have emerged as key mechanisms in cancer development, and while our search of the Monograph Volume 100 revealed that epigenetics have played a modest role in evaluating human carcinogens by the International Agency for Research on Cancer (IARC) Monographs so far, epigenetic data might play a pivotal role in the future. Here, we review (i) the current status of incorporation of epigenetics in carcinogen evaluation in the IARC Monographs Programme, (ii) potential modes of action for epigenetic carcinogens, (iii) current in vivo and in vitro technologies to detect epigenetic carcinogens, (iv) genomic regions and epigenetic modifications and their biological consequences and (v) critical technological and biological issues in assessment of epigenetic carcinogens. We also discuss the issues related to opportunities and challenges in the application of epigenetic testing in carcinogen identification and evaluation. Although the application of epigenetic assays in carcinogen evaluation is still in its infancy, important data are being generated and valuable scientific resources are being established that should catalyse future applications of epigenetic testing. PMID:23749751

  16. Assessing the benefit of accepting a single lung offer now compared with waiting for a subsequent double lung offer.

    Science.gov (United States)

    Wang, Qing; Rogers, Chris A; Bonser, Robert S; Banner, Nicholas R; Demiris, Nikolaos; Sharples, Linda D

    2011-04-27

    Comparisons of survival after single lung transplant (SLT) and bilateral lung transplant (BLT) are useful in making policy decisions, but a more relevant comparison for an individual patient is between accepting a single lung when offered and remaining on the waiting list with the potential to subsequently receive a suitable pair of lungs. U.K. data from a cohort of 1211 adult, first lung transplant candidates diagnosed with pulmonary fibrosis (PF) or chronic obstructive pulmonary disease (COPD), listed July 1995 to July 2006 and followed up till December 2007, were analyzed. A sequentially stratified proportional hazards model was used to assess mortality after SLT relative to continued waiting for BLT. For patients with PF, SLT was associated with a significant reduction in hazard relative to waiting for BLT (hazard ratio 0.81, 95% confidence interval 0.68-0.97, P=0.021), particularly for older patients with body mass index less than 20 and forced expired volume in 1 sec is less than 1 L. In contrast, our results gave no support for accepting SLT rather than waiting for BLT for patients with COPD (hazard ratio 1.08, 95% confidence interval 0.92-1.29, P=0.35). The high pretransplant risk of death for patients with PF, particularly older patients with low body mass index and poor lung function, suggests that they would benefit from taking an SLT if offered. However, there is no benefit of accepting SLT rather than waiting for BLT for patients with COPD; this reflects the low relative hazard in the absence of transplant for these patients. © 2011 by Lippincott Williams & Wilkins

  17. An estimation of the carcinogenic risk associated with the intake of multiple relevant carcinogens found in meat and charcuterie products.

    Science.gov (United States)

    Hernández, Ángel Rodríguez; Boada, Luis D; Almeida-González, Maira; Mendoza, Zenaida; Ruiz-Suárez, Norberto; Valeron, Pilar F; Camacho, María; Zumbado, Manuel; Henríquez-Hernández, Luis A; Luzardo, Octavio P

    2015-05-01

    Numerous epidemiological studies have demonstrated a link between excessive meat consumption and the incidence of various cancers, especially colorectal cancer, and it has been suggested that environmental carcinogens present in meat might be related to the increased risk of cancer associated with this food. However, there are no studies evaluating the carcinogenic potential of meat in relation to its content of carcinogens. Our purpose was to emphasize the relevance of environmental carcinogens existing in meat as a determinant of the association between cancer and meat consumption. Because within Europe, Spain shows high consumption of meat and charcuterie, we performed this study focusing on Spanish population. Based on the preferences of consumers we acquired 100 samples of meat and charcuterie that reflect the variety available in the European market. We quantified in these samples the concentration of 33 chemicals with calculated carcinogenic potential (PAHs, organochlorine pesticides, and dioxin-like PCBs). The carcinogenic risk of these contaminants was assessed for each food using a risk ratio based on the current consumption of meat and charcuterie and the maximum tolerable intake of these foods depending on the level of contamination by the carcinogens they contain. Our results indicate that the current consumption of beef, pork, lamb, chicken, and "chorizo", represents a relevant carcinogenic risk for consumers (carcinogenic risk quotient between 1.33 and 13.98). In order to reduce carcinogenic risk, the study population should halve the monthly consumption of these foods, and also not to surpass the number of 5 servings of beef/pork/chicken (considered together). Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Directory of Open Access Journals (Sweden)

    Hideki Wanibuchi

    2013-10-01

    Full Text Available This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorophenyl-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  19. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Kakehashi, Anna; Wei, Min [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan); Fukushima, Shoji [Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan)

    2013-10-28

    This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P{sub 450} inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  20. Proteomic biomarkers in lung cancer.

    Science.gov (United States)

    Pastor, M D; Nogal, A; Molina-Pinelo, S; Carnero, A; Paz-Ares, L

    2013-09-01

    The correct understanding of tumour development relies on the comprehensive study of proteins. They are the main orchestrators of vital processes, such as signalling pathways, which drive the carcinogenic process. Proteomic technologies can be applied to cancer research to detect differential protein expression and to assess different responses to treatment. Lung cancer is the number one cause of cancer-related death in the world. Mostly diagnosed at late stages of the disease, lung cancer has one of the lowest 5-year survival rates at 15 %. The use of different proteomic techniques such as two-dimensional gel electrophoresis (2D-PAGE), isotope labelling (ICAT, SILAC, iTRAQ) and mass spectrometry may yield new knowledge on the underlying biology of lung cancer and also allow the development of new early detection tests and the identification of changes in the cancer protein network that are associated with prognosis and drug resistance.

  1. Assessment of Lungs for Transplant Recovered from Uncontrolled Donation after Circulatory Determination of Death Donors.

    Science.gov (United States)

    Egan, Thomas; Blackwell, John; Birchard, Katherine; Haithcock, Benjamin; Long, Jason; Gazda, Stephen; Casey, Nissa; Thys, Caitlin

    2017-09-01

    To address the lung donor shortage, we obtained institutional review board and US Food and Drug Administration approval to transplant lungs recovered from uncontrolled donation after circulatory determination of death donors (uDCDDs). To compare outcomes of recipients of lungs recovered from uDCDDs vs. brain-dead donors. After consent and screening, lungs recovered from uDCDDs were assessed by 4 hours ex vivo lung perfusion (EVLP) and computed tomography (CT) scan. Over the course of 29 months, 502 potential uDCDDs younger than 66 years were identified in a single county, with death declaration by emergency medical services and four emergency departments in this and two other countries. We determined reasons that lungs from these uDCDDs were not able to be transplanted: uDCDDs could not have lungs recovered (224), next-of-kin could not be found or refused to discuss (67), next-of-kin refused (48), medical examiner case (39), logistics/missed (35), and miscellaneous (35). There were 247 medical contraindications: 141 pulmonary and 106 nonpulmonary. Lungs were recovered from 31 uDCDDs. Thirteen lungs did not have EVLP: 5 injured lungs (one pulmonary embolism [PE] with perforated infarct, two motor vehicle crash with severe injuries, one adhesion, and one lightning strike), two large PE, two prolonged ischemic time, two obvious chronic obstructive pulmonary disease, one technical, and one consent withdrawn. Eighteen lungs had EVLP: 10 with immediate edema (three PE, three unknown down time, three long ischemic time, and one ruptured aneurysm into L pleural space, making long cardiopulmonary resuscitation ineffective), and one myocarditis, possible lung involvement. In three lungs, CT showed edema after EVLP: one poor flush and poor EVLP performance, one edema after myocardial infarction (MI) with 10-year history of chronic heart failure, and one edema with MI, resuscitated, arrested again. One concurrent pneumonia was diagnosed by bronchoscopy, CT, and cultures; one

  2. Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.

    Science.gov (United States)

    Sweeney, Timothy E; Lofgren, Shane; Khatri, Purvesh; Rogers, Angela J

    2017-08-01

    The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

  3. Magnetic resonance lung function – a breakthrough for lung imaging and functional assessment? A phantom study and clinical trial

    Directory of Open Access Journals (Sweden)

    Rauh Manfred

    2006-08-01

    Full Text Available Abstract Background Chronic lung diseases are a major issue in public health. A serial pulmonary assessment using imaging techniques free of ionizing radiation and which provides early information on local function impairment would therefore be a considerably important development. Magnetic resonance imaging (MRI is a powerful tool for the static and dynamic imaging of many organs. Its application in lung imaging however, has been limited due to the low water content of the lung and the artefacts evident at air-tissue interfaces. Many attempts have been made to visualize local ventilation using the inhalation of hyperpolarized gases or gadolinium aerosol responding to MRI. None of these methods are applicable for broad clinical use as they require specific equipment. Methods We have shown previously that low-field MRI can be used for static imaging of the lung. Here we show that mathematical processing of data derived from serial MRI scans during the respiratory cycle produces good quality images of local ventilation without any contrast agent. A phantom study and investigations in 85 patients were performed. Results The phantom study proved our theoretical considerations. In 99 patient investigations good correlation (r = 0.8; p ≤ 0.001 was seen for pulmonary function tests and MR ventilation measurements. Small ventilation defects were visualized. Conclusion With this method, ventilation defects can be diagnosed long before any imaging or pulmonary function test will indicate disease. This surprisingly simple approach could easily be incorporated in clinical routine and may be a breakthrough for lung imaging and functional assessment.

  4. Genotoxicity and carcinogenicity risk of carbon nanotubes.

    Science.gov (United States)

    Toyokuni, Shinya

    2013-12-01

    Novel materials are often commercialized without a complete assessment of the risks they pose to human health because such assessments are costly and time-consuming; additionally, sometimes the methodology needed for such an assessment does not exist. Carbon nanotubes have the potential for widespread application in engineering, materials science and medicine. However, due to the needle-like shape and high durability of multiwalled carbon nanotubes (MWCNTs), concerns have been raised that they may induce asbestos-like pathogenicity when inhaled. Indeed, experiments in rodents supported this hypothesis. Notably, the genetic alterations in MWCNT-induced rat malignant mesothelioma were similar to those induced by asbestos. Single-walled CNTs (SWCNTs) cause mitotic disturbances in cultured cells, but thus far, there has been no report that SWCNTs are carcinogenic. This review summarizes the recent noteworthy publications on the genotoxicity and carcinogenicity of CNTs and explains the possible molecular mechanisms responsible for this carcinogenicity. The nanoscale size and needle-like rigid structure of CNTs appear to be associated with their pathogenicity in mammalian cells, where carbon atoms are major components in the backbone of many biomolecules. Publishing adverse events associated with novel materials is critically important for alerting people exposed to such materials. CNTs still have a bright future with superb economic and medical merits. However, appropriate regulation of the production, distribution and secondary manufacturing processes is required, at least to protect the workers. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. [Expert assessment of asbestos-induced lung damage].

    Science.gov (United States)

    Hartmann, W

    1990-04-01

    Asbestos is a mineral of special technical properties and therefore used in many products all over the world. The inhalation of asbestos causes chronic inflammation of lung--the asbestosis--and pleura--pleuraplaques and pleuritis--and is responsible for mesothelioma and lung cancer. Under normal conditions the diagnosis asbestosis is easy because of the typical x-ray findings and the history of intensive exposure of asbestos. In rare conditions the history of exposure is uncertain and the diagnosis might be difficult. The expected anuity depends on the loss of lung-function. First we find a restrictive ventilatory disorder i.e. a reduction in VC and compliance. Later after progress of the disease the gasexchange is impaired. In case of mesothelioma or lungcancer the person is generally expected to be unable to work.

  6. B-Lines in Assessment of Pulmonary Hypertension in Patients With Interstitial Lung Diseases: Feasibility of Transthoracic Lung Sonographic Signs.

    Science.gov (United States)

    Zheng, Xiao-Zhi; Zheng, Quan; Zhou, Jing; Yang, Bin

    2015-09-01

    This study was conducted to evaluate the value of sonographic B-lines (previously called "comet tail artifacts") in assessment of pulmonary hypertension in patients with interstitial lung diseases. One hundred thirty-four patients with clinically diagnosed interstitial lung diseases complicated by pulmonary hypertension underwent transthoracic lung sonography and Doppler echocardiography for assessment of the presence of B-lines, the distance between them, and the pulmonary artery (PA) systolic pressure. A correlation analysis and a receiver operating characteristic curve analysis were performed. All patients had diffuse bilateral B-lines. The maximum number of B-lines seen in any positive zone (not a summation) was significantly correlated with the severity of PA systolic pressure (r= 0.812; P30 mm Hg). The number of B-lines is useful in assessment of pulmonary hypertension, especially when tricuspid regurgitation and pulmonary valve regurgitation do not exist or cannot be satisfactorily measured by Doppler echocardiography. © 2015 by the American Institute of Ultrasound in Medicine.

  7. [Principles of establishing occupational exposure limits for carcinogens in Poland and in other EU countries].

    Science.gov (United States)

    Skowroń, Jolanta; Czerczak, Slawomir

    2013-01-01

    The principles of determining exposure limits for carcinogens adopted in Poland, the European Union and in other selected countries of the EC are discussed in this article. Carcinogens and/or mutagens pose a direct health risk to people exposed to them. If carcinogens cannot be eliminated from the work and living environments, their exposure should be kept at the lowest possible level. To assess health risk for carcinogens it is necessary to determine the probability of developing a disease or of death from cancer as a result of occupational exposure to carcinogenic substances.

  8. Principles of establishing occupational exposure limits for carcinogens in Poland and in other EU countries

    Directory of Open Access Journals (Sweden)

    Jolanta Skowroń

    2013-08-01

    Full Text Available The principles of determining exposure limits for carcinogens adopted in Poland, the European Union and in other selected countries of the EC are discussed in this article. Carcinogens and/or mutagens pose a direct health risk to people exposed to them. If carcinogens cannot be eliminated from the work and living environments, their exposure should be kept at the lowest possible level. To assess health risk for carcinogens it is necessary to determine the probability of developing a disease or of death from cancer as a result of occupational exposure to carcinogenic substances. Med Pr 2013;64(4:541–563

  9. The COPD Assessment Test as a Prognostic Marker in Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Fujiko Someya

    2016-01-01

    Full Text Available The chronic obstructive pulmonary disease (COPD Assessment Test (CAT, which was developed to measure the health status of patients with COPD, was applied to patients with interstitial lung disease, aiming to examine the CAT as a predictor of outcome. Over a follow-up period of more than one year, 101 consecutive patients with interstitial lung disease were evaluated by the CAT. The CAT scores of 40 in total were categorized into four subsets according to the severity. Patients with higher (more severe scores exhibited lower forced vital capacity and lung diffusion capacity for carbon monoxide. The survival rate was significantly lower in patients with higher scores (log-rank test, P = 0.0002, and the hazard ratios for death of the higher scores and lower lung diffusion capacity for carbon monoxide were independently significant. These findings suggest that CAT can indicate the risk of mortality in patients with interstitial lung disease.

  10. Assessment of respiratory symptoms and lung function among textile ...

    African Journals Online (AJOL)

    2011-04-06

    Apr 6, 2011 ... Objective:A cross-sectional study was undertaken to determine the prevalence of respiratory symptoms and pulmonary functions among Textile Workers in ... creating the need for a system of protecting workers' health and ensuring their ..... cigarette smoking among the exposed workers. Lung function tests.

  11. Assessment of an infant whole-body plethysmograph using an infant lung function model.

    Science.gov (United States)

    Reinmann, B; Stocks, J; Frey, U

    2001-04-01

    In order to facilitate international multicentre studies and improve the quality control of infant pulmonary function measurements, the European Respiratory Society-American Thoracic Society Task Force for infant lung function testing has recently developed specifications for standardized infant lung function equipment and software. A mechanical infant lung model analogue has been developed to assess whether infant lung function equipment is able to meet these requirements. However, the practical testing of infant lung function equipment using such models is highly complex because of the need to use very small pressure and flow changes, and the numerous potentially confounding factors associated with both the design of the device and the testing procedure. The aim of this study was to determine whether the infant lung model is capable of assessing the overall function of an whole-body infant- plethysmograph, using the only infant plethysmograph that was commercially available at the time as an example. The mechanical characteristics of the model such as vibrations or noise did not disturb the delicate plethysmographic measurements and thereby allowed a reliable assessment of the system. A series of tests revealed that the plethysmograph was able to measure airway resistance 1-3.5 kPa.L(-1).s with an accuracy of +/-2.5% and lung volumes 75-300 mL with an accuracy of +/-2.5% under in vitro conditions. To conclude, the infant lung model is a useful means of assessing the overall in vitro performance of infant whole-body plethysmographs, but thermal, mechanical and frequency response characteristics of such a device must be taken into account when interpreting the results of such assessments.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Reviews and Meta-Analyses (PRISMA) guidelines. Only original research articles concerning treatment response in patients with lung cancer assessed with DCE-CT were included. To assess the validity of each study we implemented Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The initial search...... after treatment. Four out of five studies that measured blood flow post anti-angiogenic treatments found that blood flow was significantly decreased. DCE-CT may be a useful tool in assessing treatment response in patients with lung cancer. It seems that particularly permeability and blood flow...

  13. Rapid diagnosis and intraoperative margin assessment of human lung cancer with fluorescence lifetime imaging microscopy

    Directory of Open Access Journals (Sweden)

    Mengyan Wang

    2017-12-01

    Full Text Available A method of rapidly differentiating lung tumor from healthy tissue is extraordinarily needed for both the diagnosis and the intraoperative margin assessment. We assessed the ability of fluorescence lifetime imaging microscopy (FLIM for differentiating human lung cancer and normal tissues with the autofluorescence, and also elucidated the mechanism in tissue studies and cell studies. A 15-patient testing group was used to compare FLIM results with traditional histopathology diagnosis. Based on the endogenous fluorescence lifetimes of the testing group, a criterion line was proposed to distinguish normal and cancerous tissues. Then by blinded examined 41 sections from the validation group of other 16 patients, the sensitivity and specificity of FLIM were determined. The cellular metabolism was studied with specific perturbations of oxidative phosphorylation and glycolysis in cell studies. The fluorescence lifetime of cancerous lung tissues is consistently lower than normal tissues, and this is due to the both decrease of reduced nicotinamide adenine dinucleotide (NADH and flavin adenine dinucleotide (FAD lifetimes. A criterion line of lifetime at 1920 ps can be given for differentiating human lung cancer and normal tissues.The sensitivity and specificity of FLIM for lung cancer diagnosis were determined as 92.9% and 92.3%. These findings suggest that NADH and FAD can be used to rapidly diagnose lung cancer. FLIM is a rapid, accurate and highly sensitive technique in the judgment during lung cancer surgery and it can be potential in earlier cancer detection.

  14. Rapid diagnosis and intraoperative margin assessment of human lung cancer with fluorescence lifetime imaging microscopy.

    Science.gov (United States)

    Wang, Mengyan; Tang, Feng; Pan, Xiaobo; Yao, Longfang; Wang, Xinyi; Jing, Yueyue; Ma, Jiong; Wang, Guifang; Mi, Lan

    2017-12-01

    A method of rapidly differentiating lung tumor from healthy tissue is extraordinarily needed for both the diagnosis and the intraoperative margin assessment. We assessed the ability of fluorescence lifetime imaging microscopy (FLIM) for differentiating human lung cancer and normal tissues with the autofluorescence, and also elucidated the mechanism in tissue studies and cell studies. A 15-patient testing group was used to compare FLIM results with traditional histopathology diagnosis. Based on the endogenous fluorescence lifetimes of the testing group, a criterion line was proposed to distinguish normal and cancerous tissues. Then by blinded examined 41 sections from the validation group of other 16 patients, the sensitivity and specificity of FLIM were determined. The cellular metabolism was studied with specific perturbations of oxidative phosphorylation and glycolysis in cell studies. The fluorescence lifetime of cancerous lung tissues is consistently lower than normal tissues, and this is due to the both decrease of reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) lifetimes. A criterion line of lifetime at 1920 ps can be given for differentiating human lung cancer and normal tissues.The sensitivity and specificity of FLIM for lung cancer diagnosis were determined as 92.9% and 92.3%. These findings suggest that NADH and FAD can be used to rapidly diagnose lung cancer. FLIM is a rapid, accurate and highly sensitive technique in the judgment during lung cancer surgery and it can be potential in earlier cancer detection.

  15. Comparison of carcinogen, carbon monoxide, and ultrafine particle emissions from narghile waterpipe and cigarette smoking: Sidestream smoke measurements and assessment of second-hand smoke emission factors

    Science.gov (United States)

    Daher, Nancy; Saleh, Rawad; Jaroudi, Ezzat; Sheheitli, Hiba; Badr, Thérèse; Sepetdjian, Elizabeth; Al Rashidi, Mariam; Saliba, Najat; Shihadeh, Alan

    2010-01-01

    The lack of scientific evidence on the constituents, properties, and health effects of second-hand waterpipe smoke has fueled controversy over whether public smoking bans should include the waterpipe. The purpose of this study was to investigate and compare emissions of ultrafine particles (UFP, tobacco smoke. Sidestream cigarette and waterpipe smoke was captured and aged in a 1 m 3 Teflon-coated chamber operating at 1.5 air changes per hour (ACH). The chamber was characterized for particle mass and number surface deposition rates. UFP and CO concentrations were measured online using a fast particle spectrometer (TSI 3090 Engine Exhaust Particle Sizer), and an indoor air quality monitor. Particulate PAH and gaseous volatile aldehydes were captured on glass fiber filters and DNPH-coated SPE cartridges, respectively, and analyzed off-line using GC-MS and HPLC-MS. PAH compounds quantified were the 5- and 6-ring compounds of the EPA priority list. Measured aldehydes consisted of formaldehyde, acetaldehyde, acrolein, methacrolein, and propionaldehyde. We found that a single waterpipe use session emits in the sidestream smoke approximately four times the carcinogenic PAH, four times the volatile aldehydes, and 30 times the CO of a single cigarette. Accounting for exhaled mainstream smoke, and given a habitual smoker smoking rate of 2 cigarettes per hour, during a typical one-hour waterpipe use session a waterpipe smoker likely generates ambient carcinogens and toxicants equivalent to 2-10 cigarette smokers, depending on the compound in question. There is therefore good reason to include waterpipe tobacco smoking in public smoking bans.

  16. Quantitative assessment of smoking-induced emphysema progression in longitudinal CT screening for lung cancer

    Science.gov (United States)

    Suzuki, H.; Mizuguchi, R.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.; Moriyama, N.

    2015-03-01

    Computed tomography has been used for assessing structural abnormalities associated with emphysema. It is important to develop a robust CT based imaging biomarker that would allow quantification of emphysema progression in early stage. This paper presents effect of smoking on emphysema progression using annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in longitudinal screening for lung cancer. The percentage of LAV (LAV%) was measured after applying CT value threshold method and small noise reduction. Progression of emphysema was assessed by statistical analysis of the annual changes represented by linear regression of LAV%. This method was applied to 215 participants in lung cancer CT screening for five years (18 nonsmokers, 85 past smokers, and 112 current smokers). The results showed that LAV% is useful to classify current smokers with rapid progression of emphysema (0.2%/year, pemphysema in CT screening for lung cancer.

  17. Threshold and non-threshold chemical carcinogens: A survey of the present regulatory landscape.

    Science.gov (United States)

    Bevan, Ruth J; Harrison, Paul T C

    2017-08-01

    For the proper regulation of a carcinogenic material it is necessary to fully understand its mode of action, and in particular whether it demonstrates a threshold of effect. This paper explores our present understanding of carcinogenicity and the mechanisms underlying the carcinogenic response. The concepts of genotoxic and non-genotoxic and threshold and non-threshold carcinogens are fully described. We provide summary tables of the types of cancer considered to be associated with exposure to a number of carcinogens and the available evidence relating to whether carcinogenicity occurs through a threshold or non-threshold mechanism. In light of these observations we consider how different regulatory bodies approach the question of chemical carcinogenesis, looking in particular at the definitions and methodologies used to derive Occupational Exposure Levels (OELs) for carcinogens. We conclude that unless proper differentiation is made between threshold and non-threshold carcinogens, inappropriate risk management measures may be put in place - and lead also to difficulties in translating carcinogenicity research findings into appropriate health policies. We recommend that clear differentiation between threshold and non-threshold carcinogens should be made by all expert groups and regulatory bodies dealing with carcinogen classification and risk assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Quantitative assessment of emphysema from whole lung CT scans: comparison with visual grading

    Science.gov (United States)

    Keller, Brad M.; Reeves, Anthony P.; Apanosovich, Tatiyana V.; Wang, Jianwei; Yankelevitz, David F.; Henschke, Claudia I.

    2009-02-01

    Emphysema is a disease of the lungs that destroys the alveolar air sacs and induces long-term respiratory dysfunction. CT scans allow for imaging of the anatomical basis of emphysema and for visual assessment by radiologists of the extent present in the lungs. Several measures have been introduced for the quantification of the extent of disease directly from CT data in order to add to the qualitative assessments made by radiologists. In this paper we compare emphysema index, mean lung density, histogram percentiles, and the fractal dimension to visual grade in order to evaluate the predictability of radiologist visual scoring of emphysema from low-dose CT scans through quantitative scores, in order to determine which measures can be useful as surrogates for visual assessment. All measures were computed over nine divisions of the lung field (whole lung, individual lungs, and upper/middle/lower thirds of each lung) for each of 148 low-dose, whole lung scans. In addition, a visual grade of each section was also given by an expert radiologist. One-way ANOVA and multinomial logistic regression were used to determine the ability of the measures to predict visual grade from quantitative score. We found that all measures were able to distinguish between normal and severe grades (p<0.01), and between mild/moderate and all other grades (p<0.05). However, no measure was able to distinguish between mild and moderate cases. Approximately 65% prediction accuracy was achieved from using quantitative score to predict visual grade, with 73% if mild and moderate cases are considered as a single class.

  19. Occupational hazards of chemical carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Indulski, J.; Szeszenia-Dabrowska, N.

    1984-01-01

    Current problems are presented resulting from the evaluation of occupational risk of chemical carcinogens in the national economy. In addition, conditions and activities facilitating the actual evaluation of exposure, i.e. one of the indirect purposes of the control program of work-induced cancer, undertaken within the Government Program PR-6 ''Cancer Control'', the problem ''Work Environment Cancerogenesis'', have been indicated. The numbers of those occupationally exposed to specific carcinogens, based on the data from sanitary-epidemiological stations, demonstrated great differences in professional preparation and technological capabilities of regional supervision authorities in the field concerned.

  20. Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chun-Hung [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China); Chou, Pei-Hsin [Department of Environmental Engineering, National Cheng-Kung University, Tainan, Taiwan (China); Chen, Pei-Jen, E-mail: chenpj@ntu.edu.tw [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China)

    2014-07-30

    Highlights: • We assess ecotoxicological impact of azole fungicides in the aquatic environment. • Carcinogenic and non-carcinogenic azoles show different CYP activities in medaka. • We compare azole-induced CYP expression and carcinogenesis between fish and rodents. • Liver CYP-enzyme induction is a key event in conazole-induced tumorigenesis. • We suggest toxicity evaluation methods for azole fungicides using medaka fish. - Abstract: Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish

  1. In situ lung perfusion is a valuable tool to assess lungs from donation after circulatory death donors category III

    NARCIS (Netherlands)

    Van de Wauwer, Caroline; Munneke, Anita J.; Engels, Gerwin E.; Berga, Foke M.; Rakhorst, Gerhard; Nijsten, Maarten W.; Mariani, Massimo A.; Erasmus, Michiel E.

    Donations after circulatory death (DCD) lung grafts are an alternative to extend the donor pool in lung transplantation. This study investigates the use of an in situ lung perfusion system (ISLP) in the donor to evaluate category III lungs. Pigs were sacrificed by ventricular fibrillation. All

  2. Lung cancer trends: smoking, obesity, and sex assessed in the Staten Island University’s lung cancer patients

    Directory of Open Access Journals (Sweden)

    Gupta S

    2014-07-01

    Full Text Available Shilpi Gupta,1 Samer Hassan,1 Vijaya R Bhatt,2 Houssein Abdul Sater,1 Asma Dilawari31Hematology-Oncology, Staten Island University Hospital, Staten Island, NY, USA; 2Hematology-Oncology, Nebraska Medical Ctr, Omaha, NE, USA; 3Hematology-Oncology, MedStar Georgetown University Hospital, Olney, Maryland, USAIntroduction: The incidence of lung cancer in the United States decreased by 1.8% from 1991 to 2005 while it increased by 0.5% in females. We assessed whether nonsmokers afflicted with lung cancer at Staten Island University Hospital are disproportionately female in comparison to national averages. We also evaluated different factors including race, histology, and body mass index (BMI in correlation with smoking history.Methods: A retrospective chart review was conducted from 2005 to 2011 on 857 patients. Patients were divided into two groups according to their smoking status: current or ever-smokers, and former or never-smokers. A chi-square test for categorical data and multivariate logistic regression analyses was used to study the relation between BMI and the other clinical and demographic data.Results: Forty-nine percent of patients were men and 51% were women with a mean age at diagnosis of 67.8 years. Current smokers were most common (50.2% followed by ever-smokers (18.2%, former smokers (15.8% and never-smokers (15.6%. Forty eight percent had stage IV lung cancer upon presentation. Never-smokers with lung cancer were 24 times more likely to be females. However, the proportion of female former smokers (31.6% was lower than the proportion of male former smokers (68.4% (P=0.001. There was no significant association between American Joint Committee on Cancer (AJCC stage, sex, race, and histological type in the two smoking groups. Current/ever-smokers tended to be younger at age of diagnosis (P=0.0003. BMI was lower in the current/ever-smokers (26.8 kg/m2 versus former/never-smokers (28.8 in males (P=0.0005. BMI was significantly higher in

  3. Lung scintigraphy in the assessment of recurrent bronchitis and pneumonia in children

    Energy Technology Data Exchange (ETDEWEB)

    Ciofetta, G. [Second Pediatric Clinic, Rome (Italy). Lab. of Pediatric Nuclear Medicine

    1997-12-01

    Recurrent bronchitis and pneumonia in childhood are a significant factor in predisposing adults to chronic respiratory disease. Lung scintigraphy in children with recurrent respiratory problems very frequently shows regional abnormalities, even in the absence of radiological sings. Structural changes, also at the histological level, are accompanied bu functional disturbances that cause lung scan abnormalities to become stable with time and are very likely responsible for persisting disease in adulthood. Moreover, any chronic respiratory condition that has been diagnosed,like cystic-fibrosis, bronchiectasis, bronchopulmonary malformations, lung fibrosis, should be assessed and followed-up by means of lung scintigraphy. Suspected radio transparent foreign-body inhalation, radiographical hypernucleus (compensatory or pathological emphysema?), functional assessment before lung surgery, suspected mucociliary function impairment, suspected interstitial pneumonia, all of the above conditions represent important indications to lung scintigraphy in children. Finally, it is wise pointing out that, in order to avoid false positive results towards the diagnosis of structural disease, any easily reversible functional impairment should be removed before the scan, by proper patient preparation: in children this is done by at least aerosol therapy with beta-agonists, local steroids and mucolytics for 1 week - 10 days.

  4. The Regulation of Carcinogenic Hazards.

    Science.gov (United States)

    Gori, Gio Batta

    1980-01-01

    It is suggested that a system of relative standards be formulated which would compare utility of substances to their relative risk as carcinogens. This would define a range of use restrictions. Substances intended for specific uses would then be regulated according to these standards. (Author/RE)

  5. SHORT COMMUNICATION CARCINOGENIC POTENCY OF ...

    African Journals Online (AJOL)

    ABSTRACT. Carcinogenic potency of polycyclic aromatic hydrocarbons (PAHs) in soils obtained from seven different sampling locations in Effurun metropolis and its environs of Niger Delta Area of Nigeria were evaluated. The 16 US EPA priority PAHs were determined with GC-MS. The concentrations of individual PAHs ...

  6. Urinary trans-anti-7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene as the most relevant biomarker for assessing carcinogenic polycyclic aromatic hydrocarbons exposure.

    Science.gov (United States)

    Barbeau, Damien; Lutier, Simon; Choisnard, Luc; Marques, Marie; Persoons, Renaud; Maitre, Anne

    2017-12-19

    Polycyclic aromatic hydrocarbons (PAH) are ubiquitous pollutants present as complex mixtures in the environment. Among them, benzo(a)pyrene (BaP) is classified as carcinogenic to humans by the International Agency of Research on Cancer. Taking into account all absorption ways, human biomonitoring allows PAH exposure assessment, but biomarkers both specific to carcinogenic effect and sufficiently sensitive are lacking. In this work, we proposed the urinary 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene (7,8,9,10-OHBaP) stemming from hydrolysis of BaP-7,8-diol-9,10-epoxide, the ultimate carcinogenic BaP metabolite, as biomarker of PAH exposure. A simple and highly sensitive analytical method, with a limit of quantification (LQ) reaching 0.06pmol/L (0.02ng/L), was described and validated. The relevance of urinary 7,8,9,10-OHBaP concentrations adjustment by creatinine was demonstrated. In a group of 24 non-occupationally PAH exposed subjects, only 15% of 7,8,9,10-OHBaP levels was below the LQ and the last daily void has been found as the best sampling time. Tobacco consumption had a significant positive effect on 7,8,9,10-OHBaP concentrations with a 90e percentile equal to 0.05nmole/mole creatinine (nmol/mol) and 0.03nmol/mol for smokers and non-smokers, respectively. In case of occupational PAH exposure, all the pre- and post-shift urinary 7,8,9,10-OHBaP levels of 7 non-smoking workers in a prebaked electrodes production plant were above the LQ. Concentrations ranged from 0.05 to 0.91nmol/mol and accumulation of 7,8,9,10-OHBaP into organism of workers during the working week was clearly observed. The best sampling time was the post-shift at the end of week but samples should also be collected at pre-shift the beginning of week to assess the background level. Finally, the urinary 7,8,9,10-OHBaP elimination kinetic through the weekend was studied using non-linear mixed effect modelling. Mean apparent urinary half-life was 31.5h with low inter

  7. [The awareness of carcinogenic effect of tobacco smoke--a questionnaire survey of students and employees of Collegium Medicum of Nicolaus Copernicus University].

    Science.gov (United States)

    Seget, Monika; Karolczak, Dominika; Wilk, Magdalena; Błaszczyk, Agata; Szylberg, Łukasz; Florek, Ewa; Marszałek, Andrzej

    2012-01-01

    Smoking is currently the most significant risk factor for health according to WHO statements. It has been proven that smoking is the cause of many diseases, for example cardiovascular and respiratory tract diseases as well as impaired fertility and decreased immunity. The adverse effects of cigarette smoking on pregnancy and health of children were also proved. However, special attention is laid on impact of smoking on the development of cancer. In tobacco smoke there are over 4,000 different chemical substances and compounds, of which more than 50 are carcinogens. The present study was aimed to assess the knowledge of students and employees of Collegium Medicum of Nicolaus Copernicus University in Torun (CM UMK), first on number and types of carcinogens contained in tobacco smoke and secondly on types of diseases caused by smoking. There were 480 responders included to the study(253 women and 227 men). Among them there were 416 students of CM UMK, 59 students of biomedical engineering at the University of Technology and Life Sciences in Bydgoszcz and 5 employees of CM UMK. Among the respondents there was considerable ignorance about the number of carcinogens contained in tobacco smoke with over 50% of them indicating the incorrect answer. Among the carcinogens there were mentioned mostly tar and nicotine, and among the diseases caused by tobacco smoke most often pointed response there were lung and larynx cancer and heart and blood vessels diseases and to reduce the weight of newborns. In summary, we can conclude that the awareness of students and employees of CM UMK about the carcinogenic properties of tobacco smoke was not sufficient. Respondents were aware of the dangers of smoking, they knew the basic carcinogenic substances and pointed a few diseases caused by smoking cigarettes. Unfortunately their knowledge does not refer to a number of diseases which in common believe are not connected to cigarette smoking, but in fact tobacco smoke is very important for

  8. Effect of cigarette smoke on the mutagenic activation of various carcinogens in hamster.

    Science.gov (United States)

    Mori, Y; Iimura, K; Furukawa, F; Nishikawa, A; Takahashi, M; Konishi, Y

    1995-01-01

    Male Syrian golden hamsters were exposed for 1 or 2 weeks to smoke produced by commercial non-filter cigarettes for 5 consecutive days in a Hamburg type II smoking machine. Postmitochondrial fractions (S9) prepared from the liver, lungs, and pancreas were used in the Ames liquid incubation assay, in order to assess the effect of cigarette smoke (CS) on the metabolic activation of four groups of procarcinogens. The mutagenic activities of five heterocyclic amines on strain TA98 in the presence of liver S9 mix were induced up to 3.7 times above controls including sham smoke control, while no significant alteration of mutagenicity was observed with 3'-hydroxymethyl-N,N-dimethyl-4-aminoazobenzene and benzo[a]pyrene on TA98 or with N-nirosobis(2-oxopropyl)amine (BOP) on TA100. A similar stimulation of metabolic activation was also observed for 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) with S9 from the lungs but not from the pancreas. The mutagenic potential of 11 carcinogens including aflatoxin B1 (AFB1) and two other heterocyclic amines was also examined using liver S9 from male hamsters pretreated with phenobarbital (PB) or 3-methylcholanthrene (MC). The numbers of revertant colonies were much higher (2-20-fold) in the presence of MC-treated liver S9 than in the presence of PB-treated liver S9, except in the case of AFB1 which showed a higher mutagenicity with PB-induced S9. 7,8-Benzoflavone considerably inhibited the activities of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and Trp-P-1 in the presence of either untreated, MC- or CS-treated liver S9, whereas metyrapone was totally lacking this effect, indicating that cytochrome P450(CYP)1A1/1A2 isoforms of hamster liver are predominantly involved in the metabolic activation of these carcinogens. CS exposure of hamsters might selectively induce hepatic CYP1A2 which cannot activate BOP. Consequently, the present findings could explain, in part, the anticarcinogenic effect of CS on BOP-induced pancreatic

  9. A call to expand regulation to all carcinogenic fibrous minerals

    Science.gov (United States)

    Baumann, F.; Steele, I.; Ambrosi, J.; Carbone, M.

    2013-05-01

    The regulatory term "asbestos" groups only the six fibrous minerals that were commercially used among approximately 400. The carcinogenicity of these six regulated minerals has been largely demonstrated and is related to fiber structure, fiber length/diameter ratio, and bio-persistence. From a public perception, the generic term "asbestos" refers to the fibrous minerals that cause asbestosis, mesothelioma and other cancers. However, other non-regulated fibrous minerals are potentially as dangerous as the regulatory asbestos because they share similar physical and chemical properties, epidemiological studies have demonstrated their relationship with asbestos-related diseases, and both in vitro and in vivo experiments have established the toxicity of these minerals. For example, the non-regulated asbestiform winchite and richterite minerals that contaminated the vermiculite mined from Libby, Montana, (USA) were associated with mesothelioma, lung cancer and asbestosis observed among the area's residents and miners. Many other examples of non-regulated carcinogenic fibrous minerals include, but are not limited to, antigorite, arfvedsonite, balangeroite, carlosturanite, erionite, fluoro-edenite, hornblende, mordenite, palygorskite, and sepiolite. To propose a regulatory definition that would provide protection from all carcinogenic fibers, we have conducted an interdisciplinary literature review to compare the characteristics of "asbestos" and of non-regulated mineral fibers that relate to carcinogenicity. We specifically studied two non-regulated fibrous minerals that are associated with asbestos-related diseases: the serpentine antigorite and the zeolite erionite. Both examples underscore the problem of regulation based on commercial, rather than scientific principles: 1) the occurrence of fibrous antigorite in materials used to pave roads has been correlated with high mesothelioma rates in New Caledonia. Antigorite was also the cause of asbestosis in Poland, and in

  10. The Effect of A Geriatric Assessment on Treatment Decisions for Patients with Lung Cancer.

    Science.gov (United States)

    Schulkes, Karlijn J G; Souwer, Esteban T D; Hamaker, Marije E; Codrington, Henk; van der Sar-van der Brugge, Simone; Lammers, Jan-Willem J; Portielje, Johanneke E A; van Elden, Leontine J R; van den Bos, Frederiek

    2017-04-01

    Decision-making for older patients with lung cancer can be complex and challenging. A geriatric assessment (GA) may be helpful and is increasingly being used since 2005 when SIOG advised to incorporate this in standard work-up for the elderly with cancer. Our aim was to evaluate the value of a geriatric assessment in decision-making for patients with lung cancer. Between January 2014 and April 2016, data on patients with lung cancer from two teaching hospitals in the Netherlands were entered in a prospective database. Outcome of geriatric assessment, non-oncologic interventions, and suggested adaptations of oncologic treatment proposals were evaluated. 83 patients (median age 79 years) were analyzed with a geriatric assessment, of which 59% were treated with a curative intent. Half of the patients were classified as ECOG PS 0 or 1. The majority of the patients (78%) suffered from geriatric impairments and 43% (n = 35) of the patients suffered from three or more geriatric impairments (out of eight analyzed domains). Nutritional status was most frequently impaired (52%). Previously undiagnosed impairments were identified in 58% of the patients, and non-oncologic interventions were advised for 43%. For 33% of patients, adaptations of the oncologic treatment were proposed. Patients with higher number of geriatric impairments more often were advised a reduced or less intensive treatment (p geriatric assessment uncovers previously unknown health impairments and provides important guidance for tailored treatment decisions in patients with lung cancer. More research on GA-stratified treatment decisions is needed.

  11. Glyphosate rodent carcinogenicity bioassay expert panel review.

    Science.gov (United States)

    Williams, Gary M; Berry, Colin; Burns, Michele; de Camargo, Joao Lauro Viana; Greim, Helmut

    2016-09-01

    Glyphosate has been rigorously and extensively tested for carcinogenicity by administration to mice (five studies) and to rats (nine studies). Most authorities have concluded that the evidence does not indicate a cancer risk to humans. The International Agency for Research on Cancer (IARC), however, evaluated some of the available data and concluded that glyphosate probably is carcinogenic to humans. The expert panel convened by Intertek assessed the findings used by IARC, as well as the full body of evidence and found the following: (1) the renal neoplastic effects in males of one mouse study are not associated with glyphosate exposure, because they lack statistical significance, strength, consistency, specificity, lack a dose-response pattern, plausibility, and coherence; (2) the strength of association of liver hemangiosarcomas in a different mouse study is absent, lacking consistency, and a dose-response effect and having in high dose males only a significant incidence increase which is within the historical control range; (3) pancreatic islet-cell adenomas (non-significant incidence increase), in two studies of male SD rats did not progress to carcinomas and lacked a dose-response pattern (the highest incidence is in the low dose followed by the high dose); (4) in one of two studies, a non-significant positive trend in the incidence of hepatocellular adenomas in male rats did not lead to progression to carcinomas; (5) in one of two studies, the non-significant positive trend in the incidence of thyroid C-cell adenomas in female rats was not present and there was no progression of adenomas to carcinomas at the end of the study. Application of criteria for causality considerations to the above mentioned tumor types and given the overall weight-of-evidence (WoE), the expert panel concluded that glyphosate is not a carcinogen in laboratory animals.

  12. Impact of Environmental Exposures on the Mutagenicity/Carcinogenicity of Heterocyclic Amines

    Energy Technology Data Exchange (ETDEWEB)

    Felton, J S; Knize, M G; Bennett, L M; Malfatti, M A; Colvin, M E; Kulp, K S

    2003-12-19

    Carcinogenic heterocyclic amines are produced from overcooked foods and are highly mutagenic in most short-term test systems. One of the most abundant of these amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces breast, colon and prostate tumors in rats. Human dietary epidemiology studies suggest a strong correlation between either meat consumption or well-done muscle meat consumption and cancers of the colon, breast, stomach, lung and esophagus. For over 20 years our laboratory has helped define the human exposure to these dietary carcinogens. In this report we describe how various environmental exposures may modulate the risk from exposure to heterocyclic amines, especially PhIP. To assess the impact of foods on PhIP metabolism in humans, we developed an LC/MS/MS method to analyze the four major PhIP urinary metabolites following the consumption of a single portion of grilled chicken. Adding broccoli to the volunteers' diet altered the kinetics of PhIP metabolism. At the cellular level we have found that PhIP itself stimulates a significant estrogenic response in MCF-7 cells, but even more interestingly, co-incubation of the cells with herbal teas appear to enhance the response. Numerous environmental chemicals found in food or the atmosphere can impact the exposure, metabolism, and cell proliferation response of heterocyclic amines.

  13. Assessment of murine lung mechanics outcome measures: alignment with those made in asthmatics

    Science.gov (United States)

    Walker, Julia K. L.; Kraft, Monica; Fisher, John T.

    2013-01-01

    Although asthma is characterized as an inflammatory disease, recent reports highlight the importance of pulmonary physiology outcome measures to the clinical assessment of asthma control and risk of asthma exacerbation. Murine models of allergic inflammatory airway disease have been widely used to gain mechanistic insight into the pathogenesis of asthma; however, several aspects of murine models could benefit from improvement. This review focuses on aligning lung mechanics measures made in mice with those made in humans, with an eye toward improving the translational utility of these measures. A brief description of techniques available to measure murine lung mechanics is provided along with a methodological consideration of their utilization. How murine lung mechanics outcome measures relate to pulmonary physiology measures conducted in humans is discussed and we recommend that, like human studies, outcome measures be standardized for murine models of asthma. PMID:23408785

  14. A functional assessment of patients two years after lung transplantation in Poland.

    Science.gov (United States)

    Jastrzębski, Dariusz T; Gumola, Anna; Wojarski, Jacek; Żegleń, Sławomir; Ochman, Marek; Czyżewski, Damian; Ziora, Dariusz; Zembala, Marian; Kozielski, Jerzy

    2014-06-01

    The aim of the study was to assess the long-term results of lung transplantation (LT) in Poland two years after the procedure. The study included patients who underwent LT between December 2004 and December 2009 in the Silesian Center for Heart Diseases in Zabrze. Various lung functions (forced vital capacity - FVC; forced expiratory volume in 1 second - FEV1), the quality of life (SF-36 questionnaire), the level of perceived dyspnea (Medical Research Council - MRC; basic dyspnea index - BDI), and the patient's mobility (the 6-minute walking test - 6MWT) were assessed before and approximately 24 months after LT. Among 35 patients who underwent LT, 20 patients were referred to our study (mean age: 46.6 ± 9.03 years). After LT, a statistically significant increase was observed in the distance achieved in the 6MWT (323.8 vs. 505.8 m), FVC (1.64 vs. 2.88 L), and FEV1 (1.37 vs. 2.09 L). An improvement in perceived dyspnea in MRC and BDI questionnaires was observed in patients with chronic obstructive pulmonary disease (COPD) after LT. The assessment of the quality of life, excluding perceived pain, showed the most significant improvement in the physical cumulative score (PCS; 25 vs. 45 points), especially in patients with idiopathic pulmonary fibrosis. Lung transplantation in Poland, in patients who live longer than 2 years after the procedure, significantly improves the mobility, lung function, perceived dyspnea, and the quality of life.

  15. Assessment of CF lung disease using motion corrected PROPELLER MRI: a comparison with CT

    Energy Technology Data Exchange (ETDEWEB)

    Ciet, Pierluigi [General Hospital Ca' Foncello, Radiology Department, Treviso (Italy); Sophia Children' s Hospital, Pediatric Pulmonology Erasmus MC, Rotterdam (Netherlands); Erasmus MC, Radiology, Rotterdam (Netherlands); Serra, Goffredo; Catalano, Carlo [University of Rome ' ' Sapienza' ' , Radiology, Rome (Italy); Bertolo, Silvia; Morana, Giovanni [General Hospital Ca' Foncello, Radiology Department, Treviso (Italy); Spronk, Sandra [Erasmus MC, Radiology, Rotterdam (Netherlands); Erasmus MC, Epidemiology, Rotterdam (Netherlands); Ros, Mirco [Ca' Foncello Hospital, Pediatrics, Treviso (Italy); Fraioli, Francesco [University College London (UCL), Institute of Nuclear Medicine, London (United Kingdom); Quattrucci, Serena [University of Rome Sapienza, Pediatrics, Rome (Italy); Assael, M.B. [Azienda Ospedaliera di Verona, Verona CF Center, Verona (Italy); Pomerri, Fabio [University of Padova, Department of Medicine-DIMED, Padova (Italy); Tiddens, Harm A.W.M. [Sophia Children' s Hospital, Pediatric Pulmonology Erasmus MC, Rotterdam (Netherlands); Erasmus MC, Radiology, Rotterdam (Netherlands)

    2016-03-15

    To date, PROPELLER MRI, a breathing-motion-insensitive technique, has not been assessed for cystic fibrosis (CF) lung disease. We compared this technique to CT for assessing CF lung disease in children and adults. Thirty-eight stable CF patients (median 21 years, range 6-51 years, 22 female) underwent MRI and CT on the same day. Study protocol included respiratory-triggered PROPELLER MRI and volumetric CT end-inspiratory and -expiratory acquisitions. Two observers scored the images using the CF-MRI and CF-CT systems. Scores were compared with intra-class correlation coefficient (ICC) and Bland-Altman plots. The sensitivity and specificity of MRI versus CT were calculated. MRI sensitivity for detecting severe CF bronchiectasis was 0.33 (CI 0.09-0.57), while specificity was 100 % (CI 0.88-1). ICCs for bronchiectasis and trapped air were as follows: MRI-bronchiectasis (0.79); CT-bronchiectasis (0.85); MRI-trapped air (0.51); CT-trapped air (0.87). Bland-Altman plots showed an MRI tendency to overestimate the severity of bronchiectasis in mild CF disease and underestimate bronchiectasis in severe disease. Motion correction in PROPELLER MRI does not improve assessment of CF lung disease compared to CT. However, the good inter- and intra-observer agreement and the high specificity suggest that MRI might play a role in the short-term follow-up of CF lung disease (i.e. pulmonary exacerbations). (orig.)

  16. Longitudinal assessment of lung function in children with sickle cell disease.

    Science.gov (United States)

    Lunt, Alan; McGhee, Emily; Sylvester, Karl; Rafferty, Gerrard; Dick, Moira; Rees, David; Height, Susan; Thein, Swee Lay; Greenough, Anne

    2016-07-01

    To prospectively assess longitudinal lung function in children with sickle cell disease (SCD). Lung function in SCD children deteriorates with increasing age and the decline is more marked in younger children who have recently suffered ACS episodes. Two prospective longitudinal studies. Two cohorts of SCD children and age and ethnic matched controls were recruited. Cohort One (47 SCD and 26 controls) had a median age of 8.8 years and follow up of 2 years and Cohort Two (45 SCD and 26 controls) a median age of 10.2 years and follow up of 10 years. Forced expiratory volume in one second (FEV1 ), vital capacity (VC), forced expiratory flow between 25% and 75% of VC (FEF 25-75 ), total lung capacity (TLC) and residual volume (RV) were measured on two occasions. In both groups of SCD children, lung function declined significantly, but in neither control group. ACS episodes were more frequent during the follow up period in Cohort One than Cohort Two (P Lung function deteriorated with increasing age in SCD children and the rate of decline was greater in younger children in whom ACS episodes were more common. Pediatr Pulmonol. 2016;51:717-723. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  17. Quantitative assessment of lung and bladder cancer risk and oral exposure to inorganic arsenic: Meta-regression analyses of epidemiological data.

    Science.gov (United States)

    Lynch, Heather N; Zu, Ke; Kennedy, Erin M; Lam, Thuy; Liu, Xiaobin; Pizzurro, Daniella M; Loftus, Christine T; Rhomberg, Lorenz R

    2017-09-01

    Inorganic arsenic (iAs) in drinking water varies geographically and is prevalent worldwide. While exposures in the US are generally low, there are some areas with higher levels of naturally occurring iAs (potentially >100μg/L) where residents rely on unregulated drinking water wells. Much of the evidence on the association between iAs and cancer comes from epidemiological studies conducted in South American and Asian populations. These populations have generally been exposed to much higher levels of iAs and have differing underlying characteristics, both of which make comparing them to Western populations difficult. A key question is whether and how one should extrapolate from these high exposure studies to estimate cancer risk at lower exposures. We conducted an independent analysis to determine the most appropriate cancer endpoints, studies, and models to support an oral carcinogenicity assessment of iAs, taking into consideration factors that affect the apparent potency of iAs across geographically and culturally distinct populations. We identified bladder and lung cancer as high-priority endpoints and used meta-regression to pool data across studies from different regions of the world to derive oral cancer slope factors (CSFs) and unit risks (excess risk per μg/L) for iAs based on the background risks of bladder and lung cancer in the US. We also calculated concentrations of iAs in water that are not likely to result in cancer risk above what is considered acceptable by the United States Environmental Protection Agency (US EPA). While we derived these factors assuming a linear, no-threshold relationship between iAs and cancer risk, we also evaluated the shape of the dose-response curves and assessed the evidence for overall nonlinearity. Overall, we found that the incremental risks of bladder and lung cancer associated with iAs were relatively low. The sensitivity analyses we conducted suggested that populations with relatively high iAs exposures appeared to

  18. Integrative Assessment of Chlorine-Induced Acute Lung Injury in Mice

    Science.gov (United States)

    Pope-Varsalona, Hannah; Concel, Vincent J.; Liu, Pengyuan; Bein, Kiflai; Berndt, Annerose; Martin, Timothy M.; Ganguly, Koustav; Jang, An Soo; Brant, Kelly A.; Dopico, Richard A.; Upadhyay, Swapna; Di, Y. P. Peter; Hu, Zhen; Vuga, Louis J.; Medvedovic, Mario; Kaminski, Naftali; You, Ming; Alexander, Danny C.; McDunn, Jonathan E.; Prows, Daniel R.; Knoell, Daren L.

    2012-01-01

    The genetic basis for the underlying individual susceptibility to chlorine-induced acute lung injury is unknown. To uncover the genetic basis and pathophysiological processes that could provide additional homeostatic capacities during lung injury, 40 inbred murine strains were exposed to chlorine, and haplotype association mapping was performed. The identified single-nucleotide polymorphism (SNP) associations were evaluated through transcriptomic and metabolomic profiling. Using ≥ 10% allelic frequency and ≥ 10% phenotype explained as threshold criteria, promoter SNPs that could eliminate putative transcriptional factor recognition sites in candidate genes were assessed by determining transcript levels through microarray and reverse real-time PCR during chlorine exposure. The mean survival time varied by approximately 5-fold among strains, and SNP associations were identified for 13 candidate genes on chromosomes 1, 4, 5, 9, and 15. Microarrays revealed several differentially enriched pathways, including protein transport (decreased more in the sensitive C57BLKS/J lung) and protein catabolic process (increased more in the resistant C57BL/10J lung). Lung metabolomic profiling revealed 95 of the 280 metabolites measured were altered by chlorine exposure, and included alanine, which decreased more in the C57BLKS/J than in the C57BL/10J strain, and glutamine, which increased more in the C57BL/10J than in the C57BLKS/J strain. Genetic associations from haplotype mapping were strengthened by an integrated assessment using transcriptomic and metabolomic profiling. The leading candidate genes associated with increased susceptibility to acute lung injury in mice included Klf4, Sema7a, Tns1, Aacs, and a gene that encodes an amino acid carrier, Slc38a4. PMID:22447970

  19. Assessment of respiratory symptoms and lung function among textile ...

    African Journals Online (AJOL)

    Background: The number of textile industries in Nigeria with large work force is on the rise. There is thus the need to assess medical challenges of its workers, one of which is respiratory ailments. Although much has been written about the subject globally, only few studies have been done in Nigeria. This study aims to ...

  20. Comparison of expert and job-exposure matrix-based retrospective exposure assessment of occupational carcinogens in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Offermans, N.S.M.; Vermeulen, R.; Burdorf, A.; Peters, S.; Goldbohm, R.A.; Koeman, T.; Tongeren, M. van; Kauppinen, T.; Kant, I.; Kromhout, H.; Brandt, P.A. van den

    2012-01-01

    Objectives: Reliable retrospective exposure assessment continues to be a challenge in most population-based studies. Several methodologies exist for estimating exposures retrospectively, of which case-by-case expert assessment and job-exposure matrices (JEMs) are commonly used. This study evaluated

  1. The Assessment of Health-Related Quality of Life in Scleroderma-Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Shahrzad M Lari

    2014-05-01

    Full Text Available Introduction: Pulmonary involvement is the most common cause of mortality and disability in patients with systemic sclerosis and it significantly affects the quality of life in these patients. Therefore, early diagnosis and treatment of pulmonary involvement seems necessary in patients with SSc. In this study, we aimed to assess the health-related quality of life (HRQoL in patients with Scleroderma-Interstitial Lung Disease (SSc-ILD and its relationship with pulmonary function parameters. Materials and Methods: Considering the inclusion and exclusion criteria, 25 patients with SSc-ILD were enrolled in this cross-sectional study from April 2012 to June 2013. Full tests of lung function, including body plethysmography and diffusing capacity of the lungs for carbon monoxide (DLCO, 6-minute walk distance (6MWD, and pulse oximetry were performed. The HRQoL was assessed using St. George’s and CAT questionnaires; also, dyspnea was evaluated for all the patients, using modified medical research council (MMRC scale. Afterwards, the relationship between the total scores of HRQoL questionnaires and the severity of lung disease was analyzed, based on the recorded variables. Results: The mean age of the patients was 40.36±9.50 years and the mean duration of the disease was 7.16±4.50 years. A statistically significant inverse correlation was observed between 6MWD (r=-0.50, P=0.01, DLCO (r=-0.67, P

  2. [Evaluation of nutritional Status in lung cancer using bio electrical impedance analysis and mini nutritional assessment].

    Science.gov (United States)

    Daghfous, Hafaoua; El Ayeb, Wejdène; Alouane, Leila; Tritar, Fatma

    2014-12-01

    Malnutrition and cachexia were a frequent problem in lung cancer and increases the risks of morbidity and mortality in these patients. Bioelectrical impedance analysis (BIA) is easy, non-invasive and reproducible method that can be performed. Evaluate nutritional status in patients with primary lung cancer by Mini Nutritional Assessment (MNA), BIA and anthropometric values (weight, arm and calf circumferences) and correlate the nutritional parameters to severity of cancer and histopathology. The nutritional status of 73 cases of primary lung cancer was evaluated by anthropometric parameters, MNA test and impedencemetrie Results: According to body mass index (BMI), malnutrition, overweight and obesity were noted in 34,2%, 13,7% and 5,5%. According to BMI, free-fat mass index (FFMI) and fat mass index (FMI), the investigations occurred malnutrition and depletion of muscle in respectively 19,2% and 23,3% of cases. Fat depletion was noted in 21,9%. Overweight and obesity were detected in 6,8% and 5,5% of cases. Assessment by MNA, revealed that 28,7% of patients were already malnourished and 49,3% of patients were at risk of malnutrition. A significant correlation existed between the score of MNA and arm and calf circumferences, FFMI and FMI. FMI was significantly lower in group of patients with small lung carcinoma. Only FFMI allows early detection of malnutrition in cancer patients overestimated by measuring BMI and arm circumference was the better indicator of depletion of muscle.

  3. Determination of some carcinogenic PAHs with toxic equivalency ...

    Indian Academy of Sciences (India)

    mental health risk associated with exposure to airborne mixtures of polycyclic aromatic hydrocarbons (PAHs);. Chemosphere 32 639–648. Pufulete M, Battershill J, Boobis A and Fielder R 2004. Approaches to carcinogenic risk assessment for polycyclic aromatic hydrocarbons: A UK perspective; Regulatory. Toxicology and ...

  4. Classification of carcinogenic and mutagenic properties using machine learning method

    DEFF Research Database (Denmark)

    Moorthy, N. S.Hari Narayana; Kumar, Surendra; Poongavanam, Vasanthanathan

    2017-01-01

    An accurate calculation of carcinogenicity of chemicals became a serious challenge for the health assessment authority around the globe because of not only increased cost for experiments but also various ethical issues exist using animal models. In this study, we provide machine learning...

  5. Assessing the nutritional status of elderly Chinese lung cancer patients using the Mini-Nutritional Assessment (MNA® tool

    Directory of Open Access Journals (Sweden)

    Zhang L

    2013-03-01

    Full Text Available Lei Zhang,1,* Yanjun Su,1,* Chen Wang,2 Yongsheng Sha,1 Hong Zhu,3 Shumin Xie,4 Sabrina Kwauk,5 Jing Zhang,2 Yunshou Lin,2 Changli Wang1,*1Department of Thoracic Surgery, Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 2Tianjin Medical University, Tianjin, 3Department of Public Health, Tianjin Medical University, Tianjin, 4Xiangya Medical School of Central-South University, Changsha, People's Republic of China; 5School of Public Health, Harvard University, Boston, Cambridge, MA, USA*These authors contributed equally to this workPurpose: This study assessed the nutritional status of elderly Chinese lung cancer inpatients using a revised version of the Mini-Nutritional Assessment (MNA® tool.Patients and methods: The revised version of the MNA tool was used to assess the nutritional status of 180 elderly Chinese lung cancer inpatients prior to their scheduled surgery between June 2010 and July 2011. Patients' demographic data, anthropometric parameters, and biochemical markers were collected and analyzed.Results: Among the 180 inpatients who underwent the MNA, 9% were malnourished (MNA score < 19, 33% were at risk of malnutrition (MNA score 19–23, and 58% were well nourished (MNA score ≥ 24. There was significant correlation between the MNA scores of patients who were malnourished, at risk of malnutrition, and well nourished (P < 0.001, as well as between total MNA score and most MNA questions. The three patient groups with different nutritional statuses differed significantly in their responses to anthropometrics and global, diet, and subjective assessments.Conclusion: Incidence rates of malnutrition prior to surgery are high among elderly Chinese lung cancer inpatients. The revised MNA is a valid and reliable tool that can be used to assess and prevent malnutrition among these inpatients.Keywords: malnutrition, MNA-SF, nutrition, inpatients, diet

  6. Nebulized cyclosporine in the rat: assessment of regional lung and extrapulmonary deposition.

    Science.gov (United States)

    Blot, F; Faurisson, F; Bernard, N; Sellam, S; Friard, S; Tavakoli, R; Carbon, C; Stern, M; Bisson, A; Pocidalo, J J; Caubarrere, I

    1999-07-27

    Nebulized cyclosporine (CsA) has been shown to limit lung allograft rejection as well as intramuscular (IM) CsA, with limited blood diffusion. The present study determined the pharmacokinetic parameters of nebulized CsA, by the assessment of regional lung deposition and extrapulmonary diffusion of CsA. CsA was given either by IM injection (10 mg/kg) or by aerosol (at 10 and 25 mg/kg doses); 70 rats were killed at 25 and 50 min, and at 2, 4, 6, 8, 12, 24, or 48 hr after CsA administration. CsA levels were measured in the whole lung, in central and peripheral parts of the lung, in whole blood, kidney, and heart. The areas under the concentration time curves (AUCs) were determined. In blood, kidney, and heart, CsA levels were significantly higher for IM than for aerosol administrations at 10 and 25 mg/kg doses. In the whole lung, the AUC was greater for the aerosol route at 25 mg/kg doses (588 ng x hr/mg) than for the low-dose (200 ng x hr/mg) or IM administration (200 ng x hr/mg). The central to peripheral index of CsA (ratio of AUC central/peripheral part of the lung) was not significantly different for both aerosol administrations (0.63 and 0.69, respectively) and for the IM route (0.81). Nebulized CsA allows better pulmonary concentration than IM administration, with equivalent central and peripheral deposition whatever the mode of administration, and results in lower levels in blood, kidney, and heart.

  7. Computed tomography assessment of pharmacological lung volume reduction induced by bronchodilators in COPD.

    Science.gov (United States)

    Tanabe, Naoya; Muro, Shigeo; Oguma, Tsuyoshi; Sato, Susumu; Kiyokawa, Hirofumi; Takahashi, Tamaki; Kudo, Megumi; Kinose, Daisuke; Kubo, Takeshi; Hoshino, Yuma; Ogawa, Emiko; Hirai, Toyohiro; Mishima, Michiaki

    2012-08-01

    Pharmacological lung volume reduction in COPD is an important goal in treatment with long-acting bronchodilators because in addition to airflow limitation, lung hyperinflation considerably affects COPD symptoms. Quantitative computed tomography (CT) simultaneously provides structural information about airway dimensions, emphysematous changes, and lung volumes, some of which are difficult to be evaluated by pulmonary function. Here, we evaluated changes in CT parameters and pulmonary function in 30 patients with COPD who underwent CT scans before and one year after starting tiotropium treatment and in 12 patients with COPD who were not treated with long-acting bronchodilators. Baseline pulmonary function and CT parameters did not differ between the two groups. One-year tiotropium therapy improved physiological-indices including residual volume (RV) and ratio of RV to total lung capacity (RV/TLC) (-235 mL, p = 0.005, and -2.9%, p = 0.0001, respectively), and CT-indices including wall area percent (WA%) and inner luminal area in right upper lobe apical and lower lobe basal segmental bronchi (-1.59%, p = 0.01, 2.27 mm(2), p = 0.0005; and -1.33%, p = 0.0008, 3.42 mm(2), p volume (LAV) and total lung volume (CT-TLV) (-92 mL, p = 0.0003, and -211 mL, p = 0.002, respectively). Changes in LAV, CT-TLV, RV, and RV/TLC were significantly greater in the tiotropium, than the non-bronchodilator group. The tiotropium-induced reduction in LAV correlated with the decrease in RV (ρ = 0.45, p = 0.01). Our findings not only indicate the value of the comprehensive CT measurements in assessing the effects of bronchodilators, including pharmacological lung volume reduction, but also further understanding of the structural changes underlying physiological improvements induced by bronchodilators.

  8. Epidemiology of Lung Cancer

    Science.gov (United States)

    Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

    2013-01-01

    Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

  9. Unilateral empyema impacts the assessment of regional lung ventilation by electrical impedance tomography.

    Science.gov (United States)

    Bläser, D; Pulletz, S; Becher, T; Schädler, D; Elke, G; Weiler, N; Frerichs, I

    2014-06-01

    Several studies have shown the ability of electrical impedance tomography (EIT) to assess regional ventilation distribution in human lungs. Fluid accumulation in the pleural space as in empyema, typically occurring on one chest side, may influence the distribution of ventilation and the corresponding EIT findings. The aim of our study was to examine this effect on the assessment of regional ventilation by EIT. Six patients suffering from unilateral empyema and intubated with a double-lumen endotracheal tube were studied. EIT data were acquired during volume-controlled ventilation with bilateral (tidal volume (V(T)): 800 ml) and unilateral ventilation (V(T): 400 ml) of the right and left lungs. Mean tidal amplitudes of the EIT signal were calculated in all image pixels. The sums of these values, expressed as relative impedance change (rel. ΔZ), were then determined in whole images and functionally defined regions-of-interest (ROI). The sums of rel. ΔZ calculated during the two cases of one-lung ventilation either on the affected or unaffected side were significantly smaller than during bilateral ventilation. However, in contrast to previous findings in patients with no pleural pathology, very low values of rel. ΔZ were found when the lung on the affected side was ventilated. ROI-based analysis rendered higher values than the whole-image analysis in this case, nonetheless, the values were significantly smaller than when the unaffected side was ventilated in spite of identical VT. In conclusion, our results indicate that the presence of empyema may affect the quantitative evaluation of regional lung ventilation by EIT.

  10. Systemic sclerosis interstitial lung disease evaluation: comparison between semiquantitative and quantitative computed tomography assessments.

    Science.gov (United States)

    Ariani, A; Lumetti, F; Silva, M; Santilli, D; Mozzani, F; Lucchini, G; Delsante, G; Sverzellati, N

    2014-01-01

    The pulmonary fibrosis extent in systemic sclerosis (SSc) has a prognostic value. Chest Computed Tomography (CT) is the gold standard to detect an interstitial lung disease (ILD). Semi-quantitative scores and quantitative methods can estimate the ILD. The first ones have a considerable inter-intraobserver variability, while quantitative scores, based on distribution of lung attenuation parameters (also called CT indexes), can be obtained through expensive and not so user-friendly software. The aim of this work is to investigate whether a DICOM-viewer open-source software (OsiriX) can obtain CT indexes correlating with semi-quantitative scores. Sixty-three chest CTs of ILD-SSc patients were assessed with two semi-quantitative methods (visual extent and limited/extensive ILD grading) and then blindly processed with OsiriX to obtain the distribution parameters of lung attenuation (kurtosis, skewness and mean). Semiquantitative assessment and CT indexes were compared through the Spearman rank test and Mann-Whitney test. All CT indexes showed a statistically significant correlation of moderate degree with the visual extent semi-quantitative assessment (p-value less than 0.05). Skewness was the lung attenuation distribution parameter with the strongest correlation (r =-0.378, p-value = 0.0023). Moreover, CT indexes of patients with an extensive and limited disease were statistically different (p less than 0.01). CT indexes correlating with a radiological semi-quantitative ILD assessment can be obtained through OsiriX. CT indexes can be considered very helpful to discriminate patients with extensive and limited ILD.

  11. A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function.

    Science.gov (United States)

    Sørli, Jorid B; Da Silva, Emilie; Bäckman, Per; Levin, Marcus; Thomsen, Birthe L; Koponen, Ismo K; Larsen, Søren T

    2016-03-01

    The lung surfactant (LS) lining is a thin liquid film covering the air-liquid interface of the respiratory tract. LS reduces surface tension, enabling lung surface expansion and contraction with minimal work during respiration. Disruption of surface tension is believed to play a key role in severe lung conditions. Inhalation of aerosols that interfere with the LS may induce a toxic response and, as a part of the safety assessment of chemicals and inhaled medicines, it may be relevant to study their impact on LS function. Here, we present a novel in vitro method, based on the constrained drop surfactometer, to study LS functionality after aerosol exposure. The applicability of the method was investigated using three inhaled asthma medicines, micronized lactose, a pharmaceutical excipient used in inhaled medication, and micronized albumin, a known inhibitor of surfactant function. The surfactometer was modified to allow particles mixed in air to flow through the chamber holding the surfactant drop. The deposited dose was measured with a custom-built quartz crystal microbalance. The alterations allowed the study of continuously increasing quantified doses of particles, allowing determination of the dose of particles that affects the LS function. The tested pharmaceuticals did not inhibit the function of a model LS even at extreme doses--neither did lactose. Micronized albumin, however, impaired surfactant function. The method can discriminate between safe inhaled aerosols--as exemplified by the approved inhaled medicines and the pharmaceutical excipient lactose--and albumin known to impair lung functionality by inhibiting LS function.

  12. After Detection: The Improved Accuracy of Lung Cancer Assessment Using Radiologic Computer-aided Diagnosis.

    Science.gov (United States)

    Amir, Guy J; Lehmann, Harold P

    2016-02-01

    The aim of this study was to evaluate the improved accuracy of radiologic assessment of lung cancer afforded by computer-aided diagnosis (CADx). Inclusion/exclusion criteria were formulated, and a systematic inquiry of research databases was conducted. Following title and abstract review, an in-depth review of 149 surviving articles was performed with accepted articles undergoing a Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-based quality review and data abstraction. A total of 14 articles, representing 1868 scans, passed the review. Increases in the receiver operating characteristic (ROC) area under the curve of .8 or higher were seen in all nine studies that reported it, except for one that employed subspecialized radiologists. This systematic review demonstrated improved accuracy of lung cancer assessment using CADx over manual review, in eight high-quality observer-performance studies. The improved accuracy afforded by radiologic lung-CADx suggests the need to explore its use in screening and regular clinical workflow. Copyright © 2015 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  13. Urban air carcinogens and their effects on health

    Energy Technology Data Exchange (ETDEWEB)

    Lechner, J.F.

    1994-11-01

    Airborne carcinogens may be relevant especially in metropolitan regions with extreme smog as a primary cause of lung cancer. Lung cancer is most common in urban environs and the incidence directly correlates with the size of the city. In addition, several, but not all formal epidemiological studies also suggest a positive correlation between lung cancer incidence and the intensity of air pollution exposure. There is further support for a role of air pollution; as of 1993, 4.4% of all of the bronchogenic adenocarcinoma cancer cases among Mexicans living in industrialized cities are under 40 years of age. It is plausible that chronic inhalation of automobile combustion products, factory emissions, and/or radon is at least partially responsible for the higher incidence of lung cancer exemplified by the never-smoking urban residents. The exceptionally high incidence of lung cancer cases among never-smokers living in highly industrialized Mexican cities offers a unique opportunity to use molecular epidemiology to test whether chronic inhalation of atmospheric pollutants increases the risk for this disease. Overall, the analysis of the genetic alterations in two cancer genes, and possibly the hprt locus should give new insight as to whether the urban never-smokers developed their cancers because of exposure to environmental pollutants.

  14. Mycotoxins as human carcinogens-the IARC Monographs classification.

    Science.gov (United States)

    Ostry, Vladimir; Malir, Frantisek; Toman, Jakub; Grosse, Yann

    2017-02-01

    Humans are constantly exposed to mycotoxins (e.g. aflatoxins, ochratoxins), mainly via food intake of plant and animal origin. The health risks stemming from mycotoxins may result from their toxicity, in particular their carcinogenicity. In order to prevent these risks, the International Agency for Research on Cancer (IARC) in Lyon (France)-through its IARC Monographs programme-has performed the carcinogenic hazard assessment of some mycotoxins in humans, on the basis of epidemiological data, studies of cancer in experimental animals and mechanistic studies. The present article summarizes the carcinogenic hazard assessments of those mycotoxins, especially aflatoxins (aflatoxin B1, B2, G1, G2 and M1), fumonisins (fumonisin B1 and B2) and ochratoxin A (OTA). New information regarding the genotoxicity of OTA (formation of OTA-DNA adducts), the role of OTA in oxidative stress and the identification of epigenetic factors involved in OTA carcinogenesis-should they indeed provide strong evidence that OTA carcinogenicity is mediated by a mechanism that also operates in humans-could lead to the reclassification of OTA.

  15. Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish.

    Science.gov (United States)

    Lin, Chun-Hung; Chou, Pei-Hsin; Chen, Pei-Jen

    2014-07-30

    Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish populations in the aquatic environment. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. A computational method for the identification of new candidate carcinogenic and non-carcinogenic chemicals.

    Science.gov (United States)

    Chen, Lei; Chu, Chen; Lu, Jing; Kong, Xiangyin; Huang, Tao; Cai, Yu-Dong

    2015-09-01

    Cancer is one of the leading causes of human death. Based on current knowledge, one of the causes of cancer is exposure to toxic chemical compounds, including radioactive compounds, dioxin, and arsenic. The identification of new carcinogenic chemicals may warn us of potential danger and help to identify new ways to prevent cancer. In this study, a computational method was proposed to identify potential carcinogenic chemicals, as well as non-carcinogenic chemicals. According to the current validated carcinogenic and non-carcinogenic chemicals from the CPDB (Carcinogenic Potency Database), the candidate chemicals were searched in a weighted chemical network constructed according to chemical-chemical interactions. Then, the obtained candidate chemicals were further selected by a randomization test and information on chemical interactions and structures. The analyses identified several candidate carcinogenic chemicals, while those candidates identified as non-carcinogenic were supported by a literature search. In addition, several candidate carcinogenic/non-carcinogenic chemicals exhibit structural dissimilarity with validated carcinogenic/non-carcinogenic chemicals.

  17. Regional anisotropy of airspace orientation in the lung as assessed with hyperpolarized helium-3 diffusion MRI.

    Science.gov (United States)

    Komlosi, Peter; Altes, Talissa A; Qing, Kun; Mooney, Karen E; Miller, G Wilson; Mata, Jaime F; de Lange, Eduard E; Tobias, William A; Cates, Gordon D; Brookeman, James R; Mugler, John P

    2015-12-01

    To evaluate regional anisotropy of lung-airspace orientation by assessing the dependence of helium-3 ((3) He) apparent diffusion coefficient (ADC) values on the direction of diffusion sensitization at two field strengths. Hyperpolarized (3) He diffusion-weighted magnetic resonance imaging (MRI) of the lung was performed at 0.43T and 1.5T in 12 healthy volunteers. A gradient-echo pulse sequence was used with a bipolar diffusion-sensitization gradient applied separately along three orthogonal directions. ADC maps, median ADC values, and signal-to-noise ratios were calculated from the diffusion-weighted images. Two readers scored the ADC maps for increased values at lung margins, major fissures, or within focal central regions. ADC values were found to depend on the direction of diffusion sensitization (P apex and base (9 of 12), and along the major fissure (8 of 12), for craniocaudal diffusion sensitization; and at the most anterior and posterior lung (10 of 12) for anteroposterior diffusion sensitization. Median ADC values at 0.43T (0.201 ± 0.017, left-right; 0.193 ± 0.019, craniocaudal; and 0.187 ± 0.017 cm(2) /s, anteroposterior) were slightly lower than those at 1.5T (0.205 ± 0.017, 0.197 ± 0.017 and 0.194 ± 0.016 cm(2) /s, respectively; P lung-airspace orientation, including that associated with preferential orientation of terminal airways near pleural surfaces. © 2015 Wiley Periodicals, Inc.

  18. [Assessment of nutritional status of patients candidates for lung resection by 2 methods].

    Science.gov (United States)

    Carnero Gregorio, M; Obeso Carillo, G A; Durán Toconas, J C; Villaverde Taboada, C; García-Mayor García, R V; Cañizares Carretero, M A; Pérez Méndez, L F

    2012-01-01

    It is important to determine the nutritional status of an individual that may be submitted to a surgical intervention since it has been shown a relationship between nutritional status impairments and the incidence of complications. We present the data from a study comparing two nutritional assessment methods. To study the rate of hyponutrition in patients candidates to lung resection in southern Galicia, and to determine if there were significant differences in the use of 2 different nutritional assessment methods. 200 patients participated in this study: 144 males (aged 29-83 years) and 56 females (aged 20-80 years). All of them were assessed for their nutritional status according to Chang's method and we also performed a patient-generated global subjective assessment (PG-GSA) according to the SENBA working group protocol. There is agreement between the 2 methods in assessing 122 patients as having "good nutritional status". There are two cases with agreement between both methods in the diagnosis of "moderate hyponutrition or risk for hyponutrition". No case of "severe hyponutrition" is diagnosed by the Chang's method. We found statistically significant differences between the observations obtained with the two methods. The Chang's method performed more accurately than the PG-GSA, so that we believe it should be the first choice method for the preoperative nutritional assessment of patients candidate to a lung resection.

  19. Bulky carcinogen-DNA adducts and exposure to environmental and occupational sources of polycyclic aromatic hydrocarbons. Influence of susceptibility genotypes on adduct level

    Energy Technology Data Exchange (ETDEWEB)

    Sabro Nielsen, P.

    1996-12-31

    PAH exposure, whether it is of occupational or environmental origin, is thought to result in an elevated risk of cancer especially in the lungs. DNA damage is considered an important step in the carcinogenic effect of PAH. Hence, methods that elucidate the steps in the carcinogenic process are important to understand the action of PAH. It may prove useful in the exposure assessment and in combination with classical epidemiological methods give better basis for risk estimation. The objective in this thesis was to evaluate the feasibility of the {sup 32}P-postlabeling method to detect carcinogen-DNA adducts for assessing exposure to DNA damaging compounds in different occupationally and environmentally exposed groups. The studies included groups, that have an elevated cancer risk due to occupational exposure to PAH. Exposure levels were supposed to be relatively low according to reports on occupational and environmental air quality programs. Another aim was to evaluate the influence of polymorphisms in metabolizing enzyme genes on DNA adduct levels. A third objective was to establish some kind of baseline DNA adduct level for individuals with supposed low exposure, and compare it to the more exposed groups. A fourth aim in these studies was to examine if biomarkers of genotoxic exposure could be useful in epidemiological studies to identify groups at risk and thereby contribute with better exposure estimates in the study of PAH related cancer risk. (EG).

  20. Prognostic value of residual pulmonary congestion at discharge assessed by lung ultrasound imaging in heart failure.

    Science.gov (United States)

    Coiro, Stefano; Rossignol, Patrick; Ambrosio, Giuseppe; Carluccio, Erberto; Alunni, Gianfranco; Murrone, Adriano; Tritto, Isabella; Zannad, Faiez; Girerd, Nicolas

    2015-11-01

    Residual pulmonary congestion at discharge is associated with poor prognosis in heart failure (HF), but its quantification through physical examination is challenging. Ultrasound imaging of lung comets (B-lines) could improve congestion evaluation. The aim of this study was to assess the short-term prognostic value of B-lines after discharge from HF hospitalisation compared with other indices of haemodynamic congestion (BNP, E/e', and inferior vena cava diameter) or clinical status (NYHA class). Sixty consecutive HF inpatients underwent clinical examination, echocardiography, and lung ultrasound at discharge, independently of, and in addition to routine management by the attending physicians. The median B-line count was 8.5 (5-34). Three-month event-free survival for the primary endpoint (all-cause death or HF hospitalisation) was 27 ± 10% in patients with ≥30 B-lines and 88 ± 5% in those with pulmonary congestion at discharge, as assessed by a B-line count ≥30, is a strong predictor of outcome. Lung ultrasonography may represent a useful tool to identify and monitor congestion and optimize therapy during and/or after hospitalisation for HF, which should be further validated in multicentre studies. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

  1. Assessment of DNA Binding and Oxidative DNA Damage by Acrylonitrile in Two Rat Target Tissues of Carcinogenicity: Implications for the Mechanism of Action.

    Science.gov (United States)

    Williams, Gary M; Kobets, Tetyana; Duan, Jian-Dong; Iatropoulos, Michael J

    2017-07-17

    Exposure to acrylonitrile induces formation of tumors at multiple sites in rats, with females being more sensitive. The present study assessed possible mechanisms of acrylonitrile tumorigenicity, covalent DNA binding, DNA breakage, and oxidative DNA damage, in two target tissues, the brain and Zymbal's glands, of sensitive female Fischer (F344) and Sprague-Dawley (SD) rats. One group received acrylonitrile in drinking water at 100 ppm for 28 days. Two other groups were administered either acrylonitrile in drinking water at 100 ppm or drinking water alone for 27 days, followed by a single oral gavage dose of 11 mg/kg bw (14)C-acrylonitrile on day 28. A positive control group received a single dose of 5 mg/kg bw of 7-(14)C-benzo[a]pyrene, on day 27 following the administration of drinking water for 26 days. Using liquid scintillation counting, no association of radiolabeled acrylonitrile with brain DNA was found. In accelerator mass spectrometry analysis, the association of (14)C of acrylonitrile with DNA in brains was detected and was similar in both strains, which may reflect acrylonitrile binding to protein as well as to DNA. Nucleotide (32)P-postlabeling assay analysis of brain samples from rats of both strains yielded no evidence of acrylonitrile DNA adducts. Negative conventional comet assay results indicate the absence of direct DNA strand breaks in the brain and Zymbal's gland in both strains of rats dosed with acrylonitrile. In both rat strains, positive results in an enhanced comet assay were found only in brain samples digested with formamidopyrimidine-DNA glycosylase but not with human 8-hydroxyguanine-DNA glycosylase, indicating possible oxidative DNA damage, other than 8-oxodG formation. In conclusion, definitive evidence of DNA binding of acrylonitrile in the brain and Zymbal's gland was not obtained under the test conditions. A role for oxidative stress in tumorigenesis in the brain but not Zymbal's gland may exist.

  2. Comparison of Lung Clearance Index and Magnetic Resonance Imaging for Assessment of Lung Disease in Children with Cystic Fibrosis.

    Science.gov (United States)

    Stahl, Mirjam; Wielpütz, Mark O; Graeber, Simon Y; Joachim, Cornelia; Sommerburg, Olaf; Kauczor, Hans-Ulrich; Puderbach, Michael; Eichinger, Monika; Mall, Marcus A

    2017-02-01

    Early onset and progression of lung disease in children with cystic fibrosis (CF) indicates that sensitive noninvasive outcome measures are needed for diagnostic monitoring and early intervention clinical trials. The lung clearance index (LCI) and chest magnetic resonance imaging (MRI) were shown to detect early lung disease in CF; however, the relationship between the two measures remains unknown. To correlate the LCI with abnormalities detected by MRI and compare the sensitivity of the two techniques to detect responses to therapy for pulmonary exacerbations in children with CF. LCI determined by age-adapted multiple breath washout techniques and MRI studies were performed in 97 clinically stable children with CF across the pediatric age range (0.2-21.1 yr). Furthermore, LCI (n = 26) or MRI (n = 10) were performed at the time of pulmonary exacerbation and after antibiotic therapy. MRI was evaluated using a dedicated morphofunctional score. The LCI correlated with the global MRI score as well as MRI-defined airway wall abnormalities, mucus plugging, and abnormal lung perfusion in infants and toddlers (P disease heterogeneity, including regional mucus plugging associated with abnormal lung perfusion in early CF lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 02270476).

  3. DNA methylation, heterochromatin and epigenetic carcinogens.

    Science.gov (United States)

    Klein, C B; Costa, M

    1997-04-01

    This paper will explore emerging concepts related to alternative carcinogenic mechanisms of 'non-mutagenic,' and hence epigenetic, carcinogens that may heritably alter DNA methylation without changing the underlying DNA sequence. In this review, we will touch on the basic concepts of DNA methylation, and will elaborate in greater detail on related topics including chromatin condensation, and heterochromatin spreading that is well known to induce gene silencing by position effect variegation in Drosophila and other species. Data from our model transgenic G12 cell system will be presented to support our hypothesis that certain carcinogens, such as nickel, may be carcinogenic not primarily because of their overt mutability, but rather as the result of their ability to promote DNA hypermethylation of important cancer-related genes. We will conclude with a discussion of the broader relevance of our findings and its application to other so-called 'epigenetic' carcinogens.

  4. Lung cancer in women

    Science.gov (United States)

    Barrera-Rodriguez, Raúl; Morales-Fuentes, Jorge

    2012-01-01

    Recent biological advances in tumor research provide clear evidence that lung cancer in females is different from that in males. These differences appear to have a direct impact on the clinical presentation, histology, and outcomes of lung cancer. Women are more likely to present with lung adenocarcinoma, tend to receive a diagnosis at an earlier age, and are more likely to be diagnosed with localized disease. Women may also be more predisposed to molecular aberrations resulting from the carcinogenic effects of tobacco, but do not appear to be more susceptible than men to developing lung cancer. The gender differences found in female lung cancer make it mandatory that gender stratification is used in clinical trials in order to improve the survival rates of patients with lung cancer. PMID:28210127

  5. Accuracy and precision of perfusion lung scintigraphy versus {sup 133}Xe-radiospirometry for preoperative pulmonary functional assessment of patients with lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mariano-Goulart, Denis [Montpellier University Hospital, Department of Nuclear Medicine, Montpellier (France); Service Central de Medecine Nucleaire, CHU Lapeyronie, Montpellier Cedex 5 (France); Barbotte, Eric; Basurko, Celia [Montpellier University Hospital, Department of Statistics and Epidemiology, Montpellier (France); Comte, F.; Rossi, Michel [Montpellier University Hospital, Department of Nuclear Medicine, Montpellier (France)

    2006-09-15

    Purpose: This study sought to determine whether {sup 133}Xe-radiospirometry (XRS) successfully selects patients able to undergo lung resection without postoperative respiratory complications and whether perfusion lung scintigraphy (PLS) is likely to provide a similar selection of patients for certain tumour stages. Methods: Two hundred and eighty-four patients with resectable lung cancer underwent preoperative assessment of postoperative forced expiratory volume in 1 s (FEV{sub 1}) by XRS and PLS. Correlations, Bland and Altman analysis and contingency tables were used to analyse the difference between the two predictive techniques. One hundred and sixty patients underwent lung resection on the basis of XRS preoperative testing only. None of them developed respiratory insufficiency. Despite a close correlation, the limits of agreement between predicted FEV{sub 1} by XRS and PLS exceeded {+-}0.3 l/s. For tumour stages T1Nx and T2N0, PLS underestimated postoperative FEV{sub 1} whereas it overestimated this parameter for stage III. XRS accurately selects patients able to undergo lung resection without postoperative pulmonary insufficiency. The agreement between XRS and PLS is unacceptable. When only PLS is available, higher thresholds for patients with stage III cancers and lower thresholds for those with stage I cancers should be used to decide on operability. (orig.)

  6. Carcinogenic mechanisms of endometrial cancer: involvement of genetics and epigenetics.

    Science.gov (United States)

    Banno, Kouji; Yanokura, Megumi; Iida, Miho; Masuda, Kenta; Aoki, Daisuke

    2014-08-01

    Endometrial cancer is increasing worldwide and the number of patients with this disease is likely to continue to grow, including younger patients. Many endometrial cancers show estrogen-dependent proliferation, but the carcinogenic mechanisms are unknown or not completely explained beyond mutations of single oncogenes and tumor suppressor genes. Possible carcinogenic mechanisms include imbalance between endometrial proliferation by unopposed estrogen and the mismatch repair (MMR) system; hypermethylation of the MMR gene hMLH1; mutation of PTEN, β-catenin and K-ras genes in type I endometrial cancer and of HER-2/neu and p53 genes in type II endometrial cancer; hypermethylation of SPRY2, RASSF1A, RSK4, CHFR and CDH1; and methylation of tumor suppressor microRNAs, including miR-124, miR-126, miR-137, miR-491, miR-129-2 and miR-152. Thus, it is likely that the carcinogenic mechanisms of endometrial cancer involve both genetic and epigenetic changes. Mutations and methylation of MMR genes induce various oncogenic changes that cause carcinogenesis, and both MMR mutation in germ cells and methylation patterns may be inherited over generations and cause familial tumorigenesis. Determination of the detailed carcinogenic mechanisms will be useful for prevention and diagnosis of endometrial cancer, risk assessment, and development of new treatment strategies targeting MMR genes. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  7. The Vancouver Lung Cancer Risk Prediction Model: Assessment by Using a Subset of the National Lung Screening Trial Cohort.

    Science.gov (United States)

    White, Charles S; Dharaiya, Ekta; Campbell, Erin; Boroczky, Lilla

    2017-04-01

    Purpose To assess the likelihood of malignancy among a subset of nodules in the National Lung Screening Trial (NLST) by using a risk calculator based on nodule and patient characteristics. Materials and Methods All authors received approval for use of NLST data. An institutional review board exemption and a waiver for informed consent were granted to the author with an academic appointment. Nodule characteristics and patient attributes with regard to benign and malignant nodules in the NLST were applied to a nodule risk calculator from a group in Vancouver, Canada. Patient populations and their nodule characteristics were compared between the NLST and Vancouver cohorts. Multiple thresholds were tested to distinguish benign nodules from malignant nodules. An optimized threshold value was used to determine positive and negative predictive values, and a full logistic regression model was applied to the NLST data set. Results Sufficient data were available for 4431 nodules (4315 benign nodules and 116 malignant nodules) from the NLST data set. The NLST and Vancouver data sets differed in that the former included fewer nodules per study, fewer nonsolid nodules, and more nodule spiculation and emphysema. A composite risk score threshold of 10% was determined to be optimal, demonstrating sensitivity, specificity, positive predictive value, and negative predictive value of 85.3%, 93.9%, 27.4%, and 99.6%, respectively. The receiver operating characteristic curve for the full regression model applied to the NLST database demonstrated an area under the receiver operating characteristic curve of 0.963 (95% confidence interval: 0.945, 0.974). Conclusion Application of an NLST data subset to the Vancouver risk calculator yielded a high discriminant value, which supports the use of a risk calculator method as a valuable approach to distinguish between benign and malignant nodules. © RSNA, 2016 Online supplemental material is available for this article.

  8. Ventilation/Perfusion Positron Emission Tomography--Based Assessment of Radiation Injury to Lung.

    Science.gov (United States)

    Siva, Shankar; Hardcastle, Nicholas; Kron, Tomas; Bressel, Mathias; Callahan, Jason; MacManus, Michael P; Shaw, Mark; Plumridge, Nikki; Hicks, Rodney J; Steinfort, Daniel; Ball, David L; Hofman, Michael S

    2015-10-01

    To investigate (68)Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r(2)=0.99, Pfit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET/CT imaging. These findings may inform future studies of functional lung avoidance using V/Q PET/CT. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

  10. Dynamic four-dimensional computed tomography for preoperative assessment of lung cancer invasion into adjacent structures†.

    Science.gov (United States)

    Choong, Cliff K C; Pasricha, Sundeep S; Li, Xun; Briggs, Peter; Ramdave, Shakher; Crossett, Marcus; Troupis, John M

    2015-02-01

    The 320-slice computed tomography (CT) provides three-dimensional and dynamic imaging resulting in the ability to assess motion analysis between two adjacent structures (the fourth dimension). Differential movements between two adjacent structures would indicate that there is no fixation between the two structures. Eight patients with non-small-cell lung cancers located adjacent to vital structures (e.g. the great vessels) (n = 4), mediastinum (n = 1) or chest wall (n = 3) where conventional CT was unable to exclude local invasion underwent dynamic four-dimensional (4D) CT assessment. In 3 patients, the lung tumour was abutting the chest wall and 1 patient had tumour abutting the mediastinum. The remaining patients included a patient with a large 14-cm left lower lobe cancer abutting the descending thoracic aorta who had previous pleurodesis; a patient with an apical right upper lobe 6-cm cancer with static imaging appearances suggestive of tumour invasion into the apex, the mediastinal surface and superior vena cava (SVC); a patient with a 3.5-cm cancer which had a broad 2.5-cm base abutting the distal aortic arch and a patient with a 14-cm left upper lobe cancer abutting the aortic arch, descending thoracic aorta and chest wall. Differential movements between the tumour and adjacent structure on 4D CT were considered indicative of the absence of frank invasion. Dynamic 4D imaging revealed differential movements between the tumour and the adjacent structures in 7 cases, suggesting the absence of overt malignant invasion. Intraoperative assessments confirmed the findings. In 1 case, a small area of fixation seen on dynamic CT corresponded intraoperatively to superficial invasion of the adventitia of the SVC. Dynamic 4D 320-slice CT is useful in the preoperative assessment of the direct invasion of lung cancer into adjacent structures and hence its resectability. © The Author 2014. Published by Oxford University Press on behalf of the European Association for

  11. In vitro assessment of Macleaya cordata crude extract bioactivity and anticancer properties in normal and cancerous human lung cells.

    Science.gov (United States)

    Liu, Min; Lin, Yu-ling; Chen, Xuan-Ren; Liao, Chi-Cheng; Poo, Wak-Kim

    2013-09-01

    The purpose of this study is to assess the bioactivity and anticancer properties of Macleaya cordata crude extract in vitro using normal fetal lung fibroblast MRC5 and adenocarcinomic epithelial cell A549 as model systems,. Treatment of extract induced cell detachment, rounding, and irregularity in shape, in both normal and adenocarcinomic human lung cells, in accompanied of significant reduction in cell proliferation. The data indicated that necrosis appeared to be involved in compromising cell growth in both types of lung cells since membrane permeability and cell granularity were elevated. Although apoptosis was evident, the responses were differential in normal and diseased lung cells. Viability of treated MRC5 cells was reduced in a dose-dependent manner, demonstrating that the normal lung cells are sensitive to the extract. Surprisingly, A549 viability was slightly elevated in response to extract exposure at low concentration, implying that cells survived were metabolically active; the viability was reduced accordingly to treatment at higher concentrations. The present findings demonstrate that the crude extract of M. cordata contains agents affecting the functioning of normal and diseased lung cells in vitro. The observed cytotoxic effects against adenocarcinomic lung cells validate the potential of using M. cordata as herbal intervention in combined with conventional chemotherapy for lung cancer treatment. Copyright © 2012 Elsevier GmbH. All rights reserved.

  12. Assessing regional lung mechanics by combining electrical impedance tomography and forced oscillation technique.

    Science.gov (United States)

    Ngo, Chuong; Spagnesi, Sarah; Munoz, Carlos; Lehmann, Sylvia; Vollmer, Thomas; Misgeld, Berno; Leonhardt, Steffen

    2017-08-29

    There is a lack of noninvasive pulmonary function tests which can assess regional information of the lungs. Electrical impedance tomography (EIT) is a radiation-free, non-invasive real-time imaging that provides regional information of ventilation volume regarding the measurement of electrical impedance distribution. Forced oscillation technique (FOT) is a pulmonary function test which is based on the measurement of respiratory mechanical impedance over a frequency range. In this article, we introduce a new measurement approach by combining FOT and EIT, named the oscillatory electrical impedance tomography (oEIT). Our oEIT measurement system consists of a valve-based FOT device, an EIT device, pressure and flow sensors, and a computer fusing the data streams. Measurements were performed on five healthy volunteers at the frequencies 3, 4, 5, 6, 7, 8, 10, 15, and 20 Hz. The measurements suggest that the combination of FOT and EIT is a promising approach. High frequency responses are visible in the derivative of the global impedance index ΔZeit(t,fos). $\\Delta {Z_{{\\text{eit}}}}(t,{f_{{\\text{os}}}}).$ The oEIT signals consist of three main components: forced oscillation, spontaneous breathing, and heart activity. The amplitude of the oscillation component decreases with increasing frequency. The band-pass filtered oEIT signal might be a new tool in regional lung function diagnostics, since local responses to high frequency perturbation could be distinguished between different lung regions.

  13. Assessment of a New E-Learning System on Thorax, Trachea, and Lung Ultrasound

    Directory of Open Access Journals (Sweden)

    Colleen Cuca

    2013-01-01

    Full Text Available Background. Lung ultrasound has become an emerging tool in acute and critical care medicine. Combined theoretical and hands-on training has been required to teach ultrasound diagnostics. Current computer technology allows for display, explanation, and animation of information in a remote-learning environment. Objective. Development and assessment of an e-learning program for lung ultrasound. Methods. An interactive online tutorial was created. A prospective learning success study was conducted with medical students using a multiple-choice test (Trial A. This e-learning program was used as preparation for a certified course followed by an evaluation of trained doctors (Trial B by linear analogue scales. Pretests were compared with postcourse tests and sustainability tests as well as a posttest of a one-day custom classroom training. Results. In Trial A, during the learning success study (n=29, the increase of correct answers was 11.7 to 17/20 in the post-test and to 16.6/20 in the sustainability test (relative change 45.1%, P<0.0001. E-learning almost equalled scores of classroom-based training regarding gain and retention of factual knowledge. In Trial B, nineteen participating doctors found a 79.5% increase of knowledge (median, 95% CI: 69%; 88%. Conclusion. The basics of lung ultrasound can be taught in a highly effective manner using e-learning.

  14. Assessment of a new e-learning system on thorax, trachea, and lung ultrasound.

    Science.gov (United States)

    Cuca, Colleen; Scheiermann, Patrick; Hempel, Dorothea; Via, Gabriele; Seibel, Armin; Barth, Magnus; Hirche, Tim O; Walcher, Felix; Breitkreutz, Raoul

    2013-01-01

    Background. Lung ultrasound has become an emerging tool in acute and critical care medicine. Combined theoretical and hands-on training has been required to teach ultrasound diagnostics. Current computer technology allows for display, explanation, and animation of information in a remote-learning environment. Objective. Development and assessment of an e-learning program for lung ultrasound. Methods. An interactive online tutorial was created. A prospective learning success study was conducted with medical students using a multiple-choice test (Trial A). This e-learning program was used as preparation for a certified course followed by an evaluation of trained doctors (Trial B) by linear analogue scales. Pretests were compared with postcourse tests and sustainability tests as well as a posttest of a one-day custom classroom training. Results. In Trial A, during the learning success study (n = 29), the increase of correct answers was 11.7 to 17/20 in the post-test and to 16.6/20 in the sustainability test (relative change 45.1%, P < 0.0001). E-learning almost equalled scores of classroom-based training regarding gain and retention of factual knowledge. In Trial B, nineteen participating doctors found a 79.5% increase of knowledge (median, 95% CI: 69%; 88%). Conclusion. The basics of lung ultrasound can be taught in a highly effective manner using e-learning.

  15. Assessment of a New E-Learning System on Thorax, Trachea, and Lung Ultrasound

    Science.gov (United States)

    Scheiermann, Patrick; Via, Gabriele; Barth, Magnus; Hirche, Tim O.; Walcher, Felix; Breitkreutz, Raoul

    2013-01-01

    Background. Lung ultrasound has become an emerging tool in acute and critical care medicine. Combined theoretical and hands-on training has been required to teach ultrasound diagnostics. Current computer technology allows for display, explanation, and animation of information in a remote-learning environment. Objective. Development and assessment of an e-learning program for lung ultrasound. Methods. An interactive online tutorial was created. A prospective learning success study was conducted with medical students using a multiple-choice test (Trial A). This e-learning program was used as preparation for a certified course followed by an evaluation of trained doctors (Trial B) by linear analogue scales. Pretests were compared with postcourse tests and sustainability tests as well as a posttest of a one-day custom classroom training. Results. In Trial A, during the learning success study (n = 29), the increase of correct answers was 11.7 to 17/20 in the post-test and to 16.6/20 in the sustainability test (relative change 45.1%, P E-learning almost equalled scores of classroom-based training regarding gain and retention of factual knowledge. In Trial B, nineteen participating doctors found a 79.5% increase of knowledge (median, 95% CI: 69%; 88%). Conclusion. The basics of lung ultrasound can be taught in a highly effective manner using e-learning. PMID:24324889

  16. Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies.

    Science.gov (United States)

    Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

    2015-03-01

    Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans.

  17. Assessment of extravascular lung water and cardiac function in trimix SCUBA diving.

    Science.gov (United States)

    Marinovic, Jasna; Ljubkovic, Marko; Obad, Ante; Breskovic, Toni; Salamunic, Ilza; Denoble, Petar J; Dujic, Zeljko

    2010-06-01

    An increasing number of recreational self-contained underwater breathing apparatus (SCUBA) divers use trimix of oxygen, helium, and nitrogen for dives deeper than 60 m of sea water. Although it was seldom linked to the development of pulmonary edema, whether SCUBA diving affects the extravascular lung water (EVLW) accumulation is largely unexplored. Seven divers performed six dives on consecutive days using compressed gas mixture of oxygen, helium, and nitrogen (trimix), with diving depths ranging from 55 to 80 m. The echocardiographic parameters (bubble grade, lung comets, mean pulmonary arterial pressure (PAP), and left ventricular function) and the blood levels of the N-terminal part of pro-brain natriuretic peptide (NT-proBNP) were assessed before and after each dive. Venous gas bubbling was detected after each dive with mean probability of decompression sickness ranging from 1.77% to 3.12%. After each dive, several ultrasonographically detected lung comets rose significantly, which was paralleled by increased pulmonary artery pressure (PAP) and decreased left ventricular contractility (reduced ejection fraction at higher end-systolic and end-diastolic volumes) as well as the elevated NT-proBNP. The number of ultrasound lung comets and mean PAP did not return to baseline values after each dive. This is the first report that asymptomatic SCUBA dives are associated with accumulation of EVLW with concomitant increase in PAP, diminished left ventricular contractility, and increased release of NT-proBNP, suggesting a significant cardiopulmonary strain. EVLW and PAP did not return to baseline during repetitive dives, indicating possible cumulative effect with increasing the risk for pulmonary edema.

  18. Capnodynamic assessment of effective lung volume during cardiac output manipulations in a porcine model.

    Science.gov (United States)

    Hällsjö Sander, Caroline; Lönnqvist, Per-Arne; Hallbäck, Magnus; Sipmann, Fernando Suarez; Wallin, Mats; Oldner, Anders; Björne, Håkan

    2016-12-01

    A capnodynamic calculation of effective pulmonary blood flow includes a lung volume factor (ELV) that has to be estimated to solve the mathematical equation. In previous studies ELV correlated to reference methods for functional residual capacity (FRC). The aim was to evaluate the stability of ELV during significant manipulations of cardiac output (CO) and assess the agreement for absolute values and trending capacity during PEEP changes at different lung conditions. Ten pigs were included. Alterations of alveolar carbon dioxide were induced by cyclic reoccurring inspiratory holds. The Sulphur hexafluoride technique for FRC measurements was used as reference. Cardiac output was altered by preload reduction and inotropic stimulation at PEEP 5 and 12 cmH2O both in normal lung conditions and after repeated lung lavages. ELV at baseline PEEP 5 was [mean (SD)], 810 (163) mL and decreased to 400 (42) mL after lavage. ELV was not significantly affected by CO alterations within the same PEEP level. In relation to FRC the overall bias (limits of agreement) was -35 (-271 to 201) mL, and percentage error 36 %. A small difference between ELV and FRC was seen at PEEP 5 cmH2O before lavage and at PEEP 12 cmH2O after lavage. ELV trending capability between PEEP steps, showed a concordance rate of 100 %. ELV was closely related to FRC and remained stable during significant changes in CO. The trending capability was excellent both before and after surfactant depletion.

  19. Accuracy of forced oscillation technique to assess lung function in geriatric COPD population

    Directory of Open Access Journals (Sweden)

    Tse HN

    2016-05-01

    Full Text Available Hoi Nam Tse,1 Cee Zhung Steven Tseng,1 King Ying Wong,2 Kwok Sang Yee,2 Lai Yun Ng1 1Medical and Geriatric Department, Respiratory Unit, Kwong Wah Hospital, 2Department of Tuberculosis and Chest Unit, Wong Tai Sin Hospital, Hong Kong, People’s Republic of China Introduction: Performing lung function test in geriatric patients has never been an easy task. With well-established evidence indicating impaired small airway function and air trapping in patients with geriatric COPD, utilizing forced oscillation technique (FOT as a supplementary tool may aid in the assessment of lung function in this population. Aims: To study the use of FOT in the assessment of airflow limitation and air trapping in geriatric COPD patients. Study design: A cross-sectional study in a public hospital in Hong Kong. ClinicalTrials.gov ID: NCT01553812. Methods: Geriatric patients who had spirometry-diagnosed COPD were recruited, with both FOT and plethysmography performed. “Resistance” and “reactance” FOT parameters were compared to plethysmography for the assessment of air trapping and airflow limitation. Results: In total, 158 COPD subjects with a mean age of 71.9±0.7 years and percentage of forced expiratory volume in 1 second of 53.4±1.7 L were recruited. FOT values had a good correlation (r=0.4–0.7 to spirometric data. In general, X values (reactance were better than R values (resistance, showing a higher correlation with spirometric data in airflow limitation (r=0.07–0.49 vs 0.61–0.67, small airway (r=0.05–0.48 vs 0.56–0.65, and lung volume (r=0.12–0.29 vs 0.43–0.49. In addition, resonance frequency (Fres and frequency dependence (FDep could well identify the severe type (percentage of forced expiratory volume in 1 second <50% of COPD with high sensitivity (0.76, 0.71 and specificity (0.72, 0.64 (area under the curve: 0.8 and 0.77, respectively. Moreover, X values could stratify different severities of air trapping, while R values could not

  20. Decision Tree of Occupational Lung Cancer Using Classification and Regression Analysis

    Directory of Open Access Journals (Sweden)

    Tae-Woo Kim

    2010-12-01

    Conclusion: We found that exposure to lung carcinogens, latency and smoking history were predictive factors of approval for occupational lung cancer. Further studies for work-relatedness of occupational disease are needed.

  1. sup 111 Indium-labeled neutrophil migration into the lungs of bleomycin-treated rabbits assessed noninvasively by external scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Haslett, C.; Shen, A.S.; Feldsien, D.C.; Allen, D.; Henson, P.M.; Cherniack, R.M. (National Jewish Center for Immunology and Respiratory Medicine, Denver, CO (USA))

    1989-09-01

    Factors controlling neutrophil migration into the lung are poorly understood, but their identification is important for our understanding of the pathogenesis of inflammatory lung diseases. Pulmonary inflammation is difficult to quantify, and neutrophils in tissues and BAL may not accurately represent cell migration. In this study, intravenously delivered pulses of rabbit neutrophils labeled with Indium-111 (111In-neutrophils) were used to monitor neutrophil migration into the lungs. Radioactivity quantified in the lung region of interest (ROI) of external gamma camera scintigrams recorded 24 h after intravenous 111In-neutrophil injection accurately reflected the actual neutrophil-associated lung tissue radioactivity. ROI radioactivity at 24 h also correlated closely with the percent of 111In-neutrophils that had migrated into lavageable air spaces, and this parameter therefore provided an index of total lung 111In-neutrophil migration. Using 24-h ROI radioactivity and percent of injected 111In-neutrophils recovered in BAL at 24 h as indices of neutrophil migration into the lung, it was found that intratracheal saline caused only a transient neutrophil migration, whereas 10 U/kg intratracheal bleomycin induced migration that persisted for as long as 3 wk. 111In-neutrophil migration into the lung, assessed by external scintigraphy, correlated with total neutrophils quantified in histologic sections (r = 0.71, p = 0.006). The data suggest that this approach will be valuable in investigating mechanisms controlling neutrophil migration in lung inflammation, and that 111In-neutrophil scintigraphy may provide a noninvasive index of total lung neutrophil load that might be useful in staging inflammation in patchy diseases such as idiopathic pulmonary fibrosis.

  2. Relevance of a Geriatric Assessment for Elderly Patients With Lung Cancer-A Systematic Review.

    Science.gov (United States)

    Schulkes, Karlijn J G; Hamaker, Marije E; van den Bos, Frederiek; van Elden, Leontine J R

    2016-09-01

    Lung cancer is predominantly a disease of the elderly: one half of all newly diagnosed patients will be > 70 years old. In the Netherlands, > 12,000 new cases are diagnosed annually. We sought to assemble all available evidence on the relevance of a geriatric assessment for lung cancer patients. A systematic Medline and Embase search was performed for studies in which a geriatric assessment was used to detect health issues or that had addressed the association between a baseline geriatric assessment (composed of ≥ 2 of the following domains: cognitive function, mood/depression, nutritional status, activities of daily living, instrumental activities of daily living, polypharmacy, objectively measured physical capacity, social support and frailty) and outcome. A total of 23 publications from 18 studies were included. The median age of patients was 76 years (range, 73-81 years). Despite generally good Eastern Cooperative Oncology Group performance status, the prevalence of geriatric impairments was high, with the median ranging from 29% for cognitive impairment to 70% for instrumental activities of daily living impairment. Objective physical capacity and nutritional status, as items of the geriatric assessment, had a consistent association with mortality. The information revealed by a geriatric assessment led to changes in oncologic treatment and nononcologic interventions. The present review has demonstrated that a geriatric assessment can detect multiple health issues not reflected in the Eastern Cooperative Oncology Group performance status. Impairments in geriatric domains have predictive value for mortality and appear to be associated with treatment completion. It would be useful to develop and validate an individualized treatment algorithm that includes these geriatric domains. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. 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

  4. Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline

    Directory of Open Access Journals (Sweden)

    Buonaguro Franco M

    2009-06-01

    Full Text Available Abstract Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV. Some HPV types, like HPV16 and HPV18, are clear and powerful carcinogens. However, the categorization of the most weakly carcinogenic HPV types is extremely challenging. The decisions are important for screening test and vaccine development. This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC Monographs Working Group to re-assess the carcinogenicity of different HPV types.

  5. Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline

    Science.gov (United States)

    Schiffman, Mark; Clifford, Gary; Buonaguro, Franco M

    2009-01-01

    Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV). Some HPV types, like HPV16 and HPV18, are clear and powerful carcinogens. However, the categorization of the most weakly carcinogenic HPV types is extremely challenging. The decisions are important for screening test and vaccine development. This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC) Monographs Working Group to re-assess the carcinogenicity of different HPV types. PMID:19486508

  6. Toxicity of Lunar Dust in Lungs Assessed by Examining Biomarkers in Exposed Mice

    Science.gov (United States)

    Lam, C.-W.; James, J. T.; Zeidler-Erdely, P. C.; Castranova, V.; Young, S. H.; Quan, C. L.; Khan-Mayberry, N.; Taylor, L. A.

    2009-01-01

    NASA plans to build an outpost on the Moon for prolonged human habitation and research. The lunar surface is covered by a layer of soil, of which the finest portion is highly reactive dust. NASA has invited NIOSH to collaboratively investigate the toxicity of lunar dust. Dust samples of respirable sizes were aerodynamically isolated from two lunar soil samples of different maturities (cosmic exposure ages) collected during the Apollo 16 mission. The lunar dust samples, titanium dioxide, or quartz, suspended in normal saline or in Survanta (a bovine lung surfactant), were given to groups of 5 mice (C-57 male) by intrapharyngeal aspiration at 1, 0.3, or 0.1 mg/mouse. The mice were euthanized 7 or 30 days later, and their lungs were lavaged to assess the toxicity biomarkers in bronchioalveolar lavage fluids. The acellular fractions were assayed for total proteins, lactate dehydrogenase activities, and cytokines; the cellular portions were assessed for total cell counts and cell differentials. Results from the high-dose groups showed that lunar dust, suspended in saline, was more toxic than TiO 2, but less toxic than quartz. Lunar dust particles aggregate and settle out rapidly in water or saline, but not in Survanta. Lunar dust suspended in Survanta manifested greater toxicity than lunar dust in saline. The increase in toxicity presumably was due to that Survanta gave a better particle dispersion in the lungs. The two lunar dust samples showed similar toxicity. The overall results showed that lunar dust is more toxic than TiO 2 but less toxic than quartz.

  7. Longitudinal assessment of lung function from infancy to childhood in patients with cystic fibrosis.

    Science.gov (United States)

    Harrison, Amy N; Regelmann, Warren E; Zirbes, Jacquelyn M; Milla, Carlos E

    2009-04-01

    Infant pulmonary function testing (IPFT) has become an important clinical tool for the evaluation of lung function in infants with Cystic Fibrosis (CF); however, it is still unclear whether lung function in infancy is predictive of lung function later in life. We hypothesized that measures of airflow obstruction by IPFT would correlate strongly with lung function by conventional spirometry later in childhood. A retrospective analysis was performed of all CF infants studied with IPFT at the University of Minnesota Children's Hospital between September 1994 and March 2003. A total of 41 patients underwent IPFT and had valid spirometry results available at age 6 or later. IPFT values, such as I:E ratio, respiratory rate, tidal volume, and T(ptef)/T(e), were calculated from tidal breathing loops. Passive respiratory system mechanics, which included C(rs), R(rs), and tau(rs), were measured by the single breath end-inspiratory occlusion technique. Forced expiratory flows, including V(max)FRC, FVC, FEF(50), and FEF(75), were obtained by rapid thoracic compression and included a full vital capacity maneuver by the multiple inflation method. FRC measurements were calculated from data obtained via nitrogen washout in a subset of patients. In addition, information on age at diagnosis and results of oropharyngeal (OP) cultures at diagnosis and on subsequent visits was recorded. Standard spirometry was performed in all patients starting at age 5. The first valid flow-volume loop after age six was selected for analysis. Significant correlations were observed for the R(rs) and the FEF(50) by IPFT and the FEV(1) and the FEF(25-75) by standard spirometry (r > 0.4 and P function. IPFT measurement of R(rs) in addition to forced expiratory flows may help select patients at the greatest risk of early lung function decline. This study supports the use of R(rs) as a surrogate variable to help assess the impact of early therapies in CF. (c) 2009 Wiley-Liss, Inc.

  8. Investigating the epigenetic effects of a prototype smoke-derived carcinogen in human cells.

    Directory of Open Access Journals (Sweden)

    Stella Tommasi

    Full Text Available Global loss of DNA methylation and locus/gene-specific gain of DNA methylation are two distinct hallmarks of carcinogenesis. Aberrant DNA methylation is implicated in smoking-related lung cancer. In this study, we have comprehensively investigated the modulation of DNA methylation consequent to chronic exposure to a prototype smoke-derived carcinogen, benzo[a]pyrene diol epoxide (B[a]PDE, in genomic regions of significance in lung cancer, in normal human cells. We have used a pulldown assay for enrichment of the CpG methylated fraction of cellular DNA combined with microarray platforms, followed by extensive validation through conventional bisulfite-based analysis. Here, we demonstrate strikingly similar patterns of DNA methylation in non-transformed B[a]PDE-treated cells vs control using high-throughput microarray-based DNA methylation profiling confirmed by conventional bisulfite-based DNA methylation analysis. The absence of aberrant DNA methylation in our model system within a timeframe that precedes cellular transformation suggests that following carcinogen exposure, other as yet unknown factors (secondary to carcinogen treatment may help initiate global loss of DNA methylation and region-specific gain of DNA methylation, which can, in turn, contribute to lung cancer development. Unveiling the initiating events that cause aberrant DNA methylation in lung cancer has tremendous public health relevance, as it can help define future strategies for early detection and prevention of this highly lethal disease.

  9. Determination of carcinogenic polycyclic aromatic hydrocarbons ...

    African Journals Online (AJOL)

    Determination of carcinogenic polycyclic aromatic hydrocarbons (pahs), anthracene in different variety of fish samples in the Bangsai river of Bangladesh. F Yeasmin, SMM Rahman, S Rana, KJ Fatema, MA Hossain ...

  10. Comparison between US and MRI in the prenatal assessment of lung malformations

    Energy Technology Data Exchange (ETDEWEB)

    Beydon, Nicole [Hopital Armand-Trousseau, Assistance Publique Hopital de Paris (APHP), Unite Fonctionnelle de Physiologie-Explorations Fonctionnelles Respiratoires (EFR), Paris Cedex 12 (France); Larroquet, Michele [Hopital Armand-Trousseau, APHP Service de Chirurgie Viscerale, Paris (France); Coulomb, Aurore [Universite Pierre et Marie Curie, Paris (France); Hopital Armand-Trousseau, APHP Service d' Anatomo-Pathologie, Paris (France); Jouannic, Jean-Marie [Universite Pierre et Marie Curie, Paris (France); Hopital Armand-Trousseau, APHP Service de Gyneco-Obstetrique, Paris (France); Ducou le Pointe, Hubert [Universite Pierre et Marie Curie, Paris (France); Hopital Armand-Trousseau, APHP Service de Radiologie, Paris (France); Clement, Annick [Universite Pierre et Marie Curie, Paris (France); Hopital Armand-Trousseau, APHP Unite Fonctionnelle de Pneumologie Pediatrique, Paris (France); Garel, Catherine [Hopital Armand-Trousseau, APHP Service de Radiologie, Paris (France)

    2013-06-15

    The contribution of MRI in the prenatal evaluation of congenital lung abnormalities (CLA) has not been extensively investigated. (1) To compare diagnostic accuracy and assessment of prognostic factors between US and MRI in CLA and (2) to assess the diagnosis agreement between prenatal imaging and postnatal diagnosis. We included 23 consecutive fetuses who underwent concomitant US and MRI during gestation as well as postnatal CT and surgery (n = 22). US-MRI sets were performed at median gestational age of 26 (n = 16) and 34 (n = 22) weeks. Postnatal diagnoses were 11 congenital pulmonary airway malformations (CPAM), 4 bronchopulmonary sequestrations (BPS), 6 hybrid lesions and 2 cysts. US and MRI agreement was significantly better during the second trimester than during the third one (P = 0.02). Disagreements were related to missed cysts (n = 5), mediastinal shift (n = 6) and vessels (n = 5). US and MRI diagnosis agreement was present in 20 cases, including 5 cases of misdiagnosis. US and MRI were concordant with postnatal diagnosis in 17 and 16 cases, respectively. In our series, no clear superiority of MRI over US in the prenatal evaluation of CLA was demonstrated, but US better demonstrated systemic feeding vessels and MRI cysts and normal lung adjacent to the lesion. (orig.)

  11. Comparison between US and MRI in the prenatal assessment of lung malformations.

    Science.gov (United States)

    Beydon, Nicole; Larroquet, Michèle; Coulomb, Aurore; Jouannic, Jean-Marie; Ducou le Pointe, Hubert; Clément, Annick; Garel, Catherine

    2013-06-01

    The contribution of MRI in the prenatal evaluation of congenital lung abnormalities (CLA) has not been extensively investigated. (1) To compare diagnostic accuracy and assessment of prognostic factors between US and MRI in CLA and (2) to assess the diagnosis agreement between prenatal imaging and postnatal diagnosis. We included 23 consecutive fetuses who underwent concomitant US and MRI during gestation as well as postnatal CT and surgery (n = 22). US-MRI sets were performed at median gestational age of 26 (n = 16) and 34 (n = 22) weeks. Postnatal diagnoses were 11 congenital pulmonary airway malformations (CPAM), 4 bronchopulmonary sequestrations (BPS), 6 hybrid lesions and 2 cysts. US and MRI agreement was significantly better during the second trimester than during the third one (P = 0.02). Disagreements were related to missed cysts (n = 5), mediastinal shift (n = 6) and vessels (n = 5). US and MRI diagnosis agreement was present in 20 cases, including 5 cases of misdiagnosis. US and MRI were concordant with postnatal diagnosis in 17 and 16 cases, respectively. In our series, no clear superiority of MRI over US in the prenatal evaluation of CLA was demonstrated, but US better demonstrated systemic feeding vessels and MRI cysts and normal lung adjacent to the lesion.

  12. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action

    Science.gov (United States)

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens. PMID:27625608

  13. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action.

    Science.gov (United States)

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

  14. An evaluation of the feasibility of assessment of volume perfusion for the whole lung by 128-slice spiral CT

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Haitao [Imaging Center of Taian Central Hospital, Taian, Shandong (China); Gao, Fei; Li, Ning; Liu, Cheng [Shandong Univ., Shandong Medical Imaging Research Inst., CT Room, Shandong (China)], e-mail: liucheng491025@sina.com

    2013-10-15

    Background: Lung perfusion based on dynamic scanning cannot provide a quantitative assessment of the whole lung because of the limited coverage of the current computed tomography (CT) detector designs. Purpose: To evaluate the feasibility of dynamic volume perfusion CT (VPCT) of the whole lung using a 128-slice CT for the quantitative assessment and visualization of pulmonary perfusion. Material and Methods: Imaging was performed in a control group of 17 subjects who had no signs of disturbance of pulmonary function or diffuse lung disease, and 15 patients (five patients with acute pulmonary embolism and 10 with emphysema) who constituted the abnormal lung group. Dynamic VPCT was performed in all subjects, and pulmonary blood flow (PBF), pulmonary blood volume (PBV), and mean transit time (MTT) were calculated from dynamic contrast images with a coverage of 20.7 cm. Regional and volumetric PBF, PBV, and MTT were statistically evaluated and comparisons were made between the normal and abnormal lung groups. Results: Regional PBF (94.2{+-}36.5, 161.8 {+-}29.6, 185.7 {+-}38.1 and 125.5 {+-}46.1, 161.9 {+-}31.4, 169.3 {+-}51.7), PBV (6.7 {+-}2.8, 10.9 {+-}3.0, 12.9 {+-}4.5 and 9.9 {+-}4.6, 10.3 {+-}2.9, 11.9 {+-}4.5), and MTT (5.8 {+-}2.4, 4.5 {+-}1.3, 4.7 {+-}2.1 and 5.6 {+-}2.3, 4.3 {+-}1.5, 4.9 {+-}1.5) demonstrated significant differences in the gravitational and isogravitational directions in the normal lung group (P < 0.05). The PBF (154.2 {+-}30.6 vs. 94.9 {+-}15.9) and PBV (11.1 {+-}4.0 vs. 6.6 {+-}1.7) by dynamic VPCT showed significant differences between normal and abnormal lungs (P < 0.05), notwithstanding the four large lungs that had coverage > 20.7 cm. Conclusion: Dynamic VPCT of the whole lung is feasible for the quantitative assessment of pulmonary perfusion by 128-slice CT, and may in future permit the evaluation of both morphological and functional features of the whole lung in a single examination.

  15. Assessing gas exchange in acute lung injury/acute respiratory distress syndrome: diagnostic techniques and prognostic relevance.

    Science.gov (United States)

    Gattinoni, Luciano; Carlesso, Eleonora; Cressoni, Massimo

    2011-02-01

    To provide the most recent insights on the assessment of gas exchange in acute lung injury. Central venous blood may be used as a surrogate of arterial blood to assess carbon dioxide tension and acid-base status. In contrast arterial oxygenation cannot be estimated with confidence from venous blood. However, the use of venous blood associated with pulse oximetry may provide the SvO2 which is useful for monitoring and targeting the resuscitation therapy. Impaired CO2 clearance and increased dead space have been confirmed as useful prognostic indices of structural lung damage and mortality in acute respiratory failure. A simplified technique based on multiple inert gas technique has been described to assess ventilation-perfusion mismatch while a new analysis of pulse oximetry has been suggested to detect lung opening and closing. Finally, new insight has been provided on the relationship between lung anatomy, as detected by computed tomography, oxygenation and CO2 clearance. Although oxygenation assessment is of primary importance during respiratory lung injury, dead space and CO2 retention are more strictly associated with outcome. The association of central venous blood analysis and pulse oximetry may provide more information than arterial blood alone.

  16. Atherosclerotic plaques in the internal carotid artery and associations with lung function assessed by different methods.

    Science.gov (United States)

    Frantz, Sophia; Nihlén, Ulf; Dencker, Magnus; Engström, Gunnar; Löfdahl, Claes-Göran; Wollmer, Per

    2012-03-01

    Previous studies on associations between reduced lung function and cardiovascular disease (CVD) have mainly been based on forced expiratory volume in 1-s (FEV(1) ) and vital capacity (VC). This study examined potential associations between five different lung function variables and plaques in the internal carotid artery (ICA). Subjects (n = 450) from a previous population-based respiratory questionnaire survey [current smokers without lower respiratory symptoms, subjects with a self-reported diagnosis of chronic obstructive pulmonary disease (COPD) and never-smokers without lower respiratory symptoms] were examined using spirometry, body plethysmography and measurements of diffusing capacity for CO (D(L,CO) ). Plaques in the ICA were assessed by ultrasonography. Two hundred and twenty subjects were current smokers, 139 ex-smokers and 89 never-smokers. COPD was diagnosed in 130 subjects (GOLD criteria). Plaques in the ICA were present in 231 subjects (52%). General linear analysis with adjustment for established risk factors for atherosclerosis, including C-reactive protein, showed that D(L,CO) was lower [77.4% versus 83.7% of predicted normal (PN), P = 0.014] and residual volume (RV) was higher (110.3% versus 104.8% of PN, P = 0.020) in subjects with than without plaques in the ICA. This analysis did not show any statistically significant association between plaques and FEV(1) or VC. The occurrence of plaques in the ICA was associated with low D(L,CO) and high RV, but not significantly with FEV(1) or COPD status. The results suggest that the relationships between reduced lung function, COPD and CVD are complex and not only linked to bronchial obstruction and low-grade systemic inflammation. © 2011 The Authors. Clinical Physiology and Functional Imaging © 2011 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  17. Assessment of regional ventilation and deformation using 4D-CT imaging for healthy human lungs during tidal breathing

    Science.gov (United States)

    Jahani, Nariman; Choi, Jiwoong; Iyer, Krishna; Hoffman, Eric A.

    2015-01-01

    This study aims to assess regional ventilation, nonlinearity, and hysteresis of human lungs during dynamic breathing via image registration of four-dimensional computed tomography (4D-CT) scans. Six healthy adult humans were studied by spiral multidetector-row CT during controlled tidal breathing as well as during total lung capacity and functional residual capacity breath holds. Static images were utilized to contrast static vs. dynamic (deep vs. tidal) breathing. A rolling-seal piston system was employed to maintain consistent tidal breathing during 4D-CT spiral image acquisition, providing required between-breath consistency for physiologically meaningful reconstructed respiratory motion. Registration-derived variables including local air volume and anisotropic deformation index (ADI, an indicator of preferential deformation in response to local force) were employed to assess regional ventilation and lung deformation. Lobar distributions of air volume change during tidal breathing were correlated with those of deep breathing (R2 ≈ 0.84). Small discrepancies between tidal and deep breathing were shown to be likely due to different distributions of air volume change in the left and the right lungs. We also demonstrated an asymmetric characteristic of flow rate between inhalation and exhalation. With ADI, we were able to quantify nonlinearity and hysteresis of lung deformation that can only be captured in dynamic images. Nonlinearity quantified by ADI is greater during inhalation, and it is stronger in the lower lobes (P Lung hysteresis estimated by the difference of ADI between inhalation and exhalation is more significant in the right lungs than that in the left lungs. PMID:26316512

  18. Volume versus diameter assessment of small pulmonary nodules in CT lung cancer screening

    NARCIS (Netherlands)

    Han, Daiwei; Heuvelmans, Marjolein A; Oudkerk, Matthijs

    Currently, lung cancer screening by low-dose chest CT is implemented in the United States for high-risk persons. A disadvantage of lung cancer screening is the large number of small-to-intermediate sized lung nodules, detected in around 50% of all participants, the large majority being benign.

  19. Lung Recruitment Assessed by Respiratory Mechanics and Computed Tomography in Patients with Acute Respiratory Distress Syndrome. What Is the Relationship?

    Science.gov (United States)

    Chiumello, Davide; Marino, Antonella; Brioni, Matteo; Cigada, Irene; Menga, Federica; Colombo, Andrea; Crimella, Francesco; Algieri, Ilaria; Cressoni, Massimo; Carlesso, Eleonora; Gattinoni, Luciano

    2016-06-01

    The assessment of lung recruitability in patients with acute respiratory distress syndrome (ARDS) may be important for planning recruitment maneuvers and setting positive end-expiratory pressure (PEEP). To determine whether lung recruitment measured by respiratory mechanics is comparable with lung recruitment measured by computed tomography (CT). In 22 patients with ARDS, lung recruitment was assessed at 5 and 15 cm H2O PEEP by using respiratory mechanics-based methods: (1) increase in gas volume between two pressure-volume curves (P-Vrs curve); (2) increase in gas volume measured and predicted on the basis of expected end-expiratory lung volume and static compliance of the respiratory system (EELV-Cst,rs); as well as by CT scan: (3) decrease in noninflated lung tissue (CT [not inflated]); and (4) decrease in noninflated and poorly inflated tissue (CT [not + poorly inflated]). The P-Vrs curve recruitment was significantly higher than EELV-Cst,rs recruitment (423 ± 223 ml vs. 315 ± 201 ml; P respiratory mechanics was 54 ± 28% (P-Vrs curve) and 39 ± 25% (EELV-Cst,rs) of the gas volume at 5 cm H2O PEEP. Recruitment measured by CT scan was 5 ± 5% (CT [not inflated]) and 6 ± 6% (CT [not + poorly inflated]) of lung tissue. Respiratory mechanics and CT measure-under the same term, "recruitment"-two different entities. The respiratory mechanics-based methods include gas entering in already open pulmonary units that improve their mechanical properties at higher PEEP. Consequently, they can be used to assess the overall improvement of inflation. The CT scan measures the amount of collapsed tissue that regains inflation. Clinical trial registered with www.clinicaltrials.gov (NCT00759590).

  20. Navigator-triggered oxygen-enhanced MRI with simultaneous cardiac and respiratory synchronization for the assessment of interstitial lung disease.

    Science.gov (United States)

    Molinari, Francesco; Eichinger, Monika; Risse, Frank; Plathow, Christian; Puderbach, Michael; Ley, Sebastian; Herth, Felix; Bonomo, Lorenzo; Kauczor, Hans-Ulrich; Fink, Christian

    2007-12-01

    To evaluate an optimized method for oxygen-enhanced MRI of the lung, using simultaneous electrocardiograph (ECG) and navigator triggering. To correlate oxygen-enhanced MRI with lung function tests assessing alveolar-capillary gas exchange. A total of 12 healthy volunteers (aged 20-32 years) and 10 patients (aged 37-87 years) with interstitial lung diseases (ILD) underwent oxygen-enhanced MRI and pulmonary functional tests (PFTs) assessing alveolar-capillary gas exchange. The paradigm room-air-oxygen-room-air was acquired with a nonselective inversion-recovery half-Fourier single-shot turbo spin-echo sequence (inversion time = 1200 msec; acquisition time = 134.5 msec; slice thickness = 20 mm; matrix size = 128 x 128), using simultaneous double triggering (navigator plus ECG trigger). Cross-correlation was performed in regions of interest (ROIs) encompassing both lungs. The number of oxygen-activated pixels over the total number of pixels in the ROIs (OAP%) of volunteers and patients was compared. OAP%s were correlated with PFTs. The mean OAP% of patients was significantly lower than that of volunteers (36.7 vs. 81.7, P = 0.001). OAP% correlated with the transfer lung factor for carbon monoxide (Tlco) (r = 0.64; P = 0.002), the transfer coefficient (Kco) (r = 0.75; P = 0.001), the arterial partial pressure (r = 0.77; P < 0.001), and the saturation (r = 0.70; P < 0.001) of oxygen. Navigator-triggered oxygen-enhanced MRI of the lung may have a potential role in the quantitative assessment of lung function in ILD. (c) 2007 Wiley-Liss, Inc.

  1. Short-term early exposure to thirdhand cigarette smoke increases lung cancer incidence in mice.

    Science.gov (United States)

    Hang, Bo; Wang, Yunshan; Huang, Yurong; Wang, Pin; Langley, Sasha A; Bi, Lei; Sarker, Altaf H; Schick, Suzaynn F; Havel, Christopher; Jacob, Peyton; Benowitz, Neal; Destaillats, Hugo; Tang, Xiaochen; Xia, Yankai; Jen, Kuang-Yu; Gundel, Lara A; Mao, Jian-Hua; Snijders, Antoine

    2018-02-12

    Exposure to thirdhand smoke (THS) is a recently described health concern that arises in many indoor environments. However, the carcinogenic potential of THS, a critical consideration in risk assessment, remains untested. Here we investigated the effects of short-term early exposure to THS on lung carcinogenesis in A/J mice. Forty weeks after THS exposure from 4 to-7 weeks of age, the mice had increased incidence of lung adenocarcinoma, tumor size and multiplicity, compared to controls. In vitro studies using cultured human lung cancer cells showed that THS exposure induced DNA double-strand breaks and increased cell proliferation and colony formation. RNA sequencing analysis revealed that THS exposure induced endoplasmic reticulum stress and activated p53 signaling. Activation of the p53 pathway was confirmed by an increase in its targets p21 and BAX. These data indicate that early exposure to THS is associated with increased lung cancer risk. ©2018 The Author(s).

  2. Carcinogenic effects of N-nitroso-3-(substituted phenylimino)-indolin-2-one derivatives.

    Science.gov (United States)

    Kumarasamy, Murali; Theivendren, Panneerselvam; Govindarajan, Rousso; Franzblau, Scott G; Ramalingam, Kirthiga

    2012-07-01

    A novel series of N-nitroso-3-(substituted phenylimino)-indolin-2-one 3a-h was synthesized and tested for carcinogenic effects. The synthesized pyrazole derivatives' chemical structures were proved by means of their infra red (IR), proton nuclear magnetic resonance ((1)H-NMR), and mass,and confirmed by elemental analyses. The carcinogenic activity was assessed by 3-(4,5dimethyl thiazole-2yl)-2,5-diphenyltetrazoliumbromide (MTT) cell-viability assay. The results show that most of the synthesized compounds exhibit significant carcinogenic activities. Among the synthesized compounds, N-nitroso-3-(2,4-dinitrophenylimino)-indolin-2-one 3h exhibited the most potent carcinogenic activity. The structure-activity relationship (SAR) studies show that the nature as well as the position of the amine are important for deciding the activity profile of the indolin-2-one derivatives, which reiterates the need for further experimental investigations.

  3. On the International Agency for Research on Cancer classification of glyphosate as a probable human carcinogen.

    Science.gov (United States)

    Tarone, Robert E

    2017-11-08

    The recent classification by International Agency for Research on Cancer (IARC) of the herbicide glyphosate as a probable human carcinogen has generated considerable discussion. The classification is at variance with evaluations of the carcinogenic potential of glyphosate by several national and international regulatory bodies. The basis for the IARC classification is examined under the assumptions that the IARC criteria are reasonable and that the body of scientific studies determined by IARC staff to be relevant to the evaluation of glyphosate by the Monograph Working Group is sufficiently complete. It is shown that the classification of glyphosate as a probable human carcinogen was the result of a flawed and incomplete summary of the experimental evidence evaluated by the Working Group. Rational and effective cancer prevention activities depend on scientifically sound and unbiased assessments of the carcinogenic potential of suspected agents. Implications of the erroneous classification of glyphosate with respect to the IARC Monograph Working Group deliberative process are discussed.

  4. Artificial sweeteners--do they bear a carcinogenic risk?

    Science.gov (United States)

    Weihrauch, M R; Diehl, V

    2004-10-01

    Artificial sweeteners are added to a wide variety of food, drinks, drugs and hygiene products. Since their introduction, the mass media have reported about potential cancer risks, which has contributed to undermine the public's sense of security. It can be assumed that every citizen of Western countries uses artificial sweeteners, knowingly or not. A cancer-inducing activity of one of these substances would mean a health risk to an entire population. We performed several PubMed searches of the National Library of Medicine for articles in English about artificial sweeteners. These articles included 'first generation' sweeteners such as saccharin, cyclamate and aspartame, as well as 'new generation' sweeteners such as acesulfame-K, sucralose, alitame and neotame. Epidemiological studies in humans did not find the bladder cancer-inducing effects of saccharin and cyclamate that had been reported from animal studies in rats. Despite some rather unscientific assumptions, there is no evidence that aspartame is carcinogenic. Case-control studies showed an elevated relative risk of 1.3 for heavy artificial sweetener use (no specific substances specified) of >1.7 g/day. For new generation sweeteners, it is too early to establish any epidemiological evidence about possible carcinogenic risks. As many artificial sweeteners are combined in today's products, the carcinogenic risk of a single substance is difficult to assess. However, according to the current literature, the possible risk of artificial sweeteners to induce cancer seems to be negligible.

  5. Factors associated with swallowing assessment after oral endotracheal intubation and mechanical ventilation for acute lung injury.

    Science.gov (United States)

    Brodsky, Martin B; González-Fernández, Marlís; Mendez-Tellez, Pedro A; Shanholtz, Carl; Palmer, Jeffrey B; Needham, Dale M

    2014-12-01

    Endotracheal intubation is associated with postextubation swallowing dysfunction, but no guidelines exist for postextubation swallowing assessments. We evaluated the prevalence, patient demographic and clinical factors, and intensive care unit (ICU) and hospital organizational factors associated with swallowing assessment after oral endotracheal intubation and mechanical ventilation in patients with acute lung injury (ALI). We performed a secondary analysis of a prospective cohort study in which investigators evaluated 178 eligible patients with ALI who were mechanically ventilated via oral endotracheal tube. The patients were recruited from 13 ICUs at four teaching hospitals in Baltimore, Maryland. Patient demographic and clinical factors, types of ICU, and hospital study sites were evaluated for their association with completion of a swallowing assessment both in the ICU and after the ICU stay before hospital discharge. Factors significantly associated with a swallow assessment were evaluated in a multivariable logistic regression model. Before hospital discharge, 79 (44%) patients completed a swallowing assessment, among whom 59 (75%) had their assessments initiated in ICU and 20 (25%) had their assessments initiated on the hospital ward. Female sex (odds ratio [OR] = 2.01; 95% confidence interval [95% CI] = 1.03-3.97), orotracheal intubation duration (OR = 1.13 per day; 95% CI = 1.05-1.22), and hospital study site (Site 3: OR = 2.41; 95% CI = 1.00-5.78) were independently associated with swallowing assessment. Although Site 3 had a twofold increase in swallowing assessments in the ICU, there was no significant difference between hospitals in the frequency of swallowing assessments completed after ICU discharge (P = 0.287) or in the proportion of patients who failed a swallowing assessment conducted in the ICU (P = 0.468) or on the ward (P = 0.746). In this multisite prospective study, female sex, intubation duration, and

  6. [Quantitative assessment of the risk of lung cancer and pleural mesothelioma among automobile mechanics].

    Science.gov (United States)

    Imbernon, E; Marchand, J-L; Garras, L; Goldberg, M

    2005-11-01

    A quantitative assessment of the risk of lung cancer and pleural mesothelioma among mechanics exposed to dust released from automobile asbestos-containing parts was performed. The population of automobile mechanics in France, according to profession and industrial sectors codes, was estimated from the data of the 1999 census. Risks were computed for a total male population of 242,360 automobile mechanics aged 16 to 60 years. Exposure to asbestos among these workers comes from maintenance tasks involving asbestos-containing parts produced before 1997 (date of the asbestos ban in France). Airborne asbestos concentration data available from the literature were highly variable. No data reporting the distribution of time spent for such tasks over a typical week of work were available. Therefore, different weekly exposure profiles were simulated, based on data from the 1994 SUMER survey. Risk models were those used for assessing asbestos health effects by all national and international agencies. Exposure scenarios mixed different levels of exposure, periods of time, proportions of exposed workers and dates of the "natural" disappearance of the automobile fleet built before asbestos was banned in brakes and other parts. The most realistic scenario hypothesizes that all automobile mechanics were exposed to asbestos, that the exposure levels ranged from 0.06 and 0.25 fibers/liter per week for the period before 1997, and between 0.01 and 0.06 fibers/liter per week afterwards until 2010. According to this scenario, the number of lifelong cancer deaths (lung and pleura) induced by asbestos exposure in this population is estimated at 602 "unavoidable" cases, due to exposure experienced before 2003; 43 other cases will occur if asbestos is not removed from existing automobiles.

  7. Spirometric assessment of lung transplant patients: one year follow-up

    Directory of Open Access Journals (Sweden)

    Paulo M. Pêgo-Fernandes

    2009-06-01

    Full Text Available OBJECTIVE: The purpose of this study was to compare spirometry data between patients who underwent single-lung or double-lung transplantation the first year after transplantation. INTRODUCTION: Lung transplantation, which was initially described as an experimental method in 1963, has become a therapeutic option for patients with advanced pulmonary diseases due to improvements in organ conservation, surgical technique, immunosuppressive therapy and treatment of post-operative infections. METHODS: We retrospectively reviewed the records of the 39 patients who received lung transplantation in our institution between August 2003 and August 2006. Twenty-nine patients survived one year post-transplantation, and all of them were followed. RESULTS: The increase in lung function in the double-lung transplant group was more substantial than that of the single-lung transplant group, exhibiting a statistical difference from the 1st month in both the forced expiratory volume in one second (FEV1 and the forced vital capacity (FVC in comparison to the pre-transplant values (p <0.05. Comparison between double-lung transplant and single lung-transplant groups of emphysema patients demonstrated a significant difference in lung function beginning in the 3rd month after transplantation. DISCUSSION: The analyses of the whole group of transplant recipients and the sub-group of emphysema patients suggest the superiority of bilateral transplant over the unilateral alternative. Although the pre-transplant values of lung function were worse in the double-lung group, this difference was no longer significant in the subsequent months after surgery. CONCLUSION: Although both groups demonstrated functional improvement after transplantation, there was a clear tendency to greater improvement in FVC and FEV1 in the bilateral transplant group. Among our subjects, double-lung transplantation improved lung function.

  8. 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

  9. Prediction of lethal pulmonary hypoplasia by means fetal lung volume in skeletal dysplasias: a three-dimensional ultrasound assessment.

    Science.gov (United States)

    Barros, Carolina Amorim; Rezende, Guilherme de Castro; Araujo Júnior, Edward; Tonni, Gabriele; Pereira, Alamanda Kfoury

    2016-01-01

    The aim of this study was to assess the capacity of three-dimensional ultrasound (3DUS) for predicting lethality in fetuses with skeletal dysplasia. Twenty-four fetuses between 20 and 32 weeks of gestation were assessed. Bilateral lung volume scans were performed three times in each fetus during one ultrasound session. The virtual organ computer-aided analysis method was used to obtain a sequence of six sections of each lung around a fixed axis, and a rotation angle of 30° was adopted. Fetal lung volume measurements were analyzed according to the reference range. After birth, lung hypoplasia was diagnosed considering clinical and radiological criteria. Of all cases of skeletal dysplasia, 18 (75%) were lethal. Among the lethal cases, after postnatal diagnosis, four were osteogenesis imperfecta type II, three were thanatophoric dysplasia and two were campomelic dysplasia. The remaining nine cases remained without a definitive diagnosis. The accuracy of 3DUS in predicting lethality in fetuses with skeletal dysplasia was high, with a sensitivity of 83.3%, specificity of 100%, positive predictive value of 100% and negative predictive value of 66.7%. The kappa index of 0.174 showed a good agreement between the possibility of lethality when the 3DUS volume measurement was altered and real lethality after birth (p lung volume measurement is a good predictor of lethal pulmonary hypoplasia in fetuses with skeletal dysplasia, with high accuracy.

  10. A case report of lung cancer in a horse trainer caused by exposure to respirable crystalline silica: an exposure assessment

    National Research Council Canada - National Science Library

    Yoon, Jin-Ha; Kim, Boowook; Choi, Byung-Soon; Park, So Young; Kwag, Hyun-Suk; Kim, In-Ah; Jeong, Ji Yeon

    2013-01-01

    Here, we present a case of lung cancer in a 48-year-old male horse trainer. To the best of our knowledge, this is the first such case report to include an exposure assessment of respirable crystalline silica (RCS) as a quartz...

  11. Assessment of Lung Morphological Changes in Acute Intoxications with Clozapine, Ethanol and Their Combination

    Directory of Open Access Journals (Sweden)

    A. M. Golubev

    2015-01-01

    Full Text Available Objective:to detect lung morphological changes in acute intoxications with clozapine, ethanol, and their combination 3 and 24 hours after poisoning.Materials and methods. Experiments were carried out in outbred male rats weighing 270—300 g. Clozapine was given in a dose of 250 mg per kg animal body weight under chloralose anesthesia. Following 3 and 24 hours, the animals were withdrawn from the experiment by decapitation. Lung histological sections from 6 rats that had received oral clozapine 250 mg/kg, 6 rats that had oral ethanol 8.6 ml/kg, and 6 rats that had a combination of ethanol and clozapine orally in the above doses were examined 3 hours after intoxication. Those from 18 rats that had been orally given the similar agents in the above doses and withdrawn from the experiment were also investigated 24 hours after drug administration. The sections were compared with those from 6 rats that had not received the above agents. Nonparametric methods (χ2 test were used for statistical processing. The investigators assessed the following morphological signs: circulatory disorders (plethora, hemorrhages, interstitial and alveolar edema, damage to the bronchial and alveolar epithelium and to the endothelium, and a cell reaction. The differences were considered significant at p<0.05.Results. In the control animal group, histological examination did not reveal any circulatory disorders and damage to the bronchial and alveolar epithelium and to the endothelium. Three hours after its administration, the animals that had received clozapine were observed to have acute pulmonary circulatory disorders (plethora in the pulmonary artery system, focal plethora of the capillaries of interalveolar septa and that of veins that increased 24 hours after its ingestion. If death occurred 3 hours after ethanol intake, there was obvious perivascular edema, plethora, and hemorrhage; some alveoli contained transudate. Moderate venous plethora was seen 24 hours

  12. Sucralose Non-Carcinogenicity: A Review of the Scientific and Regulatory Rationale.

    Science.gov (United States)

    Berry, Colin; Brusick, David; Cohen, Samuel M; Hardisty, Jerry F; Grotz, V Lee; Williams, Gary M

    2016-01-01

    Regulatory authorities worldwide have found the nonnutritive sweetener, sucralose, to be noncarcinogenic, based on a range of studies. A review of these and other studies found through a comprehensive search of electronic databases, using appropriate key terms, was conducted and results of that review are reported here. An overview of the types of studies relied upon by regulatory agencies to assess carcinogenicity potential is also provided as context. Physiochemical and pharmacokinetic/toxicokinetic studies confirm stability under conditions of use and reveal no metabolites of carcinogenic potential. In vitro and in vivo assays reveal no confirmed genotoxic activity. Long-term carcinogenicity studies in animal models provide no evidence of carcinogenic potential for sucralose. In studies in healthy adults, sucralose was well-tolerated and without evidence of toxicity or other changes that might suggest a potential for carcinogenic effects. In summary, sucralose does not demonstrate carcinogenic activity even when exposure levels are several orders of magnitude greater than the range of anticipated daily ingestion levels.

  13. Comment on the significance of positive carcinogenicity studies using gavage as the route of exposure

    Energy Technology Data Exchange (ETDEWEB)

    Perera, F.; Brennan, T.; Fouts, J.R. (Columbia Univ. School of Public Health, New York, NY (USA))

    1989-02-01

    There is continuing controversy, extending into regulatory matters, over the significance to human health of positive results in carcinogenicity studies in animals using the gavage technique as the route of exposure. This review of a nonrandom sample of 117 chemicals or chemical processes listed as known or reasonably anticipated to be carcinogenic in the National Toxicology Program's Third Annual Report on Carcinogens provides support for the validity of the gavage route in such studies. Twenty-three chemicals among the 117 substances and processes listed were positive by gavage. Twenty of these 23 chemicals were also appropriately studied by at least one other route of exposure. Nineteen or (95%) of the twenty chemicals were positive for carcinogenicity by at least one other nongavage route in carcinogenicity bioassays. All of the 23 gavage-positive chemicals induced tumors distal to the site of administration in at least one study, as did all 15 chemicals which were also positive by subcutaneous injection. The authors emphasize, however, the limited scope of the survey. Despite this limitation, the review suggests that, although gavage may not be the general method of choice for chemical administration, the results of studies wherein this route was employed are meaningful as a basis for assessing potential carcinogenic hazards.

  14. Assessment of interstitial lung disease in Sjögren's syndrome by lung ultrasound: a pilot study of correlation with high-resolution chest tomography.

    Science.gov (United States)

    Vasco, Pablo Guisado; de Luna Cardenal, Gonzalo; Garrido, Isabel Martín; Pinilla, José Manuel Luque; Rodríguez, Guadalupe Fraile; Mateo, Juan José Nava; Ruiz, Daniel Carnevalli

    2017-04-01

    The background of this study is to assess the accuracy of lung ultrasound (LUS) to diagnose interstitial lung disease (ILD) in Sjögren's syndrome (Sjs), in patients who have any alterations in pulmonary function tests (PFT) or respiratory symptoms. LUS was correlated with chest tomography (hrCT), considering it as the imaging gold standard technique to diagnose ILD. This is a pilot, multicenter, cross-sectional, and consecutive-case study. The inclusion criteria are ≥18 years old, Signs and symptoms: according to ACEG 2002 criteria, respiratory symptoms (dyspnea, cough), or any alterations in PFR. LUS was done following the International Consensus Conference on Lung Ultrasound protocol for interstitial syndrome (B pattern). Of the 50 patients in follow-up, 13 (26%) met the inclusion criteria. All were women with age 63.62 years (range 39-88). 78.6% of the cases had primary Sjs (SLE, RA, n = 2). The intra-rater reliability k is 1, according to Gwet's Ac1 and GI index (probability to concordance-e(K)-, by Cohen, of 0.52). LUS has a sensitivity of 1 (95% CI 0.398-1.0), specificity of 0.89 (95% CI 0.518-0.997), and a positive probability reason of 9.00 (95% CI 7.1-11.3) to detect ILD. The correlation of Pearson is r = 0.84 (p < 0.001). To check the accuracy of LUS to diagnose ILD, a completely bilateral criterion of yes/no for interstitial pattern was chosen, AUC reaches significance, 0.94 (0.07) (95% CI 0.81-1.0, p = 0.014). LUS reaches an excellent correlation to hrCT in Sjs affected with ILD, and might be a useful technique in daily clinical practice for the assessment of pulmonary disease in the sicca syndrome.

  15. Lung cancer in women

    Directory of Open Access Journals (Sweden)

    Barrera-Rodriguez R

    2012-12-01

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

  16. Temporal aspects of tumorigenic response to individual and mixed carcinogens. Progress report, October 1, 1978-September 30, 1979

    Energy Technology Data Exchange (ETDEWEB)

    Albert, R.E.; Burns, F.J.; Altshuler, B.

    1979-06-01

    The research proposed here is designed to obtain a better understanding of the temporal kinetics of tumor induction when one or more carcinogens are present simultaneously or sequentially for prolonged periods of time. Studies done to date under this contract have shown that carcinogenesis in mouse skin by polycyclic aromatic hydrocarbon carcinogens is consistent with the induction of dependent and autonomous cell transformations by the carcinogen followed by the conversion of autonomous tumor cells into malignancies at a rate which is determined by the level of carcinogen exposure. Dependent cell transformations remain latent in the skin unless expressed by a promoting agent. Dependent neoplasia appears to follow one-hit kinetics while malignancy is a multihit endpoint. Dose-related and time-related aspects of tumor induction are separable in the initiation-promotion system of mouse skin which along with rat skin and hamster lung is being used as a model for testing hypotheses. Results to date provide the basis for a new interpretation of the linear non-threshold extrapolation model. The broad aim of the study is to provide a basis or rationale for estimating risks associated with prolonged exposures to carcinogens found in the environment and to predict how different tissues and species respond to the carcinogens, promoters, and cocarcinogens.

  17. Immunologic methods for monitoring carcinogen exposure

    Science.gov (United States)

    Santella, Regina M.; Perera, Frederica P.; Zhang, Yu J.; Chen, Chen J.; Young, Tie L.

    1993-03-01

    Immunologic methods have been developed for monitoring human exposure to environmental and occupational carcinogens. These methods involve the development of monoclonal and polyclonal antisera which specifically recognize the carcinogens themselves or their DNA or protein adducts. Antisera recognizing the DNA adducts of several polycyclic aromatic hydrocarbon diol epoxides have been used in competitive enzyme-linked immunosorbent assays to monitor adducts in tissue or blood samples. Elevated levels of DNA adducts have been seen in mononuclear cells of smokers and in total white blood cells of foundry and coke oven workers. Environmental exposure to PAH has been measured in individuals living in a highly polluted region of Poland. Antisera recognizing PAH-DNA adducts have also been used in immunohistochemical studies to monitor adducts in specific cells of biopsy samples. The DNA adducts of aflatoxin B1 have been monitored in liver tissue of hepatocellular carcinoma patients in Taiwan. Detectable adducts were seen in 50 - 70% of the patients suggesting that dietary exposure to this carcinogen may be a risk factor for cancer induction. Thus, immunoassays for monitoring exposure to carcinogens are an important tool in epidemiologic studies.

  18. Polypropylene mesh: evidence for lack of carcinogenicity

    Science.gov (United States)

    Moalli, Pamela; Brown, Bryan; Reitman, Maureen T. F.

    2016-01-01

    Tumors related to the implantation of surgical grade polypropylene in humans have never been reported. In this commentary we present a balanced review of the information on what is known regarding the host response to polypropylene and provide data as to why the potential for carcinogenicity of polypropylene mesh is exceedingly small. PMID:24614956

  19. Toxic Potential of Carcinogenic Polycyclic Aromatic Hydrocarbons ...

    African Journals Online (AJOL)

    DR. GODSON

    Toxic Potential of Carcinogenic Polycyclic Aromatic Hydrocarbons (cPAHs) and Heavy. Metal in Crude Oil from Gokana Area, Rivers State, Nigeria. *1. IWUOHA, G;. 1. ORUBITE, O;. 1. OKITE I. 1Department of Pure and Industrial Chemistry, Faculty of Sciences, University of Port Harcourt. ABSTRACT: This article is focused ...

  20. Toxic Potential of Carcinogenic Polycyclic Aromatic Hydrocarbons ...

    African Journals Online (AJOL)

    This article is focused on ascertaining the toxic potentials of heavy metals and the levels of PAHs and cPAHs in crude oil samples from Gokana area and using the data to determine the carcinogenicity (toxicity) of the cPAHs in the crude oil. All the cPAHs namely; benzo (a) pyrene, benzo (a) Anthracene, benzo (b) ...

  1. Carcinogens formed when Meat is Cooked

    Energy Technology Data Exchange (ETDEWEB)

    Felton, J S; Salmon, C P; Knize, M G

    2003-05-30

    Diet has been associated with varying cancer rates in human populations for many years, yet the causes of the observed variation in cancer patterns have not been adequately explained (Wynder et al. 1977). Along with the effect of diet on human cancer incidence is the strong evidence that mutations are the initiating events in the cancer process (Vogelstein et al. 1992). Foods, when heated, are a good source of genotoxic carcinogens that very likely are a cause for some of these events(Doll et al. 1981). These carcinogens fall into two chemical classes: heterocyclic aromatic amines (HAA) and polycyclic aromatic hydrocarbons (PAH). There is ample evidence that many of these compounds are complete carcinogens in rodents(El-Bayoumy et al. 1995; Ohgaki et al. 1991). Heterocyclic aromatic amines are among the most potent mutagenic substances ever tested in the Ames/Salmonella mutagenicity test (Wakabayashi et al. 1992). Both classes of carcinogen cause tumors in rodents at multiple sites, (El-Bayoumy et al. 1995; Ohgaki et al. 1991) many of which are common tumor sites in people on a Western diet. An HAA, PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), and a PAH, B[a]P (benzo[a]pyrene), of comparable carcinogenic potency caused mammary gland tumors in a feeding study in female rats (El-Bayoumy et al. 1995). In addition, PhIP has recently been shown to cause carcinomas in the prostate of the male rat (Shirai et al. 1997). Complementing the rodent cancer studies are numerous human case-control and prospective studies suggesting a relationship between overheated beef, chicken, and lamb, and cancer of the colon, breast, prostate, and stomach (Sinha et al. 1999; Ward et al. 1997; Zheng et al. 1998).

  2. Assessment of metal contaminants in non-small cell lung cancer by EDX microanalysis

    Directory of Open Access Journals (Sweden)

    M. Scimeca

    2014-09-01

    Full Text Available Human cardio-respiratory diseases are strongly correlated to concentrations of atmospheric elements. Bioaccumulation of heavy metals is strictly monitored, because of its possible toxic effects. In this work, we utilized the EDX microanalysis in order to identify the potential heavy metal accumulation in the lung tissue.  To this aim, we enrolled 45 human lung biopsies: 15 non-small cell lung cancers, 15 lung benign lesions and 15 control biopsies. Lung samples were both paraffin embedded for light microscopy study and eponepoxid embedded for transmission electron microscopy. EDX microanalysis was performed on 100 nm thick unstained ultrathin-sections placed on specific copper grids. Our results demonstrated that the EDX technology was particularly efficient in the study of elemental composition of lung tissues, where we found heavy metals, such as Cobalt (Co, Chromium (Cr, Manganese (Mn and Lead (Pb. Furthermore, in malignant lesions we demonstrated the presence of multiple bio-accumulated elements. In fact, a high rate of lung cancers was associated with the presence of 3 or more bio-accumulated elements compared to benign lesions and control tissue (91.7%, 0%, 8.3%, respectively. The environmental impact on pulmonary carcinogenesis could be better clarified by demonstrating the presence of polluting agents in lung tissues. The application of EDX microanalysis on biological tissuescould shed new light in the study of the possible bioaccumulation of polluting agents in different human organs and systems.

  3. Quantitative assessment of elemental carbon in the lungs of never smokers, cigarette smokers and coal miners

    Science.gov (United States)

    Inhalation exposure to particulates such as cigarette smoke and coal dust is known to contribute to the development of chronic lung disease. The purpose of this study was to estimate the amount of elemental carbon (EC) deposits from autopsied lung samples from cigarette smokers, ...

  4. Advances in physiologic lung assessment via electron beam computed tomography (EBCT)

    Science.gov (United States)

    Hoffman, Eric A.

    1999-09-01

    Lung function has been evaluated in both health and disease states by techniques, such as pulmonary function tests, which generally study aggregate function. These decades old modalities have yielded a valuable understanding of global physiologic and pathophysiologic structure-to-function relationships. However, such approaches have reached their limits. They cannot meet the current and anticipated needs of new surgical and pharmaceutical treatments. 4-D CT can provide insights into regional lung function (ventilation and blood flow) and thus can provide information at an early stage of disease when intervention will have the greatest impact. Lung CT over the last decade has helped with further defining anatomic features in disease, but has lagged behind advances on the cellular and molecular front largely because of the failure to account for functional correlates to structural pathology. Commercially available CT scanners are now capable of volumetric data acquisition in a breath-hold and capable of multi-level slice acquisitions of the heart and lungs with a per slice scan aperture of 50 - 300 msec, allowing for regional blood flow measurements. Static, volumetric imaging of the lung is inadequate in that much of lung pathology is a dynamic phenomenon and, thus, is only detectable if the lung is imaged as air and blood are flowing. This paper review the methodologies and early physiologic findings associated with our measures of lung tissue properties coupled with regional ventilation and perfusion.

  5. Assessing the Effects of Fibrosis on Lung Function by Light Microscopy-Coupled Stereology

    DEFF Research Database (Denmark)

    Pilecki, Bartosz; Sørensen, Grith Lykke

    2017-01-01

    Pulmonary diseases such as fibrosis are characterized by structural abnormalities that lead to impairment of proper lung function. Stereological analysis of serial tissue sections allows detection and quantitation of subtle changes in lung architecture. Here, we describe a stereology-based method...

  6. EPA's evaluation of the carcinogenic potential of glyphosate

    Science.gov (United States)

    Recently, several international agencies have evaluated the carcinogenic potential of glyphosate. In March 2015, the International Agency for Research on Cancer (IARC), a subdivision of the World Health Organization (WHO), determined that glyphosate was a probable carcinogen (gro...

  7. Assessment of fatigue using the Identity- Consequence Fatigue Scale in patients with lung cancer

    Directory of Open Access Journals (Sweden)

    Ingrid Correia Nogueira

    Full Text Available ABSTRACT Objective: To evaluate the properties of the Identity-Consequence Fatigue Scale (ICFS in patients with lung cancer (LC, assessing the intensity of fatigue and associated factors. Methods: This was a cross-sectional study involving LC patients, treated at a teaching hospital in Brazil, who completed the ICFS. Patients with chronic heart disease (CHD and healthy controls, matched for age and gender, also completed the scale. Initially, a Brazilian Portuguese-language version of the ICFS was administered to 50 LC patients by two independent interviewers; to test for reproducibility, it was readministered to those same patients. At baseline, the LC patients were submitted to spirometry and the six-minute walk test, as well as completing the Epworth Sleepiness Scale (ESS, Hospital Anxiety and Depression Scale (HADS, Medical Outcomes Study 36-item Short-Form Health Survey (SF-36, and Fatigue Severity Scale (FSS. Inflammatory status was assessed by blood C-reactive protein (CRP levels. To validate the ICFS, we assessed the correlations of its scores with those variables. Results: The sample comprised 50 patients in each group (LC, CHD, and control. In the LC group, the intraclass correlation coefficients for intra-rater and inter-rater reliability regarding ICFS summary variables ranged from 0.94 to 0.76 and from 0.94 to 0.79, respectively. The ICFS presented excellent internal consistency, and Bland-Altman plots showed good test-retest reliability. The ICFS correlated significantly with FSS, HADS, and SF-36 scores, as well as with CRP levels. Mean ICFS scores in the LC group differed significantly from those in the CHD and control groups. Conclusions: The ICFS is a valid, reliable instrument for evaluating LC patients, in whom depression, quality of life, and CRP levels seem to be significantly associated with fatigue.

  8. Systems for lung volume standardization during static and dynamic MDCT-based quantitative assessment of pulmonary structure and function.

    Science.gov (United States)

    Fuld, Matthew K; Grout, Randall W; Guo, Junfeng; Morgan, John H; Hoffman, Eric A

    2012-08-01

    Multidetector-row computed tomography (MDCT) has emerged as a tool for quantitative assessment of parenchymal destruction, air trapping (density metrics), and airway remodeling (metrics relating airway wall and lumen geometry) in chronic obstructive pulmonary disease (COPD) and asthma. Critical to the accuracy and interpretability of these MDCT-derived metrics is the assurance that the lungs are scanned during a breathhold at a standardized volume. A computer monitored turbine-based flow meter system was developed to control patient breathholds and facilitate static imaging at fixed percentages of the vital capacity. Because of calibration challenges with gas density changes during multibreath xenon CT, an alternative system was required. The design incorporated dual rolling seal pistons. Both systems were tested in a laboratory environment and human subject trials. The turbine-based system successfully controlled lung volumes in 32/37 subjects, having a linear relationship for CT measured air volume between repeated scans: for all scans, the mean and confidence interval of the differences (scan1-scan2) was -9 mL (-169, 151); for total lung capacity alone 6 mL (-164, 177); for functional residual capacity alone, -23 mL (-172, 126). The dual-piston system successfully controlled lung volume in 31/41 subjects. Study failures related largely to subject noncompliance with verbal instruction and gas leaks around the mouthpiece. We demonstrate the successful use of a turbine-based system for static lung volume control and demonstrate its inadequacies for dynamic xenon CT studies. Implementation of a dual-rolling seal spirometer has been shown to adequately control lung volume for multibreath wash-in xenon CT studies. These systems coupled with proper patient coaching provide the tools for the use of CT to quantitate regional lung structure and function. The wash-in xenon CT method for assessing regional lung function, although not necessarily practical for routine

  9. [Chronic pulmonary diseases: point of view of partners and their assessments with regard to the effects of lung sports].

    Science.gov (United States)

    Nell, C; Kehr, K; Hildebrandt, O; Sohrabi, K; Cassel, W; Greulich, T; Koehler, K-I; Koehler, U

    2011-12-01

    Chronic diseases of the respiratory organs have, besides restrictions of lung function, also physical, mental and social consequences. The chronic disease impacts negatively not only the patient's own quality of life but also that of his/her partner and/or relative. As treatment modalities, besides drug therapy, above all outpatient rehabilitation measures have proved to be effective. In this pilot study we sought answers to three questions: (i) How is the quality of life of the patient's partner and/or relative influenced by the disease? How does the partner/relative assess the effect of the disease on the chronically ill patient? How does the partner/relative assess the effect of lung sports on the chronically ill patient? A specially conceived questionnaire was given to the partners/relatives of 25 patients with chronic pulmonary diseases. The patients, 23 with chronic obstructive pulmonary disease and 2 with pulmonary fibrosis, have been participating in lung sports once a week for more than three years. The average age of the patients was 67 years. The patients' illness also negatively influenced the quality of life of the partner to a considerable extent. The impact of the patients' pulmonary disease on the healthy partner was assessed as being rather moderate. Restrictions of social life were essentially influenced by the amount of assistance required by the pulmonary patient. The therapeutic effects of lung sports on the well-being of the patient were aways considered to be positive by the respective partner/relatives. A chronic pulmonary illness also has a negative influence on the partner/relative's quality of life. The necessity for extensive assistance in daily life is accompanied by a considerable negative impact on the partner's quality of life. According to the opinion of the partner/relative, lung sports have positive effects in all of the chronically ill patient's fields of life. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Relative preservation of peripheral lung function in smoking-related pulmonary emphysema: assessment with {sup 99m}Tc-MAA perfusion and dynamic {sup 133}Xe SPET

    Energy Technology Data Exchange (ETDEWEB)

    Suga, Kazuyoshi; Kume, Norihiko; Matsunaga, Naofumi; Ogasawara, Nobuhiko; Motoyama, Kazumi; Hara, Akiko; Matsumoto, Tsuneo [Department of Radiology, Yamaguchi University School of Medicine, Ube, Yamaguchi (Japan)

    2000-07-01

    In this study the cross-sectional functional differences between the central and peripheral lung in smokers with pulmonary emphysema were evaluated by lung perfusion and dynamic xenon-133 single-photon emission tomography (SPET). The subjects were 81 patients with a long-term smoking history and relatively advanced emphysema, 17 non-smoker patients with non-obstructive lung diseases and six healthy non-smokers. Regional lung functional difference between the peripheral and central lung was assessed in the upper, middle and lower lung zones by technetium-99m macroaggregated albumin SPET and dynamic {sup 133}Xe SPET. The distribution of emphysematous changes was assessed by density-mask computed tomography (CT) images which depicted abnormally low attenuation areas (LAAs) of less than -960 Hounsfield units. Two hundred and eighty-eight (59.2%) lung zones of 63 (77.7%) patients with pulmonary emphysema showed relative preservation of lung function in the peripheral lung, with a curvilinear band of normal perfusion (a stripe sign) and a significantly faster {sup 133}Xe half-clearance time (T{sub 1/2}) than in central lung (P<0.0001). Of these lung zones, 256 (88.8%) showed central-dominant LAA distributions on density-mask CT images, but the remaining 32 zones did not show any regional preference in LAA distribution. Conversely, 117 (24.0%) lung zones of 19 (23.4%) patients showed periphery-dominant perfusion defects and LAA distributions, with significantly prolonged T{sub 1/2} in the peripheral lung area (P<0.0001). The remaining 81 lung zones of the patients with pulmonary emphysema and all the lung zones of the healthy subjects and patients with non-obstructive lung diseases did not show a stripe sign, and no differences were observed in T{sub 1/2} values and LAA distributions between the central and peripheral lung. Relative preservation of peripheral lung function seems to be a characteristic feature in smoking-related pulmonary emphysema, and may indicate a

  11. An imaging flow cytometry method to assess ricin trafficking in A549 human lung epithelial cells.

    Science.gov (United States)

    Jenner, Dominic; Chong, Damien; Walker, Nicola; Green, A Christopher

    2018-02-01

    The endocytosis and trafficking of ricin in mammalian cells is an important area of research for those producing ricin anti-toxins and other ricin therapeutics. Ricin trafficking is usually observed by fluorescence microscopy techniques. This gives good resolution and leads to a detailed understanding of the internal movement of ricin within cells. However, microscopy techniques are often hampered by complex analysis and quantification techniques, and the inability to look at ricin trafficking in large populations of cells. In these studies we have directly labelled ricin and assessed if its trafficking can be observed using Imaging Flow Cytometry (IFC) both to the cytoplasmic region of cells and specifically to the Golgi apparatus. Using IDEAS® data analysis software the specific fluorescence location of the ricin within the cells was analysed. Then, using cytoplasmic masking techniques to quantify the number of cells with endocytosed cytoplasmic ricin or cells with Golgi-associated ricin, kinetic endocytosis curves were generated. Here we present, to the authors' knowledge, the first example of using imaging flow cytometry for evaluating the subcellular transport of protein cargo, using the trafficking of ricin toxin in lung cells as a model. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  12. Spatial and seasonal variations, sources, air-soil exchange, and carcinogenic risk assessment for PAHs and PCBs in air and soil of Kutahya, Turkey, the province of thermal power plants.

    Science.gov (United States)

    Dumanoglu, Yetkin; Gaga, Eftade O; Gungormus, Elif; Sofuoglu, Sait C; Odabasi, Mustafa

    2017-02-15

    Atmospheric and concurrent soil samples were collected during winter and summer of 2014 at 41 sites in Kutahya, Turkey to investigate spatial and seasonal variations, sources, air-soil exchange, and associated carcinogenic risks of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). The highest atmospheric and soil concentrations were observed near power plants and residential areas, and the wintertime concentrations were generally higher than ones measured in summer. Spatial distribution of measured ambient concentrations and results of the factor analysis showed that the major contributing PAH sources in Kutahya region were the coal combustion for power generation and residential heating (48.9%), and diesel and gasoline exhaust emissions (47.3%) while the major PCB sources were the coal (thermal power plants and residential heating) and wood combustion (residential heating) (45.4%), and evaporative emissions from previously used technical PCB mixtures (34.7%). Results of fugacity fraction calculations indicated that the soil and atmosphere were not in equilibrium for most of the PAHs (88.0% in winter, 87.4% in summer) and PCBs (76.8% in winter, 83.8% in summer). For PAHs, deposition to the soil was the dominant mechanism in winter while in summer volatilization was equally important. For PCBs, volatilization dominated in summer while deposition was higher in winter. Cancer risks associated with inhalation and accidental soil ingestion of soil were also estimated. Generally, the estimated carcinogenic risks were below the acceptable risk level of 10-6. The percentage of the population exceeding the acceptable risk level ranged from 10-6. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Assessment of bronchodilator response through changes in lung volumes in chronic airflow obstruction

    Directory of Open Access Journals (Sweden)

    J.B. Figueroa-Casas

    2003-10-01

    Full Text Available Although FEV1 improvement is routinely used to define bronchodilator (BD response, it correlates poorly with clinical effects. Changes in lung volumes (LV have shown better correlation with exercise tolerance and might be more sensitive to detect BD effects. We assessed the additional contribution of measuring LV before and after BD to detect acute improvement in lung function not demonstrated by FEV1, and the influence of the response criteria selected on this contribution. We analyzed 98 spirometries and plethismographies performed pre and post BD in patients with airflow obstruction (FEV1/FVC 10% of baseline (D>5 anD>15% were also analyzed. FEV1 identified as responders 32% of patients. Greater proportions were uncovered by slow vital capacity (51%, p5 anD>15%. Mean change and proportions of responders for each LV varied significantly (pSi bien el aumento del VEF1 es habitualmente utilizado para definir respuesta a broncodilatadores (BD, su correlación con efectos clínicos es pobre. Los cambios en volúmenes pulmonares (VP han demostrado mejor correlación con tolerancia al ejercicio y podrían ser más sensibles para detectar efectos de los BD. Nosotros evaluamos la contribución adicional de medir VP antes y después de BD para detectar mejoría funcional aguda no demostrada por cambios del VEF1, y la influencia del criterio de respuesta seleccionado en esta contribución. Se analizaron 98 espirometrías y pletismografías realizadas pre y post BD en pacientes con obstrucción al flujo aéreo (VEF1/CVF 10% del basal (D>5 y 15% fueron también analizados. El VEF1 identificó como respondedores a 32% de los pacientes. Proporciones mayores fueron identificadas por capacidad vital lenta (51%, p5 y 15%. El cambio promedio y las proporciones de respondedores para cada VP variaron significativamente (p<0.05 según que el cambio fuese expresado como porcentaje del basal o del valor predicho. Una proporción considerable de pacientes con obstrucci

  14. Genetic basis for susceptibility to lung cancer: Recent progress and future directions.

    Science.gov (United States)

    Yokota, Jun; Shiraishi, Kouya; Kohno, Takashi

    2010-01-01

    Lung cancer is the leading cause of cancer death worldwide, and cigarette smoking is the major environmental factor for its development. To elucidate the genetic differences in the susceptibility to lung cancer among individuals, genetic factors involved in tobacco-induced lung cancers have been extensively investigated and a number of genetic polymorphisms have been identified to date as candidates. Most of the polymorphisms identified are of genes encoding proteins associated with the activity to metabolize tobacco smoke carcinogens and to suppress mutations induced by those carcinogens, and functional significances have been elucidated for some of these polymorphisms. However, the significance of these polymorphisms in the contribution to lung cancer development still remains unclear. Recently, several novel lung cancer susceptibility genes, including those on chromosomes 5p15.33, 6p21, and 15q24-25.1, have been identified by large-scale genome-wide association (GWA) studies. The 15q25 region contains three nicotine acetylcholine receptor subunit genes, and their polymorphisms have been also reported as being associated with nicotine dependence. The 5p15.33 region is associated with risks specifically for lung adenocarcinoma, the commonest histological type and weakly associated with smoking. This locus has been shown to be associated with risks for a wide variety of cancers, including lung adenocarcinoma. Associations of the 6q21 region have not been consistently replicated among studies. The 6q23-25 and 13q31.3 regions were also identified by recent GWA studies as being associated with risk for lung cancer, particularly in never-smokers. However, contributions of genetic differences on these five loci to the susceptibility to overall lung cancer seem to be small. There are several molecular pathways for the development of lung adenocarcinomas, and environmental factors for their development are still unclear, especially those in never-smokers. In addition

  15. Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers.

    Science.gov (United States)

    Pfeifer, Gerd P; Denissenko, Mikhail F; Olivier, Magali; Tretyakova, Natalia; Hecht, Stephen S; Hainaut, Pierre

    2002-10-21

    It is estimated that cigarette smoking kills over 1 000 000 people each year by causing lung cancer as well as many other neoplasmas. p53 mutations are frequent in tobacco-related cancers and the mutation load is often higher in cancers from smokers than from nonsmokers. In lung cancers, the p53 mutational patterns are different between smokers and nonsmokers with an excess of G to T transversions in smoking-associated cancers. The prevalence of G to T transversions is 30% in smokers' lung cancer but only 12% in lung cancers of nonsmokers. A similar trend exists, albeit less marked, in laryngeal cancers and in head and neck cancers. This type of mutation is infrequent in most other tumors aside from hepatocellular carcinoma. At several p53 mutational hotspots common to all cancers, such as codons 248 and 273, a large fraction of the mutations are G to T events in lung cancers but are almost exclusively G to A transitions in non-tobacco-related cancers. Two important classes of tobacco smoke carcinogens are the polycyclic aromatic hydrocarbons (PAH) and the nicotine-derived nitrosamines. Recent studies have indicated that there is a strong coincidence of G to T transversion hotspots in lung cancers and sites of preferential formation of PAH adducts along the p53 gene. Endogenously methylated CpG dinucleotides are the preferred sites for G to T transversions, accounting for more than 50% of such mutations in lung tumors. The same dinucleotide, when present within CpG-methylated mutational reporter genes, is the target of G to T transversion hotspots in cells exposed to the model PAH compound benzo[a]pyrene-7,8-diol-9,10-epoxide. As summarized here, a number of other tobacco smoke carcinogens also can cause G to T transversion mutations. The available data suggest that p53 mutations in lung cancers can be attributed to direct DNA damage from cigarette smoke carcinogens rather than to selection of pre-existing endogenous mutations.

  16. Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: Assessed by micro-computed tomography and pathologic scores

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Gong Yong; Bok, Se Mi; Han, Young Min [Department of Radiology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Chung, Myung Ja [Department of Pathology, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Yoon, Kwon-Ha [Department of Radiology, Iksan Hospital, Iksan (Korea, Republic of); Kim, So Ri [Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Yong Chul, E-mail: leeyc@jbnu.ac.kr [Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju (Korea, Republic of)

    2012-08-15

    Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) agonists exhibit potent anti-fibrotic effects in the lung and other tissues. Recently, micro-computed tomography (CT) has been a useful tool for the investigation of lung diseases in small animals and is now increasingly applied to visualize and quantify the pulmonary structures. However, there is little information on the assessment for therapeutic effects of PPAR{gamma} agonists on the pulmonary fibrosis in mice using micro-CT. This study was aimed to determine the capability of micro-CT in examining the effects of rosiglitazone on pulmonary fibrosis. We used a murine model of bleomycin-induced lung fibrosis to evaluate the feasibility of micro-CT in evaluating the therapeutic potential of rosiglitazone on pulmonary fibrosis, comparing with pathologic scores. On micro-CT findings, ground glass opacity (80%) and consolidation (20%) were observed predominantly at 3 weeks after the instillation of bleomycin, and the radiologic features became more complex at 6 weeks. In bleomycin-instilled mice treated with rosiglitazone, the majority (80%) showed normal lung features on micro-CT. Radiological-pathologic correlation analyses revealed that ground glass opacity and consolidation were correlated closely with acute inflammation, while reticular opacity was well correlated with histological honeycomb appearance. These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis in mice and that the visualization of bleomycin-induced pulmonary fibrosis using micro-CT is satisfactory to assess the effects of rosiglitazone. It implies that micro-CT can be applied to evaluate therapeutic efficacies of a variety of candidate drugs for lung diseases.

  17. Development and Assessment of Countermeasure Formulations for Treatment of Lung Injury Induced by Chlorine Inhalation

    Science.gov (United States)

    Hoyle, Gary W.; Chen, Jing; Schlueter, Connie F.; Mo, Yiqun; Humphrey, David M.; Rawson, Greg; Niño, Joe A.; Carson, Kenneth H.

    2016-01-01

    Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection. Multiple parameters were varied to produce formulations with a wide range of in vitro release kinetics. Testing of selected formulations in chlorine-exposed mice demonstrated efficacy against key aspects of acute lung injury. The results show the feasibility of developing microencapsulated formulations that could be used to treat chlorine-induced acute lung injury by intramuscular injection, which represents a preferred route of administration in a mass casualty situation. PMID:26952014

  18. Quantitative assessment of global lung inflammation following radiation therapy using FDG PET/CT: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Abdulla, Sarah; Salavati, Ali; Saboury, Babak; Torigian, Drew A. [University of Pennsylvania, and Hospital of the University of Pennsylvania, Department of Radiology, Perelman School of Medicine, Philadelphia, PA (United States); Basu, Sandip [Bhabha Atomic Research Center, Tata Memorial Center Annexe, Radiation Medicine Center, Bombay (India); Alavi, Abass [University of Pennsylvania, and Hospital of the University of Pennsylvania, Department of Radiology, Perelman School of Medicine, Philadelphia, PA (United States); Hospital of the University of Pennsylvania, Department of Radiology, Division of Nuclear Medicine, Philadelphia, PA (United States)

    2014-02-15

    Radiation pneumonitis is the most severe dose-limiting complication in patients receiving thoracic radiation therapy. The aim of this study was to quantify global lung inflammation following radiation therapy using FDG PET/CT. We studied 20 subjects with stage III non-small-cell lung carcinoma who had undergone FDG PET/CT imaging before and after radiation therapy. On all PET/CT studies, the sectional lung volume (sLV) of each lung was calculated from each slice by multiplying the lung area by slice thickness. The sectional lung glycolysis (sLG) was calculated by multiplying the sLV and the lung sectional mean standardized uptake value (sSUVmean) on each slice passing through the lung. The lung volume (LV) was calculated by adding all sLVs from the lung, and the global lung glycolysis (GLG) was calculated by adding all sLGs from the lung. Finally, the lung SUVmean was calculated by dividing the GLG by the LV. The amount of inflammation in the lung parenchyma directly receiving radiation therapy was calculated by subtracting tumor measurements from GLG. In the lung directly receiving radiation therapy, the lung parenchyma SUVmean and global lung parenchymal glycolysis were significantly increased following therapy. In the contralateral lung (internal control), no significant changes were observed in lung SUVmean or GLG following radiation therapy. Global lung parenchymal glycolysis and lung parenchymal SUVmean may serve as potentially useful biomarkers to quantify lung inflammation on FDG PET/CT following thoracic radiation therapy. (orig.)

  19. Systems for Lung Volume Standardization during Static and Dynamic MDCT-based Quantitative Assessment of Pulmonary Structure and Function

    Science.gov (United States)

    Fuld, Matthew K.; Grout, Randall; Guo, Junfeng; Morgan, John H.; Hoffman, Eric A.

    2013-01-01

    Rationale and Objectives Multidetector-row Computed Tomography (MDCT) has emerged as a tool for quantitative assessment of parenchymal destruction, air trapping (density metrics) and airway remodeling (metrics relating airway wall and lumen geometry) in chronic obstructive pulmonary disease (COPD) and asthma. Critical to the accuracy and interpretability of these MDCT-derived metrics is the assurance that the lungs are scanned during a breath-hold at a standardized volume. Materials and Methods A computer monitored turbine-based flow meter system was developed to control patient breath-holds and facilitate static imaging at fixed percentages of the vital capacity. Due to calibration challenges with gas density changes during multi-breath xenon-CT an alternative system was required. The design incorporated dual rolling seal pistons. Both systems were tested in a laboratory environment and human subject trials. Results The turbine-based system successfully controlled lung volumes in 32/37 subjects, having a linear relationship for CT measured air volume between repeated scans: for all scans, the mean and confidence interval of the differences (scan1-scan2) was −9 ml (−169, 151); for TLC alone 6 ml (−164, 177); for FRC alone, −23 ml (−172, 126). The dual-piston system successfully controlled lung volume in 31/41 subjects. Study failures related largely to subject non-compliance with verbal instruction and gas leaks around the mouthpiece. Conclusion We demonstrate the successful use of a turbine-based system for static lung volume control and demonstrate its inadequacies for dynamic xenon-CT studies. Implementation of a dual-rolling seal spirometer has been shown to adequately control lung volume for multi-breath wash-in xenon-CT studies. These systems coupled with proper patient coaching provide the tools for the use of CT to quantitate regional lung structure and function. The wash-in xenon-CT method for assessing regional lung function, while not

  20. Evidence supporting product standards for carcinogens in smokeless tobacco products.

    Science.gov (United States)

    Hatsukami, Dorothy K; Stepanov, Irina; Severson, Herb; Jensen, Joni A; Lindgren, Bruce R; Horn, Kimberly; Khariwala, Samir S; Martin, Julia; Carmella, Steven G; Murphy, Sharon E; Hecht, Stephen S

    2015-01-01

    Smokeless tobacco products sold in the United States vary significantly in yields of nicotine and tobacco-specific nitrosamines (TSNA). With the passage of the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration now has the authority to establish product standards. However, limited data exist determining the relative roles of pattern of smokeless tobacco use versus constituent levels in the smokeless tobacco product in exposure of users to carcinogens. In this study, smokeless tobacco users of brands varying in nicotine and TSNA content were recruited from three different regions in the U.S. Participants underwent two assessment sessions. During these sessions, demographic and smokeless tobacco use history information along with urine samples to assess biomarkers of exposure and effect were collected. During the time between data collection, smokeless tobacco users recorded the amount and duration of smokeless tobacco use on a daily basis using their diary cards. Results showed that independent of pattern of smokeless tobacco use and nicotine yields, levels of TSNA in smokeless tobacco products played a significant role in carcinogen exposure levels. Product standards for reducing levels of TSNA in smokeless tobacco products are necessary to decrease exposure to these toxicants and potentially to reduce risk for cancer. ©2014 American Association for Cancer Research.

  1. Pulmonary permeability assessed by fluorescent-labeled dextran instilled intranasally into mice with LPS-induced acute lung injury.

    Directory of Open Access Journals (Sweden)

    Honglei Chen

    Full Text Available Several different methods have been used to assess pulmonary permeability in response to acute lung injury (ALI. However, these methods often involve complicated procedures and algorithms that are difficult to precisely control. The purpose of the current study is to establish a feasible method to evaluate alterations in lung permeability by instilling fluorescently labeled dextran (FITC-Dextran intranasally.For the mouse model of direct ALI, lipopolysaccharide (LPS was administered intranasally. FITC-Dextran was instilled intranasally one hour before the mice were euthanized. Plasma fluorescence intensities from the LPS group were significantly higher than in the control group. To determine the reliability and reproducibility of the procedure, we also measured the lung wet-to-dry weight ratio, the protein concentration of the bronchoalveolar lavage fluid, tight and adherens junction markers and pathological changes. Consistent results were observed when the LPS group was compared with the control group. Simultaneously, we found that the concentration of plasma FITC-Dextran was LPS dose-dependent. The concentration of plasma FITC-Dextran also increased with initial intranasal FITC-Dextran doses. Furthermore, increased fluorescence intensity of plasma FITC-Dextran was found in the intraperitoneally LPS-induced ALI model.In conclusion, the measurement of FITC-Dextran in plasma after intranasal instillation is a simple, reliable, and reproducible method to evaluate lung permeability alterations in vivo. The concentration of FITC-Dextran in the plasma may be useful as a potential peripheral biomarker of ALI in experimental clinical studies.

  2. A Case Report of Lung Cancer in a Horse Trainer Caused by Exposure to Respirable Crystalline Silica: An Exposure Assessment

    Directory of Open Access Journals (Sweden)

    Jin-Ha Yoon

    2013-03-01

    Full Text Available Here, we present a case of lung cancer in a 48-year-old male horse trainer. To the best of our knowledge, this is the first such case report to include an exposure assessment of respirable crystalline silica (RCS as a quartz. The trainer had no family history of lung cancer. Although he had a 15 pack/year cigarette-smoking history, he had stopped smoking 12 years prior to his diagnosis. For the past 23 years, he had performed longeing, and trained 7-12 horses per day on longeing arena surfaces covered by recycled sands, the same surfaces used in race tracks. We investigated his workplace RCS exposure, and found it to be the likely cause of his lung cancer. The 8-hour time weight average range of RCS was 0.020 to 0.086 mg/m3 in the longeing arena. Horse trainers are exposed to RCS from the sand in longeing arenas, and the exposure level is high enough to have epidemiological ramifications for the occupational risk of lung cancer.

  3. IARC monographs: 40 years of evaluating carcinogenic hazards to humans.

    Science.gov (United States)

    Pearce, Neil; Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M; Armstrong, Bruce K; Baccarelli, Andrea A; Beland, Frederick A; Berrington, Amy; Bertazzi, Pier Alberto; Birnbaum, Linda S; Brownson, Ross C; Bucher, John R; Cantor, Kenneth P; Cardis, Elisabeth; Cherrie, John W; Christiani, David C; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A; Dement, John M; Douwes, Jeroen; Eisen, Ellen A; Engel, Lawrence S; Fenske, Richard A; Fleming, Lora E; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H; Lynch, Charles F; Lynge, Elsebeth; 't Mannetje, Andrea; McMichael, Anthony J; McLaughlin, John R; Marrett, Loraine; Martuzzi, Marco; Merchant, James A; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E; Monson, Richard; Nordby, Karl-Cristian; Olshan, Andrew F; Parent, Marie-Elise; Perera, Frederica P; Perry, Melissa J; Pesatori, Angela Cecilia; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M; Rushton, Lesley; Rusiecki, Jennifer A; Rusyn, Ivan; Samet, Jonathan M; Sandler, Dale P; de Sanjose, Silvia; Schernhammer, Eva; Costantini, Adele Seniori; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silverman, Debra T; Simonato, Lorenzo; Smith, Allan H; Smith, Martyn T; Spinelli, John J; Spitz, Margaret R; Stallones, Lorann; Stayner, Leslie T; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W; Stewart, Patricia A; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E; Vainio, Harri; Vena, John; Vermeulen, Roel; Victora, Cesar G; Ward, Elizabeth M; Weinberg, Clarice R; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia Hoar

    2015-06-01

    Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.

  4. Assessing breathing motion by shape matching of lung and diaphragm surfaces

    Science.gov (United States)

    Urschler, Martin; Bischof, Horst

    2005-04-01

    Studying complex thorax breating motion is an important research topic for accurate fusion of functional and anatomical data, radiotherapy planning or reduction of breathing motion artifacts. We investigate segmented CT lung, airway and diaphragm surfaces at several different breathing states between Functional Residual and Total Lung Capacity. In general, it is hard to robustly derive corresponding shape features like curvature maxima from lung and diaphragm surfaces since diaphragm and rib cage muscles tend to deform the elastic lung tissue such that e.g. ridges might disappear. A novel registration method based on the shape context approach for shape matching is presented where we extend shape context to 3D surfaces. The shape context approach was reported as a promising method for matching 2D shapes without relying on extracted shape features. We use the point correspondences for a non-rigid thin-plate-spline registration to get deformation fields that describe the movement of lung and diaphragm. Our validation consists of experiments on phantom and real sheep thorax data sets. Phantom experiments make use of shapes that are manipulated with known transformations that simulate breathing behaviour. Real thorax data experiments use a data set showing lungs and diaphragm at 5 distinct breathing states, where we compare subsets of the data sets and qualitatively and quantitatively asses the registration performance by using manually identified corresponding landmarks.

  5. Polycyclic aromatic hydrocarbon--DNA adducts in white blood cells from lung cancer patients: no correlation with adduct levels in lung

    NARCIS (Netherlands)

    van Schooten, F. J.; Hillebrand, M. J.; van Leeuwen, F. E.; van Zandwijk, N.; Jansen, H. M.; den Engelse, L.; Kriek, E.

    1992-01-01

    Smokers of cigarettes are exposed to a number of carcinogens, including polycyclic aromatic hydrocarbons (PAHs), and are at a high risk for lung cancer. PAHs exert their carcinogenic activity after metabolic activation to reactive intermediates that can damage DNA through adduct formation. Measuring

  6. Arsenic, asbestos and radon: emerging players in lung tumorigenesis

    Directory of Open Access Journals (Sweden)

    Hubaux Roland

    2012-11-01

    Full Text Available Abstract The cause of lung cancer is generally attributed to tobacco smoking. However lung cancer in never smokers accounts for 10 to 25% of all lung cancer cases. Arsenic, asbestos and radon are three prominent non-tobacco carcinogens strongly associated with lung cancer. Exposure to these agents can lead to genetic and epigenetic alterations in tumor genomes, impacting genes and pathways involved in lung cancer development. Moreover, these agents not only exhibit unique mechanisms in causing genomic alterations, but also exert deleterious effects through common mechanisms, such as oxidative stress, commonly associated with carcinogenesis. This article provides a comprehensive review of arsenic, asbestos, and radon induced molecular mechanisms responsible for the generation of genetic and epigenetic alterations in lung cancer. A better understanding of the mode of action of these carcinogens will facilitate the prevention and management of lung cancer related to such environmental hazards.

  7. Arsenic, asbestos and radon: emerging players in lung tumorigenesis

    Science.gov (United States)

    2012-01-01

    The cause of lung cancer is generally attributed to tobacco smoking. However lung cancer in never smokers accounts for 10 to 25% of all lung cancer cases. Arsenic, asbestos and radon are three prominent non-tobacco carcinogens strongly associated with lung cancer. Exposure to these agents can lead to genetic and epigenetic alterations in tumor genomes, impacting genes and pathways involved in lung cancer development. Moreover, these agents not only exhibit unique mechanisms in causing genomic alterations, but also exert deleterious effects through common mechanisms, such as oxidative stress, commonly associated with carcinogenesis. This article provides a comprehensive review of arsenic, asbestos, and radon induced molecular mechanisms responsible for the generation of genetic and epigenetic alterations in lung cancer. A better understanding of the mode of action of these carcinogens will facilitate the prevention and management of lung cancer related to such environmental hazards. PMID:23173984

  8. Arsenic, asbestos and radon: emerging players in lung tumorigenesis.

    Science.gov (United States)

    Hubaux, Roland; Becker-Santos, Daiana D; Enfield, Katey S S; Lam, Stephen; Lam, Wan L; Martinez, Victor D

    2012-11-22

    The cause of lung cancer is generally attributed to tobacco smoking. However lung cancer in never smokers accounts for 10 to 25% of all lung cancer cases. Arsenic, asbestos and radon are three prominent non-tobacco carcinogens strongly associated with lung cancer. Exposure to these agents can lead to genetic and epigenetic alterations in tumor genomes, impacting genes and pathways involved in lung cancer development. Moreover, these agents not only exhibit unique mechanisms in causing genomic alterations, but also exert deleterious effects through common mechanisms, such as oxidative stress, commonly associated with carcinogenesis. This article provides a comprehensive review of arsenic, asbestos, and radon induced molecular mechanisms responsible for the generation of genetic and epigenetic alterations in lung cancer. A better understanding of the mode of action of these carcinogens will facilitate the prevention and management of lung cancer related to such environmental hazards.

  9. Evaluation of the carcinogenic risks at the influence of POPs.

    Science.gov (United States)

    Nazhmetdinova, Aiman; Kassymbayev, Adlet; Chalginbayeva, Altinay

    2017-12-20

    Kazakhstan is included in the list of environmentally vulnerable countries and Kyzylorda oblast in particular. This is due to its geographical, spatial and temporal and socioeconomic features. As part of the program "Integrated approaches in the management of public health in the Aral region", we have carried out an expertise on many samples of natural environments and products. Samples were selected in accordance with sampling procedures according to regulatory documents by specialists of the Pesticide Toxicology Laboratory. It is accredited by the State Standard of the Republic of Kazakhstan, for compliance with ST RK ISO/IEC 17025-2007 "General requirements for the competence of test and calibration laboratories". Gas chromatograph was used for the determination of residues of organochlorine pesticides. For the determination of dioxins, polychlorinated biphenyl was conducted on the gas chromatomass spectrometer with quadruple detector produce by Agilent Company, USA. To assess the risk, we carried out the mathematical calculations according to the risk of chemicals polluting (No P 2.1.10.1920-04, Russia). Calculation of the carcinogenic risk was carried out with the use of data on the size of the exposure and meanings of carcinogenic potential factors (slope factor and unit risk). The evaluation of persistent organic pollutants (POPs), based on the previous results of the research concerning water, soil and food products, was held in five population settlements in Kyzylorda oblast villages: Ayteke bi, Zhalagash, Zhosaly, Shieli and Aralsk town. Pollution with the POPs in the environmental objects by means of exposition and evaluation of the carcinogenic risk to human health is confirmed by the data of the statistical reporting about some morbidity in Kyzylorda oblast, such as skin diseases and subcutaneous tissue, endocrine system diseases, pregnancy complications etc. The received levels of carcinogenic risks, which were first carried out in the Republic of

  10. Assessment of quantitative analysis methods for lung F-18-fluorodeoxyglucose PET

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joon Young; Choi, Young; Choi, Joon Young; Lee, Kyung Han; Kim, Sang Eun; Choi, Yeong Seong; Kim, Byung Tae [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of); Kim, Yong Jin [College of Medicine, Hanyang Univ., Seoul (Korea, Republic of)

    1998-08-01

    The purpose of this study was to assess the diagnostic accuracy of various quantitation methods using F-18-fluorodeoxyglucose (EDG) in patients with malignant or benign lung lesion. 22 patients (13 malignant including 5 bronchoalverolar cell cancer; 9 benign lesions including 1 hamartoma and 8 active inflammation) were studied after overnight fasting. We performed dynamic PET imaging for 56 min after injection of 370 MBq (10 mCi) of FDG. Standardized uptake values normalized to patient's body weight and plasma glucose concentration (SUVglu) were calculated. The uptake rate constant of FDG and glucose metabolic rate were quantified using Patlak graphical analysis (Kpat and MRpat), three compartment-five parameter model (K5p, MR5p), and six parameter model taking into account heterogeneity of tumor tissue (K6p, MR6p). Areas under receiver operating characteristic curves (ROC) were calculated for each method. There was no significant difference of rate constant or glucose metabolic rate measured by various quantitation methods between malignant and benign lesions. The area under ROC curve were 0.73 for SUVglu, 0.66 for Kpat, 0.77 for MRpat, 0.71 for K5p, 0.73 for MR5p, 0.70 for K6p, and 0.78 for MR6p. No significant difference of area under the ROC curbe between these methods was observed except the area between Kpat vs. MRpat(p<0.05). Quantitative methods did not improve diagnostic accuracy in comparison with nonkinetic methods. However, the clinical utility of these methods needs to be evaluated further in patients with low pretest likelihood of active inflammation or bronchoalveolar cell carcinoma.

  11. Early Assessment of Treatment Responses During Radiation Therapy for Lung Cancer Using Quantitative Analysis of Daily Computed Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Paul, Jijo; Yang, Cungeng [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Wu, Hui [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou (China); Tai, An [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Dalah, Entesar [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Department of Medical Diagnostic Imaging, College of Health Science, University of Sharjah (United Arab Emirates); Zheng, Cheng [Biostatistics, Joseph. J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin (United States); Johnstone, Candice [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Kong, Feng-Ming [Department of Radiation Oncology, Indiana University, Indianapolis, Indiana (United States); Gore, Elizabeth [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Li, X. Allen, E-mail: ali@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

    2017-06-01

    Purpose: To investigate early tumor and normal tissue responses during the course of radiation therapy (RT) for lung cancer using quantitative analysis of daily computed tomography (CT) scans. Methods and Materials: Daily diagnostic-quality CT scans acquired using CT-on-rails during CT-guided RT for 20 lung cancer patients were quantitatively analyzed. On each daily CT set, the contours of the gross tumor volume (GTV) and lungs were generated and the radiation dose delivered was reconstructed. The changes in CT image intensity (Hounsfield unit [HU]) features in the GTV and the multiple normal lung tissue shells around the GTV were extracted from the daily CT scans. The associations between the changes in the mean HUs, GTV, accumulated dose during RT delivery, and patient survival rate were analyzed. Results: During the RT course, radiation can induce substantial changes in the HU histogram features on the daily CT scans, with reductions in the GTV mean HUs (dH) observed in the range of 11 to 48 HU (median 30). The dH is statistically related to the accumulated GTV dose (R{sup 2} > 0.99) and correlates weakly with the change in GTV (R{sup 2} = 0.3481). Statistically significant increases in patient survival rates (P=.038) were observed for patients with a higher dH in the GTV. In the normal lung, the 4 regions proximal to the GTV showed statistically significant (P<.001) HU reductions from the first to last fraction. Conclusion: Quantitative analysis of the daily CT scans indicated that the mean HUs in lung tumor and surrounding normal tissue were reduced during RT delivery. This reduction was observed in the early phase of the treatment, is patient specific, and correlated with the delivered dose. A larger HU reduction in the GTV correlated significantly with greater patient survival. The changes in daily CT features, such as the mean HU, can be used for early assessment of the radiation response during RT delivery for lung cancer.

  12. Testing chemical carcinogenicity by using a transcriptomics HepaRG-based model?

    Science.gov (United States)

    Doktorova, T Y; Yildirimman, Reha; Ceelen, Liesbeth; Vilardell, Mireia; Vanhaecke, Tamara; Vinken, Mathieu; Ates, Gamze; Heymans, Anja; Gmuender, Hans; Bort, Roque; Corvi, Raffaella; Phrakonkham, Pascal; Li, Ruoya; Mouchet, Nicolas; Chesne, Christophe; van Delft, Joost; Kleinjans, Jos; Castell, Jose; Herwig, Ralf; Rogiers, Vera

    2014-01-01

    The EU FP6 project carcinoGENOMICS explored the combination of toxicogenomics and in vitro cell culture models for identifying organotypical genotoxic- and non-genotoxic carcinogen-specific gene signatures. Here the performance of its gene classifier, derived from exposure of metabolically competent human HepaRG cells to prototypical non-carcinogens (10 compounds) and hepatocarcinogens (20 compounds), is reported. Analysis of the data at the gene and the pathway level by using independent biostatistical approaches showed a distinct separation of genotoxic from non-genotoxic hepatocarcinogens and non-carcinogens (up to 88 % correct prediction). The most characteristic pathway responding to genotoxic exposure was DNA damage. Interlaboratory reproducibility was assessed by blindly testing of three compounds, from the set of 30 compounds, by three independent laboratories. Subsequent classification of these compounds resulted in correct prediction of the genotoxicants. As expected, results on the non-genotoxic carcinogens and the non-carcinogens were less predictive. In conclusion, the combination of transcriptomics with the HepaRG in vitro cell model provides a potential weight of evidence approach for the evaluation of the genotoxic potential of chemical substances.

  13. ROSC-Pred: web-service for rodent organ-specific carcinogenicity prediction.

    Science.gov (United States)

    Lagunin, Alexey; Rudik, Anastasia; Druzhilovsky, Dmitry; Filimonov, Dmitry; Poroikov, Vladimir

    2017-10-23

    Identification of rodent carcinogens is an important task in risk assessment of chemicals. SAR methods were proposed to reduce the number of animal experiments. Most of these methods ignore information about organ-specificity of tumorigenesis. Our study was aimed at the creation of classification models and a freely available online service for prediction of rodent carcinogens considering the species (rats, mice), sex, and tissue-specificity from structural formula of compounds. The data from Carcinogenic Potency Database for 1011 organic compounds evaluated on the standard two-year rodent carcinogenicity bioassay was used for the creation of training sets. Structure-activity relationships models for prediction of rodent organ-specific carcinogenicity were created by PASS software, which was based on Bayesian-like approach and MNA (Multilevel Neighborhoods of Atoms) descriptors. The average prediction accuracy (AUC) for training sets calculated by leave-one-out and 10-fold cross-validation was 79% and 78.2%, respectively. Freely available on the web at http://www.way2drug.com/ROSC. alexey.lagunin@ibmc.msk.ru. Supplementary data are available at Bioinformatics online.

  14. Testing chemical carcinogenicity by using a transcriptomics HepaRG-based model?

    Science.gov (United States)

    Doktorova, T. Y.; Yildirimman, Reha; Ceelen, Liesbeth; Vilardell, Mireia; Vanhaecke, Tamara; Vinken, Mathieu; Ates, Gamze; Heymans, Anja; Gmuender, Hans; Bort, Roque; Corvi, Raffaella; Phrakonkham, Pascal; Li, Ruoya; Mouchet, Nicolas; Chesne, Christophe; van Delft, Joost; Kleinjans, Jos; Castell, Jose; Herwig, Ralf; Rogiers, Vera

    2014-01-01

    The EU FP6 project carcinoGENOMICS explored the combination of toxicogenomics and in vitro cell culture models for identifying organotypical genotoxic- and non-genotoxic carcinogen-specific gene signatures. Here the performance of its gene classifier, derived from exposure of metabolically competent human HepaRG cells to prototypical non-carcinogens (10 compounds) and hepatocarcinogens (20 compounds), is reported. Analysis of the data at the gene and the pathway level by using independent biostatistical approaches showed a distinct separation of genotoxic from non-genotoxic hepatocarcinogens and non-carcinogens (up to 88 % correct prediction). The most characteristic pathway responding to genotoxic exposure was DNA damage. Interlaboratory reproducibility was assessed by blindly testing of three compounds, from the set of 30 compounds, by three independent laboratories. Subsequent classification of these compounds resulted in correct prediction of the genotoxicants. As expected, results on the non-genotoxic carcinogens and the non-carcinogens were less predictive. In conclusion, the combination of transcriptomics with the HepaRG in vitro cell model provides a potential weight of evidence approach for the evaluation of the genotoxic potential of chemical substances. PMID:26417288

  15. 4DCT-based assessment of regional airflow distribution in healthy human lungs during tidal breathing

    Science.gov (United States)

    Choi, Jiwoong; Jahani, Nariman; Choi, Sanghun; Hoffman, Eric; Lin, Ching-Long

    2014-11-01

    Nonlinear dynamics of regional airflow distribution in healthy human lungs are studied with four-dimensional computed tomography (4DCT) quantitative imaging of four subjects. During the scanning session, subjects continuously breathed with tidal volumes controlled by the dual piston system. For each subject, 10 instantaneous volumetric image data sets (5 inspiratory and 5 expiratory phases) were reconstructed. A mass-preserving image registration was then applied to pairs of these image data to construct a breathing lung model. Regional distributions of local flow rate fractions are computed from time-varying local air volumes. The 4DCT registration-based method provides the link between local and global air volumes of the lung, allowing derivation of time-varying regional flow rates during the tidal breathing for computational fluid dynamics analysis. The local flow rate fraction remains greater in the lower lobes than in the upper lobes, being qualitatively consistent with those derived from three static CT (3SCT) images (Yin et al. JCP 2013). However, unlike 3SCT, the 4DCT data exhibit lung hysteresis between inspiration and expiration, providing more sensitive measures of regional ventilation and lung mechanics. NIH Grants U01-HL114494, R01-HL094315 and S10-RR022421.

  16. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

    2015-07-01

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  17. Particulate matter air pollution components and risk for lung cancer

    DEFF Research Database (Denmark)

    Raaschou-Nielsen, O.; Beelen, Rob; Wang, M.

    2016-01-01

    BACKGROUND: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. METHODS: We used data from 14 cohort studies in eight European countries. We...... geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models.......59; 1.12-2.26 per 2ng/m(3)) and PM10 K (1.17; 1.02-1.33 per 100ng/m(3)). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S. CONCLUSIONS: This study indicates that the association between PM in air pollution and lung cancer can be attributed...

  18. Residual volume/total lung capacity ratio confers limited additive significance to lung clearance index for assessment of adults with bronchiectasis

    Science.gov (United States)

    Yuan, Jing-jing; Huang, Yan; Li, Hui-min; Chen, Rong-chang; Zhong, Nan-shan

    2017-01-01

    Background Mosaicism and hyperinflation are common pathophysiologic features of bronchiectasis. The magnitude of ventilation heterogeneity might have been affected by the degree of hyperinflation. Some studies have evaluated the discriminative performance of lung clearance index (LCI) in bronchiectasis patients, but the additive diagnostic value of hyperinflation metrics to LCI is unknown. Objective To compare LCI and the ratio of residual volume to total lung capacity (RV/TLC), along with the LCI normalized with RV/TLC, in terms of discriminative performance, correlation and concordance with clinical variables in adults with bronchiectasis. Methods Measurement items included chest high-resolution computed tomography, multiple-breath nitrogen washout test, spirometry, and sputum culture. We analyzed bronchodilator responses by stratifying LCI and RV/TLC according to their median levels (LCIHigh/RV/TLCHigh, LCILow/RV/TLCHigh, LCIHigh/RV/TLCLow, and LCILow/RV/TLCLow). Results Data from 127 adults with clinically stable bronchiectasis were analyzed. LCI had greater diagnostic value than RV/TLC in discriminating moderate-to-severe from mild bronchiectasis, had greater concordance in reflecting clinical characteristics (including the number of bronchiectatic lobes, radiological severity score, and the presence of cystic bronchiectasis). Normalization of LCI with RV/TLC did not contribute to greater discriminative performance or concordance with clinical variables. The LCI, before and after normalization with RV/TLC, correlated statistically with age, sex, HRCT score, Pseudomonas aeruginosa colonization, cystic bronchiectasis, and ventilation heterogeneity (all PTLC levels. Conclusion LCI is superior to RV/TLC for bronchiectasis assessment. Normalization with RV/TLC is not required. Stratification of LCI and RV/TLC is not associated with significantly different bronchodilator responses. PMID:28886040

  19. Residual volume/total lung capacity ratio confers limited additive significance to lung clearance index for assessment of adults with bronchiectasis.

    Directory of Open Access Journals (Sweden)

    Wei-Jie Guan

    Full Text Available Mosaicism and hyperinflation are common pathophysiologic features of bronchiectasis. The magnitude of ventilation heterogeneity might have been affected by the degree of hyperinflation. Some studies have evaluated the discriminative performance of lung clearance index (LCI in bronchiectasis patients, but the additive diagnostic value of hyperinflation metrics to LCI is unknown.To compare LCI and the ratio of residual volume to total lung capacity (RV/TLC, along with the LCI normalized with RV/TLC, in terms of discriminative performance, correlation and concordance with clinical variables in adults with bronchiectasis.Measurement items included chest high-resolution computed tomography, multiple-breath nitrogen washout test, spirometry, and sputum culture. We analyzed bronchodilator responses by stratifying LCI and RV/TLC according to their median levels (LCIHigh/RV/TLCHigh, LCILow/RV/TLCHigh, LCIHigh/RV/TLCLow, and LCILow/RV/TLCLow.Data from 127 adults with clinically stable bronchiectasis were analyzed. LCI had greater diagnostic value than RV/TLC in discriminating moderate-to-severe from mild bronchiectasis, had greater concordance in reflecting clinical characteristics (including the number of bronchiectatic lobes, radiological severity score, and the presence of cystic bronchiectasis. Normalization of LCI with RV/TLC did not contribute to greater discriminative performance or concordance with clinical variables. The LCI, before and after normalization with RV/TLC, correlated statistically with age, sex, HRCT score, Pseudomonas aeruginosa colonization, cystic bronchiectasis, and ventilation heterogeneity (all P<0.05. Different bronchodilator responses were not significant among the four subgroups of bronchiectasis patients, including those with discordant LCI and RV/TLC levels.LCI is superior to RV/TLC for bronchiectasis assessment. Normalization with RV/TLC is not required. Stratification of LCI and RV/TLC is not associated with

  20. Residual volume/total lung capacity ratio confers limited additive significance to lung clearance index for assessment of adults with bronchiectasis.

    Science.gov (United States)

    Guan, Wei-Jie; Yuan, Jing-Jing; Huang, Yan; Li, Hui-Min; Chen, Rong-Chang; Zhong, Nan-Shan

    2017-01-01

    Mosaicism and hyperinflation are common pathophysiologic features of bronchiectasis. The magnitude of ventilation heterogeneity might have been affected by the degree of hyperinflation. Some studies have evaluated the discriminative performance of lung clearance index (LCI) in bronchiectasis patients, but the additive diagnostic value of hyperinflation metrics to LCI is unknown. To compare LCI and the ratio of residual volume to total lung capacity (RV/TLC), along with the LCI normalized with RV/TLC, in terms of discriminative performance, correlation and concordance with clinical variables in adults with bronchiectasis. Measurement items included chest high-resolution computed tomography, multiple-breath nitrogen washout test, spirometry, and sputum culture. We analyzed bronchodilator responses by stratifying LCI and RV/TLC according to their median levels (LCIHigh/RV/TLCHigh, LCILow/RV/TLCHigh, LCIHigh/RV/TLCLow, and LCILow/RV/TLCLow). Data from 127 adults with clinically stable bronchiectasis were analyzed. LCI had greater diagnostic value than RV/TLC in discriminating moderate-to-severe from mild bronchiectasis, had greater concordance in reflecting clinical characteristics (including the number of bronchiectatic lobes, radiological severity score, and the presence of cystic bronchiectasis). Normalization of LCI with RV/TLC did not contribute to greater discriminative performance or concordance with clinical variables. The LCI, before and after normalization with RV/TLC, correlated statistically with age, sex, HRCT score, Pseudomonas aeruginosa colonization, cystic bronchiectasis, and ventilation heterogeneity (all P<0.05). Different bronchodilator responses were not significant among the four subgroups of bronchiectasis patients, including those with discordant LCI and RV/TLC levels. LCI is superior to RV/TLC for bronchiectasis assessment. Normalization with RV/TLC is not required. Stratification of LCI and RV/TLC is not associated with significantly different

  1. Effects of combined exposure of F344 rats to inhaled Plutonium-239 dioxide and a chemical carcinogen (NNK)

    Energy Technology Data Exchange (ETDEWEB)

    Lundgren, D.L.; Carlton, W.W. [Purdue Univ., Lafayette, IN (United States); Griffith, W.C. [and others

    1995-12-01

    Workers in nuclear weapons facilities have a significant potential for exposure to chemical carcinogens and to radiation from external sources or from internally deposited radionuclides such as {sup 239}Pu. Although the carcinogenic effects of inhaled {sup 239}Pu and many chemicals have been studied individually, very little information is available on their combined effects. One chemical carcinogen that workers could be exposed to via tobacco smoke is the tobacco-specific nitrosamine 4-(N-methyl-n-nitrosamino)-1-(3-pyridyl)-1(3-pyridyl)-1-butanone (NNK), a product of tobacco curing and the pyrolysis of nicotine in tobacco. NNK causes lung tumors in rats, regardless of the route of administration and to a lesser extent liver, nasal, and pancreatic tumors. From the results presented, it can be concluded that exposure to a chemical carcinogen (NNK) in combination with {alpha}-particle radiation from inhaled {sup 239}PuO{sub 2} acts in, at best, an additive manner in inducing lung cancer in rats.

  2. Assessment of airway hyperresponsiveness in mouse models of allergic lung disease using detailed measurements of respiratory mechanics.

    Science.gov (United States)

    Hartney, John M; Robichaud, Annette

    2013-01-01

    This chapter provides an outline of the procedures necessary to measure airway hyperresponsiveness to inhaled methacholine in mouse models of allergic lung disease. We present a method for acquiring detailed measurements of respiratory mechanics using broadband low-frequency oscillatory waveforms applied at the subject's airway opening and analyzed using the constant phase model of the lung. We acknowledge that there are other methods of measuring airway responsiveness in allergic rodent models. However, a discussion of the merits and or detriments of these various methods have been vigorously debated in the primary literature and are beyond the scope of this chapter. The goal of this chapter is to provide a guide in how to begin these types of assays in laboratories which have little to no experience with these particular types of assessments.

  3. The carcinogenic potential of nanomaterials, their release from products and options for regulating them.

    Science.gov (United States)

    Becker, Heidi; Herzberg, Frank; Schulte, Agnes; Kolossa-Gehring, Marike

    2011-06-01

    A summary of a critical review by a working group of the German Federal Environment Agency and the German Federal Institute for Risk Assessment on the carcinogenic potential of nanomaterials is presented. After a critical review of the available data, we conclude that the potential carcinogenic risk of nanomaterials can currently be assessed only on a case-by-case basis. There is certain evidence that different forms of CNTs (carbon nanotubes) and nanoscale TiO(2) particles may induce tumours in sensitive animal models. It is assumed that the mode of action of the inhalation toxicity of asbestos-like fibres and of inhalable fractions of biopersistent fine dusts of low toxicity (nano-TiO(2)) is linked to chronic inflammatory processes. Existing epidemiological studies on carcinogenicity for these manufactured nanomaterials are not sufficiently conclusive. Generally speaking, the database is not adequate for an assessment of the carcinogenic potential of nanomaterials. Whereas a number of studies provide evidence of a nano-specific potential to induce tumours, other studies did not. This is possibly due to insufficient characterisation of the test material, difference in the experimental design, the use of different animal models and species and/or differences in dosimetry (both with regard to the appropriate dose metric and the estimated effective dose quantities). An assessment of the carcinogenic potential and its relevance for humans are currently fraught with uncertainty. Furthermore, the nano-specificity of the carcinogenic effects observed cannot be conclusively evaluated. Specific carcinogenic effects of nanomaterials may be both quantitative and qualitative. In quantitative terms, the carcinogenic effects of nanoparticles are thought to be simply more pronounced compared to the corresponding bulk material (due, for example, to the considerably larger surface area and higher number of particles relative to the mass concentration). On the other hand, certain

  4. Emissions and air exposure of carcinogens and co-carcinogens in four Nordic countries

    DEFF Research Database (Denmark)

    Fauser, Patrik; Plejdrup, Marlene Schmidt; Ketzel, Matthias

    . A list of carcinogenic andco-carcinogenic pollutants (particles, heavy metals and organic compounds) emittedfrom energy production, industrial activities, road transport, navigation, agriculture, residential heating and product use was compiled. Pollutant emissions levels for 2010and trends for 1990...... to 2010 were compiled and discussed, and modelled andmeasured atmospheric concentrations for 2010 were compiled on regional, urbanand local scales. Nordic maps of emissions and air concentrations of PM2.5, PM10, NOx,NMVOC, benzene, BaP, dioxin, cadmium and nickel were compiled for allaggregated main...

  5. Assessment of fetal lung maturity by ultrasound: objective study using gray-scale histogram.

    Science.gov (United States)

    Beck, Ana Paula Avritscher; Araujo Júnior, Edward; Leslie, Ana Teresa Figueiredo Stochero; Camano, Luiz; Moron, Antonio Fernandes

    2015-04-01

    To evaluate lung maturity using ultrasound (US), comparing the subjective and gray-scale histogram (GSH) techniques. A total of 77 single pregnancies were evaluated and divided into the following two groups: 11 women of gestational age 28 to 35 + 6 weeks and 66 women ≥ 36 weeks. The women underwent to emergency or planned cesarean section, according to fetal-maternal indications. The US was performed on the mean sagittal plane of the fetal torso, in order to observe the lung and hepatic areas. Fetal lung maturity was evaluated subjectively and through GSH. After delivery, the incidence of respiratory distress in the newborn was evaluated. The analyses were considered to be correct or incorrect, and comparisons were made using the McNemar test. In order to compare lung/hepatic echogenicity using GSH in groups with and without respiratory distress, the Student's t-test was used. The subjective evaluation identified 41 cases (53.2%) correctly and 36 (46.8%) incorrectly, while GSH found 58 (75.3%) correctly and 19 (24.7%) incorrectly (p = 0.006). There was a significant difference in mean lung/hepatic echogenicity between the groups with and without respiratory distress (1.05 versus 1.26; p = 0.002). In the group of 28 to 35 + 6 weeks, GSH presented sensitivity, specificity and accuracy in predicting respiratory distress of 61.9%, 89.1% and 81.6%, respectively. The evaluation of fetal lung maturity through GSH was more effective than the subjective method in predicting respiratory distress among newborns.

  6. Mouse lung infection model to assess Rhodococcus equi virulence and vaccine protection.

    Science.gov (United States)

    González-Iglesias, Patricia; Scortti, Mariela; MacArthur, Iain; Hapeshi, Alexia; Rodriguez, Héctor; Prescott, John F; Vazquez-Boland, José A

    2014-08-06

    The pathogenic actinomycete Rhodococcus equi causes severe purulent lung infections in foals and immunocompromised people. Although relatively unsusceptible to R. equi, mice are widely used for in vivo studies with this pathogen. The most commonly employed mouse model is based on systemic (intravenous) infection and determination of R. equi burdens in spleen and liver. Here, we investigated the murine lung for experimental infection studies with R. equi. Using a 10(7)CFU intranasal challenge in BALB/c mice, virulent R. equi consistently survived in quantifiable numbers up to 10 days in the lungs whereas virulence-deficient R. equi bacteria were rapidly cleared. An internally controlled virulence assay was developed in which the test R. equi strains are co-inoculated and monitored in the same mouse. Isogenic R. equi bacteria lacking either the plasmid vapA gene or the entire virulence plasmid were compared using this competitive assay. Both strains showed no significant differences in in vivo fitness in the lung, indicating that the single loss of the virulence factor VapA was sufficient to account for the full attenuation seen in the absence of the virulence plasmid. To test the adequacy of the lung infection model for monitoring R. equi vaccine efficacy, BALB/c mice were immunized with live R. equi and challenged intranasally. Vaccination conferred protection against acute pulmonary challenge with virulent R. equi. Our data indicate that the murine lung infection model provides a useful tool for both R. equi virulence and vaccine studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Computed tomography assessment of lung structure in patients undergoing cardiac surgery with cardiopulmonary bypass

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, R.R.; Sawada, A.Y.; Fukuda, M.J.; Neves, F.H.; Carmona, M.J.; Auler, J.O.; Malbouisson, L.M.S., E-mail: malbouisson@hcnet.usp.b [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina. Hospital das Clinicas; Pelosi, P. [Universita' degli Studi dell' Insubria, Varese (Italy). Dipt. Ambiente, Salute e Sicurezza; Rouby, J.-J. [University Pierre and Marie Curie, Paris (France). La Pitie Salpetriere Hospital. Dept. of Anesthesiology and Critical Care and Medicine

    2011-06-15

    Hypoxemia is a frequent complication after coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB), usually attributed to atelectasis. Using computed tomography (CT), we investigated postoperative pulmonary alterations and their impact on blood oxygenation. Eighteen non-hypoxemic patients (15 men and 3 women) with normal cardiac function scheduled for CABG under CPB were studied. Hemodynamic measurements and blood samples were obtained before surgery, after intubation, after CPB, at admission to the intensive care unit, and 12, 24, and 48 h after surgery. Pre- and postoperative volumetric thoracic CT scans were acquired under apnea conditions after a spontaneous expiration. Data were analyzed by the paired Student t-test and one-way repeated measures analysis of variance. Mean age was 63 {+-} 9 years. The PaO{sub 2}/FiO{sub 2} ratio was significantly reduced after anesthesia induction, reaching its nadir after CPB and partially improving 12 h after surgery. Compared to preoperative CT, there was a 31% postoperative reduction in pulmonary gas volume (P < 0.001) while tissue volume increased by 19% (P < 0.001). Non-aerated lung increased by 253 {+-} 97 g (P < 0.001), from 3 to 27%, after surgery and poorly aerated lung by 72 {+-} 68 g (P < 0.001), from 24 to 27%, while normally aerated lung was reduced by 147 {+-} 119 g (P < 0.001), from 72 to 46%. No correlations (Pearson) were observed between PaO{sub 2}/FiO{sub 2} ratio or shunt fraction at 24 h postoperatively and postoperative lung alterations. The data show that lung structure is profoundly modified after CABG with CPB. Taken together, multiple changes occurring in the lungs contribute to postoperative hypoxemia rather than atelectasis alone. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-03-15

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

  9. Evaluation of human health risks posed by carcinogenic and non-carcinogenic multiple contaminants associated with consumption of fish from Taihu Lake, China.

    Science.gov (United States)

    Yu, Yingxin; Wang, Xinxin; Yang, Dan; Lei, Bingli; Zhang, Xiaolan; Zhang, Xinyu

    2014-07-01

    The present study estimated the human daily intake and uptake of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and toxic trace elements [mercury (Hg), chromium (Cr), cadmium (Cd), and arsenic (As)] due to consumption of fish from Taihu Lake, China, and the associated potential health risks posed by these contaminants. The health risks posed by the contaminants were assessed using a risk quotient of the fish consumption rate to the maximum allowable fish consumption rate considering the contaminants for carcinogenic and non-carcinogenic effect endpoints. The results showed that fish consumption would not pose non-cancer risks. However, some species would cause a cancer risk. Relative risks of the contaminants were calculated to investigate the contaminant which posed the highest risk to humans. As a result, in view of the contaminants for carcinogenic effects, As was the contaminant which posed the highest risk to humans. However, when non-carcinogenic effects of the contaminants were considered, Hg posed the highest risk. The risk caused by PBDEs was negligible. The results demonstrated that traditional contaminants, such as As, Hg, DDTs (dichlorodiphenyltrichloroethane and its metabolites), and PCBs, require more attention in Taihu Lake than the other target contaminants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. A new approach to assess COPD by identifying lung function break-points.

    Science.gov (United States)

    Eriksson, Göran; Jarenbäck, Linnea; Peterson, Stefan; Ankerst, Jaro; Bjermer, Leif; Tufvesson, Ellen

    2015-01-01

    COPD is a progressive disease, which can take different routes, leading to great heterogeneity. The aim of the post-hoc analysis reported here was to perform continuous analyses of advanced lung function measurements, using linear and nonlinear regressions. Fifty-one COPD patients with mild to very severe disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I-IV) and 41 healthy smokers were investigated post-bronchodilation by flow-volume spirometry, body plethysmography, diffusion capacity testing, and impulse oscillometry. The relationship between COPD severity, based on forced expiratory volume in 1 second (FEV1), and different lung function parameters was analyzed by flexible nonparametric method, linear regression, and segmented linear regression with break-points. Most lung function parameters were nonlinear in relation to spirometric severity. Parameters related to volume (residual volume, functional residual capacity, total lung capacity, diffusion capacity [diffusion capacity of the lung for carbon monoxide], diffusion capacity of the lung for carbon monoxide/alveolar volume) and reactance (reactance area and reactance at 5Hz) were segmented with break-points at 60%-70% of FEV1. FEV1/forced vital capacity (FVC) and resonance frequency had break-points around 80% of FEV1, while many resistance parameters had break-points below 40%. The slopes in percent predicted differed; resistance at 5 Hz minus resistance at 20 Hz had a linear slope change of -5.3 per unit FEV1, while residual volume had no slope change above and -3.3 change per unit FEV1 below its break-point of 61%. Continuous analyses of different lung function parameters over the spirometric COPD severity range gave valuable information additional to categorical analyses. Parameters related to volume, diffusion capacity, and reactance showed break-points around 65% of FEV1, indicating that air trapping starts to dominate in moderate COPD (FEV1 =50%-80%). This may have an

  11. Assessment of lung microstructure with magnetic resonance imaging of hyperpolarized Helium-3

    DEFF Research Database (Denmark)

    Schreiber, Wolfgang G.; Morbach, Andreas E; Stavngaard, Trine

    2005-01-01

    anisotropy were performed. We found no dependency of the ADC as a function of the delay after stop of inspiration. The influence of cardiac motion was less than 10%. In the intercentre comparison study, an excellent agreement between the two sites was found. First measurements of the diffusion tensor...... motion was determined by measurements at two different delays after initiating the breath-hold, and before and after cardiac arrest. An intercentre comparison was performed in two age- and lung function-matched groups of lung-healthy volunteers at two research sites. Moreover, measurements of diffusion...

  12. Lung cancer risk among bricklayers in a pooled analysis of case-control studies.

    NARCIS (Netherlands)

    Consonni, Dario; De Matteis, Sara; Pesatori, Angela C; Bertazzi, Pier Alberto; Olsson, Ann C; Kromhout, Hans; Peters, Susan; Vermeulen, Roel Ch; Pesch, Beate; Brüning, Thomas; Kendzia, Benjamin; Behrens, Thomas; Stücker, Isabelle; Guida, Florence; Wichmann, Heinz-Erich; Brüske, Irene; Landi, Maria Teresa; Caporaso, Neil E; Gustavsson, Per; Plato, Nils; Tse, Lap Ah; Yu, Ignatius Tak-Sun; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Merletti, Franco; Richiardi, Lorenzo; Simonato, Lorenzo; Forastiere, Francesco; Siemiatycki, Jack; Parent, Marie-Élise; Tardón, Adonina; Boffetta, Paolo; Zaridze, David; Chen, Ying; Field, John K; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Lissowska, Jolanta; Szeszenia-Dabrowska, Neonila; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Rudnai, Peter; Fabiánová, Eleonóra; Stanescu Dumitru, Rodica; Bueno-de-Mesquita, Bas; Schüz, Joachim; Straif, Kurt

    Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analysed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled

  13. Carcinogenicity of Embedded Tungsten Alloys in Mice

    Science.gov (United States)

    2011-03-01

    2010 ProofNo: 1 UN CO RR EC TE D PR OO F 228 cating that the observed DU effects were not the result of foreign-body carcinogen- esis ( Brand et al...describing adverse health effects due to exposure to tungsten and tungsten-based materials. As part of an initiation rite, a French artillery...soldier drank 250 ml of a beer and wine mixture that had been used to rinse a gun barrel. Shortly after, he suffered seizures and was comatose for 24 h

  14. Variation of poorly ventilated lung units (silent spaces) measured by electrical impedance tomography to dynamically assess recruitment.

    Science.gov (United States)

    Spadaro, Savino; Mauri, Tommaso; Böhm, Stephan H; Scaramuzzo, Gaetano; Turrini, Cecilia; Waldmann, Andreas D; Ragazzi, Riccardo; Pesenti, Antonio; Volta, Carlo Alberto

    2018-01-31

    Assessing alveolar recruitment at different positive end-expiratory pressure (PEEP) levels is a major clinical and research interest because protective ventilation implies opening the lung without inducing overdistention. The pressure-volume (P-V) curve is a validated method of assessing recruitment but reflects global characteristics, and changes at the regional level may remain undetected. The aim of the present study was to compare, in intubated patients with acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS), lung recruitment measured by P-V curve analysis, with dynamic changes in poorly ventilated units of the dorsal lung (dependent silent spaces [DSSs]) assessed by electrical impedance tomography (EIT). We hypothesized that DSSs might represent a dynamic bedside measure of recruitment. We carried out a prospective interventional study of 14 patients with AHRF and ARDS admitted to the intensive care unit undergoing mechanical ventilation. Each patient underwent an incremental/decremental PEEP trial that included five consecutive phases: PEEP 5 and 10 cmH 2 O, recruitment maneuver + PEEP 15 cmH 2 O, then PEEP 10 and 5 cmH 2 O again. We measured, at the end of each phase, recruitment from previous PEEP using the P-V curve method, and changes in DSS were continuously monitored by EIT. PEEP changes induced alveolar recruitment as assessed by the P-V curve method and changes in the amount of DSS (p Recruited volume measured by the P-V curves significantly correlated with the change in DSS (r s  = 0.734, p recruitment measured using the P-V curve technique. EIT might provide useful information to titrate personalized PEEP. ClinicalTrials.gov, NCT02907840 . Registered on 20 September 2016.

  15. Brain, lung, and heart oxidative stress assessment of an over-the ...

    African Journals Online (AJOL)

    We evaluated the brain, lung, and heart oxidative stress in rats exposed to aerosol of an over-thecounter pyrethroid insecticide product in Nigeria. The experimental animals were randomly divided into four groups: group I (control) was not exposed to the insecticide aerosol, while groups II, III, and IV were exposed to 6.0 mL ...

  16. Assessment of gas compression and lung volume during air stacking maneuver.

    Science.gov (United States)

    Sarmento, A; Resqueti, V R; Fregonezi, G A F; Aliverti, A

    2017-01-01

    We reasoned that the application of positive pressure through air stacking (AS) technique could cause gas compression and the absolute lung volumes could be estimated. The aim of this study was to estimate the amount of gas compression (ΔV comp) during AS in healthy subjects positioned at 45° trunk inclination and verify if the simultaneous measurements of chest wall volume changes (ΔV CW), by optoelectronic plethysmography, and changes in lung volume (ΔV ao), by pneumotachograph, combined with pressure variation at the airways opening (ΔP ao) during AS are able to provide reliable data on absolute lung volumes. Twenty healthy subjects (mean age 23.5 ± 3.8 years) were studied during a protocol that included slow vital capacity and AS maneuvers. V comp was calculated by subtracting ΔV ao and ΔV CW occurring during AS and total lung capacity (TLC) was estimated by applying Boyle-Mariote's law using V comp and ΔP ao. During AS, 0.140 ± 0.050 L of gas was compressed with an average ΔP ao of 21.78 ± 6.18 cmH2O. No significant differences between the estimated TLC (-0.03 ± 3.0% difference, p = 0.6020), estimated FRC (-2.0 ± 12.4% difference, p = 0.5172), measured IC (1.2 ± 11.2% difference, p = 0.7627) and predicted values were found. During AS, a significant gas compression occurs and absolute lung volumes can be estimated by simultaneous measurements of ΔV CW, ΔV ao and ΔP ao.

  17. Assessment of the lung function status of the goldsmiths working in an unorganized sector of India

    Directory of Open Access Journals (Sweden)

    Subhashis Sahu

    2013-01-01

    Full Text Available Context: Exposure to various types of fumes and gases are very common in Jewelery industries. No Report is available regarding the effects of those fumes and gases on the respiratory functions of the goldsmiths. Due to lack of proper monitoring of the workplace environments in these unorganized sectors, workers get very much affected by the occupational exposures to those irritants. Aims: The present study aimed to investigate whether the occupational exposures to fumes and gases might alter the lung functions of the goldsmiths. Materials and Methods: A total of 118 goldsmiths and 66 unexposed control subjects were taken randomly for the study. The goldsmiths were further classified in 3 groups according to duration (year of exposures in the work environment, ETA 1 (less than 5 years, ETA 2 (more than 5 years but less than 10 years, and ETA 3 (more than 10 years. Peak expiratory flow rates (PEFR, forced vital capacity (FVC, and forced expiratory flow rates of different intervals (FEF 25% , FEF 50% , FEF 75% , FEF 25-75% were measured using computerized Spirometer (Maestros Mediline, India. The statistical analyses were carried out using Minitab software version 3. Results: Lung functions of the goldsmiths significantly (P < 0.01 decreased from that of the control group. Inter-group comparison also showed the deteriorations of lung functions was associated with exposure time, and more exposed workers had significantly less (P < 0.01 efficiencies of lung functions. Conclusions: Workplace fumes and gases were responsible for deterioration of the lung function status of the goldsmiths.

  18. Preliminary comparison of normalized T1 and non-contrast perfusion MRI assessments of regional lung disease in cystic fibrosis patients.

    Science.gov (United States)

    Donnola, Shannon B; Dasenbrook, Elliott C; Weaver, David; Lu, Lan; Gupta, Karishma; Prabhakaran, Anjali; Yu, Xin; Chmiel, James F; McBennett, Kimberly; Konstan, Michael W; Drumm, Mitchell L; Flask, Chris A

    2017-03-01

    Previous studies have shown that Magnetic Resonance Imaging (MRI) techniques can be used to non-invasively assess lung disease in CF patients. In this study, we compare the sensitivity of normalized T1 (nT1) and non-contrast perfusion MRI techniques to detect regional lung disease in CF patients. MRI data were obtained for eight adult CF patients without overt pulmonary exacerbation (FEV1=45-127%) and six healthy volunteers on a Siemens Espree 1.5T MRI scanner. Sagittal nT1 and perfusion data were acquired for each subject's left and right lungs. A region-of-interest analysis was used to calculate mean nT1 and perfusion values in the individual lobes of the left and right lungs for each subject. In comparison to healthy controls, CF subjects showed a significant decrease in nT1 values in the upper lobe of the left lung as well as in the upper and anterior lobes of the right lung (pmethods were able to detect regional lung disease, the additional nT1 reductions in the CF patients suggests that nT1 may be more sensitive to regional CF lung disease. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  19. Peri-diaphragmatic lung volume assessed by computed tomography correlates with quality of life in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Tanabe, Naoya; Muro, Shigeo; Fuseya, Yoshinori; Sato, Susumu; Oguma, Tsuyoshi; Kiyokawa, Hirofumi; Takahashi, Tamaki; Kinose, Daisuke; Hoshino, Yuma; Kubo, Takeshi; Hirai, Toyohiro; Mishima, Michiaki

    2012-10-01

    Health-related quality of life (HRQoL) is important in the management of chronic obstructive pulmonary disease (COPD). In patients with emphysema, lung hyperinflation identified radiologically as shortening and flattening of the diaphragm is associated with impaired HRQoL. It remains unclear whether shortening of the diaphragm and/or alteration in chest wall shape are associated with reduced pulmonary function and HRQoL. Pulmonary function testing and chest computed tomography (CT) were performed, and the St. George's Respiratory Questionnaire (SGRQ) was administered to 123 patients with COPD. Using CT images, the ratio of volume of lung region adjacent to the diaphragm dome to total lung volume (DLV%) was evaluated as a novel CT index, and conventional indices, including percent low attenuation volume (LAV%), wall area percent (WA%), total lung volume and diaphragm length (Ldi) were calculated. DLV% was significantly correlated with Ldi. DLV% and Ldi were inversely correlated with lung hyperinflation, assessed as the ratio of residual volume to total lung capacity, independent of LAV% and WA%. Unlike Ldi, DLV% was inversely associated with all components and total scores for the SGRQ, independent of the severity of emphysema and airflow limitation. Reduced lung volume around the diaphragm correlated with lung hyperinflation and HRQoL, independent of emphysema severity. This needs to be verified in additional studies. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

  20. How do organisational characteristics influence teamwork and service delivery in lung cancer diagnostic assessment programmes? A mixed-methods study.

    Science.gov (United States)

    Honein-AbouHaidar, Gladys N; Stuart-McEwan, Terri; Waddell, Tom; Salvarrey, Alexandra; Smylie, Jennifer; Dobrow, Mark J; Brouwers, Melissa C; Gagliardi, Anna R

    2017-02-23

    Diagnostic assessment programmes (DAPs) can reduce wait times for cancer diagnosis, but optimal DAP design is unknown. This study explored how organisational characteristics influenced multidisciplinary teamwork and diagnostic service delivery in lung cancer DAPs. A mixed-methods approach integrated data from descriptive qualitative interviews and medical record abstraction at 4 lung cancer DAPs. Findings were analysed with the Integrated Team Effectiveness Model. 4 DAPs at 2 teaching and 2 community hospitals in Canada. 22 staff were interviewed about organisational characteristics, target service benchmarks, and teamwork processes, determinants and outcomes; 314 medical records were reviewed for actual service benchmarks. Formal, informal and asynchronous team processes enabled service delivery and yielded many perceived benefits at the patient, staff and service levels. However, several DAP characteristics challenged teamwork and service delivery: referral volume/workload, time since launch, days per week of operation, rural-remote population, number and type of full-time/part-time human resources, staff colocation, information systems. As a result, all sites failed to meet target benchmarks (from referral to consultation median 4.0 visits, median wait time 35.0 days). Recommendations included improved information systems, more staff in all specialties, staff colocation and expanded roles for patient navigators. Findings were captured in a conceptual framework of lung cancer DAP teamwork determinants and outcomes. This study identified several DAP characteristics that could be improved to facilitate teamwork and enhance service delivery, thereby contributing to knowledge of organisational determinants of teamwork and associated outcomes. Findings can be used to update existing DAP guidelines, and by managers to plan or evaluate lung cancer DAPs. Ongoing research is needed to identify ideal roles for navigators, and staffing models tailored to case volumes

  1. Carcinogenic activity of coltsfoot, Tussilago farfara l.

    Science.gov (United States)

    Hirono, I; Mori, H; Culvenor, C C

    1976-02-01

    The carcinogenicity of young, pre-blooming flowers of coltsfoot, Tussilago farfara L., which is a herb of the tribe Senecioneae, family Compositae, and widely used as a herbal remedy, was studied in inbred strain ACI rats. Rats were divided into 4 groups: Group I received 32% coltsfoot diet for 4 days, and subsequently 16% diet until the termination of experiment. Groups II and III respectively received 8% and 4% coltsfoot diet for 600 days. Group IV was fed a normal diet as a control group. The experiments were terminated 600 days after the start of administration of coltsfoot diet. All the rats in Group I survived beyond 380 days after the start of feeding and 8 out of 12 rats developed hemangioendothelial sarcoma in the liver, whereas only one out of 10 rats developed the tumor in Group II, and no tumors were observed in Group III. Chemical studies on the dried, young flowers used in this experiment suggested that the carcinogenicity of coltsfoot is most probably due to senkirkine, a hepatotoxic pyrrolizidine alkaloid.

  2. Stromal contributions to the carcinogenic process.

    Science.gov (United States)

    Spaw, Mark; Anant, Shrikant; Thomas, Sufi Mary

    2017-04-01

    Tumor-associated stromal cells are dynamic characters that endorse the carcinogenic process in a multitude of ways. The tumor microenvironment plays a crucial role throughout the tumor progression, which includes initiation, growth, invasion, and metastasis. The tumor microenvironment consists of cellular and non-cellular components. Tumor-associated stromal cell types include the microbiome, immune cells including macrophages, dendritic and T-cells, cells associated with blood and lymphatic vessels including pericytes and endothelial cells, fibroblasts, neuronal cells, and adipocytes. The non-cellular components of the microenvironment include matrix proteins and secreted factors. The development of therapies that target the mechanisms by which stromal cells contribute to successful tumorigenesis is major goal of upcoming cancer research. The purpose of this review is to present a comprehensive discussion of the role of each of the tumor-associated stromal cell types in the carcinogenic process with a special focus on target development and therapeutic intervention. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Carcinogenicity/tumour promotion by NDL PCB

    Energy Technology Data Exchange (ETDEWEB)

    Schrenk, D. [Kaiserslautern Univ. (Germany). Food Chemistry and Environmental Toxicology

    2004-09-15

    Polychlorinated biphenyls (PCBs) belong to the group of persistent environmental pollutants exhibiting neurotoxic, teratogenic and tumour-promoting effects in experimental animal models. PCB congeners can be divided into 'dioxinlike' and 'non-dioxinlike' congeners on the basis of their ability to act as aryl hydrocarbon receptor (AhR) agonists. Like the most toxic dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 'dioxinlike' PCBs bind to the AhR and show characteristic effects on the expression of AhR-regulated genes including the induction of cytochrome P450 (CYP) 1A1. On the other hand, 'non-dioxinlike' PCB congeners have a lower or no binding affinity to the AhR, but exhibit a 'phenobarbital-type' induction of CYP 2B1/2 activity. A carcinogenic potential of PCBs has been demonstrated with technical mixtures such as Aroclors or Clophens. In these studies the liver and the thyroid gland were found to be the principal target organs of PCB-mediated carcinogenesis in rodents. No studies have been published, however, on the carcinogenicity of individual congeners. In two-stage initiation-promotion protocols in rats, both technical mixtures and individual 'dioxinlike' and 'non-dioxinlike' congeners were reported to act as liver tumour promoters.

  4. Quantitative texture-based assessment of one-year changes in fibrotic reticular patterns on HRCT in scleroderma lung disease treated with oral cyclophosphamide

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun J.; Brown, Matthew S. [David Geffen School of Medicine, UCLA, Center for Computer Vision and Imaging Biomarker, Department of Radiological Sciences, Los Angeles, CA (United States); Elashoff, Robert [David Geffen School of Medicine, UCLA, Department of Biostatistics and Biomathematics, Los Angeles, CA (United States); Li, Gang [School of Public Health, UCLA, Department of Biostatistics, Los Angeles, CA (United States); Gjertson, David W. [School of Public Health and David Geffen School of Medicine, UCLA, Department of Biostatistics and Pathology, Los Angeles (United States); Lynch, David A. [National Jewish Health, Radiology Department, Denver, CO (United States); Strollo, Diane C. [UPMC Presbyterian, Radiology Department, Pittsburgh, PA (United States); Kleerup, Eric; Tashkin, Donald P. [David Geffen School of Medicine, UCLA, Department of Med-Pul and Critical Care, Los Angeles, CA (United States); Chong, Daniel; Shah, Sumit K.; Ahmad, Shama; Abtin, Fereidoun; Goldin, Jonathan G. [David Geffen School of Medicine, UCLA, Department of Radiological Sciences, Los Angeles, CA (United States)

    2011-12-15

    The Scleroderma Lung Study showed the efficacy of cyclophosphamide in modestly improving the forced vital capacity (FVC) compared with placebo over 1 year. Using changes in texture-based scores that quantify lung fibrosis as the percentage involvement of reticulation patterns, the effectiveness of cyclophosphamide was re-assessed by examining its impact on quantitative lung fibrosis (QLF). Axial HRCT images were acquired (1-mm slice thickness, 10-mm increments) in the prone position at inspiration. A validated model for quantifying interstitial disease patterns was applied to images from 83 subjects at baseline and 12 months. Scores were calculated for six zones (upper, mid, lower of the right/left lung) and the whole lung. Average changes were compared. Correlations were performed between QLF and physiological and clinical scores. From the most severe zones identified at baseline, QLF scores decreased by 2.6% in the cyclophosphamide group, whereas they increased by 9.1% in the placebo group, leading to {proportional_to}12% difference (p = 0.0027). Between-treatment difference in whole lung QLF was {proportional_to}5% (p = 0.0190). Significant associations were observed between changes in QLF and FVC (r = -0.33), dyspnea score (r = -0.29), and consensus visual score (p = 0.0001). QLF scores provide an objective quantitative tool for assessing treatment efficacy in scleroderma-related interstitial lung disease. (orig.)

  5. Hepatic metabolism of carcinogenic β-asarone.

    Science.gov (United States)

    Cartus, Alexander T; Stegmüller, Simone; Simson, Nadine; Wahl, Andrea; Neef, Sylvia; Kelm, Harald; Schrenk, Dieter

    2015-09-21

    β-Asarone (1) belongs to the group of naturally occurring phenylpropenes like eugenol or anethole. Compound 1 is found in several plants, e.g., Acorus calamus or Asarum europaeum. Compound 1-containing plant materials and essential oils thereof are used to flavor foods and alcoholic beverages and as ingredients of many drugs in traditional phytomedicines. Although 1 has been claimed to have several positive pharmacological effects, it was found to be genotoxic and carcinogenic in rodents (liver and small intestine). The mechanism of action of carcinogenic allylic phenylpropenes consists of the metabolic activation via cytochrome P450 enzymes and sulfotransferases. In vivo experiments suggested that this pathway does not play a major role in the carcinogenicity of the propenylic compound 1 as is the case for other propenylic compounds, e.g., anethole. Since the metabolic pathways of 1 have not been investigated and its carcinogenic mode of action is unknown, we investigated the metabolism of 1 in liver microsomes of rats, bovines, porcines, and humans using (1)H NMR, HPLC-DAD, and LC-ESI-MS/MS techniques. We synthesized the majority of identified metabolites which were used as reference compounds for the quantification and final verification of metabolites. Microsomal epoxidation of the side chain of 1 presumably yielded (Z)-asarone-1',2'-epoxide (8a) which instantly was hydrolyzed to the corresponding erythro- and threo-configurated diols (9b, 9a) and the ketone 2,4,5-trimethoxyphenylacetone (13). This was the main metabolic pathway in the metabolism of 1 in all investigated liver microsomes. Hydroxylation of the side chain of 1 led to the formation of three alcohols at total yields of less than 30%: 1'-hydroxyasarone (2), (E)- and (Z)-3'-hydroxyasarone (4 and 6), with 6 being the mainly formed alcohol and 2 being detectable only in liver microsomes of Aroclor 1254-pretreated rats. Small amounts of 4 and 6 were further oxidized to the corresponding carbonyl

  6. [Communication of chemical and carcinogen risk at refinery maintenance companies].

    Science.gov (United States)

    Rossi, O; Loi, A M

    2006-01-01

    This short paper reports a communication experience about chemical/carcinogen risk aimed to characterize and to document different occasions and several ways of exposure of the workers employed in maintenance companies in a petrochemical factory. We utilized different source of information: from risk assessment document (VR) of the petrochemical plant and from job sheets of the companies on contracts of maintenance. Working this way it has been possible to create a database which includes information about chemical agents, length and the way of exposure for every worker. This database allows to improve the level of knowledge of the Occupational Health Doctors, Professionals and of the workers, moreover it is useful to take note of quality and way of exposure in the VR document.

  7. Predicting fetal lung maturity by visual assessment of amniotic fluid turbidity: comparison with fluorescence polarization assay.

    Science.gov (United States)

    Adair, C D; Sanchez-Ramos, L; McDyer, D L; Gaudier, F L; Del Valle, G O; Delke, I

    1995-10-01

    We prospectively studied 159 patients having clinically indicated amniocentesis. Amniotic fluid (3 to 5 mL) was placed in a nonheparinized glass tube. This sample was then classified as turbid (indicating maturity) or clear (indicating immaturity) on the basis of a single examiner's ability to read newspaper print through the glass tube. These results were then compared with fluorescence polarization values for the same sample. A value of 70 mg/g was considered positive evidence of fetal lung maturity. By study criteria, 62 samples (39%) indicated immaturity and 97 (61%) indicated maturity. Turbidity correctly identified 89 samples that produced fluorescence polarization values of at least 70 mg/g. Turbidity as a predictor of fetal lung maturity when compared with fluorescence polarization assay has a 91% positive and 87% negative predictive value. Visual inspection of amniotic fluid may be of value in areas where sophisticated methods are unavailable.

  8. The tobacco carcinogen NNK disturbs mitotic chromosome alignment by interrupting p53 targeting to the centrosome.

    Science.gov (United States)

    Park, Ji Eun; Jang, Yu Lim; Jang, Chang-Young

    2017-11-05

    The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the most potent risk factor among tobacco-related carcinogens in lung cancer progression and outcomes. Although genetic mutations and chromosome instability have been detected in NNK-induced lung tumors, the oncogenic mechanisms of NNK are not fully understood. Here, we show that NNK increases chromosomal instability by disrupting spindle microtubule (MT) attachment to the kinetochore (KT) and spindle dynamics. Mechanistically, NNK blocks the targeting of p53 to the centrosome during mitosis, leading to chromosome alignment defects in metaphase. Therefore, lung cancer cells with wild-type p53, such as A594 and H226B, are more resistant to the NNK treatment than p53-mutant lung cancer cells, such as A1299 and H226Br. Although NNK does not affect the levels or transcriptional activity of p53, the reduction of the p53 level at the centrosome exacerbates the NNK-induced chromosome alignment defect in A549 and H226B cells. Therefore, p53 protects against NNK-induced chromosome instability by modulating the function of centrosome-localized p53 and not by modulating transcriptional activity. We conclude that NNK may increase the risk of lung cancer progression and poorer outcomes in patients with p53 mutations by perturbing proper mitotic progression and chromosome integrity. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Quality of life assessment as a predictor of survival in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Staren Edgar D

    2011-08-01

    Full Text Available Abstract Background There are conflicting and inconsistent results in the literature on the prognostic role of quality of life (QoL in cancer. We investigated whether QoL at admission could predict survival in lung cancer patients. Methods The study population consisted of 1194 non-small cell lung cancer patients treated at our institution between Jan 2001 and Dec 2008. QoL was evaluated using EORTC-QLQ-C30 prior to initiation of treatment. Patient survival was defined as the time interval between the date of first patient visit and the date of death from any cause/date of last contact. Univariate and multivariate Cox regression evaluated the prognostic significance of QoL. Results Mean age at presentation was 58.3 years. There were 605 newly diagnosed and 589 previously treated patients; 601 males and 593 females. Stage of disease at diagnosis was I, 100; II, 63; III, 348; IV, 656; and 27 indeterminate. Upon multivariate analyses, global QoL as well as physical function predicted patient survival in the entire study population. Every 10-point increase in physical function was associated with a 10% increase in survival (95% CI = 6% to 14%, p Conclusions Baseline global QoL and physical function provide useful prognostic information in non-small cell lung cancer patients.

  10. Nonrigid registration method to assess reproducibility of breath-holding with ABC in lung cancer.

    Science.gov (United States)

    Sarrut, David; Boldea, Vlad; Ayadi, Myriam; Badel, Jean-Noël; Ginestet, Chantal; Clippe, Sébastien; Carrie, Christian

    2005-02-01

    To study the interfraction reproducibility of breath-holding using active breath control (ABC), and to develop computerized tools to evaluate three-dimensional (3D) intrathoracic motion in each patient. Since June 2002, 11 patients with non-small-cell lung cancer enrolled in a Phase II trial have undergone four CT scans: one during free-breathing (reference) and three using ABC. Patients left the room between breath-hold scans. The patient's breath was held at the same predefined phase of the breathing cycle (about 70% of the vital capacity) using the ABC device, then patients received 3D-conformal radiotherapy. Automated computerized tools for breath-hold CT scans were developed to analyze lung and tumor interfraction residual motions with 3D nonrigid registration. All patients but one were safely treated with ABC for 7 weeks. For 6 patients, the lung volume differences were 300 cm(3) and displacements >10 mm, probably owing to atelectasia and emphysema. One patient was excluded, and two others had incomplete data sets. Breath-holding with ABC was effective in 6 patients, and discrepancies were clinically accountable in 2. The proposed 3D nonrigid registration method allows for personalized evaluation of breath-holding reproducibility with ABC. It will be used to adapt the patient-specific internal margins.

  11. Exposure and Metabolic Activation Biomarkers of Carcinogenic Tobacco-Specific Nitrosamines.

    Science.gov (United States)

    Hecht, Stephen S; Stepanov, Irina; Carmella, Steven G

    2016-01-19

    Lung cancer is the leading cause of cancer death in the world, and cigarette smoking is its main cause. Oral cavity cancer is another debilitating and often fatal cancer closely linked to tobacco product use. While great strides have been made in decreasing tobacco use in the United States and some other countries, there are still an estimated 1 billion men and 250 million women in the world who are cigarette smokers and there are hundreds of millions of smokeless tobacco users, all at risk for cancer. Worldwide, lung cancer kills about three people per minute. This Account focuses on metabolites and biomarkers of two powerful tobacco-specific nitrosamine carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN), considered to be among the main causes of lung cancer and oral cavity cancer in people who use tobacco products. Three properties of NNK and NNN are critical for successful biomarker studies: they are present in all tobacco products, they are tobacco-specific and are not found in any other product, and they are strong carcinogens. NNK and NNN are converted in humans to urinary metabolites that can be quantified by mass spectrometry as biomarkers of exposure to these carcinogens. They are also metabolized to diazonium ions and related electrophiles that react with DNA to form addition products that can be detected and quantified by mass spectrometry. These urinary metabolites and DNA addition products can serve as biomarkers of exposure and metabolic activation, respectively. The biomarkers of exposure, in particular the urinary NNK metabolites 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides, have been extensively applied to document tobacco-specific lung carcinogen uptake in smokers and nonsmokers exposed to secondhand tobacco smoke. Highly sensitive mass spectrometric methods have been developed for quantitative analysis of these NNK metabolites as well as metabolites of NNN in human urine

  12. Assessment of a chemically induced model of lung squamous cell carcinoma in mice by 18F-FDG small-animal PET.

    Science.gov (United States)

    Ambrosini, Valentina; Nanni, Cristina; Pettinato, Cinzia; Fini, Milena; D'Errico, Antonia; Trepidi, Silvia; Spinelli, Antonello; Al-Nahhas, Adil; Rubello, Domenico; Zompatori, Maurizio; Fabbri, Mario; Franchi, Roberto; Fanti, Stefano

    2007-08-01

    Small-animal imaging has become a relevant research field in pre-clinical oncology. In particular, metabolic information provided by small-animal positron emission tomography (PET) is very useful to closely monitor tumour growth and assess therapy response in murine models of human disease. There are various murine models for human lung adenocarcinoma, but those for squamous cell lung carcinoma, the most common form of human cancer, are lacking. To assess the feasibility of 18F-FDG small-animal PET to monitor tumour growth in a chemically induced model of squamous cell carcinoma of the lung. Nineteen NIH Swiss mice were skin painted by N-nitroso-tris-chloroethylurea (NTCU) twice a week, with a 3 day interval, for 8 months and 10 NIH Swiss mice skin painted with NTCU solvent (acetone) were used as controls. 18F-FDG PET was performed under sevofluorane anaesthesia and oxygen supplementation at 2, 4, 6 and 8 months from initial treatment. Images were assessed by visual analysis and semi-quantitatively. When a diffuse distribution of tumour was noted, the mean of the counts/pixel measured at three lung levels, corrected for the effective dose injected and for decay, was used for comparison between mutagen-painted and control mice. Pathological evaluation was carried out from the time of the first positive PET results in a subgroup of the whole population to assess correlation with PET findings. Small animal CT was performed at 8 months in another subgroup. In both terms of visual analysis and measurement of total lung activity, 18F-FDG PET at 2 and 4 months from initial treatment were comparable in mutagen-painted and controls. At 6 months, PET images showed a faint and diffuse uptake over both lung fields in mutagen-painted mice with multiple focal areas of increased tracer uptake that merged into confluent masses at 8 months and seriously subverting lung architecture on computed tomography. Total lung activity was significantly higher in mutagen-painted versus

  13. A study to assess the feasibility of introducing early palliative care in ambulatory patients with advanced lung cancer

    Directory of Open Access Journals (Sweden)

    Jayita Kedar Deodhar

    2017-01-01

    Full Text Available Purpose: Early palliative care is beneficial in advanced lung cancer patients. We aimed to assess the feasibility of introducing early palliative care in ambulatory advanced lung cancer patients in an Indian tertiary cancer center. Methodology: In a longitudinal, single–arm, and single-center study, fifty patients were recruited and followed up every 3–4 weeks for 6 months, measuring the symptom burden using Edmonton Symptom Assessment Scale (ESAS and quality of life (QoL with European Organization for Research and Treatment of Cancer-QoL tools. The primary end point of feasibility was that at least 60% of the patients should complete 50% of the planned palliative care visits and over 50% of the patients should complete QoL questionnaires. Analysis was done using Statistical Package for the Social Sciences version 20. Results: Twenty-four of fifty patients (48% completed the planned follow-up visits. All patients completed the questionnaires at baseline and 31 (62% at their follow-up visits. The patients' main reasons for not following up in the hospital palliative care clinic were logistics and fatigue. Tiredness, pain, and appetite loss were the highest rated symptoms at baseline (ESAS scores 3, 2.2, and 2.1, respectively. Improvement in pain and anxiety scores at follow-up visits 1 and 2 was significant (P < 0.05. Scores on QoL functioning scales improved during the follow-up period. Conclusions: We did not meet the feasibility criteria for the introduction of early palliative care in our advanced lung cancer patients in a resource-limited country.

  14. Quantitative and qualitative assessment of real world data comparative effectiveness research of systemic therapies in lung oncology: A systematic review.

    Science.gov (United States)

    Peters, Bas J M; Janssen, Vivi E M T; Schramel, Franz M; van de Garde, Ewoudt M W

    2016-10-01

    The growing interest in comparative effectiveness research (CER) based on data from routine clinical practice also extends towards lung oncology. Although CER studies using real world data (RWD) have the potential to assist clinical decision-making, concerns about the quality and validity of studies with observational data subsist. The primary objective of the present study is to assess the current status of observational CER in the field of lung oncology, both quantitatively as qualitatively. We performed a systematic electronic literature database search in MEDLINE and EMBASE (up to 1 July 2015). The quality of all selected studies was assessed according to the Good ReseArch for Comparative Effectiveness (GRACE) checklist. The first selection included 657 publications. After screening the corresponding abstracts and full-text papers, 38 studies remained. A total of 36 studies included patients with advanced NSCLC. The comparison of the effectiveness of gefitinib versus erlotinib was the main objective in 22% of the studies. The median number of patients per study was 202 (range 21-10064). The number of publications increased over the years whereas the quality score remained stable over the years with several common shortcomings (checklist items M5, D1, D4, D6). The growing interest in clinical oncology CER studies using RWD is reflected in an increasing number of publications in the recent years. The studies have several common methodological shortcomings possibly limiting their applicability in clinical decision-making. To fulfil the promise of RWD CER in lung oncology effort should be continued to overcome these shortcomings. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Molecular basis of carcinogenicity of tungsten alloy particles

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Robert M.; Williams, Tim D.; Waring, Rosemary H.; Hodges, Nikolas J., E-mail: n.hodges@bham.ac.uk

    2015-03-15

    The tungsten alloy of 91% tungsten, 6% nickel and 3% cobalt (WNC 91–6–3) induces rhabdomyosarcoma when implanted into a rat thigh muscle. To investigate whether this effect is species-specific human HSkMc primary muscle cells were exposed to WNC 91–6–3 particles and responses were compared with those from a rat skeletal muscle cell line (L6-C11). Toxicity was assessed by the adenylate kinase assay and microscopy, DNA damage by the Comet assay. Caspase 3 enzyme activity was measured and oligonucleotide microarrays were used for transcriptional profiling. WNC 91–6–3 particles caused toxicity in cells adjacent to the particles and also increased DNA strand breaks. Inhibition of caspase 3 by WNC 91–6–3 occurred in rat but not in human cells. In both rat and human cells, the transcriptional response to WNC 91–6–3 showed repression of transcripts encoding muscle-specific proteins with induction of glycolysis, hypoxia, stress responses and transcripts associated with DNA damage and cell death. In human cells, genes encoding metallothioneins were also induced, together with genes related to angiogenesis, dysregulation of apoptosis and proliferation consistent with pre-neoplastic changes. An alloy containing iron, WNF 97–2–1, which is non-carcinogenic in vivo in rats, did not show these transcriptional changes in vitro in either species while the corresponding cobalt-containing alloy, WNC 97–2–1 elicited similar responses to WNC 91–6–3. Tungsten alloys containing both nickel and cobalt therefore have the potential to be carcinogenic in man and in vitro assays coupled with transcriptomics can be used to identify alloys, which may lead to tumour formation, by dysregulation of biochemical processes. - Highlights: • Use of transcriptomics to identify likely carcinogenic tungsten alloys in vitro • Cobalt containing alloys cause oxidative stress, DNA-damage and perturb apoptosis. • Presence of cobalt causes changes in gene expression

  16. Multi-dimensional scores to predict mortality in patients with idiopathic pulmonary fibrosis undergoing lung transplantation assessment.

    Science.gov (United States)

    Fisher, Jolene H; Al-Hejaili, Faris; Kandel, Sonja; Hirji, Alim; Shapera, Shane; Mura, Marco

    2017-04-01

    The heterogeneous progression of idiopathic pulmonary fibrosis (IPF) makes prognostication difficult and contributes to high mortality on the waitlist for lung transplantation (LTx). Multi-dimensional scores (Composite Physiologic index [CPI], [Gender-Age-Physiology [GAP]; RIsk Stratification scorE [RISE]) demonstrated enhanced predictive power towards outcome in IPF. The lung allocation score (LAS) is a multi-dimensional tool commonly used to stratify patients assessed for LTx. We sought to investigate whether IPF-specific multi-dimensional scores predict mortality in patients with IPF assessed for LTx. The study included 302 patients with IPF who underwent a LTx assessment (2003-2014). Multi-dimensional scores were calculated. The primary outcome was 12-month mortality after assessment. LTx was considered as competing event in all analyses. At the end of the observation period, there were 134 transplants, 63 deaths, and 105 patients were alive without LTx. Multi-dimensional scores predicted mortality with accuracy similar to LAS, and superior to that of individual variables: area under the curve (AUC) for LAS was 0.78 (sensitivity 71%, specificity 86%); CPI 0.75 (sensitivity 67%, specificity 82%); GAP 0.67 (sensitivity 59%, specificity 74%); RISE 0.78 (sensitivity 71%, specificity 84%). A separate analysis conducted only in patients actively listed for LTx (n = 247; 50 deaths) yielded similar results. In patients with IPF assessed for LTx as well as in those actually listed, multi-dimensional scores predict mortality better than individual variables, and with accuracy similar to the LAS. If validated, multi-dimensional scores may serve as inexpensive tools to guide decisions on the timing of referral and listing for LTx. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Coal fires, industrial emissions and motor vehicles as sources of environmental carcinogens.

    Science.gov (United States)

    Lawther, P J; Waller, R E

    1976-01-01

    One of the most widely studied carcinogenic agents in the environment is the polycyclic hydrocarbon, benzo(a) pyrene. As a component of soot from the inefficient combustion of coal, its association with cancer can be traced back 200 years, but its possible relevance to lung cancer as a widely distributed air relevance to lung cancer as a widely distributed air pollutant has been investigated only during the past 25 years. Domestic coal fires have been shown to be important sources, and smaller amounts come from industrial sources and from motor vehicles. There is evidence now that the concentration of benzo (a) pyrene in large towns in Britain has decreased by a factor of about ten during the last few decades, as a result of changing heating methods and smoke control. In view of the overwhelming effect of cigarette smoking, it is difficult to determine whether the benzo(a)pyrene content of the air has had any importnat effect on the development of lung cancer, but careful analysis of trends in mortality may now throw some light on this. Among other materials with carcinogenic properties that may be dispersed into the general air, asbestos is the one that has been investigated most thoroughly. The association between exposure to asbestos and the development of lung cancer and mesothelioma of the pleura has been clearly demonstrated among people occupationally exposed to the dust, but as far as the general public is concerned, any risk may be limited to the immediate vicinity of major sources. These and other hazards demonstrated among occupational gropus serve as a warning however to maintain careful scutiny of urban air pollutants in relation to the acetiology of cancer.

  18. Thorax, Trachea, and Lung Ultrasonography in Emergency and Critical Care Medicine: Assessment of an Objective Structured Training Concept

    Directory of Open Access Journals (Sweden)

    Raoul Breitkreutz

    2013-01-01

    Full Text Available Background and Study objective. Focused lung ultrasound (LUS examinations are important tools in critical care medicine. There is evidence that LUS can be used for the detection of acute thoracic lesions. However, no validated training method is available. The goal of this study was to develop and assess an objective structured clinical examination (OSCE curriculum for focused thorax, trachea, and lung ultrasound in emergency and critical care medicine (THOLUUSE. Methods. 39 trainees underwent a one-day training course in a prospective educational study, including lectures in sonoanatomy and -pathology of the thorax, case presentations, and hands-on training. Trainees’ pre- and posttest performances were assessed by multiple choice questionnaires, visual perception tests by interpretation video clips, practical performance of LUS, and identification of specific ultrasound findings. Results. Trainees postcourse scores of correct MCQ answers increased from 56±4% to 82±2% (mean± SD; P<0.001; visual perception skills increased from 54±5% to 78±3% (P<0.001; practical ultrasound skills improved, and correct LUS was performed in 94%. Subgroup analysis revealed that learning success was independent from the trainees’ previous ultrasound experience. Conclusions. THOLUUSE significantly improves theoretical and practical skills for the diagnosis of acute thoracic lesions. We propose to implement THOLUUSE in emergency medicine training.

  19. Assessment of fatigue using the Identity-Consequence Fatigue Scale in patients with lung cancer.

    Science.gov (United States)

    Nogueira, Ingrid Correia; Araújo, Amanda Souza; Morano, Maria Tereza; Cavalcante, Antonio George; Bruin, Pedro Felipe de; Paddison, Johana Susan; Silva, Guilherme Pinheiro da; Pereira, Eanes Delgado

    2017-01-01

    To evaluate the properties of the Identity-Consequence Fatigue Scale (ICFS) in patients with lung cancer (LC), assessing the intensity of fatigue and associated factors. This was a cross-sectional study involving LC patients, treated at a teaching hospital in Brazil, who completed the ICFS. Patients with chronic heart disease (CHD) and healthy controls, matched for age and gender, also completed the scale. Initially, a Brazilian Portuguese-language version of the ICFS was administered to 50 LC patients by two independent interviewers; to test for reproducibility, it was readministered to those same patients. At baseline, the LC patients were submitted to spirometry and the six-minute walk test, as well as completing the Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scale (HADS), Medical Outcomes Study 36-item Short-Form Health Survey (SF-36), and Fatigue Severity Scale (FSS). Inflammatory status was assessed by blood C-reactive protein (CRP) levels. To validate the ICFS, we assessed the correlations of its scores with those variables. The sample comprised 50 patients in each group (LC, CHD, and control). In the LC group, the intraclass correlation coefficients for intra-rater and inter-rater reliability regarding ICFS summary variables ranged from 0.94 to 0.76 and from 0.94 to 0.79, respectively. The ICFS presented excellent internal consistency, and Bland-Altman plots showed good test-retest reliability. The ICFS correlated significantly with FSS, HADS, and SF-36 scores, as well as with CRP levels. Mean ICFS scores in the LC group differed significantly from those in the CHD and control groups. The ICFS is a valid, reliable instrument for evaluating LC patients, in whom depression, quality of life, and CRP levels seem to be significantly associated with fatigue. Avaliar as propriedades da Escala de Identificação e Consequências da Fadiga (EICF) em pacientes com câncer de pulmão (CP), analisando a intensidade da fadiga e fatores associados

  20. Polonium and Lung Cancer

    Directory of Open Access Journals (Sweden)

    Vincenzo Zagà

    2011-01-01

    Full Text Available The alpha-radioactive polonium 210 (Po-210 is one of the most powerful carcinogenic agents of tobacco smoke and is responsible for the histotype shift of lung cancer from squamous cell type to adenocarcinoma. According to several studies, the principal source of Po-210 is the fertilizers used in tobacco plants, which are rich in polyphosphates containing radio (Ra-226 and its decay products, lead 210 (Pb-210 and Po-210. Tobacco leaves accumulate Pb-210 and Po-210 through their trichomes, and Pb-210 decays into Po-210 over time. With the combustion of the cigarette smoke becomes radioactive and Pb-210 and Po-210 reach the bronchopulmonary apparatus, especially in bifurcations of segmental bronchi. In this place, combined with other agents, it will manifest its carcinogenic activity, especially in patients with compromised mucous-ciliary clearance. Various studies have confirmed that the radiological risk from Po-210 in a smoker of 20 cigarettes per day for a year is equivalent to the one deriving from 300 chest X-rays, with an autonomous oncogenic capability of 4 lung cancers per 10000 smokers. Po-210 can also be found in passive smoke, since part of Po-210 spreads in the surrounding environment during tobacco combustion. Tobacco manufacturers have been aware of the alpha-radioactivity presence in tobacco smoke since the sixties.

  1. Method for converting asbestos to non-carcinogenic compounds

    Science.gov (United States)

    Selby, Thomas W.

    1996-01-01

    Hazardous and carcinogenic asbestos waste characterized by a crystalline fibrous structure is transformed into non-carcinogenic, relatively nonhazardous, and non-crystalline solid compounds and gaseous compounds which have commercial utilization. The asbestos waste is so transformed by the complete fluorination of the crystalline fibrous silicate mineral defining the asbestos.

  2. A multi-institutional study to assess adherence to lung stereotactic body radiotherapy planning goals

    Energy Technology Data Exchange (ETDEWEB)

    Woerner, Andrew; Roeske, John C.; Harkenrider, Matthew M.; Campana, Maria; Surucu, Murat, E-mail: msurucu@lumc.edu [Loyola University Medical Center, Maywood, Illinois 60153 (United States); Fan, John [Edward Cancer Center, Naperville, Illinois 60540 (United States); Aydogan, Bulent; Koshy, Matthew [Department of Radiation Oncology, University of Illinois at Chicago, Chicago, Illinois 60612 (United States); Laureckas, Robert; Vali, Faisal [Advocate Christ Medical Center, Oak Lawn, Illinois 60453 (United States)

    2015-08-15

    Purpose: A multi-institutional planning study was performed to evaluate the frequency that current guidelines established by Radiation Therapy Oncology Group (RTOG) protocols and other literature for lung stereotactic body radiotherapy (SBRT) treatments are followed. Methods: A total of 300 patients receiving lung SBRT treatments in four different institutions were retrospectively reviewed. The treatments were delivered using Linac based SBRT (160 patients) or image guided robotic radiosurgery (140). Most tumors were located peripherally (250/300). Median fractional doses and ranges were 18 Gy (8–20 Gy), 12 Gy (6–15 Gy), and 10 Gy (5–12 Gy) for three, four, and five fraction treatments, respectively. The following planning criteria derived from RTOG trials and the literature were used to evaluate the treatment plans: planning target volumes, PTV{sub V} {sub 100} ≥ 95% and PTV{sub V} {sub 95} ≥ 99%; conformality indices, CI{sub 100%} < 1.2 and CI{sub 50%} range of 2.9–5.9 dependent on PTV; total lung-ITV: V{sub 20Gy} < 10%, V{sub 12.5Gy} < 15%, and V{sub 5Gy} < 37%; contralateral lung V{sub 5Gy} < 26%; and maximum doses for spinal cord, esophagus, trachea/bronchus, and heart and great vessels. Populations were grouped by number of fractions, and dosimetric criteria satisfaction rates (CSRs) were reported. Results: Five fraction regimens were the most common lung SBRT fractionation (46%). The median PTV was 27.2 cm{sup 3} (range: 3.8–419.5 cm{sup 3}). For all plans: mean PTV{sub V} {sub 100} was 94.5% (±5.6%, planning CSR: 69.8%), mean PTV{sub V} {sub 95} was 98.1% (±4.1%, CSR: 69.5%), mean CI{sub 100%} was 1.14 (±0.21, CSR: 79.1%, and 16.5% within minor deviation), and mean CI{sub 50%} was 5.63 (±2.8, CSR: 33.0%, and 28.0% within minor deviation). When comparing plans based on location, peripherally located tumors displayed higher PTV{sub V} {sub 100} and PTV{sub V} {sub 95} CSR (71.5% and 71.9%, respectively) than centrally located tumors (61

  3. Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays

    Science.gov (United States)

    Tennant, Raymond W.; Margolin, Barry H.; Shelby, Michael D.; Zeiger, Errol; Haseman, Joseph K.; Spalding, Judson; Caspary, William; Resnick, Michael; Stasiewicz, Stanley; Anderson, Beth; Minor, Robert

    1987-05-01

    carcinogenicity and the four in vitro STTs to attempt to confirm the current findings. The standard against which the performance of STTs is measured has changed dramatically in the past decade. The high levels of concordance published in the early 1970s were accurate at the time. Nearly all known carcinogens tested were genotoxic, and there was little experimental evidence on which to base a judgment of noncarcinogenicity which, taken together, restricted assessment of test performances with noncarcinogens. With the increasing availability of results from NCI and NTP 2-year carcinogenicity studies in rodents, higher frequencies of nongenotoxic carcinogens and genotoxic noncarcinogens have been observed; this has resulted in the reduced concordance of the STT results with carcinogenicity results. It is clear that even with a battery of assays, not all rodent carcinogens are in vitro mutagens nor are all in vitro mutagens rodent carcinogens. If current in vitro STTs are expected to replace long-term rodent studies for the identification of chemical carcinogens, then that expectation should be abandoned. STTs do, however, continue to offer an economical, rapid, and dependable means to detect genotoxic chemicals. There is a range of applications in which STTs have been used successfully, from the identification of mutagenic fractions in complex mixtures such as cooked meat (32, 33) or air pollutants (34) to the early identification of genetic toxicity in the development of new chemical products (35). Requirements for the use of STT have not been consistent in both the national and international regulatory agencies. This is evident in the variety of testing requirements (8) and the different impacts that positive test results have on the registration or further testing requirements of chemicals. Consensus on these matters is not likely to occur in the near future, but agreement should be possible in certain areas. For instance, any time a new test or strategy is proposed, it is

  4. Temporal aspects of tumorigenic response to individual and mixed carcinogens. Comprehensive progress report, June 1, 1975--May 31, 1978. [Mouse skin, rats, hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Albert, R.E.; Burns, F.J.; Altshuler, B.

    1978-02-01

    The research proposed here is designed to obtain a better understanding of the temporal kinetics of tumor induction when one or more carcinogens are present simultaneously or sequentially for prolonged periods of time. Studies done to date under this contract have shown that carcinogenesis in mouse skin by polycyclic aromatic hydrocarbon carcinogens is consistent with the induction of dependent and autonomous cell transformations by the carcinogen followed by the conversion of autonomous tumor cells into malignancies at a rate which is determined by the level of carcinogen exposure. Dependent cell transformations remain latent in the skin unless expressed by a promoting agent. Dependent neoplasia appears to follow one-hit kinetics while malignancy is a multihit endpoint. Dose-related and time-related aspects of tumor induction are separable in the initiation-promotion system of mouse skin which along with rat skin and hamster lung is being used as a model for testing hypotheses. Results to date provide the basis for a new interpretation of the linear non-threshold extrapolation model. The broad aim of the study is to provide a basis or rationale for estimating risks associated with prolonged exposures to carcinogens found in the environment and to predict how different tissues and species respond to the same carcinogens.

  5. Assessing the Relationship between Lung Density and Function with Oxygen-Enhanced Magnetic Resonance Imaging in a Mouse Model of Emphysema.

    Directory of Open Access Journals (Sweden)

    Magdalena Zurek

    Full Text Available A magnetic resonance imaging method is presented that allows for the simultaneous assessment of oxygen delivery, oxygen uptake, and parenchymal density. The technique is applied to a mouse model of porcine pancreatic elastase (PPE induced lung emphysema in order to investigate how structural changes affect lung function.Nine-week-old female C57BL6 mice were instilled with saline or PPE at days 0 and 7. At day 19, oxygen delivery, oxygen uptake, and lung density were quantified from T1 and proton-density measurements obtained via oxygen-enhanced magnetic resonance imaging (OE-MRI using an ultrashort echo-time imaging sequence. Subsequently, the lungs were sectioned for histological observation. Blood-gas analyses and pulmonary functional tests via FlexiVent were performed in separate cohorts.PPE-challenged mice had reduced density when assessed via MRI, consistent with the parenchyma loss observed in the histology sections, and an increased lung compliance was detected via FlexiVent. The oxygenation levels, as assessed via the blood-gas analysis, showed no difference between PPE-challenged animals and control. This finding was mirrored in the global MRI assessments of oxygen delivery and uptake, where the changes in relaxation time indices were matched between the groups. The heterogeneity of the same parameters however, were increased in PPE-challenged animals. When the oxygenation status was investigated in regions of varying density, a reduced oxygen-uptake was found in low-density regions of PPE-challenged mice. In high-density regions the uptake was higher than that of regions of corresponding density in control animals. The oxygen delivery was proportional to the oxygen uptake in both groups.The proposed method allowed for the regional assessment of the relationship between lung density and two aspects of lung function, the oxygen delivery and uptake. When compared to global indices of lung function, an increased sensitivity for detecting

  6. Exposure to titanium dioxide and risk of lung cancer in a population-based study from Montreal.

    Science.gov (United States)

    Boffetta, P; Gaborieau, V; Nadon, L; Parent, M F; Weiderpass, E; Siemiatycki, J

    2001-08-01

    This study assessed the lung cancer risk from exposure to titanium dioxide, an important pigment with limited evidence of carcinogenicity in experimental animals but sparse data for humans. The risk of lung cancer among residents in Montreal, Canada, was analyzed, including 857 histologically confirmed cases of lung cancer diagnosed during 1979-1985 among men aged 35-70 years and a group of referents comprising 533 randomly selected, healthy residents and 533 persons with cancer in organs other than the lung. Exposure to titanium dioxide and other titanium compounds was assessed by a team of industrial hygienists on the basis of a detailed occupational questionnaire. Thirty-three cases and 43 referents were classified as exposed to titanium dioxide. The odds ratio was 0.9 [95% confidence interval (95% CI) 0.5-1.5]. No trend was apparent according to the estimated frequency, level, or duration of exposure. The odds ratio was 1.0 (95% CI 0.3-2.7) for medium or high exposure for at least 5 years. Few subjects were classified as exposed to titanium dioxide fumes or to other titanium compounds, but the risk of lung cancer was nonsignificantly increased for exposure to these agents. Although misclassification of exposure and low exposure prevalence might have resulted in false negative results, this study does not suggest that occupational exposure to titanium dioxide increases the risk of lung cancer.

  7. Carcinogenic and mutagenic risk associated to airborne particle-phase polycyclic aromatic hydrocarbons: A source apportionment

    Science.gov (United States)

    Masiol, Mauro; Hofer, Angelika; Squizzato, Stefania; Piazza, Rossano; Rampazzo, Giancarlo; Pavoni, Bruno

    2012-12-01

    Conventional risk assessment studies provide no detailed information about the role of specific sources determining the total carcinogenic and mutagenic potencies of PAH mixtures on humans health. In this study, the main emission sources of 11 particle-phase PAHs listed as carcinogenic and mutagenic agents by the IARC were identified by a risk apportionment method. The contribution of sources to the total concentration of PAHs in the study area was also quantified. A receptor model based on factor and multiple linear regression analyses was applied to estimate the source-specific risk associated to PAH inhalation in an urban background area of a large city (Venice-Mestre, Northern Italy). The proposed approach has discriminated the sources of mutagenic and carcinogenic congeners and their role in determining a serious hazard for human health. Results, interpreted on the basis of seasonal variations and atmospheric conditions, have shown that even though domestic heating is the main source of total PAHs in winter, a background pollution including traffic mainly accounts for the carcinogenic and mutagenic risk during the whole year. The findings of this work and the approach used can be easily applied to other geographic areas and provide useful information for local and regional air pollution control strategies.

  8. Carcinogenicity evaluation: comparison of tumor data from dual control groups in the CD-1 mouse.

    Science.gov (United States)

    Baldrick, Paul; Reeve, Lesley

    2007-06-01

    Current regulatory thinking allows for the use of single control groups for rodent carcinogenicity testing although there has been a trend until recently to use dual control groups. To date, virtually nothing has been published on whether a shift from dual to single control groups will affect the identification of tumorigenic risk potential in these studies. A recent evaluation of dual control carcinogenicity data in the rat (Baldrick, Toxicol Pathol 2005, 33: 283-291) showed that although no major differences in tumor incidences between the control groups were found, some interstudy variation occurred and in cases were a notable difference was seen, the use of 2 control groups, as well as robust, contemporary background data, allowed an easier interpretation of findings in drug-treated groups. In this paper, the results of 10 mouse carcinogenicity studies, performed between 1991 and 2004, with 2 control groups, are presented. As in the rat, interstudy variation was seen and in some cases, the use of dual control groups assisted in the tumor risk assessment. Thus, the continued use of 2 control groups can have a vital role in mouse carcinogenicity studies. The paper also presents an update on survival, on the range and extent of background spontaneous neoplasms and comments on genetic drift in this commonly used mouse strain.

  9. Mechanism-Based Classification of PAH Mixtures to Predict Carcinogenic Potential.

    Science.gov (United States)

    Tilton, Susan C; Siddens, Lisbeth K; Krueger, Sharon K; Larkin, Andrew J; Löhr, Christiane V; Williams, David E; Baird, William M; Waters, Katrina M

    2015-07-01

    We have previously shown that relative potency factors and DNA adduct measurements are inadequate for predicting carcinogenicity of certain polycyclic aromatic hydrocarbons (PAHs) and PAH mixtures, particularly those that function through alternate pathways or exhibit greater promotional activity compared to benzo[a]pyrene (BaP). Therefore, we developed a pathway-based approach for classification of tumor outcome after dermal exposure to PAH/mixtures. FVB/N mice were exposed to dibenzo[def,p]chrysene (DBC), BaP, or environmental PAH mixtures (Mix 1-3) following a 2-stage initiation/promotion skin tumor protocol. Resulting tumor incidence could be categorized by carcinogenic potency as DBC > BaP = Mix2 = Mix3 > Mix1 = Control, based on statistical significance. Gene expression profiles measured in skin of mice collected 12 h post-initiation were compared with tumor outcome for identification of short-term bioactivity profiles. A Bayesian integration model was utilized to identify biological pathways predictive of PAH carcinogenic potential during initiation. Integration of probability matrices from four enriched pathways (P carcinogenic potential of environmental PAH mixtures. These data further provide a 'source-to-outcome' model that could be used to predict PAH interactions during tumorigenesis and provide an example of how mode-of-action-based risk assessment could be employed for environmental PAH mixtures. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Asian Americans and disproportionate exposure to carcinogenic hazardous air pollutants: A national study.

    Science.gov (United States)

    Grineski, Sara E; Collins, Timothy W; Morales, Danielle X

    2017-07-01

    Studies have demonstrated disparate exposures to carcinogenic hazardous air pollutants (HAPs) in neighborhoods with high densities of Black and Hispanic residents in the US. Asians are the fastest growing racial/ethnic group in the US, yet they have been underemphasized in previous studies of environmental health and injustice. This cross-sectional study investigated possible disparities in residential exposure to carcinogenic HAPs among Asian Americans, including Asian American subgroups in the US (including all 50 states and the District of Columbia, n = 71,208 US census tracts) using National Air Toxics Assessment and US Census data. In an unadjusted analysis, Chinese and Korean Americans experience the highest mean cancer risks from HAPs, followed by Blacks. The aggregated Asian category ranks just below Blacks and above Hispanics, in terms of carcinogenic HAP risk. Multivariate models adjusting for socioeconomic status, population density, urban location, and geographic clustering show that an increase in proportion of Asian residents in census tracts is associated with significantly greater cancer risk from HAPs. Neighborhoods with higher proportions (as opposed to lower proportions) of Chinese, Korean, and South Asian residents have significantly greater cancer risk burdens relative to Whites. Tracts with higher concentrations of Asians speaking a non-English language and Asians that are US-born have significantly greater cancer risk burdens. Asian Americans experience substantial residential exposure to carcinogenic HAPs in US census tracts and in the US more generally. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Trace elements and carcinogenicity: a subject in review.

    Science.gov (United States)

    Mulware, Stephen Juma

    2013-04-01

    Cancer is known to be a multi-step process, which involves different stages including initiation, promotion, progression and metastasis. Chemical carcinogens including most trace elements can change any of these processes to induce their carcinogenic effects. Various studies confirm that cancer arises from the accumulation of irreversible DNA damage, which results from multiple mutations in critical genes in the body organ. Chemical carcinogens most often directly or after xenobiotic metabolism, act as genotoxic causes to induce DNA damage. Genotoxic carcinogen refers to a group of chemicals capable of producing cancer by directly altering the genetic material of target cells. Other carcinogens are however classified as non-genotoxic, which represents chemicals that are capable of producing cancer by some secondary mechanism not related to direct gene damage. They act as tumor promoters, endocrine-modifiers, receptor mediators, immunosuppressant, or inducers of tissue-specific toxicity and inflammatory responses. The diversity of modes of action, of non-genotoxic carcinogens, the tissue and species specificity and the absence of genotoxicity makes it extremely hard to predict their carcinogenic potential. The roles of trace metals (some of which are either genotoxic or non-genotoxic) in cancer development and inhibition have a complex character and have raised many questions because of their essential and toxic effects on people's health. Trace metals such as cadmium, nickel, arsenic, beryllium and chromium (VI) have been recognized as human or animal carcinogens by International Agency for Research on Cancer (IARC). The Carcinogenic capability of these metals depends mainly on factors such as oxidation states and chemical structures. The oxidative concept in metal carcinogenesis proposes that complexes formed by these metals, in vivo, in the vicinity of DNA, catalyze redox reactions, which in turn oxidize DNA. The most significant effect of reactive oxygen species

  12. Ventilation/perfusion SPECT in chronic obstructive pulmonary disease: an evaluation by reference to symptoms, spirometric lung function and emphysema, as assessed with HRCT.

    Science.gov (United States)

    Jögi, Jonas; Ekberg, Marie; Jonson, Björn; Bozovic, Gracijela; Bajc, Marika

    2011-07-01

    Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation which is not fully reversible. Despite the heterogeneity of COPD, its diagnosis and staging is currently based solely on forced expiratory volume in 1 s (FEV(1)). FEV(1) does not explain the underlying pathophysiology of airflow limitation. The relationship between FEV(1), symptoms and emphysema extent is weak. Better diagnostic tools are needed to define COPD. Tomographic lung scintigraphy [ventilation/perfusion single photon emission tomography (V/P SPECT)] visualizes regional V and P. In COPD, relations between V/P SPECT, spirometry, high-resolution computed tomography (HRCT) and symptoms have been insufficiently studied. The aim of this study was to investigate how lung function imaging and obstructive disease grading undertaken using V/P SPECT correlate with symptoms, spirometric lung function and degree of emphysema assessed with HRCT in patients with COPD. Thirty patients with stable COPD were evaluated with the Medical Research Council dyspnoea questionnaire (MRC) and the clinical COPD questionnaire (CCQ). Spirometry was performed. The extent of emphysema was assessed using HRCT. V/P SPECT was used to assess V/P patterns, total reduction in lung function and degree of obstructive disease. The total reduction in lung function and degree of obstructive disease, assessed with V/P SPECT, significantly correlated with emphysema extent (r = 0.66-0.69, p emphysema extent and spirometric lung function was weaker. No correlation between MRC, CCQ and objective measurements was found. V/P SPECT is sensitive to early changes in COPD. V/P SPECT also has the possibility to identify comorbid disease. V/P SPECT findings show a significant correlation with emphysema extent and spirometric lung function. We therefore recommend that scintigraphic signs of COPD, whenever found, should be reported. V/P SPECT can also be used to categorize the severity of functional changes in COPD as mild

  13. Association of arsenic exposure with lung cancer incidence rates in the United States.

    Directory of Open Access Journals (Sweden)

    Joseph J Putila

    Full Text Available Although strong exposure to arsenic has been shown to be carcinogenic, its contribution to lung cancer incidence in the United States is not well characterized. We sought to determine if the low-level exposures to arsenic seen in the U.S. are associated with lung cancer incidence after controlling for possible confounders, and to assess the interaction with smoking behavior.Measurements of arsenic stream sediment and soil concentration obtained from the USGS National Geochemical Survey were combined, respectively, with 2008 BRFSS estimates on smoking prevalence and 2000 U.S. Census county level income to determine the effects of these factors on lung cancer incidence, as estimated from respective state-wide cancer registries and the SEER database. Poisson regression was used to determine the association between each variable and age-adjusted county-level lung cancer incidence. ANOVA was used to assess interaction effects between covariates.Sediment levels of arsenic were significantly associated with an increase in incident cases of lung cancer (P<0.0001. These effects persisted after controlling for smoking and income (P<0.0001. Across the U.S., exposure to arsenic may contribute to up to 5,297 lung cancer cases per year. There was also a significant interaction between arsenic exposure levels and smoking prevalence (P<0.05.Arsenic was significantly associated with lung cancer incidence rates in the U.S. after controlling for smoking and income, indicating that low-level exposure to arsenic is responsible for excess cancer cases in many parts of the U.S. Elevated county smoking prevalence strengthened the association between arsenic exposure and lung cancer incidence rate, an effect previously unseen on a population level.

  14. IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

    Science.gov (United States)

    Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M.; Armstrong, Bruce K.; Baccarelli, Andrea A.; Beland, Frederick A.; Berrington, Amy; Bertazzi, Pier Alberto; Birnbaum, Linda S.; Brownson, Ross C.; Bucher, John R.; Cantor, Kenneth P.; Cardis, Elisabeth; Cherrie, John W.; Christiani, David C.; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A.; Dement, John M.; Douwes, Jeroen; Eisen, Ellen A.; Engel, Lawrence S.; Fenske, Richard A.; Fleming, Lora E.; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K.; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A.; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R.; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H.; Lynch, Charles F.; Lynge, Elsebeth; ‘t Mannetje, Andrea; McMichael, Anthony J.; McLaughlin, John R.; Marrett, Loraine; Martuzzi, Marco; Merchant, James A.; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E.; Monson, Richard; Nordby, Karl-Cristian; Olshan, Andrew F.; Parent, Marie-Elise; Perera, Frederica P.; Perry, Melissa J.; Pesatori, Angela Cecilia; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B.; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M.; Rushton, Lesley; Rusiecki, Jennifer A.; Rusyn, Ivan; Samet, Jonathan M.; Sandler, Dale P.; de Sanjose, Silvia; Schernhammer, Eva; Costantini, Adele Seniori; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silverman, Debra T.; Simonato, Lorenzo; Smith, Allan H.; Smith, Martyn T.; Spinelli, John J.; Spitz, Margaret R.; Stallones, Lorann; Stayner, Leslie T.; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W.; Stewart, Patricia A.; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E.; Vainio, Harri; Vena, John; Vermeulen, Roel; Victora, Cesar G.; Ward, Elizabeth M.; Weinberg, Clarice R.; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia Hoar

    2015-01-01

    Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. Discussion: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. Conclusions: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public’s health. Citation: Pearce N, Blair A, Vineis P, Ahrens W, Andersen A, Anto JM, Armstrong BK, Baccarelli AA, Beland FA, Berrington A, Bertazzi PA, Birnbaum LS, Brownson RC, Bucher JR, Cantor KP

  15. Development of a screening tool to prioritize testing for the carcinogenic hazard of residual aromatic extracts and related petroleum streams.

    Science.gov (United States)

    Goyak, Katy O; Kung, Ming H; Chen, Min; Aldous, Keith K; Freeman, James J

    2016-12-15

    Residual aromatic extracts (RAE) are petroleum substances with variable composition predominantly containing aromatic hydrocarbons with carbon numbers greater than C25. Because of the high boiling nature of RAEs, the aromatics present are high molecular weight, with most above the range of carcinogenic polycyclic aromatic hydrocarbons (PAHs). However, refinery distillations are imperfect; some PAHs and their heteroatom-containing analogs (collectively referred to as polycyclic aromatic content or PAC) may remain in the parent stream and be extracted into the RAE, and overall PAC content is related to the carcinogenic potential of an RAE. We describe here a real-time analytical chemistry-based tool to assess the carcinogenic hazard of RAE via the development of a functional relationship between carcinogenicity and boiling point. Samples representative of steps along the RAE manufacturing process were obtained from five refineries to evaluate relationships between mutagenicity index (MI), PAC ring content and gas chromatographic distillation (GCD) curves. As expected, a positive linear relationship between MI and PAC ring content occurred, most specifically for 3-6 ring PAC (R2=0.68). A negative correlation was found between MI and temperature at 5% vaporization by GCD (R2=0.72), indicating that samples with greater amounts of lower boiling constituents were more likely to be carcinogenic. The inverse relationship between boiling range and carcinogenicity was further demonstrated by fractionation of select RAE samples (MI=0.50+0.07; PAC=1.70+0.51wt%; n=5) into low and high boiling fractions, where lower boiling fractions were both more carcinogenic than the higher boiling fractions (MI=2.36±0.55 and 0.17±0.11, respectively) and enriched in 3-6 ring PACs (5.20+0.70wt% and 0.97+0.35wt%, respectively). The criteria defining carcinogenicity was established as 479°C for the 5% vaporization points by GCD, with an approximate 95% probability of a future sample having an

  16. Toxico-Cheminformatics and QSPR Modeling of the Carcinogenic Potency Database

    Science.gov (United States)

    Report on the development of a tiered, confirmatory scheme for prediction of chemical carcinogenicity based on QSAR studies of compounds with available mutagenic and carcinogenic data. For 693 such compounds from the Carcinogenic Potency Database characterized molecular topologic...

  17. Spirometry and volumetric capnography in lung function assessment of obese and normal-weight individuals without asthma.

    Science.gov (United States)

    Ferreira, Mariana S; Mendes, Roberto T; Marson, Fernando A L; Zambon, Mariana P; Antonio, Maria A R G M; Paschoal, Ilma A; Toro, Adyléia A D C; Severino, Silvana D; Ribeiro, Maria A G O; Ribeiro, José D

    To analyze and compare lung function of obese and healthy, normal-weight children and adolescents, without asthma, through spirometry and volumetric capnography. Cross-sectional study including 77 subjects (38 obese) aged 5-17 years. All subjects underwent spirometry and volumetric capnography. The evaluations were repeated in obese subjects after the use of a bronchodilator. At the spirometry assessment, obese individuals, when compared with the control group, showed lower values of forced expiratory volume in the first second by forced vital capacity (FEV 1 /FVC) and expiratory flows at 75% and between 25 and 75% of the FVC (p11 years (p<0.05). Even without the diagnosis of asthma by clinical criteria and without response to bronchodilator use, obese individuals showed lower FEV 1 /FVC values and forced expiratory flow, indicating the presence of an obstructive process. Volumetric capnography showed that obese individuals had higher alveolar tidal volume, with no alterations in ventilation homogeneity, suggesting flow alterations, without affecting lung volumes. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  18. Spirometry and volumetric capnography in lung function assessment of obese and normal-weight individuals without asthma

    Directory of Open Access Journals (Sweden)

    Mariana S. Ferreira

    Full Text Available Abstract Objective: To analyze and compare lung function of obese and healthy, normal-weight children and adolescents, without asthma, through spirometry and volumetric capnography. Methods: Cross-sectional study including 77 subjects (38 obese aged 5-17 years. All subjects underwent spirometry and volumetric capnography. The evaluations were repeated in obese subjects after the use of a bronchodilator. Results: At the spirometry assessment, obese individuals, when compared with the control group, showed lower values of forced expiratory volume in the first second by forced vital capacity (FEV1/FVC and expiratory flows at 75% and between 25 and 75% of the FVC (p 11 years (p < 0.05. Conclusion: Even without the diagnosis of asthma by clinical criteria and without response to bronchodilator use, obese individuals showed lower FEV1/FVC values and forced expiratory flow, indicating the presence of an obstructive process. Volumetric capnography showed that obese individuals had higher alveolar tidal volume, with no alterations in ventilation homogeneity, suggesting flow alterations, without affecting lung volumes.

  19. Assessment of Control Tissue for Gene and Protein Expression Studies: A Comparison of Three Alternative Lung Sources

    Directory of Open Access Journals (Sweden)

    Margaret R. Passmore

    2012-01-01

    Full Text Available The use of an appropriate control group in human research is essential in investigating the level of a pathological disorder. This study aimed to compare three alternative sources of control lung tissue and to determine their suitability for gene and protein expression studies. Gene and protein expression levels of the vascular endothelial growth factor (VEGF and gelatinase families and their receptors were measured using real-time reverse transcription polymerase chain reaction (RT-PCR and immunohistochemistry. The gene expression levels of VEGFA, placental growth factor (PGF, and their receptors, fms-related tyrosine kinase 1 (FLT1, and kinase insert domain receptor (KDR as well as matrix metalloproteinase-2 (MMP-2 and the inhibitors, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 and TIMP-2 were significantly higher in lung cancer resections. The gene expression level of MMP-9 was significantly lower in the corresponding samples. Altered protein expression was also detected, depending on the area assessed. The results of this study show that none of the three control groups studied are completely suitable for gene and protein studies associated with the VEGF and gelatinase families, highlighting the need for researchers to be selective in which controls they opt for.

  20. Assessment of asbestos-induced pleural disease by computed tomography--correlation with chest radiograph and lung function.

    Science.gov (United States)

    al Jarad, N; Poulakis, N; Pearson, M C; Rubens, M B; Rudd, R M

    1991-05-01

    We compared computed tomography (CT) scanning with chest radiography in the assessment of asbestos-induced pleural disease (AIPD) in 20 patients (17 men and 3 women, mean age 55 years, range 43-74 years). Involved pleura was scored on plain chest radiographs according to the International Labour Office (ILO) method of evaluating AIPD. A CT score was calculated from the measurement, using a digital length probe, of the circumference of the chest wall involved by pleural disease in each slice. The maximum width of pleural disease was taken into account in a way analogous to the ILO method for the chest radiograph. The CT score correlated with the chest radiograph score (r = +0.82, P less than 0.0006). CT demonstrated discrete plaques in 95% of patients but these were identified only in 59% patients on the radiograph. Diffuse pleural thickening was evident on the CT scan in all patients and in 70% on the radiograph. There was more inter-reader agreement about the type of pleural disease on the CT scans than on the chest radiographs. CT and chest radiograph scores inversely correlated with all lung function measurements except KCO. We conclude that increasingly extensive pleural disease is associated with increasingly severe impairment of lung function. CT scanning demonstrates the type of AIPD better than plain chest radiography.

  1. Lung morphology assessment of cystic fibrosis using MRI with ultra-short echo time at submillimeter spatial resolution

    Energy Technology Data Exchange (ETDEWEB)

    Dournes, Gael [University of Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); CHU de Bordeaux, Service d' Imagerie Thoracique et Cardiovasculaire, Service des Maladies Respiratoires, Service d' Exploration Fonctionnelle Respiratoire, Pessac (France); Centre de Recherche Cardio-thoracique de Bordeaux, INSERM, U1045, Universite de Bordeaux, Bordeaux (France); Menut, Fanny [CHU de Bordeaux, Service d' Imagerie de la Femme et de l' Enfant, Unite de Pneumologie pediatrique, Bordeaux (France); Macey, Julie; Montaudon, Michel; Berger, Patrick; Laurent, Francois [University of Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); CHU de Bordeaux, Service d' Imagerie Thoracique et Cardiovasculaire, Service des Maladies Respiratoires, Service d' Exploration Fonctionnelle Respiratoire, Pessac (France); Fayon, Michael [University of Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); CHU de Bordeaux, Service d' Imagerie de la Femme et de l' Enfant, Unite de Pneumologie pediatrique, Bordeaux (France); Chateil, Jean-Francois [CHU de Bordeaux, Service d' Imagerie de la Femme et de l' Enfant, Unite de Pneumologie pediatrique, Bordeaux (France); University of Bordeaux, Centre de Resonance Magnetique des Systemes Biologiques, Bordeaux (France); Salel, Marjorie; Corneloup, Olivier [University of Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, Bordeaux (France); CHU de Bordeaux, Service d' Imagerie Thoracique et Cardiovasculaire, Service des Maladies Respiratoires, Service d' Exploration Fonctionnelle Respiratoire, Pessac (France)

    2016-11-15

    We hypothesized that non-contrast-enhanced PETRA (pointwise encoding time reduction with radial acquisition) MR (magnetic resonance) sequencing could be an alternative to unenhanced computed tomography (CT) in assessing cystic fibrosis (CF) lung structural alterations, as well as compared agreements and concordances with those of conventional T1-weighted and T2-weighted sequences. Thirty consecutive CF patients completed both CT and MRI the same day. No contrast injection was used. Agreement in identifying structural alterations was evaluated at the segmental level using a kappa test. Intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to assess concordances and reproducibility in Helbich-Bhalla disease severity scoring. Agreement between PETRA and CT was higher than that of T1- or T2-weighted sequences, notably in assessing the segmental presence of bronchiectasis (Kappa = 0.83; 0.51; 0.49, respectively). The concordance in Helbich-Bhalla scores was very good using PETRA (ICC = 0.97), independently from its magnitude (mean difference (MD) = -0.3 [-2.8; 2.2]), whereas scoring was underestimated using both conventional T1 and T2 sequences (MD = -3.6 [-7.4; 0.1]) and MD = -4.6 [-8.2; -1.0], respectively. Intra- and interobserver reproducibility were very good for all imaging modalities (ICC = 0.86-0.98). PETRA showed higher agreement in describing CF lung morphological changes than that of conventional sequences, whereas the Helbich-Bhalla scoring matched closely with that of CT. (orig.)

  2. Motivation and preferences of exercise programmes in patients with inoperable metastatic lung cancer: a need assessment.

    Science.gov (United States)

    Kartolo, Adi; Cheng, Susanna; Petrella, Teresa

    2016-01-01

    The aim of this study is to investigate the motivation, ability, preferences, and perceived potential facilitating factors/barriers of patients with inoperable metastatic lung cancer towards exercise programmes. This is a cross-sectional study using survey adopting the Theory of Planned Behaviour (TPB) to obtain patients' experience recruited through Odette Cancer Centre, Sunnybrook Health Sciences Complex. Results were expressed in percentages, P value, and Spearman's rho. Sixty patients were recruited from January 2014 to April 2014. Patients generally had a high level across TPB measures, with 63% of them indicating that they have the motivation to exercise. Significant association in relation to motivation was established on attitudes (importance, P = 0.005, rho = 0.326; helpfulness, P = 0.015, rho = 0.348; and easiness, P = 0.001, rho = 0.375) and subjective norm of close members (P = 0.0069, rho = 0.348) and healthcare professionals (P = 0.012, rho = 0.328). Being a non-smoker (P = 0.042, rho = 0.311), having a past exercise history prior to diagnosis (P = 0.000, rho = 0.563), and absence of COPD (P = 0.016, rho = -0.312) were also shown to have a significant association with motivation to exercise. Patients were motivated to participate in an exercise programme despite contrary belief; however, they might have limited ability and preferred light intensity type of exercise such as walking. Their motivation to exercise was driven by different factors when compared to other cancer patient populations. Thus, it is important for healthcare professionals to understand the factors influencing their motivation and increase their awareness (only 26% of patients indicated receiving advice regarding exercise) to better the care towards patients with metastatic lung cancer.

  3. Multiple parametric approaches to assess acute radiation lung injury of rats

    Directory of Open Access Journals (Sweden)

    Sandeep Soni

    2016-02-01

    Full Text Available The effect of whole body gamma irradiation (WBI in single fraction was studied, as well as its influen­ce on the secretion of various biochemical markers and cellular component that could be used as acute radiation lung injury marker. Sprague dawley rats were treated with WBI (60Co of radiation dose from 1 Gy to 5 Gy (dose rate – 0.95 Gy/min. Bronchoalveolar lavage fluid was retrieved from all animals in control and radiation treated groups up to 72 h post radiation. Bronchoalveolar lavage fluid (BALF was analyzed for lactate dehydrogenase (LDH, acid phosphatase (AP, alkaline phosphatase (ALP, cell count and total protein. Intragroup and intergroup comparison of BALF parameters at different radiation doses showed significant difference. LDH was significantly increased as the dose increased from 1Gy to 5Gy (P = 0.00 after 2 h with effect size of difference (r > 0.3. ALP was significantly altered after 3Gy and 4Gy (P < 0.05. AP was significantly altered at 2Gy-5Gy (P < 0.05. Total protein level changed significantly from 1Gy to 5Gy (P < 0.00. Cellular content of BALF showed significant changes after radiation exposure. BALF parameters like LDH, AP, ALP, neutrophils, lymphocytes, total leukocyte count and total protein were sensitive to radiation exposure and their levels vary significantly up to 72 h after single whole body radiation exposure in Sprague dawley rats. It can be concluded that the biochemical indices in BALF have more wide application in evaluation of acute radiation induced lung injury.

  4. Assessment of Impact of High Particulate Concentration on Peak Expiratory Flow Rate of Lungs of Sand Stone Quarry Workers

    Directory of Open Access Journals (Sweden)

    Gopal Purohit

    2006-12-01

    Full Text Available This study was designed to assess the impact of high particulate concentration on peak expiratory flow rate of lungs of sand stone quarry workers. The workers were engaged in different types of activities such as drilling, loading and dressing. These different working conditions had different concentrations of RSPM, leading to different exposure levels in workers. It was found that exposure duration and exposure concentrations were the main factors responsible for damage to the respiratory tracts of the workers. The particles were deposited at various areas of the respiratory system and reduced the peak flow rate. It was also revealed from the study that most of the workers suffered from silicosis if the exposure duration was more than 20 years.

  5. Association between photodynamic and carcinogenic activities in polycyclic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Epstein, S.S.; Small, M.; Falk, H.L.; Mantel, N.

    1964-06-01

    The photodynamic activities of 157 polycyclic compounds of wide structural range were determined, with the use of Paramecium caudatum. High photodynamic activity was largely confined to polycyclic compounds, either homocyclic or heterocyclic, with four or five fused rings. Significant absorption of light was shown to be prerequisite but not sufficient for high photodynamic activity. A significant statistical association between photodynamic activity and carcinogenicity was demonstrated. It was shown that compounds with high photodynamic activity had 4 times greater odds of being carcinogenic than compounds with low activity. However, the photodynamic assay cannot identify a particular polycyclic compound as being carcinogenic or noncarcinogenic.

  6. Uncertainty induced by chest wall thickness assessment methods on lung activity estimation for plutonium and americium: a large population-based study.

    Science.gov (United States)

    Broggio, D; Lechaftois, X; Franck, D

    2015-03-01

    In vivo lung counting aims at assessing the retained activity in the lungs. The calibration factor relating the measured counts to the worker's specific retained lung activity can be obtained by several means and strongly depends on the chest wall thickness. Here we compare, for 374 male nuclear workers, the activity assessed with a reference protocol, where the material equivalent chest wall thickness is known from ultrasound measurements, with two other protocols. The counting system is an array of four germanium detectors.It is found that non site-specific equations for the assessment of the chest wall thickness induce large biases in the assessment of activity. For plutonium isotopes or (241)Am the proportion of workers for whom the retained activity is within ± 10% of the reference one is smaller than 10%.The use of site-specific equations raises this proportion to 20% and 58% for plutonium and (241)Am, respectively.Finally, for the studied population, when site-specific equations are used for the chest wall thickness, the standard uncertainties for the lung activity are 42% and 12.5%, for plutonium and (241)Am, respectively. Due to the relatively large size of the studied population, these values are a relatively robust estimate of the uncertainties due to the assessment of the chest wall thickness for the current practice at this site.

  7. Association between six environmental chemicals and lung cancer incidence in the United States.

    Science.gov (United States)

    Luo, Juhua; Hendryx, Michael; Ducatman, Alan

    2011-01-01

    An increased risk of lung cancer has been observed at exposure to certain industrial chemicals in occupational settings; however, less is known about their carcinogenic potential to the general population when those agents are released into the environment. We used the Toxics Release Inventory (TRI) database and Surveillance, Epidemiology, and End Results (SEER) data to conduct an ecological study at the county level. We used multiple linear regression to assess the association of age-adjusted lung cancer incidence with the quantities of on-site air and water releases of six selected industrial chemicals including arsenic, 1,3 butadiene, cadmium, chromium, formaldehyde, and nickel after controlling for other risk variables. Overall, we observed a significantly increased risk of lung cancer incidence associated with releases of chromium, formaldehyde, and nickel. The links were present for both males and females. Significant effects were present in nonmetropolitan but not metropolitan counties. Releases of arsenic, 1,3 butadiene, and cadmium were reported by small numbers of facilities, and no relationships to lung cancer incidence were detected. Our results suggest that environmental exposure to chromium, formaldehyde, and nickel from TRI sites may increase population risk of lung cancer. These findings need to be confirmed in individual-level studies, but in congruence with the precautionary principle in environmental science, support prudent efforts to limit release of these agents into the environment.

  8. Genetic Variation in GSTP1, Lung Function, Risk of Lung Cancer, and Mortality

    DEFF Research Database (Denmark)

    Nørskov, Marianne S.; Dahl, Morten; Tybjærg-Hansen, Anne

    2017-01-01

    Introduction Glutathione S-transferase pi 1 metabolizes carcinogens from tobacco smoke in the lung. We tested whether genetically altered glutathione S-transferase pi 1 activity affects lung function and risk for tobacco-related cancer and mortality in the general population. Methods We genotyped......Val was associated with increased lung function, reduced risk for lung cancer and tobacco-related cancer, and reduced all-cause mortality in the general population.......Introduction Glutathione S-transferase pi 1 metabolizes carcinogens from tobacco smoke in the lung. We tested whether genetically altered glutathione S-transferase pi 1 activity affects lung function and risk for tobacco-related cancer and mortality in the general population. Methods We genotyped...... 66,069 individuals from the white general population for two common functional variants in the glutathione S-transferase pi 1 gene (GSTP1)—amino acid isoleucine 105 changed to a valine (Ile105Val) and amino acid alanine 114 changed to a valine (Ala114Val)—and recorded lung function, lung cancer...

  9. Comparison of nicotine and carcinogen exposure with water pipe and cigarette smoking

    OpenAIRE

    Jacob, P.; Raddaha, AHA; Dempsey, D.; Havel, C; Peng, M.; Yu, L; Benowitz, NL

    2013-01-01

    Background: Smoking tobacco preparations in a water pipe (hookah) is widespread in many places of the world and is perceived by many as relatively safe.Weinvestigated biomarkers of toxicant exposure with water pipe compared with cigarette smoking. Methods: Weconducted a crossover study to assess daily nicotine and carcinogen exposure with water pipe and cigarette smoking in 13 people who were experienced in using both products. Results: When smoking an average of 3 water pipe sessions compare...

  10. Lung cancer in a patient with predominantly short tremolite fibers in his lung.

    Science.gov (United States)

    Kohyama, Norihiko; Fujiki, Masaaki; Kishimoto, Takumi; Morinaga, Kenji

    2017-09-01

    The carcinogenicity of short tremolite fibers in human has not been cleared and has been argued hitherto. A lung cancer patient had worked at a gabbro quarry. Particles isolated from the excised lung parenchyma of the patient were measured for asbestos bodies (ABs) and asbestos fibers (AFs). The concentrations of ABs were 3964 AB/g dry lung, and AFs were 5.60 × 106 fibers/g dry lung (>5 um in length) and 22.5 × 106 fibers/g dry lung (>1 um in length). AFs were mostly tremolite fibers and under 7 um in length (mean length 4.0 um, standard deviation 2.8 um). Almost all fibers were fibers will induce lung cancer and possibly mesothelioma in human. © 2017 Wiley Periodicals, Inc.

  11. Can creatine supplementation form carcinogenic heterocyclic amines in humans?

    Science.gov (United States)

    Pereira, Renato Tavares dos Santos; Dörr, Felipe Augusto; Pinto, Ernani; Solis, Marina Yazigi; Artioli, Guilherme Giannini; Fernandes, Alan Lins; Murai, Igor Hisashi; Dantas, Wagner Silva; Seguro, Antônio Carlos; Santinho, Mirela Aparecida Rodrigues; Roschel, Hamilton; Carpentier, Alain; Poortmans, Jacques Remi; Gualano, Bruno

    2015-09-01

    There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation. HCAs detection was unrelated to creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo (n = 6) or creatine supplementation (n = 3). These results directly challenge the recently suggested biological plausibility for the association between creatine use and risk of testicular germ cell cancer. Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), 2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC-MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was

  12. Indirect validation of a retrospective method of exposure assessment used in a nested case-control study of lung cancer and silica exposure.

    Science.gov (United States)

    Dosemeci, M; McLaughlin, J K; Chen, J Q; Hearl, F; McCawley, M; Wu, Z; Chen, R G; Peng, K L; Chen, A L; Rexing, S H

    1994-02-01

    Validations of retrospective methods of assessment used in occupational epidemiological studies have rarely been published. This study is an indirect validation of a quantitative retrospective assessment of exposure to silica used in a nested case-control study of lung cancer among workers at 29 metal mines and pottery factories in China. Indices of cumulative total dust and cumulative respirable dust were calculated by merging work histories with the historical exposure profile for each subject. To validate indirectly the methods of exposure assessment used in the study of lung cancer, trends for exposure response relation between the two indices of exposure to silica and risk of silicosis were evaluated with 376 patients with silicosis from the study population as the cases, and 1262 controls without silicosis for comparison. Age adjusted odds ratios (ORs) as a measure of risk of silicosis showed striking trends with both indices of exposure to silica. For cumulative respirable dust, the OR (95% confidence interval) rose from 7.6 (5.1-11.4) for low exposure to 20.0 (13.2-30.6) for medium exposure, and to 51.7 (31.0-86.8) for high exposure. The strength of the association between exposure to silica and risk of silicosis suggests that the retrospective assessment of exposure used in the case-control study of lung cancer would accurately reflect an exposure response relation between silica and lung cancer, if it existed.

  13. Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic 18F Fluorodeoxyglucose PET

    NARCIS (Netherlands)

    Meijer, T.W.H.; Geus-Oei, L.F. de; Visser, E.P.; Oyen, W.J.G.; Looijen-Salamon, M.G.; Visvikis, D.; Verhagen, A.F.T.M.; Bussink, J.; Vriens, D.

    2017-01-01

    Purpose To assess whether dynamic fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static 18F-FDG PET for tumor delineation in non-small cell lung cancer (NSCLC) radiation therapy planning by using pathology volumes as the reference standard and to

  14. ASSESSMENT OF ACUTE LUNG INJURY INDUCED BY PM 2.5 SAMPLES FROM TWO CITIES IN GERMANY WITH DIFFERING INCIDENCE OF ALLERGIES AND ASTHMA

    Science.gov (United States)

    ASSESSMENT OF ACUTE LUNG INJURY INDUCED BY PM 2.5 SAMPLES FROM TWO CITIES IN GERMANY WITH DIFFERING INCIDENCE OF ALLERGIES AND ASTHMA.LR Bishop, J Heinrich*, MK Selgrade & MI Gilmour. Experimental Toxicology Division, ORD/ NHEERL, U.S. EPA, RTP, NC. *GSF, Neuherberg,...

  15. Systematic review of the epidemiological evidence comparing lung cancer risk in smokers of mentholated and unmentholated cigarettes

    Directory of Open Access Journals (Sweden)

    Lee Peter N

    2011-04-01

    Full Text Available Abstract Background US mentholated cigarette sales have increased considerably over 50 years. Preference for mentholated cigarettes is markedly higher in Black people. While menthol itself is not genotoxic or carcinogenic, its acute respiratory effects might affect inhalation of cigarette smoke. This possibility seems consistent with the higher lung cancer risk in Black men, despite Black people smoking less and starting smoking later than White people. Despite experimental data suggesting similar carcinogenicity of mentholated and non-mentholated cigarettes, the lack of convincing evidence that mentholation increases puffing, inhalation or smoke uptake, and the similarity of lung cancer rates in Black and White females, a review of cigarette mentholation and lung cancer is timely given current regulatory interest in the topic. Methods Epidemiological studies comparing lung cancer risk in mentholated and non-mentholated cigarette smokers were identified from MedLine and other sources. Study details were extracted and strengths and weaknesses assessed. Relative risk estimates were extracted, or derived, for ever mentholated use and for long-term use, overall and by gender, race, and current/ever smoking, and meta-analyses conducted. Results Eight generally good quality studies were identified, with valid cases and controls, and appropriate adjustment for age, gender, race and smoking. The studies afforded good power to detect possible effects. However, only one study presented results by histological type, none adjusted for occupation or diet, and some provided no results by length of mentholated cigarette use. The data do not suggest any effect of mentholation on lung cancer risk. Adjusted relative risk estimates for ever use vary from 0.81 to 1.12, giving a combined estimate of 0.93 (95% confidence interval 0.84-1.02, n = 8, with no increase in males (1.01, 0.84-1.22, n = 5, females (0.80, 0.67-0.95, n = 5, White people (0.87, 0.75-1.03, n = 4

  16. Detection of genotoxic and non-genotoxic carcinogens in Xpc{sup −/−}p53{sup +/−} mice

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Joost P.M. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands); Speksnijder, Ewoud N. [Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands); Kuiper, Raoul V. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht (Netherlands); Salvatori, Daniela C.F. [Leiden University Medical Center, Central Animal Facility, Leiden (Netherlands); Schaap, Mirjam M. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands); Maas, Saskia [Leiden University Medical Center, Central Animal Facility, Leiden (Netherlands); Robinson, Joke; Verhoef, Aart; Benthem, Jan van; Luijten, Mirjam [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Steeg, Harry van, E-mail: Harry.van.Steeg@rivm.nl [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands)

    2013-01-15

    An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.

  17. Lung cancer

    Science.gov (United States)

    ... it is called metastatic cancer to the lung . Causes Lung cancer is the deadliest type of cancer for both ... under age 45. Cigarette smoking is the leading cause of lung cancer. The more cigarettes you smoke per day and ...

  18. Lung surgery

    Science.gov (United States)

    ... cavity, particularly after trauma Surgery to remove small balloon-like tissues (blebs) that cause lung collapse ( pneumothorax ) ... this surgery include: Failure of the lung to expand Injury to the lungs or blood vessels Need ...

  19. ImmunoPET for assessing the differential uptake of a CD146-specific monoclonal antibody in lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Haiyan; Kamkaew, Anyanee; Jiang, Dawei; Yang, Yunan [University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); England, Christopher G.; Hernandez, Reinier; Graves, Stephen A.; Barnhart, Todd E. [University of Wisconsin-Madison, Department of Medical Physics, Madison, WI (United States); Majewski, Rebecca L. [University of Wisconsin-Madison, Department of Biomedical Engineering, Madison, WI (United States); Cai, Weibo [University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin-Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin-Madison, Department of Biomedical Engineering, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States)

    2016-11-15

    Overexpression of CD146 in solid tumors has been linked to disease progression, invasion, and metastasis. We describe the generation of a {sup 64}Cu-labeled CD146-specific antibody and its use for quantitative immunoPET imaging of CD146 expression in six lung cancer models. The anti-CD146 antibody (YY146) was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA) and radiolabeled with {sup 64}Cu. CD146 expression was evaluated in six human lung cancer cell lines (A549, NCI-H358, NCI-H522, HCC4006, H23, and NCI-H460) by flow cytometry and quantitative western blot studies. The biodistribution and tumor uptake of {sup 64}Cu-NOTA-YY146 was assessed by sequential PET imaging in athymic nude mice bearing subcutaneous lung cancer xenografts. The correlation between CD146 expression and tumor uptake of {sup 64}Cu-NOTA-YY146 was evaluated by graphical software while ex vivo biodistribution and immunohistochemistry studies were performed to validate the accuracy of PET data and spatial expression of CD146. Flow cytometry and western blot studies showed similar findings with H460 and H23 cells showing high levels of expression of CD146. Small differences in CD146 expression levels were found among A549, H4006, H522, and H358 cells. Tumor uptake of {sup 64}Cu-NOTA-YY146 was highest in CD146-expressing H460 and H23 tumors, peaking at 20.1 ± 2.86 and 11.6 ± 2.34 %ID/g at 48 h after injection (n = 4). Tumor uptake was lowest in the H522 model (4.1 ± 0.98 %ID/g at 48 h after injection; n = 4), while H4006, A549 and H358 exhibited similar uptake of {sup 64}Cu-NOTA-YY146. A positive correlation was found between tumor uptake of {sup 64}Cu-NOTA-YY146 (%ID/g) and relative CD146 expression (r {sup 2} = 0.98, p < 0.01). Ex vivo biodistribution confirmed the accuracy of the PET data. The strong correlation between tumor uptake of {sup 64}Cu-NOTA-YY146 and CD146 expression demonstrates the potential use of this radiotracer for imaging tumors that elicit varying levels of CD146

  20. InSpire to Promote Lung Assessment in Youth: Evolving the Self-Management Paradigms of Young People With Asthma.

    Science.gov (United States)

    Elias, Pierre; Rajan, Nithin O; McArthur, Kara; Dacso, Clifford C

    2013-01-01

    Asthma is the most common chronic disease in childhood, disproportionately affecting urban, minority, and disadvantaged children. Individualized care plans supported by daily lung-function monitoring can reduce morbidity and mortality. However, despite 20 years of interventions to increase adherence, only 50% of US youth accurately follow their care plans, which leads to millions of preventable hospitalizations, emergency room visits, and sick days every year. We present a feasibility study of a novel, user-centered approach to increasing young people's lung-function monitoring and asthma self-care. Promoting Lung Assessment in Youth (PLAY) helps young people become active managers of their asthma through the Web 2.0 principles of participation, cocreation, and information sharing. Specifically, PLAY combines an inexpensive, portable spirometer with the motivational power and convenience of mobile phones and virtual-community gaming. The objective of this study was to develop and pilot test InSpire, a fully functional interface between a handheld spirometer and an interactive game and individualized asthma-care instant-messaging system housed on a mobile phone. InSpire is an application for mobile smartphones that creates a compelling world in which youth collaborate with their physicians on managing their asthma. Drawing from design-theory on global timer mechanics and role playing, we incentivized completing spirometry maneuvers by making them an engaging part of a game young people would want to play. The data can be sent wirelessly to health specialists and return care recommendations to patients in real-time. By making it portable and similar to applications normally desired by the target demographic, InSpire is able to seamlessly incorporate asthma management into their lifestyle. We describe the development process of building and testing the InSpire prototype. To our knowledge, the prototype is a first-of-its kind mobile one-stop shop for asthma management

  1. [Quantitative structure-activity relationship prediction of carcinogenicity of N-nitroso compounds based on category approach and read-across].

    Science.gov (United States)

    Liang, Q Q; Zheng, W W; He, G S; Qu, W D

    2017-07-06

    Objective: New quantitative structure-activity relationship (QSAR) method was used to predict N-nitroso compounds (NOCs) carcinogenicity. This could provide evidences for health risk assessment of the chemicals. Methods: Total 74 chemical substances of NOCs were included as target chemicals for this validation study by using QSAR Toolbox based on category approach and read-across. The included 74 NOCs were categorized and subcategorized respectively using "Organic functional groups, Norbert Haider " profiler and "DNA binding by OASIS V.1.1" profiler. Carcinogenicity of rat were used as target of prediction, the carcinogenicity results: of analogues in chemical categories were cross-read to obtain the carcinogenic predictive results of the target chemicals. Results 74 NOCs included 26 nonclic N-nitrosamines, 24 cyclic N-nitrosamines and 24 N-nitrosamides The sensitivity, specificity and concordance of the category approach and read-across for predicting carcinogenicity of 74 NOCs were 75% (48/64), 70%(7/10) and 74% (55/74) respectively. The concordance for noncyclic N-nitrosamines, cyclic N-nitrosamines and N-nitrosamides were 88% (23/26), 71% (17/24) and 63% (15/24) respectively. Conclusion: QSAR based on category approach and read-across is good for prediction of NOCs carcinogenicity, and can be used for high-throughput qualitative prediction of NOCs carcinogenicity.

  2. Comparison of in vivo genotoxic and carcinogenic potency to augment mode of action analysis: Case study with hexavalent chromium.

    Science.gov (United States)

    Thompson, Chad M; Bichteler, Anne; Rager, Julia E; Suh, Mina; Proctor, Deborah M; Haws, Laurie C; Harris, Mark A

    2016-04-01

    Recent analyses-highlighted by the International Workshops on Genotoxicity Testing Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment-have identified a correlation between (log) estimates of a carcinogen's in vivo genotoxic potency and in vivo carcinogenic potency in typical laboratory animal models, even when the underlying data have not been matched for tissue, species, or strain. Such a correlation could have important implications for risk assessment, including informing the mode of action (MOA) of specific carcinogens. When in vivo genotoxic potency is weak relative to carcinogenic potency, MOAs other than genotoxicity (e.g., endocrine disruption or regenerative hyperplasia) may be operational. Herein, we review recent in vivo genotoxicity and carcinogenicity data for hexavalent chromium (Cr(VI)), following oral ingestion, in relevant tissues and species in the context of the aforementioned correlation. Potency estimates were generated using benchmark doses, or no-observable-adverse-effect-levels when data were not amenable to dose-response modeling. While the ratio between log values for carcinogenic and genotoxic potency was ≥1 for many compounds, the ratios for several Cr(VI) datasets (including in target tissue) were less than unity. In fact, the ratios for Cr(VI) clustered closely with ratios for chloroform and diethanolamine, two chemicals posited to have non-genotoxic MOAs. These findings suggest that genotoxicity may not play a major role in the cancers observed in rodents following exposure to high concentrations of Cr(VI) in drinking water-a finding consistent with recent MOA and adverse outcome pathway (AOP) analyses concerning Cr(VI). This semi-quantitative analysis, therefore, may be useful to augment traditional MOA and AOP analyses. More case examples will be needed to further explore the general applicability and validity of this approach for human health risk assessment. Copyright © 2016 The Authors. Published by

  3. Visual assessment of early emphysema and interstitial abnormalities on CT is useful in lung cancer risk analysis

    DEFF Research Database (Denmark)

    Wille, Mathilde M. W.; Thomsen, Laura H.; Petersen, Jens

    2016-01-01

    Objectives: Screening for lung cancer should be limited to a high-risk-population, and abnormalities in low-dose computed tomography (CT) screening images may be relevant for predicting the risk of lung cancer. Our aims were to compare the occurrence of visually detected emphysema and interstitial...... abnormalities in subjects with and without lung cancer in a screening population of smokers. Methods: Low-dose chest CT examinations (baseline and latest possible) of 1990 participants from The Danish Lung Cancer Screening Trial were independently evaluated by two observers who scored emphysema and interstitial...... abnormalities. Emphysema (lung density) was also measured quantitatively. Results: Emphysema was seen more frequently and its extent was greater among participants with lung cancer on baseline (odds ratio (OR), 1.8, p = 0.017 and p = 0.002) and late examinations (OR 2.6, p

  4. Evaluation of correlation between CT image features and ERCC1 protein expression in assessing lung cancer prognosis

    Science.gov (United States)

    Tan, Maxine; Emaminejad, Nastaran; Qian, Wei; Sun, Shenshen; Kang, Yan; Guan, Yubao; Lure, Fleming; Zheng, Bin

    2014-03-01

    Stage I non-small-cell lung cancers (NSCLC) usually have favorable prognosis. However, high percentage of NSCLC patients have cancer relapse after surgery. Accurately predicting cancer prognosis is important to optimally treat and manage the patients to minimize the risk of cancer relapse. Studies have shown that an excision repair crosscomplementing 1 (ERCC1) gene was a potentially useful genetic biomarker to predict prognosis of NSCLC patients. Meanwhile, studies also found that chronic obstructive pulmonary disease (COPD) was highly associated with lung cancer prognosis. In this study, we investigated and evaluated the correlations between COPD image features and ERCC1 gene expression. A database involving 106 NSCLC patients was used. Each patient had a thoracic CT examination and ERCC1 genetic test. We applied a computer-aided detection scheme to segment and quantify COPD image features. A logistic regression method and a multilayer perceptron network were applied to analyze the correlation between the computed COPD image features and ERCC1 protein expression. A multilayer perceptron network (MPN) was also developed to test performance of using COPD-related image features to predict ERCC1 protein expression. A nine feature based logistic regression analysis showed the average COPD feature values in the low and high ERCC1 protein expression groups are significantly different (p < 0.01). Using a five-fold cross validation method, the MPN yielded an area under ROC curve (AUC = 0.669±0.053) in classifying between the low and high ERCC1 expression cases. The study indicates that CT phenotype features are associated with the genetic tests, which may provide supplementary information to help improve accuracy in assessing prognosis of NSCLC patients.

  5. Ventilation/perfusion SPECT in chronic obstructive pulmonary disease: an evaluation by reference to symptoms, spirometric lung function and emphysema, as assessed with HRCT

    Energy Technology Data Exchange (ETDEWEB)

    Joegi, Jonas; Bajc, Marika [Lund University, Skaane University Hospital, Department of Clinical Physiology, Institution of Clinical Sciences, Lund (Sweden); Ekberg, Marie [Lund University, Skaane University Hospital, Department of Respiratory Medicine and Allergology, Institution of Clinical Sciences, Lund (Sweden); Jonson, Bjoern [Lund University, Department of Clinical Physiology, Institution of Clinical Sciences, Lund (Sweden); Bozovic, Gracijela [Lund University, Skaane University Hospital, Department of Radiology, Institution of Clinical Sciences, Lund (Sweden)

    2011-07-15

    Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation which is not fully reversible. Despite the heterogeneity of COPD, its diagnosis and staging is currently based solely on forced expiratory volume in 1 s (FEV{sub 1}). FEV{sub 1} does not explain the underlying pathophysiology of airflow limitation. The relationship between FEV{sub 1}, symptoms and emphysema extent is weak. Better diagnostic tools are needed to define COPD. Tomographic lung scintigraphy [ventilation/perfusion single photon emission tomography (V/P SPECT)] visualizes regional V and P. In COPD, relations between V/P SPECT, spirometry, high-resolution computed tomography (HRCT) and symptoms have been insufficiently studied. The aim of this study was to investigate how lung function imaging and obstructive disease grading undertaken using V/P SPECT correlate with symptoms, spirometric lung function and degree of emphysema assessed with HRCT in patients with COPD. Thirty patients with stable COPD were evaluated with the Medical Research Council dyspnoea questionnaire (MRC) and the clinical COPD questionnaire (CCQ). Spirometry was performed. The extent of emphysema was assessed using HRCT. V/P SPECT was used to assess V/P patterns, total reduction in lung function and degree of obstructive disease. The total reduction in lung function and degree of obstructive disease, assessed with V/P SPECT, significantly correlated with emphysema extent (r = 0.66-0.69, p < 0.0001) and spirometric lung function (r = 0.62-0.74, p < 0.0005). The correlation between emphysema extent and spirometric lung function was weaker. No correlation between MRC, CCQ and objective measurements was found. V/P SPECT is sensitive to early changes in COPD. V/P SPECT also has the possibility to identify comorbid disease. V/P SPECT findings show a significant correlation with emphysema extent and spirometric lung function. We therefore recommend that scintigraphic signs of COPD, whenever found, should be

  6. Electronic monitoring of symptoms and lung function to assess asthma control in children.

    Science.gov (United States)

    van Vliet, Dillys; van Horck, Marieke; van de Kant, Kim; Vaassen, Sanne; Gulikers, Sjoerd; Winkens, Bjorn; Rosias, Philippe; Heynens, Jan; Muris, Jean; Essers, Brigitte; Jöbsis, Quirijn; Dompeling, Edward

    2014-09-01

    Asthma remains poorly controlled in children. Home monitoring of asthma control may help to improve the level of asthma control. To compare 2 methods to assess asthma control: (1) prospective home monitoring, based on daily assessment of forced expiratory volume in 1 second (FEV1) and electronic symptom score, and (2) Asthma Control Questionnaire (ACQ) with retrospective assessment of symptoms and FEV1. Ninety-six children with asthma were prospectively followed up during 1 year. Asthma control was assessed by home monitoring, including an electronic symptom score based on Global Initiative for Asthma (GINA) criteria and FEV1 measurements. In the hospital, the ACQ was completed and FEV₁ was measured. Kappa analysis was performed to assess levels of agreement between the 2 methods. Agreement between the 2 methods was low (κ coefficient of 0.393). In 29 children (37%), prospective home monitoring was less optimistic than the retrospective assessment of asthma control by the ACQ. This study found low agreement between asthma control based on GINA criteria by means of prospective home monitoring and the hospital ACQ. The prospective home monitor detected more cases of less well-controlled asthma than the ACQ. However, optimization of adherence to home monitor use is necessary. clinicaltrials.gov Identifier: NCT01239238. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. The function and significance of SELENBP1 downregulation in human bronchial epithelial carcinogenic process.

    Directory of Open Access Journals (Sweden)

    Gu-Qing Zeng

    Full Text Available BACKGROUND: Our quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1 was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC carcinogenesis. METHODS: iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process. SELENBP1, member of selenoproteins family and progressively downregulated in this process, was selected to further study. Both Western blotting and immunohistochemistry were performed to detect SELENBP1 expression in independent sets of tissues of bronchial epithelial carcinogenesis, and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium from preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1 downregulation on the susceptibility of benzo(apyrene (B[a]P-induced human bronchial epithelial cell transformation were determined. RESULTS: 102 differentially expressed proteins were identified by quantitative proteomics, and SELENBP1 was found and confirmed being progressively decreased in the human bronchial epithelial carcinogenic process. The sensitivity and specificity of SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79% and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. CONCLUSIONS: The present data shows for the first time that decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human bronchial epithelial cell transformation, and might serve as a novel potential biomarker for early detection of LSCC.

  8. 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.......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....

  9. Longitudinal assessment of the lung mechanics of very low birth weight preterm infants with and without bronchopulmonary dysplasia.

    Science.gov (United States)

    Mello, Rosane Reis de; Silva, Kátia Silveira da; Costa, Anniele Medeiros; Ramos, José Roberto de Moraes

    2015-01-01

    Prematurity has been correlated with altered lung mechanics. Some infants develop lung injury as a consequence of lung immaturity, invasive mechanical ventilation and exposure to oxygen, thus resulting in bronchopulmonary dysplasia. The aim here was to compare the lung mechanics of preterm infants with and without bronchopulmonary dysplasia during the first year of life. Prospective cohort study in a tertiary-level hospital. This study included premature infants at a public hospital who underwent two pulmonary function tests: one at discharge and the other at the corrected age of 4 to 8 months. Tidal volume, lung compliance and lung resistance were measured. Statistical tests were used for comparisons between infants with and without bronchopulmonary dysplasia. 102 children with mean gestational age of 29 ± 2.0 weeks were studied; 17 with bronchopulmonary dysplasia. Lung compliance (0.84 ± 0.29 versus 1.28 ± 0.46; P bronchopulmonary dysplasia than in those without the disease, but no differences were observed at the second test (compliance: 1.53 ± 0.77 versus 1.94 ± 1.01; P = 0.12; and tidal volume: 6.9 ± 1.4 versus 7.3 ± 1.6; P = 0.42). Differences in lung mechanics were observed between infants with and without bronchopulmonary dysplasia at hospital discharge but these differences were no longer detected at the final follow-up. The lung mechanics of all the infants improved over this period of time.

  10. Cell transformation assays for prediction of carcinogenic potential: state of the science and future research needs.

    Science.gov (United States)

    Creton, Stuart; Aardema, Marilyn J; Carmichael, Paul L; Harvey, James S; Martin, Francis L; Newbold, Robert F; O'Donovan, Michael R; Pant, Kamala; Poth, Albrecht; Sakai, Ayako; Sasaki, Kiyoshi; Scott, Andrew D; Schechtman, Leonard M; Shen, Rhine R; Tanaka, Noriho; Yasaei, Hemad

    2012-01-01

    Cell transformation assays (CTAs) have long been proposed as in vitro methods for the identification of potential chemical carcinogens. Despite showing good correlation with rodent bioassay data, concerns over the subjective nature of using morphological criteria for identifying transformed cells and a lack of understanding of the mechanistic basis of the assays has limited their acceptance for regulatory purposes. However, recent drivers to find alternative carcinogenicity assessment methodologies, such as the Seventh Amendment to the EU Cosmetics Directive, have fuelled renewed interest in CTAs. Research is currently ongoing to improve the objectivity of the assays, reveal the underlying molecular changes leading to transformation and explore the use of novel cell types. The UK NC3Rs held an international workshop in November 2010 to review the current state of the art in this field and provide directions for future research. This paper outlines the key points highlighted at this meeting.

  11. Investigations on in vitro anti-carcinogenic potential of L-carnosine in liver cancer cells.

    Science.gov (United States)

    Ding, Minghui; Jiao, Guihua; Shi, Haizhou; Chen, Yanrong

    2017-07-27

    This study was carried out to investigate the anti-carcinogenic effect of L-carnosine in human carcinoma cells (SNU-423). The SNU-423 cancer cells were cultured at a density of 2 × 104 cells/well in Dulbecco modified Eagle medium. After 24 h of adherence, the cells were treated with L-carnosine (0.2 and 1 mg/mL) for 48 h. Then, cell viability was assessed by sulforhodamine assay, while mitochondrial dysfunction was measured by fluorescence microscopy using chromatin-specific dye Hoechst 33258. Intracellular levels of ROS were assayed by fluorescence spectroscopy with 2',7'-dichlorofluorescein diacetate (DCFDA). L-Carnosine significantly inhibited the growth of the SNU-423 cells (p carcinogenic effects in human liver cancer cells.

  12. Cell transformation assays for prediction of carcinogenic potential: state of the science and future research needs

    Science.gov (United States)

    Creton, Stuart; Aardema, Marilyn J.; Carmichael, Paul L.; Harvey, James S.; Martin, Francis L.; Newbold, Robert F.; O’Donovan, Michael R.; Pant, Kamala; Poth, Albrecht; Sakai, Ayako; Sasaki, Kiyoshi; Scott, Andrew D.; Schechtman, Leonard M.; Shen, Rhine R.; Tanaka, Noriho; Yasaei, Hemad

    2012-01-01

    Cell transformation assays (CTAs) have long been proposed as in vitro methods for the identification of potential chemical carcinogens. Despite showing good correlation with rodent bioassay data, concerns over the subjective nature of using morphological criteria for identifying transformed cells and a lack of understanding of the mechanistic basis of the assays has limited their acceptance for regulatory purposes. However, recent drivers to find alternative carcinogenicity assessment methodologies, such as the Seventh Amendment to the EU Cosmetics Directive, have fuelled renewed interest in CTAs. Research is currently ongoing to improve the objectivity of the assays, reveal the underlying molecular changes leading to transformation and explore the use of novel cell types. The UK NC3Rs held an international workshop in November 2010 to review the current state of the art in this field and provide directions for future research. This paper outlines the key points highlighted at this meeting. PMID:21852270

  13. Home spirometry: Assessment of patient compliance and satisfaction and its impact on early diagnosis of pulmonary symptoms in post-lung transplantation patients.

    Science.gov (United States)

    Fadaizadeh, Lida; Najafizadeh, Katayoun; Shajareh, Elham; Shafaghi, Shadi; Hosseini, Mahsa; Heydari, Gholamreza

    2016-03-01

    Telemedicine is useful in monitoring patients, and in particular those, such as lung transplant recipients, suffering from chronic illnesses. This prospective cohort study was conducted on 15 lung transplant recipients. The patients provided physicians with data from spirometry as well as their clinical respiratory symptoms via SMS messages. In cases where spirometry results or clinical symptoms required follow-up, the monitoring physician contacted the patient according to guidelines and gave appropriate instructions. Qualitative assessment of satisfaction showed that the sense of increased support from medical staff was rated highest (92.9%). Telespirometry is an efficient method of monitoring lung transplant recipients which leads to patient satisfaction, compliance, adherence to study and sense of security. Nevertheless, for optimal implementation of this method, thorough training of both medical staff and patients is required. © The Author(s) 2015.

  14. Planning target volume assessment in lung tumors during 3D conformal radiotherapy by means of an aSi electronic portal imaging device in cine mode.

    Science.gov (United States)

    Caivano, R; Clemente, S; Fiorentino, A; Chiumento, C; Pedicini, P; Califano, G; Cozzolino, M; Fusco, V

    2013-08-01

    The major uncertainties in treating lung cancer are the repositioning errors and respiratory lung tumor motion. Typically, margins are added to the clinical target volume (CTV) to obtain a planning target volume (PTV) allowing the accommodation of such uncertainties. We want to test a new technique to assess the adequacy of the chosen PTV using an aSi electronic portal imaging device (EPID). Four patients affected by lung cancer and treated by radical 3D conformal radiotherapy (3DRT) were studied. During treatment the EPID was used in cine mode acquisition: acquired images were used to the aim. Treatment monitoring with an EPID in cine mode is shown to be a clinically feasible and useful tool.

  15. A review of potential human carcinogenicity of the chlorophenoxy herbicides MCPA, MCPP, and 2,4-DP.

    Science.gov (United States)

    Bond, G G; Rossbacher, R

    1993-01-01

    For the purpose of assessing the human carcinogenic potential of the chlorophenoxy herbicides MCPA, MCPP, and 2,4-DP, the relevant epidemiological and toxicological evidence is reviewed. These compounds have not produced tumours in animal studies conducted under current test guidelines, giving no reason to predict that they would be carcinogenic to humans. Epidemiological studies have been conducted on three continents; greater emphasis is placed on the studies reported from western Europe, however, as this has been the area of more use. Although several of these studies provide suggestive evidence of associations between exposure to chlorophenoxy compounds and increased risks for some uncommon cancers, it is inconsistent and far from conclusive. None of the evidence specifically implicates MCPA, MCPP, or 2,4-DP as human carcinogens. PMID:8494774

  16. N,N-dimethyl-p-toluidine, a component in dental materials, causes hematologic toxic and carcinogenic responses in rodent model systems.

    Science.gov (United States)

    Dunnick, June K; Brix, A; Sanders, J M; Travlos, G S

    2014-01-01

    Because of the potential for exposure to N,N-dimethyl-p-toluidine (DMPT) in medical devices and the lack of toxicity and carcinogenicity information available in the literature, the National Toxicology Program conducted toxicity and carcinogenicity studies of DMPT in male and female F344/N rats and B6C3F1/N mice. In these studies, a treatment-related macrocytic regenerative anemia characterized by increased levels of methemoglobin and Heinz body formation developed within a few weeks of DMPT exposure in rats and mice. DMPT induced nasal cavity, splenic, and liver toxicity in rats and mice at 3 months and 2 years. DMPT carcinogenic effects were seen in the liver of male and female rats and mice, the nasal cavity of male and female rats, and the lung and forestomach of female mice. In rodents, DMPT is distributed to many of the sites where toxic and carcinogenic effects occurred. DMPT-induced oxidative damage at these target sites may be one mechanism for the treatment-related lesions. Methemoglobinemia, as seen in these DMPT studies, is caused by oxidation of the heme moiety, and this end point served as an early alert for other target organ toxicities and carcinogenic responses that followed with longer term exposure.

  17. Brasfield and Wisconsin scoring systems have equal value as outcome assessment tools of cystic fibrosis lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Cleveland, Robert H.; Stamoulis, Catherine; Sawicki, Gregory; Kelliher, Emma; Wood, Christopher; Zurakowski, David; Lee, Edward [Boston Children' s Hospital, Harvard Medical School, Department of Radiology, Boston, MA (United States); Zucker, Evan J. [Tufts Medical School, Boston, MA (United States)

    2014-05-15

    Several imaging-based scoring systems have been used as outcome measures in assessing the severity of cystic fibrosis (CF) lung disease. It has been shown that chest radiography performs equally to computed tomography (CT). There is the opinion that of the two most commonly used chest radiograph (CXR) systems, the Brasfield system is less sensitive and reliable than the Wisconsin system. This report assesses the reproducibility and reliability of the two systems. Thirty patients with CXRs during a 5-year period were randomly selected. One hundred eighty-two studies had data for all CXRs and pulmonary function tests (PFTs), Forced Expiratory Volume in One Second (FEV-1) and Forced Vital Capacity (FVC). PFT values closest to the date of each CXR were recorded. Four radiologists scored each image twice by both the Brasfield and Wisconsin systems. Intra- and inter-rater reliability, correlation with PFTs and direct correlation of the two systems were calculated. Intra-rater agreement: r = 0.86-0.99 Brasfield, r = 0.78-0.96 Wisconsin. Inter-rater agreement: 0.76-0.90 Brasfield, r = 0.74-0.97 Wisconsin. Brasfield vs. FEV-1: r = 0.55, vs. FVC r = 0.61. Wisconsin vs. FEV-1: r = 0.57, vs. FVC r = 0.66. Correlation of the two systems: r = 0.86 (all P < 0.001). The Brasfield and Wisconsin systems performed very similarly providing equally reproducible, robust and reliable measures. (orig.)

  18. Aptamer imaging with Cu-64 labeled AS1411: preliminary assessment in lung cancer.

    Science.gov (United States)

    Li, Junling; Zheng, Huaiyu; Bates, Paula J; Malik, Tariq; Li, Xiao-Feng; Trent, John O; Ng, Chin K

    2014-02-01

    AS1411 is a 26-base guanine-rich oligonucleotide aptamer shown binding to surface nucleolin, a protein over-expressed in multiple cancer cells, thus AS1411 labeled with a PET isotope can be explored as a potential diagnostic imaging agent. Our objective was to perform preliminary biological characterization of (64)Cu-labeled AS1411 in vitro and in vivo. Four chelators (DOTA, CB-TE2A, DOTA-Bn and NOTA-Bn) were selected to label AS1411 with Cu-64. 185kBq (5μCi) of each tracer was incubated in each well with H460 cells at 37°C for 1, 3, 6, 12, 24 and 48h, respectively (n=4). For microPET/CT imaging, 7.4MBq (200μCi) of AS1411 labeled with either (64)Cu-DOTA or (64)Cu-CB-TE2A was I.V. injected and multiple scans were obtained at 1, 3, 6 and 24h post injection. Afterward in vivo biodistribution studies were performed. Percent uptake of (64)Cu-DOTA-AS1411 and (64)Cu-CB-TE2A-AS1411 was significantly higher than that of (64)Cu-DOTA-Bn-AS1411 and (64)Cu-NOTA-Bn-AS1411. About 90% of uptake for (64)Cu-DOTA-AS1411 and (64)Cu-CB-TE2A-AS1411 was internalized into cells within 3h and the internalization process was completed before 24h. Both tracers demonstrated reasonable in vivo stability and high binding affinity to the cells. MicroPET imaging with (64)Cu-CB-TE2A-AS1411 showed clear tumor uptake at both legs from 1 to 24h post injection, whereas both tumors were undetectable for up to 24h with (64)Cu-DOTA-AS1411. In addition, (64)Cu-CB-TE2A-AS1411 had faster in vivo pharmacokinetics than (64)Cu-DOTA-AS1411 with lower liver uptake and higher tumor to background contrast. CB-TE2A is a preferred chelator with higher tumor-to-background ratio, lower liver uptake and faster clearance than DOTA. Aptamer imaging with (64)Cu-CB-TE2A-AS1411 may be feasible for detecting lung cancer, if an appropriate chelator can be identified and further validation can be performed with a known control oligonucleotide. It may also be used as a companion diagnostic imaging agent for AS1411 in the

  19. Detection of Local Cancer Recurrence After Stereotactic Ablative Radiation Therapy for Lung Cancer: Physician Performance Versus Radiomic Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Mattonen, Sarah A. [Department of Medical Biophysics, The University of Western Ontario, London, Ontario (Canada); Baines Imaging Research Laboratory, London Regional Cancer Program, London, Ontario (Canada); Palma, David A., E-mail: david.palma@lhsc.on.ca [Department of Medical Biophysics, The University of Western Ontario, London, Ontario (Canada); Baines Imaging Research Laboratory, London Regional Cancer Program, London, Ontario (Canada); Department of Oncology, The University of Western Ontario, London, Ontario (Canada); Johnson, Carol [Baines Imaging Research Laboratory, London Regional Cancer Program, London, Ontario (Canada); Louie, Alexander V. [Department of Oncology, The University of Western Ontario, London, Ontario (Canada); Landis, Mark [Department of Diagnostic Radiology, London Health Sciences Centre, London, Ontario (Canada); Rodrigues, George [Department of Oncology, The University of Western Ontario, London, Ontario (Canada); Chan, Ian; Etemad-Rezai, Roya [Department of Diagnostic Radiology, London Health Sciences Centre, London, Ontario (Canada); Yeung, Timothy P.C. [Department of Medical Biophysics, The University of Western Ontario, London, Ontario (Canada); Baines Imaging Research Laboratory, London Regional Cancer Program, London, Ontario (Canada); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Ward, Aaron D. [Department of Medical Biophysics, The University of Western Ontario, London, Ontario (Canada); Baines Imaging Research Laboratory, London Regional Cancer Program, London, Ontario (Canada); Department of Oncology, The University of Western Ontario, London, Ontario (Canada)

    2016-04-01

    Purpose: Stereotactic ablative radiation therapy (SABR) is a guideline-specified treatment option for early-stage lung cancer. However, significant posttreatment fibrosis can occur and obfuscate the detection of local recurrence. The goal of this study was to assess physician ability to detect timely local recurrence and to compare physician performance with a radiomics tool. Methods and Materials: Posttreatment computed tomography (CT) scans (n=182) from 45 patients treated with SABR (15 with local recurrence matched to 30 with no local recurrence) were used to measure physician and radiomic performance in assessing response. Scans were individually scored by 3 thoracic radiation oncologists and 3 thoracic radiologists, all of whom were blinded to clinical outcomes. Radiomic features were extracted from the same images. Performances of the physician assessors and the radiomics signature were compared. Results: When taking into account all CT scans during the whole follow-up period, median sensitivity for physician assessment of local recurrence was 83% (range, 67%-100%), and specificity was 75% (range, 67%-87%), with only moderate interobserver agreement (κ = 0.54) and a median time to detection of recurrence of 15.5 months. When determining the early prediction of recurrence within <6 months after SABR, physicians assessed the majority of images as benign injury/no recurrence, with a mean error of 35%, false positive rate (FPR) of 1%, and false negative rate (FNR) of 99%. At the same time point, a radiomic signature consisting of 5 image-appearance features demonstrated excellent discrimination, with an area under the receiver operating characteristic curve of 0.85, classification error of 24%, FPR of 24%, and FNR of 23%. Conclusions: These results suggest that radiomics can detect early changes associated with local recurrence that are not typically considered by physicians. This decision support system could potentially allow for early salvage therapy of

  20. Racial differences in the relationship between number of cigarettes smoked and nicotine and carcinogen exposure.

    Science.gov (United States)

    Benowitz, Neal L; Dains, Katherine M; Dempsey, Delia; Wilson, Margaret; Jacob, Peyton

    2011-09-01

    Black smokers are reported to have higher lung cancer rates and greater tobacco dependence at lower levels of cigarette consumption compared to non-Hispanic White smokers. We studied the relationship between cigarettes per day (CPD) and biomarkers of nicotine and carcinogen exposure in Black and White smokers. In 128 Black and White smokers, we measured plasma nicotine and its main proximate metabolite cotinine, urine nicotine equivalents, 4-(methylnitrosamino)-1-(3)pyridyl-1-butanol (NNAL), and polycyclic aromatic hydrocarbon (PAH) metabolites. The dose-response between CPD and nicotine equivalents, and NNAL and PAH was flat for Black but positive for White smokers (Race × CPD interaction, all ps < .05). Regression estimates for the Race × CPD interactions were 0.042 (95% CI 0.013-0.070), 0.054 (0.023-0.086), and 0.028 (0.004-0.052) for urine nicotine equivalents, NNAL, and PAHs, respectively. In contrast there was a strong correlation between nicotine equivalents and NNAL and PAH independent of race. Nicotine and carcinogen exposure per individual cigarette was inversely related to CPD. This inverse correlation was stronger in Black compared to White smokers and stronger in menthol compared to regular cigarette smokers (not mutually adjusted). Our data indicate that Blacks on average smoke cigarettes differently than White smokers such that CPD predicts smoke intake more poorly in Black than in White smokers.

  1. Incidence and persistence of carcinogenic genital human papillomavirus infections in young women with or without Chlamydia trachomatis co-infection

    NARCIS (Netherlands)

    Vriend, Henrike J.; Bogaards, Johannes A.; van Bergen, Jan E. A. M.; Brink, Antoinette A. T. P.; van den Broek, Ingrid V. F.; Hoebe, Christian J. P. A.; King, Audrey J.; van der Sande, Marianne A. B.; Wolffs, Petra F. G.; de Melker, Hester E.

    2015-01-01

    We assessed whether infection with chlamydia increases the incidence of carcinogenic human papillomavirus (HPV) infections and if HPV persistence is affected by chlamydia co-infection. For 1982 women (16-29 years-old) participating in two consecutive rounds of a chlamydia screening implementation

  2. The International Agency for Research on Cancer (IARC) evaluation of the carcinogenicity of outdoor air pollution: focus on China.

    Science.gov (United States)

    Loomis, Dana; Huang, Wei; Chen, Guosheng

    2014-04-01

    The International Agency for Research on Cancer (IARC) has classified outdoor air pollution and the particulate matter (PM) in outdoor air pollution as carcinogenic to humans, as based on sufficient evidence of carcinogenicity in humans and experimental animals and strong support by mechanistic studies. The data with important contributions to the evaluation are reviewed, highlighting the data with particular relevance to China, and implications of the evaluation with respect to China are discussed. The air pollution levels in Chinese cities are among the highest observed in the world today and frequently exceed health-based national and international guidelines. Data from high-quality epidemiologic studies in Asia, Europe, and North America consistently show positive associations between lung cancer and PM exposure and other indicators of air pollution, which persist after adjustment for important lung cancer risk factors, such as tobacco smoking. Epidemiologic data from China are limited but nevertheless indicate an increased risk of lung cancer associated with several air pollutants. Excess cancer risk is also observed in experimental animals exposed to polluted outdoor air or extracted PM. The exposure of several species to outdoor air pollution is associated with markers of genetic damage that have been linked to increased cancer risk in humans. Numerous studies from China, especially genetic biomarker studies in exposed populations, support that the polluted air in China is genotoxic and carcinogenic to humans. The evaluation by IARC indicates both the need for further research into the cancer risks associated with exposure to air pollution in China and the urgent need to act to reduce exposure to the population.

  3. Supervised Quality Assessment Of Medical Image Registration: Application to intra-patient CT lung registration

    NARCIS (Netherlands)

    Muenzing, S.E.; Ginneken, B. van; Murphy, K.; Pluim, J.P.

    2012-01-01

    A novel method for automatic quality assessment of medical image registration is presented. The method is based on supervised learning of local alignment patterns, which are captured by statistical image features at distinctive landmark points. A two-stage classifier cascade, employing an optimal

  4. Electrical impedance tomography in the assessment of extravascular lung water in noncardiogenic acute respiratory failure

    NARCIS (Netherlands)

    Kunst, P. W.; Vonk Noordegraaf, A.; Raaijmakers, E.; Bakker, J.; Groeneveld, A. B.; Postmus, P. E.; de Vries, P. M.

    1999-01-01

    STUDY OBJECTIVES: To establish the value of electrical impedance tomography (EIT) in assessing pulmonary edema in noncardiogenic acute respiratory failure (ARF), as compared to the thermal dye double indicator dilution technique (TDD). DESIGN: Prospective clinical study. SETTING: ICU of a general

  5. Risk assessment of silicosis and lung cancer among construction workers exposed to respirable quartz

    NARCIS (Netherlands)

    Tjoe Nij, E.; Heederik, D.

    2005-01-01

    Objectives: The aim of this study was to assess the magnitude of the silicosis and cancer risk among construction workers. Methods: In 1998, 1335 of 4173 invited construction workers with expected high cumulative exposure to quartz were studied for early signs of silicosis. In 2002 the study was

  6. Beta-cryptoxanthin protection against cigarette smoke-induced inflammatory responses in the lung is due to the action of its own molecule

    Science.gov (United States)

    Higher intake of the dietary xanthophyll, beta-cryptoxanthin (BCX), has been associated with a lower risk of lung cancer death in smokers. We have previously shown that BCX feeding was effective in reducing both cigarette smoke (CS)-induced lung inflammation in ferrets and carcinogen-induced lung tu...

  7. Visual assessment of early emphysema and interstitial abnormalities on CT is useful in lung cancer risk analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wille, Mathilde M.W.; Dirksen, Asger; Shaker, Saher B. [Gentofte Hospital, Department of Respiratory Medicine, Hellerup (Denmark); Thomsen, Laura H. [Hvidovre Hospital, Department of Respiratory Medicine, Hvidovre (Denmark); Petersen, Jens [University of Copenhagen, Department of Computer Science, DIKU, Koebenhavn Oe (Denmark); Bruijne, Marleen de [University of Copenhagen, Department of Computer Science, DIKU, Koebenhavn Oe (Denmark); Erasmus MC -University Medical Center Rotterdam, Biomedical Imaging Group Rotterdam, Departments of Radiology and Medical Informatics, Rotterdam (Netherlands); Pedersen, Jesper H. [Copenhagen University Hospital, Department of Thoracic Surgery, Rigshospitalet, Koebenhavn Oe (Denmark)

    2016-02-15

    Screening for lung cancer should be limited to a high-risk-population, and abnormalities in low-dose computed tomography (CT) screening images may be relevant for predicting the risk of lung cancer. Our aims were to compare the occurrence of visually detected emphysema and interstitial abnormalities in subjects with and without lung cancer in a screening population of smokers. Low-dose chest CT examinations (baseline and latest possible) of 1990 participants from The Danish Lung Cancer Screening Trial were independently evaluated by two observers who scored emphysema and interstitial abnormalities. Emphysema (lung density) was also measured quantitatively. Emphysema was seen more frequently and its extent was greater among participants with lung cancer on baseline (odds ratio (OR), 1.8, p = 0.017 and p = 0.002) and late examinations (OR 2.6, p < 0.001 and p < 0.001). No significant difference was found using quantitative measurements. Interstitial abnormalities were more common findings among participants with lung cancer (OR 5.1, p < 0.001 and OR 4.5, p < 0.001).There was no association between presence of emphysema and presence of interstitial abnormalities (OR 0.75, p = 0.499). Even early signs of emphysema and interstitial abnormalities are associated with lung cancer. Quantitative measurements of emphysema - regardless of type - do not show the same association. (orig.)

  8. Lack of contribution of covalent benzo[a]pyrene-7,8-quinone-DNA adducts in benzo[a]pyrene-induced mouse lung tumorigenesis

    Science.gov (United States)

    Benzo[a]pyrene (B[a]P) is a potent human and rodent lung carcinogen. This activity has been ascribed in part to the formation of anti-trans-B[a]P-7,8-diol-9,10-epoxide (BPDE)-DNA adducts. Other carcinogenic mechanisms have been proposed: 1.] The induction of apurinic sites from r...

  9. Lung cancer in the meat industry.

    OpenAIRE

    Coggon, D; Pannett, B; Pippard, E C; Winter, P D

    1989-01-01

    Routine statistics of occupational mortality and incidence of cancer have consistently shown high rates of lung cancer in butchers. Possible explanations include infection by carcinogenic papilloma viruses, exposure to polycyclic aromatic hydrocarbons and nitrites in the preservation of meat, or a confounding effect of tobacco. To explore these possibilities, we have examined the mortality of 1610 men employed at three British companies processing pork, beef, lamb, bacon, and other meat produ...

  10. Preclinical Assessment of Carboplatin Treatment Efficacy in Lung Cancer by 18F-ICMT-11-Positron Emission Tomography

    Science.gov (United States)

    Witney, Timothy H.; Fortt, Robin R.; Aboagye, Eric O.

    2014-01-01

    Tumour response to therapy is assessed primarily in the clinic by monitoring reductions in tumour size. However, this approach lacks sensitivity since in many cases several weeks may elapse before there is evidence of tumour shrinkage. There is therefore a need to develop non-invasive imaging techniques for monitoring tumour treatment response in the clinic. Here, we assessed the pre-clinical utility of 18F-ICMT-11 positron emission tomography - a method for detecting caspase 3/7 activation - in non-small cell lung cancer (NSCLC). 18F-ICMT-11 uptake was compared to molecular biochemical measures of cell death in PC9 and A549 NSCLC cells following treatment with carboplatin in vitro and in vivo. Carboplatin-induced apoptosis in the ERCC1 low/mutant EGFR PC9 cells was characterised by time and dose-related increased caspase-3/7 activation, poly-ADP-ribose polymerase cleavage and Annexin V staining. 18F-ICMT-11 uptake was consequently increased up to 14-fold at 200 µM carboplatin compared to vehicle treated cells (Pcarboplatin therapy. Average PET-derived tumour 18F-ICMT-11 uptake was insensitive to changes in apoptosis in the presence of substantial pre-existing necrosis. PET-based voxel intensity sorting however, identified intra-tumoural regions of high 18F-ICMT-11 uptake, enabling accurate assessment of apoptosis and therefore therapy response. In A549 tumours that lacked high pre-therapy necrosis, carboplatin induced growth inhibition that was only minimally associated with apoptosis and thus not detectable by 18F-ICMT-11 PET. PMID:24618809

  11. A Critical Assessment of Geographic Clusters of Breast and Lung Cancer Incidences among Residents Living near the Tittabawassee and Saginaw Rivers, Michigan, USA

    Directory of Open Access Journals (Sweden)

    Olga A. Guajardo

    2009-01-01

    Full Text Available Objectives. To assess previously determined geographic clusters of breast and lung cancer incidences among residents living near the Tittabawassee and Saginaw Rivers, Michigan, using a new set of environmental factors. Materials and Methods. Breast and lung cancer data were acquired from the Michigan Department of Community Health, along with point source pollution data from the U.S. Environmental Protection Agency. The datasets were used to determine whether there is a spatial association between disease risk and environmental contamination. GIS and spatial techniques were combined with statistical analysis to investigate local risk of breast and lung cancer. Results and Conclusion. The study suggests that neighborhoods in close proximity to the river were associated with a high risk of breast cancer, while increased risk of lung cancer was detected among neighborhoods in close proximity to point source pollution and major highways. Statistically significant (P≤.001 clusters of cancer incidences were observed among residents living near the rivers. These findings are useful to researchers and governmental agencies for risk assessment, regulation, and control of environmental contamination in the floodplains.

  12. A Critical Assessment of Geographic Clusters of Breast and Lung Cancer Incidences among Residents Living near the Tittabawassee and Saginaw Rivers, Michigan, USA

    Science.gov (United States)

    Guajardo, Olga A.; Oyana, Tonny J.

    2009-01-01

    Objectives. To assess previously determined geographic clusters of breast and lung cancer incidences among residents living near the Tittabawassee and Saginaw Rivers, Michigan, using a new set of environmental factors. Materials and Methods. Breast and lung cancer data were acquired from the Michigan Department of Community Health, along with point source pollution data from the U.S. Environmental Protection Agency. The datasets were used to determine whether there is a spatial association between disease risk and environmental contamination. GIS and spatial techniques were combined with statistical analysis to investigate local risk of breast and lung cancer. Results and Conclusion. The study suggests that neighborhoods in close proximity to the river were associated with a high risk of breast cancer, while increased risk of lung cancer was detected among neighborhoods in close proximity to point source pollution and major highways. Statistically significant (P ≤ .001) clusters of cancer incidences were observed among residents living near the rivers. These findings are useful to researchers and governmental agencies for risk assessment, regulation, and control of environmental contamination in the floodplains. PMID:20049167

  13. Bcl2 Family Functions as Signaling Target in Nicotine-/NNK-Induced Survival of Human Lung Cancer Cells

    OpenAIRE

    Deng, Xingming

    2014-01-01

    Lung cancer is the leading cause of cancer death and has a strong etiological association with cigarette smoking. Nicotine and nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are two major components in cigarette smoke that significantly contribute to the development of human lung cancer. Nicotine is able to stimulate survival of both normal human lung epithelial and lung cancer cells. In contrast to nicotine, NNK is a more potent carcinogen that not only induces single-stran...

  14. Lung cancer biomarkers for the assessment of modified risk tobacco products: an oxidative stress perspective

    Science.gov (United States)

    Luettich, Karsta; Gregg, Evan O.

    2013-01-01

    Manufacturers have developed prototype cigarettes yielding reduced levels of some tobacco smoke toxicants, when tested using laboratory machine smoking under standardised conditions. For the scientific assessment of modified risk tobacco products, tests that offer objective, reproducible data, which can be obtained in a much shorter time than the requirements of conventional epidemiology are needed. In this review, we consider whether biomarkers of biological effect related to oxidative stress can be used in this role. Based on published data, urinary 8-oxo-7,8-dihydro-2-deoxyguanosine, thymidine glycol, F2-isoprostanes, serum dehydroascorbic acid to ascorbic acid ratio and carotenoid concentrations show promise, while 4-hydroxynonenal requires further qualification. PMID:23530763

  15. Comparison of nicotine and carcinogen exposure with water pipe and cigarette smoking.

    Science.gov (United States)

    Jacob, Peyton; Abu Raddaha, Ahmad H; Dempsey, Delia; Havel, Christopher; Peng, Margaret; Yu, Lisa; Benowitz, Neal L

    2013-05-01

    Smoking tobacco preparations in a water pipe (hookah) is widespread in many places of the world and is perceived by many as relatively safe. We investigated biomarkers of toxicant exposure with water pipe compared with cigarette smoking. We conducted a crossover study to assess daily nicotine and carcinogen exposure with water pipe and cigarette smoking in 13 people who were experienced in using both products. When smoking an average of 3 water pipe sessions compared with smoking 11 cigarettes per day (cpd), water pipe use was associated with a significantly lower intake of nicotine, greater exposure to carbon monoxide (CO), and a different pattern of carcinogen exposure compared with cigarette smoking, with greater exposure to benzene, and high molecular weight polycyclic aromatic hydrocarbon (PAH), but less exposure to tobacco-specific nitrosamines, 1,3-butadiene, acrolein, acrylonitrile, propylene oxide, ethylene oxide, and low molecular weight PAHs. A different pattern of carcinogen exposure might result in a different cancer risk profile between cigarette and water pipe smoking. Of particular concern is the risk of leukemia related to high levels of benzene exposure with water pipe use. Smoking tobacco in water pipes has gained popularity in the United States and around the world. Many believe that water pipe smoking is not addictive and less harmful than cigarette smoking. We provide data on toxicant exposure that will help guide regulation and public education regarding water pipe health risk.

  16. Prediction of the Carcinogenic Potential of Human Pharmaceuticals Using Repeated Dose Toxicity Data and Their Pharmacological Properties.

    Science.gov (United States)

    van der Laan, Jan Willem; Buitenhuis, Wenny H W; Wagenaar, Laura; Soffers, Ans E M F; van Someren, Eugene P; Krul, Cyrille A M; Woutersen, Ruud A

    2016-01-01

    In an exercise designed to reduce animal use, we analyzed the results of rat subchronic toxicity studies from 289 pharmaceutical compounds with the aim to predict the tumor outcome of carcinogenicity studies in this species. The results were obtained from the assessment reports available at the Medicines Evaluation Board of the Netherlands for 289 pharmaceutical compounds that had been shown to be non-genotoxic. One hundred forty-three of the 239 compounds not inducing putative preneoplastic lesions in the subchronic study did not induce tumors in the carcinogenicity study [true negatives (TNs)], whereas 96 compounds were categorized as false negatives (FNs) because tumors were observed in the carcinogenicity study. Of the remaining 50 compounds, 31 showed preneoplastic lesions in the subchronic study and tumors in the carcinogenicity study [true positives (TPs)], and 19 only showed preneoplastic lesions in subchronic studies but no tumors in the carcinogenicity study [false positives (FPs)]. In addition, we then re-assessed the prediction of the tumor outcome by integrating the pharmacological properties of these compounds. These pharmacological properties were evaluated with respect to the presence or absence of a direct or indirect proliferative action. We found support for the absence of cellular proliferation for 204 compounds (TN). For 67 compounds, the presence of cellular hyperplasia as evidence for proliferative action could be found (TP). Therefore, this approach resulted in an ability to predict non-carcinogens at a success rate of 92% and the ability to detect carcinogens at 98%. The combined evaluation of pharmacological and histopathological endpoints eventually led to only 18 unknown outcomes (17 categorized as FN and 1 as FP), thereby enhancing both the negative and positive predictivity of an evaluation based upon histopathological evaluation only. The data show the added value of a consideration of the pharmacological properties of compounds in

  17. Prediction of the carcinogenic potential of human pharmaceuticals using repeated dose toxicity data and their pharmacological properties

    Directory of Open Access Journals (Sweden)

    Jan Willem Van Der Laan

    2016-10-01

    Full Text Available In an exercise designed to reduce animal use, we analysed the results of rat sub-chronic toxicity studies from 289 pharmaceutical compounds with the aim to predict the tumour outcome of carcinogenicity studies in this species. The results were obtained from the assessment reports available at the Medicines Evaluation Board of the Netherlands for 289 pharmaceutical compounds that had been shown to be non-genotoxic. One hundred and forty-three of the 239 compounds not inducing putative preneoplastic lesions in the sub-chronic study did not induce tumours in the carcinogenicity study (True Negatives - TN, whereas 96 compounds were categorised as False Negatives (FN, because tumours were observed in the carcinogenicity study. For the remaining 50 compounds, 31 showed preneoplastic lesions in the subchronic study and tumours in the carcinogenicity study (True positives - TP, and 19 only showed preneoplastic lesions in subchronic studies but no tumours in the carcinogenicity study (False positives - FP. In addition, we then re-assessed the prediction of the tumour outcome by integrating the pharmacological properties of these compounds. These pharmacological properties were evaluated with respect to the presence or absence of a direct or indirect proliferative action. We found support for the absence of cellular proliferation for 204 compounds (TN. For 67 compounds the presence of cellular hyperplasia as evidence for proliferative action could be found (TP. Therefore, this approach resulted in an ability to predict non-carcinogens at a success rate of 92 % and the ability to detect carcinogens at 98 %. The combined evaluation of pharmacological and histopathological endpoints eventually led to only 18 unknown outcomes (17 categorised as FN. 1 as FP, thereby enhancing both the negative and positive predictivity of an evaluation based upon histopathological evaluation only. The data show the added value of a consideration of the pharmacological

  18. Exposure to carcinogens for defined job categories in Norway's offshore petroleum industry, 1970 to 2005.

    Science.gov (United States)

    Steinsvåg, Kjersti; Bråtveit, Magne; Moen, Bente E

    2007-04-01

    To identify and describe the exposure to selected known and suspected carcinogenic agents, mixtures and exposure circumstances for defined job categories in Norway's offshore petroleum industry from 1970 to 2005, in order to provide exposure information for a planned cohort study on cancer. Background information on possible exposure was obtained through company visits, including interviewing key personnel (n = 83) and collecting monitoring reports (n = 118) and other relevant documents (n = 329). On the basis of a previous questionnaire administered to present and former offshore employees in 1998, 27 job categories were defined. This study indicated possible exposure to 18 known and suspected carcinogenic agents, mixtures or exposure circumstances. Monitoring reports were obtained on seven agents (benzene, mineral oil mist and vapour, respirable and total dust, asbestos fibres, refractory ceramic fibres, formaldehyde and tetrachloroethylene). The mean exposure level of 367 personal samples of benzene was 0.037 ppm (range: less than the limit of detection to 2.6 ppm). Asbestos fibres were detected (0.03 fibres/cm3) when asbestos-containing brake bands were used in drilling draw work in 1988. Personal samples of formaldehyde in the process area ranged from 0.06 to 0.29 mg/m3. Descriptions of products containing known and suspected carcinogens, exposure sources and processes were extracted from the collected documentation and the interviews of key personnel. This study described exposure to 18 known and suspected carcinogenic agents, mixtures and exposure circumstances for 27 job categories in Norway's offshore petroleum industry. For a planned cohort study on cancer, quantitative estimates of exposure to benzene, and mineral oil mist and vapour might be developed. For the other agents, information in the present study can be used for further assessment of exposure, for instance, by expert judgement. More systematic exposure surveillance is needed in this industry

  19. Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis

    Science.gov (United States)

    Smith, Martyn T.; Guyton, Kathryn Z.; Gibbons, Catherine F.; Fritz, Jason M.; Portier, Christopher J.; Rusyn, Ivan; DeMarini, David M.; Caldwell, Jane C.; Kavlock, Robert J.; Lambert, Paul F.; Hecht, Stephen S.; Bucher, John R.; Stewart, Bernard W.; Baan, Robert A.; Cogliano, Vincent J.; Straif, Kurt

    2015-01-01

    Background: A recent review by the International Agency for Research on Cancer (IARC) updated the assessments of the > 100 agents classified as Group 1, carcinogenic to humans (IARC Monographs Volume 100, parts A–F). This exercise was complicated by the absence of a broadly accepted, systematic method for evaluating mechanistic data to support conclusions regarding human hazard from exposure to carcinogens. Objectives and Methods: IARC therefore convened two workshops in which an international Working Group of experts identified 10 key characteristics, one or more of which are commonly exhibited by established human carcinogens. Discussion: These characteristics provide the basis for an objective approach to identifying and organizing results from pertinent mechanistic studies. The 10 characteristics are the abilities of an agent to 1) act as an electrophile either directly or after metabolic activation; 2) be genotoxic; 3) alter DNA repair or cause genomic instability; 4) induce epigenetic alterations; 5) induce oxidative stress; 6) induce chronic inflammation; 7) be immunosuppressive; 8) modulate receptor-mediated effects; 9) cause immortalization; and 10) alter cell proliferation, cell death, or nutrient supply. Conclusion: We describe the use of the 10 key characteristics to conduct a systematic literature search focused on relevant end points and construct a graphical representation of the identified mechanistic information. Next, we use benzene and polychlorinated biphenyls as examples to illustrate how this approach may work in practice. The approach described is similar in many respects to those currently being implemented by the U.S. EPA’s Integrated Risk Information System Program and the U.S. National Toxicology Program. Citation: Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell JC, Kavlock RJ, Lambert P, Hecht SS, Bucher JR, Stewart BW, Baan R, Cogliano VJ, Straif K. 2016. Key characteristics of carcinogens as a

  20. Exposure assessment and modeling of quartz in Swedish iron foundries for a nested case-control study on lung cancer.

    Science.gov (United States)

    Andersson, Lena; Bryngelsson, Ing-Liss; Ngo, Yen; Ohlson, Carl-Göran; Westberg, Håkan

    2012-01-01

    Exposure assessment of quartz in Swedish iron foundries was performed based on historical and current measurement data. To evaluate the exposure-response relationship between quartz exposure and lung cancer, we modeled quartz exposure from our database of measurements using determinants job title, time period, and company. Based on these modeled exposure data, we conducted a nested case-control evaluation. In our database, the overall individual, daily time-weighted average (TWA) quartz concentrations of current and historical data varied between 0.0018 and 4.9 mg/m(3), averaging 0.083 mg/m(3). Job titles with mean TWAs for the whole study period exceeding the European Union recommended occupational exposure limit of 0.05 mg/m(3) were fettlers (0.087 mg/m(3)), furnace and ladle repair (0.42 mg/m(3)), and maintenance (0.054 mg/m(3)) workers. The mixed model analysis demonstrated significant determinants on the job level for furnace and ladle repair (β = 4.06; 95% confidence interval [CI] 2.78-5.93). For all jobs, significantly higher exposure levels occurred only during the first time period, 1968-1979 (β = 2.08; 95% CI 1.75-2.47), and a decreasing but not significant trend was noted for the three following 10-year time periods up to 2006 (β = 1.0, 0.96 and 1, respectively). Two iron foundries had significantly higher quartz concentration levels than the others (β = 1.31; 95% CI 1.00-1.71 and β = 1.63; 95% CI 1.00-2.65, respectively). The individual cumulative quartz exposure measures were categorized in low, medium, and high exposure (0.5-0.05 mg/m(3) of quartz. To conclude, certain foundry workers are still exposed to high levels of quartz, but an increased risk of lung cancer caused by quartz exposure in these Swedish iron foundries could not be confirmed at our exposure levels.

  1. Toxicity and Carcinogenicity Mechanisms of Fibrous Antigorite

    Directory of Open Access Journals (Sweden)

    Michael Balazy

    2007-03-01

    Full Text Available We studied the effects of fibrous antigorite on mesothelial MeT-5A and monocyte-macrophage J774 cell lines to further understand cellular mechanisms induced by asbestos fibers leading to lung damage and cancer. Antigorite is a mineral with asbestiform properties, which tends to associate with chrysotile or tremolite, and frequently occurs as the predominant mineral in the veins of several serpentinite rocks found abundantly in the Western Alps. Particles containing antigorite are more abundant in the breathing air of this region than those typically found in urban ambient air. Exposure of MeT-5A and J774 cells to fibrous antigorite at concentrations of 5-100 μg/ml for 72 hr induced dose-dependent cytotoxicity. Antigorite also stimulated the ROS production, induced the generation of nitrite and PGE2. MeT-5A cells were more sensitive to antigorite than J774 cells. The results of this study revealed that the fibrous antigorite stimulates cyclooxygenase and formation of hydroxyl and nitric oxide radicals. These changes represent early cellular responses to antigorite fibers, which lead to a host of pathological and neoplastic conditions because free radicals and PGE2 play important roles as mediators of tumor pathogenesis. Understanding the mechanisms of the cellular responses to antigorite and other asbestos particles should be helpful in designing rational prevention and treatment approaches.

  2. Molecular heterogeneity assessment by next-generation sequencing and response to gefitinib of EGFR mutant advanced lung adenocarcinoma.

    Science.gov (United States)

    Bria, Emilio; Pilotto, Sara; Amato, Eliana; Fassan, Matteo; Novello, Silvia; Peretti, Umberto; Vavalà, Tiziana; Kinspergher, Stefania; Righi, Luisella; Santo, Antonio; Brunelli, Matteo; Corbo, Vincenzo; Giglioli, Eliana; Sperduti, Isabella; Milella, Michele; Chilosi, Marco; Scarpa, Aldo; Tortora, Giampaolo

    2015-05-20

    Cancer molecular heterogeneity might explain the variable response of EGFR mutant lung adenocarcinomas to tyrosine kinase inhibitors (TKIs). We assessed the mutational status of 22 cancer genes by next-generation sequencing (NGS) in poor, intermediate or good responders to first-line gefitinib. Clinical outcome was correlated with Additional Coexisting Mutations (ACMs) and the EGFR Proportion of Mutated Alleles (PMA). Thirteen ACMs were found in 10/17 patients: TP53 (n=6), KRAS (n=2), CTNNB1 (n=2), PIK3CA, SMAD4 and MET (n=1 each). TP53 mutations were exclusive of poor/intermediate responders (66.7% versus 0, p=0.009). Presence of ACMs significantly affected both PFS (median 3.0 versus 12.3 months, p=0.03) and survival (3.6 months versus not reached, p=0.03). TP53 mutation was the strongest negative modifier (median PFS 4.0 versus 14.0 months). Higher EGFR PMA was present in good versus poor/intermediate responders. Median PFS and survival were longer in patients with EGFR PMA ≥0.36 (12.0 versus 4.0 months, p=0.31; not reached versus 18.0 months, p=0.59). Patients with an EGFR PMA ≥0.36 and no ACMs fared significantly better (p=0.03), with a trend towards increased survival (p=0.06). Our exploratory data suggest that a quantitative (PMA) and qualitative (ACMs) molecular heterogeneity assessment using NGS might be useful for a better selection of patients.

  3. Multi-endpoint biological monitoring in combined, carcinogenic occupational exposures.

    Science.gov (United States)

    Szendi, Katalin; Hornyák, László; Varga, Csaba

    2017-10-01

    We aimed to develop a relevant multi-endpoint biomonitoring system by studying different genotoxicity biomarkers in complex carcinogenic exposures under occupational situations. Altogether 109 workers were followed in five different workplaces. The combined carcinogenic exposures were monitored in the urine and peripheral blood samples using Ames mutagenicity test and cytogenetic analyzes. The different genotoxicity endpoints studied showed different results in the same carcinogenic exposure situations. The urinary mutagenicity tests provided more information and proved to be more sensitive compared to the cytogenetic tests in the majority of cases. In complex exposures multistep biomonitoring panel should be applied, because the exact mechanisms of the combination of single exposing agents are not known. Such a panel should involve monitoring different endpoints, e.g. point mutations, chromosomal mutations. A relatively affordable and rapid testing panel was developed using validated tests as Ames and cytogenetic assays, but its practical use should be confirmed by further investigations.

  4. Carcinogenic adducts induce distinct DNA polymerase binding orientations

    Science.gov (United States)

    Vrtis, Kyle B.; Markiewicz, Radoslaw P.; Romano, Louis J.; Rueda, David

    2013-01-01

    DNA polymerases must accurately replicate DNA to maintain genome integrity. Carcinogenic adducts, such as 2-aminofluorene (AF) and N-acetyl-2-aminofluorene (AAF), covalently bind DNA bases and promote mutagenesis near the adduct site. The mechanism by which carcinogenic adducts inhibit DNA synthesis and cause mutagenesis remains unclear. Here, we measure interactions between a DNA polymerase and carcinogenic DNA adducts in real-time by single-molecule fluorescence. We find the degree to which an adduct affects polymerase binding to the DNA depends on the adduct location with respect to the primer terminus, the adduct structure and the nucleotides present in the solution. Not only do the adducts influence the polymerase dwell time on the DNA but also its binding position and orientation. Finally, we have directly observed an adduct- and mismatch-induced intermediate state, which may be an obligatory step in the DNA polymerase proofreading mechanism. PMID:23814187

  5. Infection with the carcinogenic human liver fluke, Opisthorchis viverrini

    Science.gov (United States)

    Smout, Michael J.; Sripa, Banchob; Laha, Thewarach; Mulvenna, Jason; Gasser, Robin B.; Young, Neil D.; Bethony, Jeffrey M.; Brindley, Paul J.; Loukas, Alex

    2013-01-01

    Summary Throughout Southeast Asia there is a strikingly high incidence of cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium), particularly in people from rural settings in Laos and Northeast Thailand who are infected with the liver fluke, Opisthorchis viverrini, one of only three carcinogenic eukaryotic pathogens. More ubiquitous carcinogenic microbes, such as Helicobacter pylori, induce cancer in less than 1% of infected people, while as many as one-sixth of people with opisthorchiasis will develop CCA. The mechanisms by which O. viverrini causes cancer are multi-factorial, involving mechanical irritation from the activities and movements of the flukes, immunopathology, dietary nitrosamines and the secretion of parasite proteins that promote a tumourigenic environment. Genomic and proteomic studies of the liver fluke secretome have accelerated the discovery of parasite proteins with known/potential roles in pathogenesis and tumourigenesis, establishing a framework towards understanding, and ultimately preventing, the morbidity and mortality attributed to this highly carcinogenic parasite. PMID:21311794

  6. Canadian population risk of radon induced lung cancer: a re-assessment based on the recent cross-Canada radon survey

    Science.gov (United States)

    Chen, J.; Moir, D.; Whyte, J.

    2012-01-01

    Exposure to indoor radon has been determined to be the second leading cause of lung cancer after tobacco smoking. Canadian population risk of radon induced lung cancer was assessed in 2005 with the radon distribution characteristics determined from a radon survey carried out in the late 1970s in 19 cities. In that survey, a grab sampling method was used to measure radon levels. The observed radon concentration in 14 000 Canadian homes surveyed followed a log–normal distribution with a geometric mean (GM) of 11.2 Bq m–3 and a geometric standard deviation (GSD) of 3.9. Based on the information from that survey, it was estimated that ∼10 % of lung cancers in Canada resulted from indoor radon exposure. To gain a better understanding of radon concentrations in homes across the country, a national residential radon survey was launched in April 2009. In the recent survey, long-term (3 month or longer) indoor radon measurements were made in roughly 14 000 homes in 121 health regions across Canada. The observed radon concentrations follow, as expected, a log–normal distribution with a GM of 41.9 Bq m–3 and a GSD of 2.8. Based on the more accurate radon distribution characteristics obtained from the recent cross-Canada radon survey, a re-assessment of Canadian population risk for radon induced lung cancer was undertaken. The theoretical estimates show that 16 % of lung cancer deaths among Canadians are attributable to indoor radon exposure. These results strongly suggest the ongoing need for the Canadian National Radon Program. In particular, there is a need for a focus on education and awareness by all levels of government, and in partnership with key stakeholders, to encourage Canadians to take action to reduce the risk from indoor radon exposure. PMID:22874897

  7. Effects of carcinogenic versus non-carcinogenic AHR-active PAHs and their mixtures: lessons from ecological relevance.

    Science.gov (United States)

    Martins, Marta; Santos, José M; Diniz, Mário S; Ferreira, Ana M; Costa, Maria H; Costa, Pedro M

    2015-04-01

    Polycyclic aromatic hydrocarbons (PAHs) are priority environmental mutagens and carcinogens that occur in the aquatic environment as mixtures rather than the individual compounds for which guidelines are issued. The present work aimed at understanding the interaction effects between carcinogenic and non-carcinogenic PAHs in a model marine fish (Dicentrarchus labrax) in realistic scenarios. Laboratory assays under ecologically-relevant parameters were conducted for 28 days with sediments spiked with low-moderate concentrations (250-800ngg(-1)) of two model PAHs, phenanthrene (non-carcinogenic) and benzo[b]fluoranthene (carcinogenic to experimental animals). Both PAHs induced hepatic histopathological changes that indicate metabolic failure and inflammation, especially in animals exposed to mixtures. Phenanthrene elicited biochemical changes better related to oxidative stress (lipid peroxidation, glutathione and glutathione S-transferase activity) and CYP function, whereas B[b]F disrupted metabolic responses and defences to toxicological challenge. Conversely, mixed PAHs yielded lesions and responses that, altogether, are compatible with the AHR dependent pathway (the basis of PAH mutagenicity), potentially generating supra-additive effects. Nonetheless, the low, ecologically-relevant, concentrations of PAHs diluted dose and time-response relations. Overall, although seemingly predicting the risk of individual PAHs, environmental guidelines may not apply to mixtures by underestimating adverse effects, which calls for a redefinition of standards when determining the true risk of toxicants under realistic circumstances. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Quality Assessment of Reporting Performance for EGFR Molecular Diagnosis in Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Han, Yanxi; Zhang, Rui; Lin, Guigao; Zhang, Kuo; Xie, Jiehong; Li, Jinming

    2017-11-01

    Reports serve as a bridge between laboratories and clinicians, help synthesize an overwhelming amount of raw data into evidence-based medicine, and play a significant role in designing clinical treatments. In an effort to guarantee high-quality epidermal growth factor receptor (EGFR) gene mutation testing and reporting performance, the National Center for Clinical Laboratories launched a proficiency testing (PT) scheme reflecting clinical practices in China since 2014. This study focuses on the quality assessment of gene mutation reports. Fifty-three laboratories that submitted reports in both 2014 and 2016 EGFR gene mutation PT schemes were selected for report analysis and comparison according to predefined evaluation criteria. The average score for reports from 2014 was 14 out of 30 points. The overall scores for reports from 2016 improved substantially, yielding an average score of 20 out of 30 points. Among the evaluation criteria, general items were well documented in the reports. However, items specific to molecular diagnosis were far from satisfactory, and some items were even missing. The quality assessment of clinical written reports from 2014 and 2016 demonstrates that substantial improvements have been made in overall reporting performance. However, not all statements pertaining to important elements met expectations. To continue education, repeated PT schemes need to be executed in a timely fashion to expose and address existing shortcomings in clinical reports. There remains ample room for improvement towards generating concise, comprehensive, and readable reports. This article compares the quality of clinical gene mutation reports submitted in 2014 to those submitted in 2016 epidermal growth factor receptor proficiency testing schemes, exposes the existing shortcomings, and discusses ways to communicate results more effectively in the future. The findings demonstrate that notable progress was observed in the overall reporting performance. However, key

  9. Chemical characteristic of PM2.5 emission and inhalational carcinogenic risk of domestic Chinese cooking.

    Science.gov (United States)

    Zhang, Nan; Han, Bin; He, Fei; Xu, Jia; Zhao, Ruojie; Zhang, Yujuan; Bai, Zhipeng

    2017-08-01

    To illustrate chemical characteristic of PM2.5 emission and assess inhalational carcinogenic risk of domestic Chinese cooking, 5 sets of duplicate cooking samples were collected, using the most used 5 types of oil. The mass abundance of 14 elements, 5 water-soluble ions, organic carbon (OC), elemental carbon (EC) and 11 polycyclic aromatic hydrocarbons (PAHs) were calculated; the signature and diagnostic ratio of cooking in the domestic kitchen were analyzed; and carcinogenic risks of heavy metals and PAHs via inhalation were assessed in two scenarios. The analysis showed that OC was the primary composition in the chemical profile; Na was the most abundant element that might be due to the usage of salt; Cr and Pb, NO3- and SO42-, Phe, FL and Pyr were the main heavy metals/water-soluble ions/PAHs, respectively. Phe and FL could be used to separate cooking and stationary sources, while diagnostic ratios of BaA/(BaA + CHR), BaA/CHR, BaP/BghiP and BaP/BeP should be applied with caution, as they were influenced by various cooking conditions. Carcinogenic risks of heavy metals and PAHs were evaluated in two scenarios, simulating the condition of cooking with no ventilation and with the range hood on, respectively. The integrated risk of heavy metals and PAHs was 2.7 × 10-3 and 5.8 × 10-6, respectively, during cooking with no ventilation. While with the usage of range hood, only Cr(VI), As and Ni might induce potential carcinogenic risk. The difference in the chemical abundance in cooking sources found between this and other studies underlined the necessity of constructing locally representative source profiles under real conditions. The comparison of carcinogenic risk suggested that the potentially adverse health effects induced by inorganic compositions from cooking sources should not be ignored. Meanwhile, intervention methods, such as the operation of range hood, should be applied during cooking for health protection. Copyright © 2017 Elsevier Ltd. All rights

  10. Indoor radon exposure and lung cancer: a review of ecological studies

    OpenAIRE

    Yoon, Ji Young; Lee, Jung-Dong; Joo, So Won; Kang, Dae Ryong

    2016-01-01

    Lung cancer has high mortality and incidence rates. The leading causes of lung cancer are smoking and radon exposure. Indeed, the World Health Organization (WHO) has categorized radon as a carcinogenic substance causing lung cancer. Radon is a natural, radioactive substance; it is an inert gas that mainly exists in soil or rock. The gas decays into radioactive particles called radon progeny that can enter the human body through breathing. Upon entering the body, these radioactive elements rel...

  11. Spatiotemporal air pollution exposure assessment for a Canadian population-based lung cancer case-control study.

    Science.gov (United States)

    Hystad, Perry; Demers, Paul A; Johnson, Kenneth C; Brook, Jeff; van Donkelaar, Aaron; Lamsal, Lok; Martin, Randall; Brauer, Michael

    2012-04-04

    Few epidemiological studies of air pollution have used residential histories to develop long-term retrospective exposure estimates for multiple ambient air pollutants and vehicle and industrial emissions. We present such an exposure assessment for a Canadian population-based lung cancer case-control study of 8353 individuals using self-reported residential histories from 1975 to 1994. We also examine the implications of disregarding and/or improperly accounting for residential mobility in long-term exposure assessments. National spatial surfaces of ambient air pollution were compiled from recent satellite-based estimates (for PM2.5 and NO2) and a chemical transport model (for O3). The surfaces were adjusted with historical annual air pollution monitoring data, using either spatiotemporal interpolation or linear regression. Model evaluation was conducted using an independent ten percent subset of monitoring data per year. Proximity to major roads, incorporating a temporal weighting factor based on Canadian mobile-source emission estimates, was used to estimate exposure to vehicle emissions. A comprehensive inventory of geocoded industries was used to estimate proximity to major and minor industrial emissions. Calibration of the national PM2.5 surface using annual spatiotemporal interpolation predicted historical PM2.5 measurement data best (R2 = 0.51), while linear regression incorporating the national surfaces, a time-trend and population density best predicted historical concentrations of NO2 (R2 = 0.38) and O3 (R2 = 0.56). Applying the models to study participants residential histories between 1975 and 1994 resulted in mean PM2.5, NO2 and O3 exposures of 11.3 μg/m3 (SD = 2.6), 17.7 ppb (4.1), and 26.4 ppb (3.4) respectively. On average, individuals lived within 300 m of a highway for 2.9 years (15% of exposure-years) and within 3 km of a major industrial emitter for 6.4 years (32% of exposure-years). Approximately 50% of individuals were classified into a

  12. Accuracy and Utility of Deformable Image Registration in {sup 68}Ga 4D PET/CT Assessment of Pulmonary Perfusion Changes During and After Lung Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hardcastle, Nicholas, E-mail: nick.hardcastle@gmail.com [Department of Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne (Australia); Centre for Medical Radiation Physics, University of Wollongong, Wollongong (Australia); Hofman, Michael S. [Molecular Imaging, Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); Hicks, Rodney J. [Molecular Imaging, Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); Department of Medicine, University of Melbourne, Melbourne (Australia); Callahan, Jason [Molecular Imaging, Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); Kron, Tomas [Department of Medical Imaging and Radiation Sciences, Monash University, Clayton (Australia); The Sir Peter MacCallum Department of Oncology, Melbourne University, Victoria (Australia); MacManus, Michael P.; Ball, David L. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne (Australia); Jackson, Price [Department of Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne (Australia); Siva, Shankar [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia)

    2015-09-01

    Purpose: Measuring changes in lung perfusion resulting from radiation therapy dose requires registration of the functional imaging to the radiation therapy treatment planning scan. This study investigates registration accuracy and utility for positron emission tomography (PET)/computed tomography (CT) perfusion imaging in radiation therapy for non–small cell lung cancer. Methods: {sup 68}Ga 4-dimensional PET/CT ventilation-perfusion imaging was performed before, during, and after radiation therapy for 5 patients. Rigid registration and deformable image registration (DIR) using B-splines and Demons algorithms was performed with the CT data to obtain a deformation map between the functional images and planning CT. Contour propagation accuracy and correspondence of anatomic features were used to assess registration accuracy. Wilcoxon signed-rank test was used to determine statistical significance. Changes in lung perfusion resulting from radiation therapy dose were calculated for each registration method for each patient and averaged over all patients. Results: With B-splines/Demons DIR, median distance to agreement between lung contours reduced modestly by 0.9/1.1 mm, 1.3/1.6 mm, and 1.3/1.6 mm for pretreatment, midtreatment, and posttreatment (P<.01 for all), and median Dice score between lung contours improved by 0.04/0.04, 0.05/0.05, and 0.05/0.05 for pretreatment, midtreatment, and posttreatment (P<.001 for all). Distance between anatomic features reduced with DIR by median 2.5 mm and 2.8 for pretreatment and midtreatment time points, respectively (P=.001) and 1.4 mm for posttreatment (P>.2). Poorer posttreatment results were likely caused by posttreatment pneumonitis and tumor regression. Up to 80% standardized uptake value loss in perfusion scans was observed. There was limited change in the loss in lung perfusion between registration methods; however, Demons resulted in larger interpatient variation compared with rigid and B-splines registration

  13. Changes of lung tumour volume on CT - prediction of the reliability of assessments.

    Science.gov (United States)

    Beaumont, Hubert; Souchet, Simon; Labatte, Jean Marc; Iannessi, Antoine; Tolcher, Anthony William

    2015-10-31

    For oncological evaluations, quantitative radiology gives clinicians significant insight into patients' response to therapy. In regard to the Response Evaluation Criteria in Solid Tumours (RECIST), the classification of disease evolution partly consists in applying thresholds to the measurement of the relative change of tumour. In the case of tumour volumetry, response thresholds have not yet been established. This study proposes and validates a model for calculating thresholds for the detection of minimal tumour change when using the volume of pulmonary lesions on CT as imaging biomarker. Our work is based on the reliability analysis of tumour volume measurements documented by the Quantitative Imaging Biomarker Alliance. Statistics of measurements were entered into a multi-parametric mathematical model of the relative changes derived from the Geary-Hinkley transformation. The consistency of the model was tested by comparing modelled thresholds against Monte Carlo simulations of tumour volume measurements with additive rando