Sample records for assessing lung carcinogenic

  1. Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms. (United States)

    Ge, Guang-Zhe; Xu, Tian-Rui; Chen, Ceshi


    Tobacco usage is a major risk factor in the development, progression, and outcomes for lung cancer. Of the carcinogens associated with lung cancer, tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is among the most potent ones. The oncogenic mechanisms of NNK are not entirely understood, hindering the development of effective strategies for preventing and treating smoking-associated lung cancers. Here, we introduce the NNK-induced lung cancer animal models in different species and its potential mechanisms. Finally, we summarize several chemopreventive agents developed from these animal models.

  2. SYN-JEM : A Quantitative Job-Exposure Matrix for Five Lung Carcinogens

    NARCIS (Netherlands)

    Peters, Susan; Vermeulen, Roel; Portengen, L??tzen; Olsson, Ann; Kendzia, Benjamin; Vincent, Raymond; Savary, Barbara; LavouCrossed Sign, Jcrossed D Signr??me; Cavallo, Domenico; Cattaneo, Andrea; Mirabelli, Dario; Plato, Nils; Fevotte, Joelle; Pesch, Beate; Br??ning, Thomas; Straif, Kurt; Kromhout, Hans


    OBJECTIVE The use of measurement data in occupational exposure assessment allows more quantitative analyses of possible exposure-response relations. We describe a quantitative exposure assessment approach for five lung carcinogens (i.e. asbestos, chromium-VI, nickel, polycyclic aromatic hydrocarbons

  3. In Silico Methods for Carcinogenicity Assessment. (United States)

    Golbamaki, Azadi; Benfenati, Emilio


    Screening compounds for potential carcinogenicity is of major importance for prevention of environmentally induced cancers. A large sequence of alternative predictive models, ranging from short-term biological assays (e.g. mutagenicity tests) to theoretical models, have been attempted in this field. Theoretical approaches such as (Q)SAR are highly desirable for identifying carcinogens, since they actively promote the replacement, reduction, and refinement of animal tests. This chapter reports and describes some of the most noted (Q)SAR models based on the human expert knowledge and statistically approach, aiming at predicting the carcinogenicity of chemicals. Additionally, the performance of the selected models has been evaluated and the results are interpreted in details by applying these prediction models to some pharmaceutical molecules.

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

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


    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....

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

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    Ruano-Ravina, Alberto, E-mail: [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


    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.

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

    Luo, Juhua; Hendryx, Michael


    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…

  7. Non—Genotoxic Carcinogens.Approaches to Their Rish Assessment

    Institute of Scientific and Technical Information of China (English)

    J.A.CASTRO; M.I.DiazGomez; 等


    Epidemiological studies support the idea that most human cancers are related to chemicals present in the human environment.In turn,chemicals are believed to cause cancer via either genotoxic or non-genotoxic mechanisms.There were described in literature several simple rapid and inexpensive short term ests to reasonably predict the genotoxic nature of chemicals but in contrast,there is no reliable test or battery of tests available to predict the carcinogenicity of non-genotoxic compounds and this poses a major problem to their rish assessment.In addition,there are conflictive opinions about rish assessment needs for both classes of carcinogens.Some workers elieve that for non-genotoxic carcinogens,thresholds for exposure can be drawn while others do not.In this review,the reasons behind both of these opinions and the present hypotheses about the mechanism of action of non-genotoxic carcinogens are described and analyzed in relation to future needs.

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


    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.

  9. Critical factors in assessing risk from exposure to nasal carcinogens. (United States)

    Bogdanffy, M S; Mathison, B H; Kuykendall, J R; Harman, A E


    Anatomical, physiological, biochemical and molecular factors that contribute to chemical-induced nasal carcinogenesis are either largely divergent between test species and humans, or we know very little of them. These factors, let alone the uncertainty associated with our knowledge gap, present a risk assessor with the formidable task of making judgments about risks to human health from exposure to chemicals that have been identified in rodent studies to be nasal carcinogens. This paper summarizes some of the critical attributes of the hazard identification and dose-response aspects of risk assessments for nasal carcinogens that must be accounted for by risk assessors in order to make informed decisions. Data on two example compounds, dimethyl sulfate and hexamethylphosphoramide, are discussed to illustrate the diversity of information that can be used to develop informed hypotheses about mode of action and decisions on appropriate dosimeters for interspecies extrapolation. Default approaches to interspecies dosimetry extrapolation are described briefly and are followed by a discussion of a generalized physiologically based pharmacokinetic model that, unlike default approaches, is flexible and capable of incorporating many of the critical species-specific factors. Recent advancements in interspecies nasal dosimetry modeling are remarkable. However, it is concluded that without the development of research programs aimed at understanding carcinogenic susceptibility factors in human and rodent nasal tissues, development of plausible modes of action will lag behind the advancements made in dosimetry modeling.

  10. 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.

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


    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

  12. Assessment of carcinogenic heavy metal levels in Brazilian cigarettes. (United States)

    Viana, Gustavo Freitas de Sousa; Garcia, Karina S; Menezes-Filho, Jose Antonio


    Several studies have associated high cancer incidence with smoking habits. According to IARC, lead (Pb), cadmium (Cd), arsenic (As), nickel (Ni), and chromium (Cr) are carcinogenic to humans. These metals are present in cigarettes and their levels vary according to geographical region of tobacco cultivation, fertilizer treatment, plant variety etc. This study aims to assess these metal levels in cigarettes commercialized in Brazil. Three cigarettes of each 20 different brands were individually weighed, the tobacco filling removed, and homogenized. After desiccation, samples were subjected to microwave-assisted digestion. Analyses were performed by graphite furnace atomic absorption spectrometry. Mean levels for Pb, Cd, As, Ni, and Cr were, respectively, 0.27 ± 0.054, 0.65 ± 0.091, 0.09 ± 0.024, 1.26 ± 0.449, and 1.43 ± 0.630, in micrograms per gram of tobacco. No correlation was observed between Cd and any other metal analyzed. A mild correlation (r = 0.483, p < 0.05) was observed between Pb and Cr levels. Strong significant (p < 0.01) correlations were observed between Ni and Cr (r = 0.829), Ni and As (r = 0.799), Ni and Pb (r = 0.637), and between Cr and As (r = 0.621). Chromium and Ni levels were significantly higher in cigarettes from a multinational manufacturer. Our results show a high variability in heavy metal levels in cigarettes, representing an important exposure source of smokers and passive smokers to carcinogenic substances.

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

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    Stueckle, Todd A., E-mail: [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: [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)


    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

  14. An Interdisciplinary and Alternative Approach to Assess Carcinogenicity of Chlorobenzenes. (United States)


    carcinogenic activity of 1,4-di-, 1,2,4,5-tetra-, penta-, and hexa - chlorobenzenes in the Ito’s "Medium-Term Bioassay System" using partially...GST-P positive foci and related morphometric analyses, gene expressions of CYP1 A2, c-fos, c-jun, GSH/GSSG ratio, tissue porphyrin levels, DNA damage

  15. Inter-laboratory comparison of turkey in ovo carcinogenicity assessment (IOCA) of hepatocarcinogens. (United States)

    Enzmann, H; Brunnemann, K; Iatropoulos, M; Shpyleva, S; Lukyanova, N; Todor, I; Moore, M; Spicher, K; Chekhun, V; Tsuda, H; Williams, G


    In three independent laboratories carcinogens (diethylnitrosamine, DEN, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, NNK) and non-carcinogens (N-nitrosoproline, nicotine) were evaluated in turkey eggs for in ovo carcinogenicity assessment (IOCA). Compounds were injected into aseptic fertilized eggs. After incubation for 24 days, foci of altered hepatocytes (FAH), some with a pseudoglandular structure and/or signs of compression of the surrounding tissue were observed in the fetal liver. All laboratories were able to distinguish unequivocally the hepatocarcinogen-exposed groups from those exposed to non-carcinogens or the vehicle controls, based on the pre-specified evaluation parameters: tumor-like lesions, pseudoglandular areas and FAH. In addition to focal changes, only the carcinogens induced hepatocellular karyomegaly. Lower doses of the carcinogens, which did not induce FAH, were sufficient to induce hepatocellular karyomegaly. After exposure to 4 mg DEN, gall bladder agenesis was observed in all fetuses. The IOCA may be a valuable tool for early investigative studies on carcinogenicity and since it does not use rodents may complement chronic rat or mouse bioassays. Test substances that are positive in both rodents and fertilized turkey eggs are most probably trans-species carcinogens with particular significance for humans. The good concordance observed among the three laboratories demonstrates that the IOCA is a reliable and robust method.

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

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    Chinthalapally V. Rao


    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.

  17. The prevention of lung cancer induced by a tobacco-specific carcinogen in rodents by green and black Tea. (United States)

    Chung, F L


    A growing body of evidence from studies in laboratory animals indicates that green tea protects against cancer development at various organ sites. We have previously shown that green tea, administered as drinking water, inhibits lung tumor development in A/J mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-l-butanone (NNK), a potent nicotine-derived lung carcinogen found in tobacco. The inhibitory effect of green tea has been attributed to its major polyphenolic compound, epigallocatechin gallate (EGCG), and, to a lesser extent, to caffeine. We have also demonstrated that while levels of O6-methylguanine, a critical lesion in NNK lung tumorigenesis, were not affected in lung DNA. However, the levels of 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage, were significantly suppressed in mice treated with green tea or EGCG. These studies underscore the importance of the antioxidant activity of green tea and EGCG for their inhibitory activity against lung tumorigenesis. Unlike green tea, the effect of black tea on carcinogenesis has been scarcely studied, even though the worldwide production and consumption of black tea far exceeds that of green tea. The oxidation products found in black tea, thearubigins and theaflavins, also possess antioxidant activity, suggesting that black tea may also inhibit NNK-induced lung tumorigenesis. Indeed, bioassays in A/J mice have shown that black tea given as drinking water retarded the development of lung cancer caused by NNK. However, data on the relationship of black tea consumption with the lung cancer risk in humans are limited and inconclusive. There is a need for additional tumor bioassays in animal models to better examine the protective role of black tea against lung cancer. The development of adenocarcinomas and adenosquamous carcinomas in F344 rats upon chronic administration of NNK provides an important and relevant model for lung carcinogenesis in smokers. Thus far, no information was previously

  18. Qualitative and quantitative approaches in the dose-response assessment of genotoxic carcinogens. (United States)

    Fukushima, Shoji; Gi, Min; Kakehashi, Anna; Wanibuchi, Hideki; Matsumoto, Michiharu


    Qualitative and quantitative approaches are important issues in field of carcinogenic risk assessment of the genotoxic carcinogens. Herein, we provide quantitative data on low-dose hepatocarcinogenicity studies for three genotoxic hepatocarcinogens: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and N-nitrosodiethylamine (DEN). Hepatocarcinogenicity was examined by quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci, which are the preneoplastic lesions in rat hepatocarcinogenesis and the endpoint carcinogenic marker in the rat liver medium-term carcinogenicity bioassay. We also examined DNA damage and gene mutations which occurred through the initiation stage of carcinogenesis. For the establishment of points of departure (PoD) from which the cancer-related risk can be estimated, we analyzed the above events by quantitative no-observed-effect level and benchmark dose approaches. MeIQx at low doses induced formation of DNA-MeIQx adducts; somewhat higher doses caused elevation of 8-hydroxy-2'-deoxyquanosine levels; at still higher doses gene mutations occurred; and the highest dose induced formation of GST-P positive foci. These data indicate that early genotoxic events in the pathway to carcinogenesis showed the expected trend of lower PoDs for earlier events in the carcinogenic process. Similarly, only the highest dose of IQ caused an increase in the number of GST-P positive foci in the liver, while IQ-DNA adduct formation was observed with low doses. Moreover, treatment with DEN at low doses had no effect on development of GST-P positive foci in the liver. These data on PoDs for the markers contribute to understand whether genotoxic carcinogens have a threshold for their carcinogenicity. The most appropriate approach to use in low dose-response assessment must be approved on the basis of scientific judgment.

  19. Effects of cruciferous vegetable consumption on urinary metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in singapore chinese. (United States)

    Hecht, Stephen S; Carmella, Steven G; Kenney, Patrick M J; Low, Siew-Hong; Arakawa, Kazuko; Yu, Mimi C


    Vegetable consumption, including cruciferous vegetables, is protective against lung cancer, but the mechanisms are poorly understood. The purpose of this study was to investigate the effects of cruciferous vegetable consumption on the metabolism of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokers. The study was carried out in Singapore Chinese, whose mean daily intake of cruciferous vegetables is three times greater than that of people in the United States. Eighty-four smokers provided urine samples and were interviewed about dietary habits using a structured questionnaire, which included questions on consumption of nine commonly consumed cruciferous vegetables. Samples of these vegetables obtained in Singapore markets at three different times of year were analyzed for glucosinolates. Urine was analyzed for metabolites of NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Glucs). Glucobrassicins, which release indole-3-carbinols on chewing, were the major glucosinolates in seven of the nine cruciferous vegetables, accounting for 70.0% to 93.2% of all glucosinolates in these vegetables. There was a significant correlation (P = 0.01) between increased consumption of glucobrassicins and decreased levels of NNAL in urine after adjustment for number of cigarettes smoked per day; similar trends were observed for NNAL-Glucs (P = 0.08) and NNAL plus NNAL-Glucs (P = 0.03). These results are consistent with those of previous studies, which demonstrate that indole-3-carbinol decreases levels of urinary NNAL probably by inducing hepatic metabolism of NNK. The results are discussed with respect to the known chemopreventive activity of indole-3-carbinol against lung tumorigenesis by NNK in mice and the effects of isothiocyanates, which are also formed on consumption of cruciferous vegetables, on NNK metabolism. The results of this study demonstrate the complexities in assessing effects of

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

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


    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.

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

    DEFF Research Database (Denmark)

    van der Laan, Jan-Willem; Spindler, Per


    A Drug Information Association (DIA) workshop was held in May 2001 to discuss the outcome of the International Life Sciences Institute-Health and Environmental Sciences Institute (ILSI-HESI) project on alternative models for carcinogenicity assessment such as the P53(+/-) and XPA(+/-) knockout mo...

  2. Levels of Genotoxic and Carcinogenic Compounds in Plant food Supplements and Associated Risk Assessment

    NARCIS (Netherlands)

    Berg, van den S.J.P.L.; Restani, P.; Boersma, M.G.; Delmulle, L.; Rietjens, I.


    The present study describes the selection, analysis and risk assessment of genotoxic and carcinogenic compounds of botanicals and botanical preparations which can be found in plant food supplements (PFS). First an inventory was made of botanical compounds that are of possible concern for human healt

  3. The carcinogenic effect of localized fission fragment irradiation of rat lung. (United States)

    Batchelor, A L; Buckley, P; Gore, D J; Jenner, T J; Major, I R; Bailey, M R


    In a preliminary investigation of 'hot particle' carcinogenesis uranium oxide particles were introduced into the lungs of rats either by intubation of a liquid suspension of the particles or by inhalation of an aerosol. Subsequently the animals were briefly exposed to slow neutrons in a nuclear reactor, resulting in localized irradiation of the lung by fission fragments emitted from 235U atoms in the oxide particles. The uranium used in the intubation experiments was either enriched or depleted in 235U. Squamous cell carcinomas developed at the site of deposition of the enriched uranium oxide in many cases but no lung tumours occurred in the rats with the depleted uranium oxide, in which the lung tissue was exposed to very few fission fragments. Only enriched uranium oxide was used in the inhalation experiments. Pulmonary squamous cell carcinomas occurred after the fission fragment irradiation but were fewer than in the intubation experiments. Adenocarcinomas of the lung were seen in rats exposed to uranium oxide without subsequent irradiation by neutrons in the reactor and in rats irradiated with neutrons but not previously exposed to uranium oxide. It is concluded that (i) fission fragments were possibly implicated in the genesis of the squamous cell carcinomas, which only developed in those animals exposed to enriched uranium oxide and neutrons and (ii) the adenocarcinomas in the rats inhaling enriched uranium oxide only were likely to have been caused by protracted irradiation of the lung with alpha-rays emitted from the enriched uranium.

  4. [Assessment of carcinogenic effect of aluminosilicate ceramic fibers produced in Poland. Animal experiments]. (United States)

    Krajnow, A; Lao, I


    The effect of aluminosilicate ceramic fibres produced in Poland was assessed. The experiment was performed on two animal species: Wistar rats and BALB/C mice. The animals were administered intraperitoneally the studied fibres and krokidolit UICC--in doses of 25 and 5 mg and left for survival. All dead and sacrificed animals were examined histopathologically. Carcinogenic properties of ceramic aluminosilicate fibres were found to be rather weak. Only in 1 (2.5%) of 39 rats under study benign mesothelioma of tunica vagiualis testis was diagnosed. Peritoneal mesothelioma was found in none of 50 mice studied. For comparison the effect of krokidolit UICC was assessed. Krokidolit UICC is characterised by strong carcinogenic properties. It induced peritoneal mesothelioma in 43 mice (44.2%) and in 29 (80.5%) of 36 rats under study.

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

  6. Inter‐rater agreement in the assessment of exposure to carcinogens in the offshore petroleum industry (United States)

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


    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

  7. Regulatory Forum Opinion Piece: Carcinogen Risk Assessment: The Move from Screens to Science. (United States)

    Downes, Noel; Foster, John


    Throughout the last 50 years, the paradigm for carcinogenicity assessment has depended on lifetime bioassays in rodents. Since 1997, the International Conference on Harmonisation (ICH) S1B has permitted the use of a 2-year rodent bioassay (usually in the rat) and an alternative, genetically modified mouse model to support cancer risk assessment of pharmaceuticals. Since its introduction, it has become apparent that many of the stated advantages of the 6-month Tg mouse bioassay have, in actual fact, not been realized, and the concern exists that an albeit imperfect, 2-year mouse bioassay has been replaced by a similarly imperfect 6-month equivalent. This essay argues strongly that model systems, using cancer as the end point, should be discontinued, and that the recent initiatives, from the Organization for Economic Cooperation and Development and Institute of Peace and Conflict Studies, on "mode of action," "adverse outcome pathways," and "human relevance framework" should be embraced as being risk assessments based upon the available science. The recent suggested revisions to the ICH S1 guidelines, utilizing carcinogenicity assessment documents, go some way to developing a science-based risk assessment that does not depend almost entirely on a single, imperfect, cancer-based end point in nonrelevant animal species.

  8. Retrospective exposure assessment for carcinogenic agents in bitumen waterproofing industry in Finland and Denmark

    Energy Technology Data Exchange (ETDEWEB)

    Anttila, P.; Heikkila, P.; Makela, M.; Schlunssen, V.; Priha, E. [Finnish Institute of Occupational Health, Helsinki (Finland)


    The purpose of the study was (I) to identify the carcinogenic agents that may cause confounding when studying the exposure-response relationship between bitumen fume exposure and cancer among roofing membrane-manufacturing workers and roofers and (ii) to assess exposures to the identified carcinogens and bitumen fume in roofing membrane manufacturing and roofing in Finland and Denmark from 1950 to 2005. Information on the use of carcinogenic agents and other relevant data were collected through semi-structured interviews of senior employees in the industry. Semi-quantitative exposure assessments were made on the basis of available measurement data and information obtained from the interviews and literature. Most of the production line workers in roofing membrane plants in Finland were exposed to asbestos until the mid-1970s. Also, some of the mixer operators in the plants were exposed to asbestos in Finland during the 1970s and in Denmark from the mid-1960s to the mid-1980s. In both countries, coal tar pitch was used in roofing membrane manufacturing until the mid-1960s, and consequently, exposure to polycyclic aromatic hydrocarbons (PAHs) in the plants was high in the 1950s and still significant in the early 1960s. Exposure of production line workers to quartz dust was high until the 1980s and is still relatively high compared with current occupational exposure limit values. Bitumen roofers' exposure to coal tar-derived PAHs may have been significant in both countries until the end of 1960s. Roofers' exposure to asbestos and quartz was estimated to have been near background level.

  9. Assessment of the mutagenic, recombinagenic and carcinogenic potential of orlistat in somatic cells of Drosophila melanogaster. (United States)

    Orsolin, P C; Silva-Oliveira, R G; Nepomuceno, J C


    In this study the mutagenic, recombinagenic, carcinogenic and anticarcinogenic potential of orlistat was assessed using the somatic mutation and recombination test (SMART) and the epithelial tumor detection test (wts). The experiments were conducted on Drosophila melanogaster. In the assessment using SMART, larvae, descendants from the standard (ST) cross and the high bioactivation (HB) cross, were treated chronically with three orlistat concentrations. The results revealed a recombinagenic effect, associated with orlistat, in the descendants of the HB cross, at all three levels of concentration. Homologous recombination can function as a determinant at different stages of carcinogenesis. For verification, larvae from the wts test, descendants of the wts/TM3 virgin female and mwh/mwh male cross, were treated with the same three orlistat concentrations separately and in association with mitomicin C (0.1mM). The results did not, however, provide evidence that orlistat has carcinogenic potential nor was it associated with the reduction of tumors induced by mitomicin C in D. melanogaster.

  10. KEYNOTE LECTURES-KL1 New development in risk assessment of genotoxic carcinogens in foods

    Institute of Scientific and Technical Information of China (English)

    CHEN Jun-Shi


    @@ The no-observed-effect level (NOEL) in a study of carcinogenicity for compounds that are both genotoxic and carcinogenic represents the limit of detection in that bioassay, rather than an estimate of a possible threshold. Therefore, for those genotoxic and carcinogenic contaminants (e.g. acrylamides, PAHs, etc.) in foods it is not possible to develop health-based guidance values (e.g. ADI or PTWI) using the traditional NOEL and safety/uncertainty factors.

  11. Carcinogenic and Non-Carcinogenic Assessment of Phthalates Exposure Through Consumption of Bottled Water During the Storage Time

    Directory of Open Access Journals (Sweden)

    M Zare Jeddi


    Conclusion: The research showed that the concentration of phthalates in PET-bottled water was extremely low. Consequently, based on the risk assessment results, bottled waters regarding existence of safe for consumers and they phthalates are not considered as public health issue for consumers as phthalates does not have any risk exposure for the consumers.

  12. Non-carcinogenic risk assessment of eight metals in the source groundwater of Shaying River basin. (United States)

    Ni, Tian-hua; Diao, Wei-ping; Xu, Jian-gang; Liu, Ning


    Because of serious pollution of river water, people living along the Shaying River in China exploit the groundwater as a drinking water resource. Various pollutants including heavy metals have been detected in the groundwater at depths up to 200 m. To perform a non-carcinogenic risk assessment, the hazard index (HI) was determined for several metals present in the groundwater. High resolution inductively coupled plasma-mass spectrometry and inductively coupled plasma-atomic emission spectroscopy were used to measure the levels of Hg, Fe, Mn, Zn, Cd, Cr, Cu and Pb in source groundwater of eight tap water treatment plants (WTPs) during a 3-year period (2007-2009). Zn was present at the highest concentration of up to 101.2 μg l(-1) and Cd contributed the most (57.8%) to the HI in the WTPs, followed by Mn (14.3%) and Cr (13.1%). Both hazard quotients of individual metals and HI of total non-carcinogenic risk in each WTP were below 1.0, suggesting that the water posed negligible health risk on local residents. Temporal and spatial comparisons showed that high HIs tend to occur in low water periods (i.e., summer), and the City Pressure Station (Fuyang City) had the highest HI, followed by Yingnan Pressure Station (Yingnan Country) and Taihe WTP (Taihe Country). This study provides benchmark information useful for regulatory authorities to control the discharge of metals into the Shaying River Basin, and serves as a basis for comparison to other river systems in the world.

  13. 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; Fubini, Bice; Kane, Agnes B


    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

  14. Urinary tobacco smoke-constituent biomarkers for assessing risk of lung cancer. (United States)

    Yuan, Jian-Min; Butler, Lesley M; Stepanov, Irina; Hecht, Stephen S


    Tobacco-constituent biomarkers are metabolites of specific compounds present in tobacco or tobacco smoke. Highly reliable analytic methods, based mainly on mass spectrometry, have been developed for quantitation of these biomarkers in both urine and blood specimens. There is substantial interindividual variation in smoking-related lung cancer risk that is determined in part by individual variability in the uptake and metabolism of tobacco smoke carcinogens. Thus, by incorporating these biomarkers in epidemiologic studies, we can potentially obtain a more valid and precise measure of in vivo carcinogen dose than by using self-reported smoking history, ultimately improving the estimation of smoking-related lung cancer risk. Indeed, we have demonstrated this by using a prospective study design comparing biomarker levels in urine samples collected from smokers many years before their development of cancer versus those in their smoking counterparts without a cancer diagnosis. The following urinary metabolites were associated with lung cancer risk, independent of smoking intensity and duration: cotinine plus its glucuronide, a biomarker of nicotine uptake; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), a biomarker of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); and r-1-,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), a biomarker of polycyclic aromatic hydrocarbons (PAH). These results provide several possible new directions for using tobacco smoke-constituent biomarkers in lung cancer prevention, including improved lung cancer risk assessment, intermediate outcome determination in prevention trials, and regulation of tobacco products.

  15. The use of mechanistic data and the handling of scientific uncertainty in carcinogen risk assessments. The trichloroethylene example. (United States)

    Rudén, Christina


    The purpose of this paper is to explore how risk assessors actually use mechanistic data in carcinogen risk assessment and to discuss how the handling of scientific uncertainty may affect the outcome of the risk assessment. The analysis is performed by comparing 29 trichloroethylene risk assessment documents in general and 2 of these, namely the ECETOC (1994, Trichloroethylene: Assessment of Human Carcinogenic Hazard, Technical Report No. 60) and the OECD/EU (1996, Initial Assessment Report for the 4th SIAM (Screening Information Data Set Initial Assessment Meeting), May 1996: Trichloroethylene, sponsor country, United Kingdom [Draft]), in more detail. It is concluded that in this example the ECETOC required less evidence for considering a carcinogenic mechanism irrelevant to humans than did the OECD/EU risk assessors. There are examples of when two risk assessors have selected different primary data for their argumentation and also examples of how one and the same primary publication was interpreted differently. Biased data selection and evaluation of primary data that correlate to the risk assessor's overall conclusions have also been identified. The general comparison of all 29 TCE risk assessment documents indicates that the assessment of scientific uncertainty in the mechanistic data affects the overall conclusions.

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


    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.

  17. Quantitative assessment of the risk of lung cancer associated with occupational exposure to refractory ceramic fibers. (United States)

    Moolgavkar, S H; Luebeck, E G; Turim, J; Hanna, L


    We present the results of a quantitative assessment of the lung cancer risk associated with occupational exposure to refractory ceramic fibers (RCF). The primary sources of data for our risk assessment were two long-term oncogenicity studies in male Fischer rats conducted to assess the potential pathogenic effects associated with prolonged inhalation of RCF. An interesting feature of the data was the availability of the temporal profile of fiber burden in the lungs of experimental animals. Because of this information, we were able to conduct both exposure-response and dose-response analyses. Our risk assessment was conducted within the framework of a biologically based model for carcinogenesis, the two-stage clonal expansion model, which allows for the explicit incorporation of the concepts of initiation and promotion in the analyses. We found that a model positing that RCF was an initiator had the highest likelihood. We proposed an approach based on biological considerations for the extrapolation of risk to humans. This approach requires estimation of human lung burdens for specific exposure scenarios, which we did by using an extension of a model due to Yu. Our approach acknowledges that the risk associated with exposure to RCF depends on exposure to other lung carcinogens. We present estimates of risk in two populations: (1) a population of nonsmokers and (2) an occupational cohort of steelworkers not exposed to coke oven emissions, a mixed population that includes both smokers and nonsmokers.

  18. 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


    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 animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting...... in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials...

  19. A novel approach: chemical relational databases, and the role of the ISSCAN database on assessing chemical carcinogenicity. (United States)

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


    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.

  20. Biological effect markers for exposure to carcinogenic compound and their relevance for risk assessment

    NARCIS (Netherlands)

    Delft, J.H.M. van; Baan, R.A.; Roza, L.


    In this review data are summarized on biomarkers that are used for biological effect monitoring of human populations exposed to genotoxic carcinogens. The biomarkers are DNA and protein adducts and cytogenetic effects. Most of these biomarkers are relevant for the process of carcinogenesis. Emphasis

  1. Epidemiologic evidence for chloroprene carcinogenicity: review of study quality and its application to risk assessment. (United States)

    Bukowski, John Arthur


    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.

  2. Report on carcinogens monograph on cumene. (United States)


    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.

  3. Acrylamide-induced carcinogenicity in mouse lung involves mutagenicity: cII gene mutations in the lung of big blue mice exposed to acrylamide and glycidamide for up to 4 weeks. (United States)

    Manjanatha, Mugimane G; Guo, Li-Wu; Shelton, Sharon D; Doerge, Daniel R


    Potential health risks for humans from exposure to acrylamide (AA) and its epoxide metabolite glycidamide (GA) have garnered much attention lately because substantial amounts of AA are present in a variety of fried and baked starchy foods. AA is tumorigenic in rodents, and a large number of in vitro and in vivo studies indicate that AA is genotoxic. A recent cancer bioassay on AA demonstrated that the lung was one of the target organs for tumor induction in mice; however, the mutagenicity of AA in this tissue is unclear. Therefore, to investigate whether or not gene mutation is involved in the etiology of AA- or GA-induced mouse lung carcinogenicity, we screened for cII mutant frequency (MF) in lungs from male and female Big Blue (BB) mice administered 0, 1.4, and 7.0 mM AA or GA in drinking water for up to 4 weeks (19-111 mg/kg bw/days). Both doses of AA and GA produced significant increases in cII MFs, with the high doses producing responses 2.7-5.6-fold higher than the corresponding controls (P ≤ 0.05; control MFs = 17.2 ± 2.2 and 15.8 ± 3.5 × 10(-6) in males and females, respectively). Molecular analysis of the mutants from high doses indicated that AA and GA produced similar mutation spectra and that these spectra were significantly different from the spectra in control mice (P ≤ 0.01). The predominant types of mutations in the lung cII gene from AA- and GA-treated mice were A:T → T:A, and G:C → C:G transversions, and -1/+1 frameshifts at a homopolymeric run of Gs. The MFs and types of mutations induced by AA and GA in the lung are consistent with AA exerting its genotoxicity via metabolism to GA. These results suggest that AA is a mutagenic carcinogen in mouse lungs and therefore further studies on its potential health risk to humans are warranted. Environ. Mol. Mutagen. 56:446-456, 2015. © 2015 Wiley Periodicals, Inc.


    Directory of Open Access Journals (Sweden)

    S. M. Golovanev


    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. Use of inverted intestinal sacs to assess the effect of gastrointestinal insult on carcinogen absorption. (United States)

    Capel, I D; Cosier, R S; Pinnock, M H; Williams, D C


    Rats were subjected to various forms of treatment in the manner likely to induce gastrointestinal insult. These and control animals were sacrificed and, using inverted sacs, the rate of absorption of either dimethylnitrosamine and benzo(a)pyrene determined. The gastrointestinal injury resulting from the differing treatments did not significantly affect the absorption of benzo(a)pyrene, whereas that of dimethylnitrosamine was significantly increased after each incubation time, most notably by alcohol pretreatment. The results demonstrate that intestinal damage increases the absorption of some carcinogens.

  6. Differential expression of microRNAs in early-stage neoplastic transformation in the lungs of F344 rats chronically treated with the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. (United States)

    Kalscheuer, Stephen; Zhang, Xiaoxiao; Zeng, Yan; Upadhyaya, Pramod


    While numerous microRNAs (miRNAs) have been reported to alter their expression levels in human lung cancer tissues compared with normal tissues, the function of these miRNAs and their contribution to the long process of lung cancer development remains largely unknown. We applied a tobacco-specific carcinogen-induced cancer model to investigate the involvement of miRNAs in early lung cancer development, which could also provide information on potential, early biomarkers of lung cancers. Male F344 rats were first chronically treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a carcinogen present in tobacco products, for up to 20 weeks. The expression profiles of miRNAs in rat lungs were then determined. As measured by miRNA microarrays and confirmed by Northern blot and real-time polymerase chain reaction analyses, NNK treatment reduced the expression of a number of miRNAs, such as miR-101, miR-126*, miR-199 and miR-34. Significantly, these miRNAs overlap with previously published reports on altered miRNA expression in human lung cancer samples. These miRNAs might, therefore, represent early-response miRNAs that signify the molecular changes associated with pulmonary tumorigenesis. Moreover, we identified cytochrome P450 (CYP) 2A3, a critical enzyme in rat lungs that activates NNK to render it carcinogenic, as a potential target of miR-126*. NNK treatment in rats repressed miR-126* but induced CYP2A3 expression, a mechanism that may potentiate the oncogenic effects of NNK.

  7. PAH in airborne particulate matter.. Carcinogenic character of PM10 samples and assessment of the energy generation impact

    Energy Technology Data Exchange (ETDEWEB)

    Callen, M.S.; Cruz, M.T. de la; Lopez, J.M.; Mastral, A.M. [Instituto de Carboquimica (CSIC), Zaragoza (Spain)


    One of the main anthropogenic sources producing Polycyclic Aromatic Hydrocarbons (PAH) is related to combustion processes especially transport, power generation processes and other industrial activities. Therefore, the main cities constitute one of the main pollution sources for population. Due to the carcinogenic character of some of these pollutants, Directive 2004/107/EC established a target value of 1.0 ng/m{sup 3} with regard to Benzo(a)pyrene (BaP) for the total content in the particulate matter fraction averaged over a calendar year. Nevertheless, the consideration of only BaP can underestimate the carcinogenic character of the particulate matter. In this work, the carcinogenic character of the airborne PM10 of Zaragoza was studied during 2003-2004 by determining the concentration of BaP equivalents (BaP-eq), using toxic equivalent factors provided by Larsen and Larsen. Diagnostic ratios were used to discern regarding the main pollution sources in Zaragoza city in which the prevailing emission sources were related to diesel emissions and combustion sources. As PAH can travel long distances around the world, the impact of local pollution sources and long-range atmospheric transport on those samples exceeding 1.0 ng/m{sup 3} of BaP-eq that imply higher risk for human health were assessed by considering BaA/Chry and BaP/BeP ratios and by studying the origin of the air masses with the backward air trajectories according to the HYSPLIT model. Those samples were mainly produced during cold season. The local pollution sources were the dominant sources although one episode of long-range transport from European countries could be observed. (author)

  8. Objective and Structured Assessment of Lung Ultrasound Competence

    DEFF Research Database (Denmark)

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


    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...... a fixed number of ultrasound procedures to be performed without considering different learning rates. Recommendations do not consider different uses of lung ultrasound across specialties. OBJECTIVE: To create a reliable, valid and feasible instrument to assess lung ultrasound competence that includes...... 23 ultrasound operators of different competence levels. Examination time was measured and skill was rated by experienced observers using the assessment tool. Inter-rater agreement was examined by two observers in 9 lung ultrasound examinations. RESULTS: Consensus was obtained within 3 Delphi rounds...

  9. Green tea and its major components ameliorate immune dysfunction in mice bearing Lewis lung carcinoma and treated with the carcinogen NNK. (United States)

    Zhu, M; Gong, Y; Yang, Z; Ge, G; Han, C; Chen, J


    The protective effects of tea and/or its components on dysfunction of immune functions during tumor growth and carcinogenesis in mice were studied using two experimental models: C57/BL6J mice transplanted with Lewis lung carcinoma (LLC) and Kunming mice treated with a single dose of 4-(methylnitrosamino-)-1-(3-pyridyl)-1-butanone (NNK). In C57/BL6J mice bearing LLC, the weight of the thymus decreased, the proportion of CD4(+)-positive T lymphocytes and the ratio of CD4+ to CD8+ decreased, luminol-enhanced chemiluminescence of white blood cells in peripheral blood stimulated by zymosan increased, and plaque-forming cells (PFC) decreased. However, in LLC-bearing mice given green tea as drinking water, all immune functions were improved, along with inhibition of tumor growth. In Kunming mice treated with NNK, during the four weeks of observation, their immunologic indicators, such as phagocytosis of macrophages in the abdominal cavity, luminol-enhanced chemiluminescence of white blood cells, plaque-forming cells, and delayed-type hypersensitivity, increased or decreased to various extents compared with normal controls. However, these changes were significantly prevented in the mice given green tea, mixed tea, or tea polyphenol as drinking water. In conclusion, tea and its components ameliorated immune dysfunction in mice bearing LLC or treated with the carcinogen NNK.

  10. Reshaping the carcinogenic risk assessment of medicines: international harmonisation for drug safety, industry/regulator efficiency or both? (United States)

    Abraham, John; Reed, Tim


    The most significant institutional entity involved in the harmonisation of drug testing standards worldwide is the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), which comprises the three pharmaceutical industry associations and regulatory agencies of the EU, US and Japan. It is often claimed that such harmonisation will both accelerate the development and approval of new drugs and preserve safety standards, if not strengthen safety regimes. Drawing on extensive documentary research and interviews, this paper systematically examines whether the efforts by the ICH to improve industrial and regulatory efficiency by harmonising drug testing requirements is likely to raise, maintain or compromise safety standards in carcinogenic risk assessment of pharmaceuticals. The evidence suggests that, in the field of carcinogenicity testing, the ICH management of international harmonisation of medicines regulation is not achieving simultaneous improvements in safety standards and acceleration of drug development. Rather, the latter is being achieved at the expense of the former. Indeed, the ICH may be converting permissive regulatory practices of the past into new scientific standards for the future. These findings are significant as many expert scientific advisers to drug regulatory agencies seem to have accepted uncritically the conclusions reached by the ICH, which may affect a potential patient population of half a billion and tens of thousands of clinical trials.

  11. Assessing carcinogenic risks associated with ingesting arsenic in farmed smeltfish (Ayu, Plecoglossus altirelis) in aseniasis-endemic area of Taiwan. (United States)

    Lee, Jin-Jing; Jang, Cheng-Shin; Liang, Ching-Ping; Liu, Chen-Wuing


    This study spatially analyzed potential carcinogenic risks associated with ingesting arsenic (As) contents in aquacultural smeltfish (Plecoglossus altirelis) from the Lanyang Plain of northeastern Taiwan. Sequential indicator simulation (SIS) was adopted to reproduce As exposure distributions in groundwater based on their three-dimensional variability. A target cancer risk (TR) associated with ingesting As in aquacultural smeltfish was employed to evaluate the potential risk to human health. The probabilistic risk assessment determined by Monte Carlo simulation and SIS is used to propagate properly the uncertainty of parameters. Safe and hazardous aquacultural regions were mapped to elucidate the safety of groundwater use. The TRs determined from the risks at the 95th percentiles exceed one millionth, indicating that ingesting smeltfish that are farmed in the highly As-affected regions represents a potential cancer threat to human health. The 95th percentile of TRs is considered in formulating a strategy for the aquacultural use of groundwater in the preliminary stage.

  12. Bridging the etiologic and prognostic outlooks in individualized assessment of absolute risk of an illness: application in lung cancer. (United States)

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Brunnemann, K.D.; Hoffmann, D.


    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. (/sup 14/C)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.

  14. Report on carcinogens monograph on 1-bromopropane. (United States)


    The National Toxicology Program conducted a cancer evaluation on 1 bromopropane 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 1 bromopropane 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 1-bromopropane. This monograph provides an assessment of the available scientific information on 1 bromopropane, 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 1 bromopropane be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found inhalation exposure to 1-bromopropane caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1 bromopropane, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. These alterations, observed in mainly in vitro and toxicity studies in rodents, are relevant to possible mechanisms of human carcinogenicity and support the relevance of the cancer studies in

  15. Investigations on the carcinogenic burden by air pollution in man. XIII. Assessment of the contribution of passenger cars to air pollution by carcinogenic polycylic hydrocarbons. (United States)

    Grimmer, G; Hildebrandt, A


    A total of 100 passenger cars were tested with regard to the amount of polycyclic aromatic hydrocarbons (PAH) emitted during the EUROPA-Test (E.-Test, simulate city driving; 4 times 195 s). As determined by frequency of registration, the 20 most common car models were chosen. Each model was represented by 5 cars. The total amount of selected 14 PAH emitted by all test vehicles during an E.-test is in the range of 1-16 mg. As can be seen from the average of fuel consumption (409.4 g/E.-test) and benzo(a)pyrene emission (41.6 mug/E.-test), 1000 kg of burned fuel yield 101 mg of benzo(a)pyrene. Based on the consumption of gasoline in 1973 in West Germany (18508200 tons), an annual amount of 1.85 tons of benzo(a)pyrene is produced by gas engine vehicles. However, the biological effect of the automobile exhaust is still larger because it contains additional carcinogenic PAH. - A statistical evaluation of the results shows that different car models can not be distinguish by their PAH emission. When evaluating individual vehicles after 5 repeated E.-tests, the margin of error for any single PAH is between 6.3-10.9% (variation coefficient) for this car. A larger margin of error is obtained by pooling 5 different vehicles of the same model.

  16. Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Anna Francina, E-mail: [Environmental Health Science and Research Bureau, Health Canada, Ottawa K1A 0K9 (Canada); Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa K1S 5B6 (Canada); Williams, Andrew, E-mail: [Environmental Health Science and Research Bureau, Health Canada, Ottawa K1A 0K9 (Canada); Recio, Leslie, E-mail: [ILS, Inc., P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Waters, Michael D., E-mail: [ILS, Inc., P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Lambert, Iain B., E-mail: [Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa K1S 5B6 (Canada); Yauk, Carole L., E-mail: [Environmental Health Science and Research Bureau, Health Canada, Ottawa K1A 0K9 (Canada)


    Furan is a chemical hepatocarcinogen in mice and rats. Its previously postulated cancer mode of action (MOA) is chronic cytotoxicity followed by sustained regenerative proliferation; however, its molecular basis is unknown. To this end, we conducted toxicogenomic analysis of B3C6F1 mouse livers following three week exposures to non-carcinogenic (0, 1, 2 mg/kg bw) or carcinogenic (4 and 8 mg/kg bw) doses of furan. We saw enrichment for pathways responsible for cytotoxicity: stress-activated protein kinase (SAPK) and death receptor (DR5 and TNF-alpha) signaling, and proliferation: extracellular signal-regulated kinases (ERKs) and TNF-alpha. We also noted the involvement of NF-kappaB and c-Jun in response to furan, which are genes that are known to be required for liver regeneration. Furan metabolism by CYP2E1 produces cis-2-butene-1,4-dial (BDA), which is required for ensuing cytotoxicity and oxidative stress. NRF2 is a master regulator of gene expression during oxidative stress and we suggest that chronic NFR2 activity and chronic inflammation may represent critical transition events between the adaptive (regeneration) and adverse (cancer) outcomes. Another objective of this study was to demonstrate the applicability of toxicogenomics data in quantitative risk assessment. We modeled benchmark doses for our transcriptional data and previously published cancer data, and observed consistency between the two. Margin of exposure values for both transcriptional and cancer endpoints were also similar. In conclusion, using furan as a case study we have demonstrated the value of toxicogenomics data in elucidating dose-dependent MOA transitions and in quantitative risk assessment. - Highlights: • Global gene expression changes in furan-exposed mouse livers were analyzed. • A molecular mode of action for furan-induced hepatocarcinogenesis is proposed. • Key pathways include NRF2, SAPK, ERK and death receptor signaling. • Important roles for TNF-alpha, c-Jun, and NF

  17. Assessment of lung tumor response by perfusion CT. (United States)

    Coche, E


    Perfusion CT permits evaluation of lung cancer angiogenesis and response to therapy by demonstrating alterations in lung tumor vascularity. It is advocated that perfusion CT performed shortly after initiating therapy may provide a better evaluation of physiological changes rather than the conventional size assessment obtained with RECIST. The radiation dose,the volume of contrast medium delivered to the patient and the reproducibility of blood flow parameters remain an issue for this type of investigation.

  18. Carcinogen testing. Fact and fallacy. (United States)

    Moore, J A


    In the absence of human information on the carcinogenicity of chemical substances, one must rely primarily on information from long-term animal testing. Although far from perfect, animal studies seem to be reasonable predictors of the human experience, both qualitatively and quantitatively. Short-term tests for genotoxicity may be helpful for establishing priorities for chemical testing, but they are not as strong indicators of potential carcinogenicity as had been previously thought. New directions in toxicologic research hold the promise for scientists being able to perform more reasoned assessments of carcinogenic risk.

  19. Cobalt and antimony: genotoxicity and carcinogenicity. (United States)

    De Boeck, Marlies; Kirsch-Volders, Micheline; Lison, Dominique


    The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with

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

    Directory of Open Access Journals (Sweden)

    Pradyumna Kumar Mishra


    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.

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

    DEFF Research Database (Denmark)

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


    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 ge...

  2. Towards health impact assessment of drinking-water privatization--the example of waterborne carcinogens in North Rhine-Westphalia (Germany). (United States)

    Fehr, Rainer; Mekel, Odile; Lacombe, Martin; Wolf, Ulrike


    Worldwide there is a tendency towards deregulation in many policy sectors - this, for example, includes liberalization and privatization of drinking-water management. However, concerns about the negative impacts this might have on human health call for prospective health impact assessment (HIA) on the management of drinking-water. On the basis of an established generic 10-step HIA procedure and on risk assessment methodology, this paper aims to produce quantitative estimates concerning health effects from increased exposure to carcinogens in drinking-water. Using data from North Rhine-Westphalia in Germany, probabilistic estimates of excess lifetime cancer risk, as well as estimates of additional cases of cancer from increased carcinogen exposure levels are presented. The results show how exposure to contaminants that are strictly within current limits could increase cancer risks and case-loads substantially. On the basis of the current analysis, we suggest that with uniform increases in pollutant levels, a single chemical (arsenic) is responsible for a large fraction of expected additional risk. The study also illustrates the uncertainty involved in predicting the health impacts of changes in water quality. Future analysis should include additional carcinogens, non-cancer risks including those due to microbial contamination, and the impacts of system failures and of illegal action, which may be increasingly likely to occur under changed management arrangements. If, in spite of concerns, water is privatized, it is particularly important to provide adequate surveillance of water quality.

  3. [Assessment of sociodemographic and nutritional status of lung cancer patients]. (United States)

    Zabłocka, Katarzyna; Krawczyszyn, Monika; Pieczyńska, Joanna; Prescha, Anna; Ilow, Rafał; Porebska, Irena; Gołecki, Marcin; Kosacka, Monika; Jankowska, Renata; Grajeta, Halina; Biernat, Jadwiga


    Low sociodemographic status positively correlates with the risk of lung cancer. Nutritional status assessed during diagnosis of cancer may be a useful predictive factor for response to therapy and influences the quality of life and life expectancy after oncological therapy. The aim of this study was to assess the sociodemographic and nutritional status of patients. Lower Silesian Centre of Lung Diseases, diagnosed with lung cancer. 81 cases and 125 subjects formed the control group were included in this study. The questionnaire about sociodemographic status was performed among all respondents as well as MNA questionnaire and anthropometric measurements for evaluating nutritional status. Lower level of education, lower employment status and more frequent tobacco addiction was found in patient group then in control individuals. Nutritional status of patients was worse than the control group, which has been demonstrated mainly through a MNA questionnaire and arm circumference measurements. The risk of malnutrition or diagnosed malnutrition found in most patients assessed by MNA test may increase the likelihood of complications during treatment.

  4. 76 FR 52664 - Request for Information: Announcement of Carcinogen and Recommended Exposure Limit (REL) Policy... (United States)


    ... Carcinogen and Recommended Exposure Limit (REL) Policy Assessment AGENCY: National Institute for Occupational... review its approach to classifying carcinogens and establishing recommended exposure limits (RELs) for... recommended exposure limit (REL) for carcinogens or should lower targets be considered? (4) In...

  5. Environmental carcinogenic polycyclic aromatic hydrocarbons in soil from Himalayas, India: Implications for spatial distribution, sources apportionment and risk assessment. (United States)

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


    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.

  6. Risk assessment of bioaccessible trace elements in smoke haze aerosols versus urban aerosols using simulated lung fluids (United States)

    Huang, Xian; Betha, Raghu; Tan, Li Yun; Balasubramanian, Rajasekhar


    Smoke-haze episodes, caused by uncontrolled peat and forest fires, occur almost every year in the South-East Asian region with increased concentrations of PM2.5 (airborne particulate matter (PM) with diameter ≤ 2.5 μm). Particulate-bound trace elements (TrElems), especially carcinogenic and toxic elements, were measured during smoke haze as well as non-haze periods in 2014 as they are considered to be indicators of potential health effects. The bioaccessibilities of 13 TrElems were investigated using two types of simulated lung fluids (SLFs), Gamble's solution and artificial lysosomal fluid (ALF), instead of the commonly used leaching agent (water). The dissolution kinetics was also examined for these TrElems. Many TrElems showed higher solubility in SLFs, and were more soluble in ALF compared to the Gamble's solution. Cu, Mn and Cd were observed to be the most soluble trace elements in ALF, while in Gamble's solution the most soluble trace elements were Cu, Mn and Zn. The dissolution rates were highly variable among the elements. Health risk assessment was conducted based on the measured concentrations of TrElems and their corresponding toxicities for three possible scenarios involving interactions between carcinogenic and toxic TrElems and SLFs, using the United States Environmental Protection Agency (USEPA) human health risk assessment model. The cumulative cancer risks exceeded the acceptable level (1 in a million i.e. 1 × 10-6). However, the estimation of health quotient (HQ) indicated no significant chronic toxic health effects. The risk assessment results revealed that the assessment of bioaccessibility of particulate-bound TrElems using water as the leaching agent may underestimate the health risk.

  7. 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


    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

  8. Liposomal encapsulation of deguelin: evidence for enhanced antitumor activity in tobacco carcinogen-induced and oncogenic K-ras-induced lung tumorigenesis. (United States)

    Woo, Jong K; Choi, Dong Soon; Tran, Hai T; Gilbert, Brian E; Hong, Waun Ki; Lee, Ho-Young


    Deguelin has shown promising chemopreventive and therapeutic activities in diverse types of cancers. However, the potential side effect of deguelin over a certain dose could be the substantial hurdle in the practical application of the drug. One of the successful strategies for the use of deguelin in clinical trials could be lung-specific delivery of the drug. The present study evaluates the efficacy of liposome-encapsulated deguelin with a dose of 0.4 mg/kg, which is 10 times less than the dose (4 mg/kg) for preventive and therapeutic activities validated in previous in vivo studies. Liposomal deguelin revealed cytotoxic activity in vitro in premalignant and malignant human bronchial epithelial cells and non-small cell lung cancer cells through the same mechanistic pathway previously reported for deguelin (i.e., suppression of the heat shock protein 90 chaperone function and induction of apoptosis). Delivery of liposomal deguelin at a dose of 0.4 mg/kg by intranasal instillation resulted in markedly increased drug partitioning to the lungs compared with that of 4 mg/kg deguelin or 0.4 mg/kg liposomal deguelin administered by oral gavage. Lung-specific delivery of deguelin (0.4 mg/kg) via nasal or intratracheal instillation in a liposomal formulation also showed significant chemopreventive and therapeutic activities in 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone/benzo(a)pyrene-treated A/J mice and K-rasLAC57Bl6/129/sv F1 mice with no detectable toxicity. Our findings support the potential use of deguelin in a liposomal formulation via lung-specific delivery to improve efficacy and to reduce the potential side effects of the agent.

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


    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

  10. Uncertainty in environmental health risk assessment: a framework for analysis and an application to a chronic exposure situation involving a chemical carcinogen

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, K.T.


    The impact of uncertainty and inter-individual variability is not rigorously addressed in current environmental health risk assessments performed for regulatory purposes. The availability of such information on a systematic basis would not only serve to clarify technical assumptions underlying risk assessment, but would also greatly facilitate the application of more-sophisticated quantitative approaches to risk management decision making. Here, focusing on the particular context of regulatory risk assessment for chemical carcinogens, a taxonomy of uncertainty and variability in the elements of risk assessment is developed, potential generic sources are reviewed and a critical overview of some current approaches to incorporating uncertainty and variability into risk assessment is offered. The general problems of compounded uncertainty and creeping safety - regarding the degree to which uncertainty or safety assumed in each component of a risk assessment may be compounded or magnified in a final risk prediction - are described. A formal methodology is developed for qualitative uncertainty analysis, i.e., the quantitative analysis of the impact that modeled uncertainty and/or variability in each component of a risk assessment has on uncertainty and variability in final predicted risk.

  11. An analysis of the Gene-Tox Carcinogen Data Base. (United States)

    Nesnow, S; Bergman, H


    The Gene-Tox Carcinogen Data Base is an evaluated source of cancer data on 506 chemicals selected in part for their previous assessment in genetic toxicology bioassays. This data base has been analyzed for the distribution of these chemicals into chemical classes. The major chemical classes (6% or greater of the total data base) are: acyl-, alkyl-, and aryl-halides; alcohols and phenols; aliphatic and aromatic amines, amides, and sulfonamides; benzene-ring-containing chemicals; organo-lead, -mercury, -phosphorous compounds, metals and derivatives, phosphoric acid esters, and phosphoramides; and polycyclic aromatic hydrocarbons. Cancer studies representing a subset of the Gene-Tox Carcinogen Data Base, 199 chemicals which were rated as Sufficient Positive/Negative or Limited Positive/Negative, were examined for distribution of those studies by animal species, gender, route of chemical administration, duration of study, major tumor sites, and major tumor types. These analyses revealed that the Gene-Tox Carcinogen Data Base contains a large number of lifetime studies involving the rat and mouse treated by oral routes of administration. The major organs that were targets were: liver, lung, skin, forestomach, bladder, and mammary gland, while the major tumor types were: carcinoma, sarcoma, papilloma, and adenoma. Chemicals in the data base have been assessed for species-specific carcinogenic effects, and these results indicate that for mice and rats there is a high correspondence (85%). This number is higher than that (71%) reported by Tennant et al. (1986) based on the recent results of 72 chronic cancer bioassays performed by the National Toxicology Program. This difference is probably based on the nature of the chemicals selected for inclusion in both data bases. Although the absolute value of this correspondence is unknown, it would seem to be within this range. When chemicals in the Gene-Tox Carcinogen Data Base were examined for their previous evaluation in 73

  12. Mineral fibre persistence and carcinogenicity. (United States)

    McDonald, J C


    Epidemiological research during the past 40 years has demonstrated with increasing clarity that amphibole asbestos fibres--crocidolite, amosite and tremolite--are more carcinogenic than chrysotile. A smaller number of well-controlled studies using lung burden analyses, while adding to the specificity of this conclusion, have shown that amphibole fibres also differ from chrysotile in being far more durable and biopersistent in lung tissue. Analyses of mesothelioma and lung cancer in a large cohort of Canadian chrysotile miners and millers have recently shown that the low-level presence of fibrous tremolite in these mines, rather than the chrysotile, may well be responsible. The high risk of lung cancer, but not of mesothelioma, in the chrysotile textile industry remains anomalous and cannot be explained in this way. These various findings are directly relevant to the choice of the experimental methods which should be used for screening man-made fibres for industrial use. Although it is clear that biopersistence is a major determinant of cancer risk in animals, and perhaps also in man, other factors affecting the biological activity of mineral fibres may also be important.

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

    Directory of Open Access Journals (Sweden)

    Subotić Dragan


    additional lung function assessment. .


    Institute of Scientific and Technical Information of China (English)


    Objective To evaluate the monitoring and diagnostic potential of MR in fetal lung development using lung signal intensity changes in the fetus. Methods The lung-to-liver intensity ratio was calculated by means of region-of-interest analysis in all 35 fetuses including 7 bilateral urinary anomalies, 9 unilateral urinary anomalies, 5 pulmonary anomalies, and 14 others. Results All fetuses with urinary anomalies and pulmonary anomalies showed low ratio of lung-to-liver signal intensity. Conclusion Low ratio of lung-to-liver signal intensity on MR imaging indicates pulmonary hypoplasia after 22 weeks' gestation.

  15. Part 1. Assessment of carcinogenicity and biologic responses in rats after lifetime inhalation of new-technology diesel exhaust in the ACES bioassay. (United States)

    McDonald, Jacob D; Doyle-Eisele, Melanie; Seagrave, JeanClare; Gigliotti, Andrew P; Chow, Judith; Zielinska, Barbara; Mauderly, Joe L; Seilkop, Steven K; Miller, Rodney A


    The Health Effects Institute and its partners conceived and funded a program to characterize the emissions from heavy-duty diesel engines compliant with the 2007 and 2010 on-road emissions standards in the United States and to evaluate indicators of lung toxicity in rats and mice exposed repeatedly to 2007-compliant new-technology diesel exhaust (NTDE*). The a priori hypothesis of this Advanced Collaborative Emissions Study (ACES) was that 2007-compliant on-road diesel emissions "... will not cause an increase in tumor formation or substantial toxic effects in rats and mice at the highest concentration of exhaust that can be used ... although some biological effects may occur." This hypothesis was tested at the Lovelace Respiratory Research Institute (LRRI) by exposing rats by chronic inhalation as a carcinogenicity bioassay. Indicators of pulmonary toxicity in rats were measured after 1, 3, 12, 24, and 28-30 months of exposure. Similar indicators of pulmonary toxicity were measured in mice, as an interspecies comparison of the effects of subchronic exposure, after 1 and 3 months of exposure. A previous HEI report (Mauderly and McDonald 2012) described the operation of the engine and exposure systems and the characteristics of the exposure atmospheres during system commissioning. Another HEI report described the biologic responses in mice and rats after subchronic exposure to NTDE (McDonald et al. 2012). The primary motivation for the present chronic study was to evaluate the effects of NTDE in rats in the context of previous studies that had shown neoplastic lung lesions in rats exposed chronically to traditional technology diesel exhaust (TDE) (i.e., exhaust from diesel engines built before the 2007 U.S. requirements went into effect). The hypothesis was largely based on the marked reduction of diesel particulate matter (DPM) in NTDE compared with emissions from older diesel engine and fuel technologies, although other emissions were also reduced. The DPM

  16. 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)


    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.)

  17. Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners



    Background: High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development. Objectives: We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high...

  18. Assessing exposure to tobacco-specific carcinogen NNK using its urinary metabolite NNAL measured in US population: 2011-2012. (United States)

    Wei, Binnian; Blount, Benjamin C; Xia, Baoyun; Wang, Lanqing


    Carcinogenic tobacco-specific nitrosamines (TSNAs) such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are found only in tobacco and derived products. Food and Drug Administration of the United States (US FDA) lists NNK as one of the 93 harmful and potentially harmful constituents (HPHCs) found in tobacco products and tobacco smoke. The aim of this study was to use the urinary concentration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a major metabolite of NNK, to quantitatively estimate exposure to NNK in the US general population. In 2011-2012, the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey (NHANES) collected urine and serum samples from a representative sample of US residents. We used a serum cotinine cutoff of 10 ng/ml with combination of questionnaire data to select non-users from cigarette users and used self-reported data to determine different tobacco product user groups. We estimated the absorbed total daily dose of NNK using a probabilistic method based on a two-compartment model. The geometric mean (GM) for the daily dose of NNK among smokers aged 12-16 years was significantly higher than that for non-users at the same age stage exposed to second-hand smoke (SHS) (P<0.001). Among those exposed to SHS, the GM for daily dose of NNK in young children (6-11 years) was nearly three times of those for adults in the age range 21-59 years. Among cigarette users, non-Hispanic Whites had the highest NNK daily dose and Mexican Americans had the lowest levels. Exclusive snuff or chewing product users had significantly higher daily dose of NNK than did cigarette smokers. Our study found that the maximum daily dose of NNK for children aged from 6 to 11 years and that for a significant percentage of cigarette users, chewing product and snuff users were higher than an estimated provisional "reference" risk level.

  19. Carcinogenic effects of benzene: Cesare Maltoni's contributions. (United States)

    Mehlman, Myron A


    Cesare Maltoni's contributions to understanding, identifying, and characterizing widely used commercial chemicals in experimental animals are among the most important methods developed in the history of toxicology and serve to protect working men and women, the general population, and our environment from hazardous substances. Maltoni developed experimental methods that have reached the "platinum standard" for protection of public health. Benzene was among the 400 or more chemicals that Maltoni and his associates tested for carcinogenicity. In 1976, Maltoni reported that benzene is a potent experimental carcinogen. Maltoni's experiments clearly demonstrated that benzene is carcinogenic in Sprague-Dawley rats, Wistar rats, Swiss mice, and RF/J mice when administered by inhalation or ingestion. Benzene caused carcinomas of the Zymbal gland, oral cavity, nasal cavities; cancers of the skin, forestomach, mammary glands, and lungs; angiosarcomas and hepatomas of the liver; and hemolymphoreticular cancers. Thus, benzene was shown to be a multipotential carcinogen that produced cancers in several species of animals by various routes of administration. On November 2, 1977, Chemical Week reported that Maltoni provided a "bombshell" when he demonstrated the "first direct link" between benzene and cancer. In this paper, I shall summarize early experiments and human studies and reports; Maltoni's experimental contribution to understanding the carcinogenicity of benzene in humans and animals; earlier knowledge concerning benzene toxicity; and benzene standards and permissible exposure levels.

  20. Impact of fine particles in ambient air on lung cancer

    Institute of Scientific and Technical Information of China (English)

    Gerard Hoek; Ole Raaschou-Nielsen


    Recently, the International Agency for Research on Cancer (IARC) has classified outdoor air pol ution and the particulate matter component of outdoor air pollution as class I carcinogen. Air pollution is consistently associated with lung cancer in epidemiologic and experimental studies. The IARC assessment is specifical y designed as hazard identification, and it does not quantify the magnitude of the cancer risk. This article addresses the magnitude of the lung cancer risk in the population due to ambient air pol ution exposure.

  1. Proton magnetic resonance imaging for assessment of lung function and respiratory dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Eichinger, Monika [Deutsches Krebsforschungszentrum (DKFZ), Department of Radiology (E010), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)], E-mail:; Tetzlaff, Ralf; Puderbach, Michael [Deutsches Krebsforschungszentrum (DKFZ), Department of Radiology (E010), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Woodhouse, Neil [Unit of Academic Radiology, University of Sheffield (United Kingdom); Kauczor, H.-U. [Deutsches Krebsforschungszentrum (DKFZ), Department of Radiology (E010), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)


    Since many pulmonary diseases present with a variable regional involvement, modalities for assessment of regional lung function gained increasing attention over the last years. Together with lung perfusion and gas exchange, ventilation, as a result of the interaction of the respiratory pump and the lungs, is an indispensable component of lung function. So far, this complex mechanism is still mainly assessed indirectly and globally. A differentiation between the individual determining factors of ventilation would be crucial for precise diagnostics and adequate treatment. By dynamic imaging of the respiratory pump, the mechanical components of ventilation can be assessed regionally. Amongst imaging modalities applicable to this topic, magnetic resonance imaging (MRI), as a tool not relying on ionising radiation, is the most attractive. Recent advances in MRI technology have made it possible to assess diaphragmatic and chest wall motion, static and dynamic lung volumes, as well as regional lung function. Even though existing studies show large heterogeneity in design and applied methods, it becomes evident that MRI is capable to visualise pulmonary function as well as diaphragmatic and thoracic wall movement, providing new insights into lung physiology. Partly contradictory results and conclusions are most likely caused by technical limitations, limited number of studies and small sample size. Existing studies mainly evaluate possible imaging techniques and concentrate on normal physiology. The few studies in patients with lung cancer and emphysema already give a promising outlook for these techniques from which an increasing impact on improved and quantitative disease characterization as well as better patient management can be expected.

  2. Utility of SPECT Lung Perfusion Scans in Assessing the Early Changes in Pulmonary Function after Radiotherapy for Patients with Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Wenjie Zhang; Rong Zheng; Luiun Zhao; Luhua Wang; Shengzu Chen


    OBJECTIVE Radiation-induced lung injury commonly follows radiotherapy (RT) fortumors within and near the thorax. Lung function is usually measured by pulmonary function tests (PFTs). But RT-induced regional changes of pulmonary function cannot be accurately evaluated by PFTs. Lung perfusion scintigraphy compared with other radiographic methods can assess well regional pulmonary physiological function, and a 3-dimensional conformal radiotherapy planning system can quantitatively calculate irradiation dosage. The purpose of this study is to assess, by lung perfusion scintigraphy, early changes in the pulmonary function of patients with lung cancer when receiving thoracic 3-dimensional conformal radiotherapy (3D-CRT).METHODS Nineteen patients receiving thoracic 3D-CRT for lung cancer were studied. A single photon emission computed tomography (SPECT)lung perfusion scan, X-ray or CT scan before RT and after 40~50Gy radiation were performed. Pre-RT SPECT lung perfusion images were classified by comparing lung perfusion defects with radiological abnormalities before RT. Grade 0: There was no lung perfusion defect in the area of radiological abnormality. Grade 1: The size of the radiological abnormality was similar to the area of the lung perfusion defect. Grade 2: The area of the lung perfusion defect was bigger than the size of the radiological abnormality and extended to one lobe of the lung. Grade 3: The area of lung perfusion defect exceeded one lobe of the lung. The radiation field with more than 20 Gy was drawn as a region of interest (ROI). The proportion of radioactive dose within this ROI relative to total lung dose in one slice was calculated.RESULTS All patients had lung perfusion defects, nine patients with grade 1,five patients with grade 2 and five patients with grade 3 damage,respectively. All tumors in the 19 patients were reduced in CT or X-ray images to various degrees after 40~50 Gy radiation. The mean proportion of ROI in 19 patients was 53.7±29

  3. Assessment of Benzo(apyrene-equivalent Carcinogenicity and Mutagenicity of Residential Indoor versus Outdoor Polycyclic Aromatic Hydrocarbons Exposing Young Children in New York City

    Directory of Open Access Journals (Sweden)

    Rachel L. Miller


    Full Text Available The application of benzo(apyrene (BaP-toxic equivalent factor to polycyclic aromatic hydrocarbons (PAH concentrations can provide a more accurate risk assessment from environmental exposure to PAH. We hypothesized that BaP-equivalent toxicity determined following residential air monitoring among young urban children may vary by season. Residential indoor and outdoor air levels of PAH measured over two-weeks in a cohort of 5–6 year old children (n = 260 in New York City were normalized to the cancer and mutagen potency equivalent factor of BaP (BaP = 1. Data are presented as carcinogenic equivalents (BaP-TEQ and mutagenic equivalents (BaP-MEQ for the sum of 8 PAH (∑8PAH; MW ³ 228 and individual PAH and compared across heating versus nonheating seasons. Results show that heating compared to nonheating season was associated significantly with higher (BaP-TEQ∑8PAH and (BaP-MEQ∑8PAH both indoors and outdoors (p < 0.001. Outdoor (BaP-TEQ∑8PAH and (BaP-MEQ∑8PAH were significantly higher than the corresponding indoor measures during the heating season (p < 0.01. These findings suggest that at levels encountered in New York City air, especially during the heating season, residential exposure to PAH may pose an increased risk of cancer and mutation.

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


    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.

  5. 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


    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.

  6. TU-G-BRA-01: Assessing Radiation-Induced Reductions in Regional Lung Perfusion Following Stereotactic Radiotherapy for Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    McGurk, R; Green, R; Lawrence, M [NC Cancer Hospital, Chapel Hill, NC (United States); Schreiber, E; Das, S; Zagar, T; Marks, L [UNC School of Medicine, Chapel Hill, NC (United States); Sheikh, A; McCartney, W; Rivera, P [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States)


    Purpose: The dose-dependent nature of radiation therapy (RT)-induced lung injury following hypo-fractionated stereotactic RT is unclear. We herein report preliminary results of a prospective study assessing the magnitude of RT-induced reductions in regional lung perfusion following hypo-fractionated stereotactic RT. Methods: Four patients undergoing hypo-fractionated stereotactic lung RT (SBRT: 12 Gy x 4 fractions or 10 Gy x 5 fractions) had a pre-treatment SPECT (single-photon emission computed tomography) perfusion scan providing a 3D map of regional lung perfusion. Scans were repeated 3–6 months post-treatment. Pre- and post SPECT scans were registered to the planning CT scan (and hence the 3D dose data). Changes in regional perfusion (counts per cc on the pre-post scans) were computed in regions of the lung exposed to different doses of radiation (in 5 Gy intervals), thus defining a dose-response function. SPECT scans were internally normalized to the regions receiving <5 Gy. Results: At 3 months post-RT, the changes in perfusion are highly variable. At 6 months, there is a consistent dose-dependent reduction in regional perfusion. The average percent decline in regional perfusion was 10% at 15–20 Gy, 20% at 20–25 Gy, and 30% at 25–30 Gy representing a relatively linear dose response with an approximate 2% reduction per Gray for doses in excess of 10 Gy. There was a subtle increase in perfusion in the lung receiving <10 Gy. Conclusion: Hypo-fractionated stereotactic RT appears to cause a dose-dependent reduction in regional lung perfusion. There appears to be a threshold effect with no apparent perfusion loss at doses <10 Gy, though this might be in part due to the normalization technique used. Additional data is needed from a larger number of patients to better assess this issue. This sort of data can be used to assist optimizing RT treatment plans that minimize the risk of lung injury. Partly supported by the NIH (CA69579) and the Lance Armstrong

  7. Lung cancer symptoms and pulse oximetry in the prognostic assessment of patients with lung cancer

    Directory of Open Access Journals (Sweden)

    Harada Cecilia M


    Full Text Available Abstract Background Medical oncologists continue to use performance status as a proxy for quality of life (QOL measures, as completion of QOL instruments is perceived as time consuming, may measure aspects of QOL not affected by cancer therapy, and interpretation may be unclear. The pulse oximeter is widely used in clinical practice to predict cardiopulmonary morbidity after lung resection in cancer patients, but little is known on its role outside the surgical setting. We evaluated whether the Lung Cancer Symptom Scale and pulse oximetry may contribute to the evaluation of lung cancer patients who received standard anticancer therapy. Methods We enrolled forty-one consecutive, newly diagnosed, patients with locally advanced or metastatic lung cancer in this study. We developed a survival model with the variables gender, age, histology, clinical stage, Karnofsky performance status, wasting, LCSS symptom scores, average symptom burden index, and pulse oximetry (SpO2. Results Patient and observer-rated scores were correlated, except for the fatigue subscale. The median SpO2 was 95% (range: 86 to 98, was unrelated to symptom scores, and was weakly correlated with observer cough scores. In a multivariate survival model, SpO2 > 90% and patient scores on the LCSS appetite and fatigue subscales were independent predictors of survival. Conclusion LCSS fatigue and appetite rating, and pulse oximetry should be studied further as prognostic factors in lung cancer patients.

  8. The value of nitrogen washout/washin method in assessing alveolar recruitment volume in acute lung injury patients

    Institute of Scientific and Technical Information of China (English)



    Objective To evaluate the precision and feasibility of nitrogen washout/washin method in assessing lung recruitment of acute lung injury(ALI)patients.Methods Fifteen ALI patients underwent mechanical ventilation

  9. 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


    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.

  10. Beryllium: genotoxicity and carcinogenicity. (United States)

    Gordon, Terry; Bowser, Darlene


    Beryllium (Be) has physical-chemical properties, including low density and high tensile strength, which make it useful in the manufacture of products ranging from space shuttles to golf clubs. Despite its utility, a number of standard setting agencies have determined that beryllium is a carcinogen. Only a limited number of studies, however, have addressed the underlying mechanisms of the carcinogenicity and mutagenicity of beryllium. Importantly, mutation and chromosomal aberration assays have yielded somewhat contradictory results for beryllium compounds and whereas bacterial tests were largely negative, mammalian test systems showed evidence of beryllium-induced mutations, chromosomal aberrations, and cell transformation. Although inter-laboratory differences may play a role in the variability observed in genotoxicity assays, it is more likely that the different chemical forms of beryllium have a significant effect on mutagenicity and carcinogenicity. Because workers are predominantly exposed to airborne particles which are generated during the machining of beryllium metal, ceramics, or alloys, testing of the mechanisms of the mutagenic and carcinogenic activity of beryllium should be performed with relevant chemical forms of beryllium.

  11. Mechanisms, assessment and therapeutic implications of lung hyperinflation in COPD. (United States)

    Rossi, Andrea; Aisanov, Zaurbek; Avdeev, Sergey; Di Maria, Giuseppe; Donner, Claudio F; Izquierdo, José Luis; Roche, Nicolas; Similowski, Thomas; Watz, Henrik; Worth, Heinrich; Miravitlles, Marc


    The main complaint of patients with chronic obstructive pulmonary disease (COPD) is shortness of breath with exercise, that is usually progressive. The principal mechanism that explains this symptom is the development of lung hyperinflation (LH) which is defined by an increase of functional residual capacity (FRC) above predicted values. Patients with COPD may develop static LH (sLH) because of destruction of pulmonary parenchyma and loss of elastic recoil. In addition, dynamic LH (dLH) develops when patients with COPD breathe in before achieving a full exhalation and, as a consequence, air is trapped within the lungs with each further breath. Dynamic LH may also occur at rest but it becomes clinically relevant during exercise and exacerbation. Lung hyperinflation may have an impact beyond the lungs and the effects of LH on cardiovascular function have been extensively analysed. The importance of LH makes its identification and measurement crucial. The demonstration of LH in COPD leads to the adoption of strategies to minimise its impact on the daily activities of patients. Several strategies reduce the impact of LH; the use of long-acting bronchodilators has been shown to reduce LH and improve exercise capacity. Non pharmacologic interventions have also been demonstrated to be useful. This article describes the pathophysiology of LH, its impact on the lungs and beyond and reviews the strategies that improve LH in COPD.

  12. Residential radon-222 exposure and lung cancer: exposure assessment methodology. (United States)

    Field, R W; Steck, D J; Lynch, C F; Brus, C P; Neuberger, J S; Kross, B C


    Although occupational epidemiological studies and animal experimentation provide strong evidence that radon-222 (222Rn) progeny exposure causes lung cancer, residential epidemiological studies have not confirmed this association. Past residential epidemiological studies have yielded contradictory findings. Exposure misclassification has seriously compromised the ability of these studies to detect whether an association exists between 222Rn exposure and lung cancer. Misclassification of 222Rn exposure has arisen primarily from: 1) detector measurement error; 2) failure to consider temporal and spatial 222Rn variations within a home; 3) missing data from previously occupied homes that currently are inaccessible; 4) failure to link 222Rn concentrations with subject mobility; and 5) measuring 222Rn gas concentration as a surrogate for 222Rn progeny exposure. This paper examines these methodological dosimetry problems and addresses how we are accounting for them in an ongoing, population-based, case-control study of 222Rn and lung cancer in Iowa.

  13. The comet assay with multiple mouse organs: comparison of comet assay results and carcinogenicity with 208 chemicals selected from the IARC monographs and U.S. NTP Carcinogenicity Database. (United States)

    Sasaki, Y F; Sekihashi, K; Izumiyama, F; Nishidate, E; Saga, A; Ishida, K; Tsuda, S


    The comet assay is a microgel electrophoresis technique for detecting DNA damage at the level of the single cell. When this technique is applied to detect genotoxicity in experimental animals, the most important advantage is that DNA lesions can be measured in any organ, regardless of the extent of mitotic activity. The purpose of this article is to summarize the in vivo genotoxicity in eight organs of the mouse of 208 chemicals selected from International Agency for Research on Cancer (IARC) Groups 1, 2A, 2B, 3, and 4, and from the U.S. National Toxicology Program (NTP) Carcinogenicity Database, and to discuss the utility of the comet assay in genetic toxicology. Alkylating agents, amides, aromatic amines, azo compounds, cyclic nitro compounds, hydrazines, halides having reactive halogens, and polycyclic aromatic hydrocarbons were chemicals showing high positive effects in this assay. The responses detected reflected the ability of this assay to detect the fragmentation of DNA molecules produced by DNA single strand breaks induced chemically and those derived from alkali-labile sites developed from alkylated bases and bulky base adducts. The mouse or rat organs exhibiting increased levels of DNA damage were not necessarily the target organs for carcinogenicity. It was rare, in contrast, for the target organs not to show DNA damage. Therefore, organ-specific genotoxicity was necessary but not sufficient for the prediction of organ-specific carcinogenicity. It would be expected that DNA crosslinkers would be difficult to detect by this assay, because of the resulting inhibition of DNA unwinding. The proportion of 10 DNA crosslinkers that was positive, however, was high in the gastrointestinal mucosa, stomach, and colon, but less than 50% in the liver and lung. It was interesting that the genotoxicity of DNA crosslinkers could be detected in the gastrointestinal organs even though the agents were administered intraperitoneally. Chemical carcinogens can be classified

  14. Science, politics, and health in the brave new world of pharmaceutical carcinogenic risk assessment: technical progress or cycle of regulatory capture? (United States)

    Abraham, John; Ballinger, Rachel


    The carcinogenicity (cancer-inducing potential) of pharmaceuticals is an important risk factor for health when considering whether thousands of patients on drug trials or millions/billions of consumers in the marketplace should be exposed to a new drug. Drawing on fieldwork involving over 50 interviews and documentary research spanning 2002-2010 in Europe and the US, and on regulatory capture theory, this article investigates how the techno-regulatory standards for carcinogenicity testing of pharmaceuticals have altered since 1998. It focuses on the replacement of long-term carcinogenicity tests in rodents (especially mice) with shorter-term tests involving genetically-engineered mice (GEM). Based on evidence regarding financial/organizational control, methodological design, and interpretation of the validation and application of these new GEM tests, it is argued that regulatory agencies permitted the drug industry to shape such validation and application in ways that prioritized commercial interests over the need to protect public health. Boundary-work enabling industry scientists to define some standards of public-health policy facilitated such capture. However, as the scientific credibility of GEM tests as tools to protect public health by screening out carcinogens became inescapably problematic, a regulatory resurgence, impelled by reputational concerns, exercised more control over industry's construction and use of the tests, The extensive problems with GEM tests as public-health protective regulatory science raises the spectre that alterations to pharmaceutical carcinogenicity-testing standards since the 1990s may have been boundary-work in which the political project of decreasing the chance that companies' products are defined as carcinogenic has masqueraded as techno-science.

  15. Workshop on problem areas associated with developing carcinogen guidelines

    Energy Technology Data Exchange (ETDEWEB)


    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)

  16. Butyrylcholinesterase in guinea pig lung lavage: a novel biomarker to assess lung injury following inhalation exposure to nerve agent VX. (United States)

    Graham, Jacob R; Wright, Benjamin S; Rezk, Peter E; Gordon, Richard K; Sciuto, Alfred M; Nambiar, Madhusoodana P


    Respiratory disturbances play a central role in chemical warfare nerve agent (CWNA) induced toxicity; they are the starting point of mass casualty and the major cause of death. We developed a microinstillation technique of inhalation exposure to nerve agent VX and assessed lung injury by biochemical analysis of the bronchoalveolar lavage fluid (BALF). Here we demonstrate that normal guinea pig BALF has a significant amount of cholinesterase activity. Treatment with Huperzine A, a specific inhibitor of acetylcholinesterase (AChE), showed that a minor fraction of BALF cholinesterase is AChE. Furthermore, treatment with tetraisopropyl pyrophosphoramide (iso-OMPA), a specific inhibitor of butyrylcholinesterase (BChE), inhibited more than 90% of BChE activity, indicating the predominance of BChE in BALF. A predominance of BChE expression in the lung lavage was seen in both genders. Substrate specific inhibition indicated that nearly 30% of the cholinesterase in lung tissue homogenate is AChE. BALF and lung tissue AChE and BChE activities were strongly inhibited in guinea pigs exposed for 5 min to 70.4 and 90.4 microg/m3 VX and allowed to recover for 15 min. In contrast, BALF AChE activity was increased 63% and 128% and BChE activity was increased 77% and 88% after 24 h of recovery following 5 min inhalation exposure to 70.4 microg/m3 and 90.4 mg/m3 VX, respectively. The increase in BALF AChE and BChE activity was dose dependent. Since BChE is synthesized in the liver and present in the plasma, an increase in BALF indicates endothelial barrier injury and leakage of plasma into lung interstitium. Therefore, a measure of increased levels of AChE and BChE in the lung lavage can be used to determine the chronology of barrier damage as well as the extent of lung injury following exposure to chemical warfare nerve agents.

  17. Techniques for carcinogenicity studies. (United States)

    Weisburger, E K


    Short-term tests to detect genetic, chromosomal, or DNA damage are now required by regulatory agencies for any new compound proposed for commercial production. Furthermore, full-scale carcinogenicity tests may be required for certain compounds. In this circumstance, the compound-related factors including stability, purity, physical properties, and chemical structure and reactivity must be considered. Animal factors include species and strain of test animal, route of administration, age, sex, diet, and spontaneous tumor incidence. A team of qualified investigators with experience in various disciplines is required to conduct the studies properly. Quality control measures and adherence to the code of good laboratory practice are also necessary during all phases of the study. The investment in a carcinogenicity study therefore becomes fairly substantial in terms of both time and money.

  18. Food derived carcinogenic amnoimidazoazaarenes

    DEFF Research Database (Denmark)

    Frandsen, Henrik

    Carcinogenic aminoimidazoazaarenes are formed during cooking of meat and fish. Important factors for the formation of these compounds are meat type, cooking temperature and time. The compounds are genotoxic in bacterial and mammalian cells. In animal feeding studies the compounds tested so far we...... of the exocyclic amino group. Estimations of human cancer risk have indicated that ingestion of food containing aminoimidazoazaarenes are of importance....

  19. Assessment of genotoxic potential of Cr(VI) in the mouse duodenum: an in silico comparison with mutagenic and nonmutagenic carcinogens across tissues. (United States)

    Thompson, Chad M; Gregory Hixon, J; Proctor, Deborah M; Haws, Laurie C; Suh, Mina; Urban, Jonathan D; Harris, Mark A


    In vitro studies on hexavalent chromium [Cr(VI)] indicate that reduced forms of this metal can interact with DNA and cause mutations. Recently, Cr(VI) was shown to induce intestinal tumors in mice; however, Cr(VI) elicited redox changes, cytotoxicity and hyperplasia - suggesting involvement of tissue injury rather than direct mutagenesis. Moreover, toxicogenomic analyses indicated limited evidence for DNA damage responses. Herein, we extend these toxicogenomic analyses by comparing the gene expression patterns elicited by Cr(VI) with those of four mutagenic and four nonmutagenic carcinogens. To date, toxicogenomic profiles for mutagenic and nonmutagenic duodenal carcinogens do not exist, thus duodenal gene changes in mice were compared to those elicited by hepatocarcinogens. Specifically, duodenal gene changes in mice following exposure to Cr(VI) in drinking water were compared to hepatic gene changes previously identified as potentially discriminating mutagenic and nonmutagenic hepatocarcinogens. Using multivariate statistical analyses (including logistic regression classification), the Cr(VI) gene responses clustered apart from mutagenic carcinogens and closely with nonmutagenic carcinogens. These findings are consistent with other intestinal data supporting a nonmutagenic mode of action (MOA). These findings may be useful as part of a full weight of evidence MOA evaluation for Cr(VI)-induced intestinal carcinogenesis. Limitations to this analysis will also be discussed.

  20. 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.;


    The potential of Xpa(-/-) and Xpa(-/-)/p53(+/-) mice for short-term carcinogenicity assays was evaluated with di(2-ethylhexyl)phthalate (DEHP). Groups of 15 male and female Xpa(-/-) mice, received diets containing 0, 1,500, 3, 000, or 6,000 ppm DEHP, and wild-type (WT) and Xpa(-/-)/p53(+/-) mice 0...

  1. The ISS Carcinogens Data Bank (BDC). (United States)

    Binetti, Roberto; Ceccarelli, Federica; Costamagna, Francesca Marina; D'Angiolini, Antonella; Fabri, Alessandra; Ferri, Maurizio; Riva, Giovanni; Roazzi, Paolo; Trucchi, Daniela; Marcello, Ida


    The Data Bank on Carcinogens (Banca Dati Cancerogeni, BDC) is a factual data bank, available on the Istituto Superiore di Sanità website, aimed at supporting the risk management decision making of central and local administrators. It can also represent a valuable tool for industry. The available information on carcinogenicity evaluations/classifications produced by European Union and by other institutions (IARC, USEPA, NTP, CCTN) is presented in a concise form accompanied by bibliographic references enabling the users to consult the original sources and, in some cases, to be directly connected to the relevant website. The classifications carried out by each organization in accordance with its own criteria assign the examined agents to specific qualitative categories and do not include quantitative assessment. BDC intends to provide an easy tool for experts, researchers and risk managers dealing with carcinogenic agents.

  2. 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


    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......The aim of this study was to provide an overview of the literature available on dynamic contrast-enhanced computed tomography (DCE-CT) as a tool to evaluate treatment response in patients with lung cancer. This systematic review was compiled according to Preferred Reporting Items for Systematic...... 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...

  3. Spiritual Assessment in a Patient With Lung Cancer. (United States)

    Borneman, Tami


    CASE STUDY  Mr. G., an 82-year-old retired European man, was diagnosed with stage 4 non-small cell lung cancer (NSCLC) and recently enrolled on a phase II clinical trial. He is married and has two adult children, who are very supportive. He and his wife described themselves as nonpracticing Catholics. He had never smoked, and there was no personal or family history of cancer. Fatigue was the main side effect from the clinical trial drugs, necessitating frequent periods of rest throughout the day and ultimately requiring dose reduction. His left leg was edematous and painful, and he was diagnosed with and treated for deep-vein thrombosis. Over time, these symptoms resolved, and Mr. G. enjoyed a fairly normal quality of life (QOL). He continued to do well for almost a year, but then his cancer progressed and his performance status began to decline. When offered treatment options, he elected to discontinue the clinical trial, take a break, and then initiate single-agent chemotherapy. Mr. G. was enrolled in a palliative care research study that provided patient-tailored education by an advanced practitioner (AP). The education addressed each QOL domain: physical, psychological, social, and spiritual. When the AP connected with Mr. G. during one of his clinic appointments, he appeared very concerned. He shared that he previously had lived in a communist country and now that he was in the United States, he was afraid of losing his insurance and having to stop treatment. The conversation was interrupted as he was called in for his appointment, yet he consented to talk about the matter further by telephone. The AP contacted Mr. G. the next day. He shared a glimpse of his childhood and experience in his homeland to try to explain his current fears. After reassuring him that his insurance would not be withdrawn, the AP asked whether he would be willing to talk about his life before coming to the United States more than 50 years ago. She wanted to assess where he was

  4. Occupational Lung Cancer Surveillance in South Korea, 2006-2009 (United States)

    Kim, Hwan-Cheol; Ryu, Jeong-Seon; Won, Jong Uk; Moon, Jai Dong; Kim, Young-Chul; Koh, Sang Baek; Yong, Suk Joong; Kim, Soo Geun; Park, Jae Yong; Kim, Inah; Kim, Jung Il; Kim, Jung Won; Lee, Eui-cheol; Kim, Hyoung-Ryoul; Kim, Dae-Hwan; Kang, Dong Mug; Hong, Yun-Chul


    Objectives The lung cancer mortality in Korea has increased remarkably during the last 20 years, and has been the first leading cause of cancer-related deaths since 2000. The aim of the current study was to examine the time trends of occupational lung cancer and carcinogens exposure during the period 2006-2009 in South Korea, by assessing the proportion of occupational burden. Methods We defined occupational lung cancer for surveillance, and developed a reporting protocol and reporting website for the surveillance of occupational lung cancer. The study patients were chosen from 9 participating university hospitals in the following 7 areas: Seoul, Incheon, Wonju, Daejeon, Daegu, Busan, and Gwangju. Results The combined proportion of definite and probable occupational lung cancer among all lung cancers investigated in this study was 10.0%, 8.6%, 10.7%, and 15.8% in the years 2006 to 2009, respectively, with an average of 11.7% over the four-year study period. The main carcinogens were asbestos, crystalline silica, radon, polyaromatic hydrocarbons (PAHs), diesel exhaust particles, chromium, and nickel. Conclusion We estimated that about 11.7% of the incident lung cancer was preventable. This reveals the potential to considerably reduce lung cancer by intervention in occupational fields. PMID:22953173

  5. 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


    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

  6. Standards for Quantitative Assessment of Lung Structure: The Dawn of Stereopneumology

    Directory of Open Access Journals (Sweden)

    Georgios T. Stathopoulos


    Full Text Available SUMMARY. The lungs are complex 3D structuresstudied in the clinic and the laboratory using histologic or imaging sections. Although such 2D analyses of lung structure are considered “gold standards”, the information conveyed is often insufficient and does not represent the whole organ. Stereology, the mathematical approach to the analysis of 3D structures via 2D sampling and morphometry, the practical application of stereology, provide solutions to this problem, but had until recently not been systematically adoptedin pneumology. In an effort of minimizing the above-mentioned methodological problems and of standardizing the quantitative assessment of lung structure, the American Thoracic Society and European Respiratory Society formed a task force, which recently published its findings. The task force aimed at comprehensively reviewing current stereologic methods for lung morphometry, formulating practical guidelines for using unbiased methods for basic and translational research of lung structure, and examining the extensions of stereologic methods on non-invasive imaging of lung architecture. In the statement of the task force are included useful directives with important application in the laboratory and the clinic, the most pertinent of which are discussed in the present mini-review. Pneumon 2010, 23(2:141-152.

  7. Carcinogenic compounds in alcoholic beverages: an update. (United States)

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


    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.

  8. Cannabis and tobacco smoke are not equally carcinogenic

    Directory of Open Access Journals (Sweden)

    Melamede Robert


    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.

  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. (United States)

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


    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. 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 (United States)

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


    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, carcinogenic polyaromatic hydrocarbons (PAH), volatile aldehydes, and carbon monoxide (CO) for cigarettes and narghile (shisha, hookah) waterpipes. These smoke constituents are associated with a variety of cancers, and heart and pulmonary diseases, and span the volatility range found in 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.

  11. Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation. (United States)

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


    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.

  12. 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)


    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.)

  13. Quantitative Risk Assessment for Lung Cancer from Exposure to Metal Ore Dust

    Institute of Scientific and Technical Information of China (English)



    To quantitatively assess risk for lung cancer of metal miners,a historical cohort study was conducted.The cohort consisted of 1113 miners who were employed to underground work for at least 12 months between January 1,1960and December,12,1974,According to the records or dust concentration,a cumulative dust dose of each miner in the cohort was estimated.There wer 162 deaths in total and 45 deaths from lung cancer with a SMR of 2184,The SMR for lung cancer increased from 1019 for those with cumulative dust of less than 500mg-year to 2469 for those with the dose of greater than 4500mg-year.Furthermore,the risk in the highest category of combined cumulative dust dose and cigarette smoking was 46-fold greater than the lowest category of dust dose and smoking.This study showed that there was an exposure-response relationship between metal ore dust and lung cancer,and an interaction of lung cancer between smoking and metal ore dust exposure.

  14. Genotoxicity and carcinogenicity risk of carbon nanotubes. (United States)

    Toyokuni, Shinya


    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.

  15. 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


    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

  16. [Cannabis smoking and lung cancer]. (United States)

    Underner, M; Urban, T; Perriot, J; de Chazeron, I; Meurice, J-C


    Cannabis is the most commonly smoked illicit substance in the world. It can be smoked alone in plant form (marijuana) but it is mainly smoked mixed with tobacco. The combined smoking of cannabis and tobacco is a common-place phenomenon in our society. However, its use is responsible for severe pulmonary consequences. The specific impact of smoking cannabis is difficult to assess precisely and to distinguish from the effect of tobacco. Marijuana smoke contains polycyclic aromatic hydrocarbons and carcinogens at higher concentration than tobacco smoke. Cellular, tissue, animal and human studies, and also epidemiological studies, show that marijuana smoke is a risk factor for lung cancer. Cannabis exposure doubles the risk of developing lung cancer. This should encourage clinicians to identify cannabis use and to offer patients support in quitting.

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

    Directory of Open Access Journals (Sweden)

    Shahrzad M Lari


    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

  18. Acrylonitrile: a suspected human carcinogen. (United States)

    Koerselman, W; van der Graaf, M


    The literature on carcinogenicity of acrylonitrile (an important intermediate in the chemical industry) is reviewed. The three main conclusions are: (1) Acrylonitrile has genotoxic effects in various tests in microorganisms and in mammal cells. (2) Chronic exposure to acrylonitrile causes tumours in rats. (3) Results of epidemiological studies indicate that acrylonitrile may be a human carcinogen. From this it is clear that acrylonitrile is very probably carcinogenic to humans. Therefore the authors plead for a reduction of acrylonitrile standards to the lowest practicable limit.

  19. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Directory of Open Access Journals (Sweden)

    Hideki Wanibuchi


    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.

  20. 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: [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan)


    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.

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

    Directory of Open Access Journals (Sweden)

    Louise S. Strauch


    Full Text Available The aim of this study was to provide an overview of the literature available on dynamic contrast-enhanced computed tomography (DCE-CT as a tool to evaluate treatment response in patients with lung cancer. This systematic review was compiled according to Preferred Reporting Items for Systematic 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 yielded 651 publications, and 16 articles were included in this study. The articles were divided into groups of treatment. In studies where patients were treated with systemic chemotherapy with or without anti-angiogenic drugs, four out of the seven studies found a significant decrease in permeability 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 are important perfusion values for predicting treatment outcome. However, the heterogeneity in scan protocols, scan parameters, and time between scans makes it difficult to compare the included studies.

  2. Non-contrast-enhanced preoperative assessment of lung perfusion in patients with non-small-cell lung cancer using Fourier decomposition magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sommer, Gregor, E-mail: [Department of Radiology (E010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Clinic of Radiology and Nuclear Medicine, University of Basel Hospital, Petersgraben 4, 4031 Basel (Switzerland); Bauman, Grzegorz, E-mail: [Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Department of Medical Physics in Radiology (E020), German Cancer Research Center (DKFZ), Heidelberg (Germany); Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, Madison, 53705 WI (United States); Koenigkam-Santos, Marcel, E-mail: [Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Department of Radiology, University Hospital of the School of Medicine of Ribeirao Preto – University of Sao Paulo, Ribeirao Preto (Brazil); Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik Heidelberg gGmbH, Amalienstr. 5, 69126 Heidelberg (Germany); Draenkow, Christopher, E-mail: [Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Department of Surgery, Thoraxklinik Heidelberg gGmbH, Amalienstr. 5, 69126 Heidelberg (Germany); Heussel, Claus Peter, E-mail: [Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research, Heidelberg (Germany); Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik Heidelberg gGmbH, Amalienstr. 5, 69126 Heidelberg (Germany); and others


    Objective: To investigate non-contrast-enhanced Fourier decomposition MRI (FD MRI) for assessment of regional lung perfusion in patients with Non-Small-Cell Lung Cancer (NSCLC) in comparison to dynamic contrast-enhanced MRI (DCE MRI). Methods: Time-resolved non-contrast-enhanced images of the lungs were acquired prospectively in 15 patients using a 2D balanced steady-state free precession (b-SSFP) sequence. After non-rigid registration of the native image data, perfusion-weighted images were calculated by separating periodic changes of lung proton density at the cardiac frequency using FD. DCE MRI subtraction datasets were acquired as standard of reference. Both datasets were analyzed visually for perfusion defects. Then segmentation analyses were performed to describe perfusion of pulmonary lobes semi-quantitatively as percentages of total lung perfusion. Overall FD MRI perfusion signal was compared to velocity-encoded flow measurements in the pulmonary trunk as an additional fully quantitative reference. Results: Image quality ratings of FD MRI were significantly inferior to those of DCE MRI (P < 0.0001). Sensitivity, specificity, and accuracy of FD MRI for visual detection of perfusion defects were 84%, 92%, and 91%. Semi-quantitative evaluation of lobar perfusion provided high agreement between FD MRI and DCE MRI for both entire lungs and upper lobes, but less agreement in the lower parts of both lungs. FD perfusion signal showed high linear correlation with pulmonary arterial blood flow. Conclusion: FD MRI is a promising technique that allows for assessing regional lung perfusion in NSCLC patients without contrast media or ionizing radiation. However, for being applied in clinical routine, image quality and robustness of the technique need to be further improved.

  3. [Fiber as a carcinogenic agent]. (United States)

    Pott, F


    According to the findings that long, thin, and durable fibres have a high carcinogenic potency after intrapleural and intraperitoneal administration, the elongated shape of a particle represents a carcinogenic agent; this physical phenomenon is a special cause of cancer. It induces a biological process which can lead to cancer by several as yet unknown steps. However, the properties of the material the fibres are made of determine the carcinogenic potency of a fibre in a secondary way although they do not seem to be responsible for the true carcinogenic agent. For example, these properties determine the degree of solubility and flexibility. The persistence of fibres in the tissue is a very important property with regard to their carcinogenic effect because the formation of a tumour takes many years or some decades. It can be assumed that a fibre has to remain by the bronchial or serosa tissue until the induction of tumour cells occurs. If this hypothesis is correct, there could be a "durability threshold value" for fibres whose length and diameter would otherwise indicate a high carcinogenic potency. There are indications that other fibre properties apart from length, diameter and durability are important for tumour induction, however, at present, they cannot be included in a definition of carcinogenic fibres. It is proposed to classify all natural and man-made mineral fibres with an aspect ratio of greater than 5:1 as carcinogenic when they are longer than 3 microns, thinner than 1 micron (or can split into such fine fibres) and when they can persist in the tissue for more than 3 years.

  4. The Inflammatory-Nutritional Index: assessing nutritional status and prognosis in gastrointestinal and lung cancer patients


    Carla Alberici Pastore; Silvana Paiva Orlandi; Maria Cristina Gonzalez


    Objective: To evaluate the prognostic capacity of the Inflammatory-Nutritional Index (INI) in gastrointestinal and lung cancer patients. Methods: Longitudinal study, including patients from a chemotherapy service in Brazil, between July 2008 and May 2010. INI (Albumin/CRP) and nutritional status (by Subjective Global Assessment - SGA) were evaluated. Risk INI was defined as lower than 0.35. The mean follow-up of survival was 1.6 year. Statistical analyses were performed using Stata 11.1™. Res...

  5. Chrysotile, tremolite and carcinogenicity. (United States)

    McDonald, J C; McDonald, A D


    It has been suspected for many years that amphibole fibres in the tremolite series, a low level contaminant of chrysotile asbestos, may contribute disproportionately to the incidence of mesothelioma and perhaps other exposure-related cancers. A cohort of some 11,000 Quebec chrysotile workers, 80% of whom have now died, provided the opportunity to examine this hypothesis further. An analysis was made of deaths from mesothelioma (21), cancers of the lung (262), larynx (15), stomach (99), and colon and rectum (76), in men employed by the largest company in Thetford Mines, with closely matched referents. Risks were estimated by logistic regression for these five cancers in two groups of mines--five mines located centrally and ten mines located peripherally; tremolite contamination had been demonstrated to be some four times higher in the former than in the latter. Odds ratios for work in the central mines were raised substantially and significantly for mesothelioma and lung cancer, but not for the gastric, intestinal or laryngeal cancer sites. In the peripheral mines, there was little or no evidence of increased risk for any of the five cancers. The hypothesis that, because of the difference in distribution of fibrous tremolite, cancer risks in the central area would be greater than in the periphery was thus substantiated. That the explanation may lie in the greater biopersistence of amphibole fibres than chrysotile is important in framing policies for the use and control of asbestos and is directly relevant to the selection of man-made mineral fibre substitutes.

  6. Validity of lamellar body count as a fetal lung maturity assessment in twin pregnancy. (United States)

    Tsuda, Hiroyuki; Kotani, Tomomi; Sumigama, Seiji; Kawabata, Ichiro; Takahashi, Yuichiro; Iwagaki, Shigenori; Kigoshi, Kaori; Kikkawa, Fumitaka


    Fetal lung maturity assessment in twin pregnancy has been discussed, but is still controversial. The purpose of this study is to predict the occurrence of respiratory distress syndrome (RDS) using lamellar body count (LBC) and analyze the validity of LBC for fetal lung maturity assessment in twin pregnancy. Three-hundred two amniotic fluid samples were obtained at cesarean section from 29 to 38 weeks of gestation. Samples were analyzed immediately with no centrifugation and the number of lamellar bodies was counted using a platelet channel on the Sysmex SF-3000. There were 18 neonates (6.0%) suffering from RDS. An LBC cut-off value of 2.95×10⁴/μL resulted in 91.5% sensitivity and 83.3% specificity for predicting RDS. This cut-off value for predicting RDS was the same as that in singleton pregnancy. Moreover, the median LBC value in RDS cases was significantly lower than in non-RDS cases (1.50±1.1×10⁴/μL vs. 10.6±7.5×10⁴/μL; ptwin pregnancy and also the largest study on fetal lung maturity assessment in twin pregnancy. An LBC value of >2.95×10⁴/μL means reassuring findings for RDS even in twin pregnancy. We believe the data in this study provide valuable, new information for the management of twin pregnancies.

  7. Identification of cytochrome P450 enzymes critical for lung tumorigenesis by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): insights from a novel Cyp2abfgs-null mouse. (United States)

    Li, Lei; Megaraj, Vandana; Wei, Yuan; Ding, Xinxin


    Cytochrome P450 (P450) enzymes encoded by the mouse Cyp2abfgs gene cluster are preferentially expressed in the respiratory tract. Previous studies have demonstrated that pulmonary P450-mediated bioactivation is necessary for lung tumorigenesis induced by the tobacco-specific lung procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and that CYP2A5 mediates a noteworthy fraction, but not all, of NNK bioactivation in the lung. The aim of this study was to determine whether other P450s encoded by the Cyp2abfgs gene cluster also play significant roles in NNK lung tumorigenesis. A novel Cyp2abfgs-null mouse was generated, in which all Cyp2a, 2b, 2g, 2f and 2s genes are deleted. The Cyp2abfgs-null mouse was viable, fertile and without discernible physiological abnormalities or compensatory increases in the expression of other P450s. NNK bioactivation in vitro and NNK-induced DNA adduction and lung tumorigenesis in vivo were determined for wild-type (WT) and Cyp2abfgs-null mice; the results were compared with previous findings from Cyp2a5-null mice. The Cyp2abfgs-null mice exhibited significantly lower rates of NNK bioactivation in lung and liver microsomes, compared with either WT or Cyp2a5-null mice. The levels of lung O(6)-methyl guanine DNA adduct were also substantially reduced in Cyp2abfgs-null mice, compared with either WT or Cyp2a5-null mice. Moreover, the Cyp2abfgs-null mice were largely resistant to NNK-induced lung tumorigenesis at both low (50mg/kg) and high (200mg/kg) NNK doses, in contrast to the WT or Cyp2a5-null mice. These results indicate for the first time that, collectively, the CYP2A, 2B, 2F, 2G, and 2S enzymes are indispensable for NNK-induced lung tumorigenesis.

  8. Linearity of dose-response relationships for human carcinogenic exposures

    Energy Technology Data Exchange (ETDEWEB)

    Smith, A.H. (Univ. of California, Berkeley (USA))

    The shape of dose-response relationships is a critical factor in considering cancer risks for the work place and environmental exposure to carcinogens. Markedly different risk estimates result from assumptions of linearity versus sublinear and threshold assumptions. This paper presents evidence that the relationship between the relative risk of development of cancer and the dose rate to carcinogenic exposures is frequently linear with no evidence for thresholds. Dose-response relationships from four studies of asbestos and lung cancer were examined, all of which were consistent with a linear relationship. Analysis of the relationship between the relative risk of lung cancer and exposure to nickel in a smelter study, selected because of relatively good exposure data, demonstrated a close agreement with a linear relationship. The relationship between the level of arsenic in drinking wter and the prevalence of skin cancer also was linear for males in the highest prevalence age group in Taiwan, although there was some evidence of sublinearity for females and younger persons. Also, the relationships between the number of cigarettes smoked per day and the relative risk of lung cancer was very close to linear in many studies. The analysis of these and other studies involving human exposure to carcinogens provides empirical evidence for linearity when the response variable is a rate ratio measure, rather than a risk difference measure. Linearity in dose-response is biologically plausible, without invoking a one-hit model. Except in special circumstances. the epidemiological evidence supports linear extrapolation of cancer relative risks.

  9. A functional assessment of patients two years after lung transplantation in Poland (United States)

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


    The aim of the study The aim of the study was to assess the long-term results of lung transplantation (LT) in Poland two years after the procedure. Material and methods 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). Results 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. Conclusions 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. PMID:26336415

  10. Carcinogenicity and other health effects of acrylonitrile with reference to occupational exposure limit. (United States)

    Sakurai, H


    The occupational exposure limit for acrylonitrile (AN) has been set by many organizations on the basis of its carcinogenicity. However, recent epidemiological studies do not afford evidence supporting the hypothesis that AN is carcinogenic to humans. Review of the 18 published cohort studies revealed that, although there is not adequate evidence in humans for carcinogenicity of AN, the possibility of a causal association between high exposure to AN and lung cancer in humans cannot be excluded. It was pointed out that carcinogenic potential of AN may be weak, if any, to humans, and the current occupational exposure limit (OEL) for AN of 2 ppm was evaluated as appropriate in view of AN exposure levels reported by epidemiological studies. Based also on review of the literature on health effects other than carcinogenicity, it was concluded that the current OEL for AN is a reasonable value and there is no need for a revision at present.

  11. An assessment of the possible extent of confounding in epidemiological studies of lung cancer risk among roofers

    Energy Technology Data Exchange (ETDEWEB)

    Mundt, D.J.; van Wijngaarden, E.; Mundt, K.A. [ENVIRON International Corp., Amherst, MA (United States)


    We evaluated the likelihood and extent to which the observed increased risk of lung cancer may be due to confounding (a mixing of effects of multiple exposures) by co-exposure to other potential carcinogens present in roofing or to lifestyle variables. We conducted a review of the epidemiological and industrial hygiene literature of asphalt-exposed workers. Peer-reviewed epidemiological studies of asphalt fumes, related occupational exposures, and confounding factors were identified from MEDLINE (1966 early 2004). Industrial hygiene studies of asphalt workers were identified through MEDLINE, publicly available government documents, and asphalt industry documents. Using well established statistical methods, we quantified the extent to which lung cancer relative risk estimates among roofers reflect confounding from other exposures, using different prevalence and risk scenarios. The relative risk of lung cancer varied from 1.2 to 5.0 in 13 epidemiological studies of roofers; most studies reported a relative risk between 1.2 and 1.4. Smoking, asbestos and coal tar were the most likely confounders, but the prevalence of these factors varied over time. The results of the study indicate that much of the observed risk reported in epidemiological studies of cancer among roofers is well within the range of what may have resulted from confounding by reasonable and expected levels of smoking, asbestos or coal tar. This may be particularly true for those studies that did not adjust for these confounders and where the exposure was defined as employment in the roofing industry. In addition to poorly defined asphalt exposure, uncontrolled confounding cannot reliably be ruled out in studies of lung cancer among asphalt-exposed roofers. Therefore, it is not possible to conclude whether roofers are at increased risk of lung cancer due to asphalt exposure.

  12. Poster — Thur Eve — 70: Automatic lung bronchial and vessel bifurcations detection algorithm for deformable image registration assessment

    Energy Technology Data Exchange (ETDEWEB)

    Labine, Alexandre; Carrier, Jean-François; Bedwani, Stéphane [Centre hospitalier de l' Université de Montréal (Canada); Chav, Ramnada; De Guise, Jacques [Laboratoire de recherche en imagerie et d' orthopédie-CRCHUM, École de technologie supérieure (Canada)


    Purpose: To investigate an automatic bronchial and vessel bifurcations detection algorithm for deformable image registration (DIR) assessment to improve lung cancer radiation treatment. Methods: 4DCT datasets were acquired and exported to Varian treatment planning system (TPS) EclipseTM for contouring. The lungs TPS contour was used as the prior shape for a segmentation algorithm based on hierarchical surface deformation that identifies the deformed lungs volumes of the 10 breathing phases. Hounsfield unit (HU) threshold filter was applied within the segmented lung volumes to identify blood vessels and airways. Segmented blood vessels and airways were skeletonised using a hierarchical curve-skeleton algorithm based on a generalized potential field approach. A graph representation of the computed skeleton was generated to assign one of three labels to each node: the termination node, the continuation node or the branching node. Results: 320 ± 51 bifurcations were detected in the right lung of a patient for the 10 breathing phases. The bifurcations were visually analyzed. 92 ± 10 bifurcations were found in the upper half of the lung and 228 ± 45 bifurcations were found in the lower half of the lung. Discrepancies between ten vessel trees were mainly ascribed to large deformation and in regions where the HU varies. Conclusions: We established an automatic method for DIR assessment using the morphological information of the patient anatomy. This approach allows a description of the lung's internal structure movement, which is needed to validate the DIR deformation fields for accurate 4D cancer treatment planning.

  13. 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: [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China)


    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

  14. [The awareness of carcinogenic effect of tobacco smoke--a questionnaire survey of students and employees of Collegium Medicum of Nicolaus Copernicus University]. (United States)

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


    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

  15. Carcinogenicity of hair dye components. (United States)

    Van Duuren, B L


    The available animal carcinogenicity data on hair dye components was reviewed. From this review it became clear that certain hair dye components, some of which are still in hair dye formulations now on the market, are animal carcinogens. The compounds of concern that are still in use are: 3-amino-4-methoxyaniline, 2-nitro-4-aminoaniline and 3-nitro-4-hydroxyaniline. Certain azo dyes formerly used, and related compounds still in use, contain the benzidine moiety. Two of these compounds, Direct Blue 6 and Direct Black 38, have been shown to be metabolized in animals to the human carcinogen benzidine. Furthermore, skin absorption studies carried out with radiolabeled hair dye components applied to animal or human skin have conclusively shown that these compounds are systemically absorbed and excreted. Known cocarcinogens such as catechol and pyrogallol, which enhance benzo(a)pyrene carcinogenicity on mouse skin, are used as hair dye components. It is not known whether such compounds will enhance the carcinogenicity of substituted aniline hair dye chemicals. The available epidemiologic data are not sufficient to link hair dye use with an increased incidence in human cancer.

  16. Does the term carcinogen send the wrong message? (United States)

    Flamm, W G; Hughes, D


    The term carcinogen has been used by scientists and health regulatory officials for decades. During the last 20 years there have been attempts to redefine the term to make it more rigorous. But, as predicted two decades ago by a benchmark-setting subcommittee of the National Cancer Advisory Board, advances in scientific understanding have brought about dramatic changes in the way we are able to view the term carcinogen. These changes, their scientific bases and their effect on defining the term carcinogen are described. An alternative to the use of the term carcinogen is suggested by the recently proposed US Environmental Agency's guidelines for cancer risk assessment which appear to be in accord with current scientific understanding and the importance of considering the factors affecting the term carcinogen. The guidelines set forth four questions, the answers to which could, in our judgment, replace the need to define or use the term carcinogen which, in light of new scientific knowledge, has become more misleading than useful.

  17. Ventilation/Perfusion Positron Emission Tomography—Based Assessment of Radiation Injury to Lung

    Energy Technology Data Exchange (ETDEWEB)

    Siva, Shankar, E-mail: [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville (Australia); Hardcastle, Nicholas [Department of Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne (Australia); Centre for Medical Radiation Physics, University of Wollongong, Wollongong (Australia); Kron, Tomas [Department of Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne (Australia); Bressel, Mathias [Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne (Australia); Callahan, Jason [Centre for Molecular Imaging, Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); MacManus, Michael P.; Shaw, Mark; Plumridge, Nikki [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Hicks, Rodney J. [Centre for Molecular Imaging, Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Medicine, University of Melbourne, Parkville (Australia); Steinfort, Daniel [Department of Medicine, University of Melbourne, Parkville (Australia); Department of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne (Australia); Ball, David L. [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne (Australia); Hofman, Michael S. [Centre for Molecular Imaging, Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Department of Medicine, University of Melbourne, Parkville (Australia)


    Purpose: To investigate {sup 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). Methods and Materials: 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). Results: 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{sup 2}=0.99, P<.01), with ventilation strongly negatively linear (r{sup 2}=0.95, P<.01). Logistic models did not provide a better fit 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. Conclusions: 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

  18. 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)


    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.)

  19. Mutagenicity, carcinogenicity, and teratogenicity of acrylonitrile. (United States)

    Léonard, A; Gerber, G B; Stecca, C; Rueff, J; Borba, H; Farmer, P B; Sram, R J; Czeizel, A E; Kalina, I


    Acrylonitrile (AN) is an important intermediary for the synthesis of a variety of organic products, such as artificial fibres, household articles and resins. Although acute effects are the primary concern for an exposure to AN, potential genotoxic, carcinogenic and teratogenic risks of AN have to be taken seriously in view of the large number of workers employed in such industries and the world-wide population using products containing and possibly liberating AN. An understanding of the effect of acrylonitrile must be based on a characterization of its metabolism as well as of the resulting products and their genotoxic properties. Tests for mutagenicity in bacteria have in general been positive, those in plants and on unscheduled DNA synthesis doubtful, and those on chromosome aberrations in vivo negative. Wherever positive results had been obtained, metabolic activation of AN appeared to be a prerequisite. The extent to which such mutagenic effects are significant in man depends, however, also on the conditions of exposure. It appears from the limited data that the ultimate mutagenic factor(s), such as 2-cyanoethylene oxide, may have little opportunity to act under conditions where people are exposed because it is formed only in small amounts and is rapidly degraded. The carcinogenic action of AN has been evaluated by various agencies and ranged from 'reasonably be anticipated to be a human carcinogen' to 'cannot be excluded', the most recent evaluation being 'possibly carcinogenic to humans'. Animal data that confirm the carcinogenic potential of AN have certain limitations with respect to the choice of species, type of tumors and length of follow up. Epidemiological studies which sometimes, but not always, yielded positive results, encounter the usual difficulties of confounding factors in chemical industries. Exposure of workers to AN should continue to be carefully monitored, but AN would not have to be considered a cancer risk to the population provided

  20. [The evaluation of carcinogenic effect in rats and mice after intraperitoneal administration of refractory ceramic fibers]. (United States)

    Krajnow, A; Lao, I; Stetkiewicz, J; Wiecek, E


    The carcinogenic effect of Langfaser and Thermowool ceramic fibres was assessed in Wistar rats and BALB/C mice. Fibres were administered into the animal peritoneal cavity in doses of 25 and 5 mg, and the animals were left for survival. Langfaser and Thermowool ceramic fibres were found carcinogenic. The carcinogenic properties of Thermowool ceramic fibre can be compared to those of Krokidoit UICC asbestos.

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

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


    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.

  2. Assessment of lung function using a non-invasive oscillating gas-forcing technique. (United States)

    Clifton, Lei; Clifton, David A; Hahn, Clive E W; Farmery, Andrew D


    Conventional methods for monitoring lung function can require complex, or special, gas analysers, and may therefore not be practical in clinical areas such as the intensive care unit (ICU) or operating theatre. The system proposed in this article is a compact and non-invasive system for the measurement and monitoring of lung variables, such as alveolar volume, airway dead space, and pulmonary blood flow. In contrast with conventional methods, the compact apparatus and non-invasive nature of the proposed method could eventually allow it to be used in the ICU, as well as in general clinical settings. We also propose a novel tidal ventilation model using a non-invasive oscillating gas-forcing technique, where both nitrous oxide and oxygen are used as indicator gases. Experimental results are obtained from healthy volunteers, and are compared with those obtained using a conventional continuous ventilation model. Our findings show that the proposed technique can be used to assess lung function, and has several advantages over conventional methods such as compact and portable apparatus, easy usage, and quick estimation of cardiopulmonary variables.

  3. Assessment of a new e-learning system on thorax, trachea, and lung ultrasound. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Colleen Cuca


    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.

  5. Cystic fibrosis lung disease: genetic influences, microbial interactions, and radiological assessment

    Energy Technology Data Exchange (ETDEWEB)

    Moskowitz, Samuel M.; Gibson, Ronald L. [University of Washington, Department of Pediatrics, Seattle, WA (United States); Effmann, Eric L. [University of Washington School of Medicine, Children' s Hospital and Regional Medical Center, Department of Radiology, Seattle, WA (United States)


    Cystic fibrosis (CF) is a multiorgan disease caused by mutation of the CF transmembrane conductance regulator (CFTR) gene. Obstructive lung disease is the predominant cause of morbidity and mortality; thus, most efforts to improve outcomes are directed toward slowing or halting lung-disease progression. Current therapies, such as mucolytics, airway clearance techniques, bronchodilators, and antibiotics, aim to suppress airway inflammation and the processes that stimulate it, namely, retention and infection of mucus plaques at the airway surface. New approaches to therapy that aim to ameliorate specific CFTR mutations or mutational classes by restoring normal expression or function are being investigated. Because of its sensitivity in detecting changes associated with early airway obstruction and regional lung disease, high-resolution CT (HRCT) complements pulmonary function testing in defining disease natural history and measuring response to both conventional and experimental therapies. In this review, perspectives on the genetics and microbiology of CF provide a context for understanding the increasing importance of HRCT and other imaging techniques in assessing CF therapies. (orig.)

  6. Increase of carcinogenic risk via enhancement of cyclooxygenase-2 expression and hydroxyestradiol accumulation in human lung cells as a result of interaction between BaP and 17-beta estradiol. (United States)

    Chang, Louis W; Chang, Yun-Ching; Ho, Chia-Chi; Tsai, Ming-Hsien; Lin, Pinpin


    Animal studies demonstrated that females are more susceptible than males to benzo[a]pyrene (BaP)-induced toxicities, including lung carcinogenesis. Elevation of cyclooxygenase-2 (COX-2) expression has been shown to increase the risk of cancer development. BaP induces COX-2 expression, and an interaction between BaP and estrogen in relation to COX-2 expression is suspected. In the present study, 10 muM BaP alone only slightly increased COX-2 mRNA expression and 10 nM 17-beta estradiol (E(2)) alone slightly increased prostaglandin E2 (PGE2) secretion in human bronchial epithelial cells. However, co-treatment with BaP and E(2) potentiated COX-2 mRNA expression and significantly elevated PGE2 secretion. Utilizing specific inhibitors and reporter assays, we further investigated the potentiation mechanisms of E(2) on BaP-induced COX-2 expression. First, E(2) activated estrogen receptor to increase PGE2 secretion, which directly increased COX-2 expression. Second, E(2) potentiated BaP-induced nuclear factor-kappaB (NF-kappaB) activation, which regulates COX-2 expression. Third, although the aryl hydrocarbon receptor (AhR) did not play a role in BaP-induced COX-2 expression, the potentiation effect of E(2) itself was AhR dependent. We further demonstrated that BaP induced the production of genotoxic E(2) metabolites (2- and 4-hydroxyestradiols) via AhR-up-regulated cytochromes P450 1A1 and 1B1. These metabolites could directly activate NF-kappaB to further promote COX-2 mRNA expression in human lung epithelial cells. These findings were further supported by increased PGE2 secretion in rat lung slice cultures. Our findings that the BaP-E(2) interaction enhanced COX-2 expression and hydroxyestradiol accumulation in the media of cultivated lung cells and tissues provide the needed scientific basis for higher risk of BaP-associated lung cancer in females.

  7. Assessment of the effectiveness of radon screening programs in reducing lung cancer mortality. (United States)

    Gagnon, Fabien; Courchesne, Mathieu; Lévesque, Benoît; Ayotte, Pierre; Leclerc, Jean-Marc; Belles-Isles, Jean-Claude; Prévost, Claude; Dessau, Jean-Claude


    The present study was aimed at assessing the health consequences of the presence of radon in Quebec homes and the possible impact of various screening programs on lung cancer mortality. Lung cancer risk due to this radioactive gas was estimated according to the cancer risk model developed by the Sixth Committee on Biological Effects of Ionizing Radiations. Objective data on residential radon exposure, population mobility, and tobacco use in the study population were integrated into a Monte-Carlo-type model. Participation rates to radon screening programs were estimated from published data. According to the model used, approximately 10% of deaths due to lung cancer are attributable to residential radon exposure on a yearly basis in Quebec. In the long term, the promotion of a universal screening program would prevent less than one death/year on a province-wide scale (0.8 case; IC 99%: -3.6 to 5.2 cases/year), for an overall reduction of 0.19% in radon-related mortality. Reductions in mortality due to radon by (1) the implementation of a targeted screening program in the region with the highest concentrations, (2) the promotion of screening on a local basis with financial support, or (3) the realization of systematic investigations in primary and secondary schools would increase to 1%, 14%, and 16.4%, respectively, in the each of the populations targeted by these scenarios. Other than the battle against tobacco use, radon screening in public buildings thus currently appears as the most promising screening policy for reducing radon-related lung cancer.

  8. Glyphosate and Carcinogenicity Risk


    Ötegen, Volkan Recai; Akbaba, Muhsin; Nazlıcan, Ersin


    IARC Glyphosate's IIA classification is still controversial, because dosages of this effect is not specified and also numerous studies show the opposite. However, the results must be noted by scientific institutions and public health authorities and risk assessment must be made considering doses and real-life conditions.

  9. A Histological Assessment of Lung Injury in Rats Exposed to Inhaled Sulfur Mustard across Dose and Time (United States)


    following HD exposure at 7.5 hours (3.0 mg/kg). Histopathology of the BALT and overlying respiratory epithelium in the accessory lung lobe. Note the...USAMRICD‐TR‐15‐02  A Histological Assessment of  Lung  Injury in Rats  Exposed to Inhaled Sulfur Mustard across Dose  and Time    Derron A... Lung Injury in rats Exposed to Inhaled Sulfur Mustard across Dose and Time 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

  10. Relevance of a Geriatric Assessment for Elderly Patients With Lung Cancer-A Systematic Review. (United States)

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


    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.

  11. Lung Cancer Attributable to Indoor Radon Exposure in France: Impact of the Risk Models and Uncertainty Analysis


    Catelinois, Olivier; Rogel, Agnès; Laurier, Dominique; Billon, Solenne; Hemon, Denis; VERGER, Pierre; Tirmarche, Margot


    Objective The inhalation of radon, a well-established human carcinogen, is the principal—and omnipresent—source of radioactivity exposure for the general population of most countries. Scientists have thus sought to assess the lung cancer risk associated with indoor radon. Our aim here is to assess this risk in France, using all available epidemiologic results and performing an uncertainty analysis. Methods We examined the exposure–response relations derived from cohorts of miners and from joi...

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

    NARCIS (Netherlands)

    Offermans, Nadine S. M.; Vermeulen, Roel; Burdorf, Alex; Peters, Susan; Goldbohm, R. Alexandra; van Tongeren, Martie; Kauppinen, T.; Kant, Ijmert; Kromhout, Hans; van den Brandt, Piet A.; Koeman, T.


    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 t

  13. 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


    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.

  14. Gaps in scientific knowledge about the carcinogenic potential of asphalt/bitumen fumes. (United States)

    Schulte, Paul A


    Despite a relatively large body of published research, the potential carcinogenicity of asphalt/bitumen fumes is still a vexing question. Various uncertainties and gaps in scientific knowledge need to be addressed. These include uncertainties in chemistry, animal studies, and human studies. The chemistry of asphalt/bitumen fumes is complex and varies according to the source of the crude oil and the application parameters. The epidemiological studies, while showing weak evidence of lung cancer, are inconsistent and many confounding factors have not been addressed. Studies of animal exposure are also inconsistent regarding laboratory and field-generated fumes. There is a need for further human studies that address potential confounding factors such as smoking, diet, coal tar, and diesel exposures. Animal inhalation studies need to be conducted with asphalt/bitumen fumes that are chemically representative of roofing and paving fumes. Underlying all of this is the need for continued characterization of fumes so their use in animal and field studies can be properly assessed. Nonetheless, uncertainties such as these should not preclude appropriate public health actions to protect workers in the even that asphalt fumes are found to be a carcinogenic hazard.

  15. Stereological assessment of mouse lung parenchyma via nondestructive, multiscale micro-CT imaging validated by light microscopic histology. (United States)

    Vasilescu, Dragos M; Klinge, Christine; Knudsen, Lars; Yin, Leilei; Wang, Ge; Weibel, Ewald R; Ochs, Matthias; Hoffman, Eric A


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

  16. Dual energy CT for the assessment of lung perfusion-Correlation to scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Thieme, Sven F.; Becker, Christoph R. [Department of Clinical Radiology, Ludwig-Maximilians-University of Munich (Germany); Hacker, Marcus [Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich (Germany); Nikolaou, Konstantin; Reiser, Maximilian F. [Department of Clinical Radiology, Ludwig-Maximilians-University of Munich (Germany); Johnson, Thorsten R.C. [Department of Clinical Radiology, Ludwig-Maximilians-University of Munich (Germany)], E-mail:


    Purpose of this study was to determine the diagnostic value of dual energy CT in the assessment of pulmonary perfusion with reference to pulmonary perfusion scintigraphy. Thirteen patients received both dual energy CT (DECT) angiography (Somatom Definition, Siemens) and ventilation/perfusion scintigraphy. Median time between scans was 3 days (range, 0-90). DECT perfusion maps were generated based on the spectral properties of iodine. Two blinded observes assessed DECT angiograms, perfusion maps and scintigrams for presence and location of perfusion defects. The results were compared by patient and by segment, and diagnostic accuracy of DECT perfusion imaging was calculated regarding scintigraphy as standard of reference. Diagnostic accuracy per patient showed 75% sensitivity, 80% specificity and a negative predictive value of 66%. Sensitivity per segment amounted to 83% with 99% specificity, with 93% negative predictive value. Peripheral parts of the lungs were not completely covered by the 80 kVp detector in 85% of patients. CTA identified corresponding emboli in 66% of patients with concordant perfusion defects in DECT and scintigraphy. Dual energy CT perfusion imaging is able to display pulmonary perfusion defects with good agreement to scintigraphic findings. DECT can provide a pulmonary CT angiogram, high-resolution morphology of the lung parenchyma and perfusion information in one single exam.

  17. Genetic Determinants for Promoter Hypermethylation in the Lungs of Smokers: A Candidate Gene-Based Study


    Leng, Shuguang; Stidley, Christine A.; Liu, Yushi; Edlund, Christopher K.; Willink, Randall P.; Han, Younghun; Landi, Maria Teresa; Thun, Michael; Picchi, Maria A.; Bruse, Shannon E.; Crowell, Richard E.; Van Den Berg, David; Neil E Caporaso; Amos, Christopher I.; Siegfried, Jill M.


    The detection of tumor suppressor gene promoter methylation in sputum-derived exfoliated cells predicts early lung cancer. Here we identified genetic determinants for this epigenetic process and examined their biological effects on gene regulation. A two-stage approach involving discovery and replication was employed to assess the association between promoter hypermethylation of a 12-gene panel and common variation in 40 genes involved in carcinogen metabolism, regulation of methylation, and ...

  18. [Evaluation of the carcinogenic effect of ceramic fibers in experiments on rats and mice]. (United States)

    Krajnow, A; Lao, I; Stetkiewicz, J


    The carcinogenic effect of Kaowoll raw and thermally used ceramic fibres was assessed in experiments on rats and mice. The fibers were applied intraperitoneally in doses by 25 and 5 mg, and the animals were observed over their life-span. It was found that Kaowoll fibers were carcinogenic and that high temperature did not change these properties.

  19. 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:


    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.

  20. Assessment of Circulating microRNAs in Plasma of Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Orazio Fortunato


    Full Text Available Lung cancer is the most common cause of cancer deaths worldwide and numerous ongoing research efforts are directed to identify new strategies for its early detection. The development of non-invasive blood-based biomarkers for cancer detection in its preclinical phases is crucial to improve the outcome of this deadly disease. MicroRNAs (miRNAs are a new promising class of circulating biomarkers for cancer detection and prognosis definition, but lack of consensus on data normalization methods for circulating miRNAs and the critical issue of haemolysis, has affected the identification of circulating miRNAs with diagnostic potential. We describe here an interesting approach for profiling circulating miRNAs in plasma samples based on the evaluation of reciprocal miRNA levels measured by quantitative Real-Time PCR. By monitoring changes of plasma miRNA-ratios, it is possible to assess the deregulation of tumor-related miRNAs and identify signatures with diagnostic and prognostic value. In addition, to avoid bias due to the release of miRNAs from blood cells, a miRNA-ratios signature distinguishing haemolyzed samples was identified. The method described was validated in plasma samples of lung cancer patients, but given its reproducibility and reliability, could be potentially applied for the identification of diagnostic circulating miRNAs in other diseases.

  1. Application of the adductome approach to assess intertissue DNA damage variations in human lung and esophagus

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    Kanaly, Robert A. [Department of Technology and Ecology, Graduate School of Global Environmental Studies, Kyoto University, Kyoto 606-8501 (Japan); Department of Environmental Biosciences, International Graduate School of Arts and Sciences, Yokohama City University, Yokohama 236-0027 (Japan); Matsui, Saburo [Department of Technology and Ecology, Graduate School of Global Environmental Studies, Kyoto University, Kyoto 606-8501 (Japan); Hanaoka, Tomoyuki [Epidemiology and Prevention Division, National Cancer Center Research Institute, Tokyo 104-0045 (Japan); Matsuda, Tomonari [Department of Technology and Ecology, Graduate School of Global Environmental Studies, Kyoto University, Kyoto 606-8501 (Japan)], E-mail:


    Methods for determining the differential susceptibility of human organs to DNA damage have not yet been explored to any large extent due to technical constraints. The development of comprehensive analytical approaches by which to detect intertissue variations in DNA damage susceptibility may advance our understanding of the roles of DNA adducts in cancer etiology and as exposure biomarkers at least. A strategy designed for the detection and comparison of multiple DNA adducts from different tissue samples was applied to assess esophageal and peripherally- and centrally-located lung tissue DNA obtained from the same person. This adductome approach utilized LC/ESI-MS/MS analysis methods designed to detect the neutral loss of 2'-deoxyribose from positively ionized 2'-deoxynucleoside adducts transmitting the [M+H]{sup +} > [M+H-116]{sup +} transition over 374 transitions. In the final analyses, adductome maps were produced which facilitated the visualization of putative DNA adducts and their relative levels of occurrence and allowed for comprehensive comparisons between samples, including a calf thymus DNA negative control. The largest putative adducts were distributed similarly across the samples, however, differences in the relative amounts of putative adducts in lung and esophagus tissue were also revealed. The largest-occurring lung tissue DNA putative adducts were 90% similar (n = 50), while putative adducts in esophagus tissue DNA were shown to be 80 and 84% similar to central and peripheral lung tissue DNA respectively. Seven DNA adducts, N{sup 2}-ethyl-2'-deoxyguanosine (N{sup 2}-ethyl-dG), 1,N{sup 6}-etheno-2'-deoxyadenosine ({epsilon}dA), {alpha}-S- and {alpha}-R-methyl-{gamma}-hydroxy-1,N{sup 2}-propano-2'-deoxyguanosine (1,N{sup 2}-PdG{sub 1}, 1,N{sup 2}-PdG{sub 2}), 3-(2'-deoxyribosyl)-5,6,7,8-tetrahydro-8-hydroxy-pyrimido[1,2-a] purine-(3H)-one (8-OH-PdG) and the two stereoisomers of 3-(2'-deoxyribosyl)-5,6,7,8-tetrahydro

  2. Potential Role of Lung Ventilation Scintigraphy in the Assessment of COPD


    Cukic, Vesna; Begic, Amela


    Objective: To highlight the importance of the lung ventilation scintigraphy (LVS) to study the regional distribution of lung ventilation and to describe most frequent abnormal patterns of lung ventilation distribution obtained by this technique in COPD and to compare the information obtained by LVS with the that obtained by traditional lung function tests. Material and methods: The research was done in 20 patients with previously diagnosed COPD who were treated in Intensive care unit of Clini...

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

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    Sabro Nielsen, P.


    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).

  4. Toxicity and Carcinogenicity of Dichlorodiphenyltrichloroethane (DDT) (United States)

    Harada, Takanori; Takeda, Makio; Kojima, Sayuri; Tomiyama, Naruto


    Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p′-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT. PMID:26977256

  5. 4D cone beam CT-based dose assessment for SBRT lung cancer treatment (United States)

    Cai, Weixing; Dhou, Salam; Cifter, Fulya; Myronakis, Marios; Hurwitz, Martina H.; Williams, Christopher L.; Berbeco, Ross I.; Seco, Joao; Lewis, John H.


    The purpose of this research is to develop a 4DCBCT-based dose assessment method for calculating actual delivered dose for patients with significant respiratory motion or anatomical changes during the course of SBRT. To address the limitation of 4DCT-based dose assessment, we propose to calculate the delivered dose using time-varying (‘fluoroscopic’) 3D patient images generated from a 4DCBCT-based motion model. The method includes four steps: (1) before each treatment, 4DCBCT data is acquired with the patient in treatment position, based on which a patient-specific motion model is created using a principal components analysis algorithm. (2) During treatment, 2D time-varying kV projection images are continuously acquired, from which time-varying ‘fluoroscopic’ 3D images of the patient are reconstructed using the motion model. (3) Lateral truncation artifacts are corrected using planning 4DCT images. (4) The 3D dose distribution is computed for each timepoint in the set of 3D fluoroscopic images, from which the total effective 3D delivered dose is calculated by accumulating deformed dose distributions. This approach is validated using six modified XCAT phantoms with lung tumors and different respiratory motions derived from patient data. The estimated doses are compared to that calculated using ground-truth XCAT phantoms. For each XCAT phantom, the calculated delivered tumor dose values generally follow the same trend as that of the ground truth and at most timepoints the difference is less than 5%. For the overall delivered dose, the normalized error of calculated 3D dose distribution is generally less than 3% and the tumor D95 error is less than 1.5%. XCAT phantom studies indicate the potential of the proposed method to accurately estimate 3D tumor dose distributions for SBRT lung treatment based on 4DCBCT imaging and motion modeling. Further research is necessary to investigate its performance for clinical patient data.

  6. 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)


    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

  7. Case-control assessment of diet and lung cancer risk in African Americans and Mexican Americans. (United States)

    Pillow, P C; Hursting, S D; Duphorne, C M; Jiang, H; Honn, S E; Chang, S; Spitz, M R


    In this case-control study we determined whether dietary differences underlie some of the ethnic and sex differences in US lung cancer rates. We examined the relationship between diet and lung cancer development in 137 lung cancer cases (93 African Americans and 44 Mexican Americans) and 187 controls (78 African Americans and 109 Mexican Americans). Cases reported a higher daily mean total fat intake (p fruits (p = 0.02). Ethnic differences in diet were also observed: Mexican Americans consumed less total fat (p fruits (p lung cancer risk (p fruit consumption and lung cancer risk (p = 0.05). In conclusion, our findings support the hypothesis that diet, particularly high fat consumption and low fruit and vegetable consumption, contributes (independent of cigarette smoking) to the excess lung cancer risk in African-American men, who have the highest lung cancer rates in the United States.

  8. Urban air carcinogens and their effects on health

    Energy Technology Data Exchange (ETDEWEB)

    Lechner, J.F.


    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.

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

    Directory of Open Access Journals (Sweden)

    Paulo M. Pêgo-Fernandes


    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.

  10. Nutrition aspects of lung cancer. (United States)

    Cranganu, Andreea; Camporeale, Jayne


    Lung cancer is the most common type of cancer, excluding nonmelanoma skin cancer, and is the leading cause of cancer death in the United States. Notable carcinogens involved in the development of lung cancer include smoking, secondhand smoke, and radon. Lung cancer is divided into 2 major types: non-small-cell lung cancer, the most prevalent, and small-cell lung cancer. Treatment includes surgery, chemotherapy, radiation, or a combination of the same. Medical nutrition therapy is often required for nutrition-related side effects of cancer treatment, which include but are not limited to anorexia, nausea and vomiting, and esophagitis. The best protection against lung cancer is avoidance of airborne carcinogens and increased consumption of fruits and vegetables. Studies have shown that smokers taking large amounts of beta-carotene and vitamin A supplements had increased lung cancer incidence and mortality. However, ingestion of beta-carotene from foods, along with a diet rich in fruits and vegetables, has a protective role against lung disease. The use of complementary and alternative medicine by lung cancer patients is prevalent; therefore, clinicians should investigate whether complementary and alternative therapies are used by patients and advise them on the use of these therapies to avoid any potential side effects and interactions with conventional therapies. The article concludes with a case study of a patient with non-small-cell lung cancer and illustrates the use of medical nutrition therapy in relation to cancer treatment side effects.

  11. Gefitinib: new preparation. Non small-cell lung cancer: stricter assessment needed. (United States)


    (1) Platinum-based chemotherapy is generally used to treat advanced-stage non small-cell lung cancer (stages III and IV), but has only a modest impact on survival. There is no reference treatment. (2) Gefitinib inhibits the tyrosine kinase activity of the receptor for EGF (epidermal growth factor), which is thought to be involved in tumour growth. It has a temporary licence in France and is used on a named-patient basis, but full marketing authorisation has already been granted in Japan, the United States, and elsewhere. (3) Two double-blind dose-finding studies compared two doses of oral gefitinib monotherapy (250 mg/day and 500 mg/day) in patients in whom at least two lines of chemotherapy had failed. The results were favourable, with a median survival of 6 months and a symptomatic improvement in some patients, but they are undermined by the absence of a placebo group and by major protocol violations. (4) Two double-blind trials, each in more than 1000 patients, showed that gefitinib does not increase the efficacy of first-line platinum combinations. (5) About 15% of patients receiving gefitinib monotherapy in clinical trials stopped taking the treatment because of adverse events. The most frequent were gastrointestinal (diarrhea, nausea, vomiting) and cutaneous (rash, acne, dry skin, pruritus). (6) Interstitial pneumonitis occurred in about 1% of patients, and was fatal in about one-third of cases. (7) Gefitinib is metabolised by the cytochrome P450 isoenzyme CYP3A4, so carries a potentially high risk of interactions. (8) In practice, more thorough assessment of gefitinib is needed to determine whether this new drug is beneficial for patients with non small-cell lung cancer. Marketing authorisation is not currently justified.

  12. Implementation and evaluation of a new workflow for registration and segmentation of pulmonary MRI data for regional lung perfusion assessment (United States)

    Böttger, T.; Grunewald, K.; Schöbinger, M.; Fink, C.; Risse, F.; Kauczor, H. U.; Meinzer, H. P.; Wolf, Ivo


    Recently it has been shown that regional lung perfusion can be assessed using time-resolved contrast-enhanced magnetic resonance (MR) imaging. Quantification of the perfusion images has been attempted, based on definition of small regions of interest (ROIs). Use of complete lung segmentations instead of ROIs could possibly increase quantification accuracy. Due to the low signal-to-noise ratio, automatic segmentation algorithms cannot be applied. On the other hand, manual segmentation of the lung tissue is very time consuming and can become inaccurate, as the borders of the lung to adjacent tissues are not always clearly visible. We propose a new workflow for semi-automatic segmentation of the lung from additionally acquired morphological HASTE MR images. First the lung is delineated semi-automatically in the HASTE image. Next the HASTE image is automatically registered with the perfusion images. Finally, the transformation resulting from the registration is used to align the lung segmentation from the morphological dataset with the perfusion images. We evaluated rigid, affine and locally elastic transformations, suitable optimizers and different implementations of mutual information (MI) metrics to determine the best possible registration algorithm. We located the shortcomings of the registration procedure and under which conditions automatic registration will succeed or fail. Segmentation results were evaluated using overlap and distance measures. Integration of the new workflow reduces the time needed for post-processing of the data, simplifies the perfusion quantification and reduces interobserver variability in the segmentation process. In addition, the matched morphological data set can be used to identify morphologic changes as the source for the perfusion abnormalities.

  13. Investigation of the uptake of drugs, carcinogens and mutagens by individual mammalian cells using a scanning proton microprobe (United States)

    Cholewa, M.; Turnbull, I. F.; Legge, G. J. F.; Weigold, H.; Marcuccio, S. M.; Holan, G.; Tomlinson, E.; Wright, P. J.; Dillon, C. T.; Lay, P. A.; Bonin, A. M.


    The use of micro-PIXE [1] in measuring the quantitative uptake of drugs containing metal atoms by individual Vero cells (African green monkey kidney cell line) and V79 Chinese hamster lung cells is demonstrated. One class of drugs, heteropolytungstates, which are being assessed for activity against the HIV virus, were studied using Vero cells. The cellular uptake of a series of chromium compounds, including carcinogens and mutagens, in which the metal oxidation state was either (III), (V) or (VI), was measured using V79 cells. It was found that, unlike any other techniques, scanning proton microprobe (SPM) offers both the sensitivity and spatial resolution to carry out unicellular analysis. The use of cultured cell lines in these analyses was shown to have distinct advantages over cells such as peripheral blood lymphocytes (PBLs).

  14. 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.

  15. Unrestrained video-assisted plethysmography: a noninvasive method for assessment of lung mechanical function in small animals. (United States)

    Bates, Jason H T; Thompson-Figueroa, John; Lundblad, Lennart K A; Irvin, Charles G


    The assessment of lung mechanical function in small animals, particularly mice, is essential for investigations into the pathophysiology of pulmonary disease. The most accurate and specific methods for making this assessment are highly invasive and so provide data of questionable relevance to normality. By contrast, present noninvasive methods based on unrestrained plethysmography have no direct link to the mechanical properties of the lung. There is thus a need for a completely noninvasive method for determining lung mechanical function in small animals. In the present study, we demonstrate an extension of unrestrained plethysmography in which changes in lung volume are estimated via orthogonal video imaging of the thorax. These estimates are combined with the pressure swings recorded as mice breathe inside a heated and humidified chamber to yield an estimate of specific airway resistance (sRaw). We used this new technique, which we term "unrestrained video-assisted plethysmography" (UVAP), to measure sRaw in 11 BALB/c mice exposed to aerosols of saline, methacholine, and albuterol and obtained mean values of 0.71, 1.23 and 1.10 cmH(2)O x s, respectively. Mean breathing frequency was 4.3, 3.4, and 3.6 breaths/s, respectively, while the corresponding mean tidal volumes were 0.36, 0.44 and 0.37 ml, respectively. We conclude that UVAP, a noninvasive method, is able to provide usefully accurate estimates of sRaw and breathing pattern parameters in mice.

  16. Potential Role of Lung Ventilation Scintigraphy in the Assessment of COPD (United States)

    Cukic, Vesna; Begic, Amela


    Objective: To highlight the importance of the lung ventilation scintigraphy (LVS) to study the regional distribution of lung ventilation and to describe most frequent abnormal patterns of lung ventilation distribution obtained by this technique in COPD and to compare the information obtained by LVS with the that obtained by traditional lung function tests. Material and methods: The research was done in 20 patients with previously diagnosed COPD who were treated in Intensive care unit of Clinic for pulmonary diseases and TB “Podhrastovi” Clinical Center, University of Sarajevo in exacerbation of COPD during first three months of 2014. Each patient was undergone to testing of pulmonary function by body plethysmography and ventilation/perfusion lung scintigraphy with radio pharmaceutics Technegas, 111 MBq Tc -99m-MAA. We compared the results obtained by these two methods. Results: All patients with COPD have a damaged lung function tests examined by body plethysmography implying airflow obstruction, but LVS indicates not only airflow obstruction and reduced ventilation, but also indicates the disorders in distribution in lung ventilation. Conclusion: LVS may add further information to the functional evaluation of COPD to that provided by traditional lung function tests and may contribute to characterizing the different phenotypes of COPD. PMID:25132709

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

    Directory of Open Access Journals (Sweden)

    M. Scimeca


    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.

  18. Radiological and functional assessment of radiation-induced lung injury in the rat

    NARCIS (Netherlands)

    Vujaskovic, Z; Down, JD; van t'Veld, AA; Mooyaart, EL; Meertens, H; Piers, DA; Szabo, BG; Konings, AWT


    The purpose of this study is to develop an experimental model to measure localized radiation-induced lung injury using multiple end-points including breathing frequency, high-resolution computed tomography (CT), and radionuclide perfusion. The rats were anaesthetized and the right lung irradiated wi

  19. Assessment of Pulmonary Fibrogenic Potential of Multiwalled Carbon Nanotubes in Human Lung Cells

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    Anurag Mishra


    Full Text Available Multiwalled carbon nanotubes have been shown to possess unusual fibrogenic activity in vivo and are currently the focus of intense toxicological investigations. This study further determines the fibrogenic potential of well-dispersed MWCNT in human lung cell culture models and to develop a novel platform for understanding the cellular mechanisms of MWCNT-induced lung fibrosis. Survanta, a natural lung surfactant, showed effectiveness in dispersing agglomerates of MWCNT to fine structures similar in size to aerosolized one. At relevant low doses (0.002–0.2 μg/cm2, MWCNT exhibited a dose-dependent bio-effect on the human lung epithelial cells which is more pronounced in dispersed-MWCNT compared to non-dispersed form. Significantly elevated levels of fibrogenic mediators, such as transforming growth factor-β1 and matrix metalloprotienases-9 were observed in the dispersed-MWCNT treated lung epithelial cells. Based on previous in vivo studies showing that dispersed-MWCNT penetrated the interstitium and caused rapid interstitial fibrosis, we evaluated the potential direct interaction between lung fibroblasts and MWCNT. Direct stimulation of human lung fibroblast cell proliferation, collagen expression and fibroblast growth factor-2 were observed which suggests novel mechanisms of MWCNT-induced lung fibrosis. Our results indicate that the dispersion status of MWCNT determines their fibrogenic activity which is consistent with in vivo findings.

  20. Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies. (United States)

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


    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.

  1. Lung nodule assessment in computed tomography. Precision of attenuation measurement based on computer-aided volumetry

    Energy Technology Data Exchange (ETDEWEB)

    Knoess, Naomi; Hoffmann, B.; Fabel, M.; Wiese, C.; Bolte, H.; Heller, M.; Biederer, J. [Klinik fuer Diagnostische Radiologie, Universitaetsklinikum Schleswig-Holstein, Campus Kiel (Germany); Jochens, A. [Inst. fuer Medizinische Informatik und Statistik, Universitaetsklinikum Schleswig-Holstein Campus Kiel (Germany)


    Purpose: to compare the reproducibility (r) of CT value measurement of pulmonary nodules using volumetry software (LungCare, LC) and manual ROIs (mROI). Materials and methods: 54 artificial nodules in a chest phantom were scanned three times with CT. CT values were measured with LC and mROI. The intrascan-r was assessed with three measurements in the first scan, and the interscan-r with measurements in three consecutive scans (one observer). Intrascan-r und interobserver-r (two obs.) were assessed in the first scan and in contrast-enhanced CT of 51 nodules from 15 patients (kernels b50f and b80f). Intrascan-r and interscan-r were described as the mean range and interobserver-r as the mean difference of CT values. The significance of differences was tested using t-test and sign test. Results: reproducibility was significantly higher for volumetry-based measurements in both artificial and patient nodules (range 0.11 vs. 6.16 HU for intrascan-r, 2.22 vs. 7.03 HU for interscan-r, difference 0.11 vs. 18.42 HU for interobserver-r; patients: 1.78 vs. 13.19 HU (b50f-Kernel) and 1.88 vs. 27.4 HU (b80f-Kernel) for intrascan-r, 3.71 vs. 22.43 HU for interobserver-r). Absolute CT values differed significantly between convolution kernels (pat./mROI: 29.3 [b50f] and 151.9 HU [b80f] pat./LC: 5 [b50f] and 147 HU [b80f]). Conclusion: the reproducibility of volumetry-based measurements of CT values in pulmonary nodules is significantly higher and should therefore be recommended, e.g. in dynamic chest CT protocols. Reproducibility does not depend on absolute CT values. (orig.)

  2. Biocompatibility assessment of a long-term wearable artificial pump-lung in sheep. (United States)

    Zhou, Kang; Niu, Shuqiong; Bianchi, Giacomo; Wei, Xufeng; Garimella, Narayana; Griffith, Bartley P; Wu, Zhongjun J


    The purpose of this study was to assess the biocompatibility of a newly developed long-term wearable artificial pump-lung (APL) in a clinically relevant ovine animal model. The wearable APL device was implanted in five sheep through left thoracotomy. The device was connected between the right atrium and pulmonary artery and evaluated for 30 days. Three sheep were used as the sham control. Platelet activation was assessed by measuring platelet surface P-selectin (CD62P) expression with flow cytometry and plasma soluble P-selectin with an enzyme-linked immunosorbent assay. Thrombotic deposition on the device components and hollow fiber membranes were analyzed with digital imaging and scanning electron microscopy. Surface P-selectin of the APL and sham groups changed significantly over the study period, but without significant differences between the two groups. Soluble P-selectin for the two groups peaked in the first 24 h after the surgery. Soluble P-selectin of the APL group remained slightly elevated over the study period compared to the presurgical baseline value and was slightly higher compared to that of the sham group. Plasma free hemoglobin remained in the normal ranges in all the animals. In spite of the surgery-related alteration in laboratory tests and elevation of platelet activation status, the APL devices in all the animals functioned normally (oxygen transfer and blood pumping) during the 30-day study period. The device flow path and membrane surface were free of gross thrombus. Electron microscopy images showed only scattered thrombi on the fibers (membrane surface and weft). In summary, the APL exhibited excellent biocompatibility. Two forms of platelet activation, surgery-related and device-induced, in the animals implanted with the wearable APL were observed. The limited device-induced platelet activation did not cause gross thrombosis and impair the long-term device performance.

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

    Directory of Open Access Journals (Sweden)

    J.B. Figueroa-Casas


    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

  4. Human exposure to dioxins through the diet in Catalonia, Spain: carcinogenic and non-carcinogenic risk. (United States)

    Llobet, Juan M; Domingo, Jose L; Bocio, Ana; Casas, Conrad; Teixidó, Angel; Müller, Lutz


    The main objectives of this study were to estimate the dietary intake of dioxins by the population of Catalonia, Spain, to determine which food groups showed the greatest contribution to this intake, and to assess the health risks potentially associated with the dietary dioxin intake. From June to August 2000, food samples were randomly acquired in seven cities of Catalonia. Dioxin concentrations were determined in 108 samples belonging to the following groups: vegetables, fruits, pulses, cereals, fish and shellfish, meats and meat products, eggs, milk and dairy products, and oils and fats. Estimates of average daily food consumption were obtained from recent studies. Total dietary intake of dioxins for the general population of Catalonia was estimated to be 95.4 pg WHO-TEQ/day (78.4 pg I-TEQ/day), with fish and shellfish (31%), diary products (25%), cereals (14%) and meat (13%) showing the greatest percentages of contribution to dioxin intake. The contribution of all the rest of food groups to the total dietary intake was under 20%. The non-carcinogenic risk index of dioxin intake through the diet was in the range 0.34-1.36, while the carcinogenic risk level was 1,360 excess cancer over a lifetime of 70 years. Our results corroborate the decreasing tendency in dietary intake of dioxins found in recent studies (2000-2001) from various countries.

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

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    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: [Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju (Korea, Republic of)


    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.

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

    Directory of Open Access Journals (Sweden)

    Buonaguro Franco M


    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.

  7. The dermal carcinogenic potential of unrefined and hydrotreated lubricating oils. (United States)

    McKee, R H; Daughtrey, W C; Freeman, J J; Federici, T M; Phillips, R D; Plutnick, R T


    Unrefined lubricating oils contain relatively high levels of polycyclic aromatic hydrocarbons (PAH) and have been shown to induce tumors in mouse skin. Exxon has developed a new method of refining these materials, a severe hydrotreatment process that is optimized for PAH removal. The specific objectives of the current study were to assess PAH reduction and then to evaluate directly the dermal carcinogenic potential of the materials that spanned the range of products produced by this method. The test samples included unrefined light and heavy vacuum distillates from a naphthenic crude oil, as well as the corresponding severely hydrotreated products. Two sets of samples were prepared to assess the effects of various operating parameters in the reactor. Additionally, positive (benzo[a]pyrene), negative (white mineral oil) and vehicle (toluene) control groups were included to assess the sensitivity and specificity of the bioassay. Each sample was applied in twice-weekly aliquots to the backs of 40 male C3H mice. In the analytical studies, significant reductions in the levels of several specific PAH were demonstrated. In the dermal carcinogenesis studies, the unrefined oils and the positive control induced tumors and also significantly reduced survival. None of the mice treated with severely hydrotreated oils or with the negative or vehicle controls developed skin tumors, and survival of these mice was not significantly different from the control. Thus, the data demonstrated that this new, severe hydrotreatment process was an effective means of converting carcinogenic feedstocks to non-carcinogenic products.

  8. Lung cancer in women

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    Barrera-Rodriguez R


    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

  9. Combining QSAR modeling and text-mining techniques to link chemical structures and carcinogenic modes of action

    Directory of Open Access Journals (Sweden)

    Georgios Papamokos


    Full Text Available There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. 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.

  10. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action. (United States)

    Papamokos, George; Silins, Ilona


    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.

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

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    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)


    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.)

  12. Lung uptake of thallium-201 on resting myocardial imaging in assessment of pulmonary edema

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    Tamaki, N.; Yonekura, Y.; Yamamoto, K. (Kyoto Univ. (Japan). Hospital)


    We have noted increased lung uptake of thallium-201 on resting myocardial images in patients with congestive heart failure. To evaluate this phenomenon, lung uptake of thallium on resting myocardial imaging was examined in 328 patients with various cardiovascular diseases. Increased lung uptake was observed in 117 cases (78%) with myocardial infarction, 32 (37%) with angina pectoris, 6 (27%) with hypertensive heart disease, 7 (30%) with hypertrophic cardiomyopathy, 6 (100%) with congestive cardiomyopathy, 11 (100%) with valvular heart disease, and 7 (71%) with congenital heart disease, however, only one (5%) of normal subjects revealed increased uptake. Left ventricular ejection fraction was evaluated in 32 cases with ischemic heart disease on the same day and it was significantly decreased as the lung uptake of thallium increased. Increased thallium activity in the lung seemed to be another noninvasive marker of lift heart failure in ischemic heart disease. Lung uptake of thallium was compared with pulmonary congestive signs on chest X-ray in 29 cases. The uptake was well correlated with the degree of pulmonary edema, and thallium myocardial image revealed remarkably increased lung uptake in all the patients accompanied with pulmonary interstitial edema on chest X-ray. Therefore, this phenomenon will demonstrate pulmonary edema, since thallium may be extracted to the increased interstitial distribution space of the lung as well as the myocardium in a patient with pulmonary edema. We conclude that thallium myocardial scintigraphy is useful not only in identification and localization of myocardial ischemia or infarction, but also in evaluation of pulmonary edema at the same time.

  13. Carcinogenicity studies on fibres, metal compounds, and some other dusts in rats. (United States)

    Pott, F; Ziem, U; Reiffer, F J; Huth, F; Ernst, H; Mohr, U


    About 50 dusts were examined on their carcinogenicity in rats mainly after intraperitoneal injection and some after intratracheal instillation. In the i.p. test, very low doses between 0.05 and 0.5 mg asbestos led to tumour incidences of about 20 to 80%. Polyvinyl-pyridine-N-oxide prolonged the tumour latency after injection of actinolite. 60 mg attapulgite from three sources with short fibre lengths were not shown to be carcinogenic but an attapulgite sample with longer fibres had a moderate effect. Relatively thick rock and ceramic fibres (median greater than 1 micron) induced tumours, but slag and wollastonite fibres did not, probably because of their better solubility. Intratracheal instillations of glass microfibres (20 X 0.5 mg) led to lung tumours in 5 of 34 rats (0 in control). The carcinogenic potency of an inorganic fibre depends on its size and persistency, and possibly also on other properties, especially on the surface. Nickel powder, nickel oxide, nickel subsulfide and cadmium sulfide were all found to be carcinogenic in the two tests. Cadmium chloride and cadmium oxide could only be administered in very low doses because of their high acute toxicity. A high amount of magnetite (15 X 15 mg led to an unexpected lung tumour incidence of 69%. The i.p. test in rats proved to be very sensitive for detecting the carcinogenic potency of non-acute toxic natural and man-made mineral dusts as well as metal compounds. This means that, if a high dose of one of these dusts does not induce tumours in this test, no suspicion of carcinogenic potency can be substantiated.

  14. Assessment of regional lung ventilation by electrical impedance tomography in a patient with unilateral bronchial stenosis and a history of tuberculosis. (United States)

    Marinho, Liégina Silveira; Sousa, Nathalia Parente de; Barros, Carlos Augusto Barbosa da Silveira; Matias, Marcelo Silveira; Monteiro, Luana Torres; Beraldo, Marcelo do Amaral; Costa, Eduardo Leite Vieira; Amato, Marcelo Britto Passos; Holanda, Marcelo Alcantara


    Bronchial stenosis can impair regional lung ventilation by causing abnormal, asymmetric airflow limitation. Electrical impedance tomography (EIT) is an imaging technique that allows the assessment of regional lung ventilation and therefore complements the functional assessment of the lungs. We report the case of a patient with left unilateral bronchial stenosis and a history of tuberculosis, in whom regional lung ventilation was assessed by EIT. The EIT results were compared with those obtained by ventilation/perfusion radionuclide imaging. The patient was using nasal continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea syndrome. Therefore, we studied the effects of postural changes and of the use of nasal CPAP. The EIT revealed heterogeneous distribution of regional lung ventilation, the ventilation being higher in the right lung, and this distribution was influenced by postural changes and CPAP use. The EIT assessment of regional lung ventilation produced results similar to those obtained with the radionuclide imaging technique and had the advantage of providing a dynamic evaluation without radiation exposure.

  15. Strategies of reducing the carcinogenic risk of cytostatic agents on the basis of bioassay evaluation. (United States)

    Berger, M R


    This article described strategies that can be used to reduce the carcinogenic risk of cytostatic chemotherapy and summarizes our recent experimental results. Reduction of neoplasms caused by the carcinogenic potency inherent in cytostatic agents can be obtained. (A) by chemical modifications such as: (1) exchanging a chlorine atom in N, N'-bis-(2-chloroethyl)-N-nitrosourea (BCNU) in the chloroethyl group at N'-position for a hydroxyl group to form the less carcinogenic analog N-(2-chloroethyl)-N'-(2-hydroxyethyl)-N-nitrosourea (HECNU); (2) linking chlorambucil to the steroid prednisolone to obtain a conjugate (prednimustine) with distinctly lower carcinogenic potential than chlorambucil; (3) progressive ring halogenation of phenyl-triazenes to generate agents with decreased long-term toxic risk; (B) by replacing cyclophosphamide within the carcinogenic drug combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) by vincristine to form the combination VMF which has no detectable carcinogenic potential; (C) by coadministration of cyclophosphamide and mesna to achieve a dose-related reduction of cyclophosphamide-induced urinary bladder carcinomas; (D) by administration of dinaline, a compound which reduces the spontaneous incidence of malignant tumors in rats. These examples demonstrate that the carcinogenic risk of single agents and drug combinations used for antineoplastic chemotherapy has successfully been reduced, as assessed in long-term bioassays. Such strategies should be considered in the treatment of patients with long life expectancy following cytotoxic chemotherapy.

  16. 4DCT-based assessment of regional airflow distribution in healthy human lungs during tidal breathing (United States)

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


    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.

  17. Lung dust analysis in the assessment of past exposure of man-made mineral fibre workers. (United States)

    McDonald, J C; Case, B W; Enterline, P E; Henderson, V; McDonald, A D; Plourde, M; Sébastien, P


    In the cohort of American MMMF workers reported by ENTERLINE et al. [Ann. occup. Hyg. 31, 625-656 (1987)] autopsies were recorded in 652 (13.5%) of 4840 deaths. Lung tissue samples were sought from all pathologists and obtained in 145 (22.2%), together with similar samples from 124 matched referents. Lung fibre counts by phase contrast microscopy were 60% higher (P less than 0.05) in workers than referents. Electron microscopy (ATEM) also showed more fibres of all kinds--MMMF, asbestos and other--but no convincing excess of any one type. Lung samples of only 26% of workers contained any MMMF, almost all siliceous in nature and in low concentration. There were too few cases of lung cancer (19) for any useful conclusion; however, in the plant with the highest lung cancer SMR (200), and a probable mesothelioma, amosite at greater than 1.0 fibres per micrograms (f micrograms-1) was found in four of six workers but in none of their matched referents. Although our findings contribute little to the interpretation of the results obtained by ENTERLINE et al. they indicate the potential value of tissue analyses in monitoring epidemiological studies of MMMF exposure.

  18. Lung, liver and lymph node metastases in follow-up MSCT. Comprehensive volumetric assessment of lesion size changes

    Energy Technology Data Exchange (ETDEWEB)

    Wulff, A.M.; Fischer, S.; Biederer, J.; Heller, M.; Fabel, M. [Universitaetsklinikum Schleswig-Holstein, Kiel (Germany). Klinik fuer Diagnostische Radiologie; Bolte, H. [Universitaetsklinikum Muenster (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Freitag-Wolf, S. [Universitaetsklinikum Schleswig-Holstein, Kiel (Germany). Inst. fuer Medizinische Informatik und Statistik; Soza, G.; Tietjen, C. [Siemens AG (Germany). Imaging and IT Div. Computed Tomography


    Purpose: To investigate measurement accuracy in terms of precision and inter-rater variability in the simultaneous volumetric assessment of lung, liver and lymph node metastasis size change over time in comparison to RECIST 1.1. Materials and Methods: Three independent readers evaluated multislice CT data from clinical follow-up studies (chest/abdomen) in 50 patients with metastases. A total of 117 lung, 77 liver and 97 lymph node metastases were assessed manually (RECIST 1.1) and by volumetry with semi-automated software. The quality of segmentation and need for manual adjustments were recorded. Volumes were converted to effective diameters to allow comparison to RECIST. For statistical assessment of precision and interobserver agreement, the Wilcoxon-signed rank test and Bland-Altman plots were utilized. Results: The quality of segmentation after manual correction was acceptable to excellent in 95 % of lesions and manual corrections were applied in 21 - 36 % of all lesions, most predominantly in lymph nodes. Mean precision was 2.6 - 6.3 % (manual) with 0.2 - 1.5 % (effective) relative measurement deviation (p <.001). Inter-reader median variation coefficients ranged from 9.4 - 12.8 % (manual) and 2.9 - 8.2 % (volumetric) for different lesion types (p <.001). The limits of agreement were {+-} 9.8 to {+-} 11.2 % for volumetric assessment. Conclusion: Superior precision and inter-rater variability of volumetric over manual measurement of lesion change over time was demonstrated in a whole body setting. (orig.)

  19. 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


    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)

  20. 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)

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


    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.)

  1. Assessing nodule detection on lung cancer screening CT: the effects of tube current modulation and model observer selection on detectability maps (United States)

    Hoffman, J. M.; Noo, F.; McMillan, K.; Young, S.; McNitt-Gray, M.


    Lung cancer screening using low dose CT has been shown to reduce lung cancer related mortality and been approved for widespread use in the US. These scans keep radiation doses low while maximizing the detection of suspicious lung lesions. Tube current modulation (TCM) is one technique used to optimize dose, however limited work has been done to assess TCM's effect on detection tasks. In this work the effect of TCM on detection is investigated throughout the lung utilizing several different model observers (MO). 131 lung nodules were simulated at 1mm intervals in each lung of the XCAT phantom. A Sensation 64 TCM profile was generated for the XCAT phantom and 2500 noise realizations were created using both TCM and a fixed TC. All nodules and noise realizations were reconstructed for a total of 262 (left and right lungs) nodule reconstructions and 10 000 XCAT lung reconstructions. Single-slice Hotelling (HO) and channelized Hotelling (CHO) observers, as well as a multislice CHO were used to assess area-under-the-curve (AUC) as a function of nodule location in both the fixed TC and TCM cases. As expected with fixed TC, nodule detectability was lowest through the shoulders and leveled off below mid-lung; with TCM, detectability was unexpectedly highest through the shoulders, dropping sharply near the mid-lung and then increasing into the abdomen. Trends were the same for all model observers. These results suggest that TCM could be further optimized for detection and that detectability maps present exciting new opportunities for TCM optimization on a patient-specific level.

  2. Assessment of the relationship between lung parenchymal destruction and impaired pulmonary perfusion on a lobar level in patients with emphysema

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    Ley-Zaporozhan, Julia [Department of Radiology, Johannes Gutenberg University, Mainz (Germany) and Department of Radiology (E 010), German Cancer Research Center, Heidelberg (Germany)]. E-mail:; Ley, Sebastian [Department of Radiology (E 010), German Cancer Research Center, Heidelberg (Germany); Department of Pediatric Radiology, Ruprecht-Karls-University, Heidelberg (Germany); Eberhardt, Ralf [Department of Pulmology, Thoraxklinik, Heidelberg (Germany); Weinheimer, Oliver [Department of Radiology, Johannes Gutenberg University, Mainz (Germany); Fink, Christian [Department of Radiology (E 010), German Cancer Research Center, Heidelberg (Germany); Department of Clinical Radiology, University Hospital of Munich (Germany); Puderbach, Michael [Department of Radiology (E 010), German Cancer Research Center, Heidelberg (Germany); Eichinger, Monika [Department of Radiology (E 010), German Cancer Research Center, Heidelberg (Germany); Herth, Felix [Department of Pulmology, Thoraxklinik, Heidelberg (Germany); Kauczor, Hans-Ulrich [Department of Radiology (E 010), German Cancer Research Center, Heidelberg (Germany)


    Purpose: To assess the relationship between lung parenchymal destruction and impaired pulmonary perfusion on a lobar level using CT and MRI in patients with emphysema. Material and methods: Forty-five patients with severe emphysema (GOLD III and IV) underwent inspiratory 3D-HRCT and contrast-enhanced MR-perfusion (1.5T; 3.5 mm x 1.9 mm x 4 mm). 3D-HRCT data was analyzed using a software for detection and visualization of emphysema. Emphysema was categorized in four clusters with different volumes and presented as overlay on the CT. CT and lung perfusion were visually analyzed for three lobes on each side using a four-point-score to grade the abnormalities on CT (1: predominantly small emphysema-clusters to 4: >75% large emphysema-clusters) and MRI (1: normal perfusion to 4: no perfusion). Results: A total of 270 lobes were evaluated. At CT, the score was 1 for 9 lobes, 2 for 43, 3 for 77, and 4 for 141 lobes. At MRI, the score was 1 for 13 lobes, 2 for 45, 3 for 92, and 4 for 120 lobes. Matching of lung parenchymal destruction and reduced perfusion was found in 213 lobes (weighted kappa = 0.8). The score was higher on CT in 44, and higher on MRI in 13 lobes. Conclusion: 3D-HRCT and 3D MR-perfusion show a high lobar agreement between parenchymal destruction and reduction of perfusion in patients with severe emphysema.

  3. Artificial sweeteners--do they bear a carcinogenic risk? (United States)

    Weihrauch, M R; Diehl, V


    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.

  4. Lung Cancer and Interstitial Lung Diseases: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Kostas Archontogeorgis


    Full Text Available Interstitial lung diseases (ILDs represent a heterogeneous group of more than two hundred diseases of either known or unknown etiology with different pathogenesis and prognosis. Lung cancer, which is the major cause of cancer death in the developed countries, is mainly attributed to cigarette smoking and exposure to inhaled carcinogens. Different studies suggest a link between ILDs and lung cancer, through different pathogenetic mechanisms, such as inflammation, coagulation, dysregulated apoptosis, focal hypoxia, activation, and accumulation of myofibroblasts as well as extracellular matrix accumulation. This paper reviews current evidence on the association between lung cancer and interstitial lung diseases such as idiopathic pulmonary fibrosis, sarcoidosis, systemic sclerosis, dermatomyositis/polymyositis, rheumatoid arthritis, systemic lupus erythematosus, and pneumoconiosis.

  5. How do organisational characteristics influence teamwork and service delivery in lung cancer diagnostic assessment programmes? A mixed-methods study (United States)

    Honein-AbouHaidar, Gladys N; Stuart-McEwan, Terri; Waddell, Tom; Salvarrey, Alexandra; Smylie, Jennifer; Dobrow, Mark J; Brouwers, Melissa C; Gagliardi, Anna R


    Objectives 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. Design 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. Setting 4 DAPs at 2 teaching and 2 community hospitals in Canada. Participants 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. Results 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. Conclusions 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

  6. Lung carcinoma signaling pathways activated by smoking

    Institute of Scientific and Technical Information of China (English)

    Jing Wen; Jian-Hua Fu; Wei Zhang; Ming Guo


    Lung cancer is the leading cause of cancer death in men and women worldwide, with over a million deaths annually. Tobacco smoke is the major etiologic risk factor for lung cancer in current or previous smokers and has been strongly related to certain types of lung cancer, such as small cell lung carcinoma and squamous cell lung carcinoma. In recent years, there has been an increased incidence of lung adenocarcinoma. This change is strongly associated with changes in smoking behavior and cigarette design. Carcinogens present in tobacco products and their intermediate metabolites can activate multiple signaling pathways that contribute to lung cancer carcinogenesis. In this review, we summarize the smoking-activated signaling pathways involved in lung cancer.

  7. Quantitative texture-based assessment of one-year changes in fibrotic reticular patterns on HRCT in scleroderma lung disease treated with oral cyclophosphamide

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    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)


    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.)

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

    Directory of Open Access Journals (Sweden)

    Subhashis Sahu


    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.

  9. Heavy incense burning in temples promotes exposure risk from airborne PMs and carcinogenic PAHs. (United States)

    Chiang, Kuo-Chih; Liao, Chung-Min


    We present the mechanistic-based exposure and risk models, appraised with reported empirical data, to assess how the human exposure to airborne particulate matters (PMs) and carcinogenic polycyclic aromatic hydrocarbons (PAHs) during heavy incense burning episodes in temples. The models integrate size-dependent PM levels inside a temple from a published exploratory study associated with a human expiratory tract (HRT) model taking into account the personal exposure levels and size distributions in the HRT. The probabilistic exposure profiles of total-PAH levels inside a temple and internal PAHs doses are characterized by a physiologically based pharmacokinetic (PBPK) model with the reconstructed dose-response relationships based on an empirical three-parameter Hill equation model, describing PAHs toxicity for DNA adducts formation and lung tumor incidence responses in human white blood cells and lung. Results show that the alveolar-interstitial (AI) region has a lower mass median diameter (0.29 microm) than that in extrathoracic (ET(1), 0.37 microm), brochial (BB, 0.36 microm) and bronchiolar (bb, 0.32 microm) regions. The 50% probability (risk=0.5) of exceeding the DNA adducts frequency (DA(f)) ratio of 1.28 (95% CI: 0.55-2.40) and 1.78 (95% CI: 0.84-2.95) for external exposure of B[a]P and B[a]P(eq), respectively. The 10% (risk=0.1) probability or more of human affected by lung tumor is approximately 7.62x10(-5)% (95% CI: 3.39x10(-5)-1.71x10(-4)%) and 3.87x10(-4)% (95% CI: 1.72x10(-4)-8.69x10(-4)%) for internal exposure of B[a]P and B[a]P(eq), respectively. Our results implicate that exposure to smoke emitted from heavy incense burning may promote lung cancer risk. Our study provides a quantitative basis for objective risk prediction of heavy incense burning exposure in temples and for evaluating the effectiveness of management.

  10. Carcinogenicity of sublimed urethane in mice through the respiratory tract. (United States)

    Nomura, T; Hayashi, T; Masuyama, T; Tanaka, S; Nakajima, H; Kurokawa, N; Isa, Y


    The carcinogenicity of sublimed urethane (ethyl carbamate) in air was examined with mice. JCL:ICR mice were nursed in a plastic cage inside a vinyl chamber which was ventilated 4 times per hour. The mice were exposed to urethane gas for various periods by passing air which contained a high concentration of sublimed urethane (1.29 micrograms/ml) into the vinyl chamber, or by placing a vessel containing crystalline urethane inside the vinyl chamber so that it was filled with spontaneously-sublimed urethane gas at a low concentration (0.25 microgram/ml). When female mice were killed 5 months after exposure, lung tumor frequency increased almost linearly with the number of days of exposure in the low concentration experiment, but increased in a non-linear manner in the high concentration experiment. In terms of nearly the same total dose, i.e., (concentration of urethane gas in air) X (days of inhalation), one day of exposure to urethane gas at the low concentration induced lung tumors at a significantly higher frequency than 1/4 day of exposure to urethane gas at the high concentration. When male mice were killed at 12 months after exposure to examine the progressive change of induced tumors, malignant, invasive and metastatic tumors were found to have been induced more frequently in the lung after exposure to urethane gas at the low concentration (0.25 microgram/ml for 10 days) than at the high concentration (1.29 microgram/ml for 4 days), although the total dose in the former group was about half of that in the latter. Continuous exposure to urethane gas for a longer period at the low concentration seems to be more efficient for the induction, promotion and/or progression of lung tumors than the exposure for a shorter period at the high concentration.

  11. Cell-mediated mutagenesis by chemical carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Huberman, E.; Langenbach, R.


    The cell-mediated mutation system, with the proper choice of metabolizing cells, can be used to detect the mutagenic activities of different classes of chemical carcinogens. When fibroblastic cells were used as the metabolizing cells, a correlation between the in vivo carcinogenic activity and the in vitro mutagenic activity of 11 aromatic polycyclic hydrocarbons was observed. When primary liver cells were used as the metabolizing cells, three known liver carcinogens were demonstrated to be mutagenic by the cell-mediated assay, while two non-carcinogenic analogues were not mutagenic. These results from the cell-mediated system suggest that the reactive intermediates of the carcinogens are stable enough to be transferred from the metabolizing cells to the V79 cells. The cell-mediated mutagenesis system is a simple in vitro assay which may simulate the in vivo situation. It was concluded that this approach could be extended to the co-cultivation of cells from other organs or tissues with mutable mammalian cells.

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

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


    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

  13. A randomized trial to assess the utility of preintubation adult fiberoptic bronchoscope assessment in patients for thoracic surgery requiring one-lung ventilation (United States)

    Amin, Nayana; Tarwade, Pritee; Shetmahajan, Madhavi; Pramesh, C. S.; Jiwnani, Sabita; Mahajan, Abhishek; Purandare, Nilendu


    Background: Confirmation of placement of Double lumen endobronchial tubes (DLETT) and bronchial blockers (BBs) with the pediatric fiberoptic bronchoscope (FOB) is the most preferred practice worldwide. Most centers possess standard adult FOBs, some, particularly in developing countries might not have access to the pediatric-sized devices. We have evaluated the role of preintubation airway assessment using the former, measuring the distance from the incisors to the carina and from carina to the left and right upper lobe bronchus in deciding the depth of insertion of the lung isolation device. Methods: The study was a randomized, controlled, double-blind trial consisting of 84 patients (all >18 years) undergoing thoracic surgery over a 12-month period. In the study group (n = 38), measurements obtained during FOB with the adult bronchoscope decided the depth of insertion of the lung isolation device. In the control group (n = 46), DLETTs and BBs were placed blindly followed by clinical confirmation by auscultation. Selection of the type and size of the lung isolation device was at the discretion of the anesthesiologist conducting the case. In all cases, pediatric FOB was used to confirm accurate placement of devices. Results: Of 84 patients (DLETT used in 76 patients; BB used in 8 patients), preintubation airway measurements significantly improved the success rate of optimal placement of lung isolation device from 25% (11/44) to 50% (18/36) (P = 0.04). Our incidence of failed device placement at initial insertion was 4.7% (4/84). Incidence of malposition was 10% (8/80) with 4 cases in each group. The incidence of suboptimal placement was lower in the study group at 38.9% (14/36) versus 65.9% (29/44). Conclusions: Preintubation airway measurements with the adult FOB reduces airway manipulations and improves the success rate of optimal placement of DLETT and BB. PMID:27052065

  14. A randomized trial to assess the utility of preintubation adult fiberoptic bronchoscope assessment in patients for thoracic surgery requiring one - lung ventilation

    Directory of Open Access Journals (Sweden)

    Nayana Amin


    Full Text Available Background: Confirmation of placement of Double lumen endobronchial tubes (DLETT and bronchial blockers (BBs with the pediatric fiberoptic bronchoscope (FOB is the most preferred practice worldwide. Most centers possess standard adult FOBs, some, particularly in developing countries might not have access to the pediatric-sized devices. We have evaluated the role of preintubation airway assessment using the former, measuring the distance from the incisors to the carina and from carina to the left and right upper lobe bronchus in deciding the depth of insertion of the lung isolation device. Methods: The study was a randomized, controlled, double-blind trial consisting of 84 patients (all >18 years undergoing thoracic surgery over a 12-month period. In the study group (n = 38, measurements obtained during FOB with the adult bronchoscope decided the depth of insertion of the lung isolation device. In the control group (n = 46, DLETTs and BBs were placed blindly followed by clinical confirmation by auscultation. Selection of the type and size of the lung isolation device was at the discretion of the anesthesiologist conducting the case. In all cases, pediatric FOB was used to confirm accurate placement of devices. Results: Of 84 patients (DLETT used in 76 patients; BB used in 8 patients, preintubation airway measurements significantly improved the success rate of optimal placement of lung isolation device from 25% (11/44 to 50% (18/36 (P = 0.04. Our incidence of failed device placement at initial insertion was 4.7% (4/84. Incidence of malposition was 10% (8/80 with 4 cases in each group. The incidence of suboptimal placement was lower in the study group at 38.9% (14/36 versus 65.9% (29/44. Conclusions: Preintubation airway measurements with the adult FOB reduces airway manipulations and improves the success rate of optimal placement of DLETT and BB.

  15. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review. (United States)

    Chappell, Grace; Pogribny, Igor P; Guyton, Kathryn Z; Rusyn, Ivan


    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as "carcinogenic to humans" (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments.

  16. [Leather azo dyes: mutagenic and carcinogenic risks]. (United States)

    Clonfero, E; Venier, P; Granella, M; Levis, A G


    The paper reviews the carcinogenicity and mutagenicity data on azo dyes used in the leather industry. Two water soluble benzidine-based dyes were classified as "probably carcinogenic to humans" by the International Agency for Research on Cancer (IARC). No other dyes have been evaluated by the IARC. Of the 48 azo dyes assayed in the Salmonella/microsome test, 20 gave positive results. Attention is drawn to the important role of the in vivo metabolism of azo compounds, which includes a preliminary reduction of the azo bonds and subsequent release of the aromatic amines of the dye. A useful assay (Prival test) for evaluating the mutagenic properties of azo dyes involves a reductive step that permits the release of any genotoxic agents present in the compounds. A list of leather azo dyes is furnished that are considered as potentially harmful due to the presence of a carcinogenic aromatic amine (benzidine, p-aminobenzene and derivatives) in their formulae.

  17. Mutagenicity, carcinogenicity and teratogenicity of beryllium. (United States)

    Léonard, A; Lauwerys, R


    The carcinogenicity of a number of beryllium compounds has been confirmed in experiments on laboratory animals and this metal has to be treated as a possible carcinogenic threat to man. These carcinogenic properties are associated with mutagenic activity as shown by the results of short-term tests performed in vitro with beryllium chloride and beryllium sulfate. These soluble beryllium compounds can produce some infidelity of in vitro synthesis, forward gene mutations in microorganisms and in mammalian cells. They are also able to induce cell transformation. In addition to the positive results obtained in several short-term assays beryllium compounds have been found to bind to nucleoproteins, to inhibit certain enzymes needed for DNA synthesis, to bind nucleic acids to cell membranes and to inhibit microtubule polymerization. The teratogenicity of beryllium salts is relatively unknown and needs additional investigation.

  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


    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. Serial micro-CT assessment of the therapeutic effects of rosiglitazone in a bleomycin-induced lung fibrosis mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Eun Jung; Jin, Gong Yong; Bok, Se Mi; Han, Young Min; Lee, Young Sun; Jung, Myung Ja; Kwon, Keun Sang [Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Institute for Medical Sciences, Jeonju (Korea, Republic of)


    The aim of this study was to assess the therapeutic effects of rosiglitazone with serial micro-CT findings before and after rosiglitazone administration in a lung fibrosis mouse model induced with bleomycin. We instilled the bleomycin solution directly into the trachea in twenty mice (female, C57BL/6 mice). After the instillation with bleomycin, mice were closely observed for 3 weeks and then all mice were scanned using micro-CT without sacrifice. At 3 weeks, the mice were treated with rosiglitazone on days 21 to 27 if they had abnormal CT findings (n = 9, 45%). For the mice treated with rosiglitazone, we performed micro-CT with mouse sacrifice 2 weeks after the rosiglitazone treatment completion. We assessed the abnormal CT findings (ground glass attenuation, consolidation, bronchiectasis, reticular opacity, and honeycombing) using a five-point scale at 3 and 6 weeks using Wilcoxon-signed ranked test. The micro-CT findings were correlated with the histopathologic results. One out of nine (11.1%) mice improved completely. In terms of consolidation, all mice (100%) showed marked decrease from 3.1 ± 1.4 at 3 weeks to 0.9 ± 0.9 at 6 weeks (p = 0.006). At 6 weeks, mild bronchiectasis (n = 6, 66.7%), mild reticular opacity (n 7, 77.8%) and mild honeycomb patterns (n = 3, 33.3%) appeared. A serial micro-CT enables the evaluation of drug effects in a lung fibrosis mouse model.

  20. 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.


    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.

  1. Chicken Fetal Liver DNA Damage and Adduct Formation by Activation-Dependent DNA-Reactive Carcinogens and Related Compounds of Several Structural Classes



    The chicken egg genotoxicity assay (CEGA), which utilizes the liver of an intact and aseptic embryo-fetal test organism, was evaluated using four activation-dependent DNA-reactive carcinogens and four structurally related less potent carcinogens or non-carcinogens. In the assay, three daily doses of test substances were administered to eggs containing 9–11-day-old fetuses and the fetal livers were assessed for two endpoints, DNA breaks using the alkaline single cell gel electrophoresis (comet...

  2. State of the art toxicological and microscopic assessment of biomedical nanocrystals on the lung in vitro (United States)

    Clift, Martin J. D.; Gehr, Peter; Rothen-Rutishauser, Barbara


    Due to the ever increasing production of nanosized materials for a variety of novel applications (e.g. biomedicine), increased research has focused upon understanding the potential toxicity of these nanomaterials. In order to determine the potential toxicity of nanoparticles (NPs), it is essential that, in parallel to biochemical and toxicological testing, their specific route of uptake (if any), as well as their possible and/or subsequent intracellular localisation is investigated. By using a novel 3D in vitro triple cell co-culture model of the human epithelial airway barrier (containing epithelial cells and macrophages (apical-layer) and dendritic cells (basolateral-layer) which has been shown to mimic the architecture of the lung in vivo, in combination with a novel air-liquid interface cell exposure system, it is possible to mimic the exposure of NPs to the lung in vitro. Using both conventional and state-of-the art toxicological tests, in addition to light, laser scanning (including digital image restoration) and transmission electron microscopy methods, it has been possible to determine the interaction of both fluorescent (specifically designed core-shell nanoparticles with shell-embedded fluorophores for use in biomedicine) and electron dense NPs with the in vitro triple cell co-culture. It has been observed that the material of the engineered NPs (either gold or iron oxide) has no significant influence upon the toxicity and intracellular localisation over time. The results of these studies have shown that despite different compositions, specific NPs intended for use in biomedical applications, when exposed realistically (exposure method/concentration/primary contact cells) cause minimal effects to the lung in vitro.

  3. Lung function assessment using Xe-133 dynamic SPECT in dual-camera system

    Energy Technology Data Exchange (ETDEWEB)

    Sakaji, Katsuyuki; Akiyama, Masayuki; Nakazawa, Yasuo [Showa Univ., Tokyo (Japan). Hospital; Umeda, Hirotaka; Takenaka, Haruki; Shinozuka, Akira


    The purpose of this study was to estimate lung regional function using Xe-133 dynamic SPECT. SPECT equipment with a dual camera was used. Fourteen rotation acquisitions were obtained beginning immediately after Xe-133 gas inhalation. The time activity curve of each pixel was obtained, and T{sub 1/2} of the washout phase was calculated and mapped. Residual radioactivity was evaluated. Adequate images could be obtained at 30 seconds per rotation even with the dual-camera system. Mapping of T{sub 1/2} allowed temporal changes on one image. Three-dimensional evaluation could be made on a SPECT system using our method. (author)

  4. Longitudinal assessment of TUBB3 expression in non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Sørensen, Jens Benn


    Class-III-beta-tubulin (TUBB3) expression may be a potential predictive factor for treatment with microtubule interfering cytotoxic drugs in non-small cell lung cancer (NSCLC). Potential changes in TUBB3 expression during chemotherapy may be of interest if future choice of chemotherapy...... is to be based on TUBB3 expression. If the biomarker expression changes during chemotherapy, biopsies before initiation of chemotherapy beyond first line may be needed if treatment decision is to be based on TUBB3 expression. Thus, the aim was to explore TUBB3 expression heterogeneity and changes during...

  5. The construct validity of the health utilities index mark 3 in assessing health status in lung transplantation

    Directory of Open Access Journals (Sweden)

    Zuk Dalyce


    Full Text Available Abstract Purpose To assess the cross-sectional construct validity of the Health Utilities Index Mark 3 (HUI3 in lung transplantation. Methods Two hundred and thirteen patients (103 pre-transplant and 110 post-transplant with mean age 53 years old (SD 13 were recruited during a randomized controlled clinical trial at the out-patient clinic in a tertiary institution. At baseline, patients self-completed measures that included the HUI3, EuroQol EQ-5D, Hospital Anxiety and Depression Scale (HADS and socio-demographic questionnaire. Six-minute walk test scores and forced expiratory volume in 1 second data were collected from patient's medical records. A priori hypotheses were formulated by members of the transplant team about the expected degree of association between the measures. Correlation coefficients of Results Of the ninety predictions made, forty three were correct but in 31 the correlation was slightly lower than predicted and in 7 the correlations were much higher than predicted. In 48% of the cases, predicted and observed associations were in agreement. Predictions of associations were off by one category in 42% of the cases; in 10% of the cases the predictions were off by two categories. Conclusions This is the first study providing evidence of cross-sectional construct validity of HUI3 in lung transplantation. Results indicate that the HUI3 was able to capture the burden of lung disease before transplantation and that post-transplant patients enjoyed higher health-related quality of life than pre-transplant patients.

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

    NARCIS (Netherlands)

    Consonni, Dario; De Matteis, Sara; Olsson, Ann; Pesch, Beate; Kromhout, Hans; Straif, Kurt; Brüning, Thomas


    OBJECTIVES: Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies reported an excess of lung cancer among these workers. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case-control

  7. 40 CFR 799.9420 - TSCA carcinogenicity. (United States)


    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA carcinogenicity. 799.9420 Section 799.9420 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES... their selection. (ii) Age/weight. (A) Testing shall be started with young healthy animals as soon...

  8. 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)


    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.)

  9. Economic Issues in the Use of Office Spirometry for Lung Health Assessment

    Directory of Open Access Journals (Sweden)

    Murray Krahn


    Full Text Available The National Lung Health Education Program (United States has recently recommended using office spirometry to screen for subclinical lung disease in adult smokers. No published studies evaluate the economic consequences of this recommendation. This review article outlines the issues that must be considered when evaluating the costs and health benefits of office spirometry. Much of the available data on the effectiveness of screening is from studies that included smoking cessation interventions, making it difficult to determine the effects of screening alone. The sensitivity and specificity of screening spirometry are not known, but may not be important in the economic model, because even false positive test results are beneficial if they lead to smoking cessation. Costs to be considered include those of spirometry itself, of implementing and maintaining screening and smoking cessation programs, and of their consequences, ie, reduced morbidity (lower short term health care costs and mortality (perhaps higher long term health care costs. Despite these unique challenges, data are available to perform economic analyses regarding screening spirometry. Such analyses should play a role in future clinical policy making. Even modest quit rates attributable to screening spirometry may result in highly favourable cost effectiveness ratios.

  10. A case-control study of wood dust exposure, mutagen sensitivity, and lung cancer risk. (United States)

    Wu, X; Delclos, G L; Annegers, J F; Bondy, M L; Honn, S E; Henry, B; Hsu, T C; Spitz, M R


    The associations between lung cancer risk, mutagen sensitivity (a marker of cancer susceptibility), and a putative lung carcinogen, wood dust, were assessed in a hospital-based case-control study. There were 113 African -American and 67 Mexican-American cases with newly diagnosed, previously untreated lung cancer and 270 controls, frequency-matched on age, ethnicity, and sex. Mutagen sensitivity ( 1 chromatid break/cell after short-term bleomycin treatment) was associated with statistically significant elevated risk for lung cancer [odds ration (OR) = 4.3; 95% confidence intervals (CI) = 2.3-7.9]. Wood dust exposure was also a significant predictor of risk (overall OR = 3.5; CI = 1.4-8.6) after controlling for smoking and mutagen sensitivity. When stratified by ethnicity, wood dust exposure was s significant risk factor for African-Americans (OR = 5.5; CI = 1.6-18.9) but not for Mexican-Americans (OR = 2.0; CI = 0.5-8.1). The ORs were 3.8 and 4.8 for non-small cell lung cancer in Mexican-Americans (CI = 1.2-18.5). Stratified analysis suggested evidence of strong interactions between wood dust exposure and both mutagen sensitivity and smoking in lung cancer risk.

  11. 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


    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.

  12. Carcinogens formed when Meat is Cooked

    Energy Technology Data Exchange (ETDEWEB)

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


    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).

  13. Tumour heterogeneity in non-small cell lung carcinoma assessed by CT texture analysis: a potential marker of survival

    Energy Technology Data Exchange (ETDEWEB)

    Ganeshan, Balaji; Miles, Ken [Brighton and Sussex Medical School, Clinical Imaging Sciences Centre, Division of Clinical and Laboratory Investigation, Brighton, East Sussex (United Kingdom); Panayiotou, Elleny; Burnand, Kate [Brighton and Sussex University Hospitals NHS Trust, Brighton (United Kingdom); Dizdarevic, Sabina [Brighton and Sussex University Hospitals NHS Trust, Department of Nuclear Medicine, Royal Sussex County Hospital, Brighton (United Kingdom)


    To establish the potential for tumour heterogeneity in non-small cell lung cancer (NSCLC) as assessed by CT texture analysis (CTTA) to provide an independent marker of survival for patients with NSCLC. Tumour heterogeneity was assessed by CTTA of unenhanced images of primary pulmonary lesions from 54 patients undergoing {sup 18}F-fluorodeoxyglucose (FDG) PET-CT for staging of NSCLC. CTTA comprised image filtration to extract fine, medium and coarse features with quantification of the distribution of pixel values (uniformity) within the filtered images. Receiver operating characteristics identified thresholds for PET and CTTA parameters that were related to patient survival using Kaplan-Meier analysis. The median (range) survival was 29.5 (1-38) months. 24, 10, 14 and 6 patients had tumour stages I, II, III and IV respectively. PET stage and tumour heterogeneity assessed by CTTA were significant independent predictors of survival (PET stage: Odds ratio 3.85, 95% confidence limits 0.9-8.09, P = 0.002; CTTA: Odds ratio 56.4, 95% confidence limits 4.79-666, p = 0.001). SUV was not a significantly associated with survival. Assessment of tumour heterogeneity by CTTA of non-contrast enhanced images has the potential for to provide a novel, independent predictor of survival for patients with NSCLC. (orig.)

  14. Evidence supporting product standards for carcinogens in smokeless tobacco products. (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


    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.

  15. Assessment of impact of high particulate concentration on peak expiratory flow rate of lungs of sand stone quarry workers. (United States)

    Singh, Suresh Kumar; Chowdhary, G R; Purohit, Gopal


    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.

  16. Promotion of lung tumor growth by interleukin-17


    Xu, Beibei; Guenther, James F.; Pociask, Derek A.; Wang, Yu; Kolls, Jay K.; You, Zongbing; Chandrasekar, Bysani; Shan, Bin; Sullivan, Deborah E.; Morris, Gilbert F.


    Recent findings demonstrate that inhaled cigarette smoke, the predominant lung carcinogen, elicits a T helper 17 (Th17) inflammatory phenotype. Interleukin-17A (IL-17), the hallmark cytokine of Th17 inflammation, displays pro- and antitumorigenic properties in a manner that varies according to tumor type and assay system. To investigate the role of IL-17 in lung tumor growth, we used an autochthonous tumor model (K-RasLA1 mice) with lung delivery of a recombinant adenovirus that expresses IL-...

  17. Phase I metabolic genes and risk of lung cancer: multiple polymorphisms and mRNA expression.

    Directory of Open Access Journals (Sweden)

    Melissa Rotunno

    Full Text Available Polymorphisms in genes coding for enzymes that activate tobacco lung carcinogens may generate inter-individual differences in lung cancer risk. Previous studies had limited sample sizes, poor exposure characterization, and a few single nucleotide polymorphisms (SNPs tested in candidate genes. We analyzed 25 SNPs (some previously untested in 2101 primary lung cancer cases and 2120 population controls from the Environment And Genetics in Lung cancer Etiology (EAGLE study from six phase I metabolic genes, including cytochrome P450s, microsomal epoxide hydrolase, and myeloperoxidase. We evaluated the main genotype effects and genotype-smoking interactions in lung cancer risk overall and in the major histology subtypes. We tested the combined effect of multiple SNPs on lung cancer risk and on gene expression. Findings were prioritized based on significance thresholds and consistency across different analyses, and accounted for multiple testing and prior knowledge. Two haplotypes in EPHX1 were significantly associated with lung cancer risk in the overall population. In addition, CYP1B1 and CYP2A6 polymorphisms were inversely associated with adenocarcinoma and squamous cell carcinoma risk, respectively. Moreover, the association between CYP1A1 rs2606345 genotype and lung cancer was significantly modified by intensity of cigarette smoking, suggesting an underlying dose-response mechanism. Finally, increasing number of variants at CYP1A1/A2 genes revealed significant protection in never smokers and risk in ever smokers. Results were supported by differential gene expression in non-tumor lung tissue samples with down-regulation of CYP1A1 in never smokers and up-regulation in smokers from CYP1A1/A2 SNPs. The significant haplotype associations emphasize that the effect of multiple SNPs may be important despite null single SNP-associations, and warrants consideration in genome-wide association studies (GWAS. Our findings emphasize the necessity of post

  18. 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.

  19. Incorporating potency into EU classification for carcinogenicity and reproductive toxicity. (United States)

    Hennes, C; Batke, M; Bomann, W; Duhayon, S; Kosemund, K; Politano, V; Stinchcombe, S; Doe, J


    Although risk assessment, assessing the potential harm of each particular exposure of a substance, is desirable, it is not feasible in many situations. Risk assessment uses a process of hazard identification, hazard characterisation, and exposure assessment as its components. In the absence of risk assessment, the purpose of classification is to give broad guidance (through the label) on the suitability of a chemical in a range of use situations. Hazard classification in the EU is a process involving identification of the hazards of a substance, followed by comparison of those hazards (including degree of hazard) with defined criteria. Classification should therefore give guidance on degree of hazard as well as hazard identification. Potency is the most important indicator of degree of hazard and should therefore be included in classification. This is done for acute lethality and general toxicity by classifying on dose required to cause the effect. The classification in the EU for carcinogenicity and reproductive toxicity does not discriminate across the wide range of potencies seen (6 orders of magnitude) for carcinogenicity and for developmental toxicity and fertility. Therefore potency should be included in the classification process. The methodology in the EU guidelines for classification for deriving specific concentration limits is a rigorous process for assigning substances which cause tumours or developmental toxicity and infertility in experimental animals to high, medium or low degree of hazard categories by incorporating potency. Methods are suggested on how the degree of hazard so derived could be used in the EU classification process to improve hazard communication and in downstream risk management.

  20. Polonium and lung cancer. (United States)

    Zagà, Vincenzo; Lygidakis, Charilaos; Chaouachi, Kamal; Gattavecchia, Enrico


    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. Polonium and Lung Cancer

    Directory of Open Access Journals (Sweden)

    Vincenzo Zagà


    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.

  2. Disease-specific survival for limited-stage small-cell lung cancer affected by statistical method of assessment

    Directory of Open Access Journals (Sweden)

    Yuan Fei


    Full Text Available Abstract Background In general, prognosis and impact of prognostic/predictive factors are assessed with Kaplan-Meier plots and/or the Cox proportional hazard model. There might be substantive differences from the results using these models for the same patients, if different statistical methods were used, for example, Boag log-normal (cure-rate model, or log-normal survival analysis. Methods Cohort of 244 limited-stage small-cell lung cancer patients, were accrued between 1981 and 1998, and followed to the end of 2005. The endpoint was death with or from lung cancer, for disease-specific survival (DSS. DSS at 1-, 3- and 5-years, with 95% confidence limits, are reported for all patients using the Boag, Kaplan-Meier, Cox, and log-normal survival analysis methods. Factors with significant effects on DSS were identified with step-wise forward multivariate Cox and log-normal survival analyses. Then, DSS was ascertained for patients with specific characteristics defined by these factors. Results The median follow-up of those alive was 9.5 years. The lack of events after 1966 days precluded comparison after 5 years. DSS assessed by the four methods in the full cohort differed by 0–2% at 1 year, 0–12% at 3 years, and 0–1% at 5 years. Log-normal survival analysis indicated DSS of 38% at 3 years, 10–12% higher than with other methods; univariate 95% confidence limits were non-overlapping. Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC obstruction significantly impacted DSS. DSS assessed by the Cox and log-normal survival analysis methods for four clinical risk groups differed by 1–6% at 1 year, 15–26% at 3 years, and 0–12% at 5 years; multivariate 95% confidence limits were overlapping in all instances. Conclusion Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC obstruction all significantly impacted DSS. Apparent DSS for patients was influenced by the

  3. Lung Cancer and Occupational Exposure to Combustion Products


    Olsson, Ann


    Lung cancer, the most common cause of cancer death, is predominantly attributable to tobacco smoking. One of the many carcinogenic components of tobacco smoke are polycyclic aromatic hydrocarbons (PAH). Several occupational exposures containing high levels of PAHs are classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer (IARC). Bitumen fumes and diesel motor exhaust (DME) which are complex mixtures of agents containing small qua...

  4. Reevaluating the carcinogenicity of ortho-toluidine: a new conclusion and its implications. (United States)

    Sellers, C; Markowitz, S


    The aromatic amine ortho-toluidine has been recognized by IARC as an animal carcinogen for the past decade. Three recent epidemiological studies of worker populations have now implicated this chemical as a human bladder carcinogen. In a study by E. Ward, A. Carpenter, S. Markowitz, D. Roberts, and W. Halperin ((1991), J. Natl. Cancer Inst. 83, 501-506), workers definitely exposed to ortho-toluidine for at least 10 years experienced a Standardized Incidence Ratio (SIR) of 27.2 (90% CI = 11.8-53.7). The other major exposure was to aniline, which significant epidemiological studies have failed to confirm as a human carcinogen. In retrospect, studies by G. F. Rubino, G. Scansetti, G. Piolatto ((1982) Environ. Res. 27, 241-254) and M. J. Stasik ((1988) Int. Arch. Occup. Environ. Health 60, 21-24) also support the hypothesis that ortho-toluidine is a human bladder carcinogen. Animal studies of both ortho-toluidine and its possible confounders in these epidemiological investigations further confirm this hypothesis. When evaluated in a suitably comprehensive way, according to the traditional standards for assessing causality outlined by A. B. Hill ((1977) A Short Textbook of Medical Statistics, pp. 288-294, Lippincott, Philadelphia) the evidence that ortho-toluidine causes human bladder cancer has become much more conclusive. In this case, animal tests have proven a good predictor of human carcinogenicity.

  5. [Using the evaluation of carcinogenic risk in the mining and metallurgical enterprises of the Arctic]. (United States)

    Serebriakov, P V


    The aim of this study--hygienic assessment of the contribution of factors of working environment) in the formation of carcinogenic risk to the mining and metallurgical enterprises of the Far North, the establishment of the structural features of cancer pathology among workers of these enterprises, quantitative evaluation of individual professional cancer risk in different nosological forms and morphological variants of malignant neoplasms.

  6. A review of human carcinogens - Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish

    Energy Technology Data Exchange (ETDEWEB)

    Secretan, B.; Straif, K.; Baan, R.; Grosse, Y.; El Ghissassi, F.; Bouvard, V.; Benbrahim-Tallaa, L.; Guha, N.; Freeman, C.; Galichet, L.; Cogliano, V. [International Agency for Research on Cancer, Lyon (France)


    In October, 2009, 30 scientists from 10 countries met at the International Agency for Research on Cancer (IARC) to reassess the carcinogenicity of tobacco, areca nut, alcohol, coal smoke, and salt-preserved fish, and to identify additional tumor sites and mechanisms of carcinogenesis. These assessments will be published as Part E of Volume 100 of the IARC Monographs.

  7. [Carcinogenic activity of the pesticide propoxur]. (United States)

    Pylev, L N; Vasil'eva, L A; Smirnova, O V; Khrustalev, S A; Trukhina, G M


    Wistar rats were fed propoxur in their diet at 0, 500, 3000, and 8000 ppm during throughout their life. The number of tumors was equal in the control and experimental groups. These were hemoblastoses and breast and uterine tumors. All tumors occurred spontaneously in the rats. A few experimental animals were found to have bladder epithelial hyperplasia that might be pretumorous; however, no bladder tumors were detected. It is concluded that the investigations revealed no carcinogenic activity of propoxur.

  8. The evolving definition of carcinogenic human papillomavirus

    Directory of Open Access Journals (Sweden)

    Castle Philip E


    Full Text Available Abstract Thirteen human papillomavirus (HPV genotypes have been judged to be carcinogenic or probably carcinogenic, and the cause of virtually all cervical cancer worldwide. Other HPV genotypes could possibly be involved. Although the inclusion of possibly carcinogenic HPV genotypes may hurt test specificity, it may indirectly increase the reassurance following a negative HPV test (i.e. the negative predictive value of an HPV test for cervical precancer and cancer. The future of cervical cancer screening in low-resource setting, however, may include once-in-a-lifetime, low-cost and rapid HPV testing. However, the tradeoff of more false positives for greater reassurance may not be acceptable if the local infrastructure cannot manage the screen positives. Now is the time for the community of scientists, doctors, and public health advocates to use the data presented at the 100th International Agency for Research on Cancer monograph meeting to rationally decide the target HPV genotypes for the next generation of HPV tests for use in high-resource and low-resource settings. The implications of including possibly HPV genotypes on HPV test performance, also for guidance on the use of these tests for cervical cancer prevention programs, are discussed.

  9. International Conference on Harmonisation; proposed change to rodent carcinogenicity testing of pharmaceuticals; request for comments. Notice; request for comments. (United States)


    The Food and Drug Administration (FDA or the Agency) is considering a proposed change to the International Conference on Harmonisation (ICH) Sl guidance on rodent carcinogenicity testing. The goal of this potential change is to introduce a more comprehensive and integrated approach to address the risk of human carcinogenicity of small molecule pharmaceuticals, and to define conditions under which 2-year rodent carcinogenicity studies add value to that assessment. The basis of this proposed change is the retrospective analyses of several datasets that reflect three decades of experience with such studies. The datasets suggest that knowledge of certain pharmacologic and toxicologic data can sometimes provide sufficient information to anticipate the outcome of 2-year rodent studies and their potential value in predicting the risk of human carcinogenicity of a given pharmaceutical. FDA is requesting public comment regarding a proposed change in approach to carcinogenicity assessment, on the prospective evaluation period intended to test this new approach, and on the proposed weight-of-evidence factors for carcinogenicity assessment.

  10. 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


    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.

  11. Inhalation toxicity and carcinogenicity studies of cobalt sulfate. (United States)

    Bucher, J R; Hailey, J R; Roycroft, J R; Haseman, J K; Sills, R C; Grumbein, S L; Mellick, P W; Chou, B J


    Cobalt sulfate is a water-soluble cobalt salt with a variety of industrial and agricultural uses. Several cobalt compounds have induced sarcomas at injection sites in animals, and reports have suggested that exposure to cobalt-containing materials may cause lung cancer in humans. The present studies were done because no adequate rodent carcinogenicity studies had been performed with a soluble cobalt salt using a route relevant to occupational exposures. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate hexahydrate, 6 h/day, 5 days/week, for 104 weeks. Survival and body weights of exposed rats and mice were generally unaffected by the exposures. In rats, proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were observed in the lung in all exposed groups. Nonneoplastic lesions of the nose and larynx were also attributed to exposure to all concentrations of cobalt sulfate. In 3.0 mg/m3 male rats and in female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were increased over those in the control groups. Lung tumors occurred with significant positive trends in both sexes. The incidences of adrenal pheochromocytoma in 1.0 mg/m3 male rats and in 3.0 mg/m3 female rats were increased. Nonneoplastic lesions of the respiratory tract were less severe in mice than in rats. In mice, alveolar/bronchiolar neoplasms in 3.0 mg/m3 males and females were greater than those in the controls, and lung tumors occurred with significantly positive trends. Male mice had liver lesions consistent with a Helicobacter hepaticus infection. Incidences of liver hemangiosarcomas were increased in exposed groups of male mice; however, because of the infection, no conclusion could be reached concerning an association between liver hemangiosarcomas and cobalt sulfate. In summary, exposure to cobalt sulfate by inhalation

  12. 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)


    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

  13. 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)


    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

  14. The Impact of Homogeneous Versus Heterogeneous Emphysema on Dynamic Hyperinflation in Patients With Severe COPD Assessed for Lung Volume Reduction. (United States)

    Boutou, Afroditi K; Zoumot, Zaid; Nair, Arjun; Davey, Claire; Hansell, David M; Jamurtas, Athanasios; Polkey, Michael I; Hopkinson, Nicholas S


    Dynamic hyperinflation (DH) is a pathophysiologic hallmark of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to investigate the impact of emphysema distribution on DH during a maximal cardiopulmonary exercise test (CPET) in patients with severe COPD. This was a retrospective analysis of prospectively collected data among severe COPD patients who underwent thoracic high-resolution computed tomography, full lung function measurements and maximal CPET with inspiratory manouvers as assessment for a lung volume reduction procedure. ΔIC was calculated by subtracting the end-exercise inspiratory capacity (eIC) from resting IC (rIC) and expressed as a percentage of rIC (ΔIC%). Emphysema quantification was conducted at 3 predefined levels using the syngo PULMO-CT (Siemens AG); a difference >25% between best and worse slice was defined as heterogeneous emphysema. Fifty patients with heterogeneous (62.7% male; 60.9 ± 7.5 years old; FEV1% = 32.4 ± 11.4) and 14 with homogeneous emphysema (61.5% male; 62.5 ± 5.9 years old; FEV1% = 28.1 ± 10.3) fulfilled the enrolment criteria. The groups were matched for all baseline variables. ΔIC% was significantly higher in homogeneous emphysema (39.8% ± 9.8% vs.31.2% ± 13%, p = 0.031), while no other CPET parameter differed between the groups. Upper lobe predominance of emphysema correlated positively with peak oxygen pulse, peak oxygen uptake and peak respiratory rate, and negatively with ΔIC%. Homogeneous emphysema is associated with more DH during maximum exercise in COPD patients.

  15. Evaluation of correlation between CT image features and ERCC1 protein expression in assessing lung cancer prognosis (United States)

    Tan, Maxine; Emaminejad, Nastaran; Qian, Wei; Sun, Shenshen; Kang, Yan; Guan, Yubao; Lure, Fleming; Zheng, Bin


    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.

  16. Carcinogenicity of consumption of red and processed meat: What about environmental contaminants? (United States)

    Domingo, José L; Nadal, Martí


    In October 26, 2015, the International Agency for Research on Cancer (IARC) issued a press release informing of the recent evaluation of the carcinogenicity of red and processed meat consumption. The consumption of red meat and processed meat was classified as "probably carcinogenic to humans", and as "carcinogenic to humans", respectively. The substances responsible of this potential carcinogenicity would be generated during meat processing, such as curing and smoking, or when meat is heated at high temperatures (N-nitroso-compounds, polycyclic aromatic hydrocarbons and heterocyclic aromatic amines). However, in its assessments, the IARC did not make any reference to the role that may pose some carcinogenic environmental pollutants, which are already present in raw or unprocessed meat. The potential role of a number of environmental chemical contaminants (toxic trace elements, polycyclic aromatic hydrocarbons, polychlorinated dibenzo-p-dioxins and dibenzofurans, polychlorinated biphenyls, polybrominated diphenyl ethers, polychlorinated diphenyl ethers, polychlorinated naphthalenes and perfluoroalkyl substances) on the carcinogenicity of consumption of meat and meat products is discussed in this paper. A case-study, Catalonia (Spain), is specifically assessed, while the influence of cooking on the concentrations of environmental pollutants is also reviewed. It is concluded that although certain cooking processes could modify the levels of chemical contaminants in food, the influence of cooking on the pollutant concentrations depends not only on the particular cooking process, but even more on their original contents in each specific food item. As most of these environmental pollutants are organic, cooking procedures that release or remove fat from the meat should tend to reduce the total concentrations of these contaminants in the cooked meat.

  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)


    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. Outcome assessment for clinical trials: how many adjudicators do we need? Canadian Lung Oncology Group. (United States)

    Walter, S D; Cook, D J; Guyatt, G H; King, D; Troyan, S


    Considerable effort is often expended to adjudicate outcomes in clinical trials, but little has been written on the administration of the adjudication process and its possible impact on study results. As a case study, we describe the function and performance of an adjudication committee in a large randomized trial of two diagnostic approaches to potentially operable lung cancer. Up to five independent adjudicators independently determined two primary outcomes: tumor status at death or at final follow-up and the cause of death. Patients for whom there was any disagreement were discussed in committee until a consensus was achieved. We describe the pattern of agreement among the adjudicators and with the final consensus result. Additionally, we model the adjudication process and predict the results if a smaller committee had been used. We found that reducing the number of adjudicators from five to two or three would probably have changed the consensus outcome in less than 10% of cases. Correspondingly, the effect on the final study results (comparing primary outcomes in both randomized arms) would have been altered very little. Even using a single adjudicator would not have affected the results substantially. About 90 minutes of person-time per patient was required for activities directly related to the adjudication process, or approximately 6 months of full time work for the entire study. This level of effort could be substantially reduced by using fewer adjudicators with little impact on the results. Thus, we suggest that when high observer agreement is demonstrated or anticipated, adjudication committees should consist of no more than three members. Further work is needed to evaluate if smaller committees are adequate to detect small but important treatment effects or if they compromise validity when the level of adjudicator agreement is lower.

  19. Home spirometry: Assessment of patient compliance and satisfaction and its impact on early diagnosis of pulmonary symptoms in post-lung transplantation patients. (United States)

    Fadaizadeh, Lida; Najafizadeh, Katayoun; Shajareh, Elham; Shafaghi, Shadi; Hosseini, Mahsa; Heydari, Gholamreza


    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.

  20. 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;


    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.......499). Conclusions: 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. Key Points: • Visually detected emphysema on CT is more frequent in individuals who develop lung cancer...

  1. Inter-rater agreement for a retrospective exposure assessment of asbestos, chromium, nickel and welding fumes in a study of lung cancer and ionizing radiation. (United States)

    Seel, E A; Zaebst, D D; Hein, M J; Liu, J; Nowlin, S J; Chen, P


    A retrospective exposure assessment of asbestos, welding fumes, chromium and nickel (in welding fumes) was conducted at the Portsmouth Naval Shipyard for a nested case-control study of lung cancer risk from external ionizing radiation. These four contaminants were included because of their potential to confound or modify the effect of a lung cancer-radiation relationship. The exposure assessment included three experienced industrial hygienists from the shipyard who independently assessed exposures for 3519 shop/job/time period combinations. A consensus process was used to resolve estimates with large differences. Final exposure estimates were linked to employment histories of the 4388 study subjects to calculate their cumulative exposures. Inter-rater agreement analyses were performed on the original estimates to better understand the estimation process. Although concordance was good to excellent (78-99%) for intensity estimates and excellent (96-99%) for frequency estimates, overall simple kappa statistics indicated only slight agreement beyond chance (kappa asbestos exposures were higher in the early years and fell in the mid-1970s. Mean cumulative exposure for all study subjects was 520 fiber-days cc(-1) for asbestos and 1000 mg-days m(-3) for welding fumes. Mean exposure was much lower for nickel (140 microg-days m(-3)) and chromium (45 microg-days m(-3)). Asbestos and welding fume exposure estimates were positively associated with lung cancer in the nested case-control study. The radiation-lung cancer relationship was attenuated by the inclusion of these two confounders. This exposure assessment provided exposure estimates that aided in understanding of the lung cancer-radiation relationship at the shipyard.

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

    Institute of Scientific and Technical Information of China (English)


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

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

    DEFF Research Database (Denmark)

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


    Magnetic resonance imaging of the apparent diffusion coefficient (ADC) of hyperpolarized Helium-3 is a new technique for probing pulmonary microstructure in vivo. The aim of this study was the assessment of potential sources of systematic errors of the ADC measurement. The influence of macroscopic...

  4. Evaluation of the carcinogenic potential of pharmaceuticals. Opportunities arising from the International Conference on Harmonisation. (United States)

    Monro, A M; MacDonald, J S


    The evaluation of the carcinogenic potential of pharmaceuticals is currently undergoing dramatic changes. For the past 25 years the regulatory expectation for agents intended for long term use has been that lifespan studies (usually lasting 2 years) in 2 rodent species be conducted. These studies take at least 3 years to plan, execute and interpret, and use over 1200 animals. It is now recognised that the quality of the information obtained from these studies is unreliable for prediction of carcinogenic risk to humans. Over the past 4 years, the International Conference on Harmonisation (ICH) has recommended changes in approaches to assessing the carcinogenic potential of pharmaceuticals. In future, only one long term rodent study will be routinely required (usually in rats), provided this is complemented with a short or medium term test in one of the emerging new models for carcinogenicity, such as transgenic mice or newborn mice. However, the relevance of these new models to human cancer and their use in risk assessment is still largely unknown and this situation must be kept under review as knowledge accumulates. A long term study in a second rodent species is still an option. Dose selection has also been improved inasmuch as there are now several alternatives to the use of the maximum tolerated dose (MTD). In the past, the use of the MTD, when the normal homeostasis of the test animals is disturbed, has been considered one of the major problems with the rodent carcinogenicity bioassay. However, one of the alternative end-points to the use of the MTD, i.e. the comparison of plasma concentrations in rodents and humans, must be viewed with caution. While this may contribute to limiting the high dose level for agents of very low toxicity, the concept should not be interpreted as signifying that plasma concentrations provide a sound basis for comparing the carcinogenic activity of agents in different species. Recognition of the 4 properties (genotoxicity

  5. Lung transplant (United States)

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

  6. 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


    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.

  7. Soluble Human Epidermal Growth Factor Receptor 2 (sHER2 as a Potential Risk Assessment, Screening, and Diagnostic Biomarker of Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Andre T. Baron


    Full Text Available Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2 for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC using an unmatched case-control study design. Serum sHER2 concentrations were measured by immunoassay in 244 primary NSCLC cases and 218 healthy controls. Wilcoxon rank-sum tests, logistic regression models, and receiver operating characteristic plots were used to assess whether sHER2 is associated with lung cancer. Median serum sHER2 concentrations are higher in patients with adenocarcinoma than squamous cell carcinoma regardless of gender, and sHER2 is a weak, independent biomarker of adenocarcinoma, but not of squamous cell carcinoma, adjusted for age and gender. The age-adjusted relative risk (odds of adenocarcinoma is 3.95 (95% CI: 1.22, 12.81 and 7.93 (95% CI: 2.26, 27.82 greater for women and men with high sHER2 concentrations (≥6.60 ng/mL vs. low sHER2 concentrations (≤1.85 ng/mL, respectively. When adjusted for each other, sHER2, age, and gender discern healthy controls from patients with primary adenocarcinomas of the lung with 85.9% accuracy. We conclude that even though serum sHER2 is not a strong, stand-alone discriminatory biomarker of adenocarcinoma, sHER2 may be a useful, independent covariate in multivariate risk assessment, screening, and diagnostic models of lung cancer.

  8. Can creatine supplementation form carcinogenic heterocyclic amines in humans? (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


    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

  9. Pulmonary structure and function analysis in systemic sclerosis : clinical assessment of complicating interstitial lung disease and pulmonary vasculopathy

    NARCIS (Netherlands)

    Ninaber, Maarten


    In SSc, we evaluated the optimal percentile density score in SSc by quantitative CT densitometry, against pulmonary function. Lung volumes and the nth percentile density (between 1 and 99%) of the entire lungs were calculated from CT histograms. The nth percentile density is defined as the threshold

  10. 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)


    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.)

  11. 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;


    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....

  12. Lung cancer biomarkers for the assessment of modified risk tobacco products: an oxidative stress perspective. (United States)

    Lowe, Frazer J; Luettich, Karsta; Gregg, Evan O


    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.

  13. Exposure and Metabolic Activation Biomarkers of Carcinogenic Tobacco-Specific Nitrosamines. (United States)

    Hecht, Stephen S; Stepanov, Irina; Carmella, Steven G


    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

  14. Comparison of rat olfactory mucosal responses to carcinogenic and non-carcinogenic chloracetanilides (United States)

    Genter, M.B.; Warner, B.M.; Medvedovic, M.; Sartor, M.A.


    Alachlor and butachlor are chloracetanilide herbicides that induce olfactory tumors in rats, whereas propachlor does not. The mechanism by which alachlor induces tumors is distinct from many other nasal carcinogens, in that alachlor induces a gradual de-differentiation of the olfactory mucosa (OM) to a more respiratory-like epithelium, in contrast to other agents that induce cytotoxicity, followed by an aberrant regenerative response. We studied biochemical and genomic effects of these compounds to identify processes that occur in common between alachlor- and butachlor-treated rats. Because we have previously shown that matrix metalloproteinase-2 (MMP2) is activated in OM by alachlor, in the present studies we evaluated both MMP2 activation and changes in OM gene expression in response to carcinogenic and non-carcinogenic chloracetanilide treatments. All three chloracetanilides activated MMP2, and > 300 genes were significantly up- or downregulated between control and alachlor-treated rats. The most significantly regulated gene was vomeromodulin, which was dramatically upregulated by alachlor and butachlor treatment (>60-fold), but not by propachlor treatment. Except for similar gene responses in alachlor- and butachlor-treated rats, we did not identify clear-cut differences that would predict OM carcinogenicity in this study. PMID:19425180

  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


    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. Molecular heterogeneity assessment by next-generation sequencing and response to gefitinib of EGFR mutant advanced lung adenocarcinoma. (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


    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.

  17. Radiomics versus physician assessment for the early prediction of local cancer recurrence after stereotactic radiotherapy for lung cancer (United States)

    Mattonen, Sarah A.; Johnson, Carol; Palma, David A.; Rodrigues, George; Louie, Alexander V.; Senan, Suresh; Yeung, Timothy P. C.; Ward, Aaron D.


    Stereotactic ablative radiotherapy (SABR) has recently become a standard treatment option for patients with early-stage lung cancer, which achieves local control rates similar to surgery. Local recurrence following SABR typically presents after one year post-treatment. However, benign radiological changes mimicking local recurrence can appear on CT imaging following SABR, complicating the assessment of response. We hypothesize that subtle changes on early post- SABR CT images are important in predicting the eventual incidence of local recurrence and would be extremely valuable to support timely salvage interventions. The objective of this study was to extract radiomic image features on post-SABR follow-up images for 45 patients (15 with local recurrence and 30 without) to aid in the early prediction of local recurrence. Three blinded thoracic radiation oncologists were also asked to score follow-up images as benign injury or local recurrence. A radiomic signature consisting of five image features demonstrated a classification error of 24%, false positive rate (FPR) of 24%, false negative rate (FNR) of 23%, and area under the receiver operating characteristic curve (AUC) of 0.85 at 2-5 months post-SABR. At the same time point, three physicians assessed the majority of images as benign injury for overall errors of 34-37%, FPRs of 0-4%, and FNRs of 100%. These results suggest that radiomics can detect early changes associated with local recurrence which are not typically considered by physicians. We aim to develop a decision support system which could potentially allow for early salvage therapy of patients with local recurrence following SABR.

  18. Exposure assessment and modeling of quartz in Swedish iron foundries for a nested case-control study on lung cancer. (United States)

    Andersson, Lena; Bryngelsson, Ing-Liss; Ngo, Yen; Ohlson, Carl-Göran; Westberg, Håkan


    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.

  19. Scientific analysis of the proposed uses of the T25 dose descriptor in chemical carcinogen regulation. (United States)

    Roberts, R A; Crump, K S; Lutz, W K; Wiegand, H J; Williams, G M; Harrison, P T; Purchase, I F


    The uncertainties that surround the methods used for risk assessment of exposure to carcinogens have been highlighted by a recent document advocating an approach based on the T25 dose (the dose giving a 25% incidence of cancer in an appropriately designed animal experiment). This method relies on derivation of the T25 dose then assesses risk at the exposure dose using proportionality provided by a linear extrapolation (T25/linear). To promote discussion of the scientific issues underlying methods for the risk assessment of chemical carcinogens, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) hosted a one-day workshop in Brussels on 10 November 2000. Several invited presentations were made to participants, including scientists from regulatory authorities, industry and academia. In general, it was felt that there was sufficient basis for using the T25 dose as an index of carcinogenic potency and hence as part of the hazard assessment process. However, the use of the T25 in risk assessment has not been validated. The T25/linear and other extrapolation methods based on metrics such as LED 10 assume linearity which may be invalid. Any risk calculated using the T25/linear method would provide a precise risk figure similar to the output obtained from the Linearised Multistage (LMS) method formerly used by the Environmental Protection Agency (EPA) in the United States of America. Similarity of output does not provide validation but rather reflects their reliance on similar mathematical approaches. In addition to the T25 issue, evidence was provided that using two separate methods (linearised non-threshold model for genotoxic carcinogens; no-observable-effect level with a safety factor (NOEL/SF) method for all other toxicity including non-genotoxic carcinogens) is not justified. Since the ultimate purpose of risk assessment is to provide reliable information to risk managers and the public, there was strong support at the workshop for

  20. Occurrence, uses, and carcinogenicity of arylamines. (United States)

    Chung, King-Thom


    Arylamines are chemically synthesized and contained in oxidants, epoxy polymers, explosives, fungicides, pesticides, colorants, polyurethanes, and used in rubber, pharmacology, cosmetics, and other chemical industries. Many arylamines are ubiquitously present in cigarette smoke, cooking fume hoods, foods, automobile exhaust, industrial sites, etc. Some arylamines can be generated through azo reduction by intestinal, skin, and environmental microorganisms from azo dyes that are widely used. Arylamines can also be generated by reduction of the nitro-group containing polyhydrated hydrocarbons including muntions. Some arylamines are released by burning nitrogen containing organic materials at high temperatures. Some medical drugs are also arylamines. Furthermore, many arylamines are essential constituents of normal metabolism or the result of abnormal metabolism or dietary sources. Some arylamines are mutagenic, carcinogenic or the cause of other kinds of maladies. Some arylamine are considered the major etiological agents of bladder tumors in humans and animals but may also induce other types of cancers in various organs. The organ, tissue, and species specificity of the arylamine-inducing carcinogenesis may be determined by their availability, distribution, and the presence of metabolic activation/detoxicification enzymes of each organ or tissue of different species. The ubiquitous arylamines, therefore, pose serious hazards to human health and environment. This article will address the occurrence, uses, carcinogenicity, and other arylamines-induced diseases.

  1. Wood dust exposure and lung cancer risk: a meta-analysis. (United States)

    Hancock, David G; Langley, Mary E; Chia, Kwan Leung; Woodman, Richard J; Shanahan, E Michael


    Occupational lung cancers represent a major health burden due to their increasing prevalence and poor long-term outcomes. While wood dust is a confirmed human carcinogen, its association with lung cancer remains unclear due to inconsistent findings in the literature. We aimed to clarify this association using meta-analysis. We performed a search of 10 databases to identify studies published until June 2014. We assessed the lung cancer risk associated with wood dust exposure as the primary outcome and with wood dust-related occupations as a secondary outcome. Random-effects models were used to pool summary risk estimates. 85 publications were included in the meta-analysis. A significantly increased risk for developing lung cancer was observed among studies that directly assessed wood dust exposure (RR 1.21, 95% CI 1.05 to 1.39, n=33) and that assessed wood dust-related occupations (RR 1.15, 95% CI 1.07 to 1.23, n=59). In contrast, a reduced risk for lung cancer was observed among wood dust (RR 0.63, 95% CI 0.39 to 0.99, n=5) and occupation (RR 0.96, 95% CI 0.95 to 0.98, n=1) studies originating in Nordic countries, where softwood dust is the primary exposure. These results were independent of the presence of adjustment for smoking and exposure classification methods. Only minor differences in risk between the histological subtypes were identified. This meta-analysis provides strong evidence for an association between wood dust and lung cancer, which is critically influenced by the geographic region of the study. The reasons for this region-specific effect estimates remain to be clarified, but may suggest a differential effect for hardwood and softwood dusts.

  2. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. (United States)

    Hecht, Stephen S


    The devastating link between tobacco products and human cancers results from a powerful alliance of two factors - nicotine and carcinogens. Without either one of these, tobacco would be just another commodity, instead of being the single greatest cause of death due to preventable cancer. Nicotine is addictive and toxic, but it is not carcinogenic. This addiction, however, causes people to use tobacco products continually, and these products contain many carcinogens. What are the mechanisms by which this deadly combination leads to 30% of cancer-related deaths in developed countries, and how can carcinogen biomarkers help to reveal these mechanisms?

  3. Coal fires, industrial emissions and motor vehicles as sources of environmental carcinogens. (United States)

    Lawther, P J; Waller, R E


    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.

  4. 99mTc-MIBI Lung Scintigraphy in the Assessment of Pulmonary Involvement in Interstitial Lung Disease and Its Comparison With Pulmonary Function Tests and High-Resolution Computed Tomography: A Preliminary Study. (United States)

    Bahtouee, Mehrzad; Saberifard, Jamshid; Javadi, Hamid; Nabipour, Iraj; Raeisi, Alireza; Assadi, Majid; Eftekhari, Mohammad


    The differentiation of active inflammatory processes from an inactive form of the disease is of great value in the management of interstitial lung disease (ILD). The aim of this investigation was to assess the efficacy of 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) scans in distinguishing the severity of the disease compared to radiological and clinical parameters.In total, 19 known cases of ILD were included in this study and were followed up for 1 year. Five patients without lung disease were considered as the control group. The patients underwent pulmonary function tests (PFTs) and high-resolution computed tomography scans, followed by 99mTc-MIBI scanning. The 99mTc-MIBI scans were analyzed either qualitatively (subjectively) or semiquantitatively.All 19 ILD patients demonstrated a strong increase in 99mTc-MIBI uptake in the lungs compared to the control group. The 99mTc-MIBI scan scores were higher in the patient group in both the early phase (0.24[0.19-0.31] vs 0.11[0.10-0.15], P 0.14). The 99mTc-MIBI scan scores were not significantly correlated with the PFT findings (P > 0.05). In total, 5 patients died and 14 patients were still alive over the 1-year follow-up period. There was also a significant difference between the uptake intensity of 99mTc-MIBI and the outcome in the early phase (dead: 0.32[0.29-0.43] vs alive: 0.21[0.18-0.24], P pulmonary involvement in early views, which were well correlated with HRCT findings. These results also revealed that 99mTc-MIBI lung scans might be used as a complement to other diagnostic and clinical examinations in terms of functional information in ILD; however, further investigations are strongly required.

  5. Prognostic impact of average iodine density assessed by dual-energy spectral imaging for predicting lung tumor recurrence after stereotactic body radiotherapy. (United States)

    Aoki, Masahiko; Hirose, Katsumi; Sato, Mariko; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Fujioka, Ichitaro; Tanaka, Mitsuki; Ono, Shuichi; Takai, Yoshihiro


    The purpose of this study was to investigate the prognostic significance of average iodine density as assessed by dual-energy computed tomography (DE-CT) for lung tumors treated with stereotactic body radiotherapy (SBRT). From March 2011 to August 2014, 93 medically inoperable patients with 74 primary lung cancers and 19 lung metastases underwent DE-CT prior to SBRT of a total dose of 45-60 Gy in 5-10 fractions. Of these 93 patients, nine patients had two lung tumors. Thus, 102 lung tumors were included in this study. DE-CT was performed for pretreatment evaluation. Regions of interest were set for the entire tumor, and average iodine density was obtained using a dedicated imaging software and evaluated with regard to local control. The median follow-up period was 23.4 months (range, 1.5-54.5 months). The median value of the average iodine density was 1.86 mg/cm(3) (range, 0.40-9.27 mg/cm(3)). Two-year local control rates for the high and low average iodine density groups divided by the median value of the average iodine density were 96.9% and 75.7% (P = 0.006), respectively. Tumors with lower average iodine density showed a worse prognosis, possibly reflecting a hypoxic cell population in the tumor. The average iodine density exhibited a significant impact on local control. Our preliminary results indicate that iodine density evaluated using dual-energy spectral CT may be a useful, noninvasive and quantitative assessment of radio-resistance caused by presumably hypoxic cell populations in tumors.

  6. Novel Flurometric Tool to Assess Mitochondrial Redox State of Isolated Perfused Rat Lungs After Exposure to Hyperoxia (United States)

    Audi, Said H.; Staniszewski, Kevin S.; Haworth, Steven T.; Jacobs, Elizabeth R.; Ranji, Mahsa; Zablocki, Clement J.


    Recently, we demonstrated the utility of optical fluorometry to detect a change in the redox status of mitochondrial autofluorescent coenzymes nicotinamide adenine dinucleotide (NADH) and oxidized form of flavin adenine dinucleotide \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$({\\rm FADH}_{2})$\\end{document} (FAD), as a measure of mitochondrial function in isolated perfused rat lungs (IPL). The objective of this paper was to utilize optical fluorometry to evaluate the effect of rat exposure to hyperoxia (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${>}{95\\%}~{\\rm O}_{2}$\\end{document} for 48 h) on lung tissue mitochondrial redox status of NADH and FAD in a nondestructive manner in IPL. Surface NADH and FAD signals were measured before and after lung perfusion with perfusate containing rotenone (ROT, complex I inhibitor), potassium cyanide (KCN, complex IV inhibitor), and/or pentachlorophenol (PCP, uncoupler). ROT- or KCN-induced increase in NADH signal is considered a measure of complex I activity, and KCN-induced decrease in FAD signal is considered a measure of complex II activity. The results show that hyperoxia decreased complex I and II activities by 63% and 55%, respectively, when compared to lungs of rats exposed to room air (normoxic rats). Mitochondrial complex I and II activities in lung homogenates were also lower (77% and 63%, respectively) for hyperoxic than for normoxic lungs. These results suggest that the mitochondrial matrix is more reduced in hyperoxic lungs than in normoxic lungs, and demonstrate the ability of optical fluorometry to detect a change

  7. A complete audit cycle to assess adherence to a lung protective ventilation strategy

    Directory of Open Access Journals (Sweden)

    Emma Joynes


    Full Text Available There is clear evidence for the use of a protective ventilation protocol in patients with acute respiratory distress syndrome (ARDS. There is evidence to suggest that protective ventilation is beneficial in patients at risk of ARDS. A protective ventilation strategy was implemented on our intensive care unit in critical care patients who required mechanical ventilation for over 48 h, with and at risk for ARDS. A complete audit cycle was performed over 13 months to assess compliance with a safe ventilation protocol in intensive care. The ARDS network mechanical ventilation protocol was used as the standard for our protective ventilation strategy. This recommends ventilation with a tidal volume (Vt of 6 ml/kg of ideal body weight (IBW and plateau airway pressure of ≤30 cm H 2 O. The initial audit failed to meet this standard with Vt ′s of 9.5 ml/kg of IBW. Following the implementation of a ventilation strategy and an educational program, we demonstrate a significant improvement in practice with Vt ′s of 6.6 ml/kg of IBW in the re-audit. This highlights the importance of simple interventions and continuous education in maintaining high standards of care.

  8. 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:


    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

  9. 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: [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)


    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

  10. Multisite carcinogenicity and respiratory toxicity of inhaled 1-bromopropane in rats and mice. (United States)

    Morgan, Daniel L; Nyska, Abraham; Harbo, Sam Jens; Grumbein, Sondra L; Dill, Jeffrey A; Roycroft, Joseph H; Kissling, Grace E; Cesta, Mark F


    Two-year 1-bromopropane (1-BP) inhalation studies were conducted because of the potential for widespread exposure, the lack of chronic toxicity and carcinogenicity data, and the known carcinogenicity of structurally related compounds. Male and female F344/N rats and B6C3F1/N mice were exposed by inhalation to 0, 62.5 (mice only), 125, 250, or 500 (rats only) ppm 1-BP for 6 hr/day, 5 days/week for 105 weeks. Exposure of male and female rats to 1-BP resulted in significantly increased incidences of adenomas of the large intestine and skin neoplasms. In male rats, the incidence of malignant mesothelioma of the epididymis was statistically significantly increased at 500 ppm, but the biological significance of this common lesion is unclear. Incidences of pancreatic islet adenoma in male rats were significantly increased at all concentrations relative to concurrent controls but were within the historical control range for inhalation studies. There was no evidence of carcinogenic activity of 1-BP in male B6C3F1 mice; however, significantly increased incidences of alveolar/bronchiolar neoplasms of the lung were present in female mice. Exposure to 1-BP also resulted in increased incidences of nonneoplastic lesions in the nose of rats and mice, the larynx of rats and male mice, the trachea of female rats and male and female mice, and the lungs of mice. Inflammatory lesions with Splendore Hoeppli (S-H) material were present primarily in the nose and skin of exposed male and female rats, indicating that 1-BP caused immunosuppression.

  11. 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.


    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.

  12. Rodent carcinogenicity with the thiazolidinedione antidiabetic agent troglitazone. (United States)

    Herman, J R; Dethloff, L A; McGuire, E J; Parker, R F; Walsh, K M; Gough, A W; Masuda, H; de la Iglesia, F A


    Carcinogenic potential of the thiazolidinedione antidiabetic troglitazone was assessed in 104-week studies in mice and rats. Mice were given 50, 400, or 800 mg/kg, male rats 100, 400, or 800 mg/kg, and female rats 25, 50, or 200 mg/kg. Vehicle and placebo controls were included. Survival was significantly decreased in both sexes of both species at high doses, but was adequate for valid evaluation of carcinogenicity. Hypertrophy and hyperplasia of brown adipose tissue was observed in both species at all doses, and fatty change and hypocellularity of bone marrow was noted in mice at all doses and in female rats at 50 and 200 mg/kg. Hepatocellular vacuolation was observed in mice at 400 and 800 mg/kg, and centrilobular hepatocellular hypertrophy occurred in rats at > or = 200 mg/kg. Ventricular dilatation, myocardial fibrosis, and atrial myocyte karyomegaly in male rats at 400 and 800 mg/kg and female rats at all doses were morphologically similar to spontaneous lesions, but incidence and severity were increased compared with controls. In mice, the incidence of hemangiosarcoma was increased in females at 400 mg/kg and in both sexes at 800 mg/kg. The incidence of hepatocellular carcinoma was increased in female mice at 800 mg/kg. Troglitazone exposure [AUC((0-24))] at the lowest dose associated with increased tumor incidence in mice was 16 times human therapeutic exposure at 400 mg daily. No tumors of any type were increased in rats at exposures up to 47 times therapeutic exposure.

  13. Chronic Inorganic Arsenic Exposure In Vitro Induces a Cancer Cell Phenotype in Human Peripheral Lung Epithelial Cells (United States)

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J.


    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. PMID:25804888

  14. Diet as a confounder of the association between air pollution and female lung cancer: Hong Kong studies on exposures to environmental tobacco smoke, incense, and cooking fumes as examples. (United States)

    Koo, L C; Ho, J H


    adjusting for smoking. The last finding may be explained by the relatively better diets among smoking women who burned incense versus those who did not. Although about 94% of the Chinese women cook on a regular basis, and the cooking fires were associated with increased airborne carcinogens, nonsmoking women who cooked for more than 25 years had a 60% reduction in lung cancer risk and the trend was highly significant (P cancer risk assessments. Our conclusion is that diet can be an important confounding factor affecting lung cancer risk estimates from air pollution exposures among Chinese women living in an affluent urban environment.

  15. Changes in lung parenchyma after acute respiratory distress syndrome (ARDS): assessment with high-resolution computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Noebauer-Huhmann, I.-M.; Eibenberger, K.; Schaefer-Prokop, C.; Herold, C.J. [Vienna Univ. (Austria). Inst. fuer Radiologie; Steltzer, H.; Strasser, K.; Fridrich, P. [Dept. of General Anesthesia and Intensive Care, Univ. of Vienna (Austria); Schlick, W. [Dept. of Cardio-Thoracic Surgery, Univ. of Vienna (Austria)


    The aim of this study was to evaluate the appearance, extent, and distribution of parenchymal changes in the lung after acute respiratory distress syndrome (ARDS) as a function of disease severity and therapeutic procedures. High-resolution computed tomography (HRCT), clinical examination, and lung function tests were performed in 15 patients, 6-10 months after ARDS. The appearance and extent of parenchymal changes were compared with the severity of ARDS, as well as with clinical and therapeutic data. Lung parenchymal changes resembling those found in the presence of pulmonary fibrosis were observed in 13 of 15 patients (87%). The changes were significantly more frequent and more pronounced in the ventral than in the dorsal portions of the lung (p<0.01). A significant correlation was observed between the extent of lung alterations and the severity of ARDS (p<0.01), and the duration in which patients had received mechanical ventilation either with a peak inspiratory pressure greater than 30 mmHg (p<0.05), or with more than 70% oxygen (p<0.01). Acute respiratory distress syndrome frequently is followed by fibrotic changes in lung parenchyma. The predominantly ventral distribution of these changes indicates that they may be caused by the ventilation regimen and the oxygen therapy rather than by the ARDS. (orig.)

  16. Genotoxicity assessment of 4-methylimidazole: regulatory perspectives. (United States)

    Morita, Takeshi; Uneyama, Chikako


    4-Methylimidazole (4-MI) is formed as a result of the Maillard reaction process, and therefore is found in many foods and beverages. It is also found in soft drinks (i.e., cola) as a by-product in the production of some caramel colors. NTP bioassays revealed clear evidence of lung carcinogenicity of 4-MI in male and female mice, but not in rats and then IARC classified 4-MI as group 2B carcinogen. Genotoxicity studies with 4-MI were negative in the Ames tests and in the erythrocyte micronucleus tests with mice or rats. US California EPA (CEPA) evaluated the testing has not been adequately comprehensive to rule out a genotoxic mode of action; as target tissue of the carcinogenicity of 4-MI was lung, the lung should be used as a source tissue for in vitro metabolic activation system. Thus, CEPA defined the No Significant Risk Level (NSRL) for 10(-5) lifetime risk level of cancer by 4-MI as 29 μg/day based on the non-threshold approach. As higher levels of 4-MI than the NSRL were identified in some kinds of cola, health concerns of 4-MI were drawn the attention. On the other hand, other regulatory bodies (e.g., European Food Safety Authority, EFSA) showed no concerns of 4-MI from the use of caramel colors in food. EFSA evaluated 4-MI is not genotoxic, so, non-observed adverse effect level of 4-MI was considered to be 80 mg/kg/day. In this paper, genotoxic assessments of 4-MI in different regulatory bodies are presented and the risk evaluation of 4-MI is discussed based on new genotoxicity data.

  17. Development of lung function in very low birth weight infants with or without bronchopulmonary dysplasia: Longitudinal assessment during the first 15 months of corrected age

    Directory of Open Access Journals (Sweden)

    Schmalisch Gerd


    Full Text Available Abstract Background Very low birth weight (VLBW infants ( Methods Comprehensive lung function assessment was performed at about 50, 70, and 100 weeks of postmenstrual age in 55 sedated VLBW infants (29 with former BPD [O2 supplementation was given at 36 weeks of gestational age] and 26 VLBW infants without BPD [controls]. Mean gestational age (26 vs. 29 weeks, birth weight (815 g vs. 1,125 g, and the proportion of infants requiring mechanical ventilation for ≥7 d (55% vs. 8%, differed significantly between BPD infants and controls. Results Both body weight and length, determined over time, were persistently lower in former BPD infants compared to controls, but no significant between-group differences were noted in respiratory rate, respiratory or airway resistance, functional residual capacity as determined by body plethysmography (FRCpleth, maximal expiratory flow at the FRC (V'max FRC, or blood gas (pO2, pCO2 levels. Tidal volume, minute ventilation, respiratory compliance, and FRC determined by SF6 multiple breath washout (representing the lung volume in actual communication with the airways were significantly lower in former BPD infants compared to controls. However, these differences became non-significant after normalization to body weight. Conclusions Although somatic growth and the development of some lung functional parameters lag in former BPD infants, the lung function of such infants appears to develop in line with that of non-BPD infants when a body weight correction is applied. Longitudinal lung function testing of preterm infants after discharge from hospital may help to identify former BPD infants at risk of incomplete recovery of respiratory function; such infants are at risk of later respiratory problems.

  18. Preferential Formation of Benzo[a]pyrene Adducts at Lung Cancer Mutational Hotspots in P53 (United States)

    Denissenko, Mikhail F.; Pao, Annie; Tang, Moon-Shong; Pfeifer, Gerd P.


    Cigarette smoke carcinogens such as benzo[a]pyrene are implicated in the development of lung cancer. The distribution of benzo[a]pyrene diol epoxide (BPDE) adducts along exons of the P53 gene in BPDE-treated HeLa cells and bronchial epithelial cells was mapped at nucleotide resolution. Strong and selective adduct formation occurred at guanine positions in codons 157, 248, and 273. These same positions are the major mutational hotspots in human lung cancers. Thus, targeted adduct formation rather than phenotypic selection appears to shape the P53 mutational spectrum in lung cancer. These results provide a direct etiological link between a defined chemical carcinogen and human cancer.

  19. 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......This project (KoL 12-08) was performed for the Climate and Air Quality Group (KlimaogLuftgruppen, KoL), Nordic Council of Ministers by atmospheric emission, exposureand epidemiology experts from Denmark, Finland, Norway and Sweden. Emission inventory methods and exposure models were presented...... 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...

  20. Carcinogenic risk of copper gluconate evaluated by a rat medium-term liver carcinogenicity bioassay protocol

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Masayoshi; Usuda, Koji; Hayashi, Seigo; Ogawa, Izumi; Furukawa, Satoshi [Nissan Chemical Industries Limited, Toxicology and Environmental Science Department, Biological Research Laboratories, Saitama (Japan); Igarashi, Maki [Tokyo University of Agriculture, Laboratory of Protection of Body Function, Department of Food and Nutritional Science, Graduate School of Agriculture, Tokyo (Japan); Nakae, Dai [Tokyo University of Agriculture, Laboratory of Protection of Body Function, Department of Food and Nutritional Science, Graduate School of Agriculture, Tokyo (Japan); Tokyo Metropolitan Institute of Public Health, Tokyo (Japan)


    Carcinogenic risk and molecular mechanisms underlying the liver tumor-promoting activity of copper gluconate, an additive of functional foods, were investigated using a rat medium-term liver carcinogenicity bioassay protocol (Ito test) and a 2-week short-term administration experiment. In the medium-term liver bioassay, Fischer 344 male rats were given a single i.p. injection of N-nitrosodiethylamine at a dose of 200 mg/kg b.w. as a carcinogenic initiator. Starting 2 weeks thereafter, rats received 0, 10, 300 or 6,000 ppm of copper gluconate in diet for 6 weeks. All rats underwent 2/3 partial hepatectomy at the end of week 3, and all surviving rats were killed at the end of week 8. In the short-term experiment, rats were given 0, 10, 300 or 6,000 ppm of copper gluconate for 2 weeks. Numbers of glutathione S-transferase placental form (GST-P) positive lesions, single GST-P-positive hepatocytes and 8-oxoguanine-positive hepatocytes, and levels of cell proliferation and apoptosis in the liver were significantly increased by 6,000 ppm of copper gluconate in the medium-term liver bioassay. Furthermore, hepatic mRNA expression of genes relating to the metal metabolism, inflammation and apoptosis were elevated by 6,000 ppm of copper gluconate both in the medium-term liver bioassay and the short-term experiments. These results indicate that copper gluconate possesses carcinogenic risk toward the liver at the high dose level, and that oxidative stress and inflammatory and pro-apoptotic signaling statuses may participate in its underlying mechanisms. (orig.)

  1. The foot posture index, ankle lunge test, Beighton scale and the lower limb assessment score in healthy children: a reliability study

    Directory of Open Access Journals (Sweden)

    Evans Angela M


    Full Text Available Abstract Background Outcome measures are important when evaluating treatments and physiological progress in paediatric populations. Reliable, relevant measures of foot posture are important for such assessments to be accurate over time. The aim of the study was to assess the intra- and inter-rater reliability of common outcome measures for paediatric foot conditions. Methods A repeated measures, same-subject design assessed the intra- and inter-rater reliability of measures of foot posture, joint hypermobility and ankle range: the Foot Posture Index (FPI-6, the ankle lunge test, the Beighton scale and the lower limb assessment scale (LLAS, used by two examiners in 30 healthy children (aged 7 to 15 years. The Oxford Ankle Foot Questionnaire (OxAFQ-C was completed by participants and a parent, to assess the extent of foot and ankle problems. Results The OxAFQ-C demonstrated a mean (SD score of 6 (6 in adults and 7(5 for children, showing good agreement between parents and children, and which indicates mid-range (transient disability. Intra-rater reliability was good for the FPI-6 (ICC = 0.93 - 0.94, ankle lunge test (ICC = 0.85-0.95, Beighton scale (ICC = 0.96-0.98 and LLAS (ICC = 0.90-0.98. Inter-rater reliability was largely good for each of the: FPI-6 (ICC = 0.79, ankle lunge test (ICC = 0.83, Beighton scale (ICC = 0.73 and LLAS (ICC = 0.78. Conclusion The four measures investigated demonstrated adequate intra-rater and inter-rater reliability in this paediatric sample, which further justifies their use in clinical practice.


    Institute of Scientific and Technical Information of China (English)


    @@The ability for DNA repair is an important host factor which influences the individual susceptibility to genotoxic carcinogen exposures. It has been shown in different case-control studies that DNA repair capacity (DRC) can be reduced in lung cancer patients.We have used an alkaline comet assay to measure the cellular DRC in peri-pheral blood lymphocytes of lung cancer patients and tumor-free control

  3. Carcinogenicity and DNA adduct formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and enantiomers of its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in F-344 rats. (United States)

    Balbo, Silvia; Johnson, Charles S; Kovi, Ramesh C; James-Yi, Sandra A; O'Sullivan, M Gerard; Wang, Mingyao; Le, Chap T; Khariwala, Samir S; Upadhyaya, Pramod; Hecht, Stephen S


    4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is metabolized to enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), found in the urine of virtually all people exposed to tobacco products. We assessed the carcinogenicity in male F-344 rats of (R)-NNAL (5 ppm in drinking water), (S)-NNAL (5 ppm), NNK (5 ppm) and racemic NNAL (10 ppm) and analyzed DNA adduct formation in lung and pancreas of these rats after 10, 30, 50 and 70 weeks of treatment. All test compounds induced a high incidence of lung tumors, both adenomas and carcinomas. NNK and racemic NNAL were most potent; (R)-NNAL and (S)-NNAL had equivalent activity. Metastasis was observed from primary pulmonary carcinomas to the pancreas, particularly in the racemic NNAL group. DNA adducts analyzed were O (2)-[4-(3-pyridyl)-4-oxobut-1-yl]thymidine (O (2)-POB-dThd), 7-[4-(3-pyridyl)-4-oxobut-1-yl]guanine(7-POB-Gua),O (6)-[4-(3-pyridyl)-4-oxobut-1-yl]deoxyguanosine(O (6)-POB-dGuo),the 4-(3-pyridyl)-4-hydroxybut-1-yl(PHB)adductsO (2)-PHB-dThd and 7-PHB-Gua, O (6)-methylguanine (O (6)-Me-Gua) and 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing adducts. Adduct levels significantly decreased with time in the lungs of rats treated with NNK. Pulmonary POB-DNA adducts and O (6)-Me-Gua were similar in rats treated with NNK and (S)-NNAL; both were significantly greater than in the (R)-NNAL rats. In contrast, pulmonary PHB-DNA adduct levels were greatest in the rats treated with (R)-NNAL. Total pulmonary DNA adduct levels were similar in (S)-NNAL and (R)-NNAL rats. Similar trends were observed for DNA adducts in the pancreas, but adduct levels were significantly lower than in the lung. The results of this study clearly demonstrate the potent pulmonary carcinogenicity of both enantiomers of NNAL in rats and provide important new information regarding DNA damage by these compounds in lung and pancreas.

  4. Functional Mechanism of Lung Mosaic CT Attenuation: Assessment with Deep-Inspiration Breath-Hold Perfusion SPECT-CT Fusion Imaging and Non-Breath-Hold Technegas SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Suga, K.; Yasuhiko, K. (Dept. of Radiology, St. Hill Hospital, Ube, Yamaguchi (Japan)); Iwanaga, H.; Tokuda, O.; Matsunaga, N. (Dept. of Radiology, Yamaguchi Univ. School of Medicine, Ube, Yamaguchi (Japan))


    Background: The functional mechanism of lung mosaic computed tomography attenuation (MCA) in pulmonary vascular disease (PVD) and obstructive airway disease (OAD) has not yet been fully clarified. Purpose: To clarify the mechanism of MCA in these diseases by assessing the relationship between regional lung function and CT attenuation change at MCA sites with the use of automated deep-inspiratory breath-hold (DIBrH) perfusion single-photon emission computed tomography (SPECT)-CT fusion images and non-breath-hold Technegas SPECT. Material and Methods: Subjects were 42 PVD patients (31 pulmonary thromboembolism, four primary/two secondary pulmonary hypertension, and five Takayasu arteritis), 12 OAD patients (five acute asthma, four obliterative bronchiolitis, and three bronchiectasis), and 12 normal controls, all of whom had MCA on DIBrH CT. The relationship between regional lung function and CT attenuation change at the lung slices with MCA was assessed using DIBrH perfusion SPECT-CT fusion images and non-breath-hold Technegas SPECT. The severity of perfusion defects with or without MCA was quantified by regions-of-interest analysis. Results: On DIBrH CT and perfusion SPECT, in contrast to no noticeable CT attenuation abnormality and fairly uniform perfusion in controls, 60 MCA and 274 perfusion defects in PVD patients, and 18 MCA and 61 defects in OAD patients were identified, with a total of 77 ventilation defects on Technegas SPECT in all patients. SPECT-CT correlation showed that, throughout the 78 MCA sites of all patients, lung perfusion was persistently decreased at low CT attenuation and preserved at intervening high CT attenuation, while lung ventilation was poorly correlated with CT attenuation change. The radioactivity ratios of reduced perfusion and the intervening preserved perfusion at the 78 perfusion defects with MCA were significantly lower than those at the remaining 257 defects without MCA (P<0.0001). Conclusion: Although further validation is

  5. Potent chemopreventive effect of mangiferin on lung carcinogenesis in experimental Swiss albino mice

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    Peramaiyan Rajendran


    Full Text Available Aim of the Study: In the present study the effects of mangiferin were tested against lung cancer-bearing mice in both the pre-initiation and post-initiation periods. Materials and Methods: Healthy male Swiss albino mice (6-8 weeks old were used throughout the study. The animals were treated with mangiferin (100 mg/kg body weight dissolved in corn oil two weeks before (pre-initiation and the twelfth week after (post-initiation the establishment of B (a P (50 mg/kg body weight-induced lung carcinoma. Results: The body weight decreased and the lung weight and levels of xenobiotic and liver marker enzymes markedly increased in the carcinogen-administered animals; and mangiferin treatment brought the values of these parameters back to the near-normal ones. The activities of lysosomal enzymes in the animals with B (a P-induced experimental lung carcinogenesis were also assessed. In these animals there was an increase in the activities of lysosomal enzymes such as acidphosphatase, β-glucuronidase, N-acetyl glucosaminidase, and β-galactosidase. Conclusion: Supplementation with mangiferin attenuated all these alterations, thus indicating its anticancer effect. Overall, the above data showed that the anticancer effect of mangiferin as a chemopreventive agent was pronounced.

  6. Does the Consumption of Green Tea Reduce the Risk of Lung Cancer among Smokers?

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    Wenbin Liang


    Full Text Available Experimental and epidemiological studies were reviewed to assess whether the consumption of green tea could reduce the risk of lung cancer in smokers. Articles published since 1990 were located by searching electronic databases PubMed, Ovid and Science Direct, using keywords ‘lung cancer’, ‘tea’ and ‘smoking’ without any restriction on language. After relevant articles had been located, further papers were obtained from their reference lists. Evidence from experimental studies (in vitro animal and human trials suggested that regular intake of green tea may be protective against tobacco carcinogens. However, the mechanism behind the protective effect is only partly understood. In most of the epidemiological studies reviewed, the green tea exposure was within 5 years of the interview or follow-up, which would coincide with the induction period and latent period of lung cancer. Longer term studies are thus needed to further quantify the cancer risk. There is some evidence suggesting regular intake of green tea at high level (>3 cups per day may reduce the risk of smokers developing lung cancer. Improvement in measuring green tea intake is required in order to confirm the evidence from epidemiological studies.

  7. Does the consumption of green tea reduce the risk of lung cancer among smokers? (United States)

    Liang, Wenbin; Binns, Colin W; Jian, Le; Lee, Andy H


    Experimental and epidemiological studies were reviewed to assess whether the consumption of green tea could reduce the risk of lung cancer in smokers. Articles published since 1990 were located by searching electronic databases PubMed, Ovid and Science Direct, using keywords 'lung cancer', 'tea' and 'smoking' without any restriction on language. After relevant articles had been located, further papers were obtained from their reference lists. Evidence from experimental studies (in vitro animal and human trials) suggested that regular intake of green tea may be protective against tobacco carcinogens. However, the mechanism behind the protective effect is only partly understood. In most of the epidemiological studies reviewed, the green tea exposure was within 5 years of the interview or follow-up, which would coincide with the induction period and latent period of lung cancer. Longer term studies are thus needed to further quantify the cancer risk. There is some evidence suggesting regular intake of green tea at high level (>3 cups per day) may reduce the risk of smokers developing lung cancer. Improvement in measuring green tea intake is required in order to confirm the evidence from epidemiological studies.

  8. Assessment of human health risk associated with pyaemia in Danish finisher pigs when conducting visual-only inspection of the lungs. (United States)

    Kruse, Amanda Brinch; Larsen, Marianne Halberg; Skou, Peter Bæk; Alban, Lis


    The most important lesion to be overlooked when performing visual-only inspection of the lungs is embolic pneumonia. The aim of the present study was to assess the additional human health risk represented by overlooking cases of pyaemia represented by embolic pneumonia in finisher pigs, when conducting visual-only compared to palpation of the lungs, as is the traditional meat inspection procedure. An examination of bacteria isolated from 19 finisher pigs identified with embolic pneumonia at traditional meat inspection was undertaken. From each pig samples were taken from various organs (lungs, spleen, heart, liver and kidney), from the carpal joints (A. carpi) and flexor muscle (M. flexor digitorum superficialis) on the right foreleg. These data were included in a risk assessment following OIE guidelines. Bacteria were isolated from 78 out of 127 tissue and swap samples taken (61% positive samples). Staphylococcus aureus (N=37) was the most frequently isolated bacterium. The predominant site of S. aureus was the lung. S. aureus was detected although less frequently in low numbers in some organs (risk of a food-borne intoxication from S. aureus in relation to pyaemia in pigs was considered very low due to the low quantitative numbers of S. aureus in muscle tissue samples. Implementing visual-only inspection will reduce the exposure of S. aureus due to less cross-contamination and handling of the plucks by the meat inspectors. The human health risk associated with S. warneri was considered very low, due to the limited zoonotic potential of this bacterium. In conclusion, the additional human health risk in relation to possibly overlooking pyaemia in Danish finisher pigs was considered negligible when conducting visual-only compared to traditional meat inspection.

  9. Spatiotemporal air pollution exposure assessment for a Canadian population-based lung cancer case-control study

    Directory of Open Access Journals (Sweden)

    Hystad Perry


    Full Text Available Abstract Background 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. Methods 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. Results 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

  10. MRI of the lung

    Energy Technology Data Exchange (ETDEWEB)

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


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

  11. 99mTc-IgG-Lung Scintigraphy in the Assessment of Pulmonary Involvement in Interstitial Lung Disease and Its Comparison With Pulmonary Function Tests and High-Resolution Computed Tomography: A Preliminary Study

    Directory of Open Access Journals (Sweden)



    Full Text Available Background The discrimination of inactive inflammatory processes from the active form of the disease is of great importance in the management of interstitial lung disease (ILD. Objectives The aim of this study was to determine the efficacy of 99mTc-IgG scan for the detection of severity of disease compared to high-resolution computed tomography (HRCT and pulmonary function test (PFT. Patients and Methods Eight known cases of ILD including four cases of Mustard gas (MG intoxication and four patients with ILD of unknown cause were included in this study. A population of six patients without lung disease was considered as the control group. The patients underwent PFT and high-resolution computed tomography, followed by 99mTc-IgG scan. They were followed up for one year. 99mTc-IgG scan assessment of IgG uptake was accomplished both qualitatively (subjectively and semiquantitatively. Results All eight ILD patients demonstrated a strong increase in 99mTc-IgG uptake in the lungs, compared to the control patients. The 99mTc-IgG scan scores were higher in the patient group (0.64[95% confidence interval(CI=0.61-0.69] than the control group (0.35 (0.35[95% CI=0.28-0.40], (P 0.05. There were no significant correlations between 99mTc-IgG score and HRCT patterns including ground glass opacity, reticular fibrosis and honeycombing (P value > 0.05. Conclusion The present results confirmed that 99mTc-IgG scan could be applied to detect the severity of pulmonary involvement, which was well correlated with HRCT findings. This data also showed that the 99mTc-IgG scan might be used as a complement to HRCT in the functional evaluation of the clinical status in ILD; however, further studies are recommended.

  12. The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer. (United States)

    Travis, William D; Asamura, Hisao; Bankier, Alexander A; Beasley, Mary Beth; Detterbeck, Frank; Flieder, Douglas B; Goo, Jin Mo; MacMahon, Heber; Naidich, David; Nicholson, Andrew G; Powell, Charles A; Prokop, Mathias; Rami-Porta, Ramón; Rusch, Valerie; van Schil, Paul; Yatabe, Yasushi


    This article proposes codes for the primary tumor categories of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part-solid tumors for the eighth edition of the tumor, node, and metastasis classification of lung cancer. In 2011, new entities of AIS, MIA, and lepidic predominant adenocarcinoma were defined, and they were later incorporated into the 2015 World Health Organization classification of lung cancer. To fit these entities into the T component of the staging system, the Tis category is proposed for AIS, with Tis (AIS) specified if it is to be distinguished from squamous cell carcinoma in situ (SCIS), which is to be designated Tis (SCIS). We also propose that MIA be classified as T1mi. Furthermore, the use of the invasive size for T descriptor size follows a recommendation made in three editions of the Union for International Cancer Control tumor, node, and metastasis supplement since 2003. For tumor size, the greatest dimension should be reported both clinically and pathologically. In nonmucinous lung adenocarcinomas, the computed tomography (CT) findings of ground glass versus solid opacities tend to correspond respectively to lepidic versus invasive patterns seen pathologically. However, this correlation is not absolute; so when CT features suggest nonmucinous AIS, MIA, and lepidic predominant adenocarcinoma, the suspected diagnosis and clinical staging should be regarded as a preliminary assessment that is subject to revision after pathologic evaluation of resected specimens. The ability to predict invasive versus noninvasive size on the basis of solid versus ground glass components is not applicable to mucinous AIS, MIA, or invasive mucinous adenocarcinomas because they generally show solid nodules or consolidation on CT.

  13. Impact of fine particles in ambient air on lung cancer

    NARCIS (Netherlands)

    Hoek, Gerard; Raaschou-Nielsen, Ole


    Recently, the International Agency for Research on Cancer (IARC) has classified outdoor air pollution and the particulate matter component of outdoor air pollution as class I carcinogen. Air pollution is consistently associated with lung cancer in epidemiologic and experimental studies. The IARC ass

  14. Assessment of respiratory symptoms and lung function values among the brick field workers of West Bengal, India. (United States)

    Das, Banibrata


    Brick manufacturing process releases large amounts of silica dust into the work environment due to the use of silica-containing materials. The main aim of the study was to investigate the impairment of lung function and prevalence of respiratory symptoms among the different groups of brick field workers in comparison with control subjects. A total of 250 brick field workers and 130 unexposed control subjects were randomly selected in which demographic characteristics, respiratory symptoms, and lung function values were recorded. The result showed significantly lower p value (brick field workers when compared with control group. The prevalence of respiratory symptoms was dyspnea (46.8%), phlegm (39.2%), and chest tightness (27.6%). Dust exposure in working environment affected the lung function values and increased the respiratory symptoms among the brick field workers.

  15. Lack of contribution of covalent benzo[a]pyrene-7,8-quinone-DNA adducts in benzo[a]pyrene-induced mouse lung tumorigenesis (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...

  16. Estimating the incidence of lung cancer attributable to occupational exposure in Iran

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    Mousavi-Jarrahi Yasaman


    Full Text Available Abstract Objective The aim of this study was to estimate the fraction of lung cancer incidence in Iran attributed to occupational exposures to the well-established lung cancer carcinogens, including silica, cadmium, nickel, arsenic, chromium, diesel fumes, beryllium, and asbestos. Methods Nationwide exposure to each of the mentioned carcinogens was estimated using workforce data from the Iranian population census of 1995, available from the International Labor Organization (ILO website. The prevalence of exposure to carcinogens in each industry was estimated using exposure data from the CAREX (CARcinogen EXposure database, an international occupational carcinogen information system kept and maintained by the European Union. The magnitude of the relative risk of lung cancer for each carcinogen was estimated from local and international literature. Using the Levin modified population attributable risk (incidence fraction, lung cancer incidence (as estimated by the Tehran Population-Based Cancer Registry attributable to workplace exposure to carcinogens was estimated. Results The total workforce in Iran according to the 1995 census identified 12,488,020 men and 677,469 women. Agriculture is the largest sector with 25% of the male and 0.27% of female workforce. After applying the CAREX exposure estimate to each sector, the proportion exposed to lung carcinogens was 0.08% for male workers and 0.02% for female workers. Estimating a relative risk of 1.9 (95% CI of 1.7–2.1 for high exposure and 1.3 (95% CI 1.2–1.4 for low exposure, and employing the Levin modified formula, the fraction of lung cancer attributed to carcinogens in the workplace was 1.5% (95% CI of 1.2–1.9 for females and 12% (95% CI of 10–15 for males. These fractions correspond to an estimated incidence of 1.3 and 0.08 cases of lung cancer per 100,000 population for males and females, respectively. Conclusion The incidence of lung cancer due to occupational exposure is low in

  17. Assessment of Monte Carlo algorithm for compliance with RTOG 0915 dosimetric criteria in peripheral lung cancer patients treated with stereotactic body radiotherapy. (United States)

    Pokhrel, Damodar; Sood, Sumit; Badkul, Rajeev; Jiang, Hongyu; McClinton, Christopher; Lominska, Christopher; Kumar, Parvesh; Wang, Fen


    The purpose of the study was to evaluate Monte Carlo-generated dose distributions with the X-ray Voxel Monte Carlo (XVMC) algorithm in the treatment of peripheral lung cancer patients using stereotactic body radiotherapy (SBRT) with non-protocol dose-volume normalization and to assess plan outcomes utilizing RTOG 0915 dosimetric compliance criteria. The Radiation Therapy Oncology Group (RTOG) protocols for non-small cell lung cancer (NSCLC) currently require radiation dose to be calculated using tissue density heterogeneity corrections. Dosimetric criteria of RTOG 0915 were established based on superposition/convolution or heterogeneities corrected pencil beam (PB-hete) algorithms for dose calculations. Clinically, more accurate Monte Carlo (MC)-based algorithms are now routinely used for lung stereotactic body radiotherapy (SBRT) dose calculations. Hence, it is important to determine whether MC calculations in the delivery of lung SBRT can achieve RTOG standards. In this report, we evaluate iPlan generated MC plans for peripheral lung cancer patients treated with SBRT using dose-volume histogram (DVH) normalization to determine if the RTOG 0915 compliance criteria can be met. This study evaluated 20 Stage I-II NSCLC patients with peripherally located lung tumors, who underwent MC-based SBRT with heterogeneity correction using X-ray Voxel Monte Carlo (XVMC) algorithm (Brainlab iPlan version 4.1.2). Total dose of 50 to 54 Gy in 3 to 5 fractions was delivered to the planning target vol-ume (PTV) with at least 95% of the PTV receiving 100% of the prescription dose (V100% ≥ 95%). The internal target volume (ITV) was delineated on maximum intensity projection (MIP) images of 4D CT scans. The PTV included the ITV plus 5 mm uniform margin applied to the ITV. The PTV ranged from 11.1 to 163.0 cc (mean = 46.1 ± 38.7 cc). Organs at risk (OARs) including ribs were delineated on mean intensity projection (MeanIP) images of 4D CT scans. Optimal clinical MC SBRT plans were

  18. 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: [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)


    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.

  19. Assessment of quality of life in patients with advanced non-small cell lung carcinoma treated with a combination of carboplatin and paclitaxel

    Directory of Open Access Journals (Sweden)

    Camila Uanne Resende Avelino


    Full Text Available OBJECTIVE: Non-small cell lung carcinoma (NSCLC is the most common type of lung cancer. Most patients are diagnosed at an advanced stage, palliative chemotherapy therefore being the only treatment option. This study was aimed at evaluating the health-related quality of life (HRQoL of advanced-stage NSCLC patients receiving palliative chemotherapy with carboplatin and paclitaxel. METHODS: This was a multiple case study of advanced-stage NSCLC outpatients receiving chemotherapy at a public hospital in Rio de Janeiro, Brazil. The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire was used in conjunction with its supplemental lung cancer-specific module in order to assess HRQoL. RESULTS: Physical and cognitive functioning scale scores differed significantly among chemotherapy cycles, indicating improved and worsened HRQoL, respectively. The differences regarding the scores for pain, loss of appetite, chest pain, and arm/shoulder pain indicated improved HRQoL. CONCLUSIONS: Chemotherapy was found to improve certain aspects of HRQoL in patients with advanced-stage NSCLC.

  20. Assessment of DNA damage of Lewis lung carcinoma cells irradiated by carbon ions and X-rays using alkaline comet assay (United States)

    Li, Ping; Zhou, Li-Bin; Jin, Xiao-Dong; He, Jing; Dai, Zhong-Ying; Zhou, Guang-Ming; Gao, Qing-Xiang; Li, Sha; Li, Qiang


    DNA damage and cell reproductive death determined by alkaline comet and clonogenic survival assays were examined in Lewis lung carcinoma cells after exposure to 89.63 MeV/u carbon ion and 6 MV X-ray irradiations, respectively. Based on the survival data, Lewis lung carcinoma cells were verified to be more radiosensitive to the carbon ion beam than to the X-ray irradiation. The relative biological effectiveness (RBE) value, which was up to 1.77 at 10% survival level, showed that the DNA damage induced by the high-LET carbon ion beam was more remarkable than that induced by the low-LET X-ray irradiation. The dose response curves of “Tail DNA (%)” (TD) and “Olive tail moment” (OTM) for the carbon ion irradiation showed saturation beyond about 8 Gy. This behavior was not found in the X-ray curves. Additionally, the carbon ion beam produced a lower survival fraction at 2 Gy (SF2) value and a higher initial Olive tail moment 2 Gy (OTM2) than those for the X-ray irradiation. These results suggest that carbon ion beams having high-LET values produced more severe cell reproductive death and DNA damage in Lewis lung carcinoma cells in comparison with X-rays and comet assay might be an effective predictive test even combining with clonogenic assay to assess cellular radiosensitivity.

  1. Relationship between Structures and Carcinogenicities of Heterocyclic Amines

    Institute of Scientific and Technical Information of China (English)

    JU Xue-hai; DAI Qian-huan; CHEN Sha; WANG Wen-jun


    Semi-empirical molecular orbital calculations were performed on heterocyclic aromatic amines(HCAs). The relationship between the structures and the carcinogenicities can be rationally elucidated by the models based on the metabolism of HCAs and the Di-region theory. The degree of easiness for the formation of Di-region electrophilic centers determines the carcinogenic activity. There is a good linear relationship between the observed carcinogenicities and the PM3 calculated parameters, with r=0.973 and F=29.8>(F*0.*01).

  2. Qualitative assessment of general movements in high-risk preterm infants with chronic lung disease requiring dexamethasone therapy

    NARCIS (Netherlands)

    Bos, AF; Martijn, A; van Asperen, RM; Hadders-Algra, M; Okken, A; Prechtl, HFR


    Objective: The objective of this study was to determine in preterm infants al risk for severe chronic lung disease (1) the quality of general movements (GMs) and (2) the effect of dexamethasone treatment on spontaneous motor activity. Study design: In 15 very low birth weight infants the quality of

  3. Quantitative and qualitative assessment of real world data comparative effectiveness research of systemic therapies in lung oncology: A systematic review

    NARCIS (Netherlands)

    Peters, Bas J.M.|info:eu-repo/dai/nl/304824585; Janssen, Vivi E.M.T.; Schramel, Franz M.; van de Garde, Ewoudt M.W.|info:eu-repo/dai/nl/304841528


    Introduction 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 validi

  4. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

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    Bryan L. Stegelmeier


    Full Text Available Dehydropyrrolizidine alkaloid (DHPA-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health.

  5. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity (United States)

    Stegelmeier, Bryan L.; Colegate, Steven M.; Brown, Ammon W.


    Dehydropyrrolizidine alkaloid (DHPA)-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health. PMID:27916846

  6. Lung disease assessment in primary ciliary dyskinesia: a comparison between chest high-field magnetic resonance imaging and high-resolution computed tomography findings

    Directory of Open Access Journals (Sweden)

    Iacotucci Paola


    Full Text Available Abstract Background Primary ciliary dyskinesia (PCD is associated with pulmonary involvement that requires periodical assessment. Chest high-resolution computed tomography (HRCT has become the method of choice to evaluate chronic lung disease, but entails exposure to ionizing radiation. Magnetic resonance imaging (MRI has been proposed as a potential radiation-free technique in several chest disorders. Aim of our study is to evaluate whether high-field MRI is as effective as HRCT in identifying PCD pulmonary abnormalities. We also analyzed the relationships between the severity and extension of lung disease, and functional data. Methods Thirteen PCD patients (8 children/5 adults; median age, 15.2 yrs underwent chest HRCT and high-field 3T MRI, spirometry, and deep throat or sputum culture. Images were scored using a modified version of the Helbich system. Results HRCT and MRI total scores were 12 (range, 6–20 and 12 (range, 5–17, respectively. Agreement between HRCT and MRI scores was good or excellent (r > 0.8. HRCT and MRI total scores were significantly related to forced vital capacity (r = -0.5, p = 0.05; and r = -0.7, p = 0.009, respectively and forced expiratory volume at 1 second (r = -0.6, p = 0.03; and r = -0.7, p = 0.009, respectively. Conclusion Chest high-field 3T MRI appears to be as effective as HRCT in assessing the extent and severity of lung abnormalities in PCD. MRI scores might be used for longitudinal assessment and be an outcome surrogate in future studies.

  7. The influence of different contrast medium concentrations and injection protocols on quantitative and clinical assessment of FDG–PET/CT in lung cancer

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    Verburg, Frederik A., E-mail: [RWTH Aachen University Hospital, Department of Nuclear Medicine, Pauwelsstraße 30, 52074 Aachen (Germany); Maastricht University Medical Center, Department of Nuclear Medicine, P. Debyelaan 25, 6229 HX Maastricht (Netherlands); Kuhl, Christiane K. [RWTH Aachen University Hospital, Department of Diagnostic and Interventional Radiology, Pauwelsstraße 30, 52074 Aachen (Germany); Pietsch, Hubertus [Bayer Pharma AG, Berlin, Müllerstrasse 178, 13353 Berlin (Germany); Palmowski, Moritz [RWTH Aachen University Hospital, Department of Nuclear Medicine, Pauwelsstraße 30, 52074 Aachen (Germany); Mottaghy, Felix M. [RWTH Aachen University Hospital, Department of Nuclear Medicine, Pauwelsstraße 30, 52074 Aachen (Germany); Maastricht University Medical Center, Department of Nuclear Medicine, P. Debyelaan 25, 6229 HX Maastricht (Netherlands); Behrendt, Florian F. [RWTH Aachen University Hospital, Department of Nuclear Medicine, Pauwelsstraße 30, 52074 Aachen (Germany)


    Objectives: To compare the effects of two different contrast medium concentrations for use in computed X-ray tomography (CT) employing two different injection protocols on positron emission tomography (PET) reconstruction in combined 2-{sup 18}F-desoxyglucose (FDG) PET/CT in patients with a suspicion of lung cancer. Methods: 120 patients with a suspicion of lung cancer were enrolled prospectively. PET images were reconstructed with the non-enhanced and venous phase contrast CT obtained after injection of iopromide 300 mg/ml or 370 mg/ml using either a fixed-dose or a body surface area adapted injection protocol. Maximum and mean standardized uptake values (SUVmax and SUVmean) and contrast enhancement (HU) were determined in the subclavian vein, ascending aorta, abdominal aorta, inferior vena cava, portal vein, liver and kidney and in the suspicious lung lesion. PET data were evaluated visually for the presence of malignancy and image quality. Results: At none of the sites a significant difference in the extent of the contrast enhancement between the four different protocols was found. However, the variability of the contrast enhancement at several anatomical sites was significantly greater in the fixed dose groups than in the BSA groups for both contrast medium concentrations. At none of the sites a significant difference was found in the extent of the SUVmax and SUVmean increase as a result of the use of the venous phase contrast enhanced CT for attenuation. Visual clinical evaluation of lesions showed no differences between contrast and non-contrast PET/CT (P = 0.32). Conclusions: Contrast enhanced CT for attenuation correction in combined PET/CT in lung cancer affects neither the clinical assessment nor image quality of the PET-images. A body surface adapted contrast medium protocol reduces the interpatient variability in contrast enhancement.

  8. The relevance of external quality assessment for molecular testing for ALK positive non-small cell lung cancer: results from two pilot rounds show room for optimization.

    Directory of Open Access Journals (Sweden)

    Lien Tembuyser

    Full Text Available Molecular profiling should be performed on all advanced non-small cell lung cancer with non-squamous histology to allow treatment selection. Currently, this should include EGFR mutation testing and testing for ALK rearrangements. ROS1 is another emerging target. ALK rearrangement status is a critical biomarker to predict response to tyrosine kinase inhibitors such as crizotinib. To promote high quality testing in non-small cell lung cancer, the European Society of Pathology has introduced an external quality assessment scheme. This article summarizes the results of the first two pilot rounds organized in 2012-2013.Tissue microarray slides consisting of cell-lines and resection specimens were distributed with the request for routine ALK testing using IHC or FISH. Participation in ALK FISH testing included the interpretation of four digital FISH images.Data from 173 different laboratories was obtained. Results demonstrate decreased error rates in the second round for both ALK FISH and ALK IHC, although the error rates were still high and the need for external quality assessment in laboratories performing ALK testing is evident. Error rates obtained by FISH were lower than by IHC. The lowest error rates were observed for the interpretation of digital FISH images.There was a large variety in FISH enumeration practices. Based on the results from this study, recommendations for the methodology, analysis, interpretation and result reporting were issued. External quality assessment is a crucial element to improve the quality of molecular testing.

  9. Lung function

    Institute of Scientific and Technical Information of China (English)


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

  10. Assessment of early acute lung injury in rats exposed to aerosols of consumer products: attempt to disentangle the "Magic Nano" conundrum. (United States)

    Pauluhn, Jürgen; Hahn, Axel; Spielmann, Horst


    In Germany in 2006 a series of rapidly developing and sometimes severe cases of pulmonary health impairment were observed after normal use of the "Magic Nano Glass & Ceramic" spray and "Magic Nano Bath" spray. In contrast, the previously marketed "Magic Nano" pump spray product (handheld trigger device without propellants) was unobtrusive. Analysis of particles discharged from these products did not reveal stable (solid) nano-sized particles. The precipitous increase of pulmonary health impairment in humans caused by "Magic Nano Sprays" triggered a comparative assessment of the acute inhalation toxicity of "Magic Nano Glass & Ceramic" spray, "Magic Nano Bath" spray, and "Magic Nano" pump spray in rats. The first two test specimens were examined as spray-can aerosols using an intermittent generation principle, whereas the undiluted liquid content of the pump spray was continuously aerosolized. Groups of Wistar rats were nose-only exposed for 4 h. However, due to mortality occurring already during exposure following exposure to Glass & Ceramic spray, the exposure duration was reduced to approximately 2 h in some groups. In addition to endpoints called for by contemporary testing guidelines, respiratory tract injury was also probed by respiratory function measurements during exposure supplemented by analyses in bronchoalveolar lavage (BAL) fluid on the first postexposure day, including lung histopathology in rats exposed to Glass & Ceramic spray. The Glass & Ceramic spray caused mortality at 2269 mg/m(3) and above, the pump spray was in the beginning lethal range at 81222 mg/m(3), while the bath spray was tolerated without mortality up to the maximum tested nominal concentrations of 28100 mg/m(3). The time-adjusted 4-h LC(50) of Glass & Ceramic spray was 5098 mg/m(3). The analysis of respiratory patterns revealed changes indicative of both upper and lower respiratory tract sensory irritation. In addition to clinical signs suggestive of marked lung irritation

  11. Occupational exposures to carcinogens in Italy: an update of CAREX database. (United States)

    Mirabelli, Dario; Kauppinen, Timo


    To update estimates of the prevalence of occupational exposures to carcinogens in Italy, the 85 CAREX agents were re-assessed. The original exposure estimates in the CAREX database were updated, taking into account changes in exposure patterns and in numbers of employees by industrial class. The 21.8 million employees in Italy, 19.4 in industry and services, 2.4 in agriculture, had 4.2 million exposures. Prevalences of exposures were highest for environmental (passive) tobacco smoke (800,000 exposures), solar radiation (700,000), diesel engine exhaust (500,000), wood dust (280,000), silica (250,000), lead and inorganic lead compounds (230,000), benzene (180 000), hexavalent chromium compounds (160,000), glass wool (140,000), and PAHs (120,000). Exposures to carcinogens at work are still an issue in Italy and do not appear to be controlled as strictly as they should be.

  12. Protective effects of green tea polyphenols administered by oral intubation against chemical carcinogen-induced forestomach and pulmonary neoplasia in A/J mice. (United States)

    Katiyar, S K; Agarwal, R; Mukhtar, H


    Our studies and others have shown the cancer chemopreventive effects of chronic administration of green tea in several animal tumor models. In this study, the administration of a polyphenolic fraction isolated from green tea (GTP) by oral intubation at a dose of 5 mg in 0.2 ml water 30 min prior to challenge with carcinogen, afforded significant protection against both diethylnitrosamine (DEN)- and benzo(a)pyrene (BP)-induced forestomach and lung tumorigenesis in A/J mice. The protective effects were evident by a decrease in numbers of tumors/mouse in GTP-fed groups compared to non GTP-fed controls. In the forestomach tumorigenesis protocol, GTP afforded 71 and 66% protection against, respectively DEN- and BP-induced tumor multiplicity. In the case of lung tumorigenesis protocol, however, the protective effects of GTP were 41 and 39%, respectively. Histological examination of forestomach tumors showed significantly lesser number of squamous cell carcinoma formation in GTP-fed groups of mice compared to carcinogen alone-treated controls. When pulmonary tumors were examined histologically, no adenocarcinomas were observed in GTP-fed groups compared to 15% mice with adenocarcinomas in DEN and BP alone-treated controls. The results of this study suggest that limited doses of GTP administration by gavage 30 min prior to carcinogen challenge may afford protection against carcinogen-induced tumorigenesis in internal body organs.

  13. Investigation on the carcinogenic effects of coal tar pitch in rat respiratory tract by intratracheal instillations. (United States)

    Chang, F; Wang, L; Zhao, Q; Zhu, Q; Wu, Y; Chen, C; Syrjänen, S; Syrjänen, K


    The effects of coal tar pitch (CTP) on the tracheobronchial mucosa of Wistar rats were studied. Three groups of animals received 10 weekly intratracheal instillations of CTP at the cumulative doses of 6.48, 136.56 and 200 mg respectively. The control group of rats received 10 weekly intratracheal instillations of charcoal powder at a cumulative dose of 20 mg. The study in which the animals were killed serially revealed that CTP had conspicuous damage on the respiratory system of rats, especially on the bronchiolo-alveolar areas. The lesions induced by CTP ranged from hyperplastic, metaplastic and dysplastic changes to extensive cancers. These lesions were usually multifocal, and were more severe in the rats receiving higher dosages of CTP. The deposition of CTP particles within or adjacent to these lesions could be readily identified. Lung cancers occurred in 12.5% (4/32) and 25% (10/40) of the rats treated with 136.56 and 200 mg of CTP, whereas no tumors were found in control rats and the rats that received 6.48 mg of CTP. The overall cancer incidence significantly related to the cumulative dose of CTP. The histological types of lung cancers consisted of squamous cell carcinomas (10 out of the 14 lung cancers), adenocarcinoma (1/14), and combined squamous and adenocarcinomas (3/14). The development of CTP-induced rat lung cancers appears to derive from the hyperplasias of bronchiolo-alveolar epithelium, and processing stages of squamous metaplasias and/or dysplasias to carcinomas. The present results confirmed the carcinogenic effects of CTP on the respiratory system of rats, and provided experimental evidence for human lung carcinogenesis, particularly in those occupationally exposed to coal tars or tar products.

  14. The Weight of Evidence Does Not Support the Listing of Styrene as “Reasonably Anticipated to be a Human Carcinogen” in NTP's Twelfth Report on Carcinogens (United States)

    Rhomberg, Lorenz R.; Goodman, Julie E.; Prueitt, Robyn L.


    Styrene was listed as “reasonably anticipated to be a human carcinogen” in the twelfth edition of the National Toxicology Program's Report on Carcinogens based on what we contend are erroneous findings of limited evidence of carcinogenicity in humans, sufficient evidence of carcinogenicity in experimental animals, and supporting mechanistic data. The epidemiology studies show no consistent increased incidence of, or mortality from, any type of cancer. In animal studies, increased incidence rates of mostly benign tumors have been observed only in certain strains of one species (mice) and at one tissue site (lung). The lack of concordance of tumor incidence and tumor type among animals (even within the same species) and humans indicates that there has been no particular cancer consistently observed among all available studies. The only plausible mechanism for styrene-induced carcinogenesis—a non-genotoxic mode of action that is specific to the mouse lung—is not relevant to humans. As a whole, the evidence does not support the characterization of styrene as “reasonably anticipated to be a human carcinogen,” and styrene should not be listed in the Report on Carcinogens. PMID:23335843

  15. 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.

  16. The International Agency for Research on Cancer (IARC) evaluation of the carcinogenicity of outdoor air pollution: focus on China. (United States)

    Loomis, Dana; Huang, Wei; Chen, Guosheng


    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.

  17. The International Agency for Research on Cancer (IARC) evaluation of the carcinogenicity of outdoor air pollution:focus on China

    Institute of Scientific and Technical Information of China (English)

    Dana Loomis; Wei Huang; Guosheng Chen


    The International Agency for Research on Cancer (IARC) has classified outdoor air pol ution and the particulate matter (PM) in outdoor air pol ution 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 pol ution 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 pol ution, 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 pol utants. Excess cancer risk is also observed in experimental animals exposed to pol uted 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 pol ution in China and the urgent need to act to reduce exposure to the population.

  18. Do air quality targets really represent safe limits for lung cancer risk? (United States)

    Buonanno, G; Stabile, L; Morawska, L; Giovinco, G; Querol, X


    In order to estimate the lung cancer risk associated to airborne particles, exposure and risk-assessment studies ordinarily use particle mass concentration as dosimetry parameter. Consequently, the corresponding air quality targets are based on this metrics, neglecting the potential impact of ultrafine particles (UFPs) due to their negligible mass. The main purpose of this study was to evaluate the reliability of air quality targets in protecting Italian non-smoking people from lung cancer risk due to exposure to polycyclic aromatic hydrocarbons and some heavy metals associated with particle inhalation. A modified risk-assessment scheme was applied to estimate the cancer risk contribution from both sub-micron (mainly UFPs) and super-micron particles. We found a very high lung cancer risk related to the actual target levels due to the contribution of UFPs, in particular from indoor microenvironments. Therefore, as possible actions to reduce the lung cancer risk, we have hypothesized and tested three different scenarios: a) a reduction of the concentration of carcinogenic chemicals condensed onto particles in agreement with the current EU air pollution policy; b) the use of local ventilation systems to mitigate the exposure to cooking-generated particles; c) the improvement of the overall indoor air quality by considering a mechanical ventilation system instead of the widespread natural ventilation in order to increase the air exchange rates. Even with the simultaneous application of specific actions, performed with the best technologies available, the corresponding estimated lifetime lung cancer risk (ELCR) values for the Italian population for the entire life were equal to 1.25×10(-4) and 1.23×10(-4) for males and females, respectively, well higher with respect to the maximum tolerable lifetime cancer risk, 1×10(-5).

  19. Environmental carcinogens and mutational pathways in atherosclerosis. (United States)

    Pulliero, A; Godschalk, R; Andreassi, M G; Curfs, D; Van Schooten, F J; Izzotti, A


    Atherosclerosis is associated with DNA damage in both circulating and vessel-wall cells and DNA adducts derived from exposure to environmental mutagens are abundant in atherosclerotic vessels. Environmental chemical carcinogens identified as risk factor for atherosclerosis include polycyclic aromatic hydrocarbons (benzo(a)pyrene, dimethylbenz(a)anthracene, beta-naphthoflavone, pyrene, 3-methylcolanthrene), arsenic, cadmium, 1,3-butadiene, cigarette smoke. Accordingly, polymorphisms of genes encoding for phase I/II metabolic reaction and DNA repair are risk factor for cardiovascular diseases, although their role is negligible as compared to other risk factors. The pathogenic relevance of mutation-related molecular damage in atherosclerosis has been demonstrated in experimental animal models involving the exposure to chemical mutagens. The relevance of mutation-related events in worsening atherosclerosis prognosis has been demonstrated in human clinical studies mainly as referred to mitochondrial DNA damage. Atherosclerosis is characterized by the occurrence of high level of oxidative damage in blood vessel resulting from both endogenous and exogenous sources. Mitochondrial damage is a main endogenous source of oxidative stress whose accumulation causes activation of intrinsic apoptosis through BIRC2 inhibition and cell loss contributing to plaque development and instability. Environmental physical mutagens, including ionizing radiation, are a risk factor for atherosclerosis even at the low exposure dose occurring in case of occupational exposure or the high exposure doses occurring during radiotherapy. Conversely, the role of exciting UV radiation in atherosclerosis is still uncertain. This review summarizes the experimental and clinical evidence supporting the pathogenic role of mutation-related pathway in atherosclerosis examining the underlying molecular mechanisms.

  20. Asphalt fume dermal carcinogenicity potential: I. dermal carcinogenicity evaluation of asphalt (bitumen) fume condensates. (United States)

    Clark, Charles R; Burnett, Donald M; Parker, Craig M; Arp, Earl W; Swanson, Mark S; Minsavage, Gary D; Kriech, Anthony J; Osborn, Linda V; Freeman, James J; Barter, Robert A; Newton, Paul E; Beazley, Shelley L; Stewart, Christopher W


    Asphalt (bitumen) fume condensates collected from the headspace above paving and Type III built up roofing asphalt (BURA) tanks were evaluated in two-year dermal carcinogenicity assays in male C3H/HeNCrl mice. A third sample was generated from the BURA using a NIOSH laboratory generation method. Similar to earlier NIOSH studies, the BURA fume condensates were applied dermally in mineral oil twice per week; the paving sample was applied 7 days/week for a total weekly dose of 50 mg/wk in both studies. A single benign papilloma was observed in a group of 80 mice exposed to paving fume condensate at the end of the two-year study and only mild skin irritation was observed. The lab generated BURA fume condensate resulted in statistically significant (P<0.0001) increases in squamous cell carcinomas (35 animals or 55% of animals at risk). The field-matched BURA condensate showed a weaker but significant (P=0.0063) increase (8 carcinomas or 13% of animals) and a longer average latency (90 weeks vs. 76 for the lab fume). Significant irritation was observed in both BURA condensates. It is concluded that the paving fume condensate was not carcinogenic under the test conditions and that the field-matched BURA fume condensate produced a weak tumor response compared to the lab generated sample.

  1. Carcinogenicity and co-carcinogenicity studies on propoxur in mouse skin. (United States)

    Shukla, Y; Baqar, S M; Mehrotra, N K


    Propoxur (2-isopropoxyphenyl methylcarbamate) is a widely used broad spectrum carbamate insecticide mainly used to control household pests. Propoxur exposure is reported to inhibit cholinesterase activity in rodents. Apart from other toxic effects, propoxur was found to possess tumorigenic activity in rats after oral administration. Propoxur does not produce tumours in mice or hamsters, or bladder hyperplasia in dogs and monkeys following oral feeding. In this set of investigations the complete carcinogenic, tumour initiating and promoting potential of propoxur was evaluated in male and female Swiss albino mice, since no information was available following dermal exposure of propoxur. The animals were exposed to propoxur through topical painting on the interscapular region at a dose of 100 mg/kg body weight. The results revealed that propoxur has tumour promoting potential on mouse skin following a two-stage initiation-promotion protocol, but it failed to induce the tumour(s) at a significant level, when tested for tumour initiating and complete carcinogenic property.

  2. Open lung biopsy (United States)

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

  3. Best practices for clinical pathology testing in carcinogenicity studies. (United States)

    Young, Jamie K; Hall, Robert L; O'Brien, Peter; Strauss, Volker; Vahle, John L


    The Society of Toxicologic Pathology (STP) and American Society for Veterinary Clinical Pathology (ASCVP) convened a Clinical Pathology in Carcinogenicity Studies Working Group to recommend best practices for inclusion of clinical pathology testing in carcinogenicity studies. Regulatory guidance documents and literature were reviewed, and veterinary pathologists from North America, Japan, and Europe were surveyed regarding current practices, perceived value, and recommendations for clinical pathology testing in carcinogenicity studies. For two-year rodent carcinogenicity studies, the Working Group recommends that clinical pathology testing be limited to collection of blood smears at scheduled and unscheduled sacrifices to be examined only if indicated to aid in the diagnosis of possible hematopoietic neoplasia following histopathologic evaluation. Additional clinical pathology testing is most appropriately used to address specific issues from prior toxicity studies or known test article-related class effects. Inadequate data were available to make a recommendation concerning clinical pathology testing for alternative six-month carcinogenicity assays using genetically modified mice, although the Working Group suggests that it may be appropriate to use the same approach as for two-year carcinogenicity studies since the study goal is the same.

  4. Trichloroethylene: Mechanistic, Epidemiologic and Other Supporting Evidence of Carcinogenic Hazard (United States)

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.


    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including from hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. Strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin's lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. PMID:23973663

  5. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard. (United States)

    Rusyn, Ivan; Chiu, Weihsueh A; Lash, Lawrence H; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z


    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE.

  6. Carcinogenicity and mechanistic insights on the behavior of epoxides and epoxide-forming chemicals. (United States)

    Melnick, Ronald L


    Many epoxides and their precursors are high production volume chemicals that have major uses in the polymer industry and as intermediates in the manufacture of other chemicals. Several of these chemicals were demonstrated to be carcinogenic in laboratory animal studies conducted by the Ramazzini Foundation (e.g., vinyl chloride, acrylonitrile, styrene, styrene oxide, and benzene) and by the National Toxicology Program (e.g., ethylene oxide, 1,3-butadiene, isoprene, chloroprene, acrylonitrile, glycidol, and benzene). The most common sites of tumor induction were lung, liver, harderian gland, and circulatory system in mice; Zymbal's gland and brain in rats; and mammary gland and forestomach in both species. Differences in cancer outcome among studies of epoxide chemicals may be related to differences in study design (e.g., dose, duration, and route of exposure; observation period; animal strains), as well as biological factors affecting target organ dosimetry of the DNA-reactive epoxide (toxicokinetics) and tissue response (toxicodynamics). N7-Alkylguanine, N1-alkyladenine, and cyclic etheno adducts, as well as K-ras and p53 mutations, have been detected in animals and/or workers exposed to several of these chemicals. The classifications of these chemical carcinogens by IARC and NTP are based on animal and human data and results of mechanistic studies. Reducing occupational and environmental exposures to these chemicals will certainly reduce human cancer risks.

  7. Exposure-response estimates for diesel engine exhaust and lung cancer mortality based on data from three occupational cohorts

    NARCIS (Netherlands)

    Vermeulen, Roel; Silverman, Debra T.; Garshick, Eric; Vlaanderen, Jelle; Portengen, Lützen; Steenland, Kyle


    Background: Diesel engine exhaust (DEE) has recently been classified as a known human carcinogen. Objective: We derived a meta-exposure-response curve (ERC) for DEE and lung cancer mortality and estimated lifetime excess risks (ELRs) of lung cancer mortality based on assumed occupational and environ

  8. Carcinogenicity of azo dyes: Acid Black 52 and Yellow 3 in hamsters and rats. Volume 2. Technical report (Final)

    Energy Technology Data Exchange (ETDEWEB)

    Plankenhorn, L.J.


    This document is an appendix to a study concerning the carcinogenicity of the azo dyes acid-black-52 and yellow-3 in male and female hamsters and rats and contains individual histopathology studies of both dyes. Histopathological features were reported in tabular form for the skin, mammary gland, muscle, salivary gland, mandibular lymph node, sciatic nerve, thymus, larynx, thyroid, parathyroid, trachea, bronchus, esophagus, adrenal, stomach, duodenum, jejunem, ileum, cecum, colon, rectum, mesenteric lymph node, lung, liver, gallbladder, spleen, pancreas, kidney, heart, urinary bladder, seminal vesicle, prostate, testis, cerebrum, cerebellum, pituitary, sternabrae, femur, bone marrow, and nasal cavity.

  9. Prioritization of Louisiana Parishes based on Industrial Releases of Known or Suspected Carcinogens. (United States)

    Katner, Adrienne


    This investigation evaluated the geographic distribution of carcinogen releases by Louisiana industries to prioritize areas for regulatory oversight, research and monitoring, and to promote clinician awareness and vigilance. Data on estimated industry releases for the period between 1996 and 2011 were obtained from the US Environmental Protection Agency's Toxics Release Inventory. Chemicals associated with cancers of the prostate, lung, bladder, kidney, breast and non-Hodgkin lymphoma were identified. The Risk Screening Environmental Indicators model was used to derive measures or model scores based on chemical toxicity, fate and transport, and population characteristics. Parishes, chemicals, industries and media generating the highest model scores were identified. Parishes with the highest model scores were East Baton Rouge, Calcasieu, Caddo and St. John the Baptist. Clinicians should carefully monitor cancer cases in these areas, and if patients reside near or work in industry, an occupational and environmental history should be considered.

  10. Further evidence of benzene carcinogenicity. Results on Wistar rats and Swiss mice treated by ingestion. (United States)

    Maltoni, C; Conti, B; Perino, G; Di Maio, V


    Wistar rats and Swiss mice were treated by ingestion (stomach tube) with benzene in olive oil at a dose of 500 and 0 mg/kg b.w. once daily, 4-5 days weekly, for 104 weeks (rats) or for 78 weeks (mice). In Wistar rats, benzene caused Zymbal gland carcinomas, carcinomas of the oral cavity, and carcinomas of the nasal cavities, and an increase in the incidence of total malignant tumors. In Swiss mice, benzene produced Zymbal gland carcinomas and dysplasias and an increase in the incidence of mammary carcinomas (in females), lung tumors, and total malignant tumors. These experiments further confirm that benzene is a multipotential carcinogen as was shown before by long-term bioassays performed on Sprague-Dawley rats in the same Experimental Unit.

  11. Assessment of lung disease in children with cystic fibrosis using hyperpolarized 3-Helium MRI: comparison with Shwachman score, Chrispin-Norman score and spirometry

    Energy Technology Data Exchange (ETDEWEB)

    Beek, Edwin J.R. van [University of Sheffield, Unit of Academic Radiology, Sheffield (United Kingdom); University of Iowa, Department of Radiology, Carver College of Medicine, Iowa City (United States); University of Iowa, Department of Radiology, Iowa City, IA (United States); Hill, Catherine; Woodhouse, Neil; Fichele, Stanislao; Fleming, Sally; Wild, Jim M. [University of Sheffield, Unit of Academic Radiology, Sheffield (United Kingdom); Howe, Bridget; Bott, Sandra; Taylor, Christopher J. [University of Sheffield, Academic Unit of Child Health, Sheffield (United Kingdom)


    This study assesses the feasibility of hyperpolarized 3-Helium MRI in children with cystic fibrosis (CF) and correlates the findings with standard clinical parameters based on chest radiograph (CXR) and pulmonary function tests (PFT). An uncontrolled, observational study in eighteen children with cystic fibrosis aged 5 - 17 years (median 12.1 years), with different severity of disease was carried out. All subjects underwent routine clinical assessment including PFT and standard auxology; CXR was obtained and Shwachman and Chrispin-Norman scores calculated. Hyperpolarized 3-He magnetic resonance imaging (MRI) was carried out using a spin-exchange polarizer and a whole body 1.5 T scanner. Ventilation distribution images were obtained during a 21-second breath-hold and scored according to previously defined criteria. Spearman's non-parametric correlations test was performed to assess for statistical significance at the p<0.05 level. The children tolerated the procedure well. No desaturation events were observed during 3-He MRI. A significant, albeit moderate, correlation was found between MRI score and FEV1% predicted (r=-0.41; p=0.047) and FVC% predicted (r=-0.42; p=0.04), while there were trends of correlations between Shwachman score and MRI score (r=-0.38; p=0.06) and Shwachman score and FEV1% predicted (r=0.39; p=0.055). The feasibility of hyperpolarized 3-He MRI in children with CF was demonstrated. MRI appears to be able to demonstrate functional lung changes, although correlations with routine clinical tests are only moderate to poor. This non-ionising radiation technique could be useful for monitoring lung disease and assessing therapy in this patient population. (orig.)

  12. 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


    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

  13. Two-year carcinogenicity study of acrylamide in Wistar Han rats with in utero exposure. (United States)

    Maronpot, R R; Thoolen, R J M M; Hansen, B


    Acrylamide is an important chemical with widespread industrial and other uses in addition to generalized population exposure from certain cooked foods. Previous rat studies to assess the carcinogenic potential of acrylamide have been carried out exclusively in the Fischer 344 rat with identification of a number of tumors amongst which mesotheliomas of the tunica vaginalis is an important tumor endpoint in the classification of acrylamide as a 'probably human carcinogen. In a rat carcinogenicity study to determine the human relevance of mesotheliomas Wistar Han rats were exposed to 0, 0.5, 1.5, or 3.0mg acrylamide/kg body weight/day in drinking water starting at gestation day 6. At the end of two years, mammary gland fibroadenomas in females and thyroid follicular cell tumors in both sexes were the only tumors increased in acrylamide treated rats. These tumor endpoints have rat-specific modes of action suggesting less likelihood of human cancer risk than previously estimated. This study demonstrates that tunica vaginalis mesotheliomas are strain specific and not likely of genotoxic origin.

  14. Experimental studies on benzene carcinogenicity at the Bologna Institute of Oncology: current results and ongoing research. (United States)

    Maltoni, C; Conti, B; Cotti, G; Belpoggi, F


    In 1977 Maltoni and Scarnato were the first to demonstrate that benzene is an experimental carcinogen in rats. With that and other experiments, Maltoni et al have shown that benzene administered by ingestion (stomach tube) or inhalation is a multipotential carcinogen in rats (of two different strains) and mice and produces a variety of tumors, namely: Zymbal gland carcinomas, oral and nasal cavity carcinomas, skin carcinomas, acanthomas, dysplasias and carcinomas of forestomach, mammary malignant tumors, hepatomas, liver angiosarcomas, hemolymphoreticular neoplasias, and pulmonary tumors. The incidence of Zymbal gland carcinomas and carcinomas of the oral and nasal cavities is affected by the length of treatment by inhalation and by the age of animals. However, the available epidemiological and experimental data at present do not provide precise information on the risk of doses around or below 10 ppm. Long-term carcinogenicity bioassays at 50, 25, 10, 5 and 1 ppm may be helpful for scientific risk assessment. In addition, these experiments have shown that toluene, xylene, and ethylbenzene, at high concentrations, cause an increase in the number of total malignant tumors.

  15. Analysis of genotoxicity and the carcinogenic mode of action for ortho-phenylphenol. (United States)

    Brusick, David


    Ortho-phenylphenol (OPP) and its sodium salt (SOPP) are commercial products that have wide human exposure and have been shown in several studies to be rodent carcinogens. Genetic toxicology data were assessed in an attempt to understand the carcinogenic mode of action of OPP and SOPP. More than 130 studies were evaluated to determine if OPP, SOPP, or any of their enzymatic or nonenzymatic breakdown products react directly with DNA to induce mutation, changes in chromosome structure or number, DNA repair, or nonspecific DNA damage including strand breakage or covalent binding. The genotoxicity databases for OPP and SOPP are not only large but heterogeneous, requiring weight-of-evidence methods to arrive at a conclusion regarding their genotoxic properties and potential. Evidence derived from the available studies leads to the conclusion that study results showing OPP/SOPP directly interacting with DNA are equivocal. Clastogenicity was the most consistent type of genetic toxicity produced by OPP/SOPP (and their break-down products) and was consistently associated with other intracellular preneoplastic toxicity produced at super-threshold concentrations. The weight of evidence from the combined database supports the hypothesis that OPP/SOPP-induced DNA damage is a threshold-dependent response associated with target tissue toxicity, most likely induced by their breakdown products phenylhydroquinone and phenylbenzoquinone. It is possible that this threshold-dependent clastogenicity could contribute to the carcinogenic mode of action for OPP or SOPP.

  16. Comparison of Nicotine and Carcinogen Exposure with Water pipe and Cigarette Smoking (United States)

    Jacob, Peyton; Abu Raddaha, Ahmad H.; Dempsey, Delia; Havel, Christopher; Peng, Margaret; Yu, Lisa; Benowitz, Neal L.


    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. We investigated biomarkers of toxicant exposure with water pipe compared to cigarette smoking. Methods We conducted a cross-over 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 While smoking an average of 3 water pipe sessions compared to smoking 11 cigarettes per day, water pipe use was associated with a significantly lower intake of nicotine, greater exposure to carbon monoxide and a different pattern of carcinogen exposure compared to cigarette smoking, with greater exposure to benzene and high molecular weight PAHs, but less exposure to tobacco-specific nitrosamines, 1,3-butadiene and acrolein, acrylonitrile, propylene oxide, ethylene oxide, and low molecular weight PAHs. Conclusions 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. Impact 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. PMID:23462922

  17. Lung transplantation for cystic fibrosis

    NARCIS (Netherlands)

    Adler, Frederick R; Aurora, Paul; Barker, David H; Barr, Mark L; Blackwell, Laura S; Bosma, Otto H; Brown, Samuel; Cox, D R; Jensen, Judy L; Kurland, Geoffrey; Nossent, George D; Quittner, Alexandra L; Robinson, Walter M; Romero, Sandy L; Spencer, Helen; Sweet, Stuart C; van der Bij, Wim; Vermeulen, J; Verschuuren, Erik A M; Vrijlandt, Elianne J L E; Walsh, William; Woo, Marlyn S; Liou, Theodore G


    Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing

  18. Increased mean lung density: Another independent predictor of lung cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Sverzellati, Nicola, E-mail: [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Randi, Giorgia, E-mail: [Department of Epidemiology, Mario Negri Institute, Via La Masa 19, 20156 Milan (Italy); Spagnolo, Paolo, E-mail: [Respiratory Disease Unit, Center for Rare Lung Disease, Department of Oncology, Hematology and Respiratory Disease, University of Modena and Reggio Emilia, Via del Pozzo 71, 44124 Modena (Italy); Marchianò, Alfonso, E-mail: [Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy); Silva, Mario, E-mail: [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Kuhnigk, Jan-Martin, E-mail: [Fraunhofer MEVIS, Universitaetsallee 29, 28359 Bremen (Germany); La Vecchia, Carlo, E-mail: [Department of Occupational Health, University of Milan, Via Venezian 1, 20133 Milan (Italy); Zompatori, Maurizio, E-mail: [Department of Radiology, Cardio-Thoracic Section, S. Orsola-Malpighi Hospital, Via Albertoni 15, 40138 Bologna (Italy); Pastorino, Ugo, E-mail: [Department of Surgery, Section of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy)


    Objectives: To investigate the relationship between emphysema phenotype, mean lung density (MLD), lung function and lung cancer by using an automated multiple feature analysis tool on thin-section computed tomography (CT) data. Methods: Both emphysema phenotype and MLD evaluated by automated quantitative CT analysis were compared between outpatients and screening participants with lung cancer (n = 119) and controls (n = 989). Emphysema phenotype was defined by assessing features such as extent, distribution on core/peel of the lung and hole size. Adjusted multiple logistic regression models were used to evaluate independent associations of CT densitometric measurements and pulmonary function test (PFT) with lung cancer risk. Results: No emphysema feature was associated with lung cancer. Lung cancer risk increased with decreasing values of forced expiratory volume in 1 s (FEV{sub 1}) independently of MLD (OR 5.37, 95% CI: 2.63–10.97 for FEV{sub 1} < 60% vs. FEV{sub 1} ≥ 90%), and with increasing MLD independently of FEV{sub 1} (OR 3.00, 95% CI: 1.60–5.63 for MLD > −823 vs. MLD < −857 Hounsfield units). Conclusion: Emphysema per se was not associated with lung cancer whereas decreased FEV{sub 1} was confirmed as being a strong and independent risk factor. The cross-sectional association between increased MLD and lung cancer requires future validations.

  19. Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis (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


    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. Acrylonitrile is a multisite carcinogen in male and female B6C3F1 mice. (United States)

    Ghanayem, Burhan I; Nyska, Abraham; Haseman, Joseph K; Bucher, John R


    Acrylonitrile is a heavily produced unsaturated nitrile, which is used in the production of synthetic fibers, plastics, resins, and rubber. Acrylonitrile is a multisite carcinogen in rats after exposure via gavage, drinking water, or inhalation. No carcinogenicity studies of acrylonitrile in a second animal species were available. The current studies were designed to assess the carcinogenicity of acrylonitrile in B6C3F1 mice of both sexes. Acrylonitrile was administered by gavage at 0, 2.5, 10, or 20 mg/kg/day, 5 days per week, for 2 years. Urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine were measured as markers of exposure to acrylonitrile. In general, there were dose-related increases in urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine concentrations in all dosed groups of mice and at all time points. Survival was significantly (p acrylonitrile-dosed groups. In female mice, the incidence of benign or malignant granulosa cell tumors (combined) in the ovary in the 10 mg/kg dose group was greater than that in the vehicle control group, but because of a lack of dose response, this was considered an equivocal finding. In addition, the incidences of atrophy and cysts in the ovary of the 10 and 20 mg/kg dose groups were significantly increased. The incidences of alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in female mice treated with acrylonitrile at 10 mg/kg/day for 2 years. This was also considered an equivocal result. In conclusion, these studies demonstrated that acrylonitrile causes multiple carcinogenic effects after gavage administration to male and female B6C3F1 mice for 2 years.

  1. Mechanism-Based Classification of PAH Mixtures to Predict Carcinogenic Potential. (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


    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 < .05) for DNA damage, apoptosis, response to chemical stimulus, and interferon gamma signaling resulted in the highest classification accuracy with leave-one-out cross validation. This pathway-driven approach was successfully utilized to distinguish early regulatory events during initiation prognostic for tumor outcome and provides proof-of-concept for using short-term initiation studies to classify 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.

  2. Dynamic magnetic resonance imaging in assessing lung function in adolescent idiopathic scoliosis: a pilot study of comparison before and after posterior spinal fusion

    Directory of Open Access Journals (Sweden)

    Lam Wynnie WM


    Full Text Available Abstract Background Restrictive impairment is the commonest reported pulmonary deficit in AIS, which improves following surgical operation. However, exact mechanism of how improvement is brought about is unknown. Dynamic fast breath-hold (BH-MR imaging is a recent advance which provides direct quantitative visual assessment of pulmonary function. By using above technique, change in lung volume, chest wall and diaphragmatic motion in AIS patients before and six months after posterior spinal fusion surgery were measured. Methods 16 patients with severe right-sided predominant thoracic scoliosis (standing Cobb's angle 50° -82°, mean 60° received posterior spinal fusion without thoracoplasty were recruited into this study. BH-MR sequences were used to obtain coronal images of the whole chest during full inspiration and expiration. The following measurements were assessed: (1 inspiratory, expiratory and change in lung volume; (2 change in anteroposterior (AP and transverse (TS diameter of the chest wall at two levels: carina and apex (3 change in diaphragmatic heights. The changes in parameters before and after operation were compared using Wilcoxon signed ranks test. Patients were also asked to score their breathing effort before and after operation using a scale of 1–9 with ascending order of effort. The degree of spinal surgical correction at three planes was also assessed by reformatted MR images and correction rate of Cobb's angle was calculated. Results The individual or total inspiratory and expiratory volume showed slight but insignificant increase after operation. There was significantly increase in bilateral TS chest wall movement at carina level and increase in bilateral diaphragmatic movements between inspiration and expiration. The AP chest wall movements, however, did not significantly change. The median breathing effort after operation was lower than that before operation (p There was significant reduction in coronal Cobb's angle

  3. Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents. (United States)

    van den Brink, Willem; Emerenciana, Annette; Bellanti, Francesco; Della Pasqua, Oscar; van der Laan, Jan Willem


    Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes.

  4. Lung cancer epidemiology and risk factors in Asia and Africa

    Energy Technology Data Exchange (ETDEWEB)

    Lam, W.K.; White, N.W.; Chan-Yeung, M.M. [University of Hong Kong, Hong Kong (China)


    In Industrialized Countries, lung cancer is the most common form of cancer among males and it is growing among females. For both sexes, rates reflect smoking behaviours. The pattern appears to be different in Asia, particularly in China, where lung cancer rates in men reflect high smoking rates but high rates among non-smoking women appear to be related to other factors. The incidence of lung cancer is low in most African countries, but it is increasing. In addition to tobacco smoking, a number of aetiological factors have been identified for lung cancer: indoor exposure to environmental tobacco smoke, cooking oil vapour, coal burning or radon, outdoor air pollution and occupational exposure to asbestos and other carcinogens. Recent studies have shown that dietary factors may be important, with high consumption of vegetables and fruits being protective, while preserved foods and fatty foods are harmful, and certain infections such as Mycobacterium tuberculosis, human papillomavirus and Microsporum canis are associated with a high risk of lung cancer. Among non-smokers, the probable role of genetic predisposition in lung cancer by increasing the individual's susceptibility to environmental carcinogens is currently being studied actively. As the single most important cause for lung cancer is tobacco smoke and, with increased sales, a major epidemic is predicted for both Asia and Africa, all health care professionals, government health authorities and national and international health organizations must join in a concerted effort against tobacco. 135 refs.

  5. Effect of lung volume on airway luminal area assessed by computed tomography in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Kenta Kambara

    Full Text Available BACKGROUND: Although airway luminal area (Ai is affected by lung volume (LV, how is not precisely understood. We hypothesized that the effect of LV on Ai would differ by airway generation, lung lobe, and chronic obstructive pulmonary disease (COPD severity. METHODS: Sixty-seven subjects (15 at risk, 18, 20, and 14 for COPD stages 1, 2, and 3 underwent pulmonary function tests and computed tomography scans at full inspiration and expiration (at functional residual capacity. LV and eight selected identical airways were measured in the right lung. Ai was measured at the mid-portion of the 3(rd, the segmental bronchus, to 6(th generation of the airways, leading to 32 measurements per subject. RESULTS: The ratio of expiratory to inspiratory LV (LV E/I ratio and Ai (Ai E/I ratio was defined for evaluation of changes. The LV E/I ratio increased as COPD severity progressed. As the LV E/I ratio was smaller, the Ai E/I ratio was smaller at any generation among the subjects. Overall, the Ai E/I ratios were significantly smaller at the 5(th (61.5% and 6(th generations (63.4% and than at the 3(rd generation (73.6%, p<0.001 for each, and also significantly lower in the lower lobe than in the upper or middle lobe (p<0.001 for each. And, the Ai E/I ratio decreased as COPD severity progressed only when the ratio was corrected by the LV E/I ratio (at risk v.s. stage 3 p<0.001, stage 1 v.s. stage 3 p<0.05. CONCLUSIONS: From full inspiration to expiration, the airway luminal area shrinks more at the distal airways compared with the proximal airways and in the lower lobe compared with the other lobes. Generally, the airways shrink more as COPD severity progresses, but this phenomenon becomes apparent only when lung volume change from inspiration to expiration is taken into account.

  6. Comparative Plasma Exposure and Lung Distribution of Two Human Use Commercial Azithromycin Formulations Assessed in Murine Model: A Preclinical Study


    Virginia Rivulgo; Mónica Sparo; Mónica Ceci; Elida Fumuso; Alejandra Confalonieri; Gastón Delpech; Sánchez Bruni, Sergio F.


    Azithromycin(AZM)therapeutic failure and relapses of patients treated with generic -35 formulations have been observed in clinical practice.The main goal of this research was 36 to compare in a pre-clinical study the serum exposure and lung tissue concentrationof 37 two commercial formulations AZM-based in murine model. The current study involved 38 264 healthy Balb-C.Mice were divided in two groups (n=44): Animals of Group A 39 (Reference Formulation ?R-) were orally treated with AZM suspens...

  7. Montmorillonite Dissolution in Simulated Lung Fluids (United States)

    Schmidt, M.; Wendlandt, R. F.


    Because lung fluids" first interaction is with the surface of inhaled grains, the surface properties of inhaled mineral dusts may have a generally mitigating effect on cytotoxicity and carcinogenicity. Wendlandt et al. (Appl. Geochem. 22, 2007) investigated the surface properties of respirable-sized quartz grains in bentonites and recognized pervasive montmorillonite surface coatings on silica grains. The purpose of this study was to determine the dissolution rate and biodurability of montmorillonite in simulated lung fluids and to assess its potential to mitigate silica cytotoxicity. Modified batch reaction experiments were conducted on purified and size fractionated calcic (SAz-2; 0.4-5 μm) and sodic (DC-2; 0.4-2 μm) montmorillonites for 120 to 160 days of reaction time at 37°C in both simulated extracellular lung fluid (Lu) and simulated lysosomal fluid (Ly). Modified batch experiments simulated a flow-through setup and minimized sample handling difficulties. Reacted Lu and Ly fluid was analyzed for Mg, Al, and Si on an ICP-OE spectrometer. Steady state dissolution was reached 90-100 days after the start of the experiment and maintained for 40-60 days. Measured montmorillonite dissolution rates based on BET surface areas and Si steady state release range from 4.1x10-15 mol/m2/s at the slowest to 1.0x10-14 mol/m2/s at the fastest with relative uncertainties of less than 10%. Samples reacting in Ly (pH = 4.55) dissolved faster than those in Lu (pH = 7.40), and DC-2 dissolved faster than SAz-2. The measured range of biodurabilities was 1,300 to 3,400 years for a 1 μm grain assuming a spherical volume and a molar volume equal to that of illite. The difference in salinities of the two fluids was too slight to draw conclusions about the relationship of ionic strength to dissolution rate. Results indicate that montmorillonite dissolution is incongruent and edge controlled. Dissolution rates for DC- 2 and SAz-2 clays were comparable to those reported in the

  8. Potential Pitfall in the Assessment of Lung Cancer with FDG-PET/CT: Talc Pleurodesis Causes Intrathoracic Nodal FDG Avidity

    Directory of Open Access Journals (Sweden)

    Yingbing Wang


    Full Text Available Objective. Talc pleurodesis is a common procedure performed to treat complications related to lung cancer. The purpose of our study was to characterize any thoracic nodal findings on FDG PET/CT associated with prior talc pleurodesis. Materials and Methods. The electronic medical record identified 44 patients who underwent PET/CT between January 2006 and December 2010 and had a history of talc pleurodesis. For each exam, we evaluated the distribution pattern, size, and attenuation of intrathoracic lymph nodes and the associated standardized uptake value. Results. High-attenuation intrathoracic lymph nodes were noted in 11 patients (25%, and all had corresponding increased FDG uptake (range 2–9 mm. Involved nodal groups were anterior peridiaphragmatic (100%, paracardiac (45%, internal mammary (25%, and peri-IVC (18% nodal stations. Seven of the 11 patients (63% had involvement of multiple lymph nodal groups. Mean longitudinal PET/CT and standalone CT followups of 15±11 months showed persistence of both high-attenuation and increased uptake at these sites, without increase in nodal size suggesting metastatic disease involvement. Conclusions. FDG avid, high-attenuation lymph nodes along the lymphatic drainage pathway for parietal pleura are a relatively common finding following talc pleurodesis and should not be mistaken for nodal metastases during the evaluation of patients with history of lung cancer.

  9. Lung density

    DEFF Research Database (Denmark)

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


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

  10. Lung Cancer (United States)

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

  11. Lung transplantation (United States)

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


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

  12. Dual-phase dual-energy CT in patients with lung cancer: assessment of the additional value of iodine quantification in lymph node therapy response

    Energy Technology Data Exchange (ETDEWEB)

    Baxa, Jan; Vondrakova, Alena; Matouskova, Tana; Ferda, Jiri [Charles University Teaching Hospital Plzen, Department of Imaging Methods, Plzen (Czech Republic); Ruzickova, Olga [Charles University Teaching Hospital Plzen, Department of Pulmonary Diseases, Plzen (Czech Republic); Schmidt, Bernhard; Flohr, Thomas; Sedlmair, Martin [Siemens Healthcare, CT Physics and Applications Development, Forchheim (Germany)


    To investigate the potential contribution of iodine uptake calculation from dual-phase dual-energy CT (DE-CT) for lymph node staging and therapy response monitoring in lung cancer patients. Retrospective analysis of 27 patients with non-small cell lung carcinoma (NSCLC), who underwent dual-phase DE-CT before and after chemotherapy, was performed. Iodine uptake (mg/mL) and total iodine uptake (mg) were calculated using prototype software in the early (arterial) and late (venous) post-contrast circulatory phase in 110 mediastinal lymph nodes. The arterial enhancement fraction (AEF) was calculated and compared with lymph node size and response to chemotherapy. A significant difference of AEF was observed between enlarged (90.4 %; 32.3-238.5 %) and non-enlarged (72.7 %; -37.5-237.5 %) lymph nodes (p = 0.044) before treatment onset. A significantly different change of AEF in responding (decrease of 26.3 %; p = 0.022) and non-responding (increase of 43.0 %; p = 0.031) lymph nodes was demonstrated. A higher value of AEF before treatment was observed in lymph nodes with subsequent favourable response (88.6 % vs. 77.7 %; p = 0.122), but this difference did not reach statistical significance. The dual-phase DE-CT examination with quantification of ratio of early and late post-contrast iodine uptake is a feasible and promising method for the functional evaluation of mediastinal lymph nodes including therapy response assessment. (orig.)

  13. Analysis of intervention strategies for inhalation exposure to polycyclic aromatic hydrocarbons and associated lung cancer risk based on a Monte Carlo population exposure assessment model.

    Directory of Open Access Journals (Sweden)

    Bin Zhou

    Full Text Available It is difficult to evaluate and compare interventions for reducing exposure to air pollutants, including polycyclic aromatic hydrocarbons (PAHs, a widely found air pollutant in both indoor and outdoor air. This study presents the first application of the Monte Carlo population exposure assessment model to quantify the effects of different intervention strategies on inhalation exposure to PAHs and the associated lung cancer risk. The method was applied to the population in Beijing, China, in the year 2006. Several intervention strategies were designed and studied, including atmospheric cleaning, smoking prohibition indoors, use of clean fuel for cooking, enhancing ventilation while cooking and use of indoor cleaners. Their performances were quantified by population attributable fraction (PAF and potential impact fraction (PIF of lung cancer risk, and the changes in indoor PAH concentrations and annual inhalation doses were also calculated and compared. The results showed that atmospheric cleaning and use of indoor cleaners were the two most effective interventions. The sensitivity analysis showed that several input parameters had major influence on the modeled PAH inhalation exposure and the rankings of different interventions. The ranking was reasonably robust for the remaining majority of parameters. The method itself can be extended to other pollutants and in different places. It enables the quantitative comparison of different intervention strategies and would benefit intervention design and relevant policy making.

  14. Lung diffusing capacity for nitric oxide and carbon monoxide in relation to morphological changes as assessed by computed tomography in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Nowak Dennis


    Full Text Available Abstract Background Due to large-scale destruction, changes in membrane diffusion (Dm may occur in cystic fibrosis (CF, in correspondence to alterations observed by computed tomography (CT. Dm can be easily quantified via the diffusing capacity for nitric oxide (DLNO, as opposed to the conventional diffusing capacity for carbon monoxide (DLCO. We thus studied the relationship between DLNO as well as DLCO and a CF-specific CT score in patients with stable CF. Methods Simultaneous single-breath determinations of DLNO and DLCO were performed in 21 CF patients (mean ± SD age 35 ± 9 y, FEV1 66 ± 28%pred. Patients also underwent spirometry and bodyplethysmography. CT scans were evaluated via the Brody score and rank correlations (rS with z-scores of functional measures were computed. Results CT scores correlated best with DLNO (rS = -0.83; p S = -0.63; p CO (rS = -0.79; p NO were significantly lower than for DLCO (p 1, IVC or bodyplethysmographic (e.g., SRaw, RV/TLC indices were weaker than for DLNO or DLCO but most of them were also significant (p Conclusion In this cross sectional study in patients with CF, DLNO and DLCO reflected CT-morphological alterations of the lung better than other measures. Thus the combined diffusing capacity for NO and CO may play a future role for the non-invasive, functional assessment of structural alterations of the lung in CF.

  15. SU-E-J-179: Assessment of Tumor Volume Change and Movement During Stereotactic Body Radiotherapy (SBRT) for Lung Cancer: Is Adaptive Radiation Therapy (ART) Necessary?

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C; Lee, C [Asan Medical Center, Seoul (Korea, Republic of)


    Purpose: Delineation of gross tumor volumes (GTVs) is important for stereotactic body radiotherapy (SBRT). However, tumor volume changes during treatment response. Here, we have investigated tumor volume changes and movement during SBRT for lung cancer, as a means of examining the need for adaptive radiation therapy (ART). Methods: Fifteen tumors in 15 patients with lung cancer were treated with SBRT (total dose: 60 Gy in 4 fractions). GTVs were obtained from cone-beam computed tomography scans (CBCT1–4) taken before each of the 4 fractions was administered. GTVs were delineated and measured by radiation oncologists using a treatment planning system. Variance in the tumor position was assessed between the planning CT and the CBCT images. To investigate the dosimetric effects of tumor volume changes, planning CT and CBCT4 treatment plans were compared using the conformity index (CI), homogeneity index (HI), and Paddick’s index (PCI). Results: The GTV on CBCT1 was employed as a baseline for comparisons. GTV had decreased by a mean of 20.4% (range: 0.7% to 47.2%) on CBCT4. Most patients had smaller GTVs on CBCT4 than on CBCT1. The interfractional shifts of the tumor position between the planning CT and CBCT1–4 were as follows: right-left, −0.4 to 1.3 mm; anterior-posterior, −0.8 to 0.5 mm; and superiorinferior, −0.9 to 1.1 mm. Indices for plans from the planning CT and CBCT4 were as follows: CI = 0.94±0.02 and 1.11±0.03; HI= 1.1±0.02 and 1.10±0.03; and PCI = 1.35±0.16 and 1.11±0.02, respectively. Conclusion: CI, HI, and PCI did not differ between the planning CT and CBCTs. However, daily CBCT revealed a significant decrease in the GTV during lung SBRT. Furthermore, there was an obvious interfractional shift in tumor position. Using ART could potentially lead to a reduced GTV margin and improved regional tumor control for lung cancer patients with significantly decreased GTV.

  16. Lung Cancer Screening (United States)

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

  17. Lung Cancer Prevention (United States)

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

  18. What Is Lung Cancer? (United States)

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

  19. Toxicity and Carcinogenicity Mechanisms of Fibrous Antigorite

    Directory of Open Access Journals (Sweden)

    Michael Balazy


    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.

  20. Hepatic gene mutations induced in Big Blue rats by both the potent rat liver azo-carcinogen 6BT and its reported noncarcinogenic analogue 5BT. (United States)

    Fletcher, K; Soames, A R; Tinwell, H; Lefevre, P A; Ashby, J


    The potent rat liver carcinogen 6-p-dimethylaminophenylazobenzthiazole (6BT) and its reported noncarcinogenic analogue 5-p-dimethylaminophenylazobenzthiazole (5BT; evaluated for carcinogenicity under the similar limited bioassay conditions used for 6BT) have been studied in order to seek an explanation for their different carcinogenic activities. Both compounds act as DNA-damaging agents to the rat liver, and both have now been shown to induce lacI (-) gene mutations in the liver of Big Blue(trade mark) transgenic rats. Both compounds were mutagenic following ten daily gavage doses or following administration in diet for 10 days. Neither chemical induced cell proliferation in the liver following repeat gavage administrations. In contrast, dietary administration of 6BT, and to a lesser extent of 5BT, induced hepatic cell proliferation. The carcinogen 6BT, but not the noncarcinogen 5BT, caused proliferation of oval stem cells in the livers by both routes of administration. It is possible that mutations induced in oval cells by 6BT are responsible for its potent carcinogenicity, and that the comparative absence of these cells in 5BT-treated livers may account for the carcinogenic inactivity of 5BT. Equally, the proliferation of the oval cells may reflect changes in liver homeostasis associated with the liver toxicity observed at the dose level of 6BT used (which was, nonetheless, the dose level used in the positive cancer bioassays). It is concluded that the new data presented cannot explain the differing carcinogenic activities of 5BT and 6BT, and that the reported noncarcinogen 5BT may also be carcinogenic when adequately assessed for this activity.

  1. Biomonitoring human exposure to environmental carcinogenic chemicals

    DEFF Research Database (Denmark)

    Farmer, P.B.; Sepai, O.; Lawrence, R.;


    A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological...

  2. A Case–Referent Study of Lung Cancer and Incense Smoke, Smoking, and Residential Radon in Chinese Men


    Tse, Lap Ah; Yu, Ignatius Tak-sun; Qiu, Hong; Au, Joseph Siu Kai; Wang, Xiao-Rong


    Background: Burning incense generates large amounts of air pollutants, many of which are confirmed or suspected human lung carcinogens. Objectives: We conducted a population-based case–referent study to examine the effect of incense smoke exposure on lung cancer risk among Chinese males and explored the joint effect of cigarette smoking and exposure to residential radon. Methods: We recruited 1,208 male lung cancer incident cases and 1,069 community referents from 2004 to 2006 and estimated t...

  3. The OSIRIS Weight of Evidence approach: ITS mutagenicity and ITS carcinogenicity. (United States)

    Buist, Harrie; Aldenberg, Tom; Batke, Monika; Escher, Sylvia; Klein Entink, Rinke; Kühne, Ralph; Marquart, Hans; Pauné, Eduard; Rorije, Emiel; Schüürmann, Gerrit; Kroese, Dinant


    Risk assessment of chemicals usually implies data evaluation of in vivo tests in rodents to conclude on their hazards. The FP7 European project OSIRIS has developed integrated testing strategies (ITS) for relevant toxicological endpoints to avoid unnecessary animal testing and thus to reduce time and costs. This paper describes the implementation of ITS mutagenicity and carcinogenicity in the public OSIRIS webtool. The data requirements of REACH formed the basis for these ITS. The main goal was to implement procedures to reach a conclusion on the adequacy and validity of available data. For the mutagenicity ITS a quantitative Weight of Evidence approach based on Bayesian statistics was developed and implemented. The approach allows an overall quality assessment of all available data for the five types of mutagenicity data requirements: in vitro bacterial mutagenicity, in vitro and in vivo chromosome aberration, in vitro and in vivo mammalian mutagenicity. For the carcinogenicity ITS a tool was developed to evaluate the quality of studies not conforming (entirely) to guidelines. In a tiered approach three quality aspects are assessed: documentation (reliability), study design (adequacy) and scope of examination (validity). The quality assessment is based on expert and data driven quantitative Weight of Evidence.

  4. [Chemoprevention of tobacco-related lung cancer by cruciferous vegetable]. (United States)

    Balcerek, Maciej


    Lung cancer is the most common malignant disease in the world and the major cause of death from cancers. Around 80-90% of all human lung cancers are related to cigarette smoke. Tobacco smoke contains at least 60 carcinogens capable of causing tumors, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and polycyclic aromatic hydrocarbons (PAH) are among the most prominent pulmonary carcinogens. Prevention is the most effective way to reduce lung cancer mortality. Chemoprevention is a cancer preventive strategy to inhibit, delay or reverse carcinogenesis using naturally occurring or synthetic chemical agents. A number of epidemiological studies have shown an inverse relationship between cruciferous vegetable consumption and cancer, especially those of lung and stomach. Crucifers, such as broccoli, cauliflower, brussel sprouts and cabbage, contain a family of secondary plant metabolites known as glucosinolates, which are unique to these vegetables. Upon hydrolysis, glucosinolates yield a number of breakdown products, mostly isothiocyanates, with supposed chemopreventive properties, as shown in animal experiments. It appears that significant portion of the chemopreventive effects of isothiocyanates may be associated with the inhibition of the metabolic activation of carcinogens by cytochrome P450s (Phase I), coupled with strong induction of phase II of detoxifying enzymes.

  5. Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini

    Directory of Open Access Journals (Sweden)

    Gasser Robin B


    Full Text Available Abstract Background Cholangiocarcinoma (CCA – cancer of the bile ducts – is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome. Results Approximately 5,000 randomly selected cDNAs from the adult stage of O. viverrini were characterized and accounted for 1,932 contigs, representing ~14% of the entire transcriptome, and, presently, the largest sequence dataset for any species of liver fluke. Twenty percent of contigs were assigned GO classifications. Abundantly represented protein families included those involved in physiological functions that are essential to parasitism, such as anaerobic respiration, reproduction, detoxification, surface maintenance and feeding. GO assignments were well conserved in relation to other parasitic flukes, however, some categories were over-represented in O. viverrini, such as structural and motor proteins. An assessment of evolutionary relationships showed that O. viverrini was more similar to other parasitic (Clonorchis sinensis and Schistosoma japonicum than to free-living (Schmidtea mediterranea flatworms, and 105 sequences had close homologues in both parasitic species but not in S. mediterranea. A total of 164 O. viverrini contigs contained ORFs with signal sequences, many of which were platyhelminth-specific. Examples of convergent evolution between host and parasite secreted/membrane proteins were identified as were homologues of vaccine antigens from other helminths. Finally, ORFs representing secreted proteins with known roles in tumorigenesis were identified, and these might play roles in the pathogenesis of O. viverrini-induced CCA. Conclusion This gene discovery effort for O. viverrini should expedite molecular studies of cholangiocarcinogenesis and accelerate research focused on developing new interventions

  6. Studies in vitro to discern the structural requirements for carcinogenicity in analogues of the carcinogen 4-dimethylaminoazobenzene (butter yellow). (United States)

    Ashby, J; Styles, J A; Paton, D


    4-Dimethylaminoazobenzene (butter yellow, DAB), is the parent member of a large family of 'azo-carcinogens'. Experiments have been conducted in vitro to determine the key structural requirements for carcinogenic activity in this chemical class, and it is suggested, based on the activity observed for 4-cyano-N,N-dimethylaniline, that the 4-phenylazo group of DAB is not an essential structural feature per se. The N-oxide derivative of DAB has been evaluated in vitro and the positive response observed related to its metabolic activation. It is concluded that cyclic amines, such as pyrrolidine, can replace the N-dimethyl group of DAB with a retention of biological activity. The confusion that exists in the literature concerning the chemical identity and carcinogenic status of 2-dimethylaminobenzo[c]cinnoline has been investigated, and it is concluded that it is a potential animal carcinogen. This observation also indicates that the phenylazo group of DAB can be incorporated within an aromatic ring system with a retention of biological activity. As observed earlier with a mixture of azobenzene and DAB, azobenzene also potentiates the cell transforming properties of the above cinnoline derivative in vitro. Two charts are presented. The first attempts to integrate DAB within a much larger family of carcinogens, and the second illustrates the usefulness of structure-activity studies in general.

  7. Improved thin-layer chromatographic determination of phospholipids in gastric aspirate from newborns, for assessment of lung maturity. (United States)

    Serrano de la Cruz, D; Santillana, E; Mingo, A; Fuenmayor, G; Pantoja, A; Fernández, E


    This one-dimensional thin-layer chromatographic method is used for assay of phospholipids in the gastric aspirate of newborns. The solvent mixture (chloroform/hexane/methanol/glacial acetic acid/water, 12/7/4/3/0.3 by vol) completely resolves lecithin, sphingomyelin, phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine, and phosphatidylglycerol. The method is simple, precise, inexpensive, and rapid (chromatographic development takes less than 25 min) and gives high chromatographic resolution. We used this method to determine the lecithin/sphingomyelin densitometric ratio (L/S ratio) and the phosphatidylglycerol percentage in 200 samples of gastric aspirate and found an L/S ratio of 2.5 to be a satisfactory cutoff value for distinguishing fetal lung maturity and immaturity. We confirmed that the presence of phosphatidylglycerol excluded the possibility of respiratory distress.

  8. In vivo Gd-DTPA concentration for MR lung perfusion measurements: Assessment with computed tomography in a porcine model

    Energy Technology Data Exchange (ETDEWEB)

    Puderbach, Michael [German Cancer Research Center, Department of Radiology, Heidelberg (Germany); Deutsches Krebsforschungszentrum, Department of Radiology (E010), Heidelberg (Germany); Risse, Frank; Semmler, Wolfhard [German Cancer Research Center, Department of Medical Physics in Radiology, Heidelberg (Germany); Biederer, Juergen [University Hospital Schleswig-Holstein, Department of Diagnostic Radiology, Campus Kiel (Germany); Ley-Zaporozhan, Julia; Ley, Sebastian [German Cancer Research Center, Department of Radiology, Heidelberg (Germany); University Heidelberg, Department of Pediatric Radiology, Heidelberg (Germany); Szabo, Gabor [University Heidelberg, Department of Cardiac Surgery, Heidelberg (Germany); Kauczor, Hans-Ulrich [University of Heidelberg, Department of Radiology, Heidelberg (Germany)


    A linear relationship between MR signal and contrast-agent concentration (CAC) of the arterial-input function (AIF) is crucial for MR lung-perfusion quantification. The aim was to determine the in-vivo real maximum CAC of the AIF, using cine CT measurements in a porcine model. A dilution series (Gd-DTPA, 0-20 mM) was examined by clinical time-resolved 3D-GRE MRI and by MDCT in cine CT mode. Using the CT setup, data were acquired in five pigs immediately after the injection of 0.05 mmol and 0.07 mmol/kg BW Gd-DTPA. For phantom measurements, mean signal values were determined using a region-of-interest (ROI) analysis and for animal measurements, a ROI was placed in the pulmonary trunk of the cine CT perfusion data sets. The CT phantom measurements were used to calculate the in-vivo maximum CAC corresponding to the HU values obtained in the pulmonary trunk by the cine CT study. Linearity of the AIF of the CT perfusion measurements was verified using the MR phantom measurement results. MR phantom measurements demonstrated linearity for concentrations of 0-4 mM. CT phantom measurements showed linear relation for the entire CAC range. Comparing in-vivo and in-vitro measurements, three of five CA injections at 0.05 mmol/kg and all 0.07 mmol/kg injections exceeded the range of linearity in MRI. The CA dose for quantification of lung perfusion with time-resolved MR studies must be chosen carefully since even with low doses (0.05 mmol/kg) the CAC may exceed the range of linearity in the AIF. (orig.)

  9. Study of Peak Expiratory Flow Rate as the Assessment of Lung Function in Occupationally Exposed Petrol Pump Workers of Western Maharashtra

    Directory of Open Access Journals (Sweden)

    Patil Smita V


    Full Text Available Background: Fast urbanization trends, rapid industrial growth, globalization, and poor environmental conditions at work places have created a lot of healthrelated issues. Aim and Objectives: The aim of this study is to investigate Peak Expiratory Flow Rate (PEFR as the assessment of lung function in occupationally exposed petrol pump workers and also check whether PEFR increases or decreases with duration of exposure. Material and Methods: The study was conducted on 60 male petrol pump workers between age group of 20-40 years who were working as petrol filling attendants for more than one year from western Maharashtra. 50 normal healthy males with same socioeconomic status were chosen as controls to find out the effect of occupational exposure to petroleum product on PEFR as the assessment of lung function tests. Petrol pump workers were divided into three groups based on their duration of exposure i.e. 1- 5 yrs, 6- 10 yrs and more than 11 years. PEFR of petrol pump workers and control was measured by using a Mini Wright peak flow meter which is a portable device for measuring ventilator functions. Comparisons was done using unpaired t-test for 2 groups comparisons and one way ANOVAfor multiple groups of exposures. Results: The PEFR was significantly lower decrease (p=0.001 around petrol pump workers (389.17 as compared to control (534.2. As year of exposure increased mean value of PEFR was significantly decreased from 452.17, 378.00 and 283.64 respectively in petrol pump workers. Conclusion: The results suggested that respiratory functions i.e. PEFR of occupationally exposed petrol pump workers are significantly reduced as compared to controls, also PEFR is significantly reduced with increase in the duration of exposure.

  10. Potential health effects of exposure to carcinogenic compounds in incense smoke in temple workers. (United States)

    Navasumrit, Panida; Arayasiri, Manasawee; Hiang, Ohmar May Tin; Leechawengwongs, Manoon; Promvijit, Jeerawan; Choonvisase, Suppachai; Chantchaemsai, Samroeng; Nakngam, Netnapa; Mahidol, Chulabhorn; Ruchirawat, Mathuros


    Incense smoke is a potential hazard to human health due to various airborne carcinogens emitted from incense burning. This study aimed to evaluate the potential health effects of exposure to benzene, 1,3-butadiene, and polycyclic aromatic hydrocarbons (PAHs) emitted from incense smoke in temple workers. Exposure and health risks were assessed through the measurement of ambient exposure as well as through the use of biomarkers of exposure and early biological effects. Ambient air measurement showed that incense burning generates significantly higher levels of airborne benzene (Pincense burning may increase health risk for the development of cancer in temple workers.

  11. Mitigating role of baicalein on lysosomal enzymes and xenobiotic metabolizing enzyme status during lung carcinogenesis of Swiss albino mice induced by benzo(a)pyrene. (United States)

    Naveenkumar, Chandrashekar; Raghunandakumar, Subramanian; Asokkumar, Selvamani; Binuclara, John; Rajan, Balan; Premkumar, Thandavamoorthy; Devaki, Thiruvengadam


    The lungs mainly serve as a primary site for xenobiotic metabolism and constitute an important defense mechanism against inhalation of carcinogens. Our current study aimed to evaluate the chemotherapeutic efficacy of baicalein (BE) in Swiss albino mice exposed to tobacco-specific carcinogen benzo(a)pyrene [B(a)P] for its ability to mitigate pulmonary carcinogenesis. Here, we report that altered activities/levels of lysosomal enzymes (cathepsin-D, cathepsin-B, acid phosphatase, β-D-galactosidase, β-D-glucuronidase, and β-D-N-acetyl glucosaminidase), phase I biotransformation enzymes (cytochrome P450, cytochrome b5, NADPH-cytochrome P450 reductase, and NADH-cytochrome b5 reductase), and phase II enzymes (glutathione S-transferase, UDP-glucuronyl transferase, and DT-diaphorase) were observed in the B(a)P-induced mice. Treatment with BE significantly restored back the activities/levels of lysosomal enzymes, phase I and phase II biotransformation enzymes. Moreover, assessment of lysosomal abnormalities by transmission electron microscopic examination revealed that BE treatment effectively counteract B(a)P-induced oxidative damages. Protein expression levels studied by immunohistochemistry, immunofluorescence, and immunoblot analysis of CYP1A1 revealed that BE treatment effectively negate B(a)P-induced upregulated expression of CYP1A1. Further analysis of scanning electron microscopic studies in lung was carried out to substantiate the anticarcinogenic effect of BE. The overall data suggest that BE treatment significantly inhibits lysosomal and microsomal dysfunction, thus revealing its potent anticarcinogenic effect.

  12. Bayesian bias adjustments of the lung cancer SMR in a cohort of German carbon black production workers

    Directory of Open Access Journals (Sweden)

    Morfeld Peter


    Full Text Available Abstract Background A German cohort study on 1,528 carbon black production workers estimated an elevated lung cancer SMR ranging from 1.8-2.2 depending on the reference population. No positive trends with carbon black exposures were noted in the analyses. A nested case control study, however, identified smoking and previous exposures to known carcinogens, such as crystalline silica, received prior to work in the carbon black industry as important risk factors. We used a Bayesian procedure to adjust the SMR, based on a prior of seven independent parameter distributions describing smoking behaviour and crystalline silica dust exposure (as indicator of a group of correlated carcinogen exposures received previously in the cohort and population as well as the strength of the relationship of these factors with lung cancer mortality. We implemented the approach by Markov Chain Monte Carlo Methods (MCMC programmed in R, a statistical computing system freely available on the internet, and we provide the program code. Results When putting a flat prior to the SMR a Markov chain of length 1,000,000 returned a median posterior SMR estimate (that is, the adjusted SMR in the range between 1.32 (95% posterior interval: 0.7, 2.1 and 1.00 (0.2, 3.3 depending on the method of assessing previous exposures. Conclusions Bayesian bias adjustment is an excellent tool to effectively combine data about confounders from different sources. The usually calculated lung cancer SMR statistic in a cohort of carbon black workers overestimated effect and precision when compared with the Bayesian results. Quantitative bias adjustment should become a regular tool in occupational epidemiology to address narrative discussions of potential distortions.

  13. Does a more refined assessment of exposure to bitumen fume and confounders alter risk estimates from a nested case-control study of lung cancer among European asphalt workers?

    DEFF Research Database (Denmark)

    Agostini, Michela; Ferro, Gilles; Burstyn, Igor


    To investigate whether a refined assessment of exposure to bitumen fume among workers in the European asphalt industry within a nested case-control study resulted in a different interpretation pertaining to risk of lung cancer mortality compared with the cohort study....

  14. Potential health risks related to carcinogens in the atmospheric environment in India. (United States)

    Gurjar, B R; Mohan, M; Sidhu, K S


    In India, rapid urbanization and industrialization have contributed positively toward meeting the materialistic needs of the citizens, but have also resulted in contamination of the atmospheric environment. This paper deals with the assessment of potential health risks posed by carcinogenic substances, namely cadmium, chromium, and nickel, present in certain atmospheric environments in India. Average air concentrations of these carcinogenic metals have been assessed for different states and regions of India (C. R. Krishnamurti and P. Vishwanathan, Toxic Metals in the Indian Environment, Tata/McGraw-Hill, New Delhi, 1991). Based on these assessments, both individual and societal risks have been estimated in different states of the country, and comparisons were made. Reported concentration, release sources, potential health risks including cancer risk estimates, and ambient air interim guidelines are discussed. The reported environmental releases and cancer risk from cadmium are minimal. There is a potential for increased respiratory cancer risk from exposure to chromium and nickel in some northern Indian states. These metals are irritants to nasal passages and the respiratory tract. Chromium is also corrosive to mucus membranes. They have the potential to cause chronic respiratory problems. Since it appears that these metals may cause some adverse health effects in humans, exposure to these ambient air pollutants should be minimized by managing the release of these contaminants to the environment. There is a need for the development and strict enforcement of national and state regulatory standards.

  15. Improving prediction of carcinogenicity to reduce, refine, and replace the use of experimental animals. (United States)

    Bourcier, Todd; McGovern, Tim; Stavitskaya, Lidiya; Kruhlak, Naomi; Jacobson-Kram, David


    Cancer risk assessment of new pharmaceuticals is crucial to protect public health. However, clinical trials lack the duration needed to clearly detect drug-related tumor emergence, and biomarkers suggestive of increased cancer risk from a drug typically are not measured in clinical trials. Therefore, the carcinogenic potential of a new pharmaceutical is extrapolated predominately based on 2-y bioassays in rats and mice. A key drawback to this practice is that the results are frequently positive for tumors and can be irrelevant to human cancer risk for reasons such as dose, mode of action, and species specificity. Alternative approaches typically strive to reduce, refine, and replace rodents in carcinogenicity assessments by leveraging findings in short-term studies, both in silico and in vivo, to predict the likely tumor outcome in rodents or, more broadly, to identify a cancer risk to patients. Given the complexities of carcinogenesis and the perceived impracticality of assessing risk in the course of clinical trials, studies conducted in animals will likely remain the standard by which potential cancer risks are characterized for new pharmaceuticals in the immediate foreseeable future. However, a weight-of-evidence evaluation based on short-term toxicologic, in silico, and pharmacologic data is a promising approach to identify with reasonable certainty those pharmaceuticals that present a likely cancer risk in humans and, conversely, those that do not present a human cancer risk.

  16. Lung Transplant (United States)

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

  17. WE-G-BRD-01: Diffusion Weighted MRI for Response Assessment of Inoperable Lung Tumors for Patients Undergoing SBRT Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Tyagi, N; Wengler, K; Yorke, E; Hunt, M; Deasy, J; Rimner, A [Memorial Sloan-Kettering Cancer Center, New York, NY (United States)


    Purpose: To investigate early changes in tumor Apparent Diffusion Coefficients derived from diffusion weighted (DW)-MRI of lung cancer patients undergoing SBRT, as a possible early predictor of treatment response. Methods: DW-MRI scans were performed in this prospective phase I IRB-approved study of inoperable lung tumors at various time-points during the course of SBRT treatments. Axial DW scan using multi b-values ranging from 0–1000 s/mm{sup 2} were acquired in treatment position on a 3T Philips MR scanner during simulation, one hour after the first fraction (8 Gy), after a total of 5 fractions (40 Gy) and 4 weeks after SBRT delivery. A monoexponential model based on a least square fit from all b values was performed on a pixel-by-pixel basis and ADC was calculated. GTVs drawn on 4DCT for planning were mapped on the T2w MRI (acquired at exhale) after deformable registration. These volumes were then mapped on DWI scan for ADC calculation after rigid registration between the anatomical scan and diffusion scan. T2w scan on followup time points were deformably registered to the pretreatment T2 scan. Results: The first two patients in this study were analyzed. Median ADC values were 1.48, 1.48, 1.62 and 1.83 (10{sup −3}×) mm{sup 2}/s at pretreatment, after 8 Gy, after 40 Gy and 4 weeks posttreatment for the first patient and 1.57, 1.53, 1.66 and 1.72 (10{sup −3}×) mm{sup 2}/s for the second patient. ADC increased more significantly after 4 weeks of treatment rather than immediately post treatment, implying that late ADC value may be a better predictor of tumor response for SBRT treatment. The fraction of tumor pixels at high ADC values increased at 4 weeks post treatment. Conclusion: The observed increase in ADC values before the end of radiotherapy may be a surrogate for tumor response, but further patient accrual will be necessary to determine its value.

  18. IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

    NARCIS (Netherlands)

    Pearce, Neil E; Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M; Armstrong, Bruce K; Baccarelli, Andrea A; Beland, Frederick A; Berrington, Amy; Bertazzi, Pier A; 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-Kristian; Olshan, Andrew F; Parent, Marie-Elise; Perera, Frederica P; Perry, Melissa J; Pesatori, Angela C; 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; Seniori Constantini, Adele; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silvermann, 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 H


    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 the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' fa

  19. Binding of chemical carcinogens to macromolecules in cultured human colon

    DEFF Research Database (Denmark)


    Metabolic activation of different chemical classes of carcinogens was studied in cultured human colon epithelia. Human colon epithelia were maintained in explant culture up to 4 days. Binding of benzo(a)pyrene, dimethylnitrosamine, and 1,2- dimethylhydrazine was found in both cell DNA and protein...

  20. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard

    NARCIS (Netherlands)

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.


    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studie

  1. 18. Adduct detection in human monitoring for carcinogen exposure

    Institute of Scientific and Technical Information of China (English)


    @@Determination of the covalently bound products (adducts) of carcinogens with DNA or proteins may be used for the monitoring of exposure to these compounds. Protein adducts are generally stable and are not enzymatically repaired, and the use of these for cxposure monitoring is normally carried out with globin or albumin, because

  2. Flavonoids and alkenylbenzenes: mechanisms of mutagenic action and carcinogenic risk

    NARCIS (Netherlands)

    Rietjens, I.M.C.M.; Boersma, M.G.; Woude, van der H.; Jeurissen, S.M.F.; Schutte, M.E.; Alink, G.M.


    The present review focuses on the mechanisms of mutagenic action and the carcinogenic risk of two categories of botanical ingredients, namely the flavonoids with quercetin as an important bioactive representative, and the alkenylbenzenes, namely safrole, methyleugenol and estragole. For quercetin a

  3. Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Beyersmann, Detmar [University of Bremen (Germany). Biochemistry, Department of Biology and Chemistry; Hartwig, Andrea [Technical University of Berlin (Germany). Institute of Food Technology and Food Chemistry


    Mechanisms of carcinogenicity are discussed for metals and their compounds, classified as carcinogenic to humans or considered to be carcinogenic to humans: arsenic, antimony, beryllium, cadmium, chromium, cobalt, lead, nickel and vanadium. Physicochemical properties govern uptake, intracellular distribution and binding of metal compounds. Interactions with proteins (e.g., with zinc finger structures) appear to be more relevant for metal carcinogenicity than binding to DNA. In general, metal genotoxicity is caused by indirect mechanisms. In spite of diverse physicochemical properties of metal compounds, three predominant mechanisms emerge: (1) interference with cellular redox regulation and induction of oxidative stress, which may cause oxidative DNA damage or trigger signaling cascades leading to stimulation of cell growth; (2) inhibition of major DNA repair systems resulting in genomic instability and accumulation of critical mutations; (3) deregulation of cell proliferation by induction of signaling pathways or inactivation of growth controls such as tumor suppressor genes. In addition, specific metal compounds exhibit unique mechanisms such as interruption of cell-cell adhesion by cadmium, direct DNA binding of trivalent chromium, and interaction of vanadate with phosphate binding sites of protein phosphatases. (orig.)

  4. Cell-mediated mutagenesis and cell transformation by chemical carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Huberman, E.; Langenbach, R.


    Results are reported from studies that showed that mutagenesis of mammalian cells can be achieved by carcinogenic polycyclic hydrocarbons, nitrosamines, and aflatoxins when tested in the presence of fibroblasts and hepatocytes which are able to metabolize these carcinogens. Further, we have found that there is a relationship between the degree of mutant induction and the degree of carcinogenicity of the different chemicals tested. By simultaneously measuring the frequency of cell transformation and the frequency of mutation at one locus (ouabain resistance) in the same cell system, it was possible to estimate the genetic target site for cell transformation. The results indicated that the target site for transformation is approximately 20 times larger than that determined for ouabain resistance. The results suggest that cell transformation may be due to a mutational event and the mutation can occur in one out of a small number of the same or different genes, and that the cell-mediated mutagenesis approach may be a valuable means of detecting tissue-specific carcinogens.

  5. Management of Rheumatoid Arthritis Patients with Interstitial Lung Disease: Safety of Biological Antirheumatic Drugs and Assessment of Pulmonary Fibrosis. (United States)

    Mori, Shunsuke


    Interstitial lung disease (ILD) is one of the major causes of morbidity and mortality of patients with rheumatoid arthritis (RA). Accompanying the increased number of reports on the development or exacerbation of ILD in RA patients following therapy with biological disease-modifying antirheumatic drugs (DMARDs), RA-associated ILD (RA-ILD) has aroused renewed interest. Although such cases have been reported mainly in association with the use of tumor necrosis factor inhibitors, the use of other biological DMARDs has also become a matter of concern. Nevertheless, it is difficult to establish a causative relationship between the use of biological DMARDs and either the development or exacerbation of ILD. Such pulmonary complications may occur in the natural course of RA regardless of the use of biological DMARDs. Since rheumatologists currently aim to achieve remission in RA patients, the administration of biological DMARDs is increasing, even for those with RA-ILD. However, there are no reliable, evidence-based guidelines for deciding whether biological DMARDs can be safely introduced and continued in RA-ILD patients. A standardized staging system for pulmonary conditions of RA-ILD patients is needed when making therapeutic decisions at baseline and monitoring during biological DMARD therapy. Based on the available information regarding the safety of biological DMARDs and the predictive factors for a worse prognosis, this review discusses candidate parameters for risk evaluation of ILD in RA patients who are scheduled to receive biological antirheumatic therapy.

  6. Lactoperoxidase-catalyzed activation of carcinogenic aromatic and heterocyclic amines. (United States)

    Gorlewska-Roberts, Katarzyna M; Teitel, Candee H; Lay, Jackson O; Roberts, Dean W; Kadlubar, Fred F


    Lactoperoxidase, an enzyme secreted from the human mammary gland, plays a host defensive role through antimicrobial activity. It has been implicated in mutagenic and carcinogenic activation in the human mammary gland. The potential role of heterocyclic and aromatic amines in the etiology of breast cancer led us to examination of the lactoperoxidase-catalyzed activation of the most commonly studied arylamine carcinogens: 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), benzidine, 4-aminobiphenyl (ABP), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). In vitro activation was performed with lactoperoxidase (partially purified from bovine milk or human milk) in the presence of hydrogen peroxide and calf thymus DNA. Products formed during enzymatic activation were monitored by HPLC with ultraviolet and radiometric detection. Two of these products were characterized as hydrazo and azo derivatives by means of mass spectrometry. The DNA binding level of 3H- and 14C-radiolabeled amines after peroxidase-catalyzed activation was dependent on the hydrogen peroxide concentration, and the highest levels of carcinogen binding to DNA were observed at 100 microM H2O2. Carcinogen activation and the level of binding to DNA were in the order of benzidine > ABP > IQ > MeIQx > PhIP. One of the ABP adducts was identified, and the level at which it is formed was estimated to be six adducts/10(5) nucleotides. The susceptibility of aromatic and heterocyclic amines for lactoperoxidase-catalyzed activation and the binding levels of activated products to DNA suggest a potential role of lactoperoxidase-catalyzed activation of carcinogens in the etiology of breast cancer.

  7. Carcinogen derived biomarkers: applications in studies of human exposure to secondhand tobacco smoke


    Hecht, S


    Objective: To review the literature on carcinogen derived biomarkers of exposure to secondhand tobacco smoke (SHS). These biomarkers are specifically related to known carcinogens in tobacco smoke and include urinary metabolites, DNA adducts, and blood protein adducts.

  8. Lung cancer in younger patients

    DEFF Research Database (Denmark)

    Abbasowa, Leda; Madsen, Poul Henning


    INTRODUCTION: Lung cancer remains a leading cause of cancer-related death. The incidence increases with age and the occurrence in young patients is relatively low. The clinicopathological features of lung cancer in younger patients have not been fully explored previously. METHODS: To assess the age...... differences in the clinical characteristics of lung cancer, we conducted a retrospective analysis comparing young patients ≤ 65 years of age with an elderly group > 65 years of age. Among 1,232 patients evaluated due to suspicion of lung cancer in our fast-track setting from January-December 2013, 312 newly...... diagnosed lung cancer patients were included. RESULTS: Patients ≤ 65 years had a significantly higher representation of females (p = 0.0021), more frequent familial cancer aggregation (p = 0.028) and a lower incidence of squamous cell carcinoma (p = 0.0133). When excluding pure carcinoid tumours...

  9. Use of in silico models for prioritization of heat-induced food contaminants in mutagenicity and carcinogenicity testing. (United States)

    Frenzel, Falko; Buhrke, Thorsten; Wenzel, Irina; Andrack, Jennifer; Hielscher, Jan; Lampen, Alfonso


    Numerous Maillard reaction and lipid oxidation products are present in processed foods such as heated cereals, roasted meat, refined oils, coffee, and juices. Due to the lack of experimental toxicological data, risk assessment is hardly possible for most of these compounds. In the present study, an in silico approach was employed for the prediction of the toxicological endpoints mutagenicity and carcinogenicity on the basis of the structure of the respective compound, to examine (quantitative) structure-activity relationships for more than 800 compounds. Five software tools for mutagenicity prediction (T.E.S.T., SARpy, CAESAR, Benigni-Bossa, and LAZAR) and three carcinogenicity prediction tools (CAESAR, Benigni-Bossa, and LAZAR) were combined to yield so-called mutagenic or carcinogenic scores for every single substance. Alcohols, ketones, acids, lactones, and esters were predicted to be mutagenic and carcinogenic with low probability, whereas the software tools tended to predict a considerable mutagenic and carcinogenic potential for thiazoles. To verify the in silico predictions for the endpoint mutagenicity experimentally, twelve selected compounds were examined for their mutagenic potential using two different validated in vitro test systems, the bacterial reverse mutation assay (Ames test) and the in vitro micronucleus assay. There was a good correlation between the results of the Ames test and the in silico predictions. However, in the case of the micronucleus assay, at least three substances, 2-amino-6-methylpyridine, 6-heptenoic acid, and 2-methylphenol, were clearly positive although they were predicted to be non-mutagenic. Thus, software tools for mutagenicity prediction are suitable for prioritization among large numbers of substances, but these predictions still need experimental verification.

  10. Added value of lung perfused blood volume images using dual-energy CT for assessment of acute pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Munemasa, E-mail: [Department of Radiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Kunihiro, Yoshie [Department of Radiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Nakashima, Yoshiteru [Department of Radiology, Yamaguchi Grand Medical Center, Oosaki 77, Hofu, Yamaguchi 747-8511 (Japan); Nomura, Takafumi [Department of Radiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Kudomi, Shohei; Yonezawa, Teppei [Department of Radiology, Yamaguchi University Hospital, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Suga, Kazuyoshi [Department of Radiology, St. Hills Hospital, Imamurakita 3-7-18, Ube, Yamaguchi 755-0155 (Japan); Matsunaga, Naofumi [Department of Radiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan)


    Purpose: To investigate the added value of lung perfused blood volume (LPBV) using dual-energy CT for the evaluation of intrapulmonary clot (IPC) in patients suspected of having acute pulmonary embolism (PE). Materials and methods: Institutional review board approval was obtained for this retrospective study. Eighty-three patients suspected of having PE who underwent CT pulmonary angiography (CTPA) using a dual-energy technique were enrolled in this study. Two radiologists who were blinded retrospectively and independently reviewed CTPA images alone and the combined images with color-coded LPBV over a 4-week interval, and two separate sessions were performed with a one-month interval. Inter- and intraobserver variability and diagnostic accuracy were evaluated for each reviewer with receiver operating characteristic (ROC) curve analysis. Results: Values for inter- and intraobserver agreement, respectively, were better for CTPA combined with LPBV (ICC = 0.847 and 0.937) than CTPA alone (ICC = 0.748 and 0.861). For both readers, diagnostic accuracy (area under the ROC curve [A{sub z}]) were also superior, when CTPA alone (A{sub z} = 0.888 [reader 1] and 0.912 [reader 2]) was compared with that after the combination with LPBV images (A{sub z} = 0.966 [reader 1] and 0.959 [reader 2]) (p < 0.001). However, A{sub z} values of both images might not have significant difference in statistics, because A{sub z} value of CTPA alone was high and 95% confidence intervals overlapped in both images. Conclusion: Addition of dual-energy perfusion CT to CTPA improves detection of peripheral IPCs with better interobserver agreement.

  11. Assessment of DDR2, BRAF, EGFR and KRAS mutations as therapeutic targets in non-adenocarcinoma lung cancer patients. (United States)

    Yashima, Hideaki; Shimizu, Kimihiro; Araki, Takuya; Aomori, Tohru; Ohtaki, Yoichi; Nagashima, Toshiteru; Enokida, Yasuaki; Atsumi, Jun; Nakamura, Tomonori; Takeyoshi, Izumi; Yamamoto, Koujirou


    Molecular-targeted therapy has not been established in non-adenocarcinoma lung cancer (non-AdLC), as no targets that affect the clinical efficacy of molecular-targeted drugs have yet been identified. In this study, we investigated the frequency of genetic variations in discoidin domain receptor 2 (DDR2), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) in non-AdLC patients, in order to evaluate the possibility of genetic mutations in these genes being used as therapeutic targets for the treatment of patients with non-AdLC. For this purpose, we enrolled 150 non-AdLC patients who had undergone surgery at the Gunma University Hospital between December, 2003 and December, 2012. Genetic mutations in the EGFR, KRAS, DDR2 and BRAF genes were detected by a sequencing method or probe assay using DNA derived from cancer tissues. No somatic mutations in DDR2 or BRAF were detected in non-AdLC patients. Conversely, genetic mutations in EGFR exon 19 were found in 3 squamous cell carcinoma (SCC) and 3 adenosquamous carcinoma patients, whereas KRAS codon 12 mutations were also found in 3 SCC patients and 1 large-cell neuroendocrine carcinoma patient. EGFR and KRAS mutations were mutually exclusive. This study indicated that, although DDR2 and BRAF mutations may only rarely be used as therapeutic targets, EGFR and KRAS mutations may represent candidate therapeutic targets, at least in the non-AdLC patients investigated.


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


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

  13. Green tea and prevention of esophageal and lung cancers


    Yuan, Jian-Min


    Green tea contains high concentrations of tea polyphenols that have shown inhibitory effects against the development, progress, and growth of carcinogen-induced tumors in animal models at different organ sites, including the esophagus and lung. Green tea polyphenols also have shown to suppress cell proliferation and induce apoptosis. Besides antioxidative property, green tea polyphenols have pro-oxidative activities under certain conditions and modulate phase II metabolic enzymes that can enh...

  14. Induction of lung lesions in Wistar rats by 4-(methylnitrosamino-1-(3-pyridyl-1-butanone and its inhibition by aspirin and phenethyl isothiocyanate

    Directory of Open Access Journals (Sweden)

    Xia Dong


    Full Text Available Abstract Background The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by suitable laboratory animal models, such as animals treated with the tobacco-specific lung carcinogen 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK. In the current study, we established a novel lung cancer model in Wistar rats treated with NNK. Using this model, we assessed the effects of two chemopreventive agents, aspirin and phenethyl isothiocyanate (PEITC, on tumor progression. Methods First, rats were treated with a single-dose of NNK by intratracheal instillation; control rats received iodized oil. The animals were then sacrificed on the indicated day after drug administration and examined for tumors in the target organs. PCNA, p63 and COX-2 expression were analyzed in the preneoplastic lung lesions. Second, rats were treated with a single-dose of NNK (25 mg/kg body weight in the absence or presence of aspirin and/or PEITC in the daily diet. The control group received only the vehicle in the regular diet. The animals were sacrificed on day 91 after bronchial instillation of NNK. Lungs were collected and processed for histopathological and immunohistochemical assays. Results NNK induced preneoplastic lesions in lungs, including 33.3% alveolar hyperplasia and 55.6% alveolar atypical dysplasia. COX-2 expression increased similarly in alveolar hyperplasia and alveolar atypical dysplasia, while PCNA expression increased more significantly in the latter than the former. No p63 expression was detected in the preneoplastic lesions. In the second study, the incidences of alveolar atypical dysplasia were reduced to 10%, 10% and 0%, respectively, in the aspirin, PEITC and aspirin and PEITC groups, compared with 62.5% in the carcinogen-treated control group. COX-2 expression decreased after dietary aspirin or aspirin and PEITC treatment. PCNA expression was significantly reduced in the aspirin and PEITC

  15. Fifty years of tobacco carcinogenesis research: from mechanisms to early detection and prevention of lung cancer. (United States)

    Hecht, Stephen S; Szabo, Eva


    The recognition of the link between cigarette smoking and lung cancer in the 1964 Surgeon General's Report initiated definitive and comprehensive research on the identification of carcinogens in tobacco products and the relevant mechanisms of carcinogenesis. The resultant comprehensive data clearly illustrate established pathways of cancer induction involving carcinogen exposure, metabolic activation, DNA adduct formation, and consequent mutation of critical genes along with the exacerbating influences of inflammation, cocarcinogenesis, and tumor promotion. This mechanistic understanding has provided a framework for the regulation of tobacco products and for the development of relevant tobacco carcinogen and toxicant biomarkers that can be applied in cancer prevention. Simultaneously, the recognition of the link between smoking and lung cancer paved the way for two additional critical approaches to cancer prevention that are discussed here: detection of lung cancer at an early, curable stage, and chemoprevention of lung cancer. Recent successes in more precisely identifying at-risk populations and in decreasing lung cancer mortality with helical computed tomography screening are notable, and progress in chemoprevention continues, although challenges with respect to bringing these approaches to the general population exist. Collectively, research performed since the 1964 Report demonstrates unequivocally that the majority of deaths from lung cancer are preventable.

  16. Interstitial Lung Diseases (United States)

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

  17. Lung Carcinoid Tumor: Surgery (United States)

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

  18. Lung cancer - small cell (United States)

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

  19. Lung cancer attributable to indoor radon exposure in France using different risk models

    Energy Technology Data Exchange (ETDEWEB)

    Catelinois, O.C.; Laurier, D.L.; Rogel, A.R.; Billon, S.B.; Tirmarche, M.T. [Institute for Radiological Protection and Nuclear Safety, 92 - Fontenay aux Roses (France); Hemon, Dh. [INSERM -U170-IFR69, 94 - Villejuif (France); Verger, P.V. [Regional Health Observatory Provence Alpes Cote d' Azur, 13 - Marseille (France)


    Full text of publication follows: Radon exposure is omnipresent for the general public, but at variable levels, because radon mainly comes from granitic and volcanic subs oils as well as from certain construction materials. Inhalation of radon is the main source of exposure to radioactivity in the general population of most countries. In 1988, the International Agency for Research on Cancer declared radon to be carcinogenic for humans (lung cancer): radon is classed in the group 1. The exposure of the overall general population to a carcinogenic component led scientists to assess the lung cancer risk associated to indoor radon. The aim of this work is to provide the first lung cancer risk assessment associated with indoor radon exposure in France, using all available epidemiological results and performing an uncertainty analysis. The number of lung cancer deaths potentially associated with radon in houses is estimated for the year 1999 according to several dose-response relationships which come from either cohorts of miners or joint analysis of residential case-controls studies. The variability of indoor radon exposure in France and uncertainties related to each of the dose-response relationships are considered. The assessment of lung cancer risk associated with domestic radon exposure considers 10 dose-response relationships resulting from miners cohorts and case-control studies in the general population. A critical review of available data on smoking habits has been performed and allowed to consider the interaction between radon and tobacco. The exposure data come from measurements campaigns carried out since the beginning of the 1980's by the Institute for Radiation protection and Nuclear Safety and the Health General Directory in France. The French lung cancer mortality data are provided by the INSERM. Estimates of the number of attributable cancers are carried out for the whole country, stratified by 8 large regions and b y 96 departments for the year

  20. B-lines quantify the lung water content: a lung ultrasound versus lung gravimetry study in acute lung injury. (United States)

    Jambrik, Zoltán; Gargani, Luna; Adamicza, Agnes; Kaszaki, József; Varga, Albert; Forster, Tamás; Boros, Mihály; Picano, Eugenio


    B-lines (also termed ultrasound lung comets) obtained with lung ultrasound detect experimental acute lung injury (ALI) very early and before hemogasanalytic changes, with a simple, noninvasive, nonionizing and real-time method. Our aim was to estimate the correlation between B-lines number and the wet/dry ratio of the lung tissue, measured by gravimetry, in an experimental model of ALI. Seventeen Na-pentobarbital anesthetized, cannulated (central vein and carotid artery) minipigs were studied: five sham-operated animals served as controls and, in 12 animals, ALI was induced by injection of oleic acid (0.1 mL/kg) via the central venous catheter. B-lines were measured by echographic scanner in four predetermined chest scanning sites in each animal. At the end of each experiment, both lungs were dissected, weighed and dried to determine wet/dry weight ratio by gravimetry. After the injection of oleic acid, B-lines number increased over time. A significant correlation was found between the wet/dry ratio and B-lines number (r = 0.91, p < 0.001). These data suggest that in an experimental pig model of ALI/ARDS, B-lines assessed by lung ultrasound provide a simple, semiquantitative, noninvasive index of lung water accumulation, strongly correlated to invasive gravimetric assessment.

  1. Identification of a long non-coding RNA NR_026689 associated with lung carcinogenesis induced by NNK


    Wu, Jianjun; Li, Xun; Xu, Yiqin; Yang, Ti; Yang, Qiaoyuan; Yang, Chengfeng; Jiang, Yiguo


    Long non-coding RNAs (lncRNA) are thought to be important epigenetic regulators involved in the development of a variety of cancers. Alterations in lncRNA expression are associated with exposure to chemical carcinogens. However, it is still unclear whether lncRNA expression during lung carcinogenesis is induced by chemical carcinogens. In this study, using NNK-induced rat lung cancer model established by our previous study, we determined the lncRNA expression profiles, and an alteration in ln...

  2. Green tea and prevention of esophageal and lung cancers. (United States)

    Yuan, Jian-Min


    Green tea contains high concentrations of tea polyphenols that have shown inhibitory effects against the development, progress, and growth of carcinogen-induced tumors in animal models at different organ sites, including the esophagus and lung. Green tea polyphenols also have shown to suppress cell proliferation and induce apoptosis. Besides antioxidative property, green tea polyphenols have pro-oxidative activities under certain conditions and modulate phase II metabolic enzymes that can enhance the detoxification pathway of environmental toxicants and carcinogens. Although epidemiological studies have provided inconclusive results on the effect of green tea consumption against the development of esophageal and lung cancers in humans overall, the inverse association between green tea intake and risk of esophageal cancer risk is more consistently observed in studies with adequate control for potential confounders. Epidemiological studies also have demonstrated an inverse, albeit moderate, association between green tea consumption and lung cancer, especially in non-smokers. This article reviews data on the cancer-preventive activities of green tea extract and green tea polyphenols and possible mechanisms against the esophageal and lung carcinogenesis in experimental animals, and summarizes the current knowledge from epidemiological studies on the relationship between green tea consumption and esophageal and lung cancer risk in humans.

  3. Bronchoscopic procedures and lung biopsies in pediatric lung transplant recipients. (United States)

    Wong, Jackson Y; Westall, Glen P; Snell, Gregory I


    Bronchoscopy remains a pivotal diagnostic and therapeutic intervention in pediatric patients undergoing lung transplantation (LTx). Whether performed as part of a surveillance protocol or if clinically indicated, fibre-optic bronchoscopy allows direct visualization of the transplanted allograft, and in particular, an assessment of the patency of the bronchial anastomosis (or tracheal anastomosis following heart-lung transplantation). Additionally, bronchoscopy facilitates differentiation of infective processes from rejection episodes through collection and subsequent assessment of bronchoalveolar lavage (BAL) and transbronchial biopsy (TBBx) samples. Indeed, the diagnostic criteria for the grading of acute cellular rejection is dependent upon the histopathological assessment of biopsy samples collected at the time of bronchoscopy. Typically, performed in an out-patient setting, bronchoscopy is generally a safe procedure, although complications related to hemorrhage and pneumothorax are occasionally seen. Airway complications, including stenosis, malacia, and dehiscence are diagnosed at bronchoscopy, and subsequent management including balloon dilatation, laser therapy and stent insertion can also be performed bronchoscopically. Finally, bronchoscopy has been and continues to be an important research tool allowing a better understanding of the immuno-biology of the lung allograft through the collection and analysis of collected BAL and TBBx samples. Whilst new investigational tools continue to evolve, the simple visualization and collection of samples within the lung allograft by bronchoscopy remains the gold standard in the evaluation of the lung allograft. This review describes the use and experience of bronchoscopy following lung transplantation in the pediatric setting.

  4. Modification of lung cancer susceptibility by green tea extract as measured by the comet assay. (United States)

    Zhang, Huifeng; Spitz, Margaret R; Tomlinson, Gail E; Schabath, Matthew B; Minna, John D; Wu, Xifeng


    Green tea is widely consumed throughout the world and is known to possess various beneficial properties that may affect carcinogen metabolism, free radical scavenging, or formation of DNA adducts. Therefore, it is plausible that green tea extract may modify BPDE-induced DNA damage. In this report, we utilized the comet assay to (1) evaluate BPDE-induced DNA damage as a potential marker of cancer susceptibility and (2) assess the ability of green tea to modify BPDE-induced DNA damage. DNA damage in individual comet cells was quantified by (1) visually measuring the proportion of cells exhibiting migration versus those without and (2) the length of damaged DNA migration (comet tail). We detected a dose-response between BDPE concentration and mean comet tail length in EBV-immortalized lymphoblastiod (lymphoid) cell lines. As the concentration of BPDE increased from 0.5 to 3 microM, the length of the mean comet tail length increased proportionally in the 3590P (derived from a healthy subject) and 3640P (derived from a patient with head and neck cancer) cell lines. In separate experiments using lymphoid cells from 21 lung cancer cases and 12 healthy subjects, the mean comet tail length was significantly higher in the lung cancer cases (80.19 +/- 15.55) versus the healthy subjects (59.94 +/- 14.23) (P green tea extract was added in conjunction with BPDE, there was a notable reduction of the mean comet tail length (13.29 +/- 0.97) as compared to BPDE treatment alone (80.19 +/- 15.55) (P lung cancer cases. There were no statistical differences between the baseline (no treatments) (12.74 +/- 0.63) and the green tea extract treatment (13.06 +/- 0.97) (P = 0.21). These data suggest the modification of lung cancer susceptibility by the green tea extract. Similar results were observed for the percentage of induced comet cells and the statistical trends were similar for the 12 healthy subjects. This preliminary study demonstrated that the detection of BPDE-induced DNA damage via

  5. Bioassay of Military Relevant Compounds for Carcinogenic Activity by the Strain A Mouse Lung Tumor Bioassay (United States)


    nonwoven polyester fiber filter tops. There were four animals housed per cage, in accordance with National Cancer Institute weight-space of each), and filtered through 0.22 pm Swinnex filter (Millipore). An aliquot (5-10 1l) was removed for the determination of total Figure 1A, and the separations obtained were essentially the same as those reported by Long and Rickert.18 In all of the media from incubations

  6. Towards the regulation of aerosol emissions by their potential health impact: Assessing adverse effects of aerosols from wood combustion and ship diesel engine emissions by combining comprehensive data on the chemical composition and their toxicological effects on human lung cells (United States)

    Zimmermann, R.; Streibel, T.; Dittmar, G.; Kanashova, T.; Buters, J.; Öder, S.; Paur, H. R.; Dilger, M.; Weiss, C.; Harndorf, H.; Stengel, B.; Hirvonen, M. R.; Jokiniemi, J.; Hiller, K.; Sapcariu, S.; Sippula, O.; Orasche, J.; Müller, L.; Rheda, A.; Passig, J.; Radischat, C.; Czech, H.; Tiita, P.; Jalava, P.; Kasurinen, S.; Schwemer, T.; Yli-Prilä, P.; Tissari, J.; Lamberg, H.; Schnelle-Kreis, J.


    Ship engine emissions are important regarding lung and cardiovascular diseases in coastal regions worldwide. Bio mass burning is made responsible for adverse health effects in many cities and rural regions. The Virtual Helmholtz Institute-HICE ( addresses chemical & physical properties and health effects of anthropogenic combustion emissions. Typical lung cell responses to combustion aerosols include inflammation and apoptosis, but a molecular link with the specific chemical composition in particular of ship emissions has not been established. Through an air-liquid interface exposure system (ALI), we exposed human lung cells at-site to exhaust fumes from a ship engine running on common heavy fuel oil (HFO) and cleaner-burning diesel fuel (DF) as well as to emissions of wood combustion compliances. A special field deployable ALI-exposition system and a mobile S2-biological laboratory were developed for this study. Human alveolar basal epithelial cells (A549 etc.) are ALI-exposed to fresh, diluted (1:40-1:100) combustion aerosols and subsequently were toxicologically and molecular-biologically characterized. Advanced chemical analyses of the exhaust aerosols were combined with transcriptional, proteomic and metabolomic profiling to characterise the cellular responses. The HFO ship emissions contained high concentrations of toxic compounds (transition metals, organic toxicants) and particle masses. The cellular responses included inflammation and oxidative stress. Surprisingly, the DF ship emissions, which predominantly contain rather "pure" carbonaceous soot and much less known toxicants, induced significantly broader biological effects, affecting essential cellular pathways (e.g., mitochondrial function and intracellular transport). Therefore the use of distillate fuels for shipping (this is the current emission reduction strategy of the IMO) appears insufficient for diminishing health effects. The study suggests rather reducing the particle emissions

  7. 4-Dimethylaminoazobenzenes: carcinogenicities and reductive cleavage by microsomal azo reductase. (United States)

    Lambooy, J P; Koffman, B M


    Twenty-four 4-dimethylaminoazobenzenes (DABs) in which systematic structural modifications have been made in the prime ring have been studied for substrate specificity for microsomal azo reductase. The DABs were also evaluated for carcinogenicity and it was found that there was no correlation between carcinogenicity and extent of azo bond cleavage by azo reductase. While any substituent in the prime ring reduces the rate of cleavage of the azo bond relative to the unsubstituted dye, there is a correlation between substituent size and susceptibility to the enzyme. Substituent size was also found to be a significant factor in the induction of hepatomas by the dyes. Preliminary studies have shown that there appears to be a positive correlation between microsomal riboflavin content and the activity of the azo reductase.

  8. A study of the carcinogenicity of glycidol in Syrian hamsters. (United States)

    Lijinsky, W; Kovatch, R M


    The industrial chemical glycidol is a directly acting mutagen and a broadly acting carcinogen in rats. It was administered to Syrian golden hamsters (20 male and 20 female) by gavage of 12 mg twice a week for 60 weeks. The total dose per animal was 1.45 g or 20 mmol. Survival was not different from control hamsters treated with corn oil/ethyl acetate. Of the treated males, 9 had tumors and 13 of the treated females had tumors, some of which were adrenal cortex tumors seen in controls. More tumors were seen in the glycidol-treated hamsters than in controls, but the spleen was the only notable target organ and the number of animals with spleen hemangiosarcomas was small. Glycidol appeared to be less carcinogenic in hamsters than in rats or mice.

  9. Carcinogenic Air Toxics Exposure and Their Cancer-Related Health Impacts in the United States (United States)

    Zhou, Ying; Li, Chaoyang; Huijbregts, Mark A. J.; Mumtaz, M. Moiz


    Public health protection from air pollution can be achieved more effectively by shifting from a single-pollutant approach to a multi-pollutant approach. To develop such multi-pollutant approaches, identifying which air pollutants are present most frequently is essential. This study aims to determine the frequently found carcinogenic air toxics or hazardous air pollutants (HAPs) combinations across the United States as well as to analyze the health impacts of developing cancer due to exposure to these HAPs. To identify the most commonly found carcinogenic air toxics combinations, we first identified HAPs with cancer risk greater than one in a million in more than 5% of the census tracts across the United States, based on the National-Scale Air Toxics Assessment (NATA) by the U.S. EPA for year 2005. We then calculated the frequencies of their two-component (binary), and three-component (ternary) combinations. To quantify the cancer-related health impacts, we focused on the 10 most frequently found HAPs with national average cancer risk greater than one in a million. Their cancer-related health impacts were calculated by converting lifetime cancer risk reported in NATA 2005 to years of healthy life lost or Disability-Adjusted Life Years (DALYs). We found that the most frequently found air toxics with cancer risk greater than one in a million are formaldehyde, carbon tetrachloride, acetaldehyde, and benzene. The most frequently occurring binary pairs and ternary mixtures are the various combinations of these four air toxics. Analysis of urban and rural HAPs did not reveal significant differences in the top combinations of these chemicals. The cumulative annual cancer-related health impacts of inhaling the top 10 carcinogenic air toxics included was about 1,600 DALYs in the United States or 0.6 DALYs per 100,000 people. Formaldehyde and benzene together contribute nearly 60 percent of the total cancer-related health impacts. Our study shows that although there are many

  10. Application of the Margin of Exposure (MoE) Approach to Substances in Food that are Genotoxic and Carcinogenic Example: Benzo[a]pyrene and polycyclic aromatic hydrocarbons (United States)

    This paper presents the work of an expert group established by the International Life Sciences Institute - European branch (ILSI Europe) to follow up the recommendations of an international conference on "Risk Assessment of Compounds that are both Genotoxic and Carcinogenic: New ...

  11. Generation of in vitro data to model dose dependent in vivo DNA binding of genotoxic carcinogens and its consequences: the case of estragole

    NARCIS (Netherlands)

    Paini, A.


    Our food contains several compounds which, when tested in isolated form at high doses in animal experiments, have been shown to be genotoxic and carcinogenic. At the present state-of-the-art there is no scientific consensus on how to perform the risk assessment of these compounds when present at low

  12. Overview of bioassays for mutagens, carcinogens, and teratogens

    Energy Technology Data Exchange (ETDEWEB)

    Dumont, J.N.


    Bioassays to determine the risk of health hazards of man-made chemical substances are reviewed. The standard approach to testing a substance is the tier system, consisting of three levels of testing that are increasingly complex, lengthy, and costly. The paper describes the biological basis of bioassays, identifies various assays for mutagens, carcinogens and teratogens, and explains the problems involved in extrapolating test data to human risk estimates. Future improvements in assay techniques are discussed. (CR)

  13. Dose-response relationships for carcinogens: a review.


    Zeise, L; Wilson, R.; Crouch, E A


    We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinea...

  14. The Role of Tobacco-Derived Carcinogens in Pancreas Cancer


    Lochan, Rajiv; Reeves, Helen L.; Daly, Anne K.; Charnley, Richard M


    The extremely poor outcome from pancreas cancer is well known. However, its aetiology less well appreciated, and the molecular mechanisms underlying this are poorly understood. Tobacco usage is one of the strongest risk factors for this disease, and this is a completely avoidable hazard. In addition, there are well described hereditary diseases which predispose, and familial pancreas cancer. We have sought here to summarise the role of tobacco-derived carcinogens and the mode of their tumorig...

  15. Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane. (United States)

    Bauman, Julie E; Zang, Yan; Sen, Malabika; Li, Changyou; Wang, Lin; Egner, Patricia A; Fahey, Jed W; Normolle, Daniel P; Grandis, Jennifer R; Kensler, Thomas W; Johnson, Daniel E


    Chronic exposure to carcinogens represents the major risk factor for head and neck squamous cell carcinoma (HNSCC). Beverages derived from broccoli sprout extracts (BSE) that are rich in glucoraphanin and its bioactive metabolite sulforaphane promote detoxication of airborne pollutants in humans. Herein, we investigated the potential chemopreventive activity of sulforaphane using in vitro models of normal and malignant mucosal epithelial cells and an in vivo model of murine oral cancer resulting from the carcinogen 4-nitroquinoline-1-oxide (4NQO). Sulforaphane treatment of Het-1A, a normal mucosal epithelial cell line, and 4 HNSCC cell lines led to dose- and time-dependent induction of NRF2 and the NRF2 target genes NQO1 and GCLC, known mediators of carcinogen detoxication. Sulforaphane also promoted NRF2-independent dephosphorylation/inactivation of pSTAT3, a key oncogenic factor in HNSCC. Compared with vehicle, sulforaphane significantly reduced the incidence and size of 4NQO-induced tongue tumors in mice. A pilot clinical trial in 10 healthy volunteers evaluated the bioavailability and pharmacodynamic activity of three different BSE regimens, based upon urinary sulforaphane metabolites and NQO1 transcripts in buccal scrapings, respectively. Ingestion of sulforaphane-rich BSE demonstrated the greatest, most consistent bioavailability. Mucosal bioactivity, defined as 2-fold or greater upregulation of NQO1 mRNA, was observed in 6 of 9 evaluable participants ingesting glucoraphanin-rich BSE; 3 of 6 ingesting sulforaphane-rich BSE; and 3 of 9 after topical-only exposure to sulforaphane-rich BSE. Together, our findings demonstrate preclinical chemopreventive activity of sulforaphane against carcinogen-induced oral cancer, and support further mechanistic and clinical investigation of sulforaphane as a chemopreventive agent against tobacco-related HNSCC. Cancer Prev Res; 9(7); 547-57. ©2016 AACR.

  16. Lung surgery (United States)

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

  17. [Humidifier lung]. (United States)

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


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

  18. Lung cancer

    DEFF Research Database (Denmark)

    Hansen, H H; Rørth, M


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

  19. Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health

    DEFF Research Database (Denmark)

    Bonassi, S; Hagmar, L; Strömberg, U;


    played by exposure to carcinogens is still uncertain because of the requisite information concerning occupation and lifestyle was lacking. We evaluated in the present study whether CAs predicted cancer because they were the result of past exposure to carcinogens or because they were an intermediate end...... by country, sex, year of birth, and year of CA test were randomly selected. Occupational exposure and smoking habit were assessed by a collaborative group of occupational hygienists. Logistic regression models indicated a statistically significant increase in risk for subjects with a high level of CAs...... compared to those with a low level in the Nordic cohort (odds ratio, 2.35; 95% confidence interval, 1.31-4.23) and in the Italian cohort (odds ratio, 2.66; 95% confidence interval, 1.26-5.62). These estimates were not affected by the inclusion of occupational exposure level and smoking habit...

  20. Workplace carcinogen and pesticide exposures in Costa Rica. (United States)

    Partanen, Timo; Chaves, Jorge; Wesseling, Catharina; Chaverri, Fabio; Monge, Patricia; Ruepert, Clemens; Aragón, Aurora; Kogevinas, Manolis; Hogstedt, Christer; Kauppinen, Timo


    The CAREX data system converts national workforce volumes and proportions of workers exposed to workplace carcinogens into numbers of exposed in 55 industrial categories. CAREX was adapted for Costa Rica for 27 carcinogens and seven groups of pesticides. Widespread workplace carcinogens in the 1.3 million workforce of Costa Rica are solar radiation (333,000 workers), diesel engine exhaust (278,000), environmental tobacco smoke (71,000), hexavalent chromium compounds (55,000), benzene (52,000), wood dust (32,000), silica dust (27,000), lead and inorganic lead compounds (19,000), and polycyclic aromatic compounds (17,000). The most ubiquitous pesticides were paraquat and diquat (175,000), mancozeb, maneb, and zineb (49,000), chlorothalonil (38,000), benomyl (19,000), and chlorophenoxy herbicides (11,000). Among women, formaldehyde, radon, and methylene chloride overrode pesticides, chromium, wood dust, and silica dust in numbers of exposed. High-risk sectors included agriculture, construction, personal and household services, land and water transport and allied services, pottery and similar industries, woodworks, mining, forestry and logging, fishing, manufacturing of electrical machinery, and bar and restaurant personnel.

  1. Protection against N-nitrosodiethylamine and benzo[a]pyrene-induced forestomach and lung tumorigenesis in A/J mice by green tea. (United States)

    Katiyar, S K; Agarwal, R; Zaim, M T; Mukhtar, H


    In recent years we and others have shown the cancer chemopreventive effects of green tea in several animal tumor models. In this study we assessed the cancer chemopreventive effects of water extract of green tea (WEGT) and the polyphenolic fraction (GTP) isolated from WEGT against N-nitrosodiethylamine (DEN)- and benzo[a]pyrene (BP)-induced forestomach and lung tumorigenesis in A/J mice. The protective effects, both in forestomach and lungs, were evident by a decrease in number of tumors and the percentage of mice with tumors when WEGT and GTP were fed to animals during initiation, post-initiation and entire period of tumorigenesis protocols. Oral feeding of 0.2% GTP in drinking water to mice afforded 68-82 and 39-66% protection against DEN- and BP-induced forestomach tumorigenesis respectively. In case of pulmonary tumor multiplicity caused by DEN and BP, the protective effects of GTP were between 38-43 and 25-46% respectively. Similarly, oral feeding of 2.5% WEGT to mice also afforded 80-85 and 61-71% protection against DEN- and BP-induced forestomach tumorigenesis respectively. In case of lung tumorigenesis, the protective effects of WEGT were 43-62 and 25-51% respectively. Histological studies of forestomach tumors showed significantly lower squamous cell carcinoma counts in GTP- and WEGT-fed groups of mice compared to carcinogen alone treated control group of mice. When pulmonary tumors were examined histologically, no adenocarcinomas were observed in GTP- and WEGT-fed groups of mice compared to 20% mice with adenocarcinomas in carcinogen alone treated control group. Oral feeding of GTP and WEGT in drinking water also showed significant enhancement in the activities of glutathione S-transferase and NADP(H): quinone reductase in liver, small bowel, stomach and lung. The results of this study suggest that green tea possesses chemopreventive effects against carcinogen-induced tumorigenesis in internal body organs, and that the mechanism of such effects may

  2. Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic (18)F Fluorodeoxyglucose PET. (United States)

    Meijer, Tineke W H; de Geus-Oei, Lioe-Fee; Visser, Eric P; Oyen, Wim J G; Looijen-Salamon, Monika G; Visvikis, Dimitris; Verhagen, Ad F T M; Bussink, Johan; Vriens, Dennis


    Purpose To assess whether dynamic fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static (18)F-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 compare pharmacokinetic rate constants of (18)F-FDG metabolism, including regional variation, between NSCLC histologic subtypes. Materials and Methods The study was approved by the institutional review board. Patients gave written informed consent. In this prospective observational study, 1-hour dynamic (18)F-FDG PET/computed tomographic examinations were performed in 35 patients (36 resectable NSCLCs) between 2009 and 2014. Static and parametric images of glucose metabolic rate were obtained to determine lesion volumes by using three delineation strategies. Pathology volume was calculated from three orthogonal dimensions (n = 32). Whole tumor and regional rate constants and blood volume fraction (VB) were computed by using compartment modeling. Results Pathology volumes were larger than PET volumes (median difference, 8.7-25.2 cm(3); Wilcoxon signed rank test, P segmentation on static (18)F-FDG PET images is in best agreement with pathology volume and could be useful for NSCLC autocontouring. Differences in glycolytic rate and VB between SCC and AC are relevant for research in targeting agents and radiation therapy dose escalation. (©) RSNA, 2016 Online supplemental material is available for this article.

  3. Apparent synergy in lung carcinogenesis: interactions between N-nitrosoheptamethyleneimine, particulate cadmium and crocidolite asbestos fibres in rats

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, P.T.; Heath, J.C.


    Environmental carcinogenesis in man is widely accepted to be a multifactorial process, and in the causation of lung cancers it is suspected that low levels of systemic carcinogens may act synergistically with inhaled particulates so that some exposed individuals are at increased risk. In the present study the carcinogenic effects of low levels of industrially and environmentally significant particulate materials (crocidolite asbestos and metallic cadmium) and a putative systemic carcinogen, N-nitrosoheptamethyleneimine (NHMI), were investigated in the laboratory rat, using this as a model of potential human exposure. The overall lung tumour incidence rate in the group of animals receiving crocidolite, cadmium and NHMI (14/45) was significantly higher than in the groups of animals receiving either crocidolite and cadmium together (2/51) or crocidolite and NHMI together (7/42). The results demonstrated an apparent synergy between cadmium and NHMI in the presence of crocidolite in the causation of lung cancer in rats, a finding which was confirmed statistically. This study helps to further evaluate and define the roles of asbestos and particulate cadmium in the causation of lung cancer. It is suggested that people who are exposed through occupation and/or environment to cadmium and asbestos and to low levels of systemic carcinogens may show a significantly elevated risk of lung cancer.

  4. Inhalation cancer risk assessment of cobalt metal. (United States)

    Suh, Mina; Thompson, Chad M; Brorby, Gregory P; Mittal, Liz; Proctor, Deborah M


    Cobalt compounds (metal, salts, hard metals, oxides, and alloys) are used widely in various industrial, medical and military applications. Chronic inhalation exposure to cobalt metal and cobalt sulfate has caused lung cancer in rats and mice, as well as systemic tumors in rats. Cobalt compounds are listed as probable or possible human carcinogens by some agencies, and there is a need for quantitative cancer toxicity criteria. The U.S. Environmental Protection Agency has derived a provisional inhalation unit risk (IUR) of 0.009 per μg/m(3) based on a chronic inhalation study of soluble cobalt sulfate heptahydrate; however, a recent 2-year cancer bioassay affords the opportunity to derive IURs specifically for cobalt metal. The mechanistic data support that the carcinogenic mode of action (MOA) is likely to involve oxidative stress, and thus, non-linear/threshold mechanisms. However, the lack of a detailed MOA and use of high, toxic exposure concentrations in the bioassay (≥1.25 mg/m(3)) preclude derivation of a reference concentration (RfC) protective of cancer. Several analyses resulted in an IUR of 0.003 per μg/m(3) for cobalt metal, which is ∼3-fold less potent than the provisional IUR. Future research should focus on establishing the exposure-response for key precursor events to improve cobalt metal risk assessment.

  5. The Food and Beverage Occurrence of Furfuryl Alcohol and Myrcene—Two Emerging Potential Human Carcinogens?

    Directory of Open Access Journals (Sweden)

    Alex O. Okaru


    Full Text Available For decades, compounds present in foods and beverages have been implicated in the etiology of human cancers. The World Health Organization (WHO International Agency for Research on Cancer (IARC continues to classify such agents regarding their potential carcinogenicity in humans based on new evidence from animal and human studies. Furfuryl alcohol and β-myrcene are potential human carcinogens due to be evaluated. The major source of furfuryl alcohol in foods is thermal processing and ageing of alcoholic beverages, while β-myrcene occurs naturally as a constituent of the essential oils of plants such as hops, lemongrass, and derived products. This study aimed to summarize the occurrence of furfuryl alcohol and β-myrcene in foods and beverages using literature review data. Additionally, results of furfuryl alcohol occurrence from our own nuclear magnetic resonance (NMR analysis are included. The highest content of furfuryl alcohol was found in coffee beans (>100 mg/kg and in some fish products (about 10 mg/kg, while among beverages, wines contained between 1 and 10 mg/L, with 8 mg/L in pineapple juice. The content of β-myrcene was highest in hops. In conclusion, the data about the occurrence of the two agents is currently judged as insufficient for exposure and risk assessment. The results of this study point out the food and beverage groups that may be considered for future monitoring of furfuryl alcohol and β-myrcene.

  6. Ferns and lycopods--a potential treasury of anticancer agents but also a carcinogenic hazard. (United States)

    Tomšík, Pavel


    Many species of seedless vascular plants-ferns and lycopods-have been used as food and folk medicine since ancient times. Some of them have become the focus of intensive research concerning their anticancer properties. Studies on the anticancer effect of crude extracts are being increasingly replaced by bioactivity-guided fractionation, as well as detailed assessment of the mechanism of action. Numerous compounds-especially flavonoids such as amentoflavone and protoapigenone, and also simpler phenolic compounds, steroids, alkaloids and terpenoids-were isolated and found to be cytotoxic, particularly pro-apoptotic, or to induce cell cycle arrest in cancer cell lines in vitro. In in vivo experiments, some fern-derived compounds inhibited tumour growth with little toxicity. On the other hand, many ferns-not only the well-known Bracken (Pteridium)-may pose a significant hazard to human health due to the fact that they contain carcinogenic sesquiterpenoids and their analogues. The objective of this review is to summarise the recent state of research on the anticancer properties of ferns and lycopods, with a focus on their characteristic bioactive constituents. The carcinogenic hazard posed by ferns is also mentioned.

  7. Carcinogenicity of azo colorants: influence of solubility and bioavailability. (United States)

    Golka, Klaus; Kopps, Silke; Myslak, Zdislaw W


    In the past, azo colorants based on benzidine, 3,3'-dichlorobenzidine, 3,3'-dimethylbenzidine (o-tolidine), and 3,3'-dimethoxybenzidine (o-dianisidine) have been synthesized in large amounts and numbers. Studies in exposed workers have demonstrated that the azoreduction of benzidine-based dyes occurs in man. The metabolic conversion of benzidine-, 3,3'-dimethylbenzidine- and 3,3'-dimethoxybenzidine-based dyes to their (carcinogenic) amine precursors in vivo is a general phenomenon that must be considered for each member of this class of chemicals. Several epidemiological studies have demonstrated that the use of the benzidine-based dyes has caused bladder cancer in humans. However, in contrast to water-soluble dyes, the question of biological azoreduction of (practically insoluble) pigments has been a matter of discussion. As a majority of azo pigments are based on 3,3'-dichlorobenzidine, much of the available experimental data are focused on this group. Long-term animal carcinogenicity studies performed with pigments based on 3,3'-dichlorobenzidine did not show a carcinogenic effect. The absence of a genotoxic effect has been supported by mutagenicity studies with the 3,3'-dichlorobenzidine-based Pigment Yellow 12. Studies in which azo pigments based on 3,3'-dichlorobenzidine had been orally administered to rats, hamsters, rabbits and monkeys could generally not detect significant amounts of 3,3'-dichlorobenzidine in the urine. It, therefore, appears well established that the aromatic amine components from azo pigments based on 3,3'-dichlorobenzidine are practically not bioavailable. Hence, it is very unlikely that occupational exposure to insoluble azo pigments would be associated with a substantial risk of (bladder) cancer in man. According to current EU regulations, azo dyes based on benzidine, 3,3'-dimethoxybenzidine and 3,3'-dimethylbenzidine have been classified as carcinogens of category 2 as "substances which should be regarded as if they are carcinogenic

  8. The cellular and molecular carcinogenic effects of radon exposure: a review. (United States)

    Robertson, Aaron; Allen, James; Laney, Robin; Curnow, Alison


    Radon-222 is a naturally occurring radioactive gas that is responsible for approximately half of the human annual background radiation exposure globally. Chronic exposure to radon and its decay products is estimated to be the second leading cause of lung cancer behind smoking, and links to other forms of neoplasms have been postulated. Ionizing radiation emitted during the radioactive decay of radon and its progeny can induce a variety of cytogenetic effects that can be biologically damaging and result in an increased risk of carcinogenesis. Suggested effects produced as a result of alpha particle exposure from radon include mutations, chromosome aberrations, generation of reactive oxygen species, modification of the cell cycle, up or down regulation of cytokines and the increased production of proteins associated with cell-cycle regulation and carcinogenesis. A number of potential biomarkers of exposure, including translocations at codon 249 of TP53 in addition to HPRT mutations, have been suggested although, in conclusion, the evidence for such hotspots is insufficient. There is also substantial evidence of bystander effects, which may provide complications when calculating risk estimates as a result of exposure, particularly at low doses where cellular responses often appear to deviate from the linear, no-threshold hypothesis. At low doses, effects may also be dependent on cellular conditions as opposed to dose. The cellular and molecular carcinogenic effects of radon exposure have been observed to be both numerous and complex and the elevated chronic exposure of man may therefore pose a significant public health risk that may extend beyond the association with lung carcinogenesis.