Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

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N.B.R. Colombo

2015-01-01

Full Text Available The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress.

Analysis of radon-induced lung cancer risk by a stochastic state-vector model of radiation carcinogenesis

International Nuclear Information System (INIS)

Crawford-Brown, Douglas J.; Hofmann, Werner

2002-01-01

A biologically based state-vector model (SVM) of radiation carcinogenesis has been extended to incorporate stochasticity of cellular transitions and specific in vivo irradiation conditions in the lungs. Dose-rate-dependent cellular transitions related to the formation of double-stranded DNA breaks, repair of breaks, interactions (translocations) between breaks, fixation of breaks, cellular inactivation, stimulated mitosis and promotion through loss of intercellular communication are simulated by Monte Carlo methods. The stochastic SVM has been applied to the analysis of lung cancer incidence in uranium miners exposed to alpha-emitting radon progeny. When incorporating in vivo features of cell differentiation, stimulated cell division and heterogeneity of cellular doses into the model, excellent agreement between epidemiological data and modelling results could be obtained. At low doses, the model predicts a non-linear dose-response relationship; e.g., computed lung cancer risk at 20 WLM is about half of current lung cancer estimates based on the linear hypothesis. The model also predicts a slight dose rate effect; e.g., at a cumulative exposure of 20 WLM, calculated lung cancer incidence for an exposure rate 0.27 WLM/year (assuming an exposure time of 73 years) is smaller by a factor of 1.2 than that for an exposure rate of 10 WLM/year. (author)

Pulmonary Oxidative Stress, Inflammation and Cancer: Respirable Particulate Matter, Fibrous Dusts and Ozone as Major Causes of Lung Carcinogenesis through Reactive Oxygen Species Mechanisms

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Spyridon Loridas

2013-08-01

Full Text Available Reactive oxygen or nitrogen species (ROS, RNS and oxidative stress in the respiratory system increase the production of mediators of pulmonary inflammation and initiate or promote mechanisms of carcinogenesis. The lungs are exposed daily to oxidants generated either endogenously or exogenously (air pollutants, cigarette smoke, etc.. Cells in aerobic organisms are protected against oxidative damage by enzymatic and non-enzymatic antioxidant systems. Recent epidemiologic investigations have shown associations between increased incidence of respiratory diseases and lung cancer from exposure to low levels of various forms of respirable fibers and particulate matter (PM, at occupational or urban air polluting environments. Lung cancer increases substantially for tobacco smokers due to the synergistic effects in the generation of ROS, leading to oxidative stress and inflammation with high DNA damage potential. Physical and chemical characteristics of particles (size, transition metal content, speciation, stable free radicals, etc. play an important role in oxidative stress. In turn, oxidative stress initiates the synthesis of mediators of pulmonary inflammation in lung epithelial cells and initiation of carcinogenic mechanisms. Inhalable quartz, metal powders, mineral asbestos fibers, ozone, soot from gasoline and diesel engines, tobacco smoke and PM from ambient air pollution (PM10 and PM2.5 are involved in various oxidative stress mechanisms. Pulmonary cancer initiation and promotion has been linked to a series of biochemical pathways of oxidative stress, DNA oxidative damage, macrophage stimulation, telomere shortening, modulation of gene expression and activation of transcription factors with important role in carcinogenesis. In this review we are presenting the role of ROS and oxidative stress in the production of mediators of pulmonary inflammation and mechanisms of carcinogenesis.

Cadmium carcinogenesis

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Waalkes, Michael P.

2003-01-01

Cadmium is a heavy metal of considerable environmental and occupational concern. Cadmium compounds are classified as human carcinogens by several regulatory agencies. The most convincing data that cadmium is carcinogenic in humans comes from studies indicating occupational cadmium exposure is associated with lung cancer. Cadmium exposure has also been linked to human prostate and renal cancer, although this linkage is weaker than for lung cancer. Other target sites of cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are considered equivocal. In animals, cadmium effectively induces cancers at multiple sites and by various routes. Cadmium inhalation in rats induces pulmonary adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce tumors and/or preneoplastic lesions within the rat prostate after ingestion or injection. At relatively high doses, cadmium induces benign testicular tumors in rats, but these appear to be due to early toxic lesions and loss of testicular function, rather than from a specific carcinogenic effect of cadmium. Like many other metals, cadmium salts will induce mesenchymal tumors at the site of subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance of these is dubious. Other targets of cadmium in rodents include the liver, adrenal, pancreas, pituitary, and hematopoietic system. With the exception of testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly defined. Cadmium can cause any number of molecular lesions that would be relevant to oncogenesis in various cellular model systems. Most studies indicate cadmium is poorly mutagenic and probably acts through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis

Cadmium carcinogenesis

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Waalkes, Michael P

2003-12-10

Cadmium is a heavy metal of considerable environmental and occupational concern. Cadmium compounds are classified as human carcinogens by several regulatory agencies. The most convincing data that cadmium is carcinogenic in humans comes from studies indicating occupational cadmium exposure is associated with lung cancer. Cadmium exposure has also been linked to human prostate and renal cancer, although this linkage is weaker than for lung cancer. Other target sites of cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are considered equivocal. In animals, cadmium effectively induces cancers at multiple sites and by various routes. Cadmium inhalation in rats induces pulmonary adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce tumors and/or preneoplastic lesions within the rat prostate after ingestion or injection. At relatively high doses, cadmium induces benign testicular tumors in rats, but these appear to be due to early toxic lesions and loss of testicular function, rather than from a specific carcinogenic effect of cadmium. Like many other metals, cadmium salts will induce mesenchymal tumors at the site of subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance of these is dubious. Other targets of cadmium in rodents include the liver, adrenal, pancreas, pituitary, and hematopoietic system. With the exception of testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly defined. Cadmium can cause any number of molecular lesions that would be relevant to oncogenesis in various cellular model systems. Most studies indicate cadmium is poorly mutagenic and probably acts through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis.

Interplay between the lung microbiome and lung cancer.

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Mao, Qixing; Jiang, Feng; Yin, Rong; Wang, Jie; Xia, Wenjie; Dong, Gaochao; Ma, Weidong; Yang, Yao; Xu, Lin; Hu, Jianzhong

2018-02-28

The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer. Some recent studies have shown that certain microbes and microbiota dysbiosis are correlated with development of lung cancer. In this mini-review, we briefly summarize current research findings describing the relationship between the lung microbiome and lung cancer. We further discuss the potential mechanisms through which the lung microbiome may play a role in lung carcinogenesis and impact lung cancer treatment. A better knowledge of the interplay between the lung microbiome and lung cancer may promote the development of innovative strategies for early prevention and personalized treatment in lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Combined effects of inhaled plutonium oxide and benzo[a]pyrene on lung carcinogenesis in rats

International Nuclear Information System (INIS)

Metivier, H.; Masse, R.; Wahrendorf, J.; Lafuma, J.

1986-01-01

This study describes the effect of two intratracheal instillations (5 mg each) of benzo[a]pyrene (BP) on lung carcinogenesis in rats that had previously inhaled three levels of 239 PuO 2 . The BP does not modify survival in the high-level 239 PuO 2 -exposed rats, but markedly reduces survival in the two other groups. Median survival time with BP alone is shorter (666 days) than for the control group (838 days). Tumor incidence was increased by BP exposure, and the tumors were usually fatal, whereas tumors observed after 239 PuO 2 inhalation alone were usually not fatal. Statistical analysis of these data poses a problem because of the need to compare incidental and fatal tumors. 22 refs., 5 figs., 7 tabs

Outcome of four-dimensional stereotactic radiotherapy for centrally located lung tumors

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Nuyttens, Joost J.; Voort van Zyp, Noelle C. van der; Praag, John; Aluwini, Shafak; Klaveren, Rob J. van; Verhoef, Cornelis; Pattynama, Peter M.; Hoogeman, Mischa S.

2012-01-01

Purpose: To assess local control, overall survival, and toxicity of four-dimensional, risk-adapted stereotactic body radiotherapy (SBRT) delivered while tracking respiratory motion in patients with primary and metastatic lung cancer located in the central chest. Methods: Fifty-eight central lesions of 56 patients (39 with primary, 17 with metastatic tumors) were treated. Fifteen tumors located near the esophagus were treated with 6 fractions of 8 Gy. Other tumors were treated according to the following dose escalation scheme: 5 fractions of 9 Gy (n = 6), then 5 fractions of 10 Gy (n = 15), and finally 5 fractions of 12 Gy (n = 22). Results: Dose constraints for critical structures were generally achieved; in 21 patients the coverage of the PTV was reduced below 95% to protect adjacent organs at risk. At a median follow-up of 23 months, the actuarial 2-years local tumor control was 85% for tumors treated with a BED >100 Gy compared to 60% for tumors treated with a BED ⩽100 Gy. No grade 4 or 5 toxicity was observed. Acute grade 1–2 esophagitis was observed in 11% of patients. Conclusion: SBRT of central lung lesions can be safely delivered, with promising early tumor control in patients many of whom have severe comorbid conditions.

Contribution to the study of markers in lungs carcinogenesis and analysis of factors predicting the benefit of chemotherapy

International Nuclear Information System (INIS)

Olaussen, K.A.

2006-06-01

A better definition of early bio markers in lung carcinogenesis should enhance the development of molecular means to perform screening, diagnostic, and chemo-prevention of patients at high risk of lung cancer. We studied epigenetic deregulation of multiple promoters (p16(INK4a), HOX A9, MAGE A 1 et MAGE B2) in sputum samples from smokers at high risk and from patients with non-small cell lung cancer (N.S.C.L.C.). This molecular test, based on easily accessible sample,s can be modulated according to the aims of the investigator (e.g. screening or confirmation of diagnosis). Secondly, we have studied two candidate proteins as predictive markers of the benefit of adjuvant chemotherapy in patients with resected lung cancer. The multivariate analysis shows that tumor expression of the catalytic sub-unit of telomerase is not able to predict survival in patients included in the lAL T study' of adjuvant chemotherapy. However, tumor expression of the DNA repair protein ERCC1 identifies a sub-group of patients (ERCC1 negative) whose chances of survival are increased by 35% by means of cisplatin-based adjuvant chemotherapy. Further, tumor ERCC1 expression has a positive prognostic value in the non-treated control group. The need for a deeper understanding in cancerology of the physiological role of the ERCC1 endonuclease is discussed in this thesis. (author)

Interactions between ethanol and cigarette smoke in a mouse lung carcinogenesis model

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Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Nikolov, Manasi; La Maestra, S.; Micale, Rosanna T.; Steele, Vernon E.; De Flora, Silvio

2016-01-01

Highlights: • Cigarette smoke and ethanol are known to synergize in the upper aerodigestive tract. • Their interactions in the lower respiratory tract have poorly been explored. • Prenatal and postnatal treatments of mice with ethanol caused pulmonary alterations. • However, ethanol attenuated smoke-induced preneoplastic and neoplastic lesions in lung. • The interaction between smoke and alcohol depends on life stage and target tissue. - Abstract: Both ethanol and cigarette smoke are classified as human carcinogens. They can synergize, especially in tissues of the upper aerodigestive tract that are targeted by both agents. The main objective of the present study was to evaluate the individual and combined effects of ethanol and smoke in the respiratory tract, either following transplacental exposure and/or postnatal exposure. We designed two consecutive studies in mouse models by exposing Swiss H mice to oral ethanol and/or inhaled mainstream cigarette smoke for up to 4 months, at various prenatal and postnatal life stages. Clastogenic effects and histopathological alterations were evaluated after 4 and 8 months, respectively. Ethanol was per se devoid of clastogenic effects in mouse peripheral blood erythrocytes. However, especially in mice exposed both transplacentally throughout pregnancy and in the postnatal life, ethanol administration was associated not only with liver damage but also with pro-angiogenetic effects in the lung by stimulating the proliferation of blood vessels. In addition, these mice developed pulmonary emphysema, alveolar epithelial hyperplasias, microadenomas, and benign tumors. On the other hand, ethanol interfered in the lung carcinogenesis process resulting from the concomitant exposure of mice to smoke. In fact, ethanol significantly attenuated some smoke-related preneoplastic and neoplastic lesions in the respiratory tract, such as alveolar epithelial hyperplasia, microadenomas, and even malignant tumors. In addition, ethanol

Kinetics of badminton lunges in four directions.

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Hong, Youlian; Wang, Shao Jun; Lam, Wing Kai; Cheung, Jason Tak Man

2014-02-01

The lunge is the most fundamental skill in badminton competitions. Fifteen university-level male badminton players performed lunge maneuvers in four directions, namely, right-forward, left-forward, right-backward, and left-backward, while wearing two different brands of badminton shoes. The test compared the kinetics of badminton shoes in performing typical lunge maneuvers. A force plate and an insole measurement system measured the ground reaction forces and plantar pressures. These measurements were compared across all lunge maneuvers. The left-forward lunge generated significantly higher first vertical impact force (2.34 ± 0.52 BW) than that of the right-backward (2.06 ± 0.60 BW) and left-backward lunges (1.78 ± 0.44 BW); higher second vertical impact force (2.44 ± 0.51 BW) than that of the left-backward lunge (2.07 ± 0.38 BW); and higher maximum anterior-posterior shear force (1.48 ± 0.36 BW) than that of the left-backward lunge (1.18 ± 0.38 BW). Compared with other lunge directions, the left-forward lunge showed higher mean maximum vertical impact anterior-posterior shear forces and their respective maximum loading rates, and the plantar pressure at the total foot and heel regions. Therefore, the left-forward lunge is a critical maneuver for badminton biomechanics and related footwear research because of the high loading magnitude generated during heel impact.

Apoptotic role of natural isothiocyanate from broccoli (Brassica oleracea italica) in experimental chemical lung carcinogenesis.

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Kalpana Deepa Priya, D; Gayathri, R; Gunassekaran, G R; Murugan, S; Sakthisekaran, D

2013-05-01

Sulforaphane (SFN) [1-isothiocyanato-4-(methylsulfinyl)butane] is a naturally occurring isothiocyanate found in cruciferous vegetables such as broccoli [Brassica oleracea L. var. italica Plenck. (Brassicaceae)]. Since it is among the most potent bioactive components with antioxidant and antitumor properties, it has received intense attention in the recent years for its chemopreventive properties. The present work determined the rehabilitating role in alleviating the oxidative damage caused by benzo(a)pyrene [B(a)P] to biomolecules and the apoptotic cascade mediated by orally administered isothiocyanate-SFN (9 µmol/mouse/day) against B(a)P (100 mg/kg body weight, i.p.) induced pulmonary carcinogenesis in Swiss albino mice. Oxidative damage was assessed by measuring lipid peroxidation, 8-hydroxydeoxyguanosine, hydrogen peroxide (H2O2) production, glycoprotein components, protein carbonyl levels and DNA-protein crosslinks. DNA fragmentation by agarose gel electrophoresis and caspase-3 activity by ELISA proved apoptotic induction by SFN along with the protein expression of Bcl-2, Bax and Cyt c. SFN treatment was found to decrease the H2O2 production (p < 0.001) in cancer induced animals, proving its antioxidant potential. Apoptosis was induced by increasing the release of Cyt c (p < 0.001) from mitochondria, decreasing and increasing the expression of Bcl-2 (p < 0.01) and Bax (p < 0.001), respectively. Caspase-3 activity was also enhanced (p < 0.001) which leads to DNA fragmentation in SFN treated groups. Our results reflect the rehabilitating role of SFN in B(a)P induced lung carcinogenesis.

Pulmonary carcinogenesis from plutonium-containing particles

International Nuclear Information System (INIS)

Thomas, R.G.; Smith, D.M.; Anderson, E.C.

1980-01-01

Induction of lung tumors by various types of radiation is of paramount concern to the nuclear industry. The data presented were obtained by exposing the pulmonary system of Syrian hamsters to particles of zirconium oxide containing various amounts of either plutonium-238 or -239 as the alpha radiation source. These particles were injected intravenously and lodged permanently in the capillary bed of the lung. When less than 20% of the lung tissue was irradiated, simulating the ''hot particle'' mode, tumors were not evident with lung burdens up to 500 nCi plutonium. More diffuse irradiation significantly increased the tumor incidence, with lung burdens of 50 to 150 nCi. When plutonium-laden microspheres were administered intratracheally, tumor production was considerably increased and the addition of 3 mg of iron oxide intratracheally further increased the incidence. Using the zirconium oxide matrix for the carrier of plutonium in aerosol particles produced tumor incidences of up to 50% in Syrian hamsters exposed by inhalation. Initial pulmonary (alveolar) burdens reached 100 nCi of plutonium. Similar inhalation studies using plutonium dioxide alone (no matrix) failed to produce any increase in lung tumorigenesis. The results are discussed in terms of possible mechanisms necessary for lung carcinogenesis. (H.K.)

Radon-induced lung cancer in smokers and non-smokers: risk implications using a two-mutation carcinogenesis model

International Nuclear Information System (INIS)

Leenhouts, H.P.

1999-01-01

Three sets of data (population statistics in non-smokers, data from an investigation of the smoking habits of British doctors and a study of Colorado uranium miners) were used to analyse lung cancer in humans as a function of exposure to radon and smoking. One of the aims was to derive implications for radon risk estimates. The data were analysed using a two-mutation radiation carcinogenesis model and a stepwise determination of the model parameters. The basic model parameters for lung cancer were derived from the age dependence fit of the spontaneous lung cancer incidence in non-smokers. The effect of smoking was described by two additional parameters and, subsequently, the effect of radon by three other parameters; these five parameters define the dependence of the two mutation steps on smoking and exposure to radon. Using this approach, a consistent fit and comprehensive description of the three sets of data have been achieved, and the parameters could, at least partly, be related to cellular radiobiological data. The model results explain the different effect of radon on non-smokers and smokers as seen in epidemiological data. Although the analysis was only applied to a limited number of populations, lung cancer incidence as a result of radon exposure is estimated to be about ten times higher for people exposed at the age of about 15 than at about 50, although this effect is masked (especially for smokers) by the high lung cancer incidence from smoking. Using the model to calculate the lung cancer risks from lifetime exposure to radon, as is the case for indoor radon, higher risks were estimated than previously derived from epidemiological studies of the miners' data. The excess absolute risk per unit exposure of radon is about 1.7 times higher for smokers of 30 cigarettes per day than for non-smokers, even though, as a result of the low spontaneous tumour incidence in the non-smokers, the excess relative risk per unit exposure for the smokers is about 20 times

Radiation carcinogenesis

International Nuclear Information System (INIS)

1978-01-01

The Cancergram deals with all aspects of radiation carcinogenesis. The term radiation here includes U-V radiation and the entire electromagnetic spectrum, electron and other charged particle beams, neutrons, and alpha and beta radiation from radioactive substances. Abstracts included concern relationships between radiation and carcinogenesis in humans, experimental induction of tumors in animals by irradiation, studies on the mechanism of radiation carcinogenesis at the cellular level, studies of RBE, dose response or dose threshold in relation to radiation carcinogenesis, and methods and policies for control of radiation exposure in the general population. In general, this Cancergram excludes abstracts on radio-therapy, radiologic diagnosis, radiation pathology, and radiation biology, where these articles have no bearing on radiation carcinogenesis

A network-based biomarker approach for molecular investigation and diagnosis of lung cancer

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Chen Bor-Sen

2011-01-01

Full Text Available Abstract Background Lung cancer is the leading cause of cancer deaths worldwide. Many studies have investigated the carcinogenic process and identified the biomarkers for signature classification. However, based on the research dedicated to this field, there is no highly sensitive network-based method for carcinogenesis characterization and diagnosis from the systems perspective. Methods In this study, a systems biology approach integrating microarray gene expression profiles and protein-protein interaction information was proposed to develop a network-based biomarker for molecular investigation into the network mechanism of lung carcinogenesis and diagnosis of lung cancer. The network-based biomarker consists of two protein association networks constructed for cancer samples and non-cancer samples. Results Based on the network-based biomarker, a total of 40 significant proteins in lung carcinogenesis were identified with carcinogenesis relevance values (CRVs. In addition, the network-based biomarker, acting as the screening test, proved to be effective in diagnosing smokers with signs of lung cancer. Conclusions A network-based biomarker using constructed protein association networks is a useful tool to highlight the pathways and mechanisms of the lung carcinogenic process and, more importantly, provides potential therapeutic targets to combat cancer.

Estrogen Signaling in Lung Cancer: An Opportunity for Novel Therapy

International Nuclear Information System (INIS)

Baik, Christina S.; Eaton, Keith D.

2012-01-01

Lung cancer is the leading cause of cancer death in U.S. and represents a major public health burden. Epidemiologic data have suggested that lung cancer in women may possess different biological characteristics compared to men, as evidenced by a higher proportion of never-smokers among women with lung cancer. Emerging data indicate that female hormones such as estrogen and progesterone play a significant role in lung carcinogenesis. It has been reported that estrogen and progesterone receptors are expressed in lung cancer cell lines as well as in patient-derived tumors. Hormone related risk factors such as hormone replacement therapy have been implicated in lung carcinogenesis and several preclinical studies show activity of anti-estrogen therapy in lung cancer. In this review, we summarize the emerging evidence for the role of reproductive hormones in lung cancer and implications for lung cancer therapy

Occurrence of mutations in the epidermal growth factor receptor gene in X-ray-induced rat lung tumors

International Nuclear Information System (INIS)

Kitahashi, Tsukasa; Takahashi, Mami; Yamada, Yutaka

2008-01-01

Epidermal growth factor receptor (EGFR) gene alterations have been found in human lung cancers. However, there is no information on the factors inducing EGFR mutations. In rodents, K-ras mutations are frequently found in many lung carcinogenesis models, but hitherto, Egfr mutations have not been reported. Their presence was therefore investigated in representative lung carcinogenesis models with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosobis(2-hydroxypropyl)amine (BHP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) and ethyl carbamate (urethane), as well as X-ray irradiation. With the chemical carcinogenesis models, no mutations were detected in Egfr, which is in clear contrast to the high rates observed in either codon 12 or 61 of K-ras (21/23 of the lung tumors induced with NNK, 4/5 with MelQx, 1/4 with urethane and 7/18 with BHP). However, in the X-ray-induced lung tumors, Egfr mutations with amino acid substitution were observed in exons 18 and 21 (4/12, 33%), but no activating mutation of K-ras was detected. In addition, one and four silent mutations were identified in K-ras (exon 1) and Egfr (exons 18, 20 and 21), respectively. Most mutations in both Egfr and K-ras were G/C→A/T transitions (7/8, 88% and 31/34, 91%, respectively). Although, the mutational patterns in equivalent human lesions were not completely coincident, this first report of Egfr mutations in an experimental lung tumor model suggests that X-rays or other factors producing oxygen radicals could cause EGFR mutations in some proportion of lung cancers in humans. (author)

Chemoprevention of Lung Cancer: Prospects and Disappointments in Human Clinical Trials

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William N. Rom

2013-01-01

Full Text Available Decreasing the risk of lung cancer, or preventing its development in high-risk individuals, would have a huge impact on public health. The most effective means to decrease lung cancer incidence is to eliminate exposure to carcinogens. However, with recent advances in the understanding of pulmonary carcinogenesis and the identification of intermediate biomarkers, the prospects for the field of chemoprevention research have improved dramatically. Here we review the most recent research in lung cancer chemoprevention—focusing on those agents that have been investigated in human clinical trials. These agents fall into three major categories. First, oxidative stress plays an important role in pulmonary carcinogenesis; and therefore, antioxidants (including vitamins, selenium, green tea extracts, and isothiocyanates may be particularly effective in preventing the development of lung cancer. Second, inflammation is increasingly accepted as a crucial factor in carcinogenesis, and many investigators have focused on anti-inflammatory agents, such as glucocorticoids, NSAIDs, statins, and PPARγ agonists. Finally, the PI3K/AKT/mTOR pathway is recognized to play a central role in tobacco-induced carcinogenesis, and inhibitors of this pathway, including myoinositol and metformin, are promising agents for lung cancer prevention. Successful chemoprevention will likely require targeting of multiple pathways to carcinogenesis—both to minimize toxicity and maximize efficacy.

Experimental carcinogenesis induced by incorporated plutonium

International Nuclear Information System (INIS)

Oghiso, Yoichi

1999-01-01

The carcinogenic effects of an alpha-emitter, 239 Pu, were investigated by animal experiments as focused on both pulmonary tumors after inhalation exposures to insoluble oxide aerosols and tumor spectra induced by injection of soluble citrate. The life-span study using Wistar strain rats exposed to Pu dioxide aerosols has shown differential dose-related responses of malignancies and histopathological phenotypes of lung tumors, suggesting a threshold dose around 1.0 Gy of the lung dose. As abnormality of tumor-related genes could be supposed for the background of pulmonary carcinogenesis, the mutations of p53 tumor suppressor gene were examined by PCR-SSCP analysis using DNA fragments extracted from lung tumors. While mutations were detected in 23 cases (about 28%) among 82 lung tumors, their relations to either malignancies, histological phenotypes, dose, or oncogenesis are not yet to be elucidated. The life-span study using C3H strain mice injected with Pu citrate has shown contrast dose responses between osteosarcomas and lymphoid tumors around 10 Gy of the skeletal dose, and further indicated specific tumor spectra differed from low LET radiation exposures as shown by much more frequency of B cell type leukemic lymphomas and none of myeloid leukemias. (author)

Image-guided radiotherapy for fifty-eight patients with lung cancer

International Nuclear Information System (INIS)

Liang Jun; Zhang Tao; Wang Wenqin

2009-01-01

Objective: To study the value of image-guided radiotherapy (IGRT) in lung cancer. Methods: From Mar. 2007 to Dec. 2007,58 patients with lung cancer were treated with IGRT. Set-up errors in each axial direction was calculated based on IGRT images of each patient. The change of GTV was evaluated on both cone-beam CT and CT simulator images. Results: Twenty-two patients with left lung cancer,30 with right lung cancer, 5 with mediastinal lymphanode metastasis and one with vertebra metastasis were included. The set-up error in x, y and z axes was (0.02±0.26) cm, (0.14±0.49) cm and ( -0.13± 0.27) cm, respectively,while the rotary set-up error in each axis was -0.15 degree ± 1.59 degree, -0.01 degree ± 1.50 degree and 0.12 degree ±1.08 degree, respectively. The set-up errors were significantly decreased by using of IGRT. GTV movement was observed in 15 patients (25.9%) ,including 5 with left upper lung cancer. GTV moving to the anterior direction was observed in 9 patients,including 4 with]eft upper lung cancer. GTV reduced in 23 (44.2%) patients during treatment. Asymmetric GTV reduction of 22 lesions was observed,with a mean reductive volume of 4.9 cm 3 . When GTV began to shrink,the irradiation dose was 4 -46 Gy, with 20 -30 Gy in 9 patients. Conclusions: The use of IGRT can significantly reduce set-up errors. GTV movement and reduction are observed in some cases. The time to modify the target volume needs to be further studied. (authors)

Role of Exosomal Noncoding RNAs in Lung Carcinogenesis

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Tao Sun

2015-01-01

Full Text Available Lung cancer is the major cause of cancer death worldwide. Novel, recently discovered classes of noncoding RNAs (ncRNAs have diverse functional and regulatory activities and increasing evidence suggests crucial roles for deregulated ncRNAs in the onset and progression of cancer, including lung cancer. Exosomes are small extracellular membrane vesicles of endocytic origin that are released by many cells and are found in most body fluids. Tumor-derived exosomes mediate tumorigenesis by facilitating tumor growth and metastasis. MicroRNAs (miRNAs are a subclass of ncRNAs that are present in exosomes. miRNAs are taken up by neighboring or distant cells and modulate various functions of recipient cells. Here, we review exosome-derived ncRNAs with a focus on miRNAs and their role in lung cancer biology.

Epigenetic Therapy in Lung Cancer

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Stephen V Liu

2013-05-01

Full Text Available Epigenetic dysregulation of gene function has been strongly implicated in carcinogenesis and is one of the mechanisms contributing to the development of lung cancer. The inherent reversibility of epigenetic alterations makes them viable therapeutic targets. Here, we review the therapeutic implications of epigenetic changes in lung cancer, and recent advances in therapeutic strategies targeting DNA methylation and histone acetylation.

Carcinogenesis and low-level ionizing radiation with special reference to lung cancer and exposure to radon daughters

Energy Technology Data Exchange (ETDEWEB)

Fabrikant, J.I.

1982-04-01

Of the important health effects of ionizing radiation, three important late effects - carcinogenesis, teratogenesis and mutagenesis are of greatest concern. This is because any exposure, even at low levels, carries some risk of such deleterious effects. As the dose of radiation increases above very low levels, the risk of health effects increases. Cancer-induction is the most important late somatic effect of low-dose ionizing radiation. Solid cancers, rather than leukemia, are principal late effects in exposed individuals. Tissues vary greatly in their susceptibility to radiation carcinogenesis. The most frequently occurring radiation-induced cancers in man include, in decreasing order of susceptibility: the female breast, the thyroid gland, the blood-forming tissues, the lung, certain organs of the gastrointestinal tract, and the bones. A number of biological and physical factors affect the cancer risk, such as age, sex, life-style, LET, and RBE. Despite uncertainty about low-level radiation risks, regulatory and advisory bodies must set standards for exposure, and individuals need information to be able to make informed judgments for themselves. From the point of view of the policy maker, the overriding concern is the fact that small doses of radiation can cause people to have more cancers than would otherwise be expected. While concern for all radiation effects exists, our human experience is limited to cancer-induction in exposed populations. This discussion is limited to cancer risk estimation and decision-making in relation to the health effects on populations of exposure to low levels of ionizing radiation. Here, low-level radiation will refer to yearly whole-body doses up to 5 rems or 0.05 Sv, or to cumulative doses up to 50 rems or 0.5 Sv from low-LET radiation and from high-LET radiation. (ERB)

Carcinogenesis and low-level ionizing radiation with special reference to lung cancer and exposure to radon daughters

International Nuclear Information System (INIS)

Fabrikant, J.I.

1982-04-01

Of the important health effects of ionizing radiation, three important late effects - carcinogenesis, teratogenesis and mutagenesis are of greatest concern. This is because any exposure, even at low levels, carries some risk of such deleterious effects. As the dose of radiation increases above very low levels, the risk of health effects increases. Cancer-induction is the most important late somatic effect of low-dose ionizing radiation. Solid cancers, rather than leukemia, are principal late effects in exposed individuals. Tissues vary greatly in their susceptibility to radiation carcinogenesis. The most frequently occurring radiation-induced cancers in man include, in decreasing order of susceptibility: the female breast, the thyroid gland, the blood-forming tissues, the lung, certain organs of the gastrointestinal tract, and the bones. A number of biological and physical factors affect the cancer risk, such as age, sex, life-style, LET, and RBE. Despite uncertainty about low-level radiation risks, regulatory and advisory bodies must set standards for exposure, and individuals need information to be able to make informed judgments for themselves. From the point of view of the policy maker, the overriding concern is the fact that small doses of radiation can cause people to have more cancers than would otherwise be expected. While concern for all radiation effects exists, our human experience is limited to cancer-induction in exposed populations. This discussion is limited to cancer risk estimation and decision-making in relation to the health effects on populations of exposure to low levels of ionizing radiation. Here, low-level radiation will refer to yearly whole-body doses up to 5 rems or 0.05 Sv, or to cumulative doses up to 50 rems or 0.5 Sv from low-LET radiation and from high-LET radiation

Test of the linear-no threshold theory of radiation carcinogenesis

International Nuclear Information System (INIS)

Cohen, B.L.

1998-01-01

It is shown that testing the linear-no threshold theory (L-NT) of radiation carcinogenesis is extremely important and that lung cancer resulting from exposure to radon in homes is the best tool for doing this. A study of lung cancer rates vs radon exposure in U.S. Counties, reported in 1975, is reviewed. It shows, with extremely powerful statistics, that lung cancer rates decrease with increasing radon exposure, in sharp contrast to the prediction of L-NT, with a discrepancy of over 20 standard deviations. Very extensive efforts were made to explain an appreciable part of this discrepancy consistently with L-NT, with no success; it was concluded that L-NT fails, grossly exaggerating the cancer risk of low level radiation. Two updating studies reported in 1996 are also reviewed. New updating studies utilizing more recent lung cancer statistics and considering 450 new potential confounding factors are reported. All updates reinforce the previous conclusion, and the discrepancy with L-NT is increased. (author)

Role of Smac in Lung Carcinogenesis and Therapy

Science.gov (United States)

2017-07-01

radiotherapy and a smac mimetic. Since anti-PD1 immunotherapy is shown to be superior to platin-based cytotoxic chemotherapy and change the landscape of lung...which combining a SMAC mimetic and radiotherapy yields therapeutic synergy and whether this combination yields abscopal effects from radiotherapy. 2...lung cancer since there was a delay in obtaining the smac knockout mice. Aim 2: Determine the abscopal effect and optimize the therapeutic ratio of

The biology, function and clinical implications of exosomes in lung cancer.

Science.gov (United States)

Zhou, Li; Lv, Tangfeng; Zhang, Qun; Zhu, Qingqing; Zhan, Ping; Zhu, Suhua; Zhang, Jianya; Song, Yong

2017-10-28

Exosomes are 30-100 nm small membrane vesicles of endocytic origin that are secreted by all types of cells, and can also be found in various body fluids. Increasing evidence implicates that exosomes confer stability and can deliver their cargos such as proteins and nucleic acids to specific cell types, which subsequently serve as important messengers and carriers in lung carcinogenesis. Here, we describe the biogenesis and components of exosomes mainly in lung cancer, we summarize their function in lung carcinogenesis (epithelial mesenchymal transition, oncogenic cell transformation, angiogenesis, metastasis and immune response in tumor microenvironment), and importantly we focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer. In addition, we also discuss current challenges that might impede the clinical use of exosomes. Further studies on the functional roles of exosomes in lung cancer requires thorough research. Copyright © 2017 Elsevier B.V. All rights reserved.

Gene dosage, expression, and ontology analysis identifies driver genes in the carcinogenesis and chemoradioresistance of cervical cancer.

Directory of Open Access Journals (Sweden)

Malin Lando

2009-11-01

Full Text Available Integrative analysis of gene dosage, expression, and ontology (GO data was performed to discover driver genes in the carcinogenesis and chemoradioresistance of cervical cancers. Gene dosage and expression profiles of 102 locally advanced cervical cancers were generated by microarray techniques. Fifty-two of these patients were also analyzed with the Illumina expression method to confirm the gene expression results. An independent cohort of 41 patients was used for validation of gene expressions associated with clinical outcome. Statistical analysis identified 29 recurrent gains and losses and 3 losses (on 3p, 13q, 21q associated with poor outcome after chemoradiotherapy. The intratumor heterogeneity, assessed from the gene dosage profiles, was low for these alterations, showing that they had emerged prior to many other alterations and probably were early events in carcinogenesis. Integration of the alterations with gene expression and GO data identified genes that were regulated by the alterations and revealed five biological processes that were significantly overrepresented among the affected genes: apoptosis, metabolism, macromolecule localization, translation, and transcription. Four genes on 3p (RYBP, GBE1 and 13q (FAM48A, MED4 correlated with outcome at both the gene dosage and expression level and were satisfactorily validated in the independent cohort. These integrated analyses yielded 57 candidate drivers of 24 genetic events, including novel loci responsible for chemoradioresistance. Further mapping of the connections among genetic events, drivers, and biological processes suggested that each individual event stimulates specific processes in carcinogenesis through the coordinated control of multiple genes. The present results may provide novel therapeutic opportunities of both early and advanced stage cervical cancers.

A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk.

Science.gov (United States)

Baltar, Valéria Troncoso; Xun, Wei W; Johansson, Mattias; Ferrari, Pietro; Chuang, Shu-Chun; Relton, Caroline; Ueland, Per Magne; Midttun, Øivind; Slimani, Nadia; Jenab, Mazda; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy; Kaaks, Rudolf; Rohrmann, Sabine; Boeing, Heiner; Weikert, Cornelia; Bueno-de-Mesquita, Bas; Boshuizen, Hendriek; van Gils, Carla H; Onland-Moret, N Charlotte; Agudo, Antonio; Barricarte, Aurelio; Navarro, Carmen; Rodríguez, Laudina; Castaño, José Maria Huerta; Larrañaga, Nerea; Khaw, Kay-Tee; Wareham, Nick; Allen, Naomi E; Crowe, Francesca; Gallo, Valentina; Norat, Teresa; Krogh, Vittorio; Masala, Giovanna; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Rasmuson, Torgny; Hallmans, Göran; Roswall, Nina; Tjønneland, Anne; Riboli, Elio; Brennan, Paul; Vineis, Paolo

2013-08-01

The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms.

Comparison of four software packages for CT lung volumetry in healthy individuals

Energy Technology Data Exchange (ETDEWEB)

Nemec, Stefan F. [Harvard Medical School, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA (United States); Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Molinari, Francesco [Centre Hospitalier Regional Universitaire de Lille, Department of Radiology, Lille (France); Dufresne, Valerie [CHU de Charleroi - Hopital Vesale, Pneumologie, Montigny-le-Tilleul (Belgium); Gosset, Natacha [CHU Tivoli, Service d' Imagerie Medicale, La Louviere (Belgium); Silva, Mario; Bankier, Alexander A. [Harvard Medical School, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA (United States)

2015-06-01

To compare CT lung volumetry (CTLV) measurements provided by different software packages, and to provide normative data for lung densitometric measurements in healthy individuals. This retrospective study included 51 chest CTs of 17 volunteers (eight men and nine women; mean age, 30 ± 6 years), who underwent spirometrically monitored CT at total lung capacity (TLC), functional residual capacity (FRC), and mean inspiratory capacity (MIC). Volumetric differences assessed by four commercial software packages were compared with analysis of variance (ANOVA) for repeated measurements and benchmarked against the threshold for acceptable variability between spirometric measurements. Mean lung density (MLD) and parenchymal heterogeneity (MLD-SD) were also compared with ANOVA. Volumetric differences ranged from 12 to 213 ml (0.20 % to 6.45 %). Although 16/18 comparisons (among four software packages at TLC, MIC, and FRC) were statistically significant (P < 0.001 to P = 0.004), only 3/18 comparisons, one at MIC and two at FRC, exceeded the spirometry variability threshold. MLD and MLD-SD significantly increased with decreasing volumes, and were significantly larger in lower compared to upper lobes (P < 0.001). Lung volumetric differences provided by different software packages are small. These differences should not be interpreted based on statistical significance alone, but together with absolute volumetric differences. (orig.)

Carcinogenesis and Inflammatory Effects of Plutonium-Nitrate Retention in an Exposed Nuclear Worker and Beagle Dogs

International Nuclear Information System (INIS)

Nielsen, Christopher E.; Wang, Xihai; Robinson, Robert J.; Brooks, Antone L.; Lovaglio, Jamie A.; Patton, Kristin M.; McComish, Stacey; Tolmachev, Sergei Y.; Morgan, William F.

2014-01-01

The genetic and inflammatory response pathways elicited following plutonium exposure in archival lung tissue of an occupationally exposed human and experimentally exposed beagle dogs were investigated. These pathways include: tissue injury, apoptosis and gene expression modifications related to carcinogenesis and inflammation. In order to determine which pathways are involved, multiple lung samples from a plutonium exposed worker (Case 0269), a human control (Case 0385), and plutonium exposed beagle dogs were examined using histological staining and immunohistochemistry. Examinations were performed to identify target tissues at risk of radiation-induced fibrosis, inflammation, and carcinogenesis. Case 0269 showed interstitial fibrosis in peripheral and subpleural regions of the lung, but no pulmonary tumors. In contrast, the dogs with similar and higher doses showed pulmonary tumors primarily in brochiolo-alveolar, peripheral and subpleural alveolar regions. The TUNEL assay showed slight elevation of apoptosis in tracheal mucosa, tumor cells, and nuclear debris was present in the inflammatory regions of alveoli and lymph nodes of both the human and the dogs. The expression of apoptosis and a number of chemokine/cytokine genes was slightly but not significantly elevated in protein or gene levels compared to that of the control samples. In the beagles, mucous production was increased in the airway epithelial goblet cells and glands of trachea, and a number of chemokine/cytokine genes showed positive immunoreactivity. This analysis of archival tissue from an accidentally exposed worker and in a large animal model provides valuable information on the effects of long-term retention of plutonium in the respiratory tract and the histological evaluation study may impact mechanistic studies of radiation carcinogenesis

Comparison of Four PD-L1 Immunohistochemical Assays in Lung Cancer.

Science.gov (United States)

Hendry, Shona; Byrne, David J; Wright, Gavin M; Young, Richard J; Sturrock, Sue; Cooper, Wendy A; Fox, Stephen B

2018-03-01

Four different programmed death ligand 1 immunohistochemical assays are approved or in development as companion or complementary diagnostics to different immunotherapeutic agents in lung carcinoma. We sought to determine whether these assays are technically equivalent and whether one antibody can be used on an alternate staining platform. Serial sections of tissue microarrays constructed from 368 cases of resected lung cancer were stained for 22C3 and 28-8 on the Dako Link 48 platform (Dako, Carpinteria, Ca) and for SP142 and SP263 on the Ventana Benchmark Ultra platform (Ventana Medical Systems, Tucson, AZ) strictly as per product insert. A protocol was developed to use the 22C3 antibody on the Ventana Benchmark Ultra platform. Differences in mean tumor cell and immune cell staining were observed between the four assays (p Link 48 platform and the alternate Ventana Benchmark Ultra platform (ICC = 0.921, κ = 0.897). Concordance between the four programmed death ligand 1 immunohistochemical assays when performed and scored as intended show that apart from 28-8 and 22C3, they cannot be used interchangeably in clinical practice. A protocol was successfully developed to use 22C3 on an alternate platform, which may help to overcome some barriers to implementation. Copyright © 2017 International Association for the Study of Lung Cancer. All rights reserved.

Inactivation of TGF-β signaling in lung cancer results in increased CDK4 activity that can be rescued by ELF

International Nuclear Information System (INIS)

Baek, Hye Jung; Kim, Sang Soo; Silva, Fabio May da; Volpe, Eugene A.; Evans, Stephen; Mishra, Bibhuti; Mishra, Lopa; Blair Marshall, M.

2006-01-01

Escape from TGF-β inhibition of proliferation is a hallmark of multiple cancers including lung cancer. We explored the role of ELF, crucial TGF-β adaptor protein identified from endodermal progenitor cells, in lung carcinogenesis and cell-cycle regulation. Interestingly, elf -/- mice develop multiple defects that include lung, liver, and cardiac abnormalities. Four out of 6 lung cancer and mesothelioma cell lines displayed deficiency of ELF expression with increased CDK4 expression. Immunohistochemistry and Western blot analysis of primary human lung cancers also showed decreased ELF expression and overexpression of CDK4. Moreover, rescue of ELF in ELF-deficient cell lines decreased the expression of CDK4 and resulted in accumulation of G1/S checkpoint arrested cells. These results suggest that disruption in TGF-β signaling mediated by loss of ELF in lung cancer leads to cell-cycle deregulation by modulating CDK4 and ELF highlights a key role of TGF-β adaptor protein in suppressing early lung cancer

Multi-walled carbon nanotube-induced gene expression in the mouse lung: Association with lung pathology

International Nuclear Information System (INIS)

Pacurari, M.; Qian, Y.; Porter, D.W.; Wolfarth, M.; Wan, Y.; Luo, D.; Ding, M.; Castranova, V.; Guo, N.L.

2011-01-01

Due to the fibrous shape and durability of multi-walled carbon nanotubes (MWCNT), concerns regarding their potential for producing environmental and human health risks, including carcinogenesis, have been raised. This study sought to investigate how previously identified lung cancer prognostic biomarkers and the related cancer signaling pathways are affected in the mouse lung following pharyngeal aspiration of well-dispersed MWCNT. A total of 63 identified lung cancer prognostic biomarker genes and major signaling biomarker genes were analyzed in mouse lungs (n = 80) exposed to 0, 10, 20, 40, or 80 μg of MWCNT by pharyngeal aspiration at 7 and 56 days post-exposure using quantitative PCR assays. At 7 and 56 days post-exposure, a set of 7 genes and a set of 11 genes, respectively, showed differential expression in the lungs of mice exposed to MWCNT vs. the control group. Additionally, these significant genes could separate the control group from the treated group over the time series in a hierarchical gene clustering analysis. Furthermore, 4 genes from these two sets of significant genes, coiled-coil domain containing-99 (Ccdc99), muscle segment homeobox gene-2 (Msx2), nitric oxide synthase-2 (Nos2), and wingless-type inhibitory factor-1 (Wif1), showed significant mRNA expression perturbations at both time points. It was also found that the expression changes of these 4 overlapping genes at 7 days post-exposure were attenuated at 56 days post-exposure. Ingenuity Pathway Analysis (IPA) found that several carcinogenic-related signaling pathways and carcinogenesis itself were associated with both the 7 and 11 gene signatures. Taken together, this study identifies that MWCNT exposure affects a subset of lung cancer biomarkers in mouse lungs. - Research highlights: → Multi-Walled Carbon Nanotubes affect lung cancer biomarkers in mouse lungs. → The results suggest potentially harmful effects of MWCNT exposure on human lungs. → The results could potentially be used

Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments

Science.gov (United States)

Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B.; Wang, Ya

2016-06-01

Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk.

Lung cancer and risk factors: how to identify phenotypic markers?

International Nuclear Information System (INIS)

Clement-Duchene, Christelle

2009-01-01

Lung cancer is the leading cause of death in the world. Most lung cancer are diagnosed at an advanced stage (IIIB and IV), with a poor prognosis. The main risk factors are well known like active smoking, and occupational exposure (asbestos), but 10 a 20% occur in never smokers. In this population, various studies have been conducted in order to identify possible risk factors, and although many have been identified, none seem to explain more than a small percentage of the cases. According to the histological types, adenocarcinoma is now the more frequent type, and its association with the main risk factors (tobacco exposure, asbestos exposure) is still studied. The tumoral location is associated with the exposure to the risk factors. Finally, the survival seems to be different between gender, and between smokers, and never smokers. All these characteristics are perhaps associated with different pathways of carcinogenesis. In this context, we have analyzed a cohort of 1493 patients with lung cancer in order to identify phenotypic markers, and to understand the mechanisms of the lung carcinogenesis. (author) [fr

1977 flywheel technology symposium proceedings. [Fifty-two papers

Energy Technology Data Exchange (ETDEWEB)

Chang, G.C.; Stone, R.G. (eds.)

1978-03-01

Fifty-two papers, four paper abstracts, and four brief summaries of panel discussions are presented on flywheel energy storage technology. A separate abstract was prepared for each of 41 papers for inclusion in DOE Energy Research Abstracts (ERA). Eleven papers were processed previously for inclusion in the data base. (PMA)

``Fifty-fifty`` - an unexpectedly successful start. Implementation of Agenda 21 results in energy savings in school buildings; ``Fifty-fifty`` - ein erfreulich erfolgreicher Start. Energieeinsparung durch praktizierte Agenda 21 in Schulen

Energy Technology Data Exchange (ETDEWEB)

Schafhausen, F. [Bundesministerium fuer Umwelt, Naturschutz und Reaktorsicherheit, Bonn (Germany)

1998-10-01

The idea of the `Fifty-Fifty` pilot project was conceived at the environmental department of the Hamburg municipal authority; its implementation took place in close cooperation with the department for schools, the young, and vocational training (`BSJB`). It started in October 94 and was finalized in June 97. After its successful completion, `Fifty-Fifty` meanwhile has the status of a permanent project.- For decades it has been known that public buildings consume added energy (power and heat) as well as water not only because technical devices are lacking or obsolete but also because of negligence and carelessness. `Fifty-Fifty` endeavours to bring about a change. (orig.) [Deutsch] Geschichte des `Fifty-fifty`-Modells: Die Idee wurde von der Hamburger Umweltbehoerde entwickelt und in enger Zusammenarbeit mit der Behoerde fuer Schule, Jugend und Berufsbildung (BSJB) umgesetzt. Der Modellversuch wurde im Oktober 1994 gestartet und im Juni 1997 abgeschlossen. Nach der erfolgreichen Beendigung des Modellversuchs hat `Fifty-fifty` mittlerweile den Status eines Dauerprojekts. Seit Jahrzehnten ist bekannt, dass in oeffentlich genutzten Gebaeuden nicht nur aufgrund fehlender oder veralteter technischer Ausstattung, sondern insbesondere auch wegen eines unsachgemaessen oder gedankenlosen Verhaltens mehr Energie (Strom und Waerme) und mehr Wasser verbraucht werden. `Fifty-fifty` tut etwas dagegen. (orig.)

Chemoprevention of Lung Cancer

Science.gov (United States)

Szabo, Eva; Mao, Jenny T.; Lam, Stephen; Reid, Mary E.

2013-01-01

Background: Lung cancer is the most common cause of cancer death in men and women in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk of developing lung cancer compared with lifetime never smokers. Chemoprevention refers to the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention. Methods: Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations. Results: None of the phase 3 trials with the agents β-carotene, retinol, 13-cis-retinoic acid, α-tocopherol, N-acetylcysteine, acetylsalicylic acid, or selenium has demonstrated beneficial and reproducible results. To facilitate the evaluation of promising agents and to lessen the need for a large sample size, extensive time commitment, and expense, surrogate end point biomarker trials are being conducted to assist in identifying the most promising agents for later-stage chemoprevention trials. With the understanding of important cellular signaling pathways and the expansion of potentially important targets, agents (many of which target inflammation and the arachidonic acid pathway) are being developed and tested which may prevent or reverse lung carcinogenesis. Conclusions: By integrating biologic knowledge, additional early-phase trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points. PMID:23649449

[Expression of various matrix metalloproteinases in mice with hyperoxia-induced acute lung injury].

Science.gov (United States)

Zhang, Xiang-feng; Ding, Shao-fang; Gao, Yuan-ming; Liang, Ying; Foda, Hussein D

2006-08-01

To investigate the role of matrix metalloproteinases (MMPs) and extracellular matrix metalloproteinase inducer (EMMPRIN) in the pathogenesis of acute lung injury induced by hyperoxia. Fifty four mice were exposed in sealed cages to >98% oxygen (for 24-72 hours), and another 18 mice to room air. The severity of lung injury was assessed, and the expression of mRNA and protein of MMP-2, MMP-9 and EMMPRIN in lung tissue, after exposure for 24, 48 and 72 hours of hyperoxia were studied by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Hyperoxia caused acute lung injury; this was accompanied by increased expression of an upregulation of MMP-2, MMP-9 and EMMPRIN mRNA and protein in lung tissues. Hyperoxia causes acute lung injury in mice; increases in MMP-2, MMP-9 and EMMPRIN may play an important role in the development of hyperoxia induced lung injury in mice.

Lung cancer in uranium miners: A tissue resource and pilot study. Progress report, September 25, 1992 - May 31, 1993

International Nuclear Information System (INIS)

Samet, J.M.

1993-05-01

This project involves two related activities directed toward understanding respiratory carcinogenesis in radon-exposed former uranium miners. The first activity involves a continuation of the tissue resource of lung cancer cases from former underground uranium miners and comparison cases from non-miners. The second activity is a pilot study for a proposed longitudinal study of respiratory carcinogenesis in former uranium miners. The objectives are to facilitate the investigation of molecular changes in radon exposed lung cancer cases and to develop methods for prospectively studying clinical, cytologic, cytogenetic, and molecular changes in the multi-event process of respiratory carcinogenesis, and to assess the feasibility of recruiting former uranium miners into a longitudinal study that collects multiple biologic specimens

Estrogen, Estrogen Receptor and Lung Cancer

Directory of Open Access Journals (Sweden)

Li-Han Hsu

2017-08-01

Full Text Available Estrogen has been postulated as a contributor for lung cancer development and progression. We reviewed the current knowledge about the expression and prognostic implications of the estrogen receptors (ER in lung cancer, the effect and signaling pathway of estrogen on lung cancer, the hormone replacement therapy and lung cancer risk and survival, the mechanistic relationship between the ER and the epidermal growth factor receptor (EGFR, and the relevant clinical trials combining the ER antagonist and the EGFR antagonist, to investigate the role of estrogen in lung cancer. Estrogen and its receptor have the potential to become a prognosticator and a therapeutic target in lung cancer. On the other hand, tobacco smoking aggravates the effect of estrogen and endocrine disruptive chemicals from the environment targeting ER may well contribute to the lung carcinogenesis. They have gradually become important issues in the course of preventive medicine.

The American oil industry and the Fifty-Fifty Agreement of 1950

International Nuclear Information System (INIS)

Anderson, T.H.

1988-01-01

This paper traces the history of the Fifty-fifty Agreement of 1950, and the role of the American oil industry in that agreement. Regardless of the definition one chooses for the term foreign policy, it can now be argued with considerable force that the Fifty-fifty Agreement was, in fact, the product of American foreign policy. Defining the term narrowly as the enunciated policy of the Executive Branch of Government on matters outside the national boundary, it is clear that a consistent policy had been in place for a long time supporting exactly the type of action which was taken hear. Defining the term broadly, as the defacto cumulative thrust of all competing interest groups within a nation-state (both governmental and private) outside the national boundary, makes the assertion even more clear. Including Aramco and the parent companies in the equation leaves little doubt that the Fifty-fifty Agreement was the product of American foreign policy

Radiation carcinogenesis

International Nuclear Information System (INIS)

Adams, G.E.

1987-01-01

In this contribution about carcinogenesis induced by ionizing radiation some radiation dose-response relationships are discussed. Curves are shown of the relation between cell survival and resp. low and high LET radiation. The difference between both curves can be ascribed to endogenous repair mechanisms in the cell. The relation between single-gen mutation frequency and the surviving fractions of irradiated cells indicates that these repairing mechanisms are not error free. Some examples of reverse dose-response relationships are presented in which decreasing values of dose-rate (LET) correspond with increasing radiation induced cell transformation. Finally some molecular aspects of radiation carcinogenesis are discussed. (H.W.). 22 refs.; 4 figs

Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments.

Science.gov (United States)

Wang, Jian; Zhang, Xiangming; Wang, Ping; Wang, Xiang; Farris, Alton B; Wang, Ya

2016-06-01

Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk. Copyright © 2016 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Molecular characterization of radon-induced rat lung tumors

International Nuclear Information System (INIS)

Guillet Bastide, K.

2008-11-01

The radon gas is a well known lung carcinogenic factor in human at high doses but the cancer risk at low doses is not established. Indeed, epidemiological studies at low doses are difficult to conduct because of the human exposure to other lung carcinogenic factors. These data underlined the necessity to conduct experiments on lung tumors developed on animal model. The aim of this work was to characterize rat lung tumors by working on a series of radon-induced tumors that included adenocarcinomas (A.C.), squamous cell carcinomas (S.C.C.) and adeno-squamous carcinomas (A.S.C.), that are mixed tumors with both A.C. and S.C.C. cellular components. A C.G.H. analysis of the three types of tumors allowed us to define chromosomal recurrent unbalances and to target candidate genes potentially implicated in lung carcinogenesis, as p16Ink4a, p19Arf, Rb1, K-Ras or c-Myc. A more precise analysis of the p16Ink4a/Cdk4/Rb1 and p19Arf/Mdm2/Tp53 pathways was performed and indicated that the Rb1 pathway was frequently inactivated through an absence of p16 Ink4a protein expression, indicating that it has a major role in rat lung carcinogenesis. Finally, a comparative transcriptomic analysis of the three types of tumors allowed us to show for the first time that the complex tumors A.S.C. have a transcriptomic profile in accordance with their mixed nature but that they also display their own expression profiles specificities. This work allowed us to find molecular characteristics common to murine and human lung tumors, indicating that the model of lung tumors in rat is pertinent to search for radiation-induced lung tumors specificities and to help for a better molecular identification of this type of tumors in human. (author)

Recent progress in nickel carcinogenesis. [Cornybacterium; E. coli; S. typhimurium; B. subtillis

Energy Technology Data Exchange (ETDEWEB)

Sunderman, F.W. Jr.

1984-01-01

Research on nickel carcinogenesis from 1979 to 1983 is reviewed. Epidemiological studies have strengthened the evidence that workers in nickel refineries have increased risks of lung and sinonasal cancers, but have not substantiated increased risks of respiratory cancers in other nickel-exposed workers. Carcinogenesis bioassays have demonstrated carcinogenicity of certain nickel sulfide, hydroxide, selenide, arsenide, antimonide, and telluride compounds following parenteral administration to rodents. Positive bacterial mutagenesis tests have been obtained with Ni(II) in Cornybacterium, but not in E. coli, S. typhimurium, or B. subtilis. Transformation assays of several soluble and crystalline Ni compounds have been positive in Syrian hamster embryo cells. Ni(II) binds to DNA, RNA, and nucleoproteins, and becomes localized in nucleoli. Genotoxic effects of Ni include: (a) chromosomal aberrations, including sister-chromatid exchanges, (b) DNA strandbreaks and DNA-protein cross-links, (c) inhibition of DNA and RNA synthesis, (d) infidelity of DNA transcription, and (e) mutations at the HGPRTase locus in Chinese hamster cells and the TK locus in mouse lymphoma cells. These findings are consistent with somatic mutation as the mechanism for initiation of nickel carcinogenesis. Ni compounds cause reversible transition of double-stranded poly(dG-dC) DNA from the right-handed B-helix to the left-handed Z-helix, suggesting a mechanism whereby nickel might modulate oncogene expression. 99 references, 6 tables.

Mechanisms of radiation carcinogenesis

International Nuclear Information System (INIS)

Bekkum, D.W. van

1975-01-01

This speculative review on radiation carcinogenesis deals mainly with its immunological aspects. It need not be emphasized that the role of immunology in carcinogenesis is not yet well understood. Immunological aspects of radiation carcinogenesis comprise a large number of different parameters on the part of the host as well as on the part of the tumor itself. Only two aspects, both related to radiation, will be discussed here. One is the way in which the carcinogenic exposure to ionizing radiation may affect the immune reactivity of the irradiated organism, thereby perhaps changing its responses against the malignant cells. The second aspect is the immunological properties of cells transformed by ionizing irradiation, which may provide the targets for a host-anti-tumor reaction

Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

Directory of Open Access Journals (Sweden)

G-Andre Banat

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

Role of bacteria in oral carcinogenesis

Directory of Open Access Journals (Sweden)

R Rajeev

2012-01-01

Full Text Available Oral cancer is the most common cancer diagnosed in Indian men and is the leading cause of cancer deaths. It is considered as a multistep and multifactorial disease. Besides accumulation of genetic mutations, numerous other carcinogens are involved. In this category, viral and chemical carcinogens are well studied and documented. However, in the oral cavity, the role of microbiota in carcinogenesis is not known. Microbial populations on mouth mucosa differ between healthy and malignant sites, and certain oral bacterial species have been linked with malignancies, but the evidence is still weak in this respect. Nevertheless, oral microorganisms inevitably up-regulate cytokines and other inflammatory mediators that affect the complex metabolic pathways, and may thus be involved in carcinogenesis. Poor oral health associates statistically with prevalence of many types of cancer such as pancreatic and gastrointestinal cancer. This review presents possible carcinogenesis pathway involved in bacterial carcinogenesis, commonly implicated bacteria in oral carcinogenesis, and their role in cancer therapeutics as well.

Radionuclides in cigarettes may lead to carcinogenesis via p16INK4a inactivation

International Nuclear Information System (INIS)

Prueitt, Robyn L.; Goodman, Julie E.; Valberg, Peter A.

2009-01-01

It is widely accepted that tobacco smoke is responsible for the vast majority of lung cancers worldwide. There are many known and suspected carcinogens present in cigarette smoke, including α-emitting radioisotopes. Epidemiologic studies have shown that increased lung cancer risk is associated with exposure to ionizing radiation, and it is estimated that the majority of smoking-induced lung cancers may be at least partly attributable to the inhaled and deposited radiation dose from radioisotopes in the cigarette smoke itself. Recent research shows that silencing of the tumor suppressor gene p16 INK4a (p16) by promoter methylation plays a role in smoking-related lung cancer. Inactivation of p16 has also been associated with lung cancer incidence in radiation-exposed workers, suggesting that radionuclides in cigarette smoke may be acting with other compounds to cause smoking-induced lung cancer. We evaluated the mechanism of ionizing radiation as an accepted cause of lung cancer in terms of its dose from tobacco smoke and silencing of p16. Because both radiation and cigarette smoking are associated with inactivation of p16, and p16 inactivation has been shown to play a major role in carcinogenesis, ionizing radiation from cigarette smoke likely plays a role in lung cancer risk. How large a role it plays, relative to chemical carcinogens and other modes of action, remains to be elucidated

Influence of quartz exposure on lung cancer types in cases of lymph node-only silicosis and lung silicosis in German uranium miners.

Science.gov (United States)

Mielke, Stefan; Taeger, Dirk; Weitmann, Kerstin; Brüning, Thomas; Hoffmann, Wolfgang

2018-05-04

Inhaled crystalline quartz is a carcinogen. Analyses show differences in the distribution of lung cancer types depending on the status of silicosis. Using 2,524 lung tumor cases from the WISMUT autopsy repository database, silicosis was differentiated into cases without silicosis in lung parenchyma and its lymph nodes, with lymph node-only silicosis, or with lung silicosis including lymph node silicosis. The proportions of adenocarcinoma, squamous cell carcinoma, and small-cell lung carcinoma mortality for increasing quartz exposures were estimated in a multinomial logistic regression model. The relative proportions of the lung cancer subtypes in lymph node-only silicosis were more similar to lung silicosis than without any silicosis. The results support the hypothesis that quartz-related carcinogenesis in case of lymph node-only silicosis is more similar to that in lung silicosis than in without silicosis.

Epigenetic mechanism of radiation carcinogenesis

International Nuclear Information System (INIS)

Niwa, Ohtsura

1995-01-01

Carcinogenic action of radiations has long been thought to be due to its mutagenic activity. Since DNA damage is induced and distributes in a stochastic fashion, radiation induction of cancers was also assumed to follow a stochastic kinetics. However, recent progress in radiation research has revealed that some features of radiation carcinogenesis are not explainable by the simple action of radiation as a DNA damaging and mutagenic agent. Firstly, frequencies of radiation-induced transformation in vitro and radiation-induced mammary cancers in rats are too high to be accounted for by the frequency of radiation-induced mutation. Secondly, trans-generation carcinogenesis among F1 mice born to irradiated parents occurs also much more frequently than to be predicted by the frequency of radiation induced germline mutation. Thirdly, multistage carcinogenesis theory predicts that carcinogens give hits to the target cells so as to shorten the latency of cancers. However, latencies of radiation induced solid cancers among atomic bomb survivors are similar to those of the control population. Fourthly, although radiation elevates the frequency of cancers, the induced cancers seem to share the same spectrum of cancer types as in the unirradiated control populations. This suggests that radiation induces cancer by enhancement of the spontaneous carcinogenesis process. These data suggest that the first step of radiation carcinogenesis may not be the direct induction of mutation. Radiation may induce genetic instability which increases the spontaneous mutation rate in the cells to produce carcinogenic mutations. Growth stimulatory effect of radiation may also contribute to the process. Thus, epigenetic, but not genetic effect of radiation might better contribute in the process of carcinogenesis. (author)

Bacterial and fungal microflora in surgically removed lung cancer samples

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Toloudi Maria

2011-10-01

Full Text Available Abstract Background Clinical and experimental data suggest an association between the presence of bacterial and/or fungal infection and the development of different types of cancer, independently of chemotherapy-induced leukopenia. This has also been postulated for the development of lung cancer, however the prevalence and the exact species of the bacteria and fungi implicated, have not yet been described. Aim To determine the presence of bacterial and fungal microflora in surgically extracted samples of patients with lung cancer. Materials and methods In this single-center prospective, observational study, tissue samples were surgically extracted from 32 consecutive patients with lung cancer, and reverse-transcription polymerase chain reaction (RT-PCR was used to identify the presence of bacteria and fungi strains. Results The analysis of the electrophoresis data pointed out diversity between the samples and the strains that were identified. Mycoplasma strains were identified in all samples. Strains that appeared more often were Staphylococcus epidermidis, Streptococcus mitis and Bacillus strains, followed in descending frequency by Chlamydia, Candida, Listeria, and Haemophilus influenza. In individual patients Legionella pneumophila and Candida tropicalis were detected. Conclusions A diversity of pathogens could be identified in surgically extracted tissue samples of patients with lung cancer, with mycoplasma strains being present in all samples. These results point to an etiologic role for chronic infection in lung carcinogenesis. Confirmation of these observations and additional studies are needed to further characterize the etiologic role of inflammation in lung carcinogenesis.

Experimental radiation carcinogenesis is studies at NIRS

International Nuclear Information System (INIS)

Sado, Toshihiko

1992-01-01

Experimental radiation carcinogenesis studies conducted during the past decade at NIRS are briefly reviewed. They include the following: 1) Age dependency of susceptibility to radiation carcinogenesis. 2) Radiation-induced myeloid leukemia. 3) Mechanism of fractionated X-irradiation (FX) induced thymic lymphomas. 4) Significance of radiation-induced immunosuppression in radiation carcinogenesis in vivo. 5) Other ongoing studies. (author)

TP53 Mutations in Nonsmall Cell Lung Cancer

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Akira Mogi

2011-01-01

Full Text Available The tumor suppressor gene TP53 is frequently mutated in human cancers. Abnormality of the TP53 gene is one of the most significant events in lung cancers and plays an important role in the tumorigenesis of lung epithelial cells. Human lung cancers are classified into two major types, small cell lung cancer (SCLC and nonsmall cell lung cancer (NSCLC. The latter accounts for approximately 80% of all primary lung cancers, and the incidence of NSCLC is increasing yearly. Most clinical studies suggest that NSCLC with TP53 alterations carries a worse prognosis and may be relatively more resistant to chemotherapy and radiation. A deep understanding of the role of TP53 in lung carcinogenesis may lead to a more reasonably targeted clinical approach, which should be exploited to enhance the survival rates of patients with lung cancer. This paper will focus on the role of TP53 in the molecular pathogenesis, epidemiology, and therapeutic strategies of TP53 mutation in NSCLC.

Effects of Physalis peruviana L on Toxicity and Lung Cancer Induction by Nicotine Derived Nitrosamine Ketone in Rats.

Science.gov (United States)

El-Kenawy, Ayman El-Meghawry; Elshama, Said Said; Osman, Hosam-Eldin Hussein

2015-01-01

Nicotine-derived nitrosamine ketone (NNK) is considered a key tobacco smoke carcinogen inducing lung tumors. Physalis peruviana L (harankash) is considered one plant with marked health benefits. This study aimed to evaluate Physalis peruviana L effect on the toxic effect of NNK induced lung cancer in the rats by using pulmonary histopathological, immunohistochemical and DNA flow cytometric analyses. Sixty adult male rats were divided into four groups, each consisting of fifteen animals. The first group received saline, the second received two successive toxic doses of NNK only while the third received two successive toxic doses of NNK with a single daily dose of Physalis peruviana L. The fourth group received a single daily dose of Physalis peruviana L only. Toxic doses of NNK induced hyperplasia and adenocarcinoma in the lung and positive immunoreactivity for Ki-67 and p53 staining with disturbance of the lung DNA content. Administration of Physalis peruviana L with NNK led to a mild pulmonary hyperplasia and weak expression of Ki-67 and p53 with an improvement in the lung DNA content. Physalis peruviana L may protect against NNK induced lung carcinogenesis due to its antioxidant and anti-proliferative effects.

Epidemiology of Lung Cancer

Science.gov (United States)

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

2013-01-01

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

Transplacental arsenic carcinogenesis in mice

International Nuclear Information System (INIS)

Waalkes, Michael P.; Liu, Jie; Diwan, Bhalchandra A.

2007-01-01

Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show that a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from days 8 to 18 of gestation, and the offspring were observed for up to 2 years. The doses used in all these studies were well tolerated by both the dam and offspring. In C3H mice, two separate studies show male offspring exposed to arsenic in utero developed liver carcinoma and adrenal cortical adenoma in a dose-related fashion during adulthood. Prenatally exposed female C3H offspring show dose-related increases in ovarian tumors and lung carcinoma and in proliferative lesions (tumors plus preneoplastic hyperplasia) of the uterus and oviduct. In addition, prenatal arsenic plus postnatal exposure to the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) in C3H mice produces excess lung tumors in both sexes and liver tumors in females. Male CD1 mice treated with arsenic in utero develop tumors of the liver and adrenal and renal hyperplasia while females develop tumors of urogenital system, ovary, uterus and adrenal and hyperplasia of the oviduct. Additional postnatal treatment with diethylstilbestrol or tamoxifen after prenatal arsenic in CD1 mice induces urinary bladder transitional cell proliferative lesions, including carcinoma and papilloma, and enhances the carcinogenic response in the liver of both sexes. Overall this model has provided convincing evidence that arsenic is a transplacental carcinogen in mice with the ability to target tissues of potential human relevance, such as the urinary bladder, lung and liver. Transplacental carcinogenesis clearly occurs with other agents in humans

Environmental carcinogenesis and genetic variability

International Nuclear Information System (INIS)

Knudsen, A.G. Jr

1977-01-01

It was found that carcinogenesis in man may involve the interaction of genetic and environmental forces, and that mutation, whether germinal or somatic, seems to be involved in the origin of many, perhaps all cancers. The cancers of man may be visualized as occurring in four groups of individuals according to whether (1) neither genetic nor environmental factors are dominant, i.e. 'background' or 'spontaneous' cancer, (2) heredity alone is dominant, (3) environment alone is important, or (4) both are operating (Knudsen, 1977). The last two groups together are widely thought to contribute 70-80% of cancer cases in the United States; the relative contribution of each group is a major question to be answered

Comparative evaluation of carcinogenesis risk in case of radiation effect and pollution of atmospheric air with coal ashes and benzo(a)pyrene

International Nuclear Information System (INIS)

Knizhnikov, V.A.; Shandala, N.K.; Komleva, V.A.; Likhovajdo, N.V.; Shvetsov, A.I.

1993-01-01

Assessment of the risk of lung carcinogenesis under the effect of benzo(a)pyrene (BP) and volatil coal ash in the atmospheric air was performed as well as comparison of this risk with the risk due to ionizing radiation effect from natural and technogenic sources. White mice were used as experimental animals. It was shown that BP was rather more carcinogenic than volatile coal ash. BP inhalation at a maximum permissible concentration level (0.1 μg/100 m 3 of air) corresponds to the equivalent risk of whole-body gamma exposure at bout 2 Sv. Coal ash inhalation at the concentration of 0.05 mg/m 3 corresponds to the same equivalent risk as for radiation dose 0.05 Sv. Conclusion is made that safety standards for coal ash and BP contents in the air do not remove carcinogenesis risk for the population. Whereas carcinogenesis risk due to irradiation at the level of radiation safety standards is considerably lower

Investigation of four-dimensional computed tomography-based pulmonary ventilation imaging in patients with emphysematous lung regions

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Yamamoto, Tokihiro; Loo, Billy W Jr; Keall, Paul J [Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Dr, Stanford, CA 94305-5847 (United States); Kabus, Sven; Lorenz, Cristian; Von Berg, Jens; Blaffert, Thomas [Department of Digital Imaging, Philips Research Europe, Roentgenstrasse 24-26, D-22335 Hamburg (Germany); Klinder, Tobias, E-mail: Tokihiro@stanford.edu [Clinical Informatics, Interventional, and Translational Solutions, Philips Research North America, Briarcliff Manor, NY 10510 (United States)

2011-04-07

A pulmonary ventilation imaging technique based on four-dimensional (4D) computed tomography (CT) has advantages over existing techniques. However, physiologically accurate 4D-CT ventilation imaging has not been achieved in patients. The purpose of this study was to evaluate 4D-CT ventilation imaging by correlating ventilation with emphysema. Emphysematous lung regions are less ventilated and can be used as surrogates for low ventilation. We tested the hypothesis: 4D-CT ventilation in emphysematous lung regions is significantly lower than in non-emphysematous regions. Four-dimensional CT ventilation images were created for 12 patients with emphysematous lung regions as observed on CT, using a total of four combinations of two deformable image registration (DIR) algorithms: surface-based (DIR{sup sur}) and volumetric (DIR{sup vol}), and two metrics: Hounsfield unit (HU) change (V{sub HU}) and Jacobian determinant of deformation (V{sub Jac}), yielding four ventilation image sets per patient. Emphysematous lung regions were detected by density masking. We tested our hypothesis using the one-tailed t-test. Visually, different DIR algorithms and metrics yielded spatially variant 4D-CT ventilation images. The mean ventilation values in emphysematous lung regions were consistently lower than in non-emphysematous regions for all the combinations of DIR algorithms and metrics. V{sub HU} resulted in statistically significant differences for both DIR{sup sur} (0.14 {+-} 0.14 versus 0.29 {+-} 0.16, p = 0.01) and DIR{sup vol} (0.13 {+-} 0.13 versus 0.27 {+-} 0.15, p < 0.01). However, V{sub Jac} resulted in non-significant differences for both DIR{sup sur} (0.15 {+-} 0.07 versus 0.17 {+-} 0.08, p = 0.20) and DIR{sup vol} (0.17 {+-} 0.08 versus 0.19 {+-} 0.09, p = 0.30). This study demonstrated the strong correlation between the HU-based 4D-CT ventilation and emphysema, which indicates the potential for HU-based 4D-CT ventilation imaging to achieve high physiologic accuracy. A

Accumulation of radium in ferruginous protein bodies formed in lung tissue. Association of resulting radiation hotspots with malignant mesothelioma and other malignancies

International Nuclear Information System (INIS)

Nakamura, Eizo; Makishima, Akio; Hagino, Kyoko; Okabe, Kazunori

2009-01-01

While exposure to fibers and particles has been proposed to be associated with several different lung malignancies including mesothelioma, the mechanism for the carcinogenesis is not fully understood. Along with mineralogical observation, we have analyzed forty-four major and trace elements in extracted asbestos bodies (fibers and proteins attached to them) with coexisting fiber-free ferruginous protein bodies from extirpative lungs of individuals with malignant mesothelioma. These observations together with patients' characteristics suggest that inhaled iron-rich asbestos fibers and dust particles, and excess iron deposited by continuous cigarette smoking would induce ferruginous protein body formation resulting in ferritin aggregates in lung tissue. Chemical analysis of ferruginous protein bodies extracted from lung tissues reveals anomalously high concentrations of radioactive radium, reaching millions of times higher concentration than that of seawater. Continuous and prolonged internal exposure to hotspot ionizing radiation from radium and its daughter nuclides could cause strong and frequent DNA damage in lung tissue, initiate different types of tumour cells, including malignant mesothelioma cells, and may cause cancers. (author)

Molecular and cytogenetic characterization of radon-induced lung tumors in the rat

International Nuclear Information System (INIS)

Dano, Laurent

2000-01-01

Radon is a natural radioactive gas. This radioelement, which is an α-particle emitter, is omnipresent in the environment. Inhalation of atmospheric radon is the major exposure route in man of natural radioactivity which results in respiratory tract contamination. An increased lung cancer risk associated with radon inhalation has been shown both in humans and animals by epidemiological and experimental studies, respectively. In rats, characterization of dose-effect relationships has led to the construction of statistical models that may help theoretically in the prediction of human health involvements of both occupational and domestic chronic exposure to radon. However, little is known about the cellular and molecular mechanisms of radon-induced lung carcinogenesis. In the laboratory, a model of lung cancers induced in rats after radon inhalation is available. This model represents a good tool to identify and characterize the genetic events contributing to the development of radon-induced lung tumors. Carrying out a global approach based on the combined use of classical and molecular cytogenetic methods, the analysis of 17 neoplasms allowed the identification of chromosomal regions frequently altered in these tumors. Numerous similarities have been found between our results and the cytogenetic data for human lung cancers, suggesting common underlying genetic molecular mechanisms for lung cancer development in both species. Moreover, our study has allowed to point to tumor suppressor genes and proto-oncogenes potentially involved in radon-induced lung carcinogenesis. Thus, our results may aid further molecular studies aimed either at confirming the role of these candidate genes or at demonstrating the involvement of yet to be identified genes. (author) [fr

Fifty shades of exploitation: Fan labor and Fifty Shades of Grey

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Bethan Jones

2014-03-01

Full Text Available This exploration of the debates that have taken place in fandom over the ethics of pulling fan fiction and publishing it as original work draws on the notion of the fannish gift economy, which postulates that gifts such as fan fiction and fan art have value in the fannish community because they are designed to create and cement its social structure. Tension exists between fans who subscribe to the notion of a fannish gift economy and those who exploit fandom by using it to sell their pulled-to-publish works. An examination of E. L. James's 2012 Fifty Shades trilogy (comprising the books Fifty Shades of Grey, Fifty Shades Darker, and Fifty Shades Freed, which began as Twilight fan fiction, in addition to Twilight fan art sold through sites such as Redbubble and Etsy, demonstrates a tension between the two modes of fan expression: sale of artworks appears to be an acceptable practice in fandom, but the commercial sale of fan fic, even when marketed as original fiction, is widely contested.

Application of artificial neural network model combined with four biomarkers in auxiliary diagnosis of lung cancer.

Science.gov (United States)

Duan, Xiaoran; Yang, Yongli; Tan, Shanjuan; Wang, Sihua; Feng, Xiaolei; Cui, Liuxin; Feng, Feifei; Yu, Songcheng; Wang, Wei; Wu, Yongjun

2017-08-01

The purpose of the study was to explore the application of artificial neural network model in the auxiliary diagnosis of lung cancer and compare the effects of back-propagation (BP) neural network with Fisher discrimination model for lung cancer screening by the combined detections of four biomarkers of p16, RASSF1A and FHIT gene promoter methylation levels and the relative telomere length. Real-time quantitative methylation-specific PCR was used to detect the levels of three-gene promoter methylation, and real-time PCR method was applied to determine the relative telomere length. BP neural network and Fisher discrimination analysis were used to establish the discrimination diagnosis model. The levels of three-gene promoter methylation in patients with lung cancer were significantly higher than those of the normal controls. The values of Z(P) in two groups were 2.641 (0.008), 2.075 (0.038) and 3.044 (0.002), respectively. The relative telomere lengths of patients with lung cancer (0.93 ± 0.32) were significantly lower than those of the normal controls (1.16 ± 0.57), t = 4.072, P < 0.001. The areas under the ROC curve (AUC) and 95 % CI of prediction set from Fisher discrimination analysis and BP neural network were 0.670 (0.569-0.761) and 0.760 (0.664-0.840). The AUC of BP neural network was higher than that of Fisher discrimination analysis, and Z(P) was 0.76. Four biomarkers are associated with lung cancer. BP neural network model for the prediction of lung cancer is better than Fisher discrimination analysis, and it can provide an excellent and intelligent diagnosis tool for lung cancer.

Comparison of lung cancer cell lines representing four histopathological subtypes with gene expression profiling using quantitative real-time PCR

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Kawaguchi Makoto

2010-01-01

Full Text Available Abstract Background Lung cancers are the most common type of human malignancy and are intractable. Lung cancers are generally classified into four histopathological subtypes: adenocarcinoma (AD, squamous cell carcinoma (SQ, large cell carcinoma (LC, and small cell carcinoma (SC. Molecular biological characterization of these subtypes has been performed mainly using DNA microarrays. In this study, we compared the gene expression profiles of these four subtypes using twelve human lung cancer cell lines and the more reliable quantitative real-time PCR (qPCR. Results We selected 100 genes from public DNA microarray data and examined them by DNA microarray analysis in eight test cell lines (A549, ABC-1, EBC-1, LK-2, LU65, LU99, STC 1, RERF-LC-MA and a normal control lung cell line (MRC-9. From this, we extracted 19 candidate genes. We quantified the expression of the 19 genes and a housekeeping gene, GAPDH, with qPCR, using the same eight cell lines plus four additional validation lung cancer cell lines (RERF-LC-MS, LC-1/sq, 86-2, and MS-1-L. Finally, we characterized the four subtypes of lung cancer cell lines using principal component analysis (PCA of gene expression profiling for 12 of the 19 genes (AMY2A, CDH1, FOXG1, IGSF3, ISL1, MALL, PLAU, RAB25, S100P, SLCO4A1, STMN1, and TGM2. The combined PCA and gene pathway analyses suggested that these genes were related to cell adhesion, growth, and invasion. S100P in AD cells and CDH1 in AD and SQ cells were identified as candidate markers of these lung cancer subtypes based on their upregulation and the results of PCA analysis. Immunohistochemistry for S100P and RAB25 was closely correlated to gene expression. Conclusions These results show that the four subtypes, represented by 12 lung cancer cell lines, were well characterized using qPCR and PCA for the 12 genes examined. Certain genes, in particular S100P and CDH1, may be especially important for distinguishing the different subtypes. Our results

Amiodarone is a cost-neutral way of preventing atrial fibrillation after surgery for lung cancer

DEFF Research Database (Denmark)

Riber, Lars P.; Christensen, Thomas D.; Pilegaard, Hans K.

2014-01-01

OBJECTIVES: Our aim was to estimate the costs and health benefits of routinely administered postoperative amiodarone as a prophylactic agent in reducing the risk of atrial fibrillation in patients undergoing surgery for lung cancer. METHODS: This was a cost-effectiveness study, based.......23). There were no signs of adverse developments referable to amiodarone in this prophylactic regime. CONCLUSIONS: For patients undergoing surgery for lung cancer, routine use of postoperative prophylactic intravenous bolus and five subsequent days of oral amiodarone therapy reduces the risk of atrial...... on the randomized, controlled, double-blinded PASCART study, using avoidance of atrial fibrillation as the measure of benefit. Two hundred and fifty-four eligible, consecutively enrolled patients, undergoing surgery for lung cancer at the department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital...

Lung cancer in uranium miners: A tissue resource and pilot study. Final performance report

International Nuclear Information System (INIS)

Samet, J.; Gilliland, F.D.

1998-01-01

This project incorporates two related research projects directed toward understanding respiratory carcinogenesis in radon-exposed former uranium miners. The first project involved a continuation of the tissue resource of lung cancer cases from former underground uranium miners and comparison cases from non-miners. The second project was a pilot study for a proposed longitudinal study of respiratory carcinogenesis in former uranium miners. The objectives including facilitating the investigation of molecular changes in radon exposed lung cancer cases, developing methods for prospectively studying clinical, cytologic, cytogenetic, and molecular changes in the multi-event process of respiratory carcinogenesis, and assessing the feasibility of recruiting former uranium miners into a longitudinal study that collected multiple biological specimens. A pilot study was conducted to determine whether blood collection, induced sputum, bronchial brushing, washings, and mucosal biopsies from participants at two of the hospitals could be included efficiently. A questionnaire was developed for the extended study and all protocols for specimen collection and tissue handling were completed. Resource utilization is in progress at ITRI and the methods have been developed to study molecular and cellular changes in exfoliated cells contained in sputum as well as susceptibility factors

Lung cancer in uranium miners: A tissue resource and pilot study. Final performance report

Energy Technology Data Exchange (ETDEWEB)

Samet, J.; Gilliland, F.D.

1998-08-13

This project incorporates two related research projects directed toward understanding respiratory carcinogenesis in radon-exposed former uranium miners. The first project involved a continuation of the tissue resource of lung cancer cases from former underground uranium miners and comparison cases from non-miners. The second project was a pilot study for a proposed longitudinal study of respiratory carcinogenesis in former uranium miners. The objectives including facilitating the investigation of molecular changes in radon exposed lung cancer cases, developing methods for prospectively studying clinical, cytologic, cytogenetic, and molecular changes in the multi-event process of respiratory carcinogenesis, and assessing the feasibility of recruiting former uranium miners into a longitudinal study that collected multiple biological specimens. A pilot study was conducted to determine whether blood collection, induced sputum, bronchial brushing, washings, and mucosal biopsies from participants at two of the hospitals could be included efficiently. A questionnaire was developed for the extended study and all protocols for specimen collection and tissue handling were completed. Resource utilization is in progress at ITRI and the methods have been developed to study molecular and cellular changes in exfoliated cells contained in sputum as well as susceptibility factors.

Lung cancer in the Kashmir valley

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Koul Parvaiz

2010-01-01

Full Text Available Background: Lung cancer has been found to be the second commonest cancer according to a hospital-based data from Kashmir, India. However, no incidence studies are available. Objective: To ascertain the incidence of lung cancer in Kashmir. Materials and Methods: All newly histologically diagnosed cases of lung cancer seen in various hospital and private laboratories of the Kashmir valley were registered over a period of two years (January 1, 2004 to December 31, 2005. Also included were patients attending the various oncological service areas of the institute and those diagnosed from any other laboratory outside the state. The incidence rate was calculated using the January 2005 population as the reference population estimated using the census-based projected populations. Results: Four hundred and sixty-two incident cases of lung cancer were seen during the study period. The crude incidence rate, age standardized (world and truncated age adjusted (40-69 years, world incidence rates for lung cancer per 100 000 population were 4.01, 6.48 and 15.28 respectively (males 6.55, 10.09 and 23.94 respectively and females 1.19, 2.14 and 4.65. The age adjusted rates for males in district Srinagar was 19.34 per 100 000. One hundred and fifty nine (69.8% of the 221 had a history of Hukkah smoking. Conclusions: Even though Kashmir as a whole is a low incidence area for lung cancer (ASR of < 15, Srinagar district has the highest incidence of lung cancer among the males in Kashmir. The data presented is assumed to be the closest approximation to a population-based data registry and the geographical incidence maps of ICMR need appropriate updating

Mutagenesis and carcinogenesis resulting from environment pollution

International Nuclear Information System (INIS)

Dimitrov, B.

2001-01-01

The paper reviews different ways of environmental contamination with natural and artificial harmful substances (chemical and radioactive) and their role in the processes of mutagenesis and carcinogenesis. The recent studies of the mechanism of mutagenesis and carcinogenesis due to environmental pollution are discussed

Baicalein inhibits pulmonary carcinogenesis-associated inflammation and interferes with COX-2, MMP-2 and MMP-9 expressions in-vivo

Energy Technology Data Exchange (ETDEWEB)

Chandrashekar, Naveenkumar; Selvamani, Asokkumar; Subramanian, Raghunandhakumar; Pandi, Anandakumar; Thiruvengadam, Devaki, E-mail: devakit@yahoo.co.uk

2012-05-15

The objective of the present study is to investigate the therapeutic efficacy of baicalein (BE) on inflammatory cytokines, which is in line with tumor invasion factors and antioxidant defensive system during benzo(a)pyrene [B(a)P] (50 mg/kg body weight) induced pulmonary carcinogenesis in Swiss albino mice. After experimental period, increased levels of total and differential cell count in bronchoalveolar lavage fluid were observed. Accompanied by marked increase in immature mast cell by toluidine blue staining and mature mast cell by safranin–alcian blue staining in B(a)P-induced lung cancer bearing animals. Protein expression levels studied by immunohistochemistry and immunoblot analysis of cytokines such as tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were also found to be significantly increased in lung cancer bearing animals. B(a)P-exposed mice lung exhibits activated expression of nuclear transcription factor kappa-B as confirmed by immunofluorescence and immunoblot analysis. Administration of BE (12 mg/kg body weight) significantly counteracted all the above deleterious changes. Moreover, assessment of tumor invasion factors on protein levels by immunoblot and mRNA expression levels by RT-PCR revealed that BE treatment effectively negates B(a)P-induced upregulated expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and cyclo-oxygenase-2. Further analysis of lipid peroxidation markers such as thiobarbituric acid reactive substances, hydro-peroxides and antioxidants such as glutathione-S-transferase and reduced glutathione in lung tissue was carried out to substantiate the antioxidant effect of BE. The chemotherapeutic effect observed in the present study is attributed to the potent anti-inflammatory and antioxidant potential by BE against pulmonary carcinogenesis. -- Highlights: ► BE treatment protects from inflammatory cells and mast-cells accumulation in lungs. ► BE altered the expressions of TNF

Initiator of carcinogenesis selectively and stably inhibits stem cell differentiation: a concept that initiation of carcinogenesis involves multiple phases

International Nuclear Information System (INIS)

Scott, R.E.; Maercklein, P.B.

1985-01-01

A concept of carcinogenesis was recently devised in our laboratory that suggests the development of defects in the control of cell differentiation is associated with an early phase of carcinogenesis. To test this proposal directly, the effects of an initiator of carcinogenesis (i.e., UV irradiation) on proadipocyte stem cell differentiation and proliferation was assayed. In this regard, 3T3 T proadipocytes represent a nontransformed mesenchymal stem cell line that possesses the ability to regulate its differentiation at a distinct state in the G 1 phase of the cell cycle as well as the ability to regulate its proliferation at two additional G 1 states. The results establish that a slow dosage of 254 nm UV irradiation selectivity and stably inhibits the differentiation of a high percentage of proadipocyte stem cells without significantly altering their ability to regulate cellular proliferation in growth factor-deficient or nutrient-deficient culture conditions. Differentiation-defect proadipocyte stem cells are demonstrated not to be completely transformed but to show an increased spontaneous transformation rate, as evidenced by the formation of type III foci in high density cell cultures. These data support the role of defects in the control of differentiation in the inhibition of carcinogenesis. These observations support a concept that the initiation of carcinogenesis involves multiple phases

Fifty years after Hiroshima

International Nuclear Information System (INIS)

Imai, R.

1997-01-01

Any discussion of the nuclear-proliferation regime in the post-Cold War era, its present role and expected function in the future must take into account the outcome of the New York Non-proliferation Treaty Review Conference held in 1995, and the four factors that shaped the twentieth century: fascism and communism, nuclear energy and environmental concerns, as well as the interaction between them. none of the factors can be handled within the boundaries of a single state. After fifty years of nuclear competition both for military and energy generation purposes, international conferences on disarmament, Non-proliferation Treaty, Comprehensive Test Ban Treaty, START negotiations and agreements, there are still remaining nuclear issues. Population growth, energy demands and supplies, all related to global environmental changes must be taken into account

Mutiple simultaneous event model for radiation carcinogenesis

International Nuclear Information System (INIS)

Baum, J.W.

1979-01-01

Theoretical Radiobiology and Risk Estimates includes reports on: Multiple Simultaneous Event Model for Radiation Carcinogenesis; Cancer Risk Estimates and Neutron RBE Based on Human Exposures; A Rationale for Nonlinear Dose Response Functions of Power Greater or Less Than One; and Rationale for One Double Event in Model for Radiation Carcinogenesis

Sewage sludge does not induce genotoxicity and carcinogenesis

Science.gov (United States)

Silva, Paula Regina Pereira; Barbisan, Luis Fernando; Dagli, Maria Lúcia Zaidan; Saldiva, Paulo Hilário Nascimento

2012-01-01

Through a series of experiments, the genotoxic/mutagenic and carcinogenic potential of sewage sludge was assessed. Male Wistar rats were randomly assigned to four groups: Group 1 - negative control; Group 2 - liver carcinogenesis initiated by diethylnitrosamine (DEN; 200 mg/kg i.p.); Group 3 and G4-liver carcinogenesis initiated by DEN and fed 10,000 ppm or 50,000 ppm of sewage sludge. The animals were submitted to a 70% partial hepatectomy at the 3rd week. Livers were processed for routine histological analysis and immunohistochemistry, in order to detect glutathione S-transferase positive altered hepatocyte foci (GST-P+ AHF). Peripheral blood samples for the comet assay were obtained from the periorbital plexus immediately prior to sacrificing. Polychromatic erythrocytes (PCEs) were analyzed in femoral bone-marrow smears, and the frequencies of those micronucleated (MNPCEs) registered. There was no sewage-sludge-induced increase in frequency of either DNA damage in peripheral blood leucocytes, or MNPCEs in the femoral bone marrow. Also, there was no increase in the levels of DNA damage, in the frequency of MNPCEs, and in the development of GST-P AHF when compared with the respective control group. PMID:23055806

Understanding Carcinogenesis for Fighting Oral Cancer

OpenAIRE

Tanaka, Takuji; Ishigamori, Rikako

2011-01-01

Oral cancer is one of the major global threats to public health. Oral cancer development is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are able to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will give us important advances for...

Radiation-induced mammary carcinogenesis in rodent models. What's different from chemical carcinogenesis?

International Nuclear Information System (INIS)

Imaoka, Tatsuhiko; Nishimura, Mayumi; Iizuka, Daisuke; Daino, Kazuhiro; Takabatake, Takashi; Okamoto, Mieko; Kakinuma, Shizuko; Shimada, Yoshiya

2009-01-01

Ionizing radiation is one of a few well-characterized etiologic factors of human breast cancer. Laboratory rodents serve as useful experimental models for investigating dose responses and mechanisms of cancer development. Using these models, a lot of information has been accumulated about mammary gland cancer, which can be induced by both chemical carcinogens and radiation. In this review, we first list some experimental rodent models of breast cancer induction. We then focus on several topics that are important in understanding the mechanisms and risk modification of breast cancer development, and compare radiation and chemical carcinogenesis models. We will focus on the pathology and natural history of cancer development in these models, genetic changes observed in induced cancers, indirect effects of carcinogens, and finally risk modification by reproductive factors and age at exposure to the carcinogens. In addition, we summarize the knowledge available on mammary stem/progenitor cells as a potential target of carcinogens. Comparison of chemical and radiation carcinogenesis models on these topics indicates certain similarities, but it also indicates clear differences in several important aspects, such as genetic alterations of induced cancers and modification of susceptibility by age and reproductive factors. Identification of the target cell type and relevant translational research for human risk management may be among the important issues that are addressed by radiation carcinogenesis models. (author)

An examination of adaptive cellular protective mechanisms using a multi-stage carcinogenesis model

International Nuclear Information System (INIS)

Schollnberger, H.; Stewart, R. D.; Mitchel, R. E. J.; Hofmann, W.

2004-01-01

A multi-stage cancer model that describes the putative rate-limiting steps in carcinogenesis was developed and used to investigate the potential impact on lung cancer incidence of the hormesis mechanisms suggested by Feinendegen and Pollycove. In this deterministic cancer model, radiation and endogenous processes damage the DNA of target cells in the lung. Some fraction of the misrepaired our unrepaired DNA damage induces genomic instability and, ultimately, leads to the accumulation of malignant cells. The model accounts for cell birth and death processes. Ita also includes a rate of malignant transformation and a lag period for tumour formation. Cellular defence mechanisms are incorporated into the model by postulating dose and dose rate dependent radical scavenging. The accuracy of DNA damage repair also depends on dose and dose rate. Sensitivity studies were conducted to identify critical model inputs and to help define the shapes of the cumulative lung cancer incidence curves that may arise when dose and dose rate dependent cellular defence mechanisms are incorporated into a multi-stage cancer model. For lung cancer, both linear no-threshold (LNT) and non-LNT shaped responses can be obtained. The reported studied clearly show that it is critical to know whether or not and to what extent multiply damaged DNA sites are formed by endogenous processes. Model inputs that give rise to U-shaped responses are consistent with an effective cumulative lung cancer incidence threshold that may be as high as 300 mGy (4 mGy per year for 75 years). (Author) 11 refs

Open resections for congenital lung malformations

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Mullassery Dhanya

2008-01-01

Full Text Available Aim: Pediatric lung resection is a relatively uncommon procedure that is usually performed for congenital lesions. In recent years, thoracoscopic resection has become increasingly popular, particularly for small peripheral lesions. The aim of this study was to review our experience with traditional open lung resection in order to evaluate the existing "gold standard." Materials and Methods: We carried out a retrospective analysis of all children having lung resection for congenital lesions at our institution between 1997 and 2004. Data were collected from analysis of case notes, operative records and clinical consultation. The mean follow-up was 37.95 months. The data were analyzed using SPSS. Results: Forty-one children (13 F/28 M underwent major lung resections during the study period. Their median age was 4.66 months (1 day-9 years. The resected lesions included 21 congenital cystic adenomatoid malformations, 14 congenital lobar emphysema, four sequestrations and one bronchogenic cyst. Fifty percent of the lesions were diagnosed antenatally. Twenty-six patients had a complete lobectomy while 15 patients had parenchymal sparing resection of the lesion alone. Mean postoperative stay was 5.7 days. There have been no complications in any of the patients. All patients are currently alive, asymptomatic and well. None of the patients have any significant chest deformity. Conclusions: We conclude that open lung resection enables parenchymal sparing surgery, is versatile, has few complications and produces very good long-term results. It remains the "gold standard" against which minimally invasive techniques may be judged.

Role of oxidative stress in cadmium toxicity and carcinogenesis

International Nuclear Information System (INIS)

Liu Jie; Qu Wei; Kadiiska, Maria B.

2009-01-01

Cadmium (Cd) is a toxic metal, targeting the lung, liver, kidney, and testes following acute intoxication, and causing nephrotoxicity, immunotoxicity, osteotoxicity and tumors after prolonged exposures. Reactive oxygen species (ROS) are often implicated in Cd toxicology. This minireview focused on direct evidence for the generation of free radicals in intact animals following acute Cd overload and discussed the association of ROS in chronic Cd toxicity and carcinogenesis. Cd-generated superoxide anion, hydrogen peroxide, and hydroxyl radicals in vivo have been detected by the electron spin resonance spectra, which are often accompanied by activation of redox sensitive transcription factors (e.g., NF-κB, AP-1 and Nrf2) and alteration of ROS-related gene expression. It is generally agreed upon that oxidative stress plays important roles in acute Cd poisoning. However, following long-term Cd exposure at environmentally-relevant low levels, direct evidence for oxidative stress is often obscure. Alterations in ROS-related gene expression during chronic exposures are also less significant compared to acute Cd poisoning. This is probably due to induced adaptation mechanisms (e.g., metallothionein and glutathione) following chronic Cd exposures, which in turn diminish Cd-induced oxidative stress. In chronic Cd-transformed cells, less ROS signals are detected with fluorescence probes. Acquired apoptotic tolerance renders damaged cells to proliferate with inherent oxidative DNA lesions, potentially leading to tumorigenesis. Thus, ROS are generated following acute Cd overload and play important roles in tissue damage. Adaptation to chronic Cd exposure reduces ROS production, but acquired Cd tolerance with aberrant gene expression plays important roles in chronic Cd toxicity and carcinogenesis.

Primary hemangiopericytoma of the lung: Case report

International Nuclear Information System (INIS)

Seong, Hyun Lim; Yang, Jae Beom; Park, Chan Sup; Park, Yang Hee; Lee, Sang Seun

1990-01-01

Hemangiopericytoma may occur at any age and can arise in almost any part of the body, but seldom in the lung. Since the first report by Stout, around fifty cases of primary hemangiopericytoma of the lung have been reported in English literature journal up to 1987. We report a case of primary pulmonary hemangiopericytoma in a 19 year old man which manifest as a solitary nodule

Molecular Analysis of a Multistep Lung Cancer Model Induced by Chronic Inflammation Reveals Epigenetic Regulation of p16, Activation of the DNA Damage Response Pathway

Directory of Open Access Journals (Sweden)

David Blanco

2007-10-01

Full Text Available The molecular hallmarks of inflammation-mediated lung carcinogenesis have not been fully clarified, mainly due to the scarcity of appropriate animal models. We have used a silica-induced multistep lung carcinogenesis model driven by chronic inflammation to study the evolution of molecular markers, genetic alterations. We analyzed markers of DNA damage response (DDR, proliferative stress, telomeric stress: δ-H2AX, p16, p53, TERT. Lung cancer-related epigenetic, genetic alterations, including promoter hypermethylation status of p16(CDKN2A, APC, CDH13, Rassf1, Nore1A, as well as mutations of Tp53, epidermal growth factor receptor, K-ras, N-ras, c-H-ras, have been also studied. Our results showed DDR pathway activation in preneoplastic lesions, in association with inducible nitric oxide synthase, p53 induction. p16 was also induced in early tumorigenic progression, was inactivated in bronchiolar dysplasias, tumors. Remarkably, lack of mutations of Ras, epidermal growth factor receptor, a very low frequency of Tp53 mutations suggest that they are not required for tumorigenesis in this model. In contrast, epigenetic alterations in p16(CDKN2A, CDH13, APC, but not in Rassf1, Nore1A, were clearly observed. These data suggest the existence of a specific molecular signature of inflammation-driven lung carcinogenesis that shares some, but not all, of the molecular landmarks of chemically induced lung cancer.

Etiologic related studies of ultraviolet light-mediated carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Black, H S; Chan, J T

1976-01-01

Comparisons were made of cholesterol-5..cap alpha.. 6..cap alpha..-epoxide (CAE) levels in skin of hairless mice maintained on a regular or antioxidant supplemented diet and receiving chronic ultraviolet light (UVL) radiation over an 18-week period. Cholesterol-5..cap alpha.., 6..cap alpha..-epoxide levels in skin of animals on antioxidant supplemented diet, while reaching a peak four weeks after that of animals on regular diet, thereafter were consistently higher. Dietary antioxidants nevertheless had an inhibitory effect on UVL-induced tumors. These data are inconsistent with the theory of CAE involvement as an ultimate carcinogen in UVL-mediated carcinogenesis.

Test of the linear-no threshold theory of radiation carcinogenesis for inhaled radon decay products

International Nuclear Information System (INIS)

Cohen, B.L.

1995-01-01

Data on lung cancer mortality rates vs. average radon concentration in homes for 1,601 U.S. counties are used to test the linear-no threshold theory. The widely recognized problems with ecological studies, as applied to this work, are addressed extensively. With or without corrections for variations in smoking prevalence, there is a strong tendency for lung cancer rates to decrease with increasing radon exposure, in sharp contrast to the increase expected from the theory. The discrepancy in slope is about 20 standard deviations. It is shown that uncertainties in lung cancer rates, radon exposures, and smoking prevalence are not important and that confounding by 54 socioeconomic factors, by geography, and by altitude and climate can explain only a small fraction of the discrepancy. Effects of known radon-smoking prevalence correlations - rural people have higher radon levels and smoke less than urban people, and smokers are exposed to less radon than non-smokers - are calculated and found to be trivial. In spite of extensive efforts, no potential explanation for the discrepancy other than failure of the linear-no threshold theory for carcinogenesis from inhaled radon decay products could be found. (author)

Initiation-promotion skin carcinogenesis and immunological competence.

Science.gov (United States)

Curtis, G L; Stenbäck, F; Ryan, W L

1975-10-01

The immune competence of mice during initiation-promotion skin carcinogenesis was determined by skin allograft rejection and lymphocyte mitogenesis. The carcinogen 7, 12-dimethylbenzanthracene inhibited the cellular immune competence of mice while lymphocytes from croton oil treated mice had enhanced PWM response. Chlorphenesin, a stimulator of cellular immunity, was found to inhibit tumorigenesis in initiation-promotion skin carcinogenesis when injected during promotion.

Bronchial airway gene expression in smokers with lung or head and neck cancer

International Nuclear Information System (INIS)

Van Dyck, Eric; Nazarov, Petr V; Muller, Arnaud; Nicot, Nathalie; Bosseler, Manon; Pierson, Sandrine; Van Moer, Kris; Palissot, Valérie; Mascaux, Céline; Knolle, Ulrich; Ninane, Vincent; Nati, Romain; Bremnes, Roy M; Vallar, Laurent; Berchem, Guy; Schlesser, Marc

2014-01-01

Cigarette smoking is the major cause of cancers of the respiratory tract, including non-small cell lung cancer (NSCLC) and head and neck cancer (HNC). In order to better understand carcinogenesis of the lung and upper airways, we have compared the gene expression profiles of tumor-distant, histologically normal bronchial biopsy specimens obtained from current smokers with NSCLC or HNC (SC, considered as a single group), as well as nonsmokers (NS) and smokers without cancer (SNC). RNA from a total of 97 biopsies was used for gene expression profiling (Affymetrix HG-U133 Plus 2.0 array). Differentially expressed genes were used to compare NS, SNC, and SC, and functional analysis was carried out using Ingenuity Pathway Analysis (IPA). Smoking-related cancer of the respiratory tract was found to affect the expression of genes encoding xenobiotic biotransformation proteins, as well as proteins associated with crucial inflammation/immunity pathways and other processes that protect the airway from the chemicals in cigarette smoke or contribute to carcinogenesis. Finally, we used the prediction analysis for microarray (PAM) method to identify gene signatures of cigarette smoking and cancer, and uncovered a 15-gene signature that distinguished between SNC and SC with an accuracy of 83%. Thus, gene profiling of histologically normal bronchial biopsy specimens provided insight into cigarette-induced carcinogenesis of the respiratory tract and gene signatures of cancer in smokers

Interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway in renal carcinogenesis of uninephrectomized rats.

Science.gov (United States)

Yang, Ke-Ke; Sui, Yi; Zhou, Hui-Rong; Zhao, Hai-Lu

2017-05-01

Renin-angiotensin system and adenosine monophosphate-activated protein kinase signaling pathway both play important roles in carcinogenesis, but the interplay of renin-angiotensin system and adenosine monophosphate-activated protein kinase in carcinogenesis is not clear. In this study, we researched the interaction of renin-angiotensin system and adenosine monophosphate-activated protein kinase in renal carcinogenesis of uninephrectomized rats. A total of 96 rats were stratified into four groups: sham, uninephrectomized, and uninephrectomized treated with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Renal adenosine monophosphate-activated protein kinase and its downstream molecule acetyl coenzyme A carboxylase were detected by immunohistochemistry and western blot at 10 months after uninephrectomy. Meanwhile, we examined renal carcinogenesis by histological transformation and expressions of Ki67 and mutant p53. During the study, fasting lipid profiles were detected dynamically at 3, 6, 8, and 10 months. The results indicated that adenosine monophosphate-activated protein kinase expression in uninephrectomized rats showed 36.8% reduction by immunohistochemistry and 89.73% reduction by western blot. Inversely, acetyl coenzyme A carboxylase expression increased 83.3% and 19.07% in parallel to hyperlipidemia at 6, 8, and 10 months. The histopathology of carcinogenesis in remnant kidneys was manifested by atypical proliferation and carcinoma in situ, as well as increased expressions of Ki67 and mutant p53. Intervention with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker significantly prevented the inhibition of adenosine monophosphate-activated protein kinase signaling pathway and renal carcinogenesis in uninephrectomized rats. In conclusion, the novel findings suggest that uninephrectomy-induced disturbance in adenosine monophosphate-activated protein kinase signaling pathway resulted in hyperlipidemia and

Collective studies on carcinogenesis due to exposure to radiation

International Nuclear Information System (INIS)

Yamashita, Hisao

1980-01-01

Carcinogenesis was found in 150 of 25,692 patients who had received radiotherapy for benign diseases. Of primary diseases subjected to radiotherapy, skin diseases were the most. Carcinogenesis was found in 26 of 7,230 patients with skin diseases (0.36%) and 18 in 2286 patients with tuberculous cervical lymphadenitis (0.79%). The sites of carcinogenesis was the skin in 51 patients, the hypopharynx in 43, and the larynx in 18. Carcinogenesis was also found in 140 of 220,361 patients who had received radiotherapy for malignant tumors. As primary cancer, cancer of the cervix uteri was found in 59 of 48,662 patients, and breast cancer was found in 20 of 27,967 patients. As radiation-induced cancer, leukemia was found in 18 patients, soft tissue sarcoma in 18, skin cancer in 10, osteosarcoma in 6, cancer of the hypopharynx in 6, and cancer of the cervical esophagus in 6. It is necessary to differentiate cancer due to exposure to radiation from delayed recurrent cancer and double cancer. Irradiation fields should be restricted as small as possible in order to reduce carcinogenesis. As leukemia and carcinoma were found in a-bomb survivors exposed to very small dose of a-bomb radiation, carcinogenic mechanisms by chromosome aberrations, carcinogenic rates from a viewpoint of epidemiology, and other factors which influenced carcinogenesis are being investigated. (Tsunoda, M.)

Proliferative and morphological changes in the pulmonary epithelium of the Syrian golden hamster during carcinogenesis initiated by 210Po alpha alpha-radiation

International Nuclear Information System (INIS)

Shami, S.G.; Thibodeau, L.A.; Kennedy, A.R.; Little, J.B.

1982-01-01

The role of cellular proliferation in a two-stage model of carcinogenesis in the hamster lung was investigated. Syrian golden hamsters were treated intratracheally with either one instillation of 0.2 microCi of 210Po (Po-0 group), seven weekly instillations of BP (0-BP group), or 0.2 microCi 210Po followed 15 weeks later by either seven instillations of 0.9% NaCl solution (Po-Sal group) or seven instillations of BP (Po-BP group). All BP instillations were 3 mg each of BP:ferric oxide (1:1, w/w) carrier particles). Serial sacrifices were performed for up to 85 weeks. Two hr before sacrifice, each animal was given i.p. injections of 200 microCi of [3H]thymidine. Glycol methacrylate section autoradiographs (1 micrometer) were prepared. Labeling indices in the alveolar region, labeling of terminal bronchiolar cells, and morphological changes were examined. Equal numbers of Po-Sal and Po-BP animals developed lung tumors. No tumors were found in Po-0 or 0-BP animals. Tumor development was preceded by the appearance of hyperplastic areas of bronchiolar-type cells in the alveolar region and by changes in morphology of bronchiolar cells. Labeling indices in the alveolar region of the treated groups were slightly increased relative to untreated controls. Labeling of terminal bronchiolar cells was highest in the Po-BP and 0-BP groups and was associated with much inflammation. A single 0.9% NaCl solution instillation also increased proliferation of bronchiolar cells. We conclude that 0.9% NaCl solution instillations may potentiate carcinogenesis in the hamster lung by acting as a nonspecific stimulus to proliferation; in addition, we conclude that not all hyperplasia progresses on to form lung tumors in the Po-BP and Po-Sal groups

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

Energy Technology Data Exchange (ETDEWEB)

Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico); Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gandolfi, A. Jay, E-mail: gandolfi@pharmacy.arizona.edu [Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ (United States); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Lantz, R. Clark, E-mail: lantz@email.arizona.edu [Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); González-Cortes, Tania, E-mail: taniagc2201@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gonzalez-De Alba, Cesar, E-mail: cesargonzalezalba@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Froines, John R., E-mail: jfroines@ucla.edu [Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA (United States); Espinosa-Fematt, Jorge A., E-mail: dr.jorge.espinosa@gmail.com [School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico)

2015-09-01

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

Prevention of chinese green tea on 3,4-benzopyrene-induced lung cancer and its mechanism in animal model

Directory of Open Access Journals (Sweden)

Qihua GU

2008-08-01

Full Text Available Background and objective Chinese green tea is one of the daily consumption beverages in the world and is considered a promising cancer chemopreventive agent. In the present study, we investigate the role of lung cancer prevention by green tea and its mechanism. Methods Three groups of female SD rats were kept with the same feed. Rats in group A were administrated with 1% green tea drinking, while in group B and group C with water only. Animals in group A and group B were given 3,4-benzopyrene-corn oil mixture pulmonary injection fortnightly for 4 times, while in group C corn oil only. Rats were sacrificed 1 year after the first injection under narcotism. Lung tumors and lung tissues were performed H＆E staining for cancer identification. Each case of lung cancer was examined for expression of p53 and Bcl-2 with in situ hybridization analysis and immunohistochemistry staining. Results No cancer was found in rats in group C. However, in group B, 15 out of 20 rats were found generating lung cancer, and in group A, 6 out of 20 rats inducing lung cancer were recorded. The rate of lung carcinogenesis in rats was decreased from 75% to 30% by 1% chinese green tea oral administration (χ2=8.12, P0.05. However, significantly lower level of Bcl-2 expression was found in lung cancer tissues of group A than that of group B (P<0.05. Conclusion The results indicate that chinese green tea inhibits lung carcinogenesis. Chinese green tea can slightly upregulate expression of p53, but significantly downregulate expression of Bcl-2 in lung cancer, and this may be related to the mechanism of lung cancer prevention.

Radiation carcinogenesis in scid mice

Energy Technology Data Exchange (ETDEWEB)

Ishii, Hiroko; Nishimura, Mayumi; Kobayashi, Shigeru; Tsuji, Hideo; Shimada, Yoshiya; Ogiu, Toshiaki [National Inst. of Radiological Sciences, Chiba (Japan); Suzuki, Fumio; Sado, Toshihiko

1999-06-01

Scid mice which have the defect of DNA-dependent protein kinase catalitic subunit, exhibit the limited activities of repair from DNA double strand breaks, and are sensitive to ionizing radiation. In order to study the relationship between repair capacity for DNA double strand breaks and carcinogenesis, the effects of ionizing radiation were studied using scid homozygotes (scid/scid), scid heterozygotes (scid/+) and CB-17 (+/+) mice. Both the Scid bone marrow cells and fibroblast cell lines from Scid embryos were highly sensitivity to acute effects of ionizing radiation. Carcinogenesis experiments showed the high incidence of thymic lymphomas (80 to 90%) in 1 to 3 Gy {sup 137}Cs-{gamma}-ray-irradiated Scid mice. (author)

Diet, lifestyle, and molecular alterations that drive colorectal carcinogenesis

NARCIS (Netherlands)

Diergaarde, B.

2004-01-01

Environmental factors have been repeatedly implicated in the etiology of colorectal cancer, and much is known about the molecular events involved in colorectal carcinogenesis. The relationships between environmental risk factors and the molecular alterations that drive colorectal carcinogenesis are

Racial and Ethnic Differences in the Epidemiology and Genomics of Lung Cancer.

Science.gov (United States)

Schabath, Matthew B; Cress, Douglas; Munoz-Antonia, Teresita

2016-10-01

Lung cancer is the most common cancer in the world. In addition to the geographical and sex-specific differences in the incidence, mortality, and survival rates of lung cancer, growing evidence suggests that racial and ethnic differences exist. We reviewed published data related to racial and ethnic differences in lung cancer. Current knowledge and substantive findings related to racial and ethnic differences in lung cancer were summarized, focusing on incidence, mortality, survival, cigarette smoking, prevention and early detection, and genomics. Systems-level and health care professional-related issues likely to contribute to specific racial and ethnic health disparities were also reviewed to provide possible suggestions for future strategies to reduce the disproportionate burden of lung cancer. Although lung carcinogenesis is a multifactorial process driven by exogenous exposures, genetic variations, and an accumulation of somatic genetic events, it appears to have racial and ethnic differences that in turn impact the observed epidemiological differences in rates of incidence, mortality, and survival.

Statistical modeling and extrapolation of carcinogenesis data

International Nuclear Information System (INIS)

Krewski, D.; Murdoch, D.; Dewanji, A.

1986-01-01

Mathematical models of carcinogenesis are reviewed, including pharmacokinetic models for metabolic activation of carcinogenic substances. Maximum likelihood procedures for fitting these models to epidemiological data are discussed, including situations where the time to tumor occurrence is unobservable. The plausibility of different possible shapes of the dose response curve at low doses is examined, and a robust method for linear extrapolation to low doses is proposed and applied to epidemiological data on radiation carcinogenesis

Cell structure and proliferative activity of organ cultures of normal embryonic lung tissue of mice resistant (C57BL) and predisposed (A) to lung tumors

International Nuclear Information System (INIS)

Kolesnichenko, T.S.; Gor'kova, T.G.

1985-01-01

Local factors such as proliferative activity and the numerical ratio between epithelial and mesenchymal cells, and also the character of interaction between the tissue components in ontogeny may play an important role in the realization of sensitivity of mice of a particular line to the development of lung tumors. These characteristics of lung tissue in mice of lines A and C57BL are investigated under normal conditions and during induced carcinogenesis. Results are given of a comparative study of the relative numbers of epithelial and mesenchymal cells in organ cultures of embryonic lungs. 3 H-thymidine was added to the cultures on the 14th day of the experiment in a concentration of 1 microCi/m1 medium. An autoradiographic study of the cultures was performed

[Initiation, promotion, initiation experiments with radon and cigarette smoke: Lung tumors in rats]. Progress report

International Nuclear Information System (INIS)

Moolgavkar, S.H.

1994-01-01

During the past several years, the authors have made considerable progress in modeling carcinogenesis in general, and in modeling radiation carcinogenesis, in particular. They present an overview of their progress in developing stochastic carcinogenesis models and applying them to experimental and epidemiologic data sets. Traditionally, cancer models have been used for the analysis of incidence (or prevalence) data in epidemiology and time to tumor data in experimental studies. The relevant quantities for the analysis of these data are the hazard function and the probability of tumor. The derivation of these quantities is briefly described here. More recently, the authors began to use these models for the analysis of data on intermediate lesions on the pathway to cancer. Such data are available in experimental carcinogenesis studies, in particular in initiation and promotion studies on the mouse skin and the rat liver. If however, quantitative information on intermediate lesions on the pathway to lung cancer were to be come available at some future date, the methods that they have developed for the analysis of initiation-promotion experiments could easily be applied to the analysis of these lesions. The mathematical derivations here are couched in terms of a particular two-mutation model of carcinogenesis. Extension to models postulating more than two mutations is not always straightforward

Lung cancer in patients with idiopathic pulmonary fibrosis.

Science.gov (United States)

Karampitsakos, Theodoros; Tzilas, Vasilios; Tringidou, Rodoula; Steiropoulos, Paschalis; Aidinis, Vasilis; Papiris, Spyros A; Bouros, Demosthenes; Tzouvelekis, Argyris

2017-08-01

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease of unknown etiology. With a gradually increasing worldwide prevalence and a mortality rate exceeding that of many cancers, IPF diagnosis and management are critically important and require a comprehensive multidisciplinary approach. This approach also involves assessment of comorbid conditions, such as lung cancer, that exerts a dramatic impact on disease survival. Emerging evidence suggests that progressive lung scarring in the context of IPF represents a risk factor for lung carcinogenesis. Both disease entities present with major similarities in terms of pathogenetic pathways, as well as potential causative factors, such as smoking and viral infections. Besides disease pathogenesis, anti-cancer agents, including nintedanib, have been successfully applied in the treatment of patients with IPF while an oncologic approach with a cocktail of several pleiotropic anti-fibrotic agents is currently in the therapeutic pipeline of IPF. Nevertheless, epidemiologic association between IPF and lung cancer does not prove causality. Currently there is significant lack of knowledge supporting a direct association between lung fibrosis and cancer reflecting to disappointing therapeutic algorithms. An optimal therapeutic strategy for patients with both IPF and lung cancer represents an amenable need. This review article synthesizes the current state of knowledge regarding pathogenetic commonalities between IPF and lung cancer and focuses on clinical and therapeutic data that involve both disease entities. Copyright © 2017. Published by Elsevier Ltd.

Upregulation of intrinsic apoptotic pathway in NSAIDs mediated chemoprevention of experimental lung carcinogenesis.

Science.gov (United States)

Setia, Shruti; Sanyal, Sankar N

2012-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) act by inhibition of cyclooxygenase-2 (COX-2), which is overexpressed in cancer. The role of COX-2 and apoptosis were evaluated in 9,10-dimethylbenz(a)anthracene (DMBA)-induced lung cancer in rat and chemoprevention with indomethacin, a traditional NSAID and etoricoxib, a selective COX-2 inhibitor. The animals were divided into Control, DMBA, DMBA+ indomethacin and DMBA+ etoricoxib groups. They received a single intratracheal instillation of DMBA while NSAIDs were given orally daily for 32 weeks. Besides morphology and histology of lungs, RT-PCR, western blots and immunohistochemistry were performed for the expression of apoptotic proteins and COX enzymes. Apoptosis was studied by DNA fragmentation and fluorescent staining. The occurrence of tumors and lesions was noted in the DMBA animals, besides constricted alveolar spaces and hyperplasia. COX-1 was found to be uniformly expressed while COX-2 level was raised significantly in DMBA group. The apoptotic proteins, apaf-1, caspase-9 and caspase-3 were highly diminished in DMBA group but restored to normal level in NSAIDs groups. Also, apoptosis was suppressed in carcinogen group by DNA fragmentation analysis and fluorescent staining of the lung cells while co-administration of NSAIDs along with DMBA led to the restoration of apoptosis. DMBA administration to the rats led to tumorigenesis in the lungs, had no effects on COX-1 expression, while elevating the COX-2 levels and suppressing apoptosis. The treatment with NSAIDs led to the amelioration of these effects. However, etoricoxib which is a COX-2 specific inhibitor, was found to be more effective than the traditional NSAID, indomethacin.

Four-miRNA signature as a prognostic tool for lung adenocarcinoma.

Science.gov (United States)

Lin, Yan; Lv, Yufeng; Liang, Rong; Yuan, Chunling; Zhang, Jinyan; He, Dan; Zheng, Xiaowen; Zhang, Jianfeng

2018-01-01

The aim of this study was to generate a novel miRNA expression signature to accurately predict prognosis for patients with lung adenocarcinoma (LUAD). Using expression profiles downloaded from The Cancer Genome Atlas database, we identified multiple miRNAs with differential expression between LUAD and paired healthy tissues. We then evaluated the prognostic values of the differentially expressed miRNAs using univariate/multivariate Cox regression analysis. This analysis was ultimately used to construct a four-miRNA signature that effectively predicted patient survival. Finally, we analyzed potential functional roles of the target genes for these four miRNAs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Based on our cutoff criteria ( P 1.0), we identified a total of 187 differentially expressed miRNAs, including 148 that were upregulated in LUAD tissues and 39 that were downregulated. Four miRNAs (miR-148a-5p, miR-31-5p, miR-548v, and miR-550a-5p) were independently associated with survival based on Kaplan-Meier analysis. We generated a signature index based on the expression of these four miRNAs and stratified patients into low- and high-risk groups. Patients in the high-risk group had significantly shorter survival times than those in the low-risk group ( P =0.002). A functional enrichment analysis suggested that the target genes of these four miRNAs were involved in protein phosphorylation and the Hippo and sphingolipid signaling pathways. Taken together, our results suggest that our four-miRNA signature can be used as a prognostic tool for patients with LUAD.

Cell cycle gene expression networks discovered using systems biology: Significance in carcinogenesis

Science.gov (United States)

Scott, RE; Ghule, PN; Stein, JL; Stein, GS

2015-01-01

The early stages of carcinogenesis are linked to defects in the cell cycle. A series of cell cycle checkpoints are involved in this process. The G1/S checkpoint that serves to integrate the control of cell proliferation and differentiation is linked to carcinogenesis and the mitotic spindle checkpoint with the development of chromosomal instability. This paper presents the outcome of systems biology studies designed to evaluate if networks of covariate cell cycle gene transcripts exist in proliferative mammalian tissues including mice, rats and humans. The GeneNetwork website that contains numerous gene expression datasets from different species, sexes and tissues represents the foundational resource for these studies (www.genenetwork.org). In addition, WebGestalt, a gene ontology tool, facilitated the identification of expression networks of genes that co-vary with key cell cycle targets, especially Cdc20 and Plk1 (www.bioinfo.vanderbilt.edu/webgestalt). Cell cycle expression networks of such covariate mRNAs exist in multiple proliferative tissues including liver, lung, pituitary, adipose and lymphoid tissues among others but not in brain or retina that have low proliferative potential. Sixty-three covariate cell cycle gene transcripts (mRNAs) compose the average cell cycle network with p = e−13 to e−36. Cell cycle expression networks show species, sex and tissue variability and they are enriched in mRNA transcripts associated with mitosis many of which are associated with chromosomal instability. PMID:25808367

Ultraviolet radiation-induced carcinogenesis: mechanisms and experimental models

International Nuclear Information System (INIS)

Ramasamy, Karthikeyan; Shanmugam, Mohana; Balupillai, Agilan; Govindhasamy, Kanimozhi; Gunaseelan, Srithar; Muthusamy, Ganesan; Robert, Beualah Mary; Nagarajan, Rajendra Prasad

2017-01-01

Ultraviolet radiation (UVR) is a very prominent environmental toxic agent. UVR has been implicated in the initiation and progression of photocarcinogenesis. UVR exposure elicits numerous cellular and molecular events which include the generation of inflammatory mediators, DNA damage, epigenetic modifications, and oxidative damages mediated activation of signaling pathways. UVR-initiated signal transduction pathways are believed to be responsible for tumor promotion effects. UVR-induced carcinogenic mechanism has been well studied using various animal and cellular models. Human skin-derived dermal fibroblasts, epidermal keratinocytes, and melanocytes served as excellent cellular model systems for the understanding of UVR-mediated carcinogenic events. Apart from this, scientists developed reconstituted three-dimensional normal human skin equivalent models for the study of UVR signaling pathways. Moreover, hairless mice such as SKH-1, devoid of Hr gene, served as a valuable model for experimental carcinogenesis. Scientists have also used transgenic mice and dorsal portion shaved Swiss albino mice for UVR carcinogenesis studies. In this review, we have discussed the current progress in the study on ultraviolet B (UVB)-mediated carcinogenesis and outlined appropriate experimental models for both ultraviolet A- and UVB-mediated carcinogenesis. (author)

Latent period and temporal aspects of lung cancer among miners

International Nuclear Information System (INIS)

Sun Shiquan; Yang Xiaoou; Yang Lan; Meng Xianyu; Liu Shengen; You Zhanyun

1984-01-01

Data of lung cancer happened in the miners of this reported mine area is of great value to investigate the temporal aspects of miner's lung cancer, owing to its plenty of cases, longterm follow up and mining as child miners in early years before liberation of China. This preliminary analysis showed that the induction-latent period increased with the decrease of age at the year-of-first-employment in this mine and the protraction of follow up. In other words, even they were exposed since childhood, the excess of lung cancer never appeared until certain age for carcinogenesis. Therefore, the long-term follow up and comprehensive analysis of induction-latent period, underground duration-of-employment, time and age at start of mining would be helpful to properly estimating risk level, discovering the cause and predicting the trend of lung cancer incidence. There is no evidence to show whether child miners are more sensitive than adult miners working at the same exposure conditions

Las notas al pie en la traducción de Fifty Shades (Footnotes in the Translation of Fifty Shades

Directory of Open Access Journals (Sweden)

Xinia Valverde Jara

2017-11-01

Full Text Available Se analiza el recurso de las notas a pie de página insertas en la traducción independiente de literatura comercial en versión digital, de la trilogía Fifty Shades of Grey, Fifty Shades Darker y Fifty Shades Freed, de E. L. James. Se examina el grado de influencia de esos elementos extratextuales, y se concluye que todos ellos, organizados en un complejo proceso de traducción, en especial los del contexto de llegada, condicionan la estrategia traductológica. Abstract This study examines the use of footnotes as a translation strategy in the independent translation of commercial literature in digital format, based on the trilogy written by E. L. James, Fifty Shades of Grey, Fifty Shades Darker and Fifty Shades Freed. The analysis measures the influence of these extratextual elements within the complex translation process, specifically those of the target language context, and it is concluded that they condition the translation strategies used.

Genetic alterations during radiation-induced carcinogenesis

International Nuclear Information System (INIS)

Kodama, Seiji

1995-01-01

This paper reviews radiation-induced genetic alterations and its carcinogenesis, focusing on the previous in vitro assay outcome. A colony formation assay using Syrian hamster fetal cells and focus formation assay using mouse C3H10T1/2 cells are currently available to find malignant transformation of cells. Such in vitro assays has proposed the hypothesis that radiation-induced carcinogenesis arises from at least two-stage processes; i.e., that an early step induced by irradiation plays an important role in promoting the potential to cause the subsequent mutation. A type of genetic instability induced by radiation results in a persistently elevated frequency of spontaneous mutations, so-called the phenomenon of delayed reproductive death. One possible mechanism by which genetic instability arises has been shown to be due to the development of abnormality in the gene group involved in the maintenance mechanism of genome stability. Another possibility has also been shown to stem from the loss of telomere (the extremities of a chromosome). The importance of search for radiation-induced genetic instability is emphasized in view of the elucidation of carcinogenesis. (N.K.)

Colorectal Carcinogenesis: Role of Oxidative Stress and Antioxidants.

Science.gov (United States)

Carini, Francesco; Mazzola, Margherita; Rappa, Francesca; Jurjus, Abdo; Geagea, Alice Gerges; Al Kattar, Sahar; Bou-Assi, Tarek; Jurjus, Rosalyn; Damiani, Provvidenza; Leone, Angelo; Tomasello, Giovanni

2017-09-01

One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanisms. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documented the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yield definitive results and were performed mostly in vitro on cell populations, or in vivo in experimental animal models. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Prognostic value of PET/CT in lung cancer. Study of survival and tumor metabolic characterization

International Nuclear Information System (INIS)

Ladron de Guevara, David; Fuentes Anibal; Farina, Ciro; Corral, Camilo; Pefaur, Raul

2013-01-01

PET/CT (Positron emission tomography/computed tomography) is a hybrid image modality widely used in oncology, for staging, therapy evaluation or follow up. Aim: To evaluate the prognostic value of PET/CT in lung cancer. Material and Methods: Retrospective review of PET/CT records, selecting 51 patients with a lung malignancy, mass or nodule referred for PET/CT between December 2008 and December 2010. All had pathological confirmation of malignancy and had not been treated previously. Age, gender, body mass index, radiological features of lung tumor and metastases, and lung tumor 18 F-fluoro-2-deoxy-d-glucose uptake using the SUV (Standardized uptake value) index were recorded. Survival was analyzed using Kaplan-Meier curves and a Cox proportional regression analysis. Results: Pathology confirmed the presence of lung cancer in 47 patients aged 30 to 88 years. Four patients (7.8%) had other type of tumors such as carcinoid or lymphoma. Fifty percent of lung cancer patients died during a mean observation lapse of 18 months (range: 2-34 months). Patients with metastases, local lymph node involvement, a lung tumor size ≥ 3 cm and high tumor uptake (SUVmax > 6) had significantly lower survival. Occurrence of metastases was the only independent prognostic factor in the Cox regression. A lung lesion with a SUVmax ≥ 12 was always associated to hilar/mediastinal lymph node involvement. Conclusions: PET/CT imaging gives important prognostic information in lung cancer patients

Present status of theories and data analyses of mathematical models for carcinogenesis

International Nuclear Information System (INIS)

Kai, Michiaki; Kawaguchi, Isao

2007-01-01

Reviewed are the basic mathematical models (hazard functions), present trend of the model studies and that for radiation carcinogenesis. Hazard functions of carcinogenesis are described for multi-stage model and 2-event model related with cell dynamics. At present, the age distribution of cancer mortality is analyzed, relationship between mutation and carcinogenesis is discussed, and models for colorectal carcinogenesis are presented. As for radiation carcinogenesis, models of Armitage-Doll and of generalized MVK (Moolgavkar, Venson, Knudson, 1971-1990) by 2-stage clonal expansion have been applied to analysis of carcinogenesis in A-bomb survivors, workers in uranium mine (Rn exposure) and smoking doctors in UK and other cases, of which characteristics are discussed. In analyses of A-bomb survivors, models above are applied to solid tumors and leukemia to see the effect, if any, of stage, age of exposure, time progression etc. In miners and smokers, stages of the initiation, promotion and progression in carcinogenesis are discussed on the analyses. Others contain the analyses of workers in Canadian atomic power plant, and of patients who underwent the radiation therapy. Model analysis can help to understand the carcinogenic process in a quantitative aspect rather than to describe the process. (R.T.)

Effect of Dendrobium officinale Extraction on Gastric Carcinogenesis in Rats

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Yi Zhao

2016-01-01

Full Text Available Dendrobium officinale (Tie Pi Shi Hu in Chinese has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg were orally administered to the rats of the gastric carcinogenesis model. Compared with the cancer model group, the high dose of Dendrobium officinale extracts significantly inhibited the rate of carcinogenesis. Further analysis revealed that Dendrobium officinale extracts could regulate the DNA damage, oxidative stress, and cytokines related with carcinogenesis and induce cell apoptosis in order to prevent gastric cancer.

Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

OpenAIRE

Tanaka, Takuji; Tanaka, Mayu; Tanaka, Takahiro

2011-01-01

Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important adv...

Physiological and biochemical aspects of the effect of ionizing radiations on the lung parenchyma

International Nuclear Information System (INIS)

Pasquier, Christian.

1975-03-01

Concerning the biochemical reactions of the lung parenchyma to irradiation the following points have been developed. Role of biochemically active substances (histamine, serotonin, kinins, catecholamines, prostaglandins) in the early reaction of the lung to irradiation, their common feature being their vascular impact point. Lung irradiation and lipids (fatty acids and lipid metabolism in general); irradiation, by raising the proportion of unsaturated at the expense of saturated fatty acids, may give rise to serious physiological respiratory disorders. Lung irradiation and blood fluidity (fibrinolytic activity, heparin, platelet factors). Pulmonary interstitium and irradiation (of the three interstitium components collagen plays a preferential part). Irradiation and immunological lung reaction (reasons behind the immunological theory, immunological assistance, immunological mechanism of pulmonary reactions towards pollutants). Enzymatic lung radiolesion indicators. Three kinds of physiological changes have been considered. Vascular physiology disturbances caused by the initial biochemical reactions; anomalies of physiological or functional trials, images of the lesion formed; disorders of the cell physiology of carcinogenesis [fr

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

DEFF Research Database (Denmark)

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

2010-01-01

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

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

International Nuclear Information System (INIS)

Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P.; Gelman, Andrew E.; Jarzembowski, Jason A.; Zhang, Hao; Pritchard, Kirkwood A. Jr.; Vikis, Haris G.

2014-01-01

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting

The role of neutrophil myeloperoxidase in models of lung tumor development.

Science.gov (United States)

Rymaszewski, Amy L; Tate, Everett; Yimbesalu, Joannes P; Gelman, Andrew E; Jarzembowski, Jason A; Zhang, Hao; Pritchard, Kirkwood A; Vikis, Haris G

2014-05-09

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

Energy Technology Data Exchange (ETDEWEB)

Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P. [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Gelman, Andrew E. [Department of Surgery, Washington University in St. Louis, St. Louis, MO 63130 (United States); Jarzembowski, Jason A. [Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Zhang, Hao; Pritchard, Kirkwood A. Jr. [Department of Surgery and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Vikis, Haris G., E-mail: hvikis@mcw.edu [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States)

2014-05-09

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

Directory of Open Access Journals (Sweden)

Amy L. Rymaszewski

2014-05-01

Full Text Available Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA-initiated, butylated hydroxytoluene (BHT-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC, a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

Four Cases of Interstitial Lung Disease Induced by Erlotinib 
and A Review of the Literatures

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Xiaoling WU

2012-08-01

Full Text Available Erlotinib is an agent of oral epidermal growth factor receptor (EGFR tyrosine kinase inhibitors which are used for non-small cell lung cancer. Although this class of agents is considered to be relatively safe, the most serious, but rare, adverse reaction is drug-associated interstitial lung disease (ILD. ILD induced by gefitinib been often described, but the ILD induced by erlotinib is relatively less well known. We here describle four cases of ILD related to erlotinib and review recent literatures to help physicians earlier alert erlotinib-induced ILD. It is important to carefully monitor pulmonary symptoms in all patients who are receiving erlotinib. Early diagnosis and timely intervention is critical in the treatment of drug-induced ILD.

Carcinogenesis. Genetics and circumstances

International Nuclear Information System (INIS)

Hino, Okio

2005-01-01

Described are the author's study and aspect concerning carcinogenesis and radiation carcinogenesis, where he thinks cancer is not automatic, has a process and takes time. For radiation carcinogenic studies, he has used a model of the rat with genetically determined kidney cancer which is highly radiosensitive. That is, mutation by the so-called 2nd-hit of the causal gene (tumor suppressing gene Tsc2) is studied in the animal where the 1st-hit has been done by retrotransposon insertion, with and without exposure to radiations (X-ray, heavy particle beam and cosmic ray) for elucidating the mutation spectrum of the causal gene, the carcinogenic target, for the ultimate aim to prevent human cancer. He discusses the drama-type molecular mechanisms leading to cancer, gene abnormality and disease crisis, discontinuity in continuity in cancer formation, and importance of the timely diagnosis and appropriate therapy, and concludes the present age is becoming such one as that the nature of cancer even if genetic can be controlled by circumstances like timely and appropriate intervention. (S.I.)

Radiation and multistage carcinogenesis

International Nuclear Information System (INIS)

Day, N.E.

1984-01-01

Epidemiological data are insufficient at present to define with much precision the shape of the dose-response curve for radiation carcinogenesis at low or moderate dose levels, for different organs. The available data have to be supplemented with theoretical models for the mode of action. These models, however, often seem not to take into account the complex nature of the process of carcinogenesis. They relate more to mutational events, rather than the long process of cancer induction. In addition, they ignore the fact that in the human situation radiation is one among a large number of exposures, and even the basic form of the dose response may be dependent on the presence or absence of other factors. Information on modes of action usually comes from experimental results, where the requisite combination of exposures can be chosen in advance. Epidemiology, however, also provides information on mechanisms. The purpose of this paper is to consider some of the information that epidemiology provides on the role of radiation in increasing cancer risk in humans

Experimental, statistical, and biological models of radon carcinogenesis

International Nuclear Information System (INIS)

Cross, F.T.

1991-09-01

Risk models developed for underground miners have not been consistently validated in studies of populations exposed to indoor radon. Imprecision in risk estimates results principally from differences between exposures in mines as compared to domestic environments and from uncertainties about the interaction between cigarette-smoking and exposure to radon decay products. Uncertainties in extrapolating miner data to domestic exposures can be reduced by means of a broad-based health effects research program that addresses the interrelated issues of exposure, respiratory tract dose, carcinogenesis (molecular/cellular and animal studies, plus developing biological and statistical models), and the relationship of radon to smoking and other copollutant exposures. This article reviews experimental animal data on radon carcinogenesis observed primarily in rats at Pacific Northwest Laboratory. Recent experimental and mechanistic carcinogenesis models of exposures to radon, uranium ore dust, and cigarette smoke are presented with statistical analyses of animal data. 20 refs., 1 fig

Pulmonary infections and risk of lung cancer among persons with AIDS.

Science.gov (United States)

Shebl, Fatma M; Engels, Eric A; Goedert, James J; Chaturvedi, Anil K

2010-11-01

Lung cancer risk is significantly increased among persons with AIDS (PWA), and increased smoking may not explain all of the elevated risk, suggesting a role for additional cofactors. We investigated whether AIDS-defining pulmonary infections (recurrent pneumonia, Pneumocystis jirovecii pneumonia, and pulmonary tuberculosis) affected the risk of subsequent lung cancer over 10 years after AIDS onset among 322,675 PWA, whose records were linked with cancer registries in 11 US regions. We assessed lung cancer hazard ratios (HRs) using Cox regression and indirectly adjusted HRs for confounding by smoking. Individuals with recurrent pneumonia (n = 5317) were at significantly higher lung cancer risk than those without [HR = 1.63, 95% confidence interval (CI) = 1.08 to 2.46, adjusted for age, race, sex, HIV acquisition mode, CD4 count, and AIDS diagnosis year]. This association was especially strong among young PWA (risk was unrelated to tuberculosis [(n = 13,878) HR = 1.12, 95% CI = 0.82 to 1.53] or Pneumocystis jirovecii pneumonia [(n = 69,771) HR = 0.97, 95% CI = 0.80 to 1.18]. The increased lung cancer risk associated with recurrent pneumonia supports the hypothesis that chronic pulmonary inflammation arising from infections contributes to lung carcinogenesis.

The mitochondrial activation of silicate and its role in silicosis, black lung disease and lung cancer.

Science.gov (United States)

Hadler, H I; Cook, G L

1979-01-01

Silicate substitutes for phosphate in the transitory uncoupling of rat liver mitochondria induced by hydrazine when beta-hydroxy-butyrate is the substrate. Uncoupling is blocked by rutamycin. Just as in the case when phosphate is combined with hydrazine, ATP, ADP, PPi, and Mg++ protect against hydrazine when silicate is combined with hydrazine. A high level of ADP in the absence of added phosphate, but in the presence of silicate, induces a pseudo state three of the mitochondria. Silicate, like sulfate and arsenate which have been reported previously, is activated by the enzymes which mediate oxidative phosphorylation. These results serve to explain a role for silicate in silicosis, black lung disease, and cancer. In addition, since there is suggestive evidence in the literature that lung tissue solubilizes asbestos fibers, these results not only expand the confluence between oxidative phosphorylation and chemical carcinogenesis but are correlated with the synergistic carcinogenicity of asbestos and smoking observed by epidemiologists.

A challenge to mutation theory of radiation carcinogenesis

International Nuclear Information System (INIS)

Watanabe, Masami

2006-01-01

This paper presents an objection against the commonly accepted mutation theory in radiation carcinogenesis. First, author's studies of X-ray irradiated syrian hamster embryo (SHE) cells on malignant morphological changes and mutational change of HGPRT gene showed that the changing patterns were quite different, and as well, other studies in mice gave the essentially similar results. Thus radiation-induced carcinogenesis in cells does not simply occur by an accumulation of radiation-induced mutation. Second, as cultured cells usually used for oncogenesis studies already have the infinitively proliferative ability, the author used the primary cell culture obtained from the rodent embryo. Even those cells became immortal to be cancerous after repeated culture passage with the higher frequency of 10 3 -10 4 relative to somatic cell mutation. Cells thus seem to be easily changeable to cancerous ones. Bystander effect can cause transformation in non-irradiated cells and genetic instability by radiation can form the potentially unstable chromatin region, which induces telomere instability. The author has found that, while short-lived radicals yielded by X-ray irradiation attack DNA to induce cell death and chromosome aberration, long-lived radicals in biomolecules do not, but can cause mutation and carcinogenesis, which are reduced by vitamine C supplementation. The author concludes that the primary target in the radiation carcinogenesis in cells and even in the whole individuals is conceivably protein and not DNA. (T.I.)

Immunohistochemical analysis of Clara cell secretory protein expression in a transgenic model of mouse lung carcinogenesis

International Nuclear Information System (INIS)

Hicks, Sarah M.; Vassallo, Jeffrey D.; Dieter, Matthew Z.; Lewis, Cindy L.; Whiteley, Laurence O.; Fix, Andrew S.; Lehman-McKeeman, Lois D.

2003-01-01

Immunohistochemical methods have been widely used to determine the histogenesis of spontaneous and chemically-induced mouse lung tumors. Typically, antigens for either alveolar Type II cells or bronchiolar epithelial Clara cells are studied. In the present work, the morphological and immunohistochemical phenotype of a transgenic mouse designed to develop lung tumors arising from Clara cells was evaluated. In this model, Clara cell-specific transformation is accomplished by directed expression of the SV40 large T antigen (TAg) under the mouse Clara cell secretory protein (CC10) promoter. In heterozygous mice, early lesions at 1 month of age consisted of hyperplastic bronchiolar epithelial cells. These progressed to adenoma by 2 months as proliferating epithelium extended into adjacent alveolar spaces. By 4 months, a large portion of the lung parenchyma was composed of tumor masses. Expression of constitutive CC10 was diminished in transgenic animals at all time points. Only the occasional cell or segment of the bronchiolar epithelium stained positively for CC10 by immunohistochemistry, and all tumors were found to be uniformly negative for staining. These results were corroborated by Western blotting, where CC10 was readily detectable in whole lung homogenate from nontransgenic animals, but not detected in lung from transgenic animals at any time point. Tumors were also examined for expression of surfactant apoprotein C (SPC), an alveolar Type II cell-specific marker, and found to be uniformly negative for staining. These results indicate that, in this transgenic model, expression of CC10, which is widely used to determine whether lung tumors arise from Clara cells, was reduced and subsequently lost during Clara cell tumor progression

(Radiation carcinogenesis in the whole body system)

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Fry, R.J.M.

1990-12-14

The objectives of the trip were: to take part in and to give the summary of a Symposium on Radiation Carcinogenesis at Tokyo, and to give a talk at the National Institute of Radiological Sciences at Chiba. The breadth of the aspects considered at the conference was about as broad as is possible, from effects at the molecular level to human epidemiology, from the effects of tritium to cancer induction by heavy ions. The events induced by cancer that lead to cancer and the events that are secondary are beginning to come into better focus but much is still not known. Interest in suppressor genes is increasing rapidly in the studies of human tumors and many would predict that the three or four suppressor genes associated with cancer are only the first sighting of a much larger number.

Anticarcinogenesis effect of Gynura procumbens (Lour Merr on tongue carcinogenesis in 4NQO-induced rat

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D. Agustina

2006-09-01

Full Text Available In Indonesia Gynura procumbens (Lour Merr leaves have been long used as various cancers medication. Many in vitro and in vivo studies have demonstrated anticarcinogenesis of ethanol extract of Gynura procumbens leaves. The aim of this study was to investigate the anticarcinogenesis of the ethanol extract of Gynura procumbens leaves on 4 nitroquinoline 1-oxide (4NQO-induced rat tongue carcinogenesis. Fifty six 4 week old male Sprague Dawley rats were used in this study and divided into 7 groups. Group 1, 2 and 3 were lingually induced by 4NQO for 8 weeks. In groups 2 and 3 the extract was given simultaneously with or after 4NQO induction finished, each for 10 weeks and 26 weeks, respectively. Groups 4, 5 and 6 were induced by 4NQO for 16 weeks. However, in groups 5 and 6 the extract was given as well simultaneously with or after the 4NQO induction, each for 18 weeks, respectively. Group 7 served as the as untreated control group. The results from microscopical assessment showed that tongue squamous cell carcinomas (SCC developed in 100% (3/3 of group 1. However, only 33.3% (2/6 and 25% (2/8 of rats in groups 2 and 3, respectively demonstrated tongue SCC. Among groups 4, 5 and 6, no significant difference of tongue SCC incidence was observed. From these results it is apparent that the ethanol extract of Gynura procumbens leaves could inhibit the progression of 4NQOinduced rat tongue carcinogenesis in the initiation phase.

A correlation study on position and volume variation of primary lung cancer during respiration by four-dimensional CT

International Nuclear Information System (INIS)

Zhang Yingjie; Li Jianbin; Tian Shiyu; Li Fengxiang; Fan Tingyong; Shao Qian; Xu Min; Lu Jie

2011-01-01

Objective: To investigate the correlation of position movement of primary tumor with interested organs and skin markers, and to investigate the correlation of volume variation of primary tumors and lungs during different respiration phases for patients with lung cancer at free breath condition scanned by four-dimensional CT (4DCT) simulation. Methods: 16 patients with lung cancer were scanned at free breath condition by simulation 4DCT which connected to a respiration-monitoring system. A coordinate system was created based on image of T 5 phase,gross tumor volume (GTV) and normal tissue structures of 10 phases were contoured. The three dimensional position variation of them were measured and their correlation were analyzed, and the same for the volume variation of GTV and lungs of 10 respiratory phases. Results: Movement range of lung cancer in different lobe differed extinct: 0.8 - 5.0 mm in upper lobe, 5.7 -5.9 mm in middle lobe and 10.2 - 13.7 mm in lower lobe, respectively. Movement range of lung cancer in three dimensional direction was different: z-axis 4.3 mm ± 4.3 mm > y-axis 2.2 mm ± 1.0 mm > x-axis 1.7 mm ± 1.5 mm (χ 2 =16.22, P =0.000), respectively. There was no statistical significant correlation for movement vector of GTV and interested structures (r =-0.50 - -0.01, P =0.058 - -0.961), nor for volume variation of tumor and lung (r =0.23, P =0.520). Conclusions: Based on 4DCT, statistically significant differences of GTV centroid movement are observed at different pulmonary lobes and in three dimensional directions. So individual 4DCT measurement is necessary for definition of internal target volume margin for lung cancer. (authors)

Gene therapy for lung cancer.

Science.gov (United States)

Toloza, Eric M; Morse, Michael A; Lyerly, H Kim

2006-09-01

Lung cancer patients suffer a 15% overall survival despite advances in chemotherapy, radiation therapy, and surgery. This unacceptably low survival rate is due to the usual finding of advanced disease at diagnosis. However, multimodality strategies using conventional therapies only minimally improve survival rates even in early stages of lung cancer. Attempts to improve survival in advanced disease using various combinations of platinum-based chemotherapy have demonstrated that no regimen is superior, suggesting a therapeutic plateau and the need for novel, more specific, and less toxic therapeutic strategies. Over the past three decades, the genetic etiology of cancer has been gradually delineated, albeit not yet completely. Understanding the molecular events that occur during the multistep process of bronchogenic carcinogenesis may make these tasks more surmountable. During these same three decades, techniques have been developed which allow transfer of functional genes into mammalian cells. For example, blockade of activated tumor-promoting oncogenes or replacement of inactivated tumor-suppressing or apoptosis-promoting genes can be achieved by gene therapy. This article will discuss the therapeutic implications of these molecular changes associated with bronchogenic carcinomas and will then review the status of gene therapies for treatment of lung cancer. (c) 2006 Wiley-Liss, Inc.

Radiation carcinogenesis: radioprotectors and photosensitizers

International Nuclear Information System (INIS)

Fry, R.J.M.

1982-01-01

This paper outlines 1) some of the salient features of radiation carcinogenesis that are pertinent to the questions of how the carcinogenic effects might be influenced, 2) the effects of radioprotectors on ionizing radiation-induced cancer, and 3) the effect of photosensitizers on UVR-induced skin cancer

Radiation carcinogenesis: radioprotectors and photosensitizers

Energy Technology Data Exchange (ETDEWEB)

Fry, R.J.M.

1982-01-01

This paper outlines 1) some of the salient features of radiation carcinogenesis that are pertinent to the questions of how the carcinogenic effects might be influenced, 2) the effects of radioprotectors on ionizing radiation-induced cancer, and 3) the effect of photosensitizers on UVR-induced skin cancer.

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

International Nuclear Information System (INIS)

Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

2012-01-01

Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As 2 O 3

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

2012-06-01

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

Radiation factors and smoking interaction at lung cancer incidence for workers at a nuclear enterprise

International Nuclear Information System (INIS)

Tokarskaya, Z.B.; Khokhryakov, V.F.; Okladnikova, N.D.; Belyaeva, Z.D.; Zhuntova, G.V.

1997-01-01

It was shown on the basis of retrospective investigation of 500 workers at a nuclear enterprise (162 cases of lung cancer, 338 persons as matching control) that the interaction of external gamma-irradiation (> 2.0 Gy) and the body - burden of 239 Pu (> 9.3 kBq) at lung cancer is characterized as the multiplicative effect. Combined influence of smoking and radiation factors dependent on smoking index (SI): it changed from additive up to multiplicative and than to antagonistic with the increase of the smoking effect. The received results could be explained on the basis of a two - mutation model of radiation carcinogenesis

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair.

Science.gov (United States)

Murgia, Claudio; Caporale, Marco; Ceesay, Ousman; Di Francesco, Gabriella; Ferri, Nicola; Varasano, Vincenzo; de las Heras, Marcelo; Palmarini, Massimo

2011-03-01

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer.

Lung deformations and radiation-induced regional lung collapse in patients treated with stereotactic body radiation therapy

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Diot, Quentin, E-mail: quentin.diot@ucdenver.edu; Kavanagh, Brian; Vinogradskiy, Yevgeniy; Gaspar, Laurie; Miften, Moyed [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado 80045 (United States); Garg, Kavita [Department of Radiology, University of Colorado School of Medicine, Aurora, Colorado 80045 (United States)

2015-11-15

Purpose: To differentiate radiation-induced fibrosis from regional lung collapse outside of the high dose region in patients treated with stereotactic body radiation therapy (SBRT) for lung tumors. Methods: Lung deformation maps were computed from pre-treatment and post-treatment computed tomography (CT) scans using a point-to-point translation method. Fifty anatomical landmarks inside the lung (vessel or airway branches) were matched on planning and follow-up scans for the computation process. Two methods using the deformation maps were developed to differentiate regional lung collapse from fibrosis: vector field and Jacobian methods. A total of 40 planning and follow-ups CT scans were analyzed for 20 lung SBRT patients. Results: Regional lung collapse was detected in 15 patients (75%) using the vector field method, in ten patients (50%) using the Jacobian method, and in 12 patients (60%) by radiologists. In terms of sensitivity and specificity the Jacobian method performed better. Only weak correlations were observed between the dose to the proximal airways and the occurrence of regional lung collapse. Conclusions: The authors presented and evaluated two novel methods using anatomical lung deformations to investigate lung collapse and fibrosis caused by SBRT treatment. Differentiation of these distinct physiological mechanisms beyond what is usually labeled “fibrosis” is necessary for accurate modeling of lung SBRT-induced injuries. With the help of better models, it becomes possible to expand the therapeutic benefits of SBRT to a larger population of lung patients with large or centrally located tumors that were previously considered ineligible.

Comfrey (Symphytum officinale. L. and Experimental Hepatic Carcinogenesis: A Short-Term Carcinogenesis Model Study

Directory of Open Access Journals (Sweden)

Maria Fernanda Pereira Lavieri Gomes

2010-01-01

Full Text Available Comfrey or Symphytum officinale (L. (Boraginaceae is a very popular plant used for therapeutic purposes. Since the 1980s, its effects have been studied in long-term carcinogenesis studies, in which Comfrey extract is administered at high doses during several months and the neoplastic hepatic lesions are evaluated. However, the literature on this topic is very poor considering the studies performed under short-term carcinogenesis protocols, such as the ‘resistant hepatocyte model’ (RHM. In these studies, it is possible to observe easily the phenomena related to the early phases of tumor development, since pre-neoplastic lesions (PNLs rise in about 1–2 months of chemical induction. Herein, the effects of chronic oral treatment of rats with 10% Comfrey ethanolic extract were evaluated in a RHM. Wistar rats were sequentially treated with N-nitrosodiethylamine (ip and 2-acetilaminofluorene (po, and submitted to hepatectomy to induce carcinogenesis promotion. Macroscopic/microscopic quantitative analysis of PNL was performed. Non-parametric statistical tests (Mann–Whitney and χ2 were used, and the level of significance was set at P ≤ 0.05. Comfrey treatment reduced the number of pre-neoplastic macroscopic lesions up to 1 mm (P ≤ 0.05, the percentage of oval cells (P = 0.0001 and mitotic figures (P = 0.007, as well as the number of Proliferating Cell Nuclear Antigen (PCNA positive cells (P = 0.0001 and acidophilic pre-neoplastic nodules (P = 0.05. On the other hand, the percentage of cells presenting megalocytosis (P = 0.0001 and vacuolar degeneration (P = 0.0001 was increased. Scores of fibrosis, glycogen stores and the number of nucleolus organizing regions were not altered. The study indicated that oral treatment of rats with 10% Comfrey alcoholic extract reduced cell proliferation in this model.

Comfrey (Symphytum Officinale. l.) and Experimental Hepatic Carcinogenesis: A Short-term Carcinogenesis Model Study.

Science.gov (United States)

Gomes, Maria Fernanda Pereira Lavieri; de Oliveira Massoco, Cristina; Xavier, José Guilherme; Bonamin, Leoni Villano

2010-06-01

Comfrey or Symphytum officinale (L.) (Boraginaceae) is a very popular plant used for therapeutic purposes. Since the 1980s, its effects have been studied in long-term carcinogenesis studies, in which Comfrey extract is administered at high doses during several months and the neoplastic hepatic lesions are evaluated. However, the literature on this topic is very poor considering the studies performed under short-term carcinogenesis protocols, such as the 'resistant hepatocyte model' (RHM). In these studies, it is possible to observe easily the phenomena related to the early phases of tumor development, since pre-neoplastic lesions (PNLs) rise in about 1-2 months of chemical induction. Herein, the effects of chronic oral treatment of rats with 10% Comfrey ethanolic extract were evaluated in a RHM. Wistar rats were sequentially treated with N-nitrosodiethylamine (ip) and 2-acetilaminofluorene (po), and submitted to hepatectomy to induce carcinogenesis promotion. Macroscopic/microscopic quantitative analysis of PNL was performed. Non-parametric statistical tests (Mann-Whitney and χ(2)) were used, and the level of significance was set at P ≤ 0.05. Comfrey treatment reduced the number of pre-neoplastic macroscopic lesions up to 1 mm (P ≤ 0.05), the percentage of oval cells (P = 0.0001) and mitotic figures (P = 0.007), as well as the number of Proliferating Cell Nuclear Antigen (PCNA) positive cells (P = 0.0001) and acidophilic pre-neoplastic nodules (P = 0.05). On the other hand, the percentage of cells presenting megalocytosis (P = 0.0001) and vacuolar degeneration (P = 0.0001) was increased. Scores of fibrosis, glycogen stores and the number of nucleolus organizing regions were not altered. The study indicated that oral treatment of rats with 10% Comfrey alcoholic extract reduced cell proliferation in this model.

Lung development and postnatal survival for rats exposed in utero to a high-boiling coal liquid

Energy Technology Data Exchange (ETDEWEB)

Springer, D.L.; Hackett, P.L.; Miller, R.A.; Buschbom, R.L.

1986-01-01

The study reported determines postnatal viability and development of survivors following in utero exposure to Harmarville process solvent (HPS), a wide-boiling-range (150 to > 455/sup 0/C) coal liquid. For this study, 0.74 g kg/sup -1/ of the coal liquid was administered (by intragastric intubation) to rats from 12 to 14 dg. Offspring were evaluated for postnatal survival, growth and lung and thymus weights. Fifty-four percent of the exposed pups and 9% of the control pups died between birth and 3 days postpartum. Of the treated pups that died, 10% (6/5; pups/litters) had cleft palate, 27% (17/9) had small lungs and 33% (21/8) had both cleft palate and small lungs. No gross malformations were observed in the remaining 30% of the dead pups. Microscopic examination of lungs from HPS-treated pups revealed no evident histological abnormalities. Body, lung and thymus weights for treated animals that died were significantly less than those of controls. Surviving exposed pups weighed significantly less than control pups from 0.25 to 21 days postpartum and their thymus weights were also depressed through 21 days postpartum. These data suggest that retarded lung growth during prenatal life as a result of in utero exposure to the coal liquid contributes to a significant portion of the observed neonatal mortality. Furthermore, lung weights of survivors, although significantly lower than control values through 7 days postpartum, appeared to have recovered by 21 days postpartum.

Mechanistic study on lung cancer mortality after radon exposure in the Wismut cohort supports important role of clonal expansion in lung carcinogenesis

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Zaballa, I.; Eidemueller, M. [Helmholtz Zentrum Muenchen, Institute of Radiation Protection, Neuherberg (Germany)

2016-08-15

Lung cancer mortality after radon exposure in the Wismut cohort was analyzed using the two-stage clonal expansion (TSCE) model. A total of 2996 lung cancer deaths among the 58,695 male workers were observed during the follow-up period between 1946 and 2003. Adjustment to silica exposure was performed to find a more accurate estimation of the risk of radon exposure. An additional analysis with the descriptive excess relative risk (ERR) model was carried out for comparison. The TSCE model that best describes the data is nonlinear in the clonal expansion with radon exposure and has a saturation level at an exposure rate of d{sub r} ≅ 100 WLM/yr. The excess relative risk decreases with age and shows an inverse exposure rate effect. In comparison with the ERR model, the TSCE model predicts a considerably larger risk for low exposures rates below 50 WLM/yr. Comparison to other mechanistic studies of lung cancer after exposure to alpha particles using the TSCE model reveals an extraordinary consistency in the main features of the exposure response, given the diversity in the characteristics of the cohorts and the exposure across different studies. This suggests that a nonlinear response mechanism in the clonal expansion, with some level of saturation at large exposure rates, may be playing a crucial role in the development of lung cancer after alpha particle irradiation. (orig.)

Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

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Tanaka, Takuji [Cytopatholgy Division, Tohkai Cytopathology Institute, Cancer Research and Prevention (TCI-CaRP), 5-1-2 Minami-uzura, Gifu 500-8285 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan)

2012-07-16

Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described.

Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response.

Science.gov (United States)

Gong, Wei-Jing; Yin, Ji-Ye; Li, Xiang-Ping; Fang, Chao; Xiao, Di; Zhang, Wei; Zhou, Hong-Hao; Li, Xi; Liu, Zhao-Qian

2016-06-01

Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis and drug efficacy. Platinum-based chemotherapy is first-line treatment for lung cancer chemotherapy. In this study, we aimed to investigate the association of well-characterized lung cancer lncRNA genetic polymorphisms with the lung cancer susceptibility and platinum-based chemotherapy response. A total of 498 lung cancer patients and 213 healthy controls were recruited in the study. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Thirteen polymorphisms in HOXA distal transcript antisense RNA (HOTTIP), HOX transcript antisense intergenic RNA (HOTAIR), H19, CDKN2B antisense RNA 1 (ANRIL), colon cancer-associated transcript 2 (CCAT2), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed gene 3 (MEG3) genes were genotyped by allele-specific MALDI-TOF mass spectrometry. We found that patients with HOTTIP rs5883064 C allele or rs1859168 A allele had increased lung cancer risk (P = 0.01, P = 0.01, respectively). CCAT2 rs6983267 (P = 0.02, adenocarcinoma) and H19 rs2107425 (P = 0.02, age under 50 years) showed strong relationship with lung cancer susceptibility. CCAT2 rs6983267, H19 rs2839698, MALAT1 rs619586, and HOTAIR rs7958904 were associated with platinum-based chemotherapy response in dominant model ((P = 0.02, P = 0.04, P = 0.04, P = 0.01, respectively). ANRIL rs10120688 (P = 0.02, adenocarcinoma) and rs1333049 (P = 0.04, small-cell lung cancer), H19 rs2107425 (P = 0.02, small-cell lung cancer) and HOTAIR rs1899663 (P = 0.03, male; P = 0.03, smoker) were associated with response to platinum-based chemotherapy. HOTTIP, CCAT2, H19, HOTAIR, MALATI, ANRIL genetic polymorphisms were significantly associated with lung cancer susceptibility or platinum-based chemotherapy response. They may be potential clinical biomarkers to predict lung cancer risk and platinum

Lymphotoxin prevention of diethylnitrosamine carcinogenesis in vivo

International Nuclear Information System (INIS)

Ransom, J.H.; Evans, C.H.; DiPaolo, J.A.

1982-01-01

Development of intervention measures to control cancer would be facilitated by being able to monitor in vivo carcinogenesis by in vitro quantitation of early indices of neoplastic transformation to assess the in vivo effectiveness of preventive-therapeutic measures. Pregnant Syrian golden hamsters were used in an in vivo-in vitro transplacental model of carcinogenesis to determine the extent that in vivo administration of immunologic hormone preparations along with chemical carcinogen would prevent morphologic transformation assessed in vitro. Pregnant hamsters at 10-11 days of gestation were given injections ip of 3 mg diethylnitrosamine (DENA)/100 g body weight and were killed 2 days later when fetal cells were seeded for colony formation. The frequency of morphologically transformed colonies was assessed after 7 days of growth. Cloning efficiency and mean transformation frequency after DENA exposure were 3.6% and 1 X 10(-4) per cell seeded, respectively. The ip injection of an immunologic hormone preparation reduced the transformation frequency by 46%. The hormone preparation, containing 10,000 U of lymphotoxin but no detectable interferon, was the ultrafiltered lymphokines (greater than 10,000 mol wt) from phytohemagglutinin-stimulated hamster peritoneal leukocytes. The effect of lymphotoxin on cocarcinogenic exposure of fetal cells to DENA in vivo followed by X-irradiation in vitro was also determined. Cells exposed to 250 rad in vitro had a cloning efficiency of 0.5% and a transformation frequency of 0.4 X 10(-4) per cell seeded. After DENA injection and X-irradiation, the transformation frequency increased to 1 X 10(-4) and was inhibited 64% by lymphotoxin in vivo. Thus immunologic hormones (e.g., lymphotoxin) can prevent carcinogenesis in vivo. Furthermore, in vitro quantitation of transformation is a rapid means for evaluating therapeutic and autochthonous effector mechanisms for their ability to prevent or otherwise modulate carcinogenesis in vivo

Lower radiation weighting factor for radon indicated in mechanistic modelling of human lung cancer

International Nuclear Information System (INIS)

Brugmans, M.J.P.; Leenhouts, H.P.

2002-01-01

A two-mutation carcinogenesis (TMC) model was fitted to the age-dependent lung cancer incidence in a cohort of Dutch Hodgkin patients treated with radiotherapy. Employing the results of previous TMC analyses of lung cancer due to smoking (by British doctors) and due to exposure to radon (for Colorado miners) a model fit was obtained with an estimate for the low LET radiation effect at the cellular level. This allows risk calculations for lung cancer from low LET radiation. The excess absolute risks are in tune with the values reported in the literature, the excess relative risks differ among the exposed groups. Comparing the cellular radiation coefficients for radon and for low LET radiation leads to an estimated radiation weighting factor for radon of 3 (0.1-6). (author)

Helicobacter pylori seropositivity and risk of lung cancer.

Directory of Open Access Journals (Sweden)

Jill Koshiol

Full Text Available Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter pylori (H. pylori is a risk factor for distal stomach cancer, and a few small studies have suggested that H. pylori may be a potential risk factor for lung cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma cases, 350 squamous cell carcinoma cases, and 700 controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC cohort of male Finnish smokers. Controls were one-to-one matched by age and date of baseline serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA antigens, we calculated odds ratios (ORs and 95% confidence intervals (95% CIs for associations between H. pylori seropositivity and lung cancer risk using conditional logistic regression. H. pylori seropositivity was detected in 79.7% of cases and 78.5% of controls. After adjusting for pack-years and cigarettes smoked per day, H. pylori seropositivity was not associated with either adenocarcinoma (OR: 1.1, 95% CI: 0.75-1.6 or squamous cell carcinoma (OR: 1.1, 95% CI: 0.77-1.7. Results were similar for CagA-negative and CagA-positive H. pylori seropositivity. Despite earlier small studies suggesting that H. pylori may contribute to lung carcinogenesis, H. pylori seropositivity does not appear to be associated with lung cancer.

Hypoxic pulmonary vasoconstriction in reptiles: a comparative study of four species with different lung structures and pulmonary blood pressures.

Science.gov (United States)

Skovgaard, Nini; Abe, Augusto S; Andrade, Denis V; Wang, Tobias

2005-11-01

Low O2 levels in the lungs of birds and mammals cause constriction of the pulmonary vasculature that elevates resistance to pulmonary blood flow and increases pulmonary blood pressure. This hypoxic pulmonary vasoconstriction (HPV) diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts and is considered important for the local matching of ventilation to blood perfusion. In the present study, the effects of acute hypoxia on pulmonary and systemic blood flows and pressures were measured in four species of anesthetized reptiles with diverse lung structures and heart morphologies: varanid lizards (Varanus exanthematicus), caimans (Caiman latirostris), rattlesnakes (Crotalus durissus), and tegu lizards (Tupinambis merianae). As previously shown in turtles, hypoxia causes a reversible constriction of the pulmonary vasculature in varanids and caimans, decreasing pulmonary vascular conductance by 37 and 31%, respectively. These three species possess complex multicameral lungs, and it is likely that HPV would aid to secure ventilation-perfusion homogeneity. There was no HPV in rattlesnakes, which have structurally simple lungs where local ventilation-perfusion inhomogeneities are less likely to occur. However, tegu lizards, which also have simple unicameral lungs, did exhibit HPV, decreasing pulmonary vascular conductance by 32%, albeit at a lower threshold than varanids and caimans (6.2 kPa oxygen in inspired air vs. 8.2 and 13.9 kPa, respectively). Although these observations suggest that HPV is more pronounced in species with complex lungs and functionally divided hearts, it is also clear that other components are involved.

Dosimetric Advantages of Four-Dimensional Adaptive Image-Guided Radiotherapy for Lung Tumors Using Online Cone-Beam Computed Tomography

International Nuclear Information System (INIS)

Harsolia, Asif; Hugo, Geoffrey D.; Kestin, Larry L.; Grills, Inga S.; Yan Di

2008-01-01

Purpose: This study compares multiple planning techniques designed to improve accuracy while allowing reduced planning target volume (PTV) margins though image-guided radiotherapy (IGRT) with four-dimensional (4D) cone-beam computed tomography (CBCT). Methods and Materials: Free-breathing planning and 4D-CBCT scans were obtained in 8 patients with lung tumors. Four plans were generated for each patient: 3D-conformal, 4D-union, 4D-offline adaptive with a single correction (offline ART), and 4D-online adaptive with daily correction (online ART). For the 4D-union plan, the union of gross tumor volumes from all phases of the 4D-CBCT was created with a 5-mm expansion applied for setup uncertainty. For offline and online ART, the gross tumor volume was delineated at the mean position of tumor motion from the 4D-CBCT. The PTV margins were calculated from the random components of tumor motion and setup uncertainty. Results: Adaptive IGRT techniques provided better PTV coverage with less irradiated normal tissues. Compared with 3D plans, mean relative decreases in PTV volumes were 15%, 39%, and 44% using 4D-union, offline ART, and online ART planning techniques, respectively. This resulted in mean lung volume receiving ≥ 20Gy (V20) relative decreases of 21%, 23%, and 31% and mean lung dose relative decreases of 16%, 26%, and 31% for the 4D-union, 4D-offline ART, and 4D-online ART, respectively. Conclusions: Adaptive IGRT using CBCT is feasible for the treatment of patients with lung tumors and significantly decreases PTV volume and dose to normal tissues, allowing for the possibility of dose escalation. All analyzed 4D planning strategies resulted in improvements over 3D plans, with 4D-online ART appearing optimal

OGG1 expression and OGG1 Ser326Cys polymorphism and risk of lung cancer in a prospective study

DEFF Research Database (Denmark)

Hatt, Lotte; Loft, Steffen; Risom, Lotte

2008-01-01

Oxidative DNA damage is believed to be implicated in lung carcinogenesis. 8-OxodG is a mutagenic and abundant oxidative modification induced in DNA. OGG1, NEIL1 and MUTYH are all involved in the repair and prevention of 8-oxodG-derived mutations and may be up-regulated by oxidative stress...

Radiation carcinogenesis, laboratory studies

International Nuclear Information System (INIS)

Shellabarger, C.J.

1974-01-01

Laboratory studies on radioinduced carcinogenesis are reviewed. Some topics discussed are: radioinduced neoplasia in relation to life shortening; dose-response relationships; induction of skin tumors in rats by alpha particles and electrons; effects of hormones on tumor response; effects of low LET radiations delivered at low dose-rates; effects of fractionated neutron radiation; interaction of RBE and dose rate effects; and estimates of risks for humans from animal data. (U.S.)

Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.

Science.gov (United States)

Kravchenko, Julia; Akushevich, Igor; Seewaldt, Victoria L; Abernethy, Amy P; Lyerly, H Kim

2011-07-01

The observed bimodal patterns of breast cancer incidence in the U.S. suggested that breast cancer may be viewed as more than one biological entity. We studied the factors potentially contributing to this phenomenon, specifically focusing on how disease heterogeneity could be linked to breast carcinogenesis mechanisms. Using empirical analyses and population-based biologically motivated modeling, age-specific patterns of incidence of ductal and lobular breast carcinomas from the SEER registry (1990-2003) were analyzed for heterogeneity and characteristics of carcinogenesis, stratified by race, stage, grade, and estrogen (ER)/progesterone (PR) receptor status. The heterogeneity of breast carcinoma age patterns decreased after stratification by grade, especially for grade I and III tumors. Stratification by ER/PR status further reduced the heterogeneity, especially for ER(+)/PR(-) and ER(-)/(-) tumors; however, the residual heterogeneity was still observed. The number of rate-limiting events of carcinogenesis and the latency of ductal and lobular carcinomas differed, decreasing from grade I to III, with poorly differentiated tumors associated with the least number of carcinogenesis stages and the shortest latency. Tumor grades play important role in bimodal incidence of breast carcinoma and have distinct mechanisms of carcinogenesis. Race and cancer subtype could play modifying role. ER/PR status contributes to the observed heterogeneity, but is subdominant to tumor grade. Further studies on sources of "remaining" heterogeneity of population with breast cancer (such as genetic/epigenetic characteristics) are necessary. The results of this study could suggest stratification rather than unification of breast cancer prevention strategies, risk assessment, and treatment.

Radiogenic cell transformation and carcinogenesis

Science.gov (United States)

Yang, T. C.; Georgy, K. A.; Mei, M.; Durante, M.; Craise, L. M.

1995-01-01

Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic

Liver Development, Regeneration, and Carcinogenesis

Directory of Open Access Journals (Sweden)

Janet W. C. Kung

2010-01-01

Full Text Available The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.

Reciprocal activation of α5-nAChR and STAT3 in nicotine-induced human lung cancer cell proliferation.

Science.gov (United States)

Zhang, Yao; Jia, Yanfei; Li, Ping; Li, Huanjie; Xiao, Dongjie; Wang, Yunshan; Ma, Xiaoli

2017-07-20

Cigarette smoking is the top environmental risk factor for lung cancer. Nicotine, the addictive component of cigarettes, induces lung cancer cell proliferation, invasion and migration via the activation of nicotinic acetylcholine receptors (nAChRs). Genome-wide association studies (GWAS) show that CHRNA5 gene encoding α5-nAChR is especially relevant to lung cancer. However, the mechanism of this subunit in lung cancer is not clear. In the present study, we demonstrate that the expression of α5-nAChR is correlated with phosphorylated STAT3 (pSTAT3) expression, smoking history and lower survival of non-small cell lung cancer (NSCLC) samples. Nicotine increased the levels of α5-nAChR mRNA and protein in NSCLC cell lines and activated the JAK2/STAT3 signaling cascade. Nicotine-induced activation of JAK2/STAT3 signaling was inhibited by the silencing of α5-nAChR. Characterization of the CHRNA5 promoter revealed four STAT3-response elements. ChIP assays confirmed that the CHRNA5 promoter contains STAT3 binding sites. By silencing STAT3 expression, nicotine-induced upregulation of α5-nAChR was suppressed. Downregulation of α5-nAChR and/or STAT3 expression inhibited nicotine-induced lung cancer cell proliferation. These results suggest that there is a feedback loop between α5-nAChR and STAT3 that contributes to the nicotine-induced tumor cell proliferation, which indicates that α5-nAChR is an important therapeutic target involved in tobacco-associated lung carcinogenesis. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Prediction of lung cells oncogenic transformation for induced radon progeny alpha particles using sugarscape cellular automata.

Science.gov (United States)

Baradaran, Samaneh; Maleknasr, Niaz; Setayeshi, Saeed; Akbari, Mohammad Esmaeil

2014-01-01

Alpha particle irradiation from radon progeny is one of the major natural sources of effective dose in the public population. Oncogenic transformation is a biological effectiveness of radon progeny alpha particle hits. The biological effects which has caused by exposure to radon, were the main result of a complex series of physical, chemical, biological and physiological interactions. The cellular and molecular mechanisms for radon-induced carcinogenesis have not been clear yet. Various biological models, including cultured cells and animals, have been found useful for studying the carcinogenesis effects of radon progeny alpha particles. In this paper, sugars cape cellular automata have been presented for computational study of complex biological effect of radon progeny alpha particles in lung bronchial airways. The model has included mechanism of DNA damage, which has been induced alpha particles hits, and then formation of transformation in the lung cells. Biomarkers were an objective measure or evaluation of normal or abnormal biological processes. In the model, the metabolism rate of infected cell has been induced alpha particles traversals, as a biomarker, has been followed to reach oncogenic transformation. The model results have successfully validated in comparison with "in vitro oncogenic transformation data" for C3H 10T1/2 cells. This model has provided an opportunity to study the cellular and molecular changes, at the various stages in radiation carcinogenesis, involving human cells. It has become well known that simulation could be used to investigate complex biomedical systems, in situations where traditional methodologies were difficult or too costly to employ.

Single-dose and fractionated irradiation of four human lung cancer cell lines in vitro

International Nuclear Information System (INIS)

Brodin, O.; Lennartsson, L.; Nilsson, S.

1991-01-01

Four established human lung cancer cell lines were exposed to single-dose irradiation. The survival curves of 2 small cell lung carcinomas (SCLC) were characterized by a limited capacity for repair with small and moderate shoulders with extrapolation numbers (n) of 1.05 and 1.60 respectively. Two non-small cell lung carcinoma (NSCLC) cell lines, one squamous cell (SQCLC) and one large cell (LCLC) had large shoulders with n-values of 73 and 15 respectively. The radiosensitivity when measured as D 0 did not, however, differ as much from cell line to cell line, with values from 1.22 to 1.65. The surviving fraction after 2 Gy (SF2) was 0.24 and 0.42 respectively in the SCLC cell lines and 0.90 and 0.88 respectively in the NSCLC cell lines. Fractionated irradiation delivered according to 3 different schedules was also investigated. All the schedules delivered a total dose of 10 Gy in 5 days and were applied in 1, 2 and 5 Gy dose fractions respectively. Survival followed the pattern found after single-dose irradiation; it was lowest in the SCLC cell line with the lowest SF and highest in the two NSCLC cell lines. In the SCLC cell lines all schedules were approximately equally efficient. In the LCLC and in the SQCLC cell lines, the 5 Gy schedule killed more cells than the 1 and 2 Gy schedules. The results indicate that the size of the shoulder of the survival curve is essential when choosing the most tumoricidal fractionation schedule. (orig.)

Introduction to Genetic Mechanisms of Carcinogenesis

International Nuclear Information System (INIS)

Yang, W.K.

1983-01-01

Recent technical advances in nucleic acid research and molecular biology have made it possible to explore the complicated genetic systems of eukaryotic cells. One of the fields showing rapid progress concerns genes and gene regulatory functions related to neoplastic processes. Thus, the 35th Annual Conference of the Biology Division of Oak Ridge National Laboratory, held at Gatlinburg, April 12-15, 1982, was organized with the intention to bring together investigators working on seemingly diverse fields of cancer research to discuss and exchange their views on the genetic mechanisms of carcinogenesis. The meeting was attended by workers from chemical, physical as well as biological carcinogenesis fields, by classical geneticists as well as by molecular biologists, and by researchers interested in experimental as well as in human cancers. Included in this volume are papers by the invited speakers of the symposium as well as by those presenting poster papers at the meeting

Assessing Respiration-Induced Tumor Motion and Internal Target Volume Using Four-Dimensional Computed Tomography for Radiotherapy of Lung Cancer

International Nuclear Information System (INIS)

Liu, H. Helen; Balter, Peter; Tutt, Teresa; Choi, Bum; Zhang, Joy; Wang, Catherine; Chi, Melinda; Luo Dershan; Pan Tinsu; Hunjan, Sandeep; Starkschall, George; Rosen, Isaac; Prado, Karl; Liao Zhongxing; Chang, Joe; Komaki, Ritsuko; Cox, James D.; Mohan, Radhe; Dong Lei

2007-01-01

Purpose: To assess three-dimensional tumor motion caused by respiration and internal target volume (ITV) for radiotherapy of lung cancer. Methods and Materials: Respiration-induced tumor motion was analyzed for 166 tumors from 152 lung cancer patients, 57.2% of whom had Stage III or IV non-small-cell lung cancer. All patients underwent four-dimensional computed tomography (4DCT) during normal breathing before treatment. The expiratory phase of 4DCT images was used as the reference set to delineate gross tumor volume (GTV). Gross tumor volumes on other respiratory phases and resulting ITVs were determined using rigid-body registration of 4DCT images. The association of GTV motion with various clinical and anatomic factors was analyzed statistically. Results: The proportions of tumors that moved >0.5 cm along the superior-inferior (SI), lateral, and anterior-posterior (AP) axes during normal breathing were 39.2%, 1.8%, and 5.4%, respectively. For 95% of the tumors, the magnitude of motion was less than 1.34 cm, 0.40 cm, and 0.59 cm along the SI, lateral, and AP directions. The principal component of tumor motion was in the SI direction, with only 10.8% of tumors moving >1.0 cm. The tumor motion was found to be associated with diaphragm motion, the SI tumor location in the lung, size of the GTV, and disease T stage. Conclusions: Lung tumor motion is primarily driven by diaphragm motion. The motion of locally advanced lung tumors is unlikely to exceed 1.0 cm during quiet normal breathing except for small lesions located in the lower half of the lung

Carcinogenesis and low-level ionizing radiation with special reference to lung cancer and exposure to radon daughters

International Nuclear Information System (INIS)

Fabrikant, J.I.

1982-06-01

The quantitative estimation of the carcinogenic risk of low-dose, high-LET radiation in the case of exposure to radon daughters and lung-cancer is subject to numerous uncertainties. The greatest of these concerns the parametric values of the dose-response curve. We lack knowledge and an understanding of the dosimetry and the distribution of aggregates of radioactivity that remain localized as hot spots in specific regions of the lungs and the influence on greater or lesser risk of lung cancer per average lung dose than uniformly deposited radiation (NRC76). We have only a limited understanding of the response to exposure to high-LET radiations, such as alpha particles, for which linear risk estimates for low doses are less likely to overestimate the risk, and may, in fact, underestimate the risk (BEIR80). Other uncertainties include the length of the latency period, the RBE for alpha radiation relative to gamma radiation, the period during which the radiation risk is expressed, the risk projection model used - whether absolute or relative - for projecting risk beyond the period of observation, the effect of dose rate and protraction of dose, and the influence of differences in the natural incidence of lung cancer in different populations. In addition, uncertainties are introduced by the biological and life-style risk characteristics of humans, for example, the effect of sex, the effect of age at the time of irradiation and at the time of appearance of the cancer, the influence of length of observation or follow-up of the study populations, and the influence of perhaps the most important confounding bias, cigarette-smoking. The collective influence of these uncertainties is such as to deny great credibility to any estimate of human lung cancer risk and other cancer risk that can be made for low-dose, high-LET radon daughter radiation exposure

Carcinogenesis and low-level ionizing radiation with special reference to lung cancer and exposure to radon daughters

Energy Technology Data Exchange (ETDEWEB)

Fabrikant, J.I.

1982-06-01

The quantitative estimation of the carcinogenic risk of low-dose, high-LET radiation in the case of exposure to radon daughters and lung-cancer is subject to numerous uncertainties. The greatest of these concerns the parametric values of the dose-response curve. We lack knowledge and an understanding of the dosimetry and the distribution of aggregates of radioactivity that remain localized as hot spots in specific regions of the lungs and the influence on greater or lesser risk of lung cancer per average lung dose than uniformly deposited radiation (NRC76). We have only a limited understanding of the response to exposure to high-LET radiations, such as alpha particles, for which linear risk estimates for low doses are less likely to overestimate the risk, and may, in fact, underestimate the risk (BEIR80). Other uncertainties include the length of the latency period, the RBE for alpha radiation relative to gamma radiation, the period during which the radiation risk is expressed, the risk projection model used - whether absolute or relative - for projecting risk beyond the period of observation, the effect of dose rate and protraction of dose, and the influence of differences in the natural incidence of lung cancer in different populations. In addition, uncertainties are introduced by the biological and life-style risk characteristics of humans, for example, the effect of sex, the effect of age at the time of irradiation and at the time of appearance of the cancer, the influence of length of observation or follow-up of the study populations, and the influence of perhaps the most important confounding bias, cigarette-smoking. The collective influence of these uncertainties is such as to deny great credibility to any estimate of human lung cancer risk and other cancer risk that can be made for low-dose, high-LET radon daughter radiation exposure.

Risk-benefit analysis and cost-effectiveness analysis of lung cancer screening by spiral CT

International Nuclear Information System (INIS)

Iinuma, Takeshi

1999-01-01

Mass screening of lung cancer has been widely performed using indirect chest X-ray method in Japan. However reduction of the mortality for lung cancer is questioned. We have proposed that recently developed spiral CT should be adopted for the screening of lung cancer, since CT has an excellent detectability for small nodule. Lung Cancer Screening CT (LSCT) has been developed by author's group using spiral CT with low dose and light weight in order to make a mobile unit. In this paper risk-benefit analysis and cost-effectiveness analysis are described for the LSCT screening of lung cancer. As a risk, radiation carcinogenesis due to exposure from LSCT are compared with gain of life-expectancy by screening and men of 40 years or more and women of 45 years or more are justified. The cost per person-year is estimated for LSCT screening which is better than that of present method, although total cost is higher. The LSCT screening could be recommended if total cost is affordable. (author)

Potential for Interfraction Motion to Increase Esophageal Toxicity in Lung SBRT

OpenAIRE

Pham, Anthony Hoai-Nam; Yorke, Ellen; Rimner, Andreas; Wu, Abraham Jing-Ching

2017-01-01

Purpose: To characterize the effect of the relative motion of esophagus and tumor on radiation doses to the esophagus in patients treated with stereotactic body radiation therapy for central lung tumors. Methods and Materials: Fifty fractions of stereotactic body radiation therapy in 10 patients with lung tumors within 2.5 cm of the esophagus were reviewed. The esophagus was delineated on each treatment’s cone-beam computed tomography scan and compared to its position on the planning scan. Do...

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

Energy Technology Data Exchange (ETDEWEB)

Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Mok, Tony S.K. [Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Warner, Timothy D. [The William Harvey Research Institute, Queen Mary University of London, London (United Kingdom); Underwood, Malcolm J. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Chen, George G., E-mail: gchen@cuhk.edu.hk [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong)

2009-10-15

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB{sub 2}) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB{sub 2} but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

International Nuclear Information System (INIS)

Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S.; Mok, Tony S.K.; Warner, Timothy D.; Underwood, Malcolm J.; Chen, George G.

2009-01-01

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB 2 ) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB 2 but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

The effect of irradiation on lung function and perfusion in patients with lung cancer

International Nuclear Information System (INIS)

Abratt, Raymond P.; Willcox, Paul A.

1995-01-01

Purpose: To prospectively study the changes in lung function in patients with lung carcinoma treated with relatively high doses of irradiation. Methods and Materials: Lung function was assessed prior to and at 6 and 12 months following radiation therapy by a clinical dyspnea score, formal pulmonary function tests (lung volume spirometry and diffusion capacity) as well as an ipsilateral hemithorax lung perfusion scan. Changes in dyspnea score were evaluated by the chi-square and the Fishers exact test. Changes in formal lung function tests were compared with the t-test for dependent data and correlations with the t-test for independent data. Fifty-one patients were entered into the study. There were 42 evaluable patients at 6 months after irradiation and 22 evaluable patients at 12 months after irradiation. Results: A worsening of dyspnea score from 1 to 2, which is clinically acceptable, occurred in 50% or more of patients. However, a dyspnea score of 3, which is a serious complication, developed in only 5% of patients. The diffusion capacity (DLCO) decreased by 14% at 6 months and 12% at 12 months) (p < 0.0001). The forced vital capacity and total lung capacity decreased between 6% and 8% at 6 month and 12 months, which was statistically significant. The forced expiratory volume in 1 s decreased between 2 and 3% at 6 month and 12 months, which was not statistically significant. The ipsilateral hemithorax perfusion decreased by 17 and 20% at 6 and 12 months (p < 0.0001). There was no correlation between the initial hemithorax perfusion, or its decrease at follow up and the decrease in DLCO. Conclusion: Lung irradiation results in some loss of lung function in patients with lung cancer with a projected survival of 6 months or more. The pretreatment DLCO assessment should be useful in predicting clinical tolerance to irradiation

Effects of Src on Proliferation and Invasion of Lung Cancer Cells

Directory of Open Access Journals (Sweden)

Rui ZHENG

2011-04-01

Full Text Available Background and objective It has been proven that Src played pivotal roles in carcinogenesis, cancer progression and metastasis. The aim of this study is to explore the roles of Src phosphorylation on lung cancer cells. Methods Western blot and immunoprecipitation was used to detect the expression and phosphorylation of Src in lung cancer cells. MTT and Boyden chamber assay was used to examine the effects of inhibition of Src phosphorylation on proliferation and invasion of lung cancer cells in vitro, respectively. Results pp60src was expressed in all lung cancer cell lines in this study. All 5 non-small cell lung cancer (NSCLC cell lines had increased autophosphorylated tyrosine-418, while nearly no phosphorylated Src in small cell lung cancer SBC5 cell line was detected. The effect of inhibition of Src tyrosine kinase on cell proliferation varied among the lung cancer cell lines. Submicromolar Src tyrosine kinase inhibitor (≤1 μM remarkably suppressed the proliferation of PC-9 and A549 cells in a dose dependent manner (P < 0.05, while the same concentration of Src tyrosine kinase inhibitor had no significant effect on proliferation of H226, PC14PE6 and RERFLCOK cells. Invasiveness of lung cancer cells was significantly suppressed by Src tyrosine kinase in a dose-dependent manner (P < 0.05. Conclusion Phosphorylation of Src, but not over-expression, plays a pivotal role in proliferation and invasion of NSCLC cell lines in vitro.

Chemopreventive effect of Cynodon dactylon (L.) Pers. extract against DMH-induced colon carcinogenesis in experimental animals.

Science.gov (United States)

Albert-Baskar, Arul; Ignacimuthu, Savarimuthu

2010-07-01

The present study was aimed at evaluating the chemopreventive property of Cynodon dactylon. The antioxidant, antiproliferative and apoptotic potentials of the plant were investigated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, nitric oxide radical scavenging activity (NO(-)) and MTT assay on four cancer cell lines (COLO 320 DM, MCH-7, AGS, A549) and a normal cell line (VERO). In vivo chemopreventive property of the plant extract was studied in DMH-induced colon carcinogenesis. The methanolic extract of C. dactylon was found to be antiproliferative and antioxidative at lower concentrations and induced apoptotic cell death in COLO 320 DM cells. Treatment with methanolic extract of C. dactylon increased the levels of antioxidant enzymes and reduced the number of dysplastic crypts in DMH-induced colon of albino rats. The present investigation revealed the anticancer potential of methanolic extract of C. dactylon in COLO 320 DM cells and experimentally induced colon carcinogenesis in rats.

Surveys of radon levels in homes in the United States: A test of the linear-no-threshold dose-response relationship for radiation carcinogenesis

International Nuclear Information System (INIS)

Cohen, B.L.

1987-01-01

The University of Pittsburgh Radon Project for large scale measurements of radon concentrations in homes is described. Its principal research is to test the linear-no threshold dose-response relationship for radiation carcinogenesis by determining average radon levels in the 25 U.S. counties (within certain population ranges) with highest and lowest lung cancer rates. The theory predicts that the former should have about 3 times higher average radon levels than the latter, under the assumption that any correlation between exposure to radon and exposure to other causes of lung cancer is weak. The validity of this assumption is tested with data on average radon level vs replies to items on questionnaires; there is little correlation between radon levels in houses and smoking habits, educational attainment, or economic status of the occupants, or with urban vs rural environs which is an indicator of exposure to air pollution

Tissue misrepair hypothesis for radiation carcinogenesis

International Nuclear Information System (INIS)

Kondo, Sohei

1991-01-01

Dose-response curves for chronic leukemia in A-bomb survivors and liver tumors in patients given Thorotrast (colloidal thorium dioxide) show large threshold effects. The existence of these threshold effects can be explained by the following hypothesis. A high dose of radiation causes a persistent wound in a cellrenewable tissue. Disorder of the injured cell society partly frees the component cells from territorial restraints on their proliferation, enabling them to continue development of their cellular functions toward advanced autonomy. This progression might be achieved by continued epigenetic and genetic changes as a result of occasional errors in the otherwise concerted healing action of various endogeneous factors recruited for tissue repair. Carcinogenesis is not simply a single-cell problem but a cell-society problem. Therefore, it is not warranted to estimate risk at low doses by linear extrapolation from cancer data at high doses without knowledge of the mechanism of radiation carcinogenesis. (author) 57 refs

Quantitation of the reconstruction quality of a four-dimensional computed tomography process for lung cancer patients

International Nuclear Information System (INIS)

Lu Wei; Parikh, Parag J.; El Naqa, Issam M.; Nystrom, Michelle M.; Hubenschmidt, James P.; Wahab, Sasha H.; Mutic, Sasa; Singh, Anurag K.; Christensen, Gary E.; Bradley, Jeffrey D.; Low, Daniel A.

2005-01-01

We have developed a four-dimensional computed tomography (4D CT) technique for mapping breathing motion in radiotherapy treatment planning. A multislice CT scanner (1.5 mm slices) operated in cine mode was used to acquire 12 contiguous slices in each couch position for 15 consecutive scans (0.5 s rotation, 0.25 s between scans) while the patient underwent simultaneous quantitative spirometry measurements to provide a sorting metric. The spirometry-sorted scans were used to reconstruct a 4D data set. A critical factor for 4D CT is quantifying the reconstructed data set quality which we measure by correlating the metric used relative to internal-object motion. For this study, the internal air content within the lung was used as a surrogate for internal motion measurements. Thresholding and image morphological operations were applied to delineate the air-containing tissues (lungs, trachea) from each CT slice. The Hounsfield values were converted to the internal air content (V). The relationship between the air content and spirometer-measured tidal volume (ν) was found to be quite linear throughout the lungs and was used to estimate the overall accuracy and precision of tidal volume-sorted 4D CT. Inspection of the CT-scan air content as a function of tidal volume showed excellent correlations (typically r>0.99) throughout the lung volume. Because of the discovered linear relationship, the ratio of internal air content to tidal volume was indicative of the fraction of air change in each couch position. Theoretically, due to air density differences within the lung and in room, the sum of these ratios would equal 1.11. For 12 patients, the mean value was 1.08±0.06, indicating the high quality of spirometry-based image sorting. The residual of a first-order fit between ν and V was used to estimate the process precision. For all patients, the precision was better than 8%, with a mean value of 5.1%±1.9%. This quantitative analysis highlights the value of using spirometry

Chemopreventive effect of artesunate in 1,2-dimethylhydrazine-induced rat colon carcinogenesis

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Sazal Patyar

2017-01-01

Full Text Available Artesunate (ART is a semisynthetic derivative of artemisinin. Artemisinin and its derivatives have shown profound cytotoxicity and antitumor activity in addition to antimalarial activity in various studies. As the in vivo chemopreventive efficacy of ART in colon carcinogenesis has not been investigated so far, the aim of the current study was to study the chemopreventive effect of ART in 1,2-dimethylhydrazine (DMH-induced rat colon carcinogenesis. Animals were divided into four groups (n = 6: Group I - vehicle (1 mM ethylenediaminetetraacetic acid, Group II - DMH (20 mg/kg, Group III - DMH + 5-fluorouracil (81 mg/kg, Group IV - DMH + ART (6.7 mg/kg. After completion of 15 weeks of treatment, rats were sacrificed under ether anesthesia by cervical dislocation for assessment of lipid peroxidation (LPO, antioxidant status, average number of aberrant crypt foci (ACF, and cytokine levels. ART administration significantly decreased the average number of ACF/microscopic field. Similarly, LPO level was decreased and antioxidant activities were enhanced after ART treatment. ART decreased the levels of proinflammatory cytokines and induced apoptosis in the colons of DMH-treated rats. The results of this study suggest that ART has a beneficial effect against chemically induced colonic preneoplastic progression in rats.

Role of the chronic bacterial infection in urinary bladder carcinogenesis

International Nuclear Information System (INIS)

Higgy, N.A.

1985-01-01

The purpose of this thesis was to determine whether or not bacterial infection of the urinary bladder had a role in urinary bladder carcinogenesis. To investigate this proposition, four separate studies were conducted. The first study developed an experimental animal model where bacterial infection of the urinary bladder could be introduced and maintained for a period in excess of one year. The method of infection, inoculation of bacteria (Escherichia coli type 04) subserosally into the vesical wall, successfully caused persistent infection in the majority of animals. In the second study the temporal effects of bacterial infection on the induction of urothelial ornithine decarboxylase (ODC) and 3 H-thymidine uptake and DNA synthesis were examined. Bacterial infection of the urinary bladder induced urothelial ODC with a peak in enzyme activity 6 hr after infection. 3 H-Thymidine uptake and DNA synthesis peaked 48 hr after infection and coincided with the urothelial hyperplasia that occurred in response to the infection. In the third study the specific bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was given to rats concurrent with the urinary bacterial infection. In the fourth study rats were administered sodium nitrate and either dibutylamine or piperazine in the drinking water. The infected group developed bladder tumors while none were detected in the non-infected rats. From these studies it may be concluded that bacterial infection may have a significant role in the process of urinary bladder carcinogenesis

Inflammatory Gene Polymorphisms in Lung Cancer Susceptibility.

Science.gov (United States)

Eaton, Keith D; Romine, Perrin E; Goodman, Gary E; Thornquist, Mark D; Barnett, Matt J; Petersdorf, Effie W

2018-05-01

Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer. A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the β-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [IFNG], interleukin 10 gene [IL10], interleukin 1 alpha gene [IL1A], interleukin 1 beta gene [IL1B], interleukin 2 gene [IL2], interleukin 4 receptor gene [IL4R], interleukin 4 gene [IL4], interleukin 6 gene [IL6], prostaglandin-endoperoxide synthase 2 gene [PTGS2] (also known as COX2), transforming growth factor beta 1 gene [TGFB1], and tumor necrosis factor alpha gene [TNFA]) was evaluated. Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1β-511C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR = 0.74, [95% confidence interval (CI): 0.58-0.94] and OR = 0.71 [95% CI: 0.50-1.01], respectively, p = 0.03). Similar results were observed for the IL-1β-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR = 0.75 [95% CI: 0.59-0.95] and OR = 0.69 [95% CI: 0.46-1.03], respectively, p = 0.03). Survival was not influenced by genotype. This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

The relevance of cell transformation to carcinogenesis in vivo

International Nuclear Information System (INIS)

Little, J.B.

1989-01-01

Despite the caveats concerning rodent as opposed to human cell transformation systems, the author concludes there are several areas in which cell transformation studies with rodent cells have shown clear relevance to carcinogenesis in vivo, especially studies of carcinogenic effects of high LET radiation, particularly dependence on dose rate. In vitro studies firmly established the generality of promotion by phorbol esters tumour promotors. Initial studies on suppression of transformation, notably by protease inhibitors, has led to the confirmation of this phenomenon in in vivo carcinogenesis; development of inhibitor preparations from natural sources suitable for long-term supplementation in human diet, is under investigation. The potential importance of these modifiers is further emphasized by mechanistic studies suggesting that radiation may initiate a large fraction of exposed cell population, and expression of transformation may be controlled to a large extent by environmental conditions including the presence of promoting or suppressing agents. Finally, cell transformation systems offer the opportunity for mechanistic studies of the initial stages of carcinogenesis. Provocative results have arisen in several areas consistent with findings in experimental animals. (author)

Experimental gastric carcinogenesis in Cebus apella nonhuman primates.

Directory of Open Access Journals (Sweden)

Joana de Fátima Ferreira Borges da Costa

Full Text Available The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU. Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9(th day though on the 14(th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940(th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the

Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

Science.gov (United States)

Suzuki, Seiichiro; Karayama, Masato; Inui, Naoki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Kuroishi, Shigeki; Matsuda, Hiroyuki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Imokawa, Shiro; Asada, Kazuhiro; Masuda, Masafumi; Yamada, Takashi; Watanabe, Hiroshi; Suda, Takafumi

2016-08-01

Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

Mutation and Expression of the DCC Gene in Human Lung Cancer

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Takashi Kohno

2000-07-01

Full Text Available Chromosome 18q is frequently deleted in lung cancers, a common region of 18q deletions was mapped to chromosome 18g21. Since the DCC candidate tumor suppressor gene has been mapped in this region, mutation and expression of the DCC gene were examined in 46 lung cancer cell lines, consisting of 14 small cell lung carcinomas (SCLCs and 32 non-small cell lung carcinomas (NSCLCs, to elucidate the pathogenetic significance of DCC alterations in human lung carcinogenesis. A heterozygous missense mutation was detected in a NSCLC cell line, Ma26, while homozygous deletion was not detected in any of the cell lines. The DCC gene was expressed in 11 (24% of the 46 cell lines, the incidence of DCC expression was significantly higher in SCLCs (7/14, 50% than in NSCLCs (4/32, 13% (P = .01, Fisher's exact test. Therefore, genetic alterations of DCC are infrequent; however, the levels of DCC expression vary among lung cancer cells, in particular, between SCLCs and NSCLCs. The present result does not implicate DCC as a specific mutational target of 18q deletions in human lung cancer; however, it suggests that DCC is a potential target of inactivation by genetic defects including intron or promoter mutations and/or epigenetic alterations. The present result also suggests that DCC expression is associated with some properties of SCLCs, such as a neuroendocrine (NE feature.

Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium

International Nuclear Information System (INIS)

Beaver, Laura M.; Stemmy, Erik J.; Constant, Stephanie L.; Schwartz, Arnold; Little, Laura G.; Gigley, Jason P.; Chun, Gina; Sugden, Kent D.

2009-01-01

Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory carcinogens that release genotoxic soluble chromate, and are associated with fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the lung. We postulate that inflammatory processes and mediators may contribute to the etiology of Cr(VI) carcinogenesis, however the immediate (0-24 h) pathologic injury and immune responses after exposure to particulate chromates have not been adequately investigated. Our aim was to determine the nature of the lung injury, inflammatory response, and survival signaling responses following intranasal exposure of BALB/c mice to particulate basic zinc chromate. Factors associated with lung injury, inflammation and survival signaling were measured in airway lavage fluid and in lung tissue. A single chromate exposure induced an acute immune response in the lung, characterized by a rapid and significant increase in IL-6 and GRO-α levels, an influx of neutrophils, and a decline in macrophages in lung airways. Histological examination of lung tissue in animals challenged with a single chromate exposure revealed an increase in bronchiolar cell apoptosis and mucosal injury. Furthermore, chromate exposure induced injury and inflammation that progressed to alveolar and interstitial pneumonitis. Finally, a single Cr(VI) challenge resulted in a rapid and persistent increase in the number of airways immunoreactive for phosphorylation of the survival signaling protein Akt, on serine 473. These data illustrate that chromate induces both survival signaling and an inflammatory response in the lung, which we postulate may contribute to early oncogenesis

Distribution of polonium-210 in the human lung

International Nuclear Information System (INIS)

Cohen, Beverly S.; Eisenbud, Merril; Wrenn, McDonald E.; Harley, Naomi H.

1978-01-01

Knowledge of the distribution of 210 Po in the lungs of cigarette smokers is essential if the role of this alpha emitter in smoking related carcinogenesis is to be understood. To resolve this question the tracheobronchial tree is separated from the parenchyma and both are analyzed for 210 Po. Some polonium is cleared to the blood and systemically redistributed. Since systemic distribution should produce the same partition of the nuclide in smokers and nonsmokers, an excess found in either fraction would indicate retention of inhaled 210 Po or its grandparent 210 Pb. We will report the results of these analyses in five smokers and 5 nonsmokers. (author)

Amebic lung abscess with coexisting lung adenocarcinoma: a unusual case of amebiasis

OpenAIRE

Zhu, Hailong; Min, Xiangyang; Li, Shuai; Feng, Meng; Zhang, Guofeng; Yi, Xianghua

2014-01-01

Amebic lung abscess with concurrent lung cancer, but without either a liver abscess or amebic colitis, is extremely uncommon. Here, we report a 70-year-old man presenting with pulmonary amebiasis and coexisting lung adenocarcinoma. During his first-time hospitalization, the diagnosis of lung amebiasis was confirmed by morphological observation and PCR in formalin-fixed and paraffin-embedded sediments of pleural effusion. Almost four months later, the patient was readmitted to hospital for sim...

Comparison of spirometry and abdominal height as four-dimensional computed tomography metrics in lung

International Nuclear Information System (INIS)

Lu Wei; Low, Daniel A.; Parikh, Parag J.; Nystrom, Michelle M.; El Naqa, Issam M.; Wahab, Sasha H.; Handoko, Maureen; Fooshee, David; Bradley, Jeffrey D.

2005-01-01

An important consideration in four-dimensional CT scanning is the selection of a breathing metric for sorting the CT data and modeling internal motion. This study compared two noninvasive breathing metrics, spirometry and abdominal height, against internal air content, used as a surrogate for internal motion. Both metrics were shown to be accurate, but the spirometry showed a stronger and more reproducible relationship than the abdominal height in the lung. The abdominal height was known to be affected by sensor placement and patient positioning while the spirometer exhibited signal drift. By combining these two, a normalization of the drift-free metric to tidal volume may be generated and the overall metric precision may be improved

Reactive oxygen species mediate Cr(VI)-induced carcinogenesis through PI3K/AKT-dependent activation of GSK-3β/β-catenin signaling

International Nuclear Information System (INIS)

Son, Young-Ok; Pratheeshkumar, Poyil; Wang, Lei; Wang, Xin; Fan, Jia; Kim, Dong-Hern; Lee, Ju-Yeon; Zhang, Zhuo; Lee, Jeong-Chae; Shi, Xianglin

2013-01-01

Cr(VI) compounds are known human carcinogens that primarily target the lungs. Cr(VI) produces reactive oxygen species (ROS), but the exact effects of ROS on the signaling molecules involved in Cr(VI)-induced carcinogenesis have not been extensively studied. Chronic exposure of human bronchial epithelial cells to Cr(VI) at nanomolar concentrations (10–100 nM) for 3 months not only induced cell transformation, but also increased the potential of these cells to invade and migrate. Injection of Cr(VI)-stimulated cells into nude mice resulted in the formation of tumors. Chronic exposure to Cr(VI) increased levels of intracellular ROS and antiapoptotic proteins. Transfection with catalase or superoxide dismutase (SOD) prevented Cr(VI)-mediated increases in colony formation, cell invasion, migration, and xenograft tumors. While chronic Cr(VI) exposure led to activation of signaling cascades involving PI3K/AKT/GSK-3β/β-catenin and PI3K/AKT/mTOR, transfection with catalase or SOD markedly inhibited Cr(VI)-mediated activation of these signaling proteins. Inhibitors specific for AKT or β-catenin almost completely suppressed the Cr(VI)-mediated increase in total and active β-catenin proteins and colony formation. In particular, Cr(VI) suppressed autophagy of epithelial cells under nutrition deprivation. Furthermore, there was a marked induction of AKT, GSK-3β, β-catenin, mTOR, and carcinogenic markers in tumor tissues formed in mice after injection with Cr(VI)-stimulated cells. Collectively, our findings suggest that ROS is a key mediator of Cr(VI)-induced carcinogenesis through the activation of PI3K/AKT-dependent GSK-3β/β-catenin signaling and the promotion of cell survival mechanisms via the inhibition of apoptosis and autophagy. - Highlights: • Chronic exposure to Cr(VI) induces carcinogenic properties in BEAS-2B cells. • ROS play an important role in Cr(VI)-induced tumorigenicity of BEAS-2B cells. • PI3K/AKT/GSK-3β/β-catenin signaling involved in Cr

Reactive oxygen species mediate Cr(VI)-induced carcinogenesis through PI3K/AKT-dependent activation of GSK-3β/β-catenin signaling

Energy Technology Data Exchange (ETDEWEB)

Son, Young-Ok; Pratheeshkumar, Poyil; Wang, Lei; Wang, Xin; Fan, Jia; Kim, Dong-Hern; Lee, Ju-Yeon; Zhang, Zhuo [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536-0305 (United States); Lee, Jeong-Chae [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536-0305 (United States); School of Dentistry and Institute of Oral Biosciences, Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536-0305 (United States)

2013-09-01

Cr(VI) compounds are known human carcinogens that primarily target the lungs. Cr(VI) produces reactive oxygen species (ROS), but the exact effects of ROS on the signaling molecules involved in Cr(VI)-induced carcinogenesis have not been extensively studied. Chronic exposure of human bronchial epithelial cells to Cr(VI) at nanomolar concentrations (10–100 nM) for 3 months not only induced cell transformation, but also increased the potential of these cells to invade and migrate. Injection of Cr(VI)-stimulated cells into nude mice resulted in the formation of tumors. Chronic exposure to Cr(VI) increased levels of intracellular ROS and antiapoptotic proteins. Transfection with catalase or superoxide dismutase (SOD) prevented Cr(VI)-mediated increases in colony formation, cell invasion, migration, and xenograft tumors. While chronic Cr(VI) exposure led to activation of signaling cascades involving PI3K/AKT/GSK-3β/β-catenin and PI3K/AKT/mTOR, transfection with catalase or SOD markedly inhibited Cr(VI)-mediated activation of these signaling proteins. Inhibitors specific for AKT or β-catenin almost completely suppressed the Cr(VI)-mediated increase in total and active β-catenin proteins and colony formation. In particular, Cr(VI) suppressed autophagy of epithelial cells under nutrition deprivation. Furthermore, there was a marked induction of AKT, GSK-3β, β-catenin, mTOR, and carcinogenic markers in tumor tissues formed in mice after injection with Cr(VI)-stimulated cells. Collectively, our findings suggest that ROS is a key mediator of Cr(VI)-induced carcinogenesis through the activation of PI3K/AKT-dependent GSK-3β/β-catenin signaling and the promotion of cell survival mechanisms via the inhibition of apoptosis and autophagy. - Highlights: • Chronic exposure to Cr(VI) induces carcinogenic properties in BEAS-2B cells. • ROS play an important role in Cr(VI)-induced tumorigenicity of BEAS-2B cells. • PI3K/AKT/GSK-3β/β-catenin signaling involved in Cr

Epidermal growth factor receptor expression in radiation-induced dog lung tumors by immunocytochemical localization

Energy Technology Data Exchange (ETDEWEB)

Leung, F.L.; Park, J.F.; Dagle, G.E.

1993-06-01

In studies to determine the role of growth factors in radiation-induced lung cancer, epidermal growth factor (EGFR) expression was examined by immunocytochemistry in 51 lung tumors from beagle dogs exposed to inhaled plutonium; 21 of 51 (41%) tumors were positive for EGFR. The traction of tumors positive for EGFR and the histological type of EGFR-positive tumors in the plutonium-exposed dogs were not different from spontaneous dog lung tumors, In which 36% were positive for EGFR. EGFR involvement in Pu-induced lung tumors appeared to be similar to that in spontaneous lung tumors. However, EGFR-positive staining was observed in only 1 of 16 tumors at the three lowest Pu exposure levels, compared to 20 of 35 tumors staining positive at the two highest Pu exposure levels. The results in dogs were in good agreement with the expression of EGFR reported in human non-small cell carcinoma of the lung, suggesting that Pu-induced lung tumors in the dog may be a suitable animal model to investigate the role of EGFR expression in lung carcinogenesis. In humans, EGFR expression in lung tumors has been primarily related to histological tumor types. In individual dogs with multiple primary lung tumors, the tumors were either all EGFR positive or EGFR negative, suggesting that EGFR expression may be related to the response of the individual dog as well as to the histological type of tumor.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Mathematical card magic fifty-two new effects

CERN Document Server

Mulcahy, Colm

2013-01-01

Mathematical card effects offer both beginning and experienced magicians an opportunity to entertain with a minimum of props. Featuring mostly original creations, Mathematical Card Magic: Fifty-Two New Effects presents an entertaining look at new mathematically based card tricks. Each chapter contains four card effects, generally starting with simple applications of a particular mathematical principle and ending with more complex ones. Practice a handful of the introductory effects and, in no time, you'll establish your reputation as a "mathemagician." Delve a little deeper into each chapter and the mathematics gets more interesting. The author explains the mathematics as needed in an easy-to-follow way. He also provides additional details, background, and suggestions for further explorations.Suitable for recreational math buffs and amateur card lovers or as a text in a first-year seminar, this color book offers a diverse collection of new mathemagic principles and effects.

Chronic ultraviolet exposure-induced p53 gene alterations in sencar mouse skin carcinogenesis model

International Nuclear Information System (INIS)

Tong, Ying; Smith, M.A.; Tucker, S.B.

1997-01-01

Alterations of the tumor suppressor gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12124 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → G, and one A → T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin. 40 refs., 5 figs., 1 tab

Chemically induced immunotoxicity in a medium-term multiorgan bioassay for carcinogenesis with Wistar rats

International Nuclear Information System (INIS)

Spinardi-Barbisan, Ana Lucia Tozzi; Kaneno, Ramon; Barbisan, Luis Fernando; Viana de Camargo, Joao Lauro; Rodrigues, Maria Aparecida Marchesan

2004-01-01

A variety of chemicals can adversely affect the immune system and influence tumor development. The modifying potential of chemical carcinogens on the lymphoid organs and cytokine production of rats submitted to a medium-term initiation-promotion bioassay for carcinogenesis was investigated. Male Wistar rats were sequentially initiated with N-nitrosodiethylamine (DEN), N-methyl-N-nitrosourea (MNU), N-butyl-N-(4hydroxybutyl)nitrosamine (BBN), dihydroxy-di-n-propylnitrosamine (DHPN), and 1,2-dimethylhydrazine (DMH) during 4 weeks. Two initiated groups received phenobarbital (PB) or 2-acetylaminofluorene (2-AAF) for 25 weeks and two noninitiated groups received only PB or 2-AAF. A nontreated group was used as control. Lymphohematopoietic organs, liver, kidneys, lung, intestines, and Zymbal's gland were removed for histological analysis. Interleukin (IL)-2, IL-12, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-10, and transforming growth factor beta1 (TGF-β1) levels were determined by ELISA in spleen cell culture supernatants. At the fourth week, exposure to the initiating carcinogens resulted in cell depletion of the thymus, spleen and bone marrow, and impairment of IL-2, IL-12, and IFN-γ production. However, at the 30th week, no important alterations were observed both in lymphoid organs and cytokine production in the different groups. The results indicate that the initiating carcinogens used in the present protocol exert toxic effects on the lymphoid organs and affect the production of cytokines at the initiation step of carcinogenesis. This early and reversible depression of the immune surveillance may contribute to the survival of initiated cells facilitating the development of future neoplasia

Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development.

Science.gov (United States)

Ataca, Dalya; Caikovski, Marian; Piersigilli, Alessandra; Moulin, Alexandre; Benarafa, Charaf; Earp, Sarah E; Guri, Yakir; Kostic, Corinne; Arsenijevic, Yvan; Soininen, Raija; Apte, Suneel S; Brisken, Cathrin

2016-11-15

The ADAMTS family comprises 19 secreted metalloproteinases that cleave extracellular matrix components and have diverse functions in numerous disease and physiological contexts. A number of them remain 'orphan' proteases and among them is ADAMTS18, which has been implicated in developmental eye disorders, platelet function and various malignancies. To assess in vivo function of ADAMTS18, we generated a mouse strain with inactivated Adamts18 alleles. In the C57Bl6/Ola background, Adamts18-deficient mice are born in a normal Mendelian ratio, and are viable but show a transient growth delay. Histological examination revealed a 100% penetrant eye defect resulting from leakage of lens material through the lens capsule occurring at embryonic day (E)13.5, when the lens grows rapidly. Adamts18-deficient lungs showed altered bronchiolar branching. Fifty percent of mutant females are infertile because of vaginal obstruction due to either a dorsoventral vaginal septum or imperforate vagina. The incidence of ovarian rete is increased in the mutant mouse strain. Thus, Adamts18 is essential in the development of distinct tissues and the new mouse strain is likely to be useful for investigating ADAMTS18 function in human disease, particularly in the contexts of infertility and carcinogenesis. © 2016. Published by The Company of Biologists Ltd.

Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development

Directory of Open Access Journals (Sweden)

Dalya Ataca

2016-11-01

Full Text Available The ADAMTS family comprises 19 secreted metalloproteinases that cleave extracellular matrix components and have diverse functions in numerous disease and physiological contexts. A number of them remain ‘orphan’ proteases and among them is ADAMTS18, which has been implicated in developmental eye disorders, platelet function and various malignancies. To assess in vivo function of ADAMTS18, we generated a mouse strain with inactivated Adamts18 alleles. In the C57Bl6/Ola background, Adamts18-deficient mice are born in a normal Mendelian ratio, and are viable but show a transient growth delay. Histological examination revealed a 100% penetrant eye defect resulting from leakage of lens material through the lens capsule occurring at embryonic day (E13.5, when the lens grows rapidly. Adamts18-deficient lungs showed altered bronchiolar branching. Fifty percent of mutant females are infertile because of vaginal obstruction due to either a dorsoventral vaginal septum or imperforate vagina. The incidence of ovarian rete is increased in the mutant mouse strain. Thus, Adamts18 is essential in the development of distinct tissues and the new mouse strain is likely to be useful for investigating ADAMTS18 function in human disease, particularly in the contexts of infertility and carcinogenesis.

Synchronous lung tumours in a patient with metachronous colorectal carcinoma and a germline MSH2 mutation.

LENUS (Irish Health Repository)

Canney, A

2012-02-01

Mutations of DNA mismatch repair genes are characterised by microsatellite instability and are implicated in carcinogenesis. This mutation susceptible phenotype has been extensively studied in patients with hereditary non-polyposis colon carcinoma, but little is known of the contribution of such mutations in other tumour types, particularly non-small-cell lung carcinoma. This report describes the occurrence of two synchronous lung tumours, one mimicking a metastatic colon carcinoma, in a male patient with a history of metachronous colonic carcinoma. Immunohistochemistry supported a pulmonary origin for both lesions. Mismatch repair protein immunohistochemistry showed loss of MSH2 and MSH6 expression in both colonic tumours and in one lung tumour showing enteric differentiation. Subsequent mutational analysis demonstrated a deleterious germline mutation of the MSH2 mismatch repair gene. The significance of these findings and the practical diagnostic difficulties encountered in this case are discussed.

The next fifty years

International Nuclear Information System (INIS)

Scaldwell, Reg

1995-01-01

The General Manager of the reactor division of Centronics, a world class manufacturer of reactor control systems and radiation detectors, describes its achievements and looks forward to speculate on what the next fifty years may mean in terms of technological development. Tables are given of the locations of Centronics Fission Chambers and of reactors controlled with Centronic Detectors. (UK)

Radiation carcinogenesis: Epidemiology and biological significance

International Nuclear Information System (INIS)

Boice, J.D.; Fraumeni, J.F.

1984-01-01

Epidemiologic studies of populations exposed to radiation have led to the identification of a preventable cause of cancer, but in the long run perhaps the most important contribution of radiation studies will be to provide insights into the basic processes of human carcinogenesis. In this volume, key investigators of major epidemiologic projects summarize their observations to date, including information to help assess the effects of low-level exposures. Experimentalists and theorists emphasize the relevance of laboratory and epidemiologic data in elucidating carcinogenic risks and mechanisms in man. This volume was prepared with several objectives in mind: (a) organize and synthesize knowledge on radiation carcinogenesis through epidemiologic and experimental approaches; (b) illustrate and explore ways of utilizing this information to gain insights into the fundamental mechanisms of cancer development; (c) stimulate the formation of hypotheses suited to experimental or epidemiologic testing, theoretical modeling, and multidisciplinary approaches; and (d) identify recent advances that clarify dose-response relationships and the influence of low-dose exposures, provide leads to carcinogenic mechanisms and host-environmental interactions, and suggest strategies for future research and preventive action

Towards a systemic paradigm in carcinogenesis: linking epigenetics and genetics.

Science.gov (United States)

Burgio, Ernesto; Migliore, Lucia

2015-04-01

For at least 30 years cancer has been defined as a genetic disease and explained by the so-called somatic mutation theory (SMT), which has dominated the carcinogenesis field. Criticism of the SMT has recently greatly increased, although still not enough to force all SMT supporters to recognize its limits. Various researchers point out that cancer appears to be a complex process concerning a whole tissue; and that genomic mutations, although variably deleterious and unpredictably important in determining the establishment of the neoplastic phenotype, are not the primary origin for a malignant neoplasia. We attempt to describe the inadequacies of the SMT and demonstrate that epigenetics is a more logical cause of carcinogenesis. Many previous models of carcinogenesis fall into two classes: (i) in which some biological changes inside cells alone lead to malignancy; and (ii) requiring changes in stroma/extracellular matrix. We try to make clear that in the (ii) model genomic instability is induced by persistent signals coming from the microenvironment, provoking epigenetic and genetic modifications in tissue stem cells that can lead to cancer. In this perspective, stochastic mutations of DNA are a critical by-product rather then the primary cause of cancer. Indirect support for such model of carcinogenesis comes from the in vitro and vivo experiments showing apparent 'reversion' of cancer phenotypes obtained via physiological factors of cellular differentiation (cytokines and other signaling molecules) or drugs, even if the key mutations are not 'reversed'.

Experimental study of the combined effect of cigarette smoke and an active burden of radon-222

International Nuclear Information System (INIS)

Chameaud, J.; Perraud, R.; Chretien, J.; Masse, R.; Lafuma, J.

1978-01-01

Previous studies on the carcinogenic effect of radon-222 derivatives have yielded accurate relationships, for each radon dose, between the dose value and the frequencies and latency times of lung cancers. In the present work, one hundred rats were subjected, over one-and-a-half months, to a total dose of 3600 WLM, chosen because it corresponds to a 30% occurrence of cancers. Fifty of these animals then inhaled cigarette smoke during 50 ten-minute sessions per week. The total time for these inhalations was 350 hours spread over about six months. In the 'radon' group (50 rats), 17 animals were found to have lung cancer. In the 'radon + tobacco' group (50 rats), 32 cancers were observed; moreover, the tumours in this group were much more extensive, multifocal and invasive. Animals subjected to cigarette smoke alone have never shown lung cancer. The effect of tobacco as a co-factor in carcinogenesis has thus been varified experimentally, although inhaled cigarette smoke alone is not carcinogenic in rats. (author)

Mdm2 overexpression and p14(ARF) inactivation are two mutually exclusive events in primary human lung tumors.

Science.gov (United States)

Eymin, Béatrice; Gazzeri, Sylvie; Brambilla, Christian; Brambilla, Elisabeth

2002-04-18

Pathways involving p53 and pRb tumor suppressor genes are frequently deregulated during lung carcinogenesis. Through its location at the interface of these pathways, Mdm2 can modulate the function of both p53 and pRb genes. We have examined here the pattern of expression of Mdm2 in a series of 192 human lung carcinomas of all histological types using both immunohistochemical and Western blot analyses and four distinct antibodies mapping different epitopes onto the Mdm2 protein. Using Immunohistochemistry (IHC), Mdm2 was overexpressed as compared to normal lung in 31% (60 out of 192) of all tumors analysed, whatever their histological types. Western blotting was performed on 28 out of the 192 tumoral samples. Overexpression of p85/90, p74/76 and p57 Mdm2 isoforms was detected in 18% (5 out of 28), 25% (7 out of 28) and 39% (11 out of 28) of the cases respectively. Overall, overexpression of at least one isoform was observed in 14 out of 28 (50%) lung tumors and concomittant overexpression of at least two isoforms in 7 out of 28 (25%) cases. A good concordance (82%) was observed between immunohistochemical and Western blot data. Interestingly, a highly significant inverse relationship was detected between p14(ARF) loss and Mdm2 overexpression either in NSCLC (P=0.0089) or in NE lung tumors (P1 ratio was correlated with a high grade phenotype among NE tumors overexpressing Mdm2 (P=0.0021). Taken together, these data strongly suggest that p14(ARF)and Mdm2 act on common pathway(s) to regulate p53 and/or pRb-dependent or independent functions and that the Mdm2 : p14(ARF) ratio might act as a rheostat in modulating the activity of both proteins.

Molecular mechanisms in radiation carcinogenesis: introduction

International Nuclear Information System (INIS)

Setlow, R.B.

1975-01-01

Molecular studies of radiation carcinogenesis are discussed in relation to theories for extrapolating from cellular and animal models to man. Skin cancer is emphasized because of sunlight-induced photochemical damage to DNA. It is emphasized that cellular and animal models are needed as well as molecular theories for quantitative evaluation of hazardous environmental agents. (U.S.)

Modelling lung cancer due to radon and smoking in WISMUT miners: Preliminary results

International Nuclear Information System (INIS)

Bijwaard, H.; Dekkers, F.; Van Dillen, T.

2011-01-01

A mechanistic two-stage carcinogenesis model has been applied to model lung-cancer mortality in the largest uranium-miner cohort available. Models with and without smoking action both fit the data well. As smoking information is largely missing from the cohort data, a method has been devised to project this information from a case-control study onto the cohort. Model calculations using 256 projections show that the method works well. Preliminary results show that if an explicit smoking action is absent in the model, this is compensated by the values of the baseline parameters. This indicates that in earlier studies performed without smoking information, the results obtained for the radiation parameters are still valid. More importantly, the inclusion of smoking-related parameters shows that these mainly influence the later stages of lung-cancer development. (authors)

Somatic mutations affect key pathways in lung adenocarcinoma

Science.gov (United States)

Ding, Li; Getz, Gad; Wheeler, David A.; Mardis, Elaine R.; McLellan, Michael D.; Cibulskis, Kristian; Sougnez, Carrie; Greulich, Heidi; Muzny, Donna M.; Morgan, Margaret B.; Fulton, Lucinda; Fulton, Robert S.; Zhang, Qunyuan; Wendl, Michael C.; Lawrence, Michael S.; Larson, David E.; Chen, Ken; Dooling, David J.; Sabo, Aniko; Hawes, Alicia C.; Shen, Hua; Jhangiani, Shalini N.; Lewis, Lora R.; Hall, Otis; Zhu, Yiming; Mathew, Tittu; Ren, Yanru; Yao, Jiqiang; Scherer, Steven E.; Clerc, Kerstin; Metcalf, Ginger A.; Ng, Brian; Milosavljevic, Aleksandar; Gonzalez-Garay, Manuel L.; Osborne, John R.; Meyer, Rick; Shi, Xiaoqi; Tang, Yuzhu; Koboldt, Daniel C.; Lin, Ling; Abbott, Rachel; Miner, Tracie L.; Pohl, Craig; Fewell, Ginger; Haipek, Carrie; Schmidt, Heather; Dunford-Shore, Brian H.; Kraja, Aldi; Crosby, Seth D.; Sawyer, Christopher S.; Vickery, Tammi; Sander, Sacha; Robinson, Jody; Winckler, Wendy; Baldwin, Jennifer; Chirieac, Lucian R.; Dutt, Amit; Fennell, Tim; Hanna, Megan; Johnson, Bruce E.; Onofrio, Robert C.; Thomas, Roman K.; Tonon, Giovanni; Weir, Barbara A.; Zhao, Xiaojun; Ziaugra, Liuda; Zody, Michael C.; Giordano, Thomas; Orringer, Mark B.; Roth, Jack A.; Spitz, Margaret R.; Wistuba, Ignacio I.; Ozenberger, Bradley; Good, Peter J.; Chang, Andrew C.; Beer, David G.; Watson, Mark A.; Ladanyi, Marc; Broderick, Stephen; Yoshizawa, Akihiko; Travis, William D.; Pao, William; Province, Michael A.; Weinstock, George M.; Varmus, Harold E.; Gabriel, Stacey B.; Lander, Eric S.; Gibbs, Richard A.; Meyerson, Matthew; Wilson, Richard K.

2009-01-01

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers—including NF1, APC, RB1 and ATM—and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment. PMID:18948947

Triple SILAC quantitative proteomic analysis reveals differential abundance of cell signaling proteins between normal and lung cancer-derived exosomes.

Science.gov (United States)

Clark, David J; Fondrie, William E; Yang, Austin; Mao, Li

2016-02-05

Exosomes are 30-100 nm sized membrane vesicles released by cells into the extracellular space that mediate intercellular communication via transfer of proteins and other biological molecules. To better understand the role of these microvesicles in lung carcinogenesis, we employed a Triple SILAC quantitative proteomic strategy to examine the differential protein abundance between exosomes derived from an immortalized normal bronchial epithelial cell line and two non-small cell lung cancer (NSCLC) cell lines harboring distinct activating mutations in the cell signaling molecules: Kirsten rat sarcoma viral oncogene homolog (KRAS) or epidermal growth factor receptor (EGFR). In total, we were able to quantify 721 exosomal proteins derived from the three cell lines. Proteins associated with signal transduction, including EGFR, GRB2 and SRC, were enriched in NSCLC exosomes, and could actively regulate cell proliferation in recipient cells. This study's investigation of the NSCLC exosomal proteome has identified enriched protein cargo that can contribute to lung cancer progression, which may have potential clinical implications in biomarker development for patients with NSCLC. The high mortality associated with lung cancer is a result of late-stage diagnosis of the disease. Current screening techniques used for early detection of lung cancer lack the specificity for accurate diagnosis. Exosomes are nano-sized extracellular vesicles, and the increased abundance of select protein cargo in exosomes derived from cancer cells may be used for diagnostic purposes. In this paper, we applied quantitative proteomic analysis to elucidate abundance differences in exosomal protein cargo between two NSCLC cell lines with distinctive oncogene mutations and an immortalized normal bronchial epithelial cell line. This study revealed proteins associated with cell adhesion, the extracellular matrix, and a variety of signaling molecules were enriched in NSCLC exosomes. The present data reveals

Upper airway gene expression in smokers: the mouth as a "window to the soul" of lung carcinogenesis?

Science.gov (United States)

Spira, Avrum

2010-03-01

This perspective on Boyle et al. (beginning on page 266 in this issue of the journal) explores transcriptomic profiling of upper airway epithelium as a biomarker of host response to tobacco smoke exposure. Boyle et al. have shown a striking relationship between smoking-related gene expression changes in the mouth and bronchus. This relationship suggests that buccal gene expression may serve as a relatively noninvasive surrogate marker of the physiologic response of the lung to tobacco smoke that could be used in large-scale screening and chemoprevention studies for lung cancer.

Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

Directory of Open Access Journals (Sweden)

Ki Baik Hahm

2011-07-01

Full Text Available Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Hahm, Ki Baik, E-mail: hahmkb@gachon.ac.kr [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Gastroenterology, Gachon Graduate School of Medicine, Gil Hospital, Incheon 406-840 (Korea, Republic of)

2011-07-25

Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

International Nuclear Information System (INIS)

Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua; Hahm, Ki Baik

2011-01-01

Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis

Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments

International Nuclear Information System (INIS)

Rajkumar, Lakshmanaswamy; Guzman, Raphael C; Yang, Jason; Thordarson, Gudmundur; Talamantes, Frank; Nandi, Satyabrata

2004-01-01

Women who have undergone a full-term pregnancy before the age of 20 have one-half the risk of developing breast cancer compared with women who have never gone through a full-term pregnancy. This protective effect is observed universally among women of all ethnic groups. Parity in rats and mice also protects them against chemically induced mammary carcinogenesis. Seven-week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the rats were treated with natural or synthetic estrogens and progestins for 7–21 days by subcutaneous implantation of silastic capsules. In our current experiment, we demonstrate that short-term sustained exposure to natural or synthetic estrogens along with progestins is effective in preventing mammary carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for 3 weeks significantly reduced the incidence of mammary cancer. Short-term exposure to ethynyl estradiol plus megesterol acetate or norethindrone was effective in decreasing the incidence of mammary cancers. Tamoxifen plus progesterone treatment for 3 weeks was able to confer only a transient protection from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was effective in conferring protection against mammary cancers. The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations

Inflammatory and redox reactions in colorectal carcinogenesis.

Science.gov (United States)

Guina, Tina; Biasi, Fiorella; Calfapietra, Simone; Nano, Mario; Poli, Giuseppe

2015-03-01

It has been established that there is a relationship between chronic inflammation and cancer development. The constant colonic inflammation typical of inflammatory bowel diseases is now considered a risk factor for colorectal carcinoma (CRC) development. The inflammatory network of signaling molecules is also required during the late phases of carcinogenesis, to enable cancer cells to survive and to metastasize. Oxidative reactions are an integral part of the inflammatory response, and are generally associated with CRC development. However, when the malignant phenotype is acquired, increased oxidative status induces antioxidant defenses in cancer cells, favoring their aggressiveness. This contradictory behavior of cancer cells toward redox status is of great significance for potential anticancer therapies. This paper summarizes the essential background information relating to the molecules involved in regulating oxidative stress and inflammation during carcinogenesis. Understanding more of their function in CRC stages might provide the foundation for future developments in CRC treatment. © 2015 New York Academy of Sciences.

Cervical lung hernia

Science.gov (United States)

Lightwood, Robin G.; Cleland, W. P.

1974-01-01

Lightwood, R. G., and Cleland, W. P. (1974).Thorax, 29, 349-351. Cervical lung hernia. Lung hernias occur in the cervical position in about one third of cases. The remainder appear through the chest wall. Some lung hernias are congenital, but trauma is the most common cause. The indications for surgery depend upon the severity of symptoms. Repair by direct suture can be used for small tears in Sibson's (costovertebral) fascia while larger defects have been closed using prosthetic materials. Four patients with cervical lung hernia are described together with an account of their operations. PMID:4850946

Biological Complexities in Radiation Carcinogenesis and Cancer Radiotherapy: Impact of New Biological Paradigms

Directory of Open Access Journals (Sweden)

Hossein Mozdarani

2012-01-01

Full Text Available Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the use of ionizing radiation is also one of the major modalities in cancer treatment. Various known cellular and molecular events are involved in carcinogenesis. Apart from the known phenomena, there could be implications for carcinogenesis and cancer prevention due to other biological processes such as the bystander effect, the abscopal effect, intrinsic radiosensitivity and radioadaptation. Bystander effects have consequences for mutation initiated cancer paradigms of radiation carcinogenesis, which provide the mechanistic justification for low-dose risk estimates. The abscopal effect is potentially important for tumor control and is mediated through cytokines and/or the immune system (mainly cell-mediated immunity. It results from loss of growth and stimulatory and/or immunosuppressive factors from the tumor. Intrinsic radiosensitivity is a feature of some cancer prone chromosomal breakage syndromes such as ataxia telangectiasia. Radiosensitivity is manifested as higher chromosomal aberrations and DNA repair impairment is now known as a good biomarker for breast cancer screening and prediction of prognosis. However, it is not yet known whether this effect is good or bad for those receiving radiation or radiomimetic agents for treatment. Radiation hormesis is another major concern for carcinogenesis. This process which protects cells from higher doses of radiation or radio mimic chemicals, may lead to the escape of cells from mitotic death or apoptosis and put cells with a lower amount of damage into the process of cancer induction. Therefore, any of these biological phenomena could have impact on another process giving rise to genome instability of cells which are not in the field of radiation but still receiving a lower amount of radiation. For prevention of radiation induced carcinogenesis or risk assessment as well as for successful radiation

Interaction Between Dietary Factors and Inflammation in Prostate Carcinogenesis

National Research Council Canada - National Science Library

De Marzo, Angelo M

2007-01-01

We are investigating whether inflammation can enhance prostate carcinogenesis in a rat model of dietary charred meat carcinogen induced cancers, and, whether antioxidant and other chemopreventative...

Interactions between Dietary Factors and Inflammation in Prostate Carcinogenesis

National Research Council Canada - National Science Library

DeMarzo, Angelo M

2006-01-01

We are investigating whether inflammation can enhance prostate carcinogenesis in a rat model of dietary charred meat carcinogen induced cancers, and, whether antioxidant and other chemopreventative...

The fifty-year-old woman and midlife stress.

Science.gov (United States)

Campbell, S

It has been assumed that the fifties are a relatively stable decade; however, women in their fifties are susceptible to many stresses, internal and external. The possibilities of widowhood, divorce, or poverty, combined with intra- and interpersonal strains, make this a time of insecurity about aging for many women. Some suggestions as to why women nonetheless cope successfully with aging are considered.

Cellular adaptation as an important response during chemical carcinogenesis

International Nuclear Information System (INIS)

Farber, E.

1992-01-01

Since disease processes are largely expressions of how living organisms react and respond to perturbations in the external and internal environments, adaptive or protective responses and their modulations and mechanisms are of the greatest concern in fundamental studies of disease pathogenesis. Such considerations are also of the greatest relevance in toxicology, including how living organisms respond to low levels of single and multiple xenobiotics and radiations. As the steps and mechanisms during cancer development are studied in greater depth, phenomena become apparent that suggest that adaptive reactions and responses may play important or even critical roles in the process of carcinogenesis. The question becomes whether the process of carcinogenesis is fundamentally an adversarial one (i.e., an abnormal cell in a vulnerable host), or is it more in the nature of a physiological selection or differentiation, which has survival value for the host as an adaptive phenomena? The very early initial interactions of mutagenic chemical carcinogens, radiations and viruses with DNA prejudice most to consider the adversarial 'abnormal' view as the appropriate one. Yet, the unusually common nature of the earliest altered rare cells that appear during carcinogenesis, their unusually bland nature, and their spontaneous differentiation to normal-appearing adult liver should be carefully considered

Modulation of Estrogen Chemical Carcinogenesis by Botanical Supplements used for Postmenopausal Women’s Health

Science.gov (United States)

Snelten, Courtney S.; Dietz, Birgit; Bolton, Judy L.

2012-01-01

Breast cancer risk has been associated with long-term estrogen exposure including traditional hormone therapy (HT, formally hormone replacement therapy). To avoid traditional HT and associated risks, women have been turning to botanical supplements such as black cohosh, red clover, licorice, hops, dong gui, and ginger to relieve menopausal symptoms despite a lack of efficacy evidence. The mechanisms of estrogen carcinogenesis involve both hormonal and chemical pathways. Botanical supplements could protect women from estrogen carcinogenesis by modulating key enzymatic steps [aromatase, P4501B1, P4501A1, catechol-O-methyltransferase (COMT), NAD(P)H quinone oxidoreductase 1 (NQO1), and reactive oxygen species (ROS) scavenging] in estradiol metabolism leading to estrogen carcinogenesis as outlined in Figure 1. This review summarizes the influence of popular botanical supplements used for women’s health on these key steps in the estrogen chemical carcinogenesis pathway, and suggests that botanical supplements may have added chemopreventive benefits by modulating estrogen metabolism. PMID:24223609

Role of Stat in Skin Carcinogenesis: Insights Gained from Relevant Mouse Models

International Nuclear Information System (INIS)

Macias, E.; Rao, D.; DiGiovanni, J.; DiGiovanni, J.; DiGiovanni, J.

2013-01-01

Signal transducer and activator of transcription 3 (Stat) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat-deficient mice have revealed that Stat plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat-deficient mouse models has demonstrated that Stat is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat in skin tumor progression. Studies using similar Stat-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat is an attractive target for skin cancer prevention and treatment.

Anti- and Protumorigenic Effects of PPARγ in Lung Cancer Progression: A Double-Edged Sword

Directory of Open Access Journals (Sweden)

Howard Li

2012-01-01

Full Text Available Peroxisome proliferator-activated receptor-γ (PPARγ is a member of the nuclear receptor superfamily of ligand-activated transcription factors that plays an important role in the control of gene expression linked to a variety of physiological processes, including cancer. Ligands for PPARγ include naturally occurring fatty acids and the thiazolidinedione class of antidiabetic drugs. Activation of PPARγ in a variety of cancer cells leads to inhibition of growth, decreased invasiveness, reduced production of proinflammatory cytokines, and promotion of a more differentiated phenotype. However, systemic activation of PPARγ has been reported to be protumorigenic in some in vitro systems and in vivo models. Here, we review the available data that implicate PPARγ in lung carcinogenesis and highlight the challenges of targeting PPARγ in lung cancer treatments.

Lung cancer incidence after smoking and exposure to radon using a two-mutation model

International Nuclear Information System (INIS)

Leenhouts, H.P.

1997-01-01

A study to analyze lung cancer in humans as a function of exposure to radon and smoking, used three types of data: population statistics in non-smokers habits of British radiologists and radon exposure of the Colorado uranium miners. Using a simplified two-mutation carcinogenesis model and only six unknown variables yielded a coherent description of lung cancer dependence on exposure to radon and smoking. For risk estimates the radiation effect of radon can be concluded to be highly dependent on smoking habits, e.g. the radiation effect differs (in absolute terms) by a factor of about 7 between non-smokers, but the relative risk is much higher in non-smokers than in smokers. The results to data justify a thorough investigation of the analysis method to realize improved radon risk estimates. (author)

Lung cancer incidence after smoking and exposure to radon using a two-mutation model

Energy Technology Data Exchange (ETDEWEB)

Leenhouts, H.P. [RIVM, Bilthoven (Netherlands)

1997-03-01

A study to analyze lung cancer in humans as a function of exposure to radon and smoking, used three types of data: population statistics in non-smokers habits of British radiologists and radon exposure of the Colorado uranium miners. Using a simplified two-mutation carcinogenesis model and only six unknown variables yielded a coherent description of lung cancer dependence on exposure to radon and smoking. For risk estimates the radiation effect of radon can be concluded to be highly dependent on smoking habits, e.g. the radiation effect differs (in absolute terms) by a factor of about 7 between non-smokers, but the relative risk is much higher in non-smokers than in smokers. The results to data justify a thorough investigation of the analysis method to realize improved radon risk estimates. (author)

Mouse Models of the Skin: Models to Define Mechanisms of Skin Carcinogenesis

International Nuclear Information System (INIS)

Wheeler, D. L.; Verma, A. K.; Denning, M. F.

2013-01-01

The multistep model of mouse skin carcinogenesis has facilitated identification of irreversible genetic events of initiation and progression, and epigenetic events of tumor promotion. Mouse skin tumor initiation can be accomplished by a single exposure to a sufficiently small dose of a carcinogen, and this step is rapid and irreversible. However, promotion of skin tumor formation requires a repeated and prolonged exposure to a promoter, and that tumor promotion is reversible. Investigations focused on the mechanisms of mouse carcinogenesis have resulted in the identifications of potential molecular targets of cancer induction and progression useful in planning strategies for human cancer prevention trials. This special issue contains eight papers that focus on mouse models used to study individual proteins expressed in the mouse skin and the role they play in differentiation, tissue homeostasis, skin carcinogenesis, and chemo prevention of skin cancer.

Deficiency in Poly(ADP-ribose Polymerase-1 (PARP-1 Accelerates Aging and Spontaneous Carcinogenesis in Mice

Directory of Open Access Journals (Sweden)

Tatiana S. Piskunova

2008-01-01

Full Text Available Genetic and biochemical studies have shown that PARP-1 and poly(ADP-ribosylation play an important role in DNA repair, genomic stability, cell death, inflammation, telomere maintenance, and suppressing tumorigenesis, suggesting that the homeostasis of poly(ADP-ribosylation and PARP-1 may also play an important role in aging. Here we show that PARP-1−/− mice exhibit a reduction of life span and a significant increase of population aging rate. Analysis of noninvasive parameters, including body weight gain, body temperature, estrous function, behavior, and a number of biochemical indices suggests the acceleration of biological aging in PARP-1−/− mice. The incidence of spontaneous tumors in both PARP-1−/− and PARP-1+/+ groups is similar; however, malignant tumors including uterine tumors, lung adenocarcinomas and hepatocellular carcinomas, develop at a significantly higher frequency in PARP-1−/− mice than PARP-1+/+ mice (72% and 49%, resp.; < .05. In addition, spontaneous tumors appear earlier in PARP-1−/− mice compared to the wild type group. Histopathological studies revealed a wide spectrum of tumors in uterus, ovaries, liver, lungs, mammary gland, soft tissues, and lymphoid organs in both groups of the mice. These results demonstrate that inactivation of DNA repair gene PARP-1 in mice leads to acceleration of aging, shortened life span, and increased spontaneous carcinogenesis.

Brief report: Afatinib and cetuximab in four patients with EGFR exon 20 insertion positive advanced non-small-cell lung cancer.

Science.gov (United States)

van Veggel, Bianca; de Langen, Adrianus J; Hashemi, Sayed; Monkhorst, Kim; Heideman, Daniëlle A M; Thunnissen, Erik; Smit, Egbert F

2018-04-24

Epidermal growth factor receptor (EGFR) exon 20 insertions comprise 4-9% of EGFR mutated non-small-cell lung cancer (NSCLC). Despite being an oncogenic driver, they are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). We hypothesized that dual EGFR blockade with afatinib, an irreversible EGFR TKI, and cetuximab, a monoclonal antibody against EGFR, could induce tumor responses. Four patients with EGFR exon 20 insertion positive NSCLC were treated with afatinib 40 mg once daily and cetuximab 250-500 mg/m 2 every two weeks. All patients had stage IV adenocarcinoma of the lung harboring an EGFR exon 20 insertion mutation. Previous lines of treatment consisted of platinum doublet chemotherapy (n=4) and EGFR TKI (n=2). Three out of four patients showed a partial response according to RECIST 1.1. Median progression-free survival was 5.4 months (95% confidence interval 0.0 - 14.2 months; range 2.7 - 17.6 months). Toxicity was manageable with appropriate skin management and dose reduction being required in two patients. Dual EGFR blockade with afatinib and cetuximab may induce tumor responses in patients with EGFR exon 20 insertion positive NSCLC. Copyright © 2018. Published by Elsevier Inc.

[Histologic study on impeding leukoplakia carcinogenesis of golden hamster cheek pouch about Erigeron breviscapus (Vant) Hand-Mazz].

Science.gov (United States)

Zhou, C T; Zhong, W J; Hua, L; Hu, H F; Jin, Z G

2000-06-01

To observe the effect of Erigeron breviscapus (Vant) Hand Mazz (HEr) in impeding oral leukoplakia carcinogenesis, and to seek effective Chinese herb medicine that can impede precarcinoma of oral mucosas. 132 golden hamsters were randomly divided into model group (60 animals), HEr group (60 animals), and control group 12 animals. Salley's leukoplakia carcinogenesis model of golden hamster cheek pouch was used in this study. HEr was injected into the stomach to impede evolution of carcinogenesis. Pathological specimens were observed via naked eye and light microscope between model group and HEr group. Results were compared. Observation via naked-eye showed that leukoplakia rate of HEr group (18.2%) was lower than that of model group (27.3%). Observation via light microscope showed that carcinogenesis rate descended one fold and displasia rate descended 0.4 fold in HEr group. HEr has exact effect in impeding leukoplakia carcinogenesis.

LungMAP: The Molecular Atlas of Lung Development Program.

Science.gov (United States)

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

2017-11-01

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

Experimental radiation carcinogenesis: what have we learned

Energy Technology Data Exchange (ETDEWEB)

Fry, R.J.M.

1980-01-01

The author reviews the need for animal experiments in development of a biological model for radioinduced carcinogenesis. He concludes they are vital for: (1) study of mechanisms; (2) establishment of generalizations; (3) elucidation of dose-response and time-dose relationships; and (4) determination of dose-distributions and their results, particularly for radionuclides. (PSB)

Experimental radiation carcinogenesis: what have we learned

International Nuclear Information System (INIS)

Fry, R.J.M.

1980-01-01

The author reviews the need for animal experiments in development of a biological model for radioinduced carcinogenesis. He concludes they are vital for: (1) study of mechanisms; (2) establishment of generalizations; (3) elucidation of dose-response and time-dose relationships; and (4) determination of dose-distributions and their results, particularly for radionuclides

Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice

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Sur, Subhayan, E-mail: subhayansur18@gmail.com [Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal (India); Pal, Debolina; Roy, Rituparna; Barua, Atish [Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal (India); Roy, Anup [North Bengal Medical College and Hospital, West Bengal (India); Saha, Prosenjit [Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal (India); Panda, Chinmay Kumar, E-mail: ckpanda.cnci@gmail.com [Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal (India)

2016-06-01

The aim of this study is to understand the molecular mechanisms of N-nitrosodiethylamine (NDEA) induced multi-organ carcinogenesis in tongue and liver of the same mouse and restriction of carcinogenesis by Epigallocatechin gallate (EGCG) and Theaflavin (TF), if any. For that purpose, cellular proliferation/apoptosis, prevalence of CD44 positive stem cell population and expressions of some key regulatory genes of self renewal Wnt and Hedgehog (Hh) pathways and some of their associated genes were analyzed in the NDEA induced tongue and liver lesions in absence or presence of EGCG/TF. Chronic NDEA exposure in oral cavity could decrease mice body weights and induce tongue and liver carcinogenesis with similar histological stages (severe dysplasia up to 30th weeks of NDEA administration). Increasing mice body weights were seen in continuous and post EGCG/TF treated groups. EGCG/TF treatment could restrict both the carcinogenesis at similar histological stages showing potential chemopreventive effect in continuous treated groups (mild dysplasia) followed by pre treatment (moderate dysplasia) and therapeutic efficacy in post treated groups (mild dysplasia) up to 30th week. The mechanism of carcinogenesis by NDEA and restriction by the EGCG/TF in both tongue and liver were similar and found to be associated with modulation in cellular proliferation/apoptosis and prevalence of CD44 positive population. The up-regulation of self renewal Wnt/β-catenin, Hh/Gli1 pathways and their associated genes Cyclin D1, cMyc and EGFR along with down regulation of E-cadherin seen during the carcinogenesis processes were found to be modulated during the restriction processes by EGCG/TF. - Highlights: • Simultaneous tongue and liver carcinogenesis in mice by oral NDEA administration • Restriction of both carcinogenesis by EGCG and TF at early pre-malignant stages • The mechanisms of carcinogenesis and restriction were similar in both the organs. • Changes in proliferation

Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice

International Nuclear Information System (INIS)

Sur, Subhayan; Pal, Debolina; Roy, Rituparna; Barua, Atish; Roy, Anup; Saha, Prosenjit; Panda, Chinmay Kumar

2016-01-01

The aim of this study is to understand the molecular mechanisms of N-nitrosodiethylamine (NDEA) induced multi-organ carcinogenesis in tongue and liver of the same mouse and restriction of carcinogenesis by Epigallocatechin gallate (EGCG) and Theaflavin (TF), if any. For that purpose, cellular proliferation/apoptosis, prevalence of CD44 positive stem cell population and expressions of some key regulatory genes of self renewal Wnt and Hedgehog (Hh) pathways and some of their associated genes were analyzed in the NDEA induced tongue and liver lesions in absence or presence of EGCG/TF. Chronic NDEA exposure in oral cavity could decrease mice body weights and induce tongue and liver carcinogenesis with similar histological stages (severe dysplasia up to 30th weeks of NDEA administration). Increasing mice body weights were seen in continuous and post EGCG/TF treated groups. EGCG/TF treatment could restrict both the carcinogenesis at similar histological stages showing potential chemopreventive effect in continuous treated groups (mild dysplasia) followed by pre treatment (moderate dysplasia) and therapeutic efficacy in post treated groups (mild dysplasia) up to 30th week. The mechanism of carcinogenesis by NDEA and restriction by the EGCG/TF in both tongue and liver were similar and found to be associated with modulation in cellular proliferation/apoptosis and prevalence of CD44 positive population. The up-regulation of self renewal Wnt/β-catenin, Hh/Gli1 pathways and their associated genes Cyclin D1, cMyc and EGFR along with down regulation of E-cadherin seen during the carcinogenesis processes were found to be modulated during the restriction processes by EGCG/TF. - Highlights: • Simultaneous tongue and liver carcinogenesis in mice by oral NDEA administration • Restriction of both carcinogenesis by EGCG and TF at early pre-malignant stages • The mechanisms of carcinogenesis and restriction were similar in both the organs. • Changes in proliferation

Nucleophosmin in the pathogenesis of arsenic-related bladder carcinogenesis revealed by quantitative proteomics

International Nuclear Information System (INIS)

Chen Shuhui; Wang Yiwen; Hsu Jueliang; Chang Hongyi; Wang Chiyun; Shen Potsun; Chiang Chiwu; Chuang Jingjing; Tsai Hungwen; Gu Powen; Chang Fangchih; Liu Hsiaosheng; Chow Nanhaw

2010-01-01

To investigate the molecular mechanisms of arsenic (As)-associated carcinogenesis, we performed proteomic analysis on E7 immortalized human uroepithelial cells after treatment with As in vitro. Quantitative proteomics was performed using stable isotope dimethyl labeling coupled with two-dimensional liquid chromatography peptide separation and mass spectrometry (MS)/MS analysis. Among 285 proteins, a total of 26 proteins were upregulated (ratio > 2.0) and 18 proteins were downregulated (ratio < 0.65) by As treatment, which are related to nucleotide binding, lipid metabolism, protein folding, protein biosynthesis, transcription, DNA repair, cell cycle control, and signal transduction. This study reports the potential significance of nucleophosmin (NPM) in the As-related bladder carcinogenesis. NPM was universally expressed in all of uroepithelial cell lines examined, implying that NPM may play a role in human bladder carcinogenesis. Upregulation of NPM tends to be dose- and time-dependent after As treatment. Expression of NPM was associated with cell proliferation, migration and anti-apoptosis. On the contrary, soy isoflavones inhibited the expression of NPM in vitro. The results suggest that NPM may play a role in the As-related bladder carcinogenesis, and soybean-based foods may have potential in the suppression of As/NPM-related tumorigenesis.

The reliability of lung crackle characteristics in cystic fibrosis and bronchiectasis patients in a clinical setting

International Nuclear Information System (INIS)

Marques, Alda; Bruton, Anne; Barney, Anna

2009-01-01

Lung sounds provide useful information for assessing and monitoring respiratory patients, but standard auscultation is subjective. Computer aided lung sound analysis (CALSA) enables the quantification and characterisation of added lung sounds (e.g. crackles). At present, little is known about the reliability of these sound characteristics. Therefore, the aim of this study was to explore the reliability of crackle initial deflection width (IDW) and two-cycle deflection (2CD) in a clinical population. Fifty-four subjects (37 bronchiectasis, 17 cystic fibrosis) were recruited from out-patient clinics. Three repeated lung sound recordings were taken at seven anatomical sites with a digital stethoscope connected to a laptop computer. The intra-subject reliability of crackle IDW and 2CD was found to be 'good' to 'excellent', estimated by the analysis of variance, intraclass correlation coefficient (IDW 0.76;0.85, 2CD 0.83;0.94), Bland and Altman 95% limits of agreement (IDW −0.50;0.47 ms, 2CD −2.12;1.87 ms) and smallest real difference (IDW 0.30;0.66 ms, 2CD 1.57;2.42 ms). Crackle 2CD was found to be more reliable than IDW. It is concluded that crackle IDW and 2CD characterized by CALSA have good test–retest reliability. This technique requires further evaluation since CALSA has potential to diagnose or monitor respiratory conditions, and provide an objective physiological measure for respiratory interventions

The Murine Lung Microbiome Changes During Lung Inflammation and Intranasal Vancomycin Treatment

Science.gov (United States)

Barfod, Kenneth Klingenberg; Vrankx, Katleen; Mirsepasi-Lauridsen, Hengameh Chloé; Hansen, Jitka Stilund; Hougaard, Karin Sørig; Larsen, Søren Thor; Ouwenhand, Arthur C.; Krogfelt, Karen Angeliki

2015-01-01

Most microbiome research related to airway diseases has focused on the gut microbiome. This is despite advances in culture independent microbial identification techniques revealing that even healthy lungs possess a unique dynamic microbiome. This conceptual change raises the question; if lung diseases could be causally linked to local dysbiosis of the local lung microbiota. Here, we manipulate the murine lung and gut microbiome, in order to show that the lung microbiota can be changed experimentally. We have used four different approaches: lung inflammation by exposure to carbon nano-tube particles, oral probiotics and oral or intranasal exposure to the antibiotic vancomycin. Bacterial DNA was extracted from broncho-alveolar and nasal lavage fluids, caecum samples and compared by DGGE. Our results show that: the lung microbiota is sex dependent and not just a reflection of the gut microbiota, and that induced inflammation can change lung microbiota. This change is not transferred to offspring. Oral probiotics in adult mice do not change lung microbiome detectible by DGGE. Nasal vancomycin can change the lung microbiome preferentially, while oral exposure does not. These observations should be considered in future studies of the causal relationship between lung microbiota and lung diseases. PMID:26668669

Radiation carcinogenesis and related radiobiology. Special listing

International Nuclear Information System (INIS)

1980-01-01

The special listing of Current Cancer Research Projects is a publication of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute. Each Listing contains descriptions of ongoing projects in one selected cancer research area. The research areas include: Human cancer and exposure to radiation; Experimental radiation carcinogenesis and radiation biology

Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin

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Sood, Shilpa; Choudhary, Shambhunath; Wang, Hwa-Chain Robert, E-mail: hcrwang@utk.edu

2013-09-06

Highlights: •Triclocarban exposure induces breast epithelial cell carcinogenesis. •Triclocarban induces the Erk–Nox pathway, ROS elevation, and DNA damage. •Physiological doses of triclocarban induce cellular carcinogenesis. •Non-cytotoxic curcumin blocks triclocarban-induced carcinogenesis and pathways. -- Abstract: More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens and co-carcinogens. To identify co-carcinogens with abilities to induce cellular pre-malignancy, we studied the activity of triclocarban (TCC), an antimicrobial agent commonly used in household and personal care products. Here, we demonstrated, for the first time, that chronic exposure to TCC at physiologically-achievable nanomolar concentrations resulted in progressive carcinogenesis of human breast cells from non-cancerous to pre-malignant. Pre-malignant carcinogenesis was measured by increasingly-acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth and increased cell proliferation, without acquisition of cellular tumorigenicity. Long-term TCC exposure also induced constitutive activation of the Erk–Nox pathway and increases of reactive oxygen species (ROS) in cells. A single TCC exposure induced transient induction of the Erk–Nox pathway, ROS elevation, increased cell proliferation, and DNA damage in not only non-cancerous breast cells but also breast cancer cells. Using these constitutively- and transiently-induced changes as endpoints, we revealed that non-cytotoxic curcumin was effective in intervention of TCC-induced cellular pre-malignancy. Our results lead us to suggest that the co-carcinogenic potential of TCC should be seriously considered in epidemiological studies to reveal the significance of TCC in the development of sporadic breast cancer. Using TCC-induced transient and constitutive endpoints as targets will likely help identify non-cytotoxic preventive

LIFETIME PHYSICAL INACTIVITY IS ASSOCIATED WITH LUNG CANCER RISK AND MORTALITY.

Science.gov (United States)

Cannioto, Rikki; Etter, John Lewis; LaMonte, Michael J; Ray, Andrew D; Joseph, Janine M; Al Qassim, Emad; Eng, Kevin H; Moysich, Kirsten B

2018-01-01

Investigations of the independent associations of physical inactivity with cancer endpoints have been mounting in the epidemiological literature, in part due to the high prevalence of physical inactivity among cancer patients and to evidence that inactivity associates with carcinogenesis via pathways independent of obesity. Yet, physical inactivity is not currently recognized as a well-established risk or prognostic factor for lung cancer. As such, we examined the associations of lifetime physical inactivity with lung cancer risk and mortality in a hospital-based, case-control study. Materials and Methods: The analyses included data from 660 lung cancer patients and 1335 matched cancer-free controls. Multivariable logistic regression analyses were utilized to assess the association between lifetime physical inactivity and lung cancer risk, and Cox proportional hazards models were utilized to estimate the association between lifetime physical inactivity and mortality among lung cancer cases. Results: We observed a significant positive association between lifetime physical inactivity and lung cancer risk: [Odds ratio (OR)=2.23, 95% confidence interval (CI): 1.77-2.81]; the association remained significant among never smokers (OR=3.00, 95% CI:1.33-6.78) and non-smokers (OR=2.33, 95% CI: 1.79-3.02). We also observed a significant positive association between lifetime physical inactivity and lung cancer mortality [Hazard ratio (HR)=1.40, 95% CI: 1.14-1.71]; the association remained significant in non-smokers (HR=1.51, 95% CI: 1.16-1.95). These data add to the body of evidence suggesting that physical inactivity is an independent risk and prognostic factor for cancer. Additional research utilizing prospectively collected data is needed to substantiate the current findings.

Fifty years of nuclear magnetic resonance

International Nuclear Information System (INIS)

Martinez Valderrama, Juan Crisostomo

1997-01-01

Short information about the main developments of nuclear magnetic resonance during their fifty existence years is presented. Beside two examples of application (HETCOR and INADEQUATE) to the structural determination of organic compounds are described

Transcriptome Analysis of Individual Stromal Cell Populations Identifies Stroma-Tumor Crosstalk in Mouse Lung Cancer Model

Directory of Open Access Journals (Sweden)

Hyejin Choi

2015-02-01

Full Text Available Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systematically dissect the contribution of specific hematopoietic stromal cells in lung cancer. RNA deep-sequencing analysis of individually sorted myeloid lineage and tumor epithelial cells revealed cell-type-specific differentially regulated genes, indicative of activated stroma. We developed a computational model for crosstalk signaling discovery based on ligand-receptor interactions and downstream signaling networks and identified known and novel tumor-stroma paracrine and tumor autocrine crosstalk-signaling pathways in NSCLC. We provide cellular and molecular insights into components of the lung cancer microenvironment that contribute to carcinogenesis. This study has the potential for development of therapeutic strategies that target tumor-stroma interactions and may complement conventional anti-cancer treatments.

Isolation and Characterization of Human Lung Lymphatic Endothelial Cells

Science.gov (United States)

Lorusso, Bruno; Falco, Angela; Madeddu, Denise; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Gervasi, Andrea; Rinaldi, Laura; Lagrasta, Costanza; Maselli, Davide; Gnetti, Letizia; Silini, Enrico M.; Quaini, Eugenio; Ampollini, Luca; Carbognani, Paolo; Quaini, Federico

2015-01-01

Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL-LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy. PMID:26137493

Tc99m glucoheptonate in detection of lung tumors

International Nuclear Information System (INIS)

Pfeiff, D.N.E.; Nascimento, C.B.L.; Riesgo, A.; Ferreira, E.D.; Kwiatowski, A.; Bornemann, C.

1989-01-01

The authors intended, with this study, the use and the efficacy of pulmonary scintigraphy with GHA Tc99 as auxiliary method in the diagnosis of lung tumors. Fifty-five patients were studied clinically and radiologically and afterwards with GHA Tc99 pulmonary scintigraphy. The data were confronted with pathologic findings. In thirty-nine of this patients the isotope were captivate in the place of the tumour. (author) [pt

Lung cancer: Incidence and survival in Rabat, Morocco.

Science.gov (United States)

Lachgar, A; Tazi, M A; Afif, M; Er-Raki, A; Kebdani, T; Benjaafar, N

2016-12-01

Lung cancer is the most common cancer worldwide, but epidemiologic data from developing countries are lacking. This article reports lung cancer incidence and survival in Rabat, the capital of Morocco. All lung cancer cases diagnosed between 2005 and 2008 were analyzed using data provided by the Rabat Cancer Registry. The standardized rate was reported using age adjustment with respect to the world standard population, and the observed survival rates were calculated using the Kaplan-Meier method. Three hundred fifty-one cases were registered (314 males and 37 females), aged 27-90 years (median, 59 years). The most common pathological type was adenocarcinoma (40.2%) followed by squamous cell carcinoma (31.9%); the majority of cases were diagnosed at stage IV (52%). The age-standardized incidence rate was 25.1 and 2.7 per 100,000 for males and females, respectively, and the overall observed survival rates at 1 and 5 years were 31.7% and 3.4%, respectively. The clinical stage of disease was the only independent predictor of survival. The survival rate of lung cancer in Rabat is very poor. This finding explains the need for measures to reduce the prevalence of tobacco and to improve diagnostic and therapeutic facilities for lung cancer. Copyright © 2016. Published by Elsevier Masson SAS.

Melatonin as a potential anticarcinogen for non-small-cell lung cancer

Science.gov (United States)

Han, Jing; Wang, Dongjin; Di, Shouyin; Hu, Wei; Liu, Dong; Li, Xiaofei; Reiter, Russel J.; Yan, Xiaolong

2016-01-01

Non-small-cell lung cancer (NSCLC) is a leading cause of death from cancer worldwide. Melatonin, an indoleamine discovered in the pineal gland, exerts pleiotropic anticancer effects against a variety of cancer types. In particular, melatonin may be an important anticancer drug in the treatment of NSCLC. Herein, we review the correlation between the disruption of the melatonin rhythm and NSCLC incidence; we also evaluate the evidence related to the effects of melatonin in inhibiting lung carcinogenesis. Special focus is placed on the oncostatic effects of melatonin, including anti-proliferation, induction of apoptosis, inhibition of invasion and metastasis, and enhancement of immunomodulation. We suggest the drug synergy of melatonin with radio- or chemotherapy for NSCLC could prove to be useful. Taken together, the information complied herein may serve as a comprehensive reference for the anticancer mechanisms of melatonin against NSCLC, and may be helpful for the design of future experimental research and for advancing melatonin as a therapeutic agent for NSCLC. PMID:27102150

Estrogen receptor beta, a possible tumor suppressor involved in ovarian carcinogenesis

Science.gov (United States)

Lazennec, Gwendal

2006-01-01

Ovarian cancer is one of the leading cause of death from gynecological tumors in women. Several lines of evidence suggest that estrogens may play an important role in ovarian carcinogenesis, through their receptors, ERα and ERβ. Interestingly, malignant ovarian tumors originating from epithelial surface constitute about 90% of ovarian cancers and expressed low levels of ERβ, compared to normal tissues. In addition, restoration of ERβ in ovarian cancer cells, leads to strong inhibition of their proliferation and invasion, while apoptosis is enhanced. In this manuscript, recent data suggesting a possible tumor-suppressor role for ERβ in ovarian carcinogenesis are discussed. PMID:16399219

Hypoxia and cell cycle deregulation in endometrial carcinogenesis

NARCIS (Netherlands)

Horrée, N.

2007-01-01

Because uterine endometrial carcinoma is the most common malignancy of the female genital tract and 1 of every 5 patients dies of this disease, understanding the mechanisms of carcinogenesis and progression of endometrial carcinoma is important. In general, this thesis can be summarized as a study

Experimental Hepatic Carcinogenesis: Oxidative Stress and Natural Antioxidants

Directory of Open Access Journals (Sweden)

Velid Unsal

2017-08-01

Full Text Available Hepatocellular carcinoma is one of the most common cancers in the world, and it is influenced by agents such as DEN, 2-AAF, phenobarbital, alcohol, aflatoxin B1 metabolite or hepatitis viruses (B and C. Oxidative stress is becoming recognized as a key factor in the progression of hepatocarcinogenesis. Reactive oxygen species can play a leading role in initiation and promotion of hepatic carcinogenesis. The metabolites of DEN Diethylnitrosamine (DEN mediate the binding of tumour promoters by covalently binding to the DNA with one or two oxidation-providing electrons. 2-AAF is the inducer of DEN, and it is involved in tumour formation in the bladder and liver. Reactive Oxygen species (ROS; carbohydrates, lipids, DNA and enzymes, such as affect all important structures. Additionally, an excessive amount of ROS is highly toxic to cells. Antioxidants are protects against ROS, toxic substances, carcinogens. This review focuses on the literature on studies of Hepatic Carcinogenesis, oxidative stress and antioxidant therapy.

Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

Directory of Open Access Journals (Sweden)

Payne CM

2011-05-01

Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

Palytoxin: exploiting a novel skin tumor promoter to explore signal transduction and carcinogenesis.

Science.gov (United States)

Wattenberg, Elizabeth V

2007-01-01

Palytoxin is a novel skin tumor promoter, which has been used to help probe the role of different types of signaling mechanisms in carcinogenesis. The multistage mouse skin model indicates that tumor promotion is an early, prolonged, and reversible phase of carcinogenesis. Understanding the molecular mechanisms underlying tumor promotion is therefore important for developing strategies to prevent and treat cancer. Naturally occurring tumor promoters that bind to specific cellular receptors have proven to be useful tools for investigating important biochemical events in multistage carcinogenesis. For example, the identification of protein kinase C as the receptor for the prototypical skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) (also called phorbol 12-myristate 13-acetate, PMA) provided key evidence that tumor promotion involves the aberrant modulation of signaling cascades that govern cell fate and function. The subsequent discovery that palytoxin, a marine toxin isolated from zoanthids (genus Palythoa), is a potent skin tumor promoter yet does not activate protein kinase C indicated that investigating palytoxin action could help reveal new aspects of tumor promotion. Interestingly, the putative receptor for palytoxin is the Na(+),K(+)-ATPase. This review focuses on palytoxin-stimulated signaling and how palytoxin has been used to investigate alternate biochemical mechanisms by which important targets in carcinogenesis can be modulated.

Null effect of dietary restriction on prostate carcinogenesis in the Wistar-Unilever rat.

Science.gov (United States)

McCormick, David L; Johnson, William D; Haryu, Todd M; Bosland, Maarten C; Lubet, Ronald A; Steele, Vernon E

2007-01-01

Chronic dietary restriction inhibits carcinogenesis in several sites in laboratory animals. To determine the effects of dietary restriction on prostate carcinogenesis, prostate cancers were induced in male Wistar-Unilever rats by a sequential regimen of cyproterone acetate (50 mg/day; 21 days); testosterone propionate (100 mg/kg/day; 3 days); N-methyl-N-nitrosourea [MNU; 30 mg/kg; single dose]; and testosterone (subcutaneous implants of 2 pellets containing 40 mg each). Dietary restriction (0% [ad libitum control], 15%, or 30%) was initiated 2 wk post-MNU, and continued until study termination at 12 mo. Dietary restriction induced a rapid suppression of body weight gain but conferred no protection against prostate carcinogenesis. 74% of carcinogen-treated ad libitum controls developed accessory sex gland cancers, versus cancer incidences of 64% and 72% in groups restricted by 15% and 30%, respectively. Similarly, 44% of dietary controls developed cancers limited to the dorsolateral/prostate, versus incidences of 45% and 53% in groups restricted by 15% and 30%. The results of the present study do not support the hypothesis that prostate carcinogenesis can be prevented by reducing caloric intake. Reducing mean body weight by up to 25% through chronic dietary restriction has no effect on the induction of prostate cancers in the Wistar-Unilever rat model.

Biologically based modelling and simulation of carcinogenesis at low doses

International Nuclear Information System (INIS)

Ouchi, Noriyuki B.

2003-01-01

The process of the carcinogenesis is studied by computer simulation. In general, we need a large number of experimental samples to detect mutations at low doses, but in practice it is difficult to get such a large number of data. To satisfy the requirements of the situation at low doses, it is good to study the process of carcinogenesis using biologically based mathematical model. We have mainly studied it by using as known as 'multi-stage model'; the model seems to get complicated, as we adopt the recent new findings of molecular biological experiments. Moreover, the basic idea of the multi-stage model is based on the epidemiologic data of log-log variation of cancer incidence with age, it seems to be difficult to compare with experimental data of irradiated cell culture system, which has been increasing in recent years. Taking above into consideration, we concluded that we had better make new model with following features: 1) a unit of the target system is a cell, 2) the new information of the molecular biology can be easily introduced, 3) having spatial coordinates for checking a colony formation or tumorigenesis. In this presentation, we will show the detail of the model and some simulation results about the carcinogenesis. (author)

Amebic lung abscess with coexisting lung adenocarcinoma: a unusual case of amebiasis.

Science.gov (United States)

Zhu, Hailong; Min, Xiangyang; Li, Shuai; Feng, Meng; Zhang, Guofeng; Yi, Xianghua

2014-01-01

Amebic lung abscess with concurrent lung cancer, but without either a liver abscess or amebic colitis, is extremely uncommon. Here, we report a 70-year-old man presenting with pulmonary amebiasis and coexisting lung adenocarcinoma. During his first-time hospitalization, the diagnosis of lung amebiasis was confirmed by morphological observation and PCR in formalin-fixed and paraffin-embedded sediments of pleural effusion. Almost four months later, the patient was readmitted to hospital for similar complaints. On readmission, lung adenocarcinoma was diagnosed by liquid-based sputum cytology and thought to be delayed because coexisting amebic lung abscess. This case demonstrated that sediments of pleural effusion may be used for further pathological examination after routine cytology has shown negative results. At the same time, we concluded that lung cancer may easily go undetected in the patients with pulmonary amebiasis and repetitive evaluation by cytology and imaging follow-up are useful to find potential cancer.

Estimating radiation-induced cancer risk using MVK two-stage model for carcinogenesis

International Nuclear Information System (INIS)

Kai, M.; Kusama, T.; Aoki, Y.

1993-01-01

Based on the carcinogenesis model as proposed by Moolgavkar et al., time-dependent relative risk models were derived for projecting the time variation in excess relative risk. If it is assumed that each process is described by time-independent linear dose-response relationship, the time variation in excess relative risk is influenced by the parameter related with the promotion process. The risk model based carcinogenesis theory would play a marked role in estimating radiation-induced cancer risk in constructing a projection model or transfer model

Nuclear magnetic resonance evaluation of fifty children with cancer

International Nuclear Information System (INIS)

Cohen, M.D.; Klatte, E.C.; Smith, J.A.; Carr, B.E.; Martin-Simmerman, P.

1985-01-01

Fifty children with cancer have been studied by MR. The patients studied include ten with lymphoma, nine with neuroblastoma, five with rhabdomyosarcoma, six with leukemia, five with Ewings sarcoma, four with Wilms tumor and several with other miscellaneous tumors. The results of scanning show that MR is well tolerated by children. Primary tumor has been identified in every case. Metastases have been identified in many patients. MR has proved helpful in identifying the organ of origin of a tumor. Because of excellent vessel visualization it is helpful in planning surgical resection of a tumor. In addition, in a number of patients MR has proved helpful in monitoring the response of tumor to nonsurgical therapy. With continued improvement in image quality it is believed that MR has a major role to play in pediatric tumor imaging [fr

Correlation between US and MRI for prenatal lung volumetry in diaphragmatic hernia, and use of Doppler to identify the ipsilateral lung cap

Energy Technology Data Exchange (ETDEWEB)

Castellote, Amparo; Mencho, Sandra; Cadavid, Lina; Piqueras, Joaquim; Enriquez, Goya [University Children' s Hospital Vall d' Hebron, Department of Pediatric Radiology, Barcelona (Spain); Carreras, Elena; Higueras, Teresa [University Hospital Vall d' Hebron, Department of Obstetrics and Gynecology, Barcelona (Spain)

2011-12-15

Pulmonary hypoplasia is a common cause of neonatal death. To describe the correlation between relative fetal lung volume (RFLV) and lung-to-head ratio (LHR) in fetuses with unilateral diaphragmatic hernia. Additionally, to describe identification of the ipsilateral lung cap by power Doppler. Single-institution study of consecutive fetuses with diaphragmatic hernia. LHR (by US) and RFLV (by MRI) were correlated in fetuses with and without an ipsilateral lung cap seen at MRI. In four, color/power Doppler was used to follow the pulmonary artery of the ipsilateral lung to identify the compressed cap. The study included 48 fetuses of 20-38 weeks' gestational age (mean, 26 weeks). Mean LHR was 1.52 (range, 0.6-3) in fetuses with a lung cap and 1.15 (range, 0.6-2.58) in fetuses without (P = 0.043). Mean RFLV was 47.4% (range, 18-80%) in fetuses with and 32.9% (range, 14-57%) in fetuses without a lung cap (P = 0.005). RFLV and LHR correlated (r = 0.41, P = 0.01 in those with a cap; r = 0.50, P = 0.05 in those without). Power Doppler identified the ipsilateral lung cap and pulsed Doppler confirmed pulmonary vascularization in four of four fetuses. LHR underestimates lung volume in fetuses with an ipsilateral lung cap. Power Doppler may be useful for identifying the cap. (orig.)

Comparison of the diagnosis using FDG-PET and AC-PET with histopathological features in lung adenocarcinomas

International Nuclear Information System (INIS)

Koizumi, Satoko

2011-01-01

Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a useful tool for lung cancer diagnosis because of its good sensitivity and specificity. However, FDG-PET is problematically causing the false negative in cases of well differentiated lung adenocarcinomas which are low grade malignancies. Acetate (AC)-PET using 11 C-acetate is thought to be a superior detection tool for low grade malignancies. In this study, comparison of each type of PET in relation with histopathological features of lung adenocarcinomas was conducted. Samples obtained from 81 lesions in 75 patients with a lung adenocarcinoma who were operated at various institutions of our collaborators between 2005 and 2009 following FDG-PET and AC-PET procedures were examined. These samples consisted of fifty-seven cases of a well differentiated adenocarcinoma and twenty-four cases of a moderately- or a poorly-differentiated adenocarcinoma. Relationships between the histopathological factors (ly, v, p) as well as the lymphatic microvessel and microvessel densities in a tumor and FDG- and AC-PET findings were evaluated. AC-PET was more sensitive than FDG-PET (0.58 vs 0.74, p=0.0001). FDG-PET showed a correlation with invasiveness of the tumor and intratumoral lymphatic microvessel density (p<0.05). Furthermore, AC-PET possessed a superior sensitivity for the detection of well differentiated adenocarcinomas, and tumors without ly, v, or p factors. In lung adenocarcinoma AC-PET showed better sensitivity than FDG-PET and true positive in all cases of stage I B or more. FDG-PET showed the correlation with the pathological invasiveness (ly, v, p) of a tumor and the intratumoral lymphatic microvessel density. (author)

Gross tumor volume dependency on phase sorting methods of four-dimensional computed tomography images for lung cancer

Energy Technology Data Exchange (ETDEWEB)

Lee, Soo Yong; Lim, Sang Wook; Ma, Sun Young; Yu, Je Sang [Dept. of Radiation Oncology, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan (Korea, Republic of)

2017-09-15

To see the gross tumor volume (GTV) dependency according to the phase selection and reconstruction methods, we measured and analyzed the changes of tumor volume and motion at each phase in 20 cases with lung cancer patients who underwent image-guided radiotherapy. We retrospectively analyzed four-dimensional computed tomography (4D-CT) images in 20 cases of 19 patients who underwent image-guided radiotherapy. The 4D-CT images were reconstructed by the maximum intensity projection (MIP) and the minimum intensity projection (Min-IP) method after sorting phase as 40%–60%, 30%–70%, and 0%–90%. We analyzed the relationship between the range of motion and the change of GTV according to the reconstruction method. The motion ranges of GTVs are statistically significant only for the tumor motion in craniocaudal direction. The discrepancies of GTV volume and motion between MIP and Min-IP increased rapidly as the wider ranges of duty cycles are selected. As narrow as possible duty cycle such as 40%–60% and MIP reconstruction was suitable for lung cancer if the respiration was stable. Selecting the reconstruction methods and duty cycle is important for small size and for large motion range tumors.

Genomic instability in quartz dust exposed rat lungs: Is inflammation responsible?

Energy Technology Data Exchange (ETDEWEB)

Albrecht, C; Schins, R P F [Institut fuer Umweltmedizinische Forschung (IUF) at the Heinrich Heine University Duesseldorf (Germany); Demircigil, G Cakmak; Coskun, Erdem [Gazi University, Faculty of Pharmacy, Department of Toxicology, Ankara (Turkey); Schooten, F J van [Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Health Risk Analysis and Toxicology, University of Maastricht (Netherlands); Borm, P J A [Centre of Expertise in Life Sciences (Cel), Hogeschool Zuyd, Heerlen (Netherlands); Knaapen, A M, E-mail: catrin.albrecht@uni-duesseldorf.d

2009-02-01

Exposure to quartz dusts has been associated with lung cancer and fibrosis. Although the responsible mechanisms are not completely understood, progressive inflammation with associated induction of persistent oxidative stress has been discussed as a key event for these diseases. Previously we have evaluated the kinetics of pulmonary inflammation in the rat model following a single intratracheal instillation of 2mg DQ12 quartz, either in its native form or upon its surface modification with polyvinylpyridine-N-oxide or aluminium lactate. This model has been applied now to evaluate the role of inflammation in the kinetics of induction of DNA damage and response at 3, 7, 28, and 90 days after treatment. Bronchoalveolar lavage (BAL) cell counts and differentials as well as BAL fluid myeloperoxidase activity were used as markers of inflammation. Whole lung homogenate was investigated to determine the induction of the oxidative and pre-mutagenic DNA lesion 8-hydroxy-2-deoxy-guanosine (8-OHdG) by HPLC/ECD, while mRNA and protein expression of oxidative stress and DNA damage response genes including hemeoxygenase-1 (HO-1) and apurinic/apyrimidinic endonuclease (APE/Ref-1) were evaluated using Western blotting and real time PCR. Isolated lung epithelial cells from the treated rats were used for DNA strand breakage analysis using the alkaline comet assay as well as for micronucleus scoring in May-Gruenwald-Giemsa stained cytospin preparations. In the rats that were treated with quartz, no increased 8-OHdG levels were observed, despite the presence of a marked and persistent inflammation. However, DNA strand breakage in the lung epithelial cells of the quartz treated rats was significantly enhanced at 3 days, but not at 28 days. Moreover, significantly enhanced micronucleus frequencies were observed for all four time points investigated. In the animals that were treated with the PVNO modified quartz, micronuclei scores did not differ from controls, while in those treated with

Age-dependent change in biological characteristics of stem cells in radiation-induced mammary carcinogenesis

International Nuclear Information System (INIS)

Shimada, Yoshiya; Nishimura, Mayumi; Kakinuma, Shizuko; Imaoka, Tatsuhiko; Yasukawa-Barnes, Jane; Gould, Michael N.; Clifton, Kelly H.

2003-01-01

If you ask what types of cells are the targets for carcinogenesis, a popular answer would be that cancer arises from stem cells. Stem cells are cells that are capable of both self-renewal and generation of differentiated progenies. If the hypothesis of 'cancer as stem cell disease' is correct, the risk of carcinogenesis should be a function of the number of stem cells and their responsiveness of carcinogen-induced damage. In the present study, we addressed the feasibility of this hypothesis using the rat mammary carcinogenesis model. One of the important conclusions emerging from studies on atomic bomb survivors concerns age-related changes in the susceptibility to breast cancer. The relative risk of breast cancer is very high among women exposed to ionizing radiation before or during puberty, and it decreases thereafter. Little information is available, however, on age-related changes in the radiobiological nature of mammary stem cells. We examined age-associated changes in the number of mammary stem-like cells (clonogens) and their susceptibility to radiation in terms of cell death and carcinogenic initiation frequency. The results were as follows. (1) During the prepubertal period, the total number of mammary clonogens per rat increased exponentially with a population doubling time of ∼4 days. After puberty, the doubling time lengthened to ∼30 days. The total number of clonogens in abdominal and inguinal mammary glands was ∼200 in 2-week-old rats, while it was ∼5600 in 8-week-old rats. (2) The survival curves of clonogenic cells after irradiation indicated that radiation sensitivity of the cells before and during puberty was much higher than after puberty. (3) The initiation frequency of the clonogens from prepubertal rats after 5 Gy irradiation was four times higher than that of the clonogens from post-pubertal rats. These results suggest that changes in the number of stem cells and their radiobiological characteristics underlie the age

Age-dependent change in biological characteristics of stem cells in radiation-induced mammary carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Shimada, Yoshiya; Nishimura, Mayumi; Kakinuma, Shizuko; Imaoka, Tatsuhiko [National Institute of Radiological Sciences, Anagawa, Chiba (Japan); Yasukawa-Barnes, Jane; Gould, Michael N.; Clifton, Kelly H. [Univ. of Wisconsin, Department of Human Oncology, Madison, WI (United States)

2003-07-01

If you ask what types of cells are the targets for carcinogenesis, a popular answer would be that cancer arises from stem cells. Stem cells are cells that are capable of both self-renewal and generation of differentiated progenies. If the hypothesis of 'cancer as stem cell disease' is correct, the risk of carcinogenesis should be a function of the number of stem cells and their responsiveness of carcinogen-induced damage. In the present study, we addressed the feasibility of this hypothesis using the rat mammary carcinogenesis model. One of the important conclusions emerging from studies on atomic bomb survivors concerns age-related changes in the susceptibility to breast cancer. The relative risk of breast cancer is very high among women exposed to ionizing radiation before or during puberty, and it decreases thereafter. Little information is available, however, on age-related changes in the radiobiological nature of mammary stem cells. We examined age-associated changes in the number of mammary stem-like cells (clonogens) and their susceptibility to radiation in terms of cell death and carcinogenic initiation frequency. The results were as follows. (1) During the prepubertal period, the total number of mammary clonogens per rat increased exponentially with a population doubling time of {approx}4 days. After puberty, the doubling time lengthened to {approx}30 days. The total number of clonogens in abdominal and inguinal mammary glands was {approx}200 in 2-week-old rats, while it was {approx}5600 in 8-week-old rats. (2) The survival curves of clonogenic cells after irradiation indicated that radiation sensitivity of the cells before and during puberty was much higher than after puberty. (3) The initiation frequency of the clonogens from prepubertal rats after 5 Gy irradiation was four times higher than that of the clonogens from post-pubertal rats. These results suggest that changes in the number of stem cells and their radiobiological characteristics

Carcinogenesis related to intense pulsed light and UV exposure

DEFF Research Database (Denmark)

Hedelund, L; Lerche, C; Wulf, H C

2006-01-01

This study examines whether intense pulsed light (IPL) treatment has a carcinogenic potential itself or may influence ultraviolet (UV)-induced carcinogenesis. Secondly, it evaluates whether UV exposure may influence IPL-induced side effects. Hairless, lightly pigmented mice (n=144) received three...

End-Binding Protein 1 (EB1) Up-regulation is an Early Event in Colorectal Carcinogenesis

Science.gov (United States)

Stypula-Cyrus, Yolanda; Mutyal, Nikhil N.; Cruz, Mart Angelo Dela; Kunte, Dhananjay P.; Radosevich, Andrew J.; Wali, Ramesh; Roy, Hemant K.; Backman, Vadim

2014-01-01

End-binding protein (EB1) is a microtubule protein that binds to the tumor suppressor adenomatous polyposis coli (APC). While EB1 is implicated as a potential oncogene, its role in cancer progression is unknown. Therefore, we analyzed EB1/APC expression at the earliest stages of colorectal carcinogenesis and in the uninvolved mucosa ("field effect") of human and animal tissue. We also performed siRNA-knockdown in colon cancer cell lines. EB1 is up-regulated in early and field carcinogenesis in the colon, and the cellular/nano-architectural effect of EB1 knockdown depended on the genetic context. Thus, dysregulation of EB1 is an important early event in colon carcinogenesis. PMID:24492008

Deutsches Atomforum turns fifty

International Nuclear Information System (INIS)

Geisler, Maja

2009-01-01

Fifty years ago, the Deutsches Atomforum e. V. was founded to promote the peaceful uses of nuclear power in Germany. On July 1, 2009, the organization celebrated its fiftieth birthday in Berlin. The anniversary was celebrated in the Berlin electricity plant, Germany's oldest existing building for commercial electricity generation. DAtF President Dr. Walter Hohlefelder welcomed some 200 high-ranking guests from politics, industry, and from the nuclear community, above all, the Chancellor of the Federal Republic of Germany, Dr. Angela Merkel, and, as keynote speaker, Professor Dr. Arnulf Baring. (orig.)

History of Lung Transplantation.

Science.gov (United States)

Dabak, Gül; Şenbaklavacı, Ömer

2016-04-01

History of lung transplantation in the world can be traced back to the early years of the 20 th century when experimental vascular anastomotic techniques were developed by Carrel and Guthrie, followed by transplantation of thoracic organs on animal models by Demikhov and finally it was James Hardy who did the first lung transplantation attempt on human. But it was not until the discovery of cyclosporine and development of better surgical techniques that success could be achieved in that field by the Toronto Lung Transplant Group led by Joel Cooper. Up to the present day, over 51.000 lung transplants were performed in the world at different centers. The start of lung transplantation in Turkey has been delayed for various reasons. From 1998 on, there were several attempts but the first successful lung transplant was performed at Sureyyapasa Hospital in 2009. Today there are four lung transplant centers in Turkey; two in Istanbul, one in Ankara and another one in Izmir. Three lung transplant centers from Istanbul which belong to private sector have newly applied for licence from the Ministry of Health.

Chronology of p53 protein accumulation in gastric carcinogenesis

NARCIS (Netherlands)

Craanen, M. E.; Blok, P.; Dekker, W.; Offerhaus, G. J.; Tytgat, G. N.

1995-01-01

p53 Protein accumulation in early gastric carcinoma was studied in relation to the histological type (Lauren classification) and the type of growth pattern, including the chronology of p53 protein accumulation during carcinogenesis. Forty five, paraffin embedded gastrectomy specimens from early

Mechanisms of carcinogenesis prevention by flavonoids

Directory of Open Access Journals (Sweden)

G. A. Belitsky

2014-01-01

Full Text Available The mechanisms of anticancerogenic effects of flavanoids and isocyanates from the plants widely consumed in the midland belt of Russia were reviewed. Data of studies both in vitro and in vivo were analyzed. Special attention was paid to inhibition of targets responsible for carcinogen metabolic activation, carcinogenesis promotion and tumor progression as well as neoangiogenesis. Besides that the antioxidant properties of flavonoids and their effects on cell cycle regulation, apoptosis initiation and cell mobility were considered.

External radiation carcinogenesis

International Nuclear Information System (INIS)

Fry, R.J.M.; Storer, J.B.

1987-01-01

There have been many reviews of the subject of radiation carcinogenesis in general and of specific radiation-induced cancers. The aim of this article is not to give an exhaustive, and perhaps exhausting, review of all that has been published since the thorough treatise of Walburg in volume 4 of this series but rather to concentrate on the questions that still remain of importance and recent contributions to the answers. In the years since 1974 a vast amount of information has been reported, and the authors assess what gain there has been in knowledge. For example, it is in the 13 years since the last review that the great majority of data for the carcinogenic effects of neutrons has appeared. It is over 50 years since the discovery of the neutron, and yet knowledge of the carcinogenic effects of neutrons is far from adequate

Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival.

Directory of Open Access Journals (Sweden)

Maria Teresa Landi

2008-02-01

Full Text Available Tobacco smoking is responsible for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure.We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1. Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p1.5, for each comparison, consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001 and TTK (p = 0.002 expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers.Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers.

Effectiveness of Bioactive Food Components in Experimental Colon Carcinogenesis

Directory of Open Access Journals (Sweden)

Emília Hijová

2009-01-01

Full Text Available The aim of the present study was the evaluation of possible protective effects of selected bioactive food components in experimental N,N-dimethylhydrazine (DMH-induced colon carcinogenesis. Wistar albino rats (n = 92 were fed a high fat diet or conventional laboratory diet. Two weeks after the beginning of the trial, DMH injections were given to six groups of rats at the dose of 20 mg/kg b.w. twice weekly. The activity of bacterial enzymes in faeces and serum bile acid concentrations were determined. High fat diet, DMH injections, and their combination significantly increased the activies of β-galactosidase, β-glucuronidase, and α-glucosidase (p p < 0.001, as well as the bile acid concentration compared to the group at the highest risk. The protective effects of selected bioactive food components in experimentally induced colon carcinogenesis allow for their possible use in cancer prevention or treatment.

Differential epigenetic regulation of TOX subfamily high mobility group box genes in lung and breast cancers.

Directory of Open Access Journals (Sweden)

Mathewos Tessema

Full Text Available Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190 and 23% breast (n = 80 tumors were methylated. Expression of two novel TOX2 transcripts identified was significantly reduced in primary lung tumors than distant normal lung (p<0.05. These transcripts were silenced in methylated lung and breast cancer cells and 5-Aza-2-deoxycytidine treatment re-expressed both. Extension of these assays to TOX, TOX3, and TOX4 genes that share similar genomic structure and protein homology with TOX2 revealed distinct methylation profiles by smoking status, histology, and cancer type. TOX was almost exclusively methylated in breast (43% than lung (5% cancer, whereas TOX3 was frequently methylated in lung (58% than breast (30% tumors. TOX4 was unmethylated in all samples and showed the highest expression in normal lung. Compared to TOX4, expression of TOX, TOX2 and TOX3 in normal lung was 25, 44, and 88% lower, respectively, supporting the premise that reduced promoter activity confers increased susceptibility to methylation during lung carcinogenesis. Genome-wide assays revealed that siRNA-mediated TOX2 knockdown modulated multiple pathways while TOX3 inactivation targeted neuronal development and function. Although these knockdowns did not result in further phenotypic changes of lung cancer cells in vitro, the impact on tissue remodeling, inflammatory response, and cell differentiation pathways suggest a potential role for TOX2 in modulating tumor microenvironment.

Etoricoxib in the Prevention of Rat Mammary Carcinogenesis

Directory of Open Access Journals (Sweden)

P. Orendáš

2007-01-01

Full Text Available Several experimental studies suggest that non-steroidal antiinflammatory drugs have chemopreventive effects in mammary carcinogenesis. In this study, tumour suppressive effects of a selective inhibitor of cyclooxygenase-2 (COX-2 etoricoxib in the prevention of N-methyl-Nnitrosourea (NMU-induced mammary carcinogenesis in Sprague-Dawley rats were evaluated. Etoricoxib was administered in the diet, at two concentrations: 1 0.01 mg/g (ETO 0.001% and 2 0.025 mg/g (ETO 0.0025%. Although the chemopreventive effects were not statistically significant, remarkable tumour suppressive effects with the concentration of ETO 0.0025% were recorded. The incidence decreased by 4.31% and tumour frequency per group decreased by 6.67% when compared to the control group. Latency (the period from carcinogen administration to the first tumour appearance increased by 7.28% in dose-dependent manner. The results of our experiments point to dose-dependent tumour suppressive effects of a higher concentration of etoricoxib (ETO 0.0025% when compared to the control group. They suggest that higher etoricoxib concentrations may enhance its tumour suppressive effects.

A test of the linear-no threshold theory of radiation carcinogenesis

International Nuclear Information System (INIS)

Cohen, B.L.

1990-01-01

It has been pointed out that, while an ecological study cannot determine whether radon causes lung cancer, it can test the validity of a linear-no threshold relationship between them. The linear-no threshold theory predicts a substantial positive correlation between the average radon exposure in various counties and their lung cancer mortality rates. Data on living areas of houses in 411 counties from all parts of the United States exhibit, rather, a substantial negative correlation with the slopes of the lines of regression differing from zero by 10 and 7 standard deviations for males and females, respectively, and from the positive slope predicted by the theory by at least 16 and 12 standard deviations. When the data are segmented into 23 groups of states or into 7 regions of the country, the predominantly negative slopes and correlations persist, applying to 18 of the 23 state groups and 6 of the 7 regions. Five state-sponsored studies are analyzed, and four of these give a strong negative slope (the other gives a weak positive slope, in agreement with our data for that state). A strong negative slope is also obtained in our data on basements in 253 counties. A random selection-no charge study of 39 high and low lung cancer counties (+4 low population states) gives a much stronger negative correlation. When nine potential confounding factors are included in a multiple linear regression analysis, the discrepancy with theory is reduced only to 12 and 8.5 standard deviations for males and females, respectively. When the data are segmented into four groups by population, the multiple regression vs radon level gives a strong negative slope for each of the four groups. Other considerations are introduced to reduce the discrepancy, but it remains very substantial

Modulation by metformin of molecular and histopathological alterations in the lung of cigarette smoke-exposed mice

International Nuclear Information System (INIS)

Izzotti, Alberto; Balansky, Roumen; D'Agostini, Francesco; Longobardi, Mariagrazia; Cartiglia, Cristina; Micale, Rosanna T; La Maestra, Sebastiano; Camoirano, Anna; Ganchev, Gancho; Iltcheva, Marietta; Steele, Vernon E; De Flora, Silvio

2014-01-01

The anti-diabetic drug metformin is endowed with anti-cancer properties. Epidemiological and experimental studies, however, did not provide univocal results regarding its role in pulmonary carcinogenesis. We used Swiss H mice of both genders in order to detect early molecular alterations and tumors induced by mainstream cigarette smoke. Based on a subchronic toxicity study, oral metformin was used at a dose of 800 mg/kg diet, which is 3.2 times higher than the therapeutic dose in humans. Exposure of mice to smoke for 4 months, starting at birth, induced a systemic clastogenic damage, formation of DNA adducts, oxidative DNA damage, and extensive downregulation of microRNAs in lung after 10 weeks. Preneoplastic lesions were detectable after 7.5 months in both lung and urinary tract along with lung tumors, both benign and malignant. Modulation by metformin of 42 of 1281 pulmonary microRNAs in smoke-free mice highlighted a variety of mechanisms, including modulation of AMPK, stress response, inflammation, NFκB, Tlr9, Tgf, p53, cell cycle, apoptosis, antioxidant pathways, Ras, Myc, Dicer, angiogenesis, stem cell recruitment, and angiogenesis. In smoke-exposed mice, metformin considerably decreased DNA adduct levels and oxidative DNA damage, and normalized the expression of several microRNAs. It did not prevent smoke-induced lung tumors but inhibited preneoplastic lesions in both lung and kidney. In conclusion, metformin was able to protect the mouse lung from smoke-induced DNA and microRNA alterations and to inhibit preneoplastic lesions in lung and kidney but failed to prevent lung adenomas and malignant tumors induced by this complex mixture

Radiation carcinogenesis and related radiobiology. Special listing

International Nuclear Information System (INIS)

1978-01-01

This Special Listing of Current Cancer Research Projects is a service of the International Cancer Research Data Bank (ICRDB) program of the National Cancer Institute. Each listing contains descriptions of ongoing projects in one selected cancer research area. The descriptions are provided by cancer scientists in about 50 different countries. Research areas covered in this listing are: Human cancer and exposure to radiation; experimental radiation carcinogenesis and radiation biology

Radon, smoking and human papilloma virus as risk factors for lung cancer in an environmental epidemiological study

Directory of Open Access Journals (Sweden)

G. P. Malinovsky

2017-01-01

Full Text Available The aim of the study: to analyze the risk of lung cancer caused by exposure to indoor radon using an environmental study, taking into account recent data on the possible effect of Human Papillomavirus, based on lung cancer mortality and radon exposure in the Russian regions.Materials and methods: in the analysis, linear dependencies of lung cancer against influencing factors were used. The average radon concentration for the regions of Russia was earlier reconstructed on the basis of the annual reports of the form 4-DOZ. Information on morbidity and mortality from malignant neoplasms in Russia was obtained from annual reports issued by the Р. Hertsen Moscow Oncology Research Institute. As a surrogate of the level of infection with Human Papillomavirus, the incidence of cervix cancer was used. The smoking prevalence was estimated applying data on the incidence of tongue cancer.Results: taking into account smoking and infection with Human Papillomavirus, it is possible to obtain estimates of lung cancer excess relative risk when induced by radon in dwellings consistent with the results of case-control studies.Conclusion: the analysis of regionally aggregated data on deaths from lung cancer in Russia, the average level of indoor radon concentrations and significant risk factors for lung cancer confirms the linear threshold-free concept of radiation-induced carcinogenesis.

The level of claudin-7 is reduced as an early event in colorectal carcinogenesis

DEFF Research Database (Denmark)

Lange, Jette Bornholdt; Friis, Stine; Godiksen, Sine

2011-01-01

-regulation of the oncogenic serine protease, matriptase, induces leakiness in epithelial barriers both in vivo and in vitro. We found in an in-silico search tight co-regulation between matriptase and claudin-7 expression. We have previously shown that the matriptase expression level decreases during colorectal carcinogenesis....... In the present study we investigated whether claudin-7 expression is likewise decreased during colorectal carcinogenesis, thereby causing or contributing to the compromised epithelial leakiness of dysplastic tissue....

Detection of early lung cancer lesions in surgical resections and in bronchial and transbronchial biopsies

International Nuclear Information System (INIS)

Rott, T.; Jerse, M.; Tercelj, M.; Erzen, J.

2006-01-01

Background. Overall bad prognosis of lung cancer is mostly due to too late detection of early lung cancer, which may be treated with good success. Therefore, different diagnostic methods are developing for more efficient detection of early lung cancer: besides modern radiological, bronchoscopic methods with additional fluorescence techniques, quantitative cytological investigations, also histological and molecular investigations are included. Histology may reveal early preinvasive lung cancer lesions, associated early during multistep lung carcinogenesis with molecular genetic changes. Patients and methods. Preinvasive epithelial lung cancer lesions we searched in two groups of patients. In the first group of 316 patients from the period March 2003 - August 2006, 498 bronchial and transbronchial biopsies were examined for squamous metaplasia and dysplasia, carcinoma in situ, and invasive tumours. In the second group of 238 patients from the period January 2004 - August 2006, resected primary lung tumours were analysed for preinvasive and invasive neuroendocrine tumours and atypical adenomatous hyperplasia. Results. The most frequent changes in bronchial and transbronchial biopsies were squamous metaplasia (46.5%), simple or goblet cell hyperplasia of the bronchial epithelium (44.3%), malignant tumours (20.66%) and squamous dysplasia (16.1%), but rare carcinoma in situ (0.63%). Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia was found in 15 (6.3%) cases in the vicinity of 238 resected lung cancer specimens, carcinoid in 12 patients (5%), and mostly combined large cell neuroendocrine cancer in 21 patients (8.8%). Atypical adenomatous hyperplasia was found in 2 patients. Conclusions. Classical histological analysis should be focused on detection of early preinvasive epithelial lung cancer lesions. Additional available molecular investigations may reveal gradual genetic changes characteristic for a series of the preinvasive epithelial histological changes

Measuring interfraction and intrafraction lung function changes during radiation therapy using four-dimensional cone beam CT ventilation imaging

Energy Technology Data Exchange (ETDEWEB)

Kipritidis, John, E-mail: john.kipritidis@sydney.edu.au; Keall, Paul J. [Radiation Physics Laboratory, Sydney Medical School, University of Sydney, Sydney NSW 2006 (Australia); Hugo, Geoffrey; Weiss, Elisabeth; Williamson, Jeffrey [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States)

2015-03-15

Purpose: Adaptive ventilation guided radiation therapy could minimize the irradiation of healthy lung based on repeat lung ventilation imaging (VI) during treatment. However the efficacy of adaptive ventilation guidance requires that interfraction (e.g., week-to-week), ventilation changes are not washed out by intrafraction (e.g., pre- and postfraction) changes, for example, due to patient breathing variability. The authors hypothesize that patients undergoing lung cancer radiation therapy exhibit larger interfraction ventilation changes compared to intrafraction function changes. To test this, the authors perform the first comparison of interfraction and intrafraction lung VI pairs using four-dimensional cone beam CT ventilation imaging (4D-CBCT VI), a novel technique for functional lung imaging. Methods: The authors analyzed a total of 215 4D-CBCT scans acquired for 19 locally advanced non-small cell lung cancer (LA-NSCLC) patients over 4–6 weeks of radiation therapy. This set of 215 scans was sorted into 56 interfraction pairs (including first day scans and each of treatment weeks 2, 4, and 6) and 78 intrafraction pairs (including pre/postfraction scans on the same-day), with some scans appearing in both sets. VIs were obtained from the Jacobian determinant of the transform between the 4D-CBCT end-exhale and end-inhale images after deformable image registration. All VIs were deformably registered to their corresponding planning CT and normalized to account for differences in breathing effort, thus facilitating image comparison in terms of (i) voxelwise Spearman correlations, (ii) mean image differences, and (iii) gamma pass rates for all interfraction and intrafraction VI pairs. For the side of the lung ipsilateral to the tumor, we applied two-sided t-tests to determine whether interfraction VI pairs were more different than intrafraction VI pairs. Results: The (mean ± standard deviation) Spearman correlation for interfraction VI pairs was r{sup -}{sub Inter

Measuring interfraction and intrafraction lung function changes during radiation therapy using four-dimensional cone beam CT ventilation imaging

International Nuclear Information System (INIS)

Kipritidis, John; Keall, Paul J.; Hugo, Geoffrey; Weiss, Elisabeth; Williamson, Jeffrey

2015-01-01

Purpose: Adaptive ventilation guided radiation therapy could minimize the irradiation of healthy lung based on repeat lung ventilation imaging (VI) during treatment. However the efficacy of adaptive ventilation guidance requires that interfraction (e.g., week-to-week), ventilation changes are not washed out by intrafraction (e.g., pre- and postfraction) changes, for example, due to patient breathing variability. The authors hypothesize that patients undergoing lung cancer radiation therapy exhibit larger interfraction ventilation changes compared to intrafraction function changes. To test this, the authors perform the first comparison of interfraction and intrafraction lung VI pairs using four-dimensional cone beam CT ventilation imaging (4D-CBCT VI), a novel technique for functional lung imaging. Methods: The authors analyzed a total of 215 4D-CBCT scans acquired for 19 locally advanced non-small cell lung cancer (LA-NSCLC) patients over 4–6 weeks of radiation therapy. This set of 215 scans was sorted into 56 interfraction pairs (including first day scans and each of treatment weeks 2, 4, and 6) and 78 intrafraction pairs (including pre/postfraction scans on the same-day), with some scans appearing in both sets. VIs were obtained from the Jacobian determinant of the transform between the 4D-CBCT end-exhale and end-inhale images after deformable image registration. All VIs were deformably registered to their corresponding planning CT and normalized to account for differences in breathing effort, thus facilitating image comparison in terms of (i) voxelwise Spearman correlations, (ii) mean image differences, and (iii) gamma pass rates for all interfraction and intrafraction VI pairs. For the side of the lung ipsilateral to the tumor, we applied two-sided t-tests to determine whether interfraction VI pairs were more different than intrafraction VI pairs. Results: The (mean ± standard deviation) Spearman correlation for interfraction VI pairs was r - Inter =0.52±0

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

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

2009-06-01

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

ANTIBODIES TO BENZO[A]PYRENE, ESTRADIOL AND PROGESTERONE AND GENE POLYMORPHISMS OF CYTOKINES: ASSOCIATIONS WITH LUNG CANCER IN MEN

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A. N. Glushkov

2018-01-01

evidence that IgA-Bp and IgA-Es could stimulate initiation and promotion of lung carcinogenesis. On the contrary, IgA-Pg could inhibit the promotion of carcinogenesis. Immunoassay of these antibodies combined with molecular biology studies of IL10 gene variants are recommended for the lung cancer risk assessment.

Lung cancer risk associated with Thr495Pro polymorphism of GHR in Chinese population.

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Cao, Guochun; Lu, Hongna; Feng, Jifeng; Shu, Jian; Zheng, Datong; Hou, Yayi

2008-04-01

The incidence of lung cancer has been increasing over recent decades. Previous studies showed that polymorphisms of the genes involved in carcinogen-detoxication, DNA repair and cell cycle control comprise risk factors for lung cancer. Recent observations revealed that the growth hormone receptor (GHR) might play important roles in carcinogenesis and Rudd et al. found that the Thr495Pro polymorphism of GHR was strongly associated with lung cancer risk in Caucasians living in the UK (OR = 12.98, P = 0.0019, 95% CI: 1.77-infinity). To test whether this variant of GHR would modify the risk of lung cancer in Chinese population, we compared the polymorphism between 778 lung cancer patients and 781 healthy control subjects. Our results indicate that the frequency of 495Thr (2.8%) allele in cases was significantly higher than in controls (OR = 2.04, P = 0.006, 95% CI: 1.21-3.42) which indicated this allele might be a risk factor for lung cancer. Further analyses revealed Thr495Pro variant was associated with lung cancer in the subpopulation with higher risk for lung cancer: male subpopulation, still-smokers subpopulation and the subpopulation with familial history of cancer. In different histological types of lung cancer, Thr495Pro SNP was significantly associated with small cell and squamous cell lung cancer, but not with adenocarcinoma, which suggested a potential interaction between this polymorphism and metabolic pathways related to smoking. The potential gene-environment interaction on lung cancer risk was evaluated using MDR software. A significant redundant interaction between Thr495Pro polymorphism and smoking dose and familial history of cancer was identified and the combination of genetic factors and smoking status or familial history of cancer barely increased the cancer risk prediction accuracy. In conclusion, our results suggested that the Thr495Pro polymorphism of GHR was associated with the risk of lung cancer in a redundant interaction with smoking and

Curcumin: the spicy modulator of breast carcinogenesis.

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Banik, Urmila; Parasuraman, Subramani; Adhikary, Arun Kumar; Othman, Nor Hayati

2017-07-19

Worldwide breast cancer is the most common cancer in women. For many years clinicians and the researchers are examining and exploring various therapeutic modalities for breast cancer. Yet the disease has remained unconquered and the quest for cure is still going on. Present-day strategy of breast cancer therapy and prevention is either combination of a number of drugs or a drug that modulates multiple targets. In this regard natural products are now becoming significant options. Curcumin exemplifies a promising natural anticancer agent for this purpose. This review primarily underscores the modulatory effect of curcumin on the cancer hallmarks. The focus is its anticancer effect in the complex pathways of breast carcinogenesis. Curcumin modulates breast carcinogenesis through its effect on cell cycle and proliferation, apoptosis, senescence, cancer spread and angiogenesis. Largely the NFkB, PI3K/Akt/mTOR, MAPK and JAK/STAT are the key signaling pathways involved. The review also highlights the curcumin mediated modulation of tumor microenvironment, cancer immunity, breast cancer stem cells and cancer related miRNAs. Using curcumin as a therapeutic and preventive agent in breast cancer is perplexed by its diverse biological activity, much of which remains inexplicable. The information reviewed here should point toward potential scope of future curcumin research in breast cancer.

Establishment and Characterization of a Novel Chinese Human Lung Adenocarcinoma Cell Line CPA-Yang2 in Immunodeficient Mice

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Shunfang YANG

2009-10-01

Full Text Available Background and objective The recurrence, metastasis and multidrug resistance (MDR in lung cancer are the tough problems worldwide. This study was to establish a novel chinese lung adenocarcinoma cell line with high metastasis potential for exploring the mechanism of reccurrence, development and MDR in lung cancer. Methods The cell came from the abdominal dropsy of a fifty-six years old female patient with lung adenocarcinoma and the tumor markers CA125, CYFRA21-1, CEA, NSE were detected to be higher secretion by radioimmunoassay in the abdominal dropsy. Tumorigenicity of immunodeficient mice was confirmed in 8th passage. The cell growth curve was mapped. Analysis of chromosome karyotype was tested. The gene expression was measured by real-time quantitative PCR. Results The tumorigenesis rate started at 8th passage in 3/10 immunodeficient mice via subcutaneously and the fully tumorigenicity was at 11th passage as well as later passages. Under the microscope, the cell showed oval-shap and adherence. The chromosome karyotype analysis of the cells was sub-triploid. Approximately 1×106 and 1.5×106 cancerous cells were injected into left cardiac ventricle and tail vein of immunodeficient mice respectively. The results showed multiorgan metastasis in the mice after three-four weeks, including mandible, scapula, humerus, vertebral column, femur, rib and brain, liver, adrenal gland, pulmonary in the mice after inoculation. The bone metastasis rate was 100% in the tumor bearing mice by bone scintigraphy and pathology. Quantitative real-time PCR was used to examined and compared with SPC-A-1 lung adenocarcinoma, ESM1, VEGF-C, IL-6, IL-8, AR genes were overexpressed. The novel cell was named CPA-Yang2. Conclusion The characteristics of novel strain CPA-Yang2 is a highly metastasis cell line of Chinese lung adenocarcinoma. It has stable traits, highly metastasis ability and maybe is a MDR lung cancerous cell line. Of course, it’s a good experimental

Unevenness on aerosol inhalation lung images and lung function

International Nuclear Information System (INIS)

Teshima, Takeo; Isawa, Toyoharu; Hirano, Tomio; Ebina, Akio; Shiraishi, Koichiro; Konno, Kiyoshi

1985-01-01

The unevenness or inhomogeneity of aerosol deposition patterns on radioaerosol inhalation lung images has been interpreted rather qualitatively in the clinical practice. We have reported our approach to quantitatively analyze the radioactive count distribution on radioaerosol inhalation lung images in relation to the actual lung function data. We have defined multiple indexes to express the shape and the unevenness of the count distribution of the lung images. To reduce as much as possible the number of indexes to be used in the regression functions, the method of selection of variables was introduced to the multiple regression analysis. Because some variables showed greater coefficients of simple correlation, while others did not, multicollinearity of variables had to be taken into consideration. For this reason, we chose a principal components regression analysis. The multiple regression function for each item of pulmonary function data thus established from analysis of 67 subjects appeared usable as a predictor of the actual lung function: for example, % VC (vital capacity) could be estimated by using four indexes out of the multiple ones with a coefficient of multiple correlation (R) of 0.753, and FEVsub(1.0) % (forced expiratory volume in one second divided by forced expiratory volume), by 7 indexes with R = 0.921. Pulmonary function data regarding lung volumes and lung mechanics were estimated more accurately with greater R's than those for lung diffusion, but even in the latter the prediction was still statistically significant at p less than 0.01. We believe the multiple regression functions thus obtained are useful for estimating not only the overall but also the regional function of the lungs. (author)

Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia

DEFF Research Database (Denmark)

Alanin, Mikkel Christian; Aanaes, Kasper; Hoiby, Niels

2017-01-01

patients (62%). Four patients with preoperative P. aeruginosa lung colonization (25%) had no regrowth during follow-up; 2 of these had P. aeruginosa sinusitis. Sinonasal symptoms were improved 12 months after ESS and we observed a trend toward better lung function after ESS. Conclusion We demonstrated...... an improvement in CRS-related symptoms after ESS and adjuvant therapy. In selected PCD patients, the suggested regimen may postpone chronic lung infection with P. aeruginosa and stabilize lung function....

Vasculature surrounding a nodule: A novel lung cancer biomarker.

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Wang, Xiaohua; Leader, Joseph K; Wang, Renwei; Wilson, David; Herman, James; Yuan, Jian-Min; Pu, Jiantao

2017-12-01

To investigate whether the vessels surrounding a nodule depicted on non-contrast, low-dose computed tomography (LDCT) can discriminate benign and malignant screen detected nodules. We collected a dataset consisting of LDCT scans acquired on 100 subjects from the Pittsburgh Lung Screening study (PLuSS). Fifty subjects were diagnosed with lung cancer and 50 subjects had suspicious nodules later proven benign. For the lung cancer cases, the location of the malignant nodule in the LDCT scans was known; while for the benign cases, the largest nodule in the LDCT scan was used in the analysis. A computer algorithm was developed to identify surrounding vessels and quantify the number and volume of vessels that were connected or near the nodule. A nonparametric receiver operating characteristic (ROC) analysis was performed based on a single nodule per subject to assess the discriminability of the surrounding vessels to provide a lung cancer diagnosis. Odds ratio (OR) were computed to determine the probability of a nodule being lung cancer based on the vessel features. The areas under the ROC curves (AUCs) for vessel count and vessel volume were 0.722 (95% CI=0.616-0.811, plung cancer group 9.7 (±9.6) compared to the non-lung cancer group 4.0 (±4.3) CONCLUSION: Our preliminary results showed that malignant nodules are often surrounded by more vessels compared to benign nodules, suggesting that the surrounding vessel characteristics could serve as lung cancer biomarker for indeterminate nodules detected during LDCT lung cancer screening using only the information collected during the initial visit. Copyright © 2017 Elsevier B.V. All rights reserved.

Histomorphological features of combined forms of tuberculosis and lung cancer

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Savenkov Y.F.

2017-04-01

Full Text Available The were studied pathological features of combined forms of tuberculosis and non-small cell lung cancer in 72 patients who underwent radical surgical resection interventions from transsternal access with mediastinal lymph node dissection, with predominance of pneumonectomy - 63.9%. There were identified three main categories of pathological changes: cancer on the background of post-tuberculosis changes, cancer in tuberculoma, cancer in the wall of the active cavity. Post-tuberculosis changes were presented by dense centers, fibrosis, cirrhosis areas, sanitized cavities with histological predominance of coarse fiber connective tissue with giant cell granulomas, with areas characterized by the appearance of the lung tissue with atypical proliferation and metaplasia of bronchopulmonary epithelium, which is a precancerous condition. This malignant tumor process was presented mainly by adenocarcinomas and squamous cell cancer and differred by polymorphic macro- and microscopic picture. Cancer in tuberculoma and fibrous wall cavity differed by pronounced activity of tuberculosis process in the form of lymphohistiocytic infiltration, foci of caseous necrosis and presence of expressed granulation layer of Pirogov-Langhans’ cells. The basic morphological causes of carcinogenesis due to secondary changes of lung tissue in patients with tuberculosis were determined. The features of metastasis of malignant tumors on the background of specific tuberculous and post-tuberculosis changes in regional lymph nodes and the interrelation between the frequency of metastatic lesions with severity of tuberculosis and post-tuberculosis changes in them were studied; this has clinical significance in the surgical treatment of patients with concomitant forms of tuberculosis and lung cancer.

Age and Space Irradiation Modulate Tumor Progression: Implications for Carcinogenesis Risk

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National Aeronautics and Space Administration — Age plays a major role in tumor incidence and is an important consideration when modeling the carcinogenesis process or estimating cancer risks. Epidemiological data...

Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis

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Wan, Lei; Tan, Hsueh-Li; Thomas-Ahner, Jennifer M.; Pearl, Dennis K.; Erdman, John W.; Moran, Nancy E.; Clinton, Steven K.

2014-01-01

Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4-10 wk-of-age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone-repletion (2.5 mg/kg/d initiated 1 wk after castration). Ten-wk-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia (PIN). Of the 200 prostate cancer-related genes measured by quantitative NanoString®, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (Plycopene feeding (Srd5a1) and by tomato-feeding (Srd5a2, Pxn, and Srebf1). Additionally, tomato-feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, while lycopene-feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early stages of prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. PMID:25315431

The relationship between the peripheral lung cancer and the bronchi, pulmonary artery and vein: a multislice helical CT observation

International Nuclear Information System (INIS)

Liu Xueguo; Liang Mingzhu; Chen Cuifen; Qin Peixin; Zhong Guomei; He Yanguo; Liu Xiaobing; Han Mingqun; Yi Xianping; Wang Yong; Zhang Hao

2008-01-01

Objective: To investigate the relationships between the peripheral lung cancer and pulmonary vessels or bronchi by 16-row multislice computed tomography (MSCT) and analyze the related factors. Methods: Fifty-four patients with peripheral lung cancer confirmed pathologically underwent contrast-enhanced MSCT. Multiplanar reformation (MPR) and maximum intensity projection (MIP) in all patients were used to demonstrate the relationships between the peripheral lung cancer and pulmonary vessels, bronchi. The relationships were categorized five types: Type 1, erupted at the edge of nodule. Type 2, erupted at the center of nodule. Type 3, penetrated through the nodule. Type 4, contacting the nodule but stretched or encased. Type 5, contacting the nodule but smoothly compressed. The pathology type, stage, size, density and location of the peripheral lung cancer were recorded and the relationships with five types were evaluated by using Chi-square test and correlation analysis. Results: (1) Tumor-bronchi relationship: type 1 (33,61.1%) was more often seen in ≥2.0 cm and solid lesions with stage II-IV, while Type 2(14,25.9%) was often seen in < 2.0 cm and part-solid or non-solid lesions with stage I. (2) Tumor-PA relationship: Type 1 was more often seen in ≥2.0 cm and solid lesions with stage II-IV, while Type 2 was often seen in part-solid or non-solid lesions with stage I. (3) Tumor-PV relationship: type 4 was the most common type (29, 53.7%). Type 2 (13, 24.1%) was more often seen in part-solid or non-solid lesions. (4) Tumor-bronchi relationship and tumor-PA relationship had a positive correlation (r0.5265, P<0.01). Conclusions: MSCT can demonstrate the relations between the peripheral lung cancer and bronchi, PA and PV. It is useful for the differential diagnosis and prognosis evaluation of the lung cancer. (authors)

High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

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Ocak, S; Sos, M L; Thomas, R K; Massion, P P

2009-08-01

During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

Information dynamics in carcinogenesis and tumor growth.

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Gatenby, Robert A; Frieden, B Roy

2004-12-21

The storage and transmission of information is vital to the function of normal and transformed cells. We use methods from information theory and Monte Carlo theory to analyze the role of information in carcinogenesis. Our analysis demonstrates that, during somatic evolution of the malignant phenotype, the accumulation of genomic mutations degrades intracellular information. However, the degradation is constrained by the Darwinian somatic ecology in which mutant clones proliferate only when the mutation confers a selective growth advantage. In that environment, genes that normally decrease cellular proliferation, such as tumor suppressor or differentiation genes, suffer maximum information degradation. Conversely, those that increase proliferation, such as oncogenes, are conserved or exhibit only gain of function mutations. These constraints shield most cellular populations from catastrophic mutator-induced loss of the transmembrane entropy gradient and, therefore, cell death. The dynamics of constrained information degradation during carcinogenesis cause the tumor genome to asymptotically approach a minimum information state that is manifested clinically as dedifferentiation and unconstrained proliferation. Extreme physical information (EPI) theory demonstrates that altered information flow from cancer cells to their environment will manifest in-vivo as power law tumor growth with an exponent of size 1.62. This prediction is based only on the assumption that tumor cells are at an absolute information minimum and are capable of "free field" growth that is, they are unconstrained by external biological parameters. The prediction agrees remarkably well with several studies demonstrating power law growth in small human breast cancers with an exponent of 1.72+/-0.24. This successful derivation of an analytic expression for cancer growth from EPI alone supports the conceptual model that carcinogenesis is a process of constrained information degradation and that malignant

Radon, cigarette smoke, and lung cancer: A re-analysis of the Colorado Plateau uranium miners' data [see comments

International Nuclear Information System (INIS)

Moolgavkar, S.H.; Luebeck, E.G.; Krewski, D.; Zielinski, J.M.

1993-01-01

Much of our knowledge regarding the interaction of radon and tobacco smoke in the etiology of human lung cancer derives from studies of uranium miners. In this article, we present a re-analysis of lung cancer mortality in the Colorado Plateau miners' cohort within the framework of the two-mutation clonal expansion model of carcinogenesis. This analysis takes into account the patterns of exposure to radon and cigarette smoke experienced by individuals in the cohort. A simultaneous re-analysis of the British doctors' cohort indicated that those model parameters relating to the effects of tobacco were comparable in the two data sets. We found no evidence of interaction between radon and tobacco smoke with respect to their joint effect on the first or second stage mutation rates or on the rate of proliferation of initiated cells. The age-specific relative risks associated with joint exposure to radon and cigarette smoke, however, were supra-additive but submultiplicative. The analysis also confirmed that fractionation of radon exposures leads to higher lung cancer risks. Finally, we present some estimates of lung cancer risk from environmental radon exposure for non-smokers and smokers

Sexist Attitudes Among Emerging Adult Women Readers of Fifty Shades Fiction.

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Altenburger, Lauren E; Carotta, Christin L; Bonomi, Amy E; Snyder, Anastasia

2017-02-01

Stereotypical sexist representations of men and women in popular culture reinforce rigid views of masculinity (e.g., males as being strong, in control, masterful, and aggressive) and femininity (e.g., women as being fragile and weak, unassertive, peaceful, irrational, and driven by emotions). The present study examined associations between the fictional series Fifty Shades-one popular culture mechanism that includes pervasive traditional gender role representations-and underlying sexist beliefs among a sample of 715 women ages 18-24 years. Analyses revealed associations between Fifty Shades readership and sexism, as measured through the Ambivalent Sexism Inventory. Namely women who reported reading Fifty Shades had higher levels of ambivalent, benevolent, and hostile sexism. Further, those who interpreted Fifty Shades as "romantic" had higher levels of ambivalent and benevolent sexism. Our findings support prior empirical studies noting associations between interacting with aspects of popular culture, such as television and video games, and individual beliefs and behaviors.

High-Fat, High-Calorie Diet Enhances Mammary Carcinogenesis and Local Inflammation in MMTV-PyMT Mouse Model of Breast Cancer

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Cowen, Sarah [Department of Surgery, West Virginia University Health Sciences Center, Morgantown, WV 26506 (United States); Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506 (United States); McLaughlin, Sarah L. [Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506 (United States); Hobbs, Gerald [Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506 (United States); Department of Statistics, West Virginia University, Morgantown, WV 26506 (United States); Coad, James [Department of Pathology, West Virginia University Health Sciences Center, Morgantown, WV 26506 (United States); Martin, Karen H. [Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506 (United States); Department of Neurobiology and Anatomy, West Virginia University Health Sciences Center, Morgantown, WV 26506 (United States); Olfert, I. Mark [Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506 (United States); Department of Human Performance and Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, WV 26506 (United States); Vona-Davis, Linda, E-mail: lvdavis@hsc.wvu.edu [Department of Surgery, West Virginia University Health Sciences Center, Morgantown, WV 26506 (United States); Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506 (United States)

2015-06-26

Epidemiological studies provide strong evidence that obesity and the associated adipose tissue inflammation are risk factors for breast cancer; however, the molecular mechanisms are poorly understood. We evaluated the effect of a high-fat/high-calorie diet on mammary carcinogenesis in the immunocompetent MMTV-PyMT murine model. Four-week old female mice (20/group) were randomized to receive either a high-fat (HF; 60% kcal as fat) or a low-fat (LF; 16% kcal) diet for eight weeks. Body weights were determined, and tumor volumes measured by ultrasound, each week. At necropsy, the tumors and abdominal visceral fat were weighed and plasma collected. The primary mammary tumors, adjacent mammary fat, and lungs were preserved for histological and immunohistochemical examination and quantification of infiltrating macrophages, crown-like structure (CLS) formation, and microvessel density. The body weight gains, visceral fat weights, the primary mammary tumor growth rates and terminal weights, were all significantly greater in the HF-fed mice. Adipose tissue inflammation in the HF group was indicated by hepatic steatosis, pronounced macrophage infiltration and CLS formation, and elevations in plasma monocyte chemoattractant protein-1 (MCP-1), leptin and proinflammatory cytokine concentrations. HF intake was also associated with higher tumor-associated microvascular density and the proangiogenic factor MCP-1. This study provides preclinical evidence in a spontaneous model of breast cancer that mammary adipose tissue inflammation induced by diet, enhances the recruitment of macrophages and increases tumor vascular density suggesting a role for obesity in creating a microenvironment favorable for angiogenesis in the progression of breast cancer.

High-Fat, High-Calorie Diet Enhances Mammary Carcinogenesis and Local Inflammation in MMTV-PyMT Mouse Model of Breast Cancer

International Nuclear Information System (INIS)

Cowen, Sarah; McLaughlin, Sarah L.; Hobbs, Gerald; Coad, James; Martin, Karen H.; Olfert, I. Mark; Vona-Davis, Linda

2015-01-01

Epidemiological studies provide strong evidence that obesity and the associated adipose tissue inflammation are risk factors for breast cancer; however, the molecular mechanisms are poorly understood. We evaluated the effect of a high-fat/high-calorie diet on mammary carcinogenesis in the immunocompetent MMTV-PyMT murine model. Four-week old female mice (20/group) were randomized to receive either a high-fat (HF; 60% kcal as fat) or a low-fat (LF; 16% kcal) diet for eight weeks. Body weights were determined, and tumor volumes measured by ultrasound, each week. At necropsy, the tumors and abdominal visceral fat were weighed and plasma collected. The primary mammary tumors, adjacent mammary fat, and lungs were preserved for histological and immunohistochemical examination and quantification of infiltrating macrophages, crown-like structure (CLS) formation, and microvessel density. The body weight gains, visceral fat weights, the primary mammary tumor growth rates and terminal weights, were all significantly greater in the HF-fed mice. Adipose tissue inflammation in the HF group was indicated by hepatic steatosis, pronounced macrophage infiltration and CLS formation, and elevations in plasma monocyte chemoattractant protein-1 (MCP-1), leptin and proinflammatory cytokine concentrations. HF intake was also associated with higher tumor-associated microvascular density and the proangiogenic factor MCP-1. This study provides preclinical evidence in a spontaneous model of breast cancer that mammary adipose tissue inflammation induced by diet, enhances the recruitment of macrophages and increases tumor vascular density suggesting a role for obesity in creating a microenvironment favorable for angiogenesis in the progression of breast cancer

Targeted deletion of Nrf2 reduces urethane-induced lung tumor development in mice.

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Alison K Bauer

Full Text Available Nrf2 is a key transcription factor that regulates cellular redox and defense responses. However, permanent Nrf2 activation in human lung carcinomas promotes pulmonary malignancy and chemoresistance. We tested the hypothesis that Nrf2 has cell survival properties and lack of Nrf2 suppresses chemically-induced pulmonary neoplasia by treating Nrf2(+/+ and Nrf2(-/- mice with urethane. Airway inflammation and injury were assessed by bronchoalveolar lavage analyses and histopathology, and lung tumors were analyzed by gross and histologic analysis. We used transcriptomics to assess Nrf2-dependent changes in pulmonary gene transcripts at multiple stages of neoplasia. Lung hyperpermeability, cell death and apoptosis, and inflammatory cell infiltration were significantly higher in Nrf2(-/- mice compared to Nrf2(+/+ mice 9 and 11 wk after urethane. Significantly fewer lung adenomas were found in Nrf2(-/- mice than in Nrf2(+/+ mice at 12 and 22 wk. Nrf2 modulated expression of genes involved cell-cell signaling, glutathione metabolism and oxidative stress response, and immune responses during early stage neoplasia. In lung tumors, Nrf2-altered genes had roles in transcriptional regulation of cell cycle and proliferation, carcinogenesis, organismal injury and abnormalities, xenobiotic metabolism, and cell-cell signaling genes. Collectively, Nrf2 deficiency decreased susceptibility to urethane-induced lung tumorigenesis in mice. Cell survival properties of Nrf2 were supported, at least in part, by reduced early death of initiated cells and heightened advantage for tumor cell expansion in Nrf2(+/+ mice relative to Nrf2(-/- mice. Our results were consistent with the concept that Nrf2 over-activation is an adaptive response of cancer conferring resistance to anti-cancer drugs and promoting malignancy.

Time factors in radiation carcinogenesis

International Nuclear Information System (INIS)

Sasaki, Shunsaku

1995-01-01

Results of experiments using B6C3F 1 female mice were made subject of analysis on the time factors in radiation carcinogenesis. In the experiment for examination of influence of age at irradiation on the lifetime risk and on distribution of ages at death, mice were irradiated at day 12, 14 or 17 of the prenatal period, or day 0, 7, 35, 105, 240 or 365 of the postnatal period with doses ranging from 0.48 to 5.7 Gy gamma-rays from 137 Cs. In the experiment to examine the reduction factor for carcinogenic effect by multiple fractionation of gamma-rays dose 1.9 or 3.8 Gy was divided into 10 fractions, which were delivered once a week during period from 5 to 15 weeks of age. All mice were allowed to live out their life spans under a specific pathogen free condition. The cumulative relative risk for mortality from all causes except lymphoma and leukemia was shown to decrease with age when mice were irradiated at the fetal, neonatal, suckling, adolescent or young adult period, whereas, the decrease in the cumulative relative risk was very little when gamma-rays were given at the intermediate adult period. The lifetime risk for the increase in mortality and for the induction of solid tumors was highest in mice irradiated during neonatal, suckling or adolescent period. Age-dependence of susceptibility to radiation carcinogenesis was different for each type of neoplasm. However, the most susceptible period for induction of each type of neoplasm concentrated in the age from neonatal to adolescent period. Radiation-induced late effects were apparently reduced by multiple fractionation of radiation dose, but the reduction factor for the increase in the long-term mortality did not exceed 2.0. (author)

Volume adjustment of lung density by computed tomography scans in patients with emphysema

DEFF Research Database (Denmark)

Shaker, S B; Dirksen, A; Laursen, Lars Christian

2004-01-01

of pulmonary emphysema derived from CT scans. These parameters are markedly influenced by changes in the level of inspiration. The variability of lung density due to within-subject variation in TLV was explored by plotting TLV against PD and RA. RESULTS: The coefficients for volume adjustment for PD were...... relatively stable over a wide range from the 10th to the 80th percentile, whereas for RA the coefficients showed large variability especially in the lower range, which is the most relevant for quantitation of pulmonary emphysema. CONCLUSION: Volume adjustment is mandatory in repeated CT densitometry......PURPOSE: To determine how to adjust lung density measurements for the volume of the lung calculated from computed tomography (CT) scans in patients with emphysema. MATERIAL AND METHODS: Fifty patients with emphysema underwent 3 CT scans at 2-week intervals. The scans were analyzed with a software...

Clinical value of 99Tcm-octreotide SPECT/CT in diagnostics of lung cancer

International Nuclear Information System (INIS)

Liu Xiaofang; Li Mei; Liu Yong; Li Ran; Xu Jie; Sun yongchang; Dai Haojie

2012-01-01

Objective: To evaluate the clinical value of 99 Tc m -Octreotide SPECT-CT in the diagnosis of lung cancer. Methods: Sixty-five consecutive patients with suspected lung cancer received intravenous injection of 740 MBq 99 Tc m -Octreotide and additional SPECT images of the chest were performed at 4h post injection. The SPECT/CT images were interpreted separately. The tumor uptake of 99 Tc m -Octreotide was visually determined and then measured and expressed as the activity ratio of tumor to normal tissues (T/N). The differences between lung cancer and benign lung lesion and between SCLC and NSCLC, and between adenocarcinoma and squamous carcinoma were studied by statistical analysis. Moreover, the receiver operating characteristic ROC curves were plotted and the predicted probabilities and areas under the curve were calculated. Results: Fifty-one patients and fourteen patients in 65 cases were diagnosed as lung cancer and benign lung lesion by histopathological analysis, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of 99 Tc m -Octreotide SPECT/CT in diagnosis of lung cancer were 92.2%, 85.7%, 95.9% and 75%, respectively. The area under ROC curve was 0.889 (P 99 Tc m -Octreotide SPECT/CT could play an important role in the diagnosis of lung cancer, and it may be useful for identifying SCLC and NSCLC. (authors)

Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors

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Chia PL

2014-11-01

Full Text Available Puey Ling Chia,1 Paul Mitchell,1 Alexander Dobrovic,2–4 Thomas John1,2,4 1Department of Medical Oncology, Olivia-Newton John Cancer and Wellness Centre, Victoria, Australia; 2Ludwig Institute for Cancer Research, Austin Health, Victoria, Australia; 3Department of Pathology, University of Melbourne, Victoria, Australia; 4School of Cancer Medicine, La Trobe University, Victoria, Australia Abstract: Improved understanding of molecular drivers of carcinogenesis has led to significant progress in the management of lung cancer. Patients with non-small-cell lung cancer (NSCLC with anaplastic lymphoma kinase (ALK gene rearrangements constitute about 4%–5% of all NSCLC patients. ALK+ NSCLC cells respond well to small molecule ALK inhibitors such as crizotinib; however, resistance invariably develops after several months of treatment. There are now several newer ALK inhibitors, with the next generation of agents targeting resistance mutations. In this review, we will discuss the prevalence and clinical characteristics of ALK+ lung cancer, current treatment options, and future directions in the management of this subset of NSCLC patients. Keywords: anaplastic lymphoma kinase (ALK, gene rearrangements, lung cancer, kinase inhibitors, lung adenocarcinoma

Mass preserving image registration for lung CT

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Gorbunova, Vladlena; Sporring, Jon; Lo, Pechin Chien Pau

2012-01-01

This paper presents a mass preserving image registration algorithm for lung CT images. To account for the local change in lung tissue intensity during the breathing cycle, a tissue appearance model based on the principle of preservation of total lung mass is proposed. This model is incorporated...... on four groups of data: 44 pairs of longitudinal inspiratory chest CT scans with small difference in lung volume; 44 pairs of longitudinal inspiratory chest CT scans with large difference in lung volume; 16 pairs of expiratory and inspiratory CT scans; and 5 pairs of images extracted at end exhale and end...

Defining the role of polyamines in colon carcinogenesis using mouse models

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Natalia A Ignatenko

2011-01-01

Full Text Available Genetics and diet are both considered important risk determinants for colorectal cancer, a leading cause of death in the US and worldwide. Genetically engineered mouse (GEM models have made a significant contribution to the characterization of colorectal cancer risk factors. Reliable, reproducible, and clinically relevant animal models help in the identification of the molecular events associated with disease progression and in the development of effictive treatment strategies. This review is focused on the use of mouse models for studying the role of polyamines in colon carcinogenesis. We describe how the available mouse models of colon cancer such as the multiple intestinal neoplasia (Min mice and knockout genetic models facilitate understanding of the role of polyamines in colon carcinogenesis and help in the development of a rational strategy for colon cancer chemoprevention.

The bystander effect in experimental systems and compatibility with radon-induced lung cancer in humans

International Nuclear Information System (INIS)

Little, M.P.; Wakeford, R.

2002-01-01

Bystander effects following exposure to α-particles have been observed in C3H 10T 1/2 cells and in other experimental systems, and imply that linearly extrapolating low-dose risks from high-dose data might materially underestimate risk. The ratio of lung cancer risk among persons exposed to low and high doses of radon daughters is 2.4-4.0, with an upper 95% confidence limit (CL) of about 14. Assuming that the bystander effect observed in the C3H 10T 1/2 data applies to human lung cells in vivo, the epidemiological data imply that the number of neighbouring cells that can contribute to the bystander effect is between 0 and 1, with an upper 95% CL of about 7. As a consequence, the bystander effect observed in the C3H 10T 1/2 system probably does not play a large part in the process of radon-induced lung carcinogenesis in humans. Other experimental data relating to the bystander effect after α-particle exposure are surveyed; some of these data are more compatible with the epidemiological data. (author)

Carcinogenesis

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Fry, R.J.M.

1975-01-01

The long-term aims are concerned with various aspects of the natural history and biology of cancer, the mechanism of induction and of the advancement of time of appearance of tumors, the development of systems suitable for the assay of oncogenesis and cocarcinogenesis, and the elucidation of some of the factors important to the problem of extrapolation of estimates of risk made in experimental systems to the estimate of risk in man. It is necessary to have a number of test systems in order to study the various factors related to cocarcinogenesis; some of these are clearly tissue specific. The liver tumor system is clearly useful for certain compounds, and the liver is an excellent tissue for the study of the mechanisms of cocarcinogenesis. This year we report on the relatively rapid induction of what appears histologically to be carcinoma of the thyroid by aminotriazole. In a collaborative study with the Neutron and Gamma-Ray Toxicity Group, we have established a new example of synergism in carcinogenesis, namely between radiation and pituitary hormone(s) in the production of Harderian gland tumors. Not only does a synergistic effect on incidence occur, but also on the degree of malignancy of the tumor induced. We thus have three different model systems for the study of various aspects of cocarcinogenesis: various chemicals, including nononcogenic polycyclic hydrocarbons, in liver tumorigenesis; ionizing radiation and aminotriazole in thyroid tumorigenesis; and in conjunction with the JANUS Program, the interaction of radiation and hormones in the production of Harderian gland, mammary gland, and other tumors

E-cadherin Mediates the Preventive Effect of Vitamin D3 in Colitis-associated Carcinogenesis.

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Xin, Yu; He, Longmei; Luan, Zijian; Lv, Hong; Yang, Hong; Zhou, Ying; Zhao, Xinhua; Zhou, Weixun; Yu, Songlin; Tan, Bei; Wang, Hongying; Qian, Jiaming

2017-09-01

Vitamin D3 is beneficial in ameliorating or preventing inflammation and carcinogenesis. Here, we evaluated if vitamin D3 has a preventive effect on colitis-associated carcinogenesis. Administration of azoxymethane (AOM), followed with dextran sulfate sodium (DSS), was used to simulate colitis-associated colon cancer in mice. The supplement of vitamin D3 at different dosages (15, 30, 60 IU·g·w), started before AOM or immediately after DSS treatment (post 60), was sustained to the end of the experiment. Dietary vitamin D3 significantly reduced the number of tumors and tumor burden in a dose-dependent manner. Of note, vitamin D3 in high doses showed significant preventive effects on carcinogenesis regardless of administration before or after AOM-DSS treatment. Cell proliferation decreased in vitamin D3 groups compared with the control group after inhibition of expression of β-catenin and its downstream target gene cyclin D1 in the colon. In vitro, vitamin D3 reduced the transcriptional activity and nuclear level of β-catenin, and it also increased E-cadherin expression and its binding affinity for β-catenin. Moreover, repression of E-cadherin was rescued by supplemental vitamin D3 in mouse colons. Taken together, our results indicate that vitamin D3 effectively suppressed colonic carcinogenesis in the AOM-DSS mouse model. Our findings further suggest that upregulation of E-cadherin contributes to the preventive effect of vitamin D3 on β-catenin activity.

Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case-control study in a Japanese population

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Takayama Koichi

2011-10-01

Full Text Available Abstract Background Cigarette smoking is an established risk factor of lung cancer development while the current epidemiological evidence is suggestive of an increased lung cancer risk associated with alcohol consumption. Dietary folate, which is present in a wide range of fresh fruits and vegetables, may be a micronutrient that has a beneficial impact on lung carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR plays a crucial role in regulating folate metabolism, which affects both DNA synthesis/repair and methylation. We examined if smoking or alcohol consumption modify associations between MTHFR polymorphisms and lung cancer risk. Methods We evaluated the role of the MTHFR C677T (rs1801133 and A1298C (rs1801131 polymorphisms in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Logistic regression was used to assess the adjusted odds ratios (OR and 95% confidence intervals (95% CI. Results The TT genotype of the C677T polymorphism was significantly associated with an increased risk of lung cancer (OR = 2.27, 95% CI = 1.42 - 3.62, P Conclusions The C677T polymorphism was significantly associated with lung cancer risk. Although the A1298C polymorphism was not associated with lung cancer risk, a significant interaction with drinking was observed. Future studies incorporating data on folate intake may undoubtedly lead to a more thorough understanding of the role of the MTHFR polymorphisms in lung cancer development.

Frequency of Epidermal Growth Factor Receptor Mutation in Smokers with Lung Cancer Without Pulmonary Emphysema.

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Takeda, Kenichi; Yamasaki, Akira; Igishi, Tadashi; Kawasaki, Yuji; Ito-Nishii, Shizuka; Izumi, Hiroki; Sakamoto, Tomohiro; Touge, Hirokazu; Kodani, Masahiro; Makino, Haruhiko; Yanai, Masaaki; Tanaka, Natsumi; Matsumoto, Shingo; Araki, Kunio; Nakamura, Hiroshige; Shimizu, Eiji

2017-02-01

Chronic obstructive pulmonary disease is a smoking-related disease, and is categorized into the emphysema and airway dominant phenotypes. We examined the relationship between emphysematous changes and epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma. The medical records for 250 patients with lung adenocarcinoma were retrospectively reviewed. All patients were categorized into the emphysema or non-emphysema group. Wild-type EGFR was detected in 136 (54%) and mutant EGFR in 48 (19%). Emphysematous changes were observed in 87 (36%) patients. EGFR mutation was highly frequent in the non-emphysema group (p=0.0014). Multivariate logistic regression analysis showed that emphysema was an independent risk factor for reduced frequency of EGFR mutation (Odds Ratio=3.47, p=0.005). Our data showed a relationship between emphysematous changes and EGFR mutation status. There might be mutually exclusive genetic risk factors for carcinogenesis and development of emphysematous changes. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Dysregulation of Autophagy Contributes to Anal Carcinogenesis.

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Evie H Carchman

Full Text Available Autophagy is an intracellular catabolic process that removes and recycles unnecessary/dysfunctional cellular components, contributing to cellular health and survival. Autophagy is a highly regulated cellular process that responds to several intracellular signals, many of which are deregulated by human papillomavirus (HPV infection through the expression of HPV-encoded oncoproteins. This adaptive inhibitory response helps prevent viral clearance. A strong correlation remains between HPV infection and the development of squamous cell carcinoma (SCC of the anus, particularly in HIV positive and other immunosuppressed patients. We hypothesize that autophagy is inhibited by HPV-encoded oncoproteins thereby promoting anal carcinogenesis (Fig 1.HPV16 transgenic mice (K14E6/E7 and non-transgenic mice (FVB/N, both of which do not spontaneously develop anal tumors, were treated topically with the chemical carcinogen, 7,12-Dimethylbenz[a]anthracene (DMBA, to induce anal cancer. The anuses at different time points of treatment (5, 10, 15 and 20 weeks were analyzed using immunofluorescence (IF for two key autophagy marker proteins (LC3β and p62 in addition to histological grading. The anuses from the K14E6/E7 mice were also analyzed for visual evidence of autophagic activity by electron microscopy (EM. To see if there was a correlation to humans, archival anal specimens were assessed histologically for grade of dysplasia and then analyzed for LC3β and p62 protein content. To more directly examine the effect of autophagic inhibition on anal carcinogenesis, nontransgenic mice that do not develop anal cancer with DMBA treatment were treated with a known pharmacologic inhibitor of autophagy, chloroquine, and examined for tumor development and analyzed by IF for autophagic proteins.Histologically, we observed the progression of normal anoderm to invasive SCC with DMBA treatment in K14E6/E7 mice but not in nontransgenic, syngeneic FVB/N background control mice

Fifty years of Erlangen radiochemistry

International Nuclear Information System (INIS)

Morell, W.

2007-01-01

On June 29, 2006, the Radiochemical Laboratory of AREVA NP GmbH (formerly Siemens AG) in Erlangen celebrated its fiftieth anniversary. The occasion was marked by an event attended by more than 1,000 guests, among them Werner Gebauhr, the 85-year-old founder and first head of the Laboratory; the Managing Directors of AREVA NP GmbH, Ralf Gueldner and Ruediger Steuerlein; representatives of universities, research institutions, power utilities, and public authorities. The present head of the Radiochemical Laboratory, Wilfred Morell, sketched the highlights of the work performed over the past fifty years, which ranged from solid-state and very-high-purity materials technologies to development and service activities for nuclear technology. Manfred Erve, head of the Technical Center of AREVA NP GmbH, of which the Radiochemical Laboratory is a part, emphasized the changes in priorities over the past fifty years, which had always been met successfully by Radiochemistry. In the scientific part of the event, Wolfgang Schwarz (E.ON Kernkraftwerk GmbH, KKW Isar), Ulf Ilg (EnBW Kraftwerk AG, KKW Philippsburg), and Hans-Josef Allelein (Gesellschaft fuer Anlagen- und Reaktorsicherheit mbH) explained 3 major subject areas in which Erlangen Radio-chemistry over many years has contributed basic findings (see other articles in this atw issue). On the occasion of the anniversary, a comprehensive booklet was published under the title of '50 Jahre Radiochemie Erlangen - 1956-2006'. (orig.)

Volume Adjustment of Lung Density by Computed Tomography Scans in Patients with Emphysema

International Nuclear Information System (INIS)

Shaker, S.B.; Dirksen, A.; Laursen, L.C.; Skovgaard, L.T.; Holstein-Rathlou, N.H.

2004-01-01

Purpose: To determine how to adjust lung density measurements for the volume of the lung calculated from computed tomography (CT) scans in patients with emphysema. Material and Methods: Fifty patients with emphysema underwent 3 CT scans at 2-week intervals. The scans were analyzed with a software package that detected the lung in contiguous images and subsequently generated a histogram of the pixel attenuation values. The total lung volume (TLV), lung weight, percentile density (PD), and relative area of emphysema (RA) were calculated from this histogram. RA and PD are commonly applied measures of pulmonary emphysema derived from CT scans. These parameters are markedly influenced by changes in the level of inspiration. The variability of lung density due to within-subject variation in TLV was explored by plotting TLV against PD and RA. Results: The coefficients for volume adjustment for PD were relatively stable over a wide range from the 10th to the 80th percentile, whereas for RA the coefficients showed large variability especially in the lower range, which is the most relevant for quantitation of pulmonary emphysema. Conclusion: Volume adjustment is mandatory in repeated CT densitometry and is more robust for PD than for RA. Therefore, PD seems more suitable for monitoring the progression of emphysema

TU-F-17A-09: Four-Dimensional Cone Beam CT Ventilation Imaging Can Detect Interfraction Lung Function Variations for Locally Advanced Lung Cancer Patients

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Kipritidis, J; Keall, P [Radiation Physics Laboratory, University of Sydney, Sydney NSW 2006 Australia (Australia); Hugo, G; Weiss, E; Williamson, J [Department of Radiation Oncology, Virginia Commonwealth University, Richmond VA (United States)

2014-06-15

Purpose: Four-dimensional cone beam CT ventilation imaging (4D-CBCT VI) is a novel functional lung imaging modality requiring validation. We hypothesize that 4D-CBCT VI satisfies a necessary condition for validity: that intrafraction variations (e.g. due to poor 4D-CBCT image quality) are substantially different to interfraction variations (e.g. due to changes in underlying function). We perform the first comparison of intrafraction (pre/post fraction) and interfraction (week-to-week) 4D-CBCT VIs for locally advanced non small cell lung cancer (LA NSCLC) patients undergoing radiation therapy. Methods: A total of 215 4D-CBCT scans were acquired for 19 LA NSCLC patients over 4-6 weeks of radiation therapy, including 75 pairs of pre-/post-fraction scans on the same day. 4D-CBCT VIs were obtained by applying state-of-the-art, B-spline deformable image registration to obtain the Jacobian determinant of deformation between the end-exhale and end-inhale phases. All VIs were deformably registered to the corresponding first day scan, normalized between the 10th and 90th percentile values and cropped to the ipsilateral lung only. Intrafraction variations were assessed by computing the mean and standard deviation of voxel-wise differences between all same-day pairs of pre-/post-fraction VIs. Interfraction differences were computed between first-day VIs and treatment weeks 2, 4 and 6 for all 19 patients. We tested the hypothesis by comparing cumulative distribution functions (CDFs) of intrafraction and interfraction ventilation differences using two-sided Kolmogorov-Smirnov goodness-of-fit tests. Results: The (mean ± std. dev.) of intrafraction differences was (−0.007 ± 0.079). Interfraction differences for weeks 2, 4 and 6 were (−0.035 ± 0.103), (−0.006 ± 0.094) and (−0.019 ± 0.127) respectively. For week 2, the changes in CDFs for intrafraction and interfraction differences approached statistical significance (p=0.099). Conclusion: We have shown that 4D-CBCT VI

Carcinogenesis associated with parasites other than Schistosoma, Opisthorchis and Clonorchis: A systematic review.

Science.gov (United States)

Machicado, Claudia; Marcos, Luis A

2016-06-15

Only three helminths (Schistosoma haematobium, Opisthorchis viverrini and Clonorchis sinensis) are directly associated with carcinogenesis in humans whereas the role of other parasites in cancer remains unclear. This study aimed to perform a systematic review to identify recent insights in the role of other parasite infections in carcinogenesis. We conducted systematic searches of MEDLINE and EMBASE on July 2015. Our primary outcome was the association between parasitic infections and carcinogenesis. Out of 1,266 studies, 19 were selected for detailed evaluation (eight for helminths and 11 for protozoa). The mechanisms of helminth-induced cancer included chronic inflammation, sustained proliferation, modulation of the host immune system, reprogramming of glucose metabolism and redox signaling, induction of genomic instability and destabilization of suppressor tumor proteins, stimulation of angiogenesis, resisting cell death, and activation of invasion and metastasis. In addition to the current knowledge, the following parasites were found in cancers or tumors: Echinococcus, Strongyloides, Fasciola, Heterakis, Platynosomum and Trichuris. Additional parasites were found in this systematic review that could potentially be associated with cancers or tumors but further evidence is needed to elaborate a cause-effect relationship. © 2016 UICC.

Lactobacillus salivarius Ren prevent the early colorectal carcinogenesis in 1, 2-dimethylhydrazine-induced rat model.

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Zhu, J; Zhu, C; Ge, S; Zhang, M; Jiang, L; Cui, J; Ren, F

2014-07-01

The objective of this study was to investigate the impact of Lactobacillus salivarius Ren (LS) on modulating colonic micro flora structure and influencing host colonic health in a rat model with colorectal precancerous lesions. Male F344 rats were injected with 1, 2-dimethylhydrazine (DMH) and treated with LS of two doses (5 × 10(8) and 1 × 10(10) CFU kg(-1) body weight) for 15 weeks. The colonic microflora profiles, luminal metabolites, epithelial proliferation and precancerous lesions [aberrant crypt foci (ACF)] were determined. A distinct segregation of colonic microflora structures was observed in LS-treated group. The abundance of one Prevotella-related strain was increased, and the abundance of one Bacillus-related strain was decreased by LS treatment. These changes were accompanied by increased short-chain fatty acid levels and decreased azoreductase activity. LS treatment also reduced the number of ACF by c. 40% and suppressed epithelial proliferation. Lactobacillus salivarius Ren improved the colonic microflora structures and the luminal metabolisms in addition preventing the early colorectal carcinogenesis in DMH-induced rat model. Colonic microflora is an important factor in colorectal carcinogenesis. Modulating the structural shifts of microflora may provide a novel option for preventing colorectal carcinogenesis. This study suggested a potential probiotic-based approach to modulate the intestinal microflora in the prevention of colorectal carcinogenesis. © 2014 The Society for Applied Microbiology.

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

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Shen MIAO

2009-03-01

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

Study of late effects of lung irradiation with telecobalt on lung function

International Nuclear Information System (INIS)

Wolkewitz, J.

1980-01-01

Two groups of patients, one with malignant chest tumors before radiation and one more than nine months after radiation treatment of their tumors, are examined by assessment of different lung function parameters. In addition, four patients can be examined both before and more than nine months after radiation treatment for chest tumors. It is seen that the patients whose X-rays show signs of localized radiation fibrosis do not have the typical lung function problems noted in diffuse radiation fibroses. In patients with radiographic signs of localized radiation fibrosis, combined ventilation disturbances of obstruction and restriction type are more frequent and accompanied by a slight increase in the mean pulmonary arterial pressure. These modifications of the lung function cannot solely be attributed to the radiation treatment, as the lung function is also influenced by concomitant pulmonary affections such as chronic bronchitis or renewed growth of the irradiated tumor. (orig.) [de

65Zn kinetics as a biomarker of DMH induced colon carcinogenesis

International Nuclear Information System (INIS)

Chadha, Vijayta Dani

2012-01-01

Dietary factors are considered crucial for the prevention of initiating events in the multistep progression of colon carcinoma. There is substantial evidence that zinc may play a pivotal role in host defense against several malignancies, including colon cancer. The present study was conducted to evaluate the kinetics of zinc utilization following experimental colon carcinogenesis in rat model. The rats were segregated into two groups viz., untreated control and DMH treated. Colon carcinogenesis was established through weekly subcutaneous injections of DMH (30mg/Kg body weight) for 16 weeks. Whole body 65 Zn kinetics followed two compartment kinetics, with Tb1 representing the initial fast component of the biological half-life and Tb2, the slower component. The present study revealed a significant depression in the Tb1 and Tb2 components of 65 Zn in DMH treated rats. Further, DMH treatment caused a significant increase in the percent uptake values of 65 Zn in the colon, small intestine, kidney and blood, whereas a significant decrease was observed in the liver. Subcellular distribution revealed a significant increase in 65 Zn uptake in the mitochondrial and microsomal fractions following 16 weeks of DMH supplementation. The present study demonstrated a slow mobilization of zinc during promotion of experimentally induced colon carcinogenesis and provides a physiological basis for the role of zinc in colon tumorigenesis, a paradigm which may have clinical implications in the management of colon cancer. (author)

Meat processing and colon carcinogenesis: cooked, nitrite-treated, and oxidized high-heme cured meat promotes mucin-depleted foci in rats.

Science.gov (United States)

Santarelli, Raphaëlle L; Vendeuvre, Jean-Luc; Naud, Nathalie; Taché, Sylviane; Guéraud, Françoise; Viau, Michelle; Genot, Claude; Corpet, Denis E; Pierre, Fabrice H F

2010-07-01

Processed meat intake is associated with colorectal cancer risk, but no experimental study supports the epidemiologic evidence. To study the effect of meat processing on carcinogenesis promotion, we first did a 14-day study with 16 models of cured meat. Studied factors, in a 2 x 2 x 2 x 2 design, were muscle color (a proxy for heme level), processing temperature, added nitrite, and packaging. Fischer 344 rats were fed these 16 diets, and we evaluated fecal and urinary fat oxidation and cytotoxicity, three biomarkers of heme-induced carcinogenesis promotion. A principal component analysis allowed for selection of four cured meats for inclusion into a promotion study. These selected diets were given for 100 days to rats pretreated with 1,2-dimethylhydrazine. Colons were scored for preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF). Cured meat diets significantly increased the number of ACF/colon compared with a no-meat control diet (P = 0.002). Only the cooked nitrite-treated and oxidized high-heme meat significantly increased the fecal level of apparent total N-nitroso compounds (ATNC) and the number of MDF per colon compared with the no-meat control diet (P nitrite-treated and oxidized cured meat specifically increased the MDF number compared with similar nonnitrite-treated meat (P = 0.03) and with similar nonoxidized meat (P = 0.004). Thus, a model cured meat, similar to ham stored aerobically, increased the number of preneoplastic lesions, which suggests colon carcinogenesis promotion. Nitrite treatment and oxidation increased this promoting effect, which was linked with increased fecal ATNC level. This study could lead to process modifications to make nonpromoting processed meat. 2010 AACR.

Evaluation of concentrations of major and trace elements in human lung using INAA and PIXE

International Nuclear Information System (INIS)

Altaf, W.J.; Spyrou, N.M.

1997-01-01

The elemental concentrations of Br, Ca, Ce, Cl, Co, Cr, Cs, F, Fe, Hf, K, Mg, Mn, Na, O, Rb, Sb, Sc, Se, V and Zn in 15 human lung autopsy samples, taken from subjects aged more than fifty years old, were determined by instrumental neutron activation analysis (INAA) using reactor neutrons in conjunction with a high resolution detection system. Two modes of irradiation and counting were applied; namely cyclic neutron activation analysis (CNAA) and conventional neutron activation analysis. Proton induced X-ray emission (PIXE) analysis, using a proton beam emerging from a 2 MV Van de Graaff accelerator, was additionally employed and Ge, Ni, P and Ti were also identified in the lung tissue. Detection of the X-ray spectra was performed using a high resolution Si(Li) semiconductor. The relevance of these results, including a comparison between the concentrations of elements measured in a pig's lung using CNAA and those found in the human lung is discussed. (author)

Nimesulide has a role of radio-sensitizer against lung carcinoma A549 cells

International Nuclear Information System (INIS)

Won, Joo Yoon; Park, Jong Kuk; Hong, Sung Hee

2006-01-01

Cyclooxygenases (COX) are key enzymes in the prostaglandin synthesis. There are two isoforms of the COX enzyme, COX-1 and COX-2. COX-2 expression is associated with carcinogenesis in variety of cancers and to render cells resistant to apoptotic stimuli. Increased expression of COX-2 is shown in non-small cell lung cancer (NSCLC), specifically in adenocarcinomas. Radiotherapy has been the important treatment for NSCLC. In recent studies, newer molecules that target specific pathophysiology or molecular pathways have been tested for the radiation sensitizers. COX-2 inhibitors are shown to enhanced radioresponse of cultured human cancer cell lines and immunodeficient mice. However, little is known about the molecular and biochemical mechanisms how NSAIDs enhance radioresponse of tumor cells. Nimesulide (methanesulfonamide, N-(4-nitro-2- phenoxyphenyl)), selective COX-2 inhibitors, is a drug with anti-inflammatory, anti-pyretic and analgesic properties. Nimesulide has the specific affinity to inhibit the inducible form of cyclooxygenase (COX-2) rather than the constitutive form (COX-1), and is well tolerated by adult, elderly and pediatric patients. Nimesulide was found also to have a chemopreventive activity against colon, urinary bladder, breast, tongue, and liver carcinogenesis. In this study, we examined whether nimesulide can increase radiation induced cell death and its mechanism in NSCLC cells A549

Lung disease with chronic obstruction in opium smokers in Singapore

Science.gov (United States)

Da Costa, J. L.; Tock, E. P. C.; Boey, H. K.

1971-01-01

Fifty-four opium smokers with chronic obstructive lung disease were studied for two-and-a-half years. Forty-eight patients had a cough for at least two years before the onset of inappropriate exertional dyspnoea. Fine, bubbling adventitious sounds suggesting small airway disease were heard on auscultation over the middle and lower lobes in 38 patients. The prevalence of inflammatory lung disease and chronic respiratory failure in this series is suggested as the main cause for the frequent finding of right ventricular hypertrophy and congestive heart failure. Physiological studies revealed moderate to severe airways obstruction with gross over-inflation and, in 32 patients, an additional restrictive defect probably due to peribronchiolar fibrosis. Radiological evidence of chronic bronchitis and bronchiolitis was observed in 45 patients, `pure' chronic bronchiolitis in six patients, and `widespread' emphysema in 25 patients respectively. Necropsy examinations in nine patients, however, showed destructive emphysema of variable severity in all. Chronic bronchiolitis often associated with striking bronchiolectasis was present in six cases. More severe bronchiolar rather than bronchial inflammation was noted. The heavy opium smokers had characteristic nodular shadows on chest radiography, sometimes associated with a striking reticular pattern not seen in `pure' cigarette smokers. This was due to gross pigmented dust (presumably carbon) deposition in relation to blood vessels, lymphatics, and bronchioles, and also within the alveoli. It is speculated that the initial lesion is an acquired bronchiolitis. Opium smoking induces an irritative bronchopathy favouring repeated attacks of acute bronchiolitis and eventually resulting in obliterative bronchiolitis, peribronchiolar fibrosis, chronic bronchitis, and destructive emphysema. Images PMID:5134057

Gene alterations in radiation-induced F344 rat lung tumors

International Nuclear Information System (INIS)

Kelly, G.; Hahn, F.F.

1994-01-01

The p53 tumor suppressor gene is frequently altered in all major histopathologic types of human lung tumors. Reported p53 mutations include base substitutions, allelic loss, rearrangements, and deletions. Point mutations resulting in base substitutions are clustered within a highly conserved region of the gene encoding exons 508, and mutations in this region substantially extend the half-life of the p53 protein. In addition to its prominent importance in lung carcinogenesis, the p53 gene plays a critical role in the cellular response to genetic damage caused by radiation. Specifically, the protein product of p53 induces a pause or block at the G 1 to S boundary of the cell cycle following radiation-caused DNA damage. This G 1 block may allow the cell time to repair the damaged DNA prior to replication. Cells lacking a functional p53 protein fail to pause for repair and consequently accumulate mutations in the genome at an accelerated rate. p53 has also been implicated as a controlling factor in apoptosis or in programmed cell death induced by DNA-damaging agents, such as ionizing radiation. The p53 gene is mutated in approximately 50% of squamous cell carcinomas from uranium miners who inhaled high doses of radon daughters. The purpose of the present study was to determine if a similar percentage of squamous cell carcinomas with p53 mutations developed in the lungs of rats exposed to aerosols of 239 PuO 2

The association between methylated CDKN2A and cervical carcinogenesis, and its diagnostic value in cervical cancer: a meta-analysis

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Li J

2016-08-01

Full Text Available Jinyun Li,1,2,* Chongchang Zhou,1,* Haojie Zhou,3,* Tianlian Bao,1 Tengjiao Gao,1 Xiangling Jiang,1 Meng Ye1,2 1Department of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, 2Department of Medical Oncology, Affiliated Hospital, Ningbo University, 3Department of Molecular Diagnosis, Ningbo Diagnostic Pathology Center, Ningbo, Zhejiang, People’s Republic of China *These authors are co-first authors of this work Background: Cervical cancer is the second deadliest gynecologic malignancy, characterized by apparently precancerous lesions and cervical intraepithelial neoplasia (CIN, and having a long course from the development of CIN to cervical cancer. Cyclin-dependent kinase inhibitor 2A (CDKN2A is a well-documented tumor suppressor gene and is commonly methylated in cervical cancer. However, the relationship between methylated CDKN2A and carcinogenesis in cervical cancer is inconsistent, and the diagnostic accuracy of methylated CDKN2A is underinvestigated. In this study, we attempted to quantify the association between CDKN2A methylation and the carcinogenesis of cervical cancer, and its diagnostic power.Methods: We systematically reviewed four electronic databases and identified 26 studies involving 1,490 cervical cancers, 1,291 CINs, and 964 controls. A pooled odds ratio (OR with corresponding 95% confidence intervals (95% CI was calculated to evaluate the association between methylated CDKN2A and the carcinogenesis of cervical cancer. Specificity, sensitivity, the area under the receiver operating characteristic curve, and the diagnostic odds ratio were computed to assess the effect of methylated CDKN2A in the diagnosis of cervical cancer.Results: Our results indicated an upward trend in the methylation frequency of CDKN2A in the carcinogenesis of cervical cancer (cancer vs control: OR =23.67, 95% CI =15.54–36.06; cancer vs CIN: OR =2.53, 95% CI =1.79–3.5; CIN vs control: OR =9.68, 95% CI =5.82–16.02. The

An experimental two-stage rat model of lung carcinoma initiated by radon exposure

International Nuclear Information System (INIS)

Poncy, J.L.; Laroque, P.; Fritsch, P.; Monchaux, G.; Masse, R.; Chameaud, J.

1992-01-01

We present the results of a two-stage biological model of lung carcinogenesis in rats. The histogenesis of these tumors was examined, and DNA content of lung cells was measured by flow cytometry during the evolving neoplastic stage. Tumors were induced in rat lungs after radon inhalation (1600 WLM) followed by a promoter treatment; six intramuscular injections of 5,6-benzoflavone (25 mg/kg of body weight/injection) every 2 wk. Less than 3 mo after the first injection of benzoflavone, squamous cell carcinoma was observed in the lungs of all rats exposed to radon. The preneoplastic lesions gradually developed as follows: hyperplastic bronchiolar-type cells migrated to the alveoli from cells that proliferated in bronchioles and alveolar ducts; initial lesions were observed in almost all respiratory bronchioles. From some hyperplasias, epidermoid metaplasias arose distally, forming nodular epidermoid lesions in alveoli, which progressed to form squamous papilloma and, finally, epidermoid carcinomas. The histogenesis of these experimentally induced epidermoid carcinomas showed the bronchioloalveolar origin of the tumor. This factor must be considered when comparing these with human lesions; in humans, lung epidermoid carcinomas are thought to arise mainly in the first bronchial generations. The labeling index of pulmonary tissue after incorporation of 3 H-thymidine by the cells was 0.2% in control rats. This index reached a value of 1 to 2% in the hyperplastic area of the bronchioles and 10 to 15% in epidermoid nodules and epidermoid tumors, respectively. DNA cytometric analysis was performed on cell suspensions obtained after enzymatic treatment of paraffin sections of lungs from rats sacrificed during different stags of neoplastic transformations. Data showed the early appearance of a triploid cell population that grew during the evolution of nodular epidermoid lesions to epidermoid carcinomas

Gastric microbiota and carcinogenesis: the role of non-Helicobacter pylori bacteria: a systematic review

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Emanuel Dias-Jácome

Full Text Available Background and aim: Helicobacter pylori is the strongest risk factor for gastric cancer. However, recent advances in DNA sequencing technology have revealed a complex microbial community in the stomach that could also contribute to the development of gastric cancer. The aim of this study was to present recent scientific evidence regarding the role of non-Helicobacter pylori bacteria in gastric carcinogenesis. Methods: A systematic review of original articles published in PubMed in the last ten years related to gastric microbiota and gastric cancer in humans was performed. Results: Thirteen original articles were included. The constitution of gastric microbiota appears to be significantly affected by gastric cancer and premalignant lesions. In fact, differences in gastric microbiota have been documented, depending on Helicobacter pylori status and gastric conditions, such as non-atrophic gastritis, intestinal metaplasia and cancer. Gastric carcinogenesis can be associated with an increase in many bacteria (such as Lactobacillus coleohominis, Klebsiella pneumoniae or Acinetobacter baumannii as well as decrease in others (such as Porphyromonas spp, Neisseria spp, Prevotella pallens or Streptococcus sinensis. However, there is no conclusive data that confirms if these changes in microbiota are a cause or consequence of the process of carcinogenesis. Conclusions: Even though there is limited evidence in humans, microbiota differences between normal individuals, pre-malignant lesions and gastric cancer could suggest a progressive shift in the constitution of gastric microbiota in carcinogenesis, possibly resulting from a complex cross-talk between gastric microbiota and Helicobacter pylori. However, further studies are needed to elucidate the specific role (if any of different microorganisms.

Gastric microbiota and carcinogenesis: the role of non-Helicobacter pylori bacteria - A systematic review.

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Dias-Jácome, Emanuel; Libânio, Diogo; Borges-Canha, Marta; Galaghar, Ana; Pimentel-Nunes, Pedro

2016-09-01

Helicobacter pylori is the strongest risk factor for gastric cancer. However, recent advances in DNA sequencing technology have revealed a complex microbial community in the stomach that could also contribute to the development of gastric cancer. The aim of this study was to present recent scientific evidence regarding the role of non-Helicobacter pylori bacteria in gastric carcinogenesis. A systematic review of original articles published in PubMed in the last ten years related to gastric microbiota and gastric cancer in humans was performed. Thirteen original articles were included. The constitution of gastric microbiota appears to be significantly affected by gastric cancer and premalignant lesions. In fact, differences in gastric microbiota have been documented, depending on Helicobacter pylori status and gastric conditions, such as non-atrophic gastritis, intestinal metaplasia and cancer. Gastric carcinogenesis can be associated with an increase in many bacteria (such as Lactobacillus coleohominis, Klebsiella pneumoniae or Acinetobacter baumannii) as well as decrease in others (such as Porphyromonas spp, Neisseria spp, Prevotella pallens or Streptococcus sinensis). However, there is no conclusive data that confirms if these changes in microbiota are a cause or consequence of the process of carcinogenesis. Even though there is limited evidence in humans, microbiota differences between normal individuals, pre-malignant lesions and gastric cancer could suggest a progressive shift in the constitution of gastric microbiota in carcinogenesis, possibly resulting from a complex cross-talk between gastric microbiota and Helicobacter pylori. However, further studies are needed to elucidate the specific role (if any) of different microorganisms.

Four-dimensional optical coherence tomography imaging of total liquid ventilated rats

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Kirsten, Lars; Schnabel, Christian; Gaertner, Maria; Koch, Edmund

2013-06-01

Optical coherence tomography (OCT) can be utilized for the spatially and temporally resolved visualization of alveolar tissue and its dynamics in rodent models, which allows the investigation of lung dynamics on the microscopic scale of single alveoli. The findings could provide experimental input data for numerical simulations of lung tissue mechanics and could support the development of protective ventilation strategies. Real four-dimensional OCT imaging permits the acquisition of several OCT stacks within one single ventilation cycle. Thus, the entire four-dimensional information is directly obtained. Compared to conventional virtual four-dimensional OCT imaging, where the image acquisition is extended over many ventilation cycles and is triggered on pressure levels, real four-dimensional OCT is less vulnerable against motion artifacts and non-reproducible movement of the lung tissue over subsequent ventilation cycles, which widely reduces image artifacts. However, OCT imaging of alveolar tissue is affected by refraction and total internal reflection at air-tissue interfaces. Thus, only the first alveolar layer beneath the pleura is visible. To circumvent this effect, total liquid ventilation can be carried out to match the refractive indices of lung tissue and the breathing medium, which improves the visibility of the alveolar structure, the image quality and the penetration depth and provides the real structure of the alveolar tissue. In this study, a combination of four-dimensional OCT imaging with total liquid ventilation allowed the visualization of the alveolar structure in rat lung tissue benefiting from the improved depth range beneath the pleura and from the high spatial and temporal resolution.

Columbia physics in the fifties: Untold tales

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J. Sucher

2000-07-01

Full Text Available Eyvind Wichmann and I were both graduate students at Columbia University in the fifties, a decade of remarkable creativity by a star-studded physics faculty, which included some ten Nobel Laureates. I share some reminiscences about our time there and explain the role played in our relationship by an eightball.

Application of evolutionary games to modeling carcinogenesis.

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Swierniak, Andrzej; Krzeslak, Michal

2013-06-01

We review a quite large volume of literature concerning mathematical modelling of processes related to carcinogenesis and the growth of cancer cell populations based on the theory of evolutionary games. This review, although partly idiosyncratic, covers such major areas of cancer-related phenomena as production of cytotoxins, avoidance of apoptosis, production of growth factors, motility and invasion, and intra- and extracellular signaling. We discuss the results of other authors and append to them some additional results of our own simulations dealing with the possible dynamics and/or spatial distribution of the processes discussed.

Nickel induces transcriptional down-regulation of DNA repair pathways in tumorigenic and non-tumorigenic lung cells.

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Scanlon, Susan E; Scanlon, Christine D; Hegan, Denise C; Sulkowski, Parker L; Glazer, Peter M

2017-06-01

The heavy metal nickel is a known carcinogen, and occupational exposure to nickel compounds has been implicated in human lung and nasal cancers. Unlike many other environmental carcinogens, however, nickel does not directly induce DNA mutagenesis, and the mechanism of nickel-related carcinogenesis remains incompletely understood. Cellular nickel exposure leads to signaling pathway activation, transcriptional changes and epigenetic remodeling, processes also impacted by hypoxia, which itself promotes tumor growth without causing direct DNA damage. One of the mechanisms by which hypoxia contributes to tumor growth is the generation of genomic instability via down-regulation of high-fidelity DNA repair pathways. Here, we find that nickel exposure similarly leads to down-regulation of DNA repair proteins involved in homology-dependent DNA double-strand break repair (HDR) and mismatch repair (MMR) in tumorigenic and non-tumorigenic human lung cells. Functionally, nickel induces a defect in HDR capacity, as determined by plasmid-based host cell reactivation assays, persistence of ionizing radiation-induced DNA double-strand breaks and cellular hypersensitivity to ionizing radiation. Mechanistically, we find that nickel, in contrast to the metalloid arsenic, acutely induces transcriptional repression of HDR and MMR genes as part of a global transcriptional pattern similar to that seen with hypoxia. Finally, we find that exposure to low-dose nickel reduces the activity of the MLH1 promoter, but only arsenic leads to long-term MLH1 promoter silencing. Together, our data elucidate novel mechanisms of heavy metal carcinogenesis and contribute to our understanding of the influence of the microenvironment on the regulation of DNA repair pathways. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Systematic Approach to Determining the Identifiability of Multistage Carcinogenesis Models.

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Brouwer, Andrew F; Meza, Rafael; Eisenberg, Marisa C

2017-07-01

Multistage clonal expansion (MSCE) models of carcinogenesis are continuous-time Markov process models often used to relate cancer incidence to biological mechanism. Identifiability analysis determines what model parameter combinations can, theoretically, be estimated from given data. We use a systematic approach, based on differential algebra methods traditionally used for deterministic ordinary differential equation (ODE) models, to determine identifiable combinations for a generalized subclass of MSCE models with any number of preinitation stages and one clonal expansion. Additionally, we determine the identifiable combinations of the generalized MSCE model with up to four clonal expansion stages, and conjecture the results for any number of clonal expansion stages. The results improve upon previous work in a number of ways and provide a framework to find the identifiable combinations for further variations on the MSCE models. Finally, our approach, which takes advantage of the Kolmogorov backward equations for the probability generating functions of the Markov process, demonstrates that identifiability methods used in engineering and mathematics for systems of ODEs can be applied to continuous-time Markov processes. © 2016 Society for Risk Analysis.

Fifty years ago - nuclear physics at Cambridge

International Nuclear Information System (INIS)

Burcham, W.E.

1982-01-01

Fifty years ago, the Cavendish saw the first nuclear transformations using artificially accelerated particles, and was soon to provide confirmation of the discovery of the positron. In 1932, the Cavendish Laboratory under the guiding hand of Rutherford was a world focus for research and with these discoveries saw the birth of modern particle physics. (orig.).

The effect of synthetic immunomodulator thymogen on radiation carcinogenesis in rats

International Nuclear Information System (INIS)

Anisimov, V.N.; Miretskij, G.I.; Morozov, V.G.; Pavel'eva, I.A.; Khavinson, V.Kh.

1992-01-01

Five month-old female rats were given a mixture of Sr-90 and Cs-137 in drinking water in the dose of 0.1 and 0.2 μCi/day per animal over 12 months. Some animals received 12 monthly course of a synthetic immunomodulating dipeptide-thymogen in the dose of 5 μg/animal for 5 consecutive days. Radionuclide-treated rats showed higher occurence of tumors on the whole and of breast adenocarcinoma, in particular. Thymogen was shown to inhibit Sr-90- and Cs-137-induced radiation carcinogenesis, namely, a decrease in the total tumor and cancer occurence was observed. The animals receiving thymogen alone showed longer life span, slower rate of aging and lower overall tumor and cancer occurence. In this study, the ability of asynthetic peptide immunomodulator-thymogen to inhibit spontaneous and radionuclide-induced carcinogenesis in female rats was first established

Overview of osseous tissue findings from the lifespan carcinogenesis studies: From whole animals to molecules

International Nuclear Information System (INIS)

Miller, S.C.; Jee, W.S.S.; Bruenger, F.B.; Lloyd, R.D.; Taylor, G.N.

1991-01-01

This summary presents some of the findings from the 226 Ra and 239 Pu lifespan carcinogenesis studies in Beagle dogs and discusses these findings relative to the tissue, cellular and molecular biology of osseous tissues. This report attempts to integrate some of the dosimetric and pathological findings with current understanding of the factors that may influence carcinogenesis (and non-carcinogenic pathologies) at the various levels of biological organization. Emphasis is placed on the findings from the 226 Ra study, as this study has recently been completely reviewed and verified

XRCC3 Thr241Met Polymorphism is not Associated with Lung Cancer Risk in a Romanian Population.

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Catana, Andreea; Pop, Monica; Marginean, Dragos Horea; Blaga, Ioana Cristina; Porojan, Mihai Dumitru; Popp, Radu Anghel; Pop, Ioan Victor

2016-01-01

Deoxyribonucleic Acid (DNA) repair mechanisms play a critical role in protecting the cellular genome against carcinogens. X-ray cross-complementing gene 3 (XRCC3) is involved in DNA repair and therefore certain genetic polymorphisms that occur in DNA repair genes may affect the ability to repair DNA defects and may represent a risk factor in carcinogenesis. The purpose of our study was to investigate the association between XRCC3 gene substitution of Threonine with Methionine in codon 241 of XRCC3 gene (Thr241Met) polymorphism and the risk of lung cancer, in a Romanian population. We recruited 93 healthy controls and 85 patients with lung cancer, all smokers. Thr241Met, XRCC3 gene genotyping was determined by multiplex Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Statistical analysis (OR, recessive model), did not revealed an increased risk for lung cancer, for the variant 241Met allele and Thr241Met genotypes (p=0.138, OR=0.634, CI=0.348-1.157; p=0.023, OR=0.257, CI=0.085-6.824). Also, there were no positive statistical associations between Thr241Met polymorphism of XRCC3 gene, gender, tobacco and various histopathological tumor type of lung cancer. In conclusion, the results of the study suggest that the XRCC3 gene Thr241Met polymorphism is not associated with an increased risk for the development of lung cancer in this Romanian group.

The effects of immune modulation on plutonium dioxide lung carcinogenesis in the rat

International Nuclear Information System (INIS)

Nolibe, D.; Discour, M.; Masse, R.; Lafuma, J.

1979-01-01

After inhalation of radioactive particles only some rats developed lung tumors. It was interesting to see whether this was a random effect or the result of different individual susceptibilities. Among the possible individual differences, cell mediated mechanisms and genetic factors have been reported. The relationships between cancerogenesis and host immune status are tested on rats submitted to an inhalation of plutonium dioxide particles after depression by azathioprine, hydrocortisone or thymectomy. The effects of immuno stimulation by BCG are also studied. The influence of genetic factors is studied with the same protocol on two strains of Wistar rats outbred or inbred. The incidence, nature, size, extension and metastases of tumors are compared between the groups. Results give a good evidence that AZA treated rats and thymectomized rats have a greater incidence of spontaneous tumors. This effect is observed at different levels in the two strains of rats. According to strain used, immunodepression have no or weak enhancing effect on PuO 2 tumor induction, but significant effect of development of tumors is always observed. A shift towards bronchogenic type is also observed. BCG have also an enhancing effect on development of tumors and no protective effect on their incidence

Epigenome remodelling in breast cancer: insights from an early in vitro model of carcinogenesis.

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Locke, Warwick J; Clark, Susan J

2012-11-15

Epigenetic gene regulation has influence over a diverse range of cellular functions, including the maintenance of pluripotency, differentiation, and cellular identity, and is deregulated in many diseases, including cancer. Whereas the involvement of epigenetic dysregulation in cancer is well documented, much of the mechanistic detail involved in triggering these changes remains unclear. In the current age of genomics, the development of new sequencing technologies has seen an influx of genomic and epigenomic data and drastic improvements in both resolution and coverage. Studies in cancer cell lines and clinical samples using next-generation sequencing are rapidly delivering spectacular insights into the nature of the cancer genome and epigenome. Despite these improvements in technology, the timing and relationship between genetic and epigenetic changes that occur during the process of carcinogenesis are still unclear. In particular, what changes to the epigenome are playing a driving role during carcinogenesis and what influence the temporal nature of these changes has on cancer progression are not known. Understanding the early epigenetic changes driving breast cancer has the exciting potential to provide a novel set of therapeutic targets or early-disease biomarkers or both. Therefore, it is important to find novel systems that permit the study of initial epigenetic events that potentially occur during the first stages of breast cancer. Non-malignant human mammary epithelial cells (HMECs) provide an exciting in vitro model of very early breast carcinogenesis. When grown in culture, HMECs are able to temporarily escape senescence and acquire a pre-malignant breast cancer-like phenotype (variant HMECs, or vHMECs). Cultured HMECs are composed mainly of cells from the basal breast epithelial layer. Therefore, vHMECs are considered to represent the basal-like subtype of breast cancer. The transition from HMECs to vHMECs in culture recapitulates the epigenomic

Dutch Lung Surgery Audit: A National Audit Comprising Lung and Thoracic Surgery Patients.

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Berge, Martijn Ten; Beck, Naomi; Heineman, David Jonathan; Damhuis, Ronald; Steup, Willem Hans; van Huijstee, Pieter Jan; Eerenberg, Jan Peter; Veen, Eelco; Maat, Alexander; Versteegh, Michel; van Brakel, Thomas; Schreurs, Wilhemina Hendrika; Wouters, Michel Wilhelmus

2018-04-21

The nationwide Dutch Lung Surgery Audit (DLSA) started in 2012 to monitor and evaluate the quality of lung surgery in the Netherlands as an improvement tool. This outline describes the establishment, structure and organization of the audit by the Dutch Society of Lung Surgeons (NVvL) and the Dutch Society of Cardiothoracic Surgeons (NVT), in collaboration with the Dutch Institute for Clinical Auditing (DICA). In addition, first four-year results are presented. The NVvL and NVT initiated a web-based registration including weekly updated online feedback for participating hospitals. Data verification by external data managers is performed on regular basis. The audit is incorporated in national quality improvement programs and participation in the DLSA is mandatory by health insurance organizations and the National Healthcare Inspectorate. Between 1 January 2012 and 31 December 2015, all hospitals performing lung surgery participated and a total of 19,557 patients were registered from which almost half comprised lung cancer patients. Nationwide the guideline adherence increased over the years and 96.5% of lung cancer patients were discussed in preoperative multidisciplinary teams. Overall postoperative complications and mortality after non-small cell lung cancer surgery were 15.5% and 2.0%, respectively. The audit provides reliable benchmarked information for caregivers and hospital management with potential to start local, regional or national improvement initiatives. Currently, the audit is further completed with data from non-surgical lung cancer patients including treatment data from pulmonary oncologists and radiation oncologists. This will ultimately provide a comprehensive overview of lung cancer treatment in The Netherlands. Copyright © 2018. Published by Elsevier Inc.

Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis.

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Antsiferova, Maria; Martin, Caroline; Huber, Marcel; Feyerabend, Thorsten B; Förster, Anja; Hartmann, Karin; Rodewald, Hans-Reimer; Hohl, Daniel; Werner, Sabine

2013-12-15

The growth and differentiation factor activin A is a key regulator of tissue repair, inflammation, fibrosis, and tumorigenesis. However, the cellular targets, which mediate the different activin functions, are still largely unknown. In this study, we show that activin increases the number of mature mast cells in mouse skin in vivo. To determine the relevance of this finding for wound healing and skin carcinogenesis, we mated activin transgenic mice with CreMaster mice, which are characterized by Cre recombinase-mediated mast cell eradication. Using single- and double-mutant mice, we show that loss of mast cells neither affected the stimulatory effect of overexpressed activin on granulation tissue formation and reepithelialization of skin wounds nor its protumorigenic activity in a model of chemically induced skin carcinogenesis. Furthermore, mast cell deficiency did not alter wounding-induced inflammation and new tissue formation or chemically induced angiogenesis and tumorigenesis in mice with normal activin levels. These findings reveal that mast cells are not major targets of activin during wound healing and skin cancer development and also argue against nonredundant functions of mast cells in wound healing and skin carcinogenesis in general.

Is radiation an appropriate model for chemical mutagenesis and carcinogenesis

International Nuclear Information System (INIS)

Bond, V.P.

1982-01-01

This chapter attempts to show why the quadratic, or ''linear quadratic,'' relationship holds for organ dose-single cell radiation effects, and to explore the extension of this relationship to chemical exposures in general. Demonstrates that although the ''αD + βD 2 relationship'' may be unexpected for normal pharmacologicalmedical dose-response relationships, a linear, no-threshold curve of this kind is expected for all stochastic-type (accidental or risk) situations with health consequences (e.g. all common accidents) including exposure to ''low-level radiation'' (LLR). Discusses the stochastic or risk approach, relevant radiobiology, and the stochastic for chemicals. Assumes that even though actual mutational rates cannot be expected to apply to the relevance of Tradescantia or any other single cell system as a predictor for mutagenesis and carcinogenesis in animals and man, the cardinal principles of genetics largely transcend species and the particular environment in which the cell is located. Concludes that with regard to LLR, the curve shapes and other relationships developed for Tradescantia would be expected to apply in principle to animal and human mutagenesis and carcinogenesis

International Activities in Radiation-Induced Carcinogenesis. Survey Paper

Energy Technology Data Exchange (ETDEWEB)

Komarov, E. [World Health Organization, Geneva (Switzerland)

1969-11-15

During the past 10 years special attention has been paid to the problem of late effects of radiation and in particular to radiation-induced carcinogenesis and leukaemogenesis. In the UNSCEAR report of 1958-1962 this.problem was mentioned as being of considerable importance from the point of view of estimation of risk to the population from environmental radiation. In 1964 a special report was prepared by UNSCEAR on radiation- induced carcinogenesis. In the ICRP publication No. 8, a chapter dealing with assessment of somatic risks discussed the problem of leukaemia and other neoplasms and particularly stressed the problem of thyroid carcinoma-and bone sarcoma. WHO panels of experts discussed the problem in 1960-1966 and made some recommendations for international activity in this field. In spite of the amount of scientific attention that has been given in recent years to experimental radiobiology in animals and lower forms, it has become abundantly clear that information directly applicable to humans is woefully inadequate and that there is a desperate need for carefully collected data from man on which to base public health planning and day to day work in radiation protection. This has long been recognized in the technical program of WHO in the emphasis given to the practical importance of epidemiology in human radiobiology and the degree to which it depends upon international collaboration.

Lung volumes: measurement, clinical use, and coding.

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Flesch, Judd D; Dine, C Jessica

2012-08-01

Measurement of lung volumes is an integral part of complete pulmonary function testing. Some lung volumes can be measured during spirometry; however, measurement of the residual volume (RV), functional residual capacity (FRC), and total lung capacity (TLC) requires special techniques. FRC is typically measured by one of three methods. Body plethysmography uses Boyle's Law to determine lung volumes, whereas inert gas dilution and nitrogen washout use dilution properties of gases. After determination of FRC, expiratory reserve volume and inspiratory vital capacity are measured, which allows the calculation of the RV and TLC. Lung volumes are commonly used for the diagnosis of restriction. In obstructive lung disease, they are used to assess for hyperinflation. Changes in lung volumes can also be seen in a number of other clinical conditions. Reimbursement for measurement of lung volumes requires knowledge of current procedural terminology (CPT) codes, relevant indications, and an appropriate level of physician supervision. Because of recent efforts to eliminate payment inefficiencies, the 10 previous CPT codes for lung volumes, airway resistance, and diffusing capacity have been bundled into four new CPT codes.

Review: the Contribution of both Nature and Nurture to Carcinogenesis and Progression in Solid Tumours.

Science.gov (United States)

Hyndman, Iain Joseph

2016-04-01

Cancer is a leading cause of mortality worldwide. Cancer arises due to a series of somatic mutations that accumulate within the nucleus of a cell which enable the cell to proliferate in an unregulated manner. These mutations arise as a result of both endogenous and exogenous factors. Genes that are commonly mutated in cancer cells are involved in cell cycle regulation, growth and proliferation. It is known that both nature and nurture play important roles in cancer development through complex gene-environment interactions; however, the exact mechanism of these interactions in carcinogenesis is presently unclear. Key environmental factors that play a role in carcinogenesis include smoking, UV light and oncoviruses. Angiogenesis, inflammation and altered cell metabolism are important factors in carcinogenesis and are influenced by both genetic and environmental factors. Although the exact mechanism of nature-nurture interactions in solid tumour formation are not yet fully understood, it is evident that neither nature nor nurture can be considered in isolation. By understanding more about gene-environment interactions, it is possible that cancer mortality could be reduced.

The scientific basis for the establishment of threshold levels and dose response relationships of carcinogenesis

International Nuclear Information System (INIS)

1975-01-01

The International Atomic Energy Agency hosted a two day Symposium from 2-3 December 1974 at its Headquarters, organized by the 'International Academy for Environmental Safety and the Forum fur Wissenschaft, Wirtschaft und Politik' on the subject 'Scientific Basis for the Establishment of Threshold. Levels and Dose Response Relationships of Carcinogenesis'. Following an introductory paper by the Radiation Biology Section of the Agency on 'Radiation Carcinogenesis - Dose Response Relationship, Threshold and Risk Estimates', a series of papers dealt with this problem in chemical carcinogenesis.It was suggested that more experiments should be done using non-human primates for tests of carcinogens, especially chemicals. Preliminary experiments using monkeys with a potent carcinogen - nitrosoamine - indicate that there could possibly be a dose where no effect can be observed during the 5 year period of study. It was also pointed out that the overall cost/benefit and risk/ benefit relationships should be taken into consideration in determining limits for chemicals which are potentially carcinogenic but are used routinely by the public and industries; these considerations have been weighed in setting exposure limits for radiation

Validity of clinical outcome measures to evaluate ankle range of motion during the weight-bearing lunge test.

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Hall, Emily A; Docherty, Carrie L

2017-07-01

To determine the concurrent validity of standard clinical outcome measures compared to laboratory outcome measure while performing the weight-bearing lunge test (WBLT). Cross-sectional study. Fifty participants performed the WBLT to determine dorsiflexion ROM using four different measurement techniques: dorsiflexion angle with digital inclinometer at 15cm distal to the tibial tuberosity (°), dorsiflexion angle with inclinometer at tibial tuberosity (°), maximum lunge distance (cm), and dorsiflexion angle using a 2D motion capture system (°). Outcome measures were recorded concurrently during each trial. To establish concurrent validity, Pearson product-moment correlation coefficients (r) were conducted, comparing each dependent variable to the 2D motion capture analysis (identified as the reference standard). A higher correlation indicates strong concurrent validity. There was a high correlation between each measurement technique and the reference standard. Specifically the correlation between the inclinometer placement at 15cm below the tibial tuberosity (44.9°±5.5°) and the motion capture angle (27.0°±6.0°) was r=0.76 (p=0.001), between the inclinometer placement at the tibial tuberosity angle (39.0°±4.6°) and the motion capture angle was r=0.71 (p=0.001), and between the distance from the wall clinical measure (10.3±3.0cm) to the motion capture angle was r=0.74 (p=0.001). This study determined that the clinical measures used during the WBLT have a high correlation with the reference standard for assessing dorsiflexion range of motion. Therefore, obtaining maximum lunge distance and inclinometer angles are both valid assessments during the weight-bearing lunge test. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

A Review of ERCC1 Gene in Bladder Cancer: Implications for Carcinogenesis and Resistance to Chemoradiotherapy

Directory of Open Access Journals (Sweden)

Atsunari Kawashima

2012-01-01

Full Text Available The excision repair cross-complementing group 1 (ERCC1 gene performs a critical incision step in DNA repair and is reported to be correlated with carcinogenesis and resistance to drug or ionizing radiation therapy. We reviewed the correlation between ERCC1 and bladder cancer. In carcinogenesis, several reports discussed the relation between ERCC1 single nucleotide polymorphisms and carcinogenesis in bladder cancer only in case-control studies. Regarding the relation between ERCC1 and resistance to chemoradiotherapy, in vitro and clinical studies indicate that ERCC1 might be related to resistance to radiation therapy rather than cisplatin therapy. It is controversial whether ERCC1 predicts prognosis of bladder cancer treated with cisplatin-based chemotherapy. Tyrosine kinase receptors or endothelial-mesenchymal transition are reported to regulate the expression of ERCC1, and further study is needed to clarify the mechanism of ERCC1 expression and resistance to chemoradiotherapy in vitro and to discover novel therapies for advanced and metastatic bladder cancer.

A Review of ERCC1 Gene in Bladder Cancer: Implications for Carcinogenesis and Resistance to Chemoradiotherapy.

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Kawashima, Atsunari; Takayama, Hitoshi; Tsujimura, Akira

2012-01-01

The excision repair cross-complementing group 1 (ERCC1) gene performs a critical incision step in DNA repair and is reported to be correlated with carcinogenesis and resistance to drug or ionizing radiation therapy. We reviewed the correlation between ERCC1 and bladder cancer. In carcinogenesis, several reports discussed the relation between ERCC1 single nucleotide polymorphisms and carcinogenesis in bladder cancer only in case-control studies. Regarding the relation between ERCC1 and resistance to chemoradiotherapy, in vitro and clinical studies indicate that ERCC1 might be related to resistance to radiation therapy rather than cisplatin therapy. It is controversial whether ERCC1 predicts prognosis of bladder cancer treated with cisplatin-based chemotherapy. Tyrosine kinase receptors or endothelial-mesenchymal transition are reported to regulate the expression of ERCC1, and further study is needed to clarify the mechanism of ERCC1 expression and resistance to chemoradiotherapy in vitro and to discover novel therapies for advanced and metastatic bladder cancer.

Radiotherapeutic results for primary lung cancer

International Nuclear Information System (INIS)

Mitomo, Osamu; Shinozaki, Jun; Suzuki, Yoshihiko; Niibe, Hideo; Mitsuhashi, Norio; Nakajima, Nobuaki.

1988-01-01

From June 1978 to March 1984, 311 patients with lung cancer were registered at the radiological department of National Takasaki Hospital. One hundred fifty-one of them, who had been verified histologically and irradiated with total doses of more than 60 Gy for the primary lung tumor, were analized. Many patients were more than 60 years old (82 %) and had squamous cell carcinoma (64 %). These percentages may be associated with distributions of patients treated by radiotherapy because of inoperability. The five-year-relative survival rate was 13 % in all patients (54 % for Stage I, 32 % for Stage II, 0 % for Stage III, 10 % for Stage IV). Comparing squamous cell carcinoma and adenocarcinoma, the latter had a better prognosis for two years, but over three years, squamous cell carcinoma did. The five-year survival rate was 10 % for squamous cell carcinoma and 6 % for adenocarcinoma, showing no statistically significant difference. No predominant differences of prognosis between the older group (more than 70 years old) and the younger group (less than 70 years old) was demonstrated. Thus, old age is not always a factor in bad prognosis. (author)

Molecular Mechanism of Gastric Carcinogenesis in Helicobacter pylori-Infected Rodent Models

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Takeshi Toyoda

2014-06-01

Full Text Available Since the discovery of Helicobacter pylori (H. pylori, many efforts have been made to establish animal models for the investigation of the pathological features and molecular mechanisms of gastric carcinogenesis. Among the animal models, Mongolian gerbils and mice are particularly useful for the analysis of H. pylori-associated inflammatory reactions and gastric cancer development. Inhibitors of oxidative stress, cyclooxygenase-2 (COX-2 and nuclear factor-κB, exert preventive effects on chronic gastritis and the development of adenocarcinomas in H. pylori-infected gerbils. Genetically-modified mouse models, including transgenic and knockout mice, have also revealed the importance of p53, COX-2/prostaglandin, Wnt/β-catenin, proinflammatory cytokines, gastrin and type III mucin in the molecular mechanisms of gastric carcinogenesis. Microarray technology is available for comprehensive gene analysis in the gastric mucosa of mouse models, and epigenetics, such as DNA methylation, could be an alternative approach to correlate the observations in animal models with the etiology in humans.

High glucose contributes to the proliferation and migration of non-small cell lung cancer cells via GAS5-TRIB3 axis.

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Ding, Cheng-Zhi; Guo, Xu-Feng; Wang, Guo-Lei; Wang, Hong-Tao; Xu, Guang-Hui; Liu, Yuan-Yuan; Wu, Zhen-Jiang; Chen, Yu-Hang; Wang, Jiao; Wang, Wen-Guang

2018-01-24

Despite the growing number of studies exhibited an association of diabetes mellitus (DM) and lung cancer progression, the concrete mechanism of DM aggravating lung cancer has not been elucidated. This study was to investigate whether and how high glucose (HG) contribute to the proliferation and migration of non-small cell lung cancer (NSCLC) cells in vitro. In the present study, we confirmed that HG promoted the proliferation and migration of NSCLC cells, and also induced an anti-apoptosis effect on NSCLC cells. Moreover, HG inhibited the expression of GAS5 in NSCLC cells but elevated the protein level of TRIB3. GAS5 overexpression promoted the degradation of TRIB3 protein by ubiquitination and inhibited the HG induced-proliferation, anti-apoptosis and migration of NSCLC cells. Importantly, TRIB3 overexpression reversed the effects of GAS5 on the HG-treated NSCLC cells. Taken together, down-regulated GAS5 by HG significantly enhanced the proliferation, anti-apoptosis and migration in NSCLC cells through TRIB3, thus promoting the carcinogenesis of NSCLC. ©2018 The Author(s).

Information Systems Curricula: A Fifty Year Journey

Science.gov (United States)

Longenecker, Herbert E., Jr.; Feinstein, David; Clark, Jon D.

2013-01-01

This article presents the results of research to explore the nature of changes in skills over a fifty year period spanning the life of Information Systems model curricula. Work begun in 1999 was expanded both backwards in time, as well as forwards to 2012 to define skills relevant to Information Systems curricula. The work in 1999 was based on job…

Perfusion lung scanning: differentiation of primary from thromboembolic pulmonary hypertension

International Nuclear Information System (INIS)

Lisbona, R.; Kreisman, H.; Novales-Diaz, J.; Derbekyan, V.

1985-01-01

Of eight patients with pulmonary arterial hypertension, final diagnosis established by autopsy or angiography, four had primary hypertension and four hypertension from thromboembolism. The perfusion lung scan was distinctly different in the two groups. The lung scan in primary pulmonary hypertension was associated with nonsegmental, patchy defects of perfusion, while in thromboembolic hypertensives it was characterized by segmental and/or lobar defects of perfusion with or without subsegmental defects. The perfusion lung scan is a valuable, noninvasive study in the evaluation of the patient with pulmonary hypertension of undetermined cause and in the exclusion of occult large-vessel pulmonary thromboembolism

Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8)

DEFF Research Database (Denmark)

Soria, Jean-Charles; Felip, Enriqueta; Cobo, Manuel

2015-01-01

BACKGROUND: There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced...... squamous cell carcinoma of the lung. METHODS: We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum...... be an additional option for the treatment of patients with squamous cell carcinoma of the lung. FUNDING: Boehringer Ingelheim....

A Catalog of Genes Homozygously Deleted in Human Lung Cancer and the Candidacy of PTPRD as a Tumor Suppressor Gene

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Kohno, Takashi; Otsuka, Ayaka; Girard, Luc; Sato, Masanori; Iwakawa, Reika; Ogiwara, Hideaki; Sanchez-Cespedes, Montse; Minna, John D.; Yokota, Jun

2010-01-01

A total of 176 genes homozygously deleted in human lung cancer were identified by DNA array-based whole genome scanning of 52 lung cancer cell lines and subsequent genomic PCR in 74 cell lines, including the 52 cell lines scanned. One or more exons of these genes were homozygously deleted in one (1%) to 20 (27%) cell lines. These genes included known tumor suppressor genes, e.g., CDKN2A/p16, RB1, and SMAD4, and candidate tumor suppressor genes whose hemizygous or homozygous deletions were reported in several types of human cancers, such as FHIT, KEAP1, and LRP1B/LRP-DIP. CDKN2A/p16 and p14ARF located in 9p21 were most frequently deleted (20/74, 27%). The PTPRD gene was most frequently deleted (8/74, 11%) among genes mapping to regions other than 9p21. Somatic mutations, including a nonsense mutation, of the PTPRD gene were detected in 8/74 (11%) of cell lines and 4/95 (4%) of surgical specimens of lung cancer. Reduced PTPRD expression was observed in the majority (>80%) of cell lines and surgical specimens of lung cancer. Therefore, PTPRD is a candidate tumor suppressor gene in lung cancer. Microarray-based expression profiling of 19 lung cancer cell lines also indicated that some of the 176 genes, such as KANK and ADAMTS1, are preferentially inactivated by epigenetic alterations. Genetic/epigenetic as well as functional studies of these 176 genes will increase our understanding of molecular mechanisms behind lung carcinogenesis. PMID:20073072

Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence

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Rothschild SI

2014-09-01

Full Text Available Sacha I Rothschild Department of Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland Abstract: The therapeutic landscape in non-small-cell lung cancer (NSCLC is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here. Keywords: nintedanib, lung cancer, angiokinase inhibitor, VEGFR, PDGF, FGFR

Multistep carcinogenesis of normal human fibroblasts. Human fibroblasts immortalized by repeated treatment with Co-60 gamma rays were transformed into tumorigenic cells with Ha-ras oncogenes.

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Namba, M; Nishitani, K; Fukushima, F; Kimoto, T

1988-01-01

Two normal mortal human fibroblast cell strains were transformed into immortal cell lines, SUSM-1 and KMST-6, by treatment with 4-nitroquinoline 1-oxide (4NQO) and Co-60 gamma rays, respectively. These immortalized cell lines showed morphological changes of cells and remarkable chromosome aberrations, but neither of them grew in soft agar or formed tumors in nude mice. The immortal cell line, KMST-6, was then converted into neoplastic cells by treatment with Harvey murine sarcoma virus (Ha-MSV) or the c-Ha-ras oncogene derived from a human lung carcinoma. These neoplastically transformed cells acquired anchorage-independent growth potential and developed tumors when transplanted into nude mice. All the tumors grew progressively without regression until the animals died of tumors. In addition, the tumors were transplantable into other nude mice. Normal human fibroblasts, on the other hand, were not transformed into either immortal or tumorigenic cells by treatment with Ha-MSV or c-Ha-ras alone. Our present data indicate that (1) the chemical carcinogen, 4NQO, or gamma rays worked as an initiator of carcinogenesis in normal human cells, giving rise to immortality, and (2) the ras gene played a role in the progression of the immortally transformed cells to more malignant cells showing anchorage-independent growth and tumorigenicity. In other words, the immortalization process of human cells seems to be a pivotal or rate-limiting step in the carcinogenesis of human cells.

Whole body exposure of mice to secondhand smoke induces dose-dependent and persistent promutagenic DNA adducts in the lung

International Nuclear Information System (INIS)

Kim, Sang-In; Arlt, Volker M.; Yoon, Jae-In; Cole, Kathleen J.; Pfeifer, Gerd P.; Phillips, David H.; Besaratinia, Ahmad

2011-01-01

Secondhand smoke (SHS) exposure is a known risk factor for lung cancer in lifelong nonsmokers. However, the underlying mechanism of action of SHS in lung carcinogenesis remains elusive. We have investigated, using the 32 P-postlabeling assay, the genotoxic potential of SHS in vivo by determining the formation and kinetics of repair of DNA adducts in the lungs of mice exposed whole body to SHS for 2 or 4 months (5 h/day, 5 days/week), and an ensuing one-month recovery period. We demonstrate that exposure of mice to SHS elicits a significant genotoxic response as reflected by the elevation of DNA adduct levels in the lungs of SHS-exposed animals. The increases in DNA adduct levels in the lungs of SHS-exposed mice are dose-dependent as they are related to the intensity and duration of SHS exposure. After one month of recovery in clean air, the levels of lung DNA adducts in the mice exposed for 4 months remain significantly higher than those in the mice exposed for 2 months (P < 0.0005), levels in both groups being significantly elevated relative to controls (P < 0.00001). Our experimental findings accord with the epidemiological data showing that exposure to smoke-derived carcinogens is a risk factor for lung cancer; not only does the magnitude of risk depend upon carcinogen dose, but it also becomes more irreversible with prolonged exposure. The confirmation of epidemiologic data by our experimental findings is of significance because it strengthens the case for the etiologic involvement of SHS in nonsmokers' lung cancer. Identifying the etiologic factors involved in the pathogenesis of lung cancer can help define future strategies for prevention, early detection, and treatment of this highly lethal malignancy.

Mammary carcinogenesis in rats: basic facts and recent results in Brookhaven

International Nuclear Information System (INIS)

Shellabarger, C.J.; Stone, J.P.; Holtzman, s.

1982-01-01

Some research results from experiments investigating neutron-induced mammary carcinogenesis in rats are presented. The additive effects of neutrons and 3-methylcholanthrene on mammary adenocarcinoma were determined. Synergism between diethylstilbestrol and neutrons was likewise studied. Differences in mammary neoplastic response between strains of laboratory rats was also investigated

Deterrence, denuclearization, and proliferation: Alternative visions of the next fifty years

International Nuclear Information System (INIS)

Lehman, R.F. II.

1994-01-01

The great library of Alexandria may have contained fewer volumes than the number which have been written on the subject of nuclear weapons in the Cold War. With the end of the Cold War, a new nuclear library is in the making. Much thought is being given to the next steps in nuclear policy, strategy, forces, arms control, and nonproliferation. For this very distinguished conference, however, I have been asked to look further ahead indeed, forward fifty-years. Prognostication is always a risky business. Detailed predictions beyond the shortest duration are difficult to label as ''scientific'' even in the social sciences. Forecasting ahead fifty years in an age of ever accelerating change would seem to be hopeless. Projecting the future of nuclear weapons, however, may not be as complex as one might think. Detailing the future fifty years from now is not necessary. We want to inform upcoming decisions by examining the possibilities, not write a history in advance of what is to happen. Our look forward con benefit from a brief look back fifty years. In retrospect, those years passed quickly, and with each additional year, analysts make them appear more simple than they seemed at the time. This paper contributes further to this process of oversimplification, as we say, ''for heuristic purposes.'' When in doubt, I have erred on the side of being provocative

Deterrence, denuclearization, and proliferation: Alternative visions of the next fifty years

Energy Technology Data Exchange (ETDEWEB)

Lehman, R.F. II

1994-02-12

The great library of Alexandria may have contained fewer volumes than the number which have been written on the subject of nuclear weapons in the Cold War. With the end of the Cold War, a new nuclear library is in the making. Much thought is being given to the next steps in nuclear policy, strategy, forces, arms control, and nonproliferation. For this very distinguished conference, however, I have been asked to look further ahead indeed, forward fifty-years. Prognostication is always a risky business. Detailed predictions beyond the shortest duration are difficult to label as ``scientific`` even in the social sciences. Forecasting ahead fifty years in an age of ever accelerating change would seem to be hopeless. Projecting the future of nuclear weapons, however, may not be as complex as one might think. Detailing the future fifty years from now is not necessary. We want to inform upcoming decisions by examining the possibilities, not write a history in advance of what is to happen. Our look forward con benefit from a brief look back fifty years. In retrospect, those years passed quickly, and with each additional year, analysts make them appear more simple than they seemed at the time. This paper contributes further to this process of oversimplification, as we say, ``for heuristic purposes.`` When in doubt, I have erred on the side of being provocative.

Dysregulation of microRNAs in colonic field carcinogenesis: implications for screening.

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Dhananjay P Kunte

Full Text Available Colorectal cancer (CRC screening tests often have a trade-off between efficacy and patient acceptability/cost. Fecal tests (occult blood, methylation engender excellent patient compliance but lack requisite performance underscoring the need for better population screening tests. We assessed the utility of microRNAs (miRNAs as markers of field carcinogenesis and their potential role for CRC screening using the azoxymethane (AOM-treated rat model. We found that 63 miRNAs were upregulated and miR-122, miR-296-5p and miR-503# were downregulated in the uninvolved colonic mucosa of AOM rats. We monitored the expression of selected miRNAs in colonic biopsies of AOM rats at 16 weeks and correlated it with tumor development. We noted that the tumor bearing rats had significantly greater miRNA modulation compared to those without tumors. The miRNAs showed good diagnostic performance with an area under the receiver operator curve (AUROC of >0.7. We also noted that the miRNA induction in the colonic mucosa was mirrorred in the mucus layer fecal colonocytes isolated from AOM rat stool and the degree of miRNA induction was greater in the tumor bearing rats compared to those without tumors. Lastly, we also noted significant miRNA modulation in the Pirc rats- the genetic model of colon carcinogenesis, both in the uninvolved colonic mucosa and the fecal colonocytes. We thus demonstrate that miRNAs are excellent markers of field carcinogenesis and could accurately predict future neoplasia. Based on our results, we propose an accurate, inexpensive, non-invasive miRNA test for CRC risk stratification based on rectal brushings or from abraded fecal colonocytes.

Lung fibrosis quantified by HRCT in scleroderma patients with different disease forms and ANA specificities

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S. Mancin

2011-09-01

Full Text Available Objective: to define the prevalence of interstitial lung fibrosis in systemic sclerosis (SSc and its relationship with the different clinical forms of disease and ANA specificities. Methods: fifty patients with SSc were submitted to pulmonary high resolution computed tomography (HRCT. Lung abnormalities were evaluated according to Warrick’s score that considers both the severity and the extent of fibrotic lesions. Results: pulmonary HRCT abnormalities were observed in 84% of SSc patients. Ground glass aspects (60%, irregular pleural margins (56% and septal/subpleural lines (68% were the most common lesions. The distribution of these abnormalities favoured the posterior basilar segments of both lungs. HRCT findings were significantly more frequent in males and in patients with the cutaneous diffuse form of SSc and with the specific antibody anti-Scl70. Conclusions: HRCT is a very useful method for the diagnosis of interstitial lung fibrosis in SSc. Warrick’s score permits to quantify the HRCT findings and to evaluate their relationship with the disease clinical forms and ANA specificities.

Primary lung cancer in Assiut University Hospitals: Pattern of presentation within four years (January 2011: December 2014

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Amany Omar

2017-10-01

Conclusions: Knowing that the incidence of lung cancer increased globally in both male and female, the relatively lower male to female ratio when compared with other studies, may reflect at least an increasing in the lung cancer rates among female. Smoking still remains the major risk factor in pathogenesis of primary lung cancer. COPD could be considered an important respiratory disorder that tied to bronchogenic carcinoma risk. Interestingly, the incidence of adenocarcinoma surpassed that of squamous cell carcinoma. Unfortunately, presentation of the patient at later stages of illness was common.

Ionizing radiation, inflammation, and their interactions in colon carcinogenesis in Mlh1-deficient mice.

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Morioka, Takamitsu; Miyoshi-Imamura, Tomoko; Blyth, Benjamin J; Kaminishi, Mutsumi; Kokubo, Toshiaki; Nishimura, Mayumi; Kito, Seiji; Tokairin, Yutaka; Tani, Shusuke; Murakami-Murofushi, Kimiko; Yoshimi, Naoki; Shimada, Yoshiya; Kakinuma, Shizuko

2015-03-01

Genetic, physiological and environmental factors are implicated in colorectal carcinogenesis. Mutations in the mutL homolog 1 (MLH1) gene, one of the DNA mismatch repair genes, are a main cause of hereditary colon cancer syndromes such as Lynch syndrome. Long-term chronic inflammation is also a key risk factor, responsible for colitis-associated colorectal cancer; radiation exposure is also known to increase colorectal cancer risk. Here, we studied the effects of radiation exposure on inflammation-induced colon carcinogenesis in DNA mismatch repair-proficient and repair-deficient mice. Male and female Mlh1(-/-) and Mlh1(+/+) mice were irradiated with 2 Gy X-rays when aged 2 weeks or 7 weeks and/or were treated with 1% dextran sodium sulfate (DSS) in drinking water for 7 days at 10 weeks old to induce mild inflammatory colitis. No colon tumors developed after X-rays and/or DSS treatment in Mlh1(+/+) mice. Colon tumors developed after DSS treatment alone in Mlh1(-/-) mice, and exposure to radiation prior to DSS treatment increased the number of tumors. Histologically, colon tumors in the mice resembled the subtype of well-to-moderately differentiated adenocarcinomas with tumor-infiltrating lymphocytes of human Lynch syndrome. Immunohistochemistry revealed that expression of both p53 and β-catenin and loss of p21 and adenomatosis polyposis coli proteins were observed at the later stages of carcinogenesis, suggesting a course of molecular pathogenesis distinct from typical sporadic or colitis-associated colon cancer in humans. In conclusion, radiation exposure could further increase the risk of colorectal carcinogenesis induced by inflammation under the conditions of Mlh1 deficiency. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Expression Patterns of Cancer Stem Cell Markers During Specific Celecoxib Therapy in Multistep Rat Colon Carcinogenesis Bioassays.

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Salim, Elsayed I; Hegazi, Mona M; Kang, Jin Seok; Helmy, Hager M

2016-01-01

The purpose of this study was to investigate the role of colon cancer stem cells (CSCs) during chemicallyinduced rat multi-step colon carcinogenesis with or without the treatment with a specific cyclooxygenase-2 inhibitor drug (celecoxib). Two experiments were performed, the first, a short term 12 week colon carcinogenesis bioassay in which only surrogate markers for colon cancer, aberrant crypt foci (ACF) lesions, were formed. The other experiment was a medium term colon cancer rat assay in which tumors had developed after 32 weeks. Treatment with celecoxib lowered the numbers of ACF, as well as the tumor volumes and multiplicities after 32 weeks. Immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were downregulated after treatment by celecoxib. Also different cell surface antigens known to associate with CSCs such as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared between the two experiments and showed differential expression patterns depending on the stage of carcinogenesis and treatment with celecoxib. Flow cytometric analysis demonstrated that the numbers of CD133 cells were increased in the colonic epithelium after 12 weeks while those of CD44 but not CD133 cells were increased after 32 weeks. Moreover, aldehyde dehydrogenase-1 activity levels in the colonic epithelium (a known CSC marker) detected by ELISA assay were found down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data have also shown that the protective effect of celecoxib on these specific markers and populations of CSCs and on other molecular processes such as apoptosis targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. Therefore, uncovering these distinction roles of CSCs during different phases of carcinogenesis and during specific treatment could be useful for targeted therapy.

Venice: Fifty years after the great flood of November 4, 1966

Science.gov (United States)

Rizzoli, P. M.

2017-12-01

Fifty years ago Venice and its lagoon suffered the most devastating flood in their millennial history. The causes of the increasingly recurring floods will be examined, namely the man-induced subsidence in the period 1925-1970 and the storm surges of the Adriatic sea. The engineering solution designed for their protection , named the MOSE system, will be discussed in detail. The MOSE was started in 2003 and is near completion. It consists of four barriers , invisible in normal conditions, which will close the inlets to the lagoon under the prediction of a forthcoming flood. Finally, the perspective of the MOSE capability of protecting the city under scenarios of future global sea level rise will be assessed. This assessment must critically take into account that Venice and its lagoon are confined in the northernmost corner of the semi-enclosed, marginal Mediterranean sea for which the uncertainties of future sea level rise greatly exceed the uncertainties of the global averages.

Lung transplant recipients holding companion animals: impact on physical health and quality of life.

Science.gov (United States)

Irani, S; Mahler, C; Goetzmann, L; Russi, E W; Boehler, A

2006-02-01

Since lung transplant recipients are susceptible to infections and inhaled pollution, many centers warn against pets. However, data supporting this recommendation are lacking. Our program is less restrictive regarding pets. This study, for the first time, investigates the association of pets with physiological and psychological parameters in these patients. A questionnaire concerning pets was sent to 104 lung transplant recipients. Lung function tests, levels of exhaled nitric oxide (FE(NO)), need for antibiotic treatments and hospitalizations, creatinine clearance, body mass index (BMI) and demographic data were assessed. Additionally, the questionnaire of life satisfaction (FLZ), a question on summarized life satisfaction (LS), the life orientation test (LOT), the hospital anxiety depression scale (HADS) and the social support questionnaire (F-SozU) were assessed. Response rate was 86%. Fifty-two percent defined themselves as pet owners, whereas 48% did not. The two groups did not differ in demographic or physiological data. Significant differences in FLZ (79/65, p = 0.04), in LS (4.3/3.9, p = 0.01), LOT (32/29, p = 0.006) and F-SozU (4.5/4.2, p = 0.04) were found in favor of pet owners. In lung transplant recipients keeping pets the frequency of somatic complications is not higher compared to lung transplant recipients without pets. After lung transplantation, pets are associated with a better quality of life.

Humidifier disinfectant-associated lung injury in adults: Prognostic factors in predicting short-term outcome

International Nuclear Information System (INIS)

Koo, Hyun Jung; Do, Kyung-Hyun; Chae, Eun Jin; Kim, Hwa Jung; Song, Joon Seon; Jang, Se Jin; Hong, Sang-Bum; Huh, Jin Won; Lee, En; Hong, Soo-Jong

2017-01-01

To identify clinical and radiologic findings that affect disease severity and short-term prognosis of humidifier disinfectant-associated lung injury in adults and to compare computed tomography (CT) findings between the patients with and without death or lung transplantation. Fifty-nine adults (mean age, 34 years; M/F = 12:47) were enrolled in this retrospective study. Medical records and prospective surveillance data were used to assess clinical and radiological factors associated with a poor clinical outcome. Multivariate generalized estimating equation models were used to analyse serial CT findings. Overall cumulative major events including lung transplantation and mortality were assessed using the Kaplan-Meier method. Almost half needed ICU admission (47.5 %) and 17 died (28.8 %). Young age, peripartum and low O_2 saturation were factors associated with ICU admission. On initial chest radiographs, consolidation (P < 0.001) and ground-glass opacity (P = 0.01) were significantly noted in patients who required ICU admission. CT findings including consolidation (odds ratio (OR), 1.02), pneumomediastinum (OR, 1.66) and pulmonary interstitial emphysema (OR, 1.61) were the risk factors for lung transplantation and mortality. Clinical and radiologic findings are related to the risks of lung transplantation and mortality of humidifier disinfectant-associated lung injury. Consolidation, pneumomediastinum and pulmonary interstitial emphysema were short-term prognostic CT findings. (orig.)

Humidifier disinfectant-associated lung injury in adults: Prognostic factors in predicting short-term outcome

Energy Technology Data Exchange (ETDEWEB)

Koo, Hyun Jung; Do, Kyung-Hyun; Chae, Eun Jin [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Songpa-gu, Seoul (Korea, Republic of); Kim, Hwa Jung [University of Ulsan College of Medicine, Cancer Center, Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, Seoul (Korea, Republic of); Song, Joon Seon; Jang, Se Jin [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of); Hong, Sang-Bum; Huh, Jin Won [University of Ulsan College of Medicine, Department of Pulmonary and Critical Care Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, En [Inje University Haundae Paik Hospital, Department of Pediatrics, Busan (Korea, Republic of); Hong, Soo-Jong [University of Ulsan College of Medicine, Department of Pediatrics, Childhood Asthma and Atopy Center, Environmental Health Center, Asan Medical Center, Seoul (Korea, Republic of)

2017-01-15

To identify clinical and radiologic findings that affect disease severity and short-term prognosis of humidifier disinfectant-associated lung injury in adults and to compare computed tomography (CT) findings between the patients with and without death or lung transplantation. Fifty-nine adults (mean age, 34 years; M/F = 12:47) were enrolled in this retrospective study. Medical records and prospective surveillance data were used to assess clinical and radiological factors associated with a poor clinical outcome. Multivariate generalized estimating equation models were used to analyse serial CT findings. Overall cumulative major events including lung transplantation and mortality were assessed using the Kaplan-Meier method. Almost half needed ICU admission (47.5 %) and 17 died (28.8 %). Young age, peripartum and low O{sub 2} saturation were factors associated with ICU admission. On initial chest radiographs, consolidation (P < 0.001) and ground-glass opacity (P = 0.01) were significantly noted in patients who required ICU admission. CT findings including consolidation (odds ratio (OR), 1.02), pneumomediastinum (OR, 1.66) and pulmonary interstitial emphysema (OR, 1.61) were the risk factors for lung transplantation and mortality. Clinical and radiologic findings are related to the risks of lung transplantation and mortality of humidifier disinfectant-associated lung injury. Consolidation, pneumomediastinum and pulmonary interstitial emphysema were short-term prognostic CT findings. (orig.)

[Origin exploration of "the fifty-nine acupoints for febrile disease"].

Science.gov (United States)

Li, Guangyi

2017-02-12

Fifty-nine acupoints for febrile disease is recorded in Huangdi Neijing ( Huangdi's Internal Classics ). By analyzing the combination of these acupoints, the writer discovered the acupoint composition and detected their origins from Huangdi's Internal Classics , in which the terms biaoben, qijie and beishu are involved in the theoretic evidence. The writer thought the "fifty-nine acupoints for febrile disease" implied the self-evolution of some acupuncture school in ancient time, which was formed by absorbing the theoretic experiences of the other schools. It is necessary to analyze and interpret the other literatures besides Huangdi's Internal Classics and probably obtain the further reorganization on it.

A polymorphism in miR-1262 regulatory region confers the risk of lung cancer in Chinese population.

Science.gov (United States)

Xie, Kaipeng; Chen, Mengxi; Zhu, Meng; Wang, Cheng; Qin, Na; Liang, Cheng; Song, Ci; Dai, Juncheng; Jin, Guangfu; Shen, Hongbing; Lin, Dongxin; Ma, Hongxia; Hu, Zhibin

2017-09-01

It has been proposed that the majority of disease-associated loci identified by genome-wide association studies (GWAS) are enriched in non-coding regions, such as the promoter, enhancer or non-coding RNA genes. Thus, we performed a two-stage case-control study to systematically evaluate the association of genetic variants in miRNA regulatory regions (promoter and enhancer) with lung cancer risk in 7,763 subjects (discovery stage: 2,331 cases and 3,077 controls; validation stage: 1,065 cases and 1,290 controls). As a result, we identified that rs12740674 (C > T) in miR-1262 enhancer was significantly associated with the increased risk of lung cancer (additive model in discovery stage: adjusted OR = 1.31, 95%CI = 1.13-1.53, p = 3.846 × 10 -4 in Nanjing GWAS; adjusted OR = 1.20, 95%CI = 1.00-1.44, p = 0.041 in Beijing GWAS; validation stage: adjusted OR = 1.20, 95%CI = 1.03-1.41, p = 0.024). In meta-analysis, the p value for the association between rs12740674 and lung cancer risk reached 6.204 × 10 -6 (adjusted OR = 1.24, 95%CI = 1.13-1.36). Using 3DSNP database, The Cancer Genome Atlas (TCGA) data and functional assays, we observed that the risk T allele of rs12740674 reduced the expression level of miR-1262 in lung tissue through chromosomal looping, and overexpression of miR-1262 inhibited lung cancer cell proliferation probably through targeting the expression levels of ULK1 and RAB3D. Our findings confirmed the important role that genetic variants of noncoding sequence play in lung cancer susceptibility and indicated that rs12740674 in miR-1262 may be biologically relevant to lung carcinogenesis. © 2017 UICC.

Quantification of nanoscale density fluctuations by electron microscopy: probing cellular alterations in early carcinogenesis

International Nuclear Information System (INIS)

Pradhan, Prabhakar; Damania, Dhwanil; Turzhitsky, Vladimir; Subramanian, Hariharan; Backman, Vadim; Joshi, Hrushikesh M; Dravid, Vinayak P; Roy, Hemant K; Taflove, Allen

2011-01-01

Most cancers are curable if they are diagnosed and treated at an early stage. Recent studies suggest that nanoarchitectural changes occur within cells during early carcinogenesis and that such changes precede microscopically evident tissue alterations. It follows that the ability to comprehensively interrogate cell nanoarchitecture (e.g., macromolecular complexes, DNA, RNA, proteins and lipid membranes) could be critical to the diagnosis of early carcinogenesis. We present a study of the nanoscale mass-density fluctuations of biological tissues by quantifying their degree of disorder at the nanoscale. Transmission electron microscopy images of human tissues are used to construct corresponding effective disordered optical lattices. The properties of nanoscale disorder are then studied by statistical analysis of the inverse participation ratio (IPR) of the spatially localized eigenfunctions of these optical lattices at the nanoscale. Our results show an increase in the disorder of human colonic epithelial cells in subjects harboring early stages of colon neoplasia. Furthermore, our findings strongly suggest that increased nanoscale disorder correlates with the degree of tumorigenicity. Therefore, the IPR technique provides a practicable tool for the detection of nanoarchitectural alterations in the earliest stages of carcinogenesis. Potential applications of the technique for early cancer screening and detection are also discussed

Identification of Novel Targets for Lung Cancer Therapy Using an Induced Pluripotent Stem Cell Model.

Science.gov (United States)

Shukla, Vivek; Rao, Mahadev; Zhang, Hongen; Beers, Jeanette; Wangsa, Darawalee; Wangsa, Danny; Buishand, Floryne O; Wang, Yonghong; Yu, Zhiya; Stevenson, Holly; Reardon, Emily; McLoughlin, Kaitlin C; Kaufman, Andrew; Payabyab, Eden; Hong, Julie A; Zhang, Mary; Davis, Sean R; Edelman, Daniel C; Chen, Guokai; Miettinen, Markku; Restifo, Nicholas; Ried, Thomas; Meltzer, Paul S; Schrump, David S

2018-04-01

small cell lung cancer lines and specimens. Overexpression of the additional sex combs like-3 gene correlated with increased genomic copy number in small cell lung cancer lines. Knock-down of the additional sex combs like-3 gene inhibited proliferation, clonogenicity, and teratoma formation by lung induced pluripotent stem cells and significantly diminished in vitro clonogenicity and growth of small cell lung cancer cells in vivo. Collectively, these studies highlight the potential utility of this lung induced pluripotent stem cell model for elucidating epigenetic mechanisms contributing to pulmonary carcinogenesis and suggest that additional sex combs like-3 is a novel target for small cell lung cancer therapy.

Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study.

Science.gov (United States)

Needham, Dale M; Colantuoni, Elizabeth; Mendez-Tellez, Pedro A; Dinglas, Victor D; Sevransky, Jonathan E; Dennison Himmelfarb, Cheryl R; Desai, Sanjay V; Shanholtz, Carl; Brower, Roy G; Pronovost, Peter J

2012-04-05

To evaluate the association of volume limited and pressure limited (lung protective) mechanical ventilation with two year survival in patients with acute lung injury. Prospective cohort study. 13 intensive care units at four hospitals in Baltimore, Maryland, USA. 485 consecutive mechanically ventilated patients with acute lung injury. Two year survival after onset of acute lung injury. 485 patients contributed data for 6240 eligible ventilator settings, as measured twice daily (median of eight eligible ventilator settings per patient; 41% of which adhered to lung protective ventilation). Of these patients, 311 (64%) died within two years. After adjusting for the total duration of ventilation and other relevant covariates, each additional ventilator setting adherent to lung protective ventilation was associated with a 3% decrease in the risk of mortality over two years (hazard ratio 0.97, 95% confidence interval 0.95 to 0.99, P=0.002). Compared with no adherence, the estimated absolute risk reduction in two year mortality for a prototypical patient with 50% adherence to lung protective ventilation was 4.0% (0.8% to 7.2%, P=0.012) and with 100% adherence was 7.8% (1.6% to 14.0%, P=0.011). Lung protective mechanical ventilation was associated with a substantial long term survival benefit for patients with acute lung injury. Greater use of lung protective ventilation in routine clinical practice could reduce long term mortality in patients with acute lung injury. Clinicaltrials.gov NCT00300248.

Experimental photoimmunology: immunologic ramifications of UV-induced carcinogenesis

International Nuclear Information System (INIS)

Daynes, R.A.; Bernhard, E.J.; Gurish, M.F.; Lynch, D.H.

1981-01-01

The use of animal model systems to investigate the sequence of events which lead to the induction and progression of skin tumors following chronic ultraviolet light (UVL) exposure has clearly shown that the direct mutagenic effects of UVL is only one of the components involved in this process. In spite of the fact that overt carcinogenesis is only one of the many effects produced by UV light, most hypotheses as to the mechanism by which UVL can cause the mutations necessary to achieve the transformed phenotype have focused on the direct effects of UVL on DNA and the generation of carcinogenic compounds. Investigations during the last 5 yr, however, have clearly demonstrated that immunologic factors are also critically important in the pathogenesis of UV-induced skin cancers. A complete understanding of UV-carcinogenesis must therefore consider the mechanisms which allow the transformed cell to evade immunologic rejection by the host in addition to those aspects which deal with conversion of a normal cell to a cancer cell. It is the object of this review to provide both a historical account of the work which established the immunologic consequences of chronic UVL exposure and the results of recent experiments designed to investigate the kinetics and mechanisms by which UVL affects the immunologic apparatus. In addition, a hypothetical model is presented to explain the sequence of events which ultimately lead to the emergence of the suppressor T-cells which regulate antitumor immune responses

Glutaminolysis and carcinogenesis of oral squamous cell carcinoma.

Science.gov (United States)

Cetindis, Marcel; Biegner, Thorsten; Munz, Adelheid; Teriete, Peter; Reinert, Siegmar; Grimm, Martin

2016-02-01

Glutaminolysis is a crucial factor for tumor metabolism in the carcinogenesis of several tumors but has not been clarified for oral squamous cell carcinoma (OSCC) yet. Expression of glutaminolysis-related solute carrier family 1, member 5 (SLC1A5)/neutral amino acid transporter (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLDH) was analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry. SLC1A5/ASCT2 and GLS were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue, while GLDH was weakly detected. Compared with SIN I-III SLC1A5/ASCT2 and GLS expression were significantly increased in OSCC. GLDH expression did not significantly differ from SIN I-III compared with OSCC. This study shows the first evidence of glutaminolysis-related SLC1A5/ASCT2, GLS, and GLDH expression in OSCC. The very weak GLDH expression indicates that glutamine metabolism is rather related to nucleotide or protein/hexosamine biosynthesis or to the function as an antioxidant (glutathione) than to energy production or generation of lactate through entering the tricarboxylic acid cycle. Overcoming glutaminolysis by targeting c-Myc oncogene (e.g. by natural compounds) and thereby cross-activation of mammalian target of rapamycin complex 1 or SLC1A5/ASCT2, GLS inhibitors may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies.

Inherent aerobic capacity-dependent differences in breast carcinogenesis.

Science.gov (United States)

Thompson, Henry J; Jones, Lee W; Koch, Lauren G; Britton, Steven L; Neil, Elizabeth S; McGinley, John N

2017-09-01

Although regular physical activity is associated with improvement in aerobic capacity and lower breast cancer risk, there are heritable sets of traits that affect improvement in aerobic capacity in response to physical activity. Although aerobic capacity segregates risk for a number of chronic diseases, the effect of the heritable component on cancer risk has not been evaluated. Therefore, we investigated breast carcinogenesis in rodent models of heritable fitness in the absence of induced physical activity. Female offspring of N:NIH rats selectively bred for low (LIAC) or high (HIAC) inherent aerobic capacity were injected intraperitoneally with 1-methyl-1-nitrosurea (70 mg/kg body wt). At study termination 33 weeks post-carcinogen, cancer incidence (14.0 versus 47.3%; P < 0.001) and multiplicity (0.18 versus 0.85 cancers per rat; P < 0.0001) were significantly decreased in HIAC versus LIAC rats, respectively. HIAC had smaller visceral and subcutaneous body fat depots than LIAC and activity of two proteins that regulated the mammalian target of rapamycin, protein kinase B (Akt), and adenosine monophosphate-activated protein kinase were suppressed and activated, respectively, in HIAC. Although many factors distinguish between HIAC and LIAC, it appears that the protective effect of HIAC against breast carcinogenesis is mediated, at least in part, via alterations in core metabolic signaling pathways deregulated in the majority of human breast cancers. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Takuji, E-mail: tmntt08@gmail.com [Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-Cho, Gifu 500-8513 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Shimizu, Masahito; Kochi, Takahiro; Shirakami, Yohei [Department of Internal Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Mori, Takayuki [Department of Pharmacy, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki 503-8502 (Japan); Watanabe, Naoki [Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-Cho, Gifu 500-8513 (Japan); Naiki, Takafumi [Department of Clinical Laboratory, Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu 500-8513 (Japan); Moriwaki, Hisataka [Department of Internal Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Yoshimi, Kazuto; Serikawa, Tadao; Kuramoto, Takashi [The Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501 (Japan)

2014-07-21

Despite widening interest in the possible association between infection/inflammation and cancer development, knowledge of this issue in relation to oral cancer remains inadequate. This study aimed to determine the susceptibility of Apc-mutant Kyoto Apc Delta (KAD) rats, which are vulnerable to developing inflammation-associated colorectal carcinogenesis, to 4-nitroquinoline 1-oxide (4-NQO)-induced tongue carcinogenesis in order to clarify the role of inflammation in oral cancer. KAD (20 males and 22 females) and F344/NS1c (22 males and 23 females) rats received drinking water with or without 4-NQO (20 ppm) for eight weeks. Histopathological and immunohistochemical analyses of the tongue were performed at week 20. Additionally, the mRNA expression of inflammatory cytokines in the tongue mucosa was determined at week 8. Tongue squamous cell carcinoma (SCC) developed in the KAD and F344/NS1c rats that received 4-NQO. Regardless of gender, the incidence and multiplicity of tongue SCC were greater in the KAD rats than in the F344/NS1c rats. In addition, the multiplicity of tongue SCC in the female KAD rats was significantly greater than that observed in the male KAD (p < 0.01) and female F344/NS1c rats (p < 0.05). The levels of inflammation and the mRNA expression of inflammatory cytokines in the tongue in the 4-NQO-treated female KAD rats were the highest among the rats given 4-NQO. These results show that KAD rats, particularly females, are susceptible to 4-NQO-induced tongue carcinogenesis, suggesting the utility of models employing KAD rats for investigating the pathobiology of oral (tongue) carcinogenesis associated with inflammation.

Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis

International Nuclear Information System (INIS)

Tanaka, Takuji; Shimizu, Masahito; Kochi, Takahiro; Shirakami, Yohei; Mori, Takayuki; Watanabe, Naoki; Naiki, Takafumi; Moriwaki, Hisataka; Yoshimi, Kazuto; Serikawa, Tadao; Kuramoto, Takashi

2014-01-01

Despite widening interest in the possible association between infection/inflammation and cancer development, knowledge of this issue in relation to oral cancer remains inadequate. This study aimed to determine the susceptibility of Apc-mutant Kyoto Apc Delta (KAD) rats, which are vulnerable to developing inflammation-associated colorectal carcinogenesis, to 4-nitroquinoline 1-oxide (4-NQO)-induced tongue carcinogenesis in order to clarify the role of inflammation in oral cancer. KAD (20 males and 22 females) and F344/NS1c (22 males and 23 females) rats received drinking water with or without 4-NQO (20 ppm) for eight weeks. Histopathological and immunohistochemical analyses of the tongue were performed at week 20. Additionally, the mRNA expression of inflammatory cytokines in the tongue mucosa was determined at week 8. Tongue squamous cell carcinoma (SCC) developed in the KAD and F344/NS1c rats that received 4-NQO. Regardless of gender, the incidence and multiplicity of tongue SCC were greater in the KAD rats than in the F344/NS1c rats. In addition, the multiplicity of tongue SCC in the female KAD rats was significantly greater than that observed in the male KAD (p < 0.01) and female F344/NS1c rats (p < 0.05). The levels of inflammation and the mRNA expression of inflammatory cytokines in the tongue in the 4-NQO-treated female KAD rats were the highest among the rats given 4-NQO. These results show that KAD rats, particularly females, are susceptible to 4-NQO-induced tongue carcinogenesis, suggesting the utility of models employing KAD rats for investigating the pathobiology of oral (tongue) carcinogenesis associated with inflammation

Iron and thiols as two major players in carcinogenesis: friends or foes?

Science.gov (United States)

Toyokuni, Shinya

2014-01-01

Iron is the most abundant metal in the human body and mainly works as a cofactor for proteins such as hemoglobin and various enzymes. No independent life forms on earth can survive without iron. However, excess iron is intimately associated with carcinogenesis by increasing oxidative stress via its catalytic activity to generate hydroxyl radicals. Biomolecules with redox-active sulfhydryl function(s) (thiol compounds) are necessary for the maintenance of mildly reductive cellular environments to counteract oxidative stress, and for the execution of redox reactions for metabolism and detoxification. Involvement of glutathione S-transferase and thioredoxin has long attracted the attention of cancer researchers. Here, I update recent findings on the involvement of iron and thiol compounds during carcinogenesis and in cancer cells. It is now recognized that the cystine/glutamate transporter (antiporter) is intimately associated with ferroptosis, an iron-dependent, non-apoptotic form of cell death, observed in cancer cells, and also with cancer stem cells; the former with transporter blockage but the latter with its stabilization. Excess iron in the presence of oxygen appears the most common known mutagen. Ironically, the persistent activation of antioxidant systems via genetic alterations in Nrf2 and Keap1 also contributes to carcinogenesis. Therefore, it is difficult to conclude the role of iron and thiol compounds as friends or foes, which depends on the quantity/distribution and induction/flexibility, respectively. Avoiding further mutation would be the most helpful strategy for cancer prevention, and myriad of efforts are being made to sort out the weaknesses of cancer cells.

Antibiotic suppression of intestinal microbiota reduces heme-induced lipoperoxidation associated with colon carcinogenesis in rats.

Science.gov (United States)

Martin, O C B; Lin, C; Naud, N; Tache, S; Raymond-Letron, I; Corpet, D E; Pierre, F H

2015-01-01

Epidemiological studies show that heme iron from red meat is associated with increased colorectal cancer risk. In carcinogen-induced-rats, a heme iron-rich diet increases the number of precancerous lesions and raises associated fecal biomarkers. Heme-induced lipoperoxidation measured by fecal thiobarbituric acid reagents (TBARs) could explain the promotion of colon carcinogenesis by heme. Using a factorial design we studied if microbiota could be involved in heme-induced carcinogenesis, by modulating peroxidation. Rats treated or not with an antibiotic cocktail were given a control or a hemoglobin-diet. Fecal bacteria were counted on agar and TBARs concentration assayed in fecal water. The suppression of microbiota by antibiotics was associated with a reduction of crypt height and proliferation and with a cecum enlargement, which are characteristics of germ-free rats. Rats given hemoglobin diets had increased fecal TBARs, which were suppressed by the antibiotic treatment. A duplicate experiment in rats given dietary hemin yielded similar results. These data show that the intestinal microbiota is involved in enhancement of lipoperoxidation by heme iron. We thus suggest that microbiota could play a role in the heme-induced promotion of colorectal carcinogenesis.

The European initiative for quality management in lung cancer care

DEFF Research Database (Denmark)

Blum, Torsten G; Rich, Anna; Baldwin, David

2014-01-01

. The Task Force undertook four projects: 1) a narrative literature search on quality management of lung cancer; 2) a survey of national and local infrastructure for lung cancer care in Europe; 3) a benchmarking project on the quality of (inter)national lung cancer guidelines in Europe; and 4) a feasibility...... study of prospective data collection in a pan-European setting. There is little peer-reviewed literature on quality management in lung cancer care. The survey revealed important differences in the infrastructure of lung cancer care in Europe. The European guidelines that were assessed displayed wide...... countries. The European Initiative for Quality Management in Lung Cancer Care has provided the first comprehensive snapshot of lung cancer care in Europe....

Young Women's Perceptions of the Relationship in Fifty Shades of Grey.

Science.gov (United States)

Bonomi, Amy E; Nichols, Emily M; Carotta, Christin L; Kiuchi, Yuya; Perry, Samantha

2016-02-01

Millions of women are interacting with Fifty Shades of Grey-a best-selling novel and film. Yet, to date, no social science study has been undertaken to examine women's perceptions of the Fifty Shades relationship narrative in its film adaptation-what they deem appealing, what they deem unappealing, and what they would welcome or resist in their own relationship. In the present study, we used focus groups to examine women's perceptions of the relationship patterns in the Fifty Shades of Grey film. Focus groups were conducted with 35 young adult women (randomly sampled from the registrar's office of a large Midwestern university) immediately after watching the Fifty Shades film with the study team at a local theater within two days of the film's release. Seven semistructured questions concentrating on reactions to the relationship patterns between Christian Grey and Anastasia Steele depicted in the Fifty Shades film were asked, including general reactions, appealing and unappealing characteristics, romantic and dangerous elements, and aspects that participants would tolerate (or not tolerate) in their own relationships. While participants assessed parts of the relationship between Christian and Anastasia as exciting and romantic, they consistently indicated an unappealing lack of health in the relationship. Participants expressed grave concerns over Christian's stalking, controlling, manipulative, and emotionally abusive behavior, anger in sexual interactions, and neglect of Anastasia's needs. At the same time, they sympathized with and rationalized Christian's behaviors as a function of his personality, needs, and abilities. A small contingent implicated Anastasia in the unhealthy relationship process, whereas a broader majority of participants highlighted the challenges with trying to "speak up" in an unhealthy relationship like Christian and Anastasia's. When asked where participants would draw the line in their own relationship, participants indicated they would

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-03-15

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

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

International Nuclear Information System (INIS)

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

2017-01-01

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

Effects of dietary beef, pork, chicken and salmon on intestinal carcinogenesis in A/J Min/+ mice.

Directory of Open Access Journals (Sweden)

Christina Steppeler

Full Text Available The International Agency for Research on Cancer has classified red meat as "probably carcinogenic to humans" (Group 2A. In mechanistic studies exploring the link between intake of red meat and CRC, heme iron, the pigment of red meat, is proposed to play a central role as a catalyzer of luminal lipid peroxidation and cytotoxicity. In the present work, the novel A/J Min/+ mouse was used to investigate the effects of dietary beef, pork, chicken, or salmon (40% muscle food (dry weight and 60% powder diet on Apc-driven intestinal carcinogenesis, from week 3-13 of age. Muscle food diets did not differentially affect carcinogenesis in the colon (flat ACF and tumors. In the small intestine, salmon intake resulted in a lower tumor size and load than did meat from terrestrial animals (beef, pork or chicken, while no differences were observed between the effects of white meat (chicken and red meat (pork and beef. Additional results indicated that intestinal carcinogenesis was not related to dietary n-6 polyunsaturated fatty acids, intestinal formation of lipid peroxidation products (thiobarbituric acid reactive substances, TBARS, or cytotoxic effects of fecal water on Apc-/+ cells. Notably, the amount of heme reaching the colon appeared to be relatively low in this study. The greatest tumor load was induced by the reference diet RM1, underlining the importance of the basic diets in experimental CRC. The present study in A/J Min/+ mice does not support the hypothesis of a role of red meat in intestinal carcinogenesis.

The Quality of Curative-intent Radiotherapy for Non-small Cell Lung Cancer in the UK.

Science.gov (United States)

McAleese, J; Baluch, S; Drinkwater, K

2015-09-01

Lung cancer is the leading cause of cancer-related death in the UK. The quality of curative-intent radiotherapy is associated with better outcomes. National quality standards from the National Institute for Health and Care Excellence (NICE) on patient work-up and treatment selection were used, with guidance from the Royal College of Radiologists on the technical delivery of radiotherapy, to assess the quality of curative-intent non-small cell lung cancer radiotherapy and to describe current UK practice. Radiotherapy departments completed one questionnaire for each patient started on curative-intent radiotherapy for 8 weeks in 2013. Eighty-two per cent of centres returned a total of 317 proformas. Patient selection with positron emission tomography/computed tomography, performance status and Forced Expiratory Volume in 1 second (FEV1) was usually undertaken. Fifty-six per cent had pathological confirmation of mediastinal lymph nodes and 22% staging brain scans; 20% were treated with concurrent chemoradiation, 12% with Stereotactic Ablative Radiotherapy (SABR) and 8% with Continuous Hyperfractionated Accelerated Radiotherapy (CHART). Sixty-three per cent of patients received 55 Gy/20 fractions. Although respiratory compensation was routinely undertaken, only 33% used four-dimensional computed tomography. Seventy per cent of patients were verified with cone beam computed tomography. There was consistency of practice in dosimetric constraints for organs at risk and follow-up. This audit has described current UK practice. The latest recommendations for patient selection with pathological confirmation of mediastinal lymph nodes, brain staging and respiratory function testing are not universally followed. Although there is evidence of increasing use of newer techniques such as four-dimensional computed tomography and cone beam image-guided radiotherapy, there is still variability in access. Efforts should be made to improve access to modern technologies and quality

Investigating the Role of FIP200 in Mammary Carcinogenesis Using a Transgenic Mouse Model

National Research Council Canada - National Science Library

Nagy, Tamas

2007-01-01

...) deletion in mammary-specific polyoma middle-T transgenic mice. We monitored mammary carcinogenesis in positive control (FAKFlox/Flox; MMTV-PyVT) and target (FAKFlox/Flox; MMTV-Cre; MMTV-PyVT) females...

P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs

DEFF Research Database (Denmark)

Ciofu, Oana; Johansen, Helle Krogh; Aanaes, Kasper

2013-01-01

BACKGROUND: Pseudomonas aeruginosa cells are present as biofilms in the paranasal sinuses and the lungs of chronically infected cystic fibrosis (CF) patients. Since different inflammatory responses and selective antibiotic pressures are acting in the sinuses compared with the lungs, we compared...... the adaptive profiles of mucoid and non-mucoid isolates from the two locations. METHODS: We studied the genetic basis of phenotypic diversification and gene expression profiles in sequential lung and sinus P. aeruginosa isolates from four chronically infected CF patients, including pre- and post-lung...... transplantation isolates. RESULTS: The same phenotypes caused by similar mutations and similar gene expression profiles were found in mucoid and non-mucoid isolates from the paranasal sinuses and from the lungs before and after transplantation. CONCLUSION: Bilateral exchange of P. aeruginosa isolates between...

Fifty years of Cuba's medical diplomacy: from idealism to pragmatism.

Science.gov (United States)

Feinsilver, Julie M

2010-01-01

Medical diplomacy, the collaboration between countries to simultaneously produce health benefits and improve relations, has been a cornerstone of Cuban foreign policy since the outset of the revolution fifty years ago. It has helped Cuba garner symbolic capital (goodwill, influence, and prestige) well beyond what would have been possible for a small, developing country, and it has contributed to making Cuba a player on the world stage. In recent years, medical diplomacy has been instrumental in providing considerable material capital (aid, credit, and trade), as the oil-for-doctors deals with Venezuela demonstrates. This has helped keep the revolution afloat in trying economic times. What began as the implementation of the one of the core values of the revolution, namely health as a basic human right for all peoples, has continued as both an idealistic and a pragmatic pursuit. This article examines the factors that enabled Cuba to conduct medical diplomacy over the past fifty years, the rationale behind the conduct of this type of soft power politics, the results of that effort, and the mix of idealism and pragmatism that has characterized the experience. Moreover, it presents a typology of medical diplomacy that Cuba has used over the past fifty years.

Failure of catalase to protect against aflatoxin B1-induced mouse lung tumorigenicity

International Nuclear Information System (INIS)

Guindon, Katherine A.; Foley, Julie F.; Maronpot, Robert R.; Massey, Thomas E.

2008-01-01

The carcinogenic mycotoxin aflatoxin B 1 (AFB 1 ) induces 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in mouse lung, an effect that can be prevented by treatment with polyethylene glycol-conjugated catalase (PEG-CAT). G → T transversion mutation in K-ras, an early event in AFB 1 -induced mouse lung carcinogenesis, is thought to result from AFB 1 -8,9-exo-epoxide binding to DNA to form AFB 1 -N 7 -guanine, but may also result from formation of 8-OHdG. Therefore, oxidative DNA damage may be important in AFB 1 carcinogenicity. The objective of this study was to determine whether PEG-CAT would prevent AFB 1 tumorigenicity. Mouse lung tumorigenesis was assessed following treatment of female A/J mice with 300 kU/kg PEG-CAT ip and/or 50 mg/kg AFB 1 . Mice were killed 7 months post-treatment and tumors greater than 1 mm in diameter were excised. Unexpectedly, the mean number of tumors per mouse in the PEG-CAT + AFB 1 group (8.81 ± 3.64, n = 47) was greater than that of the group treated with AFB 1 alone (7.05 ± 3.45, n = 42) (P 1 were larger than those from mice treated with AFB 1 alone (P 1 and PEG-CAT + AFB 1 groups (P > 0.05). In vitro incubation with mouse liver catalase (CAT) resulted in conversion of [ 3 H]AFB 1 into a DNA-binding species, a possible explanation for the results observed in vivo. These results demonstrate that PEG-CAT is not protective against AFB 1 carcinogenicity in mouse lung despite preventing DNA oxidation

Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study.

Directory of Open Access Journals (Sweden)

Jianxin Shi

2016-12-01

Full Text Available Lung adenocarcinoma (LUAD is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression.We performed an integrative genomic analysis, incorporating whole exome sequencing (WES, determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE study. We detected driver genes by testing whether the nonsynonymous mutation rate was significantly higher than the background mutation rate and replicated our findings in public datasets with 724 samples. We performed subclonality analysis for mutations based on mutant allele data and copy number alteration data. We also tested the association between mutation signatures and clinical outcomes, including distant metastasis, survival, and tumor grade. We identified and replicated two novel candidate driver genes, POU class 4 homeobox 2 (POU4F2 (mutated in 9 [8.9%] samples and ZKSCAN1 (mutated in 6 [5.9%] samples, and characterized their major deleterious mutations. ZKSCAN1 was part of a mutually exclusive gene set that included the RTK/RAS/RAF pathway genes BRAF, EGFR, KRAS, MET, and NF1, indicating an important driver role for this gene. Moreover, we observed strong associations between methylation in specific genomic regions and somatic mutation patterns. In the tumor evolution analysis, four driver genes had a significantly lower fraction of subclonal mutations (FSM, including TP53 (p = 0.007, KEAP1 (p = 0.012, STK11 (p = 0.0076, and EGFR (p = 0.0078, suggesting a tumor initiation role for these genes. Subclonal mutations were significantly enriched in APOBEC-related signatures (p < 2.5×10-50. The total number of somatic mutations (p = 0.0039 and the fraction of transitions (p = 5.5×10-4 were associated with increased risk of

Influence of lavage therapy on the distribution patterns of inhaled, relatively insoluble particles in the lung

International Nuclear Information System (INIS)

Snipes, M.B.; Runkle, G.E.; Muggenburg, B.A.

1977-01-01

Four Beagle dogs were exposed by inhalation to a polydisperse fused aluminosilicate aerosol labeled with 147 Pm and 169 Yb. The left or right lung of each dog was lavaged one or five times to remove a portion of the lung burden. Autoradiographic and computer techniques were combined to determine the dispersion pattern of radioactive particles still in the lung after lavage therapy. For all four dogs the dispersion pattern of particles in the lung was the same for the lavaged and non-lavaged lung lobes. Examination of the autoradiograms indicated that lavage therapy did not preferentially remove particles from some areas of the lung. The similarity of particle dispersion patterns suggests that a minimal relocation of particles in lung results from lavage therapy

Radiation carcinogenesis in mouse thymic lymphomas

International Nuclear Information System (INIS)

Kominami, Ryo; Niwa, Ohtsura

2006-01-01

Ionizing radiation is a well-known carcinogen for various human tissues and a complete carcinogen that is able to initiate and promote neoplastic progression. Studies of radiation-induced mouse thymic lymphomas, one of the classic models in radiation carcinogenesis, demonstrated that even the unirradiated thymus is capable of developing into full malignancy when transplanted into the kidney capsule or subcutaneous tissue of irradiated mice. This suggests that radiation targets tissues other than thymocytes to allow expansion of cells with tumorigenic potential in the thymus. The idea is regarded as the ''indirect mechanism'' for tumor development. This paper reviews the indirect mechanism and genes affecting the development of thymic lymphomas that we have analyzed. One is the Bcl11b/Rit1 tumor suppressor gene and the other is Mtf-1 gene affecting tumor susceptibility. (author)

Dietary fish oil (MaxEPA) enhances pancreatic carcinogenesis in azaserine-treated rats

NARCIS (Netherlands)

Appel, M.J.; Woutersen, R.A.

1996-01-01

In the present study the putative chemopreventive effect of dietary fish oil (MaxEPA) on azaserine-induced pancreatic carcinogenesis in rats was investigated. Groups of rats were maintained on a semipurified low-fat (LF; 5 wt%) diet or on semipurified high-fat (HF; 25 wt%) diets containing 5 wt%

Deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 knockout mice.

Science.gov (United States)

Zhang, Danqing; Kobayashi, Toshiyuki; Kojima, Tetsuo; Kanenishi, Kenji; Hagiwara, Yoshiaki; Abe, Masaaki; Okura, Hidehiro; Hamano, Yoshitomo; Sun, Guodong; Maeda, Masahiro; Jishage, Kou-ichi; Noda, Tetsuo; Hino, Okio

2011-04-01

Genetic crossing experiments were performed between tuberous sclerosis-2 (Tsc2) KO and expressed in renal carcinoma (Erc) KO mice to analyze the function of the Erc/mesothelin gene in renal carcinogenesis. We found the number and size of renal tumors were significantly less in Tsc2+/-;Erc-/- mice than in Tsc2+/-;Erc+/+ and Tsc2+/-;Erc+/- mice. Tumors from Tsc2+/-;Erc-/- mice exhibited reduced cell proliferation and increased apoptosis, as determined by proliferating cell nuclear antigen (Ki67) and TUNEL analysis, respectively. Adhesion to collagen-coated plates in vitro was enhanced in Erc-restored cells and decreased in Erc-suppressed cells with siRNA. Tumor formation by Tsc2-deficient cells in nude mice was remarkably suppressed by stable knockdown of Erc with shRNA. Western blot analysis showed that the phosphorylation of focal adhesion kinase, Akt and signal transducer and activator of transcription protein 3 were weaker in Erc-deficient/suppressed cells compared with Erc-expressed cells. These results indicate that deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 KO mice and inhibits the phosphorylation of several kinases of cell adhesion mechanism. This suggests that Erc/mesothelin may have an important role in the promotion and/or maintenance of carcinogenesis by influencing cell-substrate adhesion via the integrin-related signal pathway. © 2011 Japanese Cancer Association.

Recent progress in nickel carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Sunderman, F.W. Jr.

1984-01-01

Positive bacterial mutagenesis tests have been obtained with Ni(II) in Corynybacterium, but not in E. coli, S. typhimurium, or B. subtilis. Transformation assays of several soluble and crystalline Ni compounds have been positive in Syrian hamster embryo cells. Ni(II) binds to DNA, RNA, and nucleoproteins, and becomes localized in nucleoli. Genotoxic effects of Ni include: (a) chromosomal aberrations, including sister-chromatid exchanges, (b) DNA strandbreaks and DNA-protein crosslinks, (c) inhibition of DNA and RNA synthesis, (d) infidelity of DNA transcription, and (e) mutations at the HGPRTase locus in Chinese hamster cells and the TK locus in mouse lymphoma cells. These findings are consistent with somatic mutation as the mechanism for initiation of nickel carcinogenesis. Ni compounds cause reversible transition of double-stranded poly(dG-dC) DNA from the right-handed B-helix to the left-handed Z-helix, suggesting a mechanism whereby nickel might modulate oncogene expression. 99 references, 4 tables.

Chemoprevention by Probiotics During 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats.

Science.gov (United States)

Walia, Sohini; Kamal, Rozy; Dhawan, D K; Kanwar, S S

2018-04-01

Probiotics are believed to have properties that lower the risk of colon cancer. However, the mechanisms by which they exert their beneficial effects are relatively unknown. To assess the impact of probiotics in preventing induction of colon carcinogenesis in rats. The rats were divided into six groups viz., normal control, Lactobacillus plantarum (AdF10)-treated, Lactobacillus rhamnosus GG (LGG)-treated, 1,2-dimethylhydrazine (DMH)-treated, L. plantarum (AdF10) + DMH-treated and L. rhamnosus GG (LGG) + DMH-treated. Both the probiotics were supplemented daily at a dose of 2 × 10 10 cells per day. DMH at a dose of 30 mg/kg body weight was administered subcutaneously twice a week for the first 4 weeks and then once every week for a duration of 16 weeks. Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase as protein expression of genes involved in apoptosis were assessed during DMH-induced colon carcinogenesis in rats. DMH treatment decreased the activity of GSH, GPx, GST, SOD and catalase. However, AdF10 and LGG supplementation to DMH-treated rats significantly increased the activity of these enzymes. Further, DMH treatment revealed alterations in the protein expressions of various genes involved in the p53-mediated apoptotic pathway such as p53, p21, Bcl-2, Bax, caspase-9 and caspase-3, which, however, were shifted towards normal control levels upon simultaneous supplementation with probiotics. The present study suggests that probiotics can provide protection against oxidative stress and apoptotic-related protein disregulation during experimentally induced colon carcinogenesis.

contribution to carcinogenesis

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Aneta Białkowska

2014-01-01

Full Text Available The centrosomes are subcellular organelles composed of two centrioles surrounded by a pericentriolar material. In animal cells they are responsible for the organization of the interphase microtubule cytoskeleton including microtubule nucleation and elongation, their attachment and release. The centrosomes are also involved in the construction of the mitotic spindle and chromosome segregation. More than a century ago it was suggested that these structures might be involved in human diseases, including cancer. Cancer cells show a high frequency of centrosome aberrations, especially amplification. Centrosome defects may increase the incidence of multipolar mitoses that lead to chromosomal segregation abnormalities and aneuploidy, which is the predominant type of genomic instability found in human solid tumors. The number of these organelles in cells is strictly controlled and is dependent on the proper process of centrosome duplication. Multiple genes that are frequently found mutated in cancers encode proteins which participate in the regulation of centrosome duplication and the numeral integrity of centrosomes. In recent years there has been growing interest in the potential participation of centrosomes in the process of carcinogenesis, especially because centrosome abnormalities are observed in premalignant stages of cancer development. The common presence of abnormal centrosomes in cancer cells and the role these organelles play in the cells suggest that the factors controlling the number of centrosomes may be potential targets for cancer therapy.

Effect of complex polyphenols on colon carcinogenesis.

Science.gov (United States)

Caderni, G; Remy, S; Cheynier, V; Morozzi, G; Dolara, P

1999-06-01

Complex polyphenols and tannins from wine (WCPT) are being considered increasingly as potential cancer chemopreventive agents, since epidemiological studies suggest that populations consuming a high amount of polyphenols in the diet may have a lower incidence of some types of cancer. We studied the effect of WCPT on a series of parameters related to colon carcinogenesis in rats. WCPT were administered to F344 rats at a dose of 14 or 57 mg/kg/d, mixed with the diet. The higher dose is about ten times the exposure to polyphenols of a moderate drinker of red wine. In rats treated with WCPT, we measured fecal bile acids and long chain fatty acids, colon mucosa cell proliferation, apoptosis and, after administration of colon carcinogens, the number and size of aberrant crypt foci (ACF) and nuclear aberrations. Colon mucosa proliferation was not varied by chronic administration (90 d) of WCPT (14 or 57 mg/kg/d). The highest dose of WCPT decreased the number of cells in the colon crypts, but did not increase apoptosis. WCPT (57 mg/kg) administered before or after the administration of azoxymethane (AOM) did not vary the number or multiplicity of ACF in the colon. The number of nuclear aberrations (NA) in colon mucosa was studied after administration of 1,2-dimethylhydrazine (DMH) and 2-amino-3-methylimidazo (4,5-f)quinoline (IQ), colon-specific carcinogens which require metabolic activation. The effect of DMH and IQ was not varied by pre-feeding WCPT (57 mg/kg) for 10 d. Similarly, the levels of total, secondary bile acids and long chain fatty acids did not varied significantly in animals fed WCPT for 90 d. WCPT administration does not influence parameters related to colon carcinogenesis in the rat.

Evaluation of concomitant use of non-specific immunopotentiator on 172 cases of primary lung cancer (Stage III, IV) treated with radiation combined with chemotherapy

International Nuclear Information System (INIS)

Ogawa, Yasuhiro; Kimura, Shuji; Imajo, Yoshinari; Hamada, Fumio; Miyaji, Chihiro

1982-01-01

The clinical effect of concomitant use of non-specific immunopotentiator OK-432 and/or PSK was studied about 172 cases of primary lung cancer (Stage III, IV). In 91 cases in stage III, fifty percent survival period was found to be 11.5 months for 63 cases with OK-432 and/or PSK, and 7.5 months for 28 cases without immunotherapy, respectively. In 81 cases in stage IV, fifty percent survival period was found to be 6.7 months for 45 cases with OK-432 and/or PSK, and 3.3 months for 36 cases without immunotherapy, respectively. (author)

Genetic and molecular analysis of radon-induced rat lung tumours

International Nuclear Information System (INIS)

Guilly, M.N.; Joubert, Ch.; Levalois, C.; Dano, L.; Chevillard, S.

2002-01-01

We have a model of radon-induced rat lung tumours, which allow us to analyse the cytogenetic and molecular alterations of the tumours. The aim is to better understand the mechanisms of radio-induced carcinogenesis and to define if it exists a specificity of radio-induced genetic alterations as compared to the genetic alterations found in the sporadic tumours. We have started our analysis by developing global cytogenetic and molecular approaches. We have shown that some alterations are recurrent. The genes that are potentially involved are the oncogene MET and the tumour suppressor Bene p16, which are also frequently altered in human lung tumours. Simultaneously, we have focussed our analysis by targeting the search of mutation in the tumour suppressor gene TP3. We have found that 8 of 39 tumours were mutated by deletion in the coding sequence of TP53. This high frequency of deletion, which is not observed in the human p53 mutation database could constitute a signature of radio-induced alterations. On this assumption, this type of alteration should not be only found on TP53 Bene but also in other suppressor genes which are inactivated by a mutation such as p16 for example. The work we are carrying out on radio-induced tumours among humans and animals is directed to this end. (author)

[Observation on alpha-SMA during Erigeron Breviscapus (Vant) Hand-Mazz obstructs the evolution of carcinogenesis of golden hamster cheek pouch].

Science.gov (United States)

Zhou, C T; Zhang, S L; Ding, R Y; Hua, L; Zhong, W J

2000-06-01

To observe dynamically that Erigeron Breviscapus (Vant) Hand-Mazz (HEr) affects the expression of alpha-smooth muscle actin (alpha-SMA). To discuss the probable mechanism of obstructing leukoplakia carcinogenesis of this medicine. 120 golden hamsters were randomly divided into model group (48), HEr group (48) and control group (6). HEr was applied to obstruct the evolution of carcinogenesis of golden hamster cheek pouch. Immunohistochemistry was used to detect the expression level of alpha-SMA with cheek pouch specimen that besmears DMBA in 4-9 weeks. Results were compared with model group. Vessel density dyed with alpha-SMA continuously of HEr group was 65.76 significantly higher than that of model group 42.12 (P<0.001). High classification cases in HEr group were much more than model group when cases were divided into five groups as follow: 100%, 50%, 20%, 10%, 3% (P<0.01). HEr can raise the expression level of alpha-SMA exactly during the evolution of leukoplakia carcinogenesis of golden hamster, which shows that this medicine obstructs carcinogenesis by keeping the normal physiological function of vascular myoepithelial cell and integrity of vascular basement membrane.

Radioimmunoscintigraphy in lung cancer diagnosing

International Nuclear Information System (INIS)

Hadjikostova, H.

1999-01-01

As the lung cancer is the leading cause of death from cancer at males, the exact staging is essential. Monoclonal antibodies marked with radionuclides like 131 I, 111 In, 99m Tc, etc., allow detecting and staging the small cell lung cancer with sensibility 90%, specificity 45% and accuracy 85%. It is suggested this method to be applied simultaneously with computerized tomography. The diagnostic possibility of radioimmunoscintigraphy (RIS) in earlier detection, recurrence or metastasis as well as follow up the effect of therapy performed at patients with lung cancer are reviewed. RIS is performed with IODOMAB-R-2 (Sorin Biomedica) 131 I antiCEA Mob F(ab') 2 , dose 92.5-185 MBq. Planar images were performed 72 hours after i.v. injection. Four patients with epidermoid squamous cell cancer were examined. Positive results were obtained at 3 patients and one false negative. In general sensitivity of radioimmunoscintigraphy of lung cancer is 75-90%. However there are difficulties at its application linked with necessity of permanent availability of radiolabelled antibodies with high specific activity at the moment of their injection. Despite all radioimmunoscintigraphy is developing as an useful diagnostic method for evaluation and follow up of lung cancer patients

Strawberry Phytochemicals Inhibit Azoxymethane/Dextran Sodium Sulfate-Induced Colorectal Carcinogenesis in Crj: CD-1 Mice

Directory of Open Access Journals (Sweden)

Ni Shi

2015-03-01

Full Text Available Human and experimental colon carcinogenesis are enhanced by a pro-inflammatory microenvironment. Pharmacologically driven chemopreventive agents and dietary variables are hypothesized to have future roles in the prevention of colon cancer by targeting these processes. The current study was designed to determine the ability of dietary lyophilized strawberries to inhibit inflammation-promoted colon carcinogenesis in a preclinical animal model. Mice were given a single i.p. injection of azoxymethane (10 mg kg−1 body weight. One week after injection, mice were administered 2% (w/v dextran sodium sulfate in drinking water for seven days and then an experimental diet containing chemically characterized lyophilized strawberries for the duration of the bioassay. Mice fed control diet, or experimental diet containing 2.5%, 5.0% or 10.0% strawberries displayed tumor incidence of 100%, 64%, 75% and 44%, respectively (p < 0.05. The mechanistic studies demonstrate that strawberries reduced expression of proinflammatory mediators, suppressed nitrosative stress and decreased phosphorylation of phosphatidylinositol 3-kinase, Akt, extracellular signal-regulated kinase and nuclear factor kappa B. In conclusion, strawberries target proinflammatory mediators and oncogenic signaling for the preventive efficacies against colon carcinogenesis in mice. This works supports future development of fully characterized and precisely controlled functional foods for testing in human clinical trials for this disease.

The incorporation of SPECT functional lung imaging into inverse radiotherapy planning for non-small cell lung cancer

International Nuclear Information System (INIS)

Christian, Judith A.; Partridge, Mike; Nioutsikou, Elena; Cook, Gary; McNair, Helen A.; Cronin, Bernadette; Courbon, Frederic; Bedford, James L.; Brada, Michael

2005-01-01

Background and purpose: Patients with non-small cell lung cancer (NSCLC) often have inhomogeneous lung perfusion. Radiotherapy planning computed tomography (CT) scans have been accurately co-registered with lung perfusion single photon emission computed tomography (SPECT) scans to design radiotherapy treatments which limit dose to healthy 'perfused' lung. Patients and methods: Patients with localised NSCLC had CT and SPECT scans accurately co-registered in the planning system. The SPECT images were used to define a volume of perfused 'functioning' lung (FL). Inverse planning software was used to create 3D-conformal plans, the planning objective being either to minimise the dose to whole lungs (WL) or to minimise the dose to FL. Results: Four plans were created for each of six patients. The mean difference in volume between WL and FL was 1011.7 cm 3 (range 596.2-1581.1 cm 3 ). One patient with bilateral upper lobe perfusion deficits had a 16% reduction in FLV 2 (the percentage volume of functioning lung receiving ≥20 Gy). The remaining patients had inhomogeneous perfusion deficits such that inverse planning was not able to sufficiently optimise beam angles to avoid functioning lung. Conclusion: SPECT perfusion images can be accurately co-registered with radiotherapy planning CT scans and may be helpful in creating treatment plans for patients with large perfusion deficits

Bovine milk-derived α-lactalbumin inhibits colon inflammation and carcinogenesis in azoxymethane and dextran sodium sulfate-treated mice.

Science.gov (United States)

Yamaguchi, Makoto; Takai, Shoko; Hosono, Akira; Seki, Taiichiro

2014-01-01

Cyclooxygenase-2 is expressed early in colon carcinogenesis and plays crucial role in the progress of the disease. Recently, we found that α-lactalbumin had anti-inflammatory activity by inhibiting cyclooxygenase-2. In experiment 1, we investigated the effects of α-lactalbumin on the colon carcinogenesis initiated with azoxymethane (AOM) followed by promotion with dextran sodium sulfate (DSS) in mice. Dietary treatment with α-lactalbumin decreased fecal occult blood score at 3 days after DSS intake. α-Lactalbumin also decreased the colon tumor at week 9. In experiment 2, AOM-treated mice were sacrificed at 7 days after DSS intake. The plasma and colon prostaglandin E2 (PGE2) levels in AOM/DSS-treated mice were higher than those in the DSS-treated mice without initiation by AOM. α-Lactalbumin decreased PGE2 in both plasma and colon. These results suggest that α-lactalbumin effectively inhibited colon carcinogenesis, and the inhibition may be due to the decreased PGE2 by inhibiting cyclooxygenase-2 at cancer promotion stages.

Perspectives in the paradigm of radiation-induced carcinogenesis

International Nuclear Information System (INIS)

Sugakhara, T.; Vatanabe, M.; Niva, O.; Nikajdo, O.

1995-01-01

Carcinogenesis is analysed as a multistage process consisting of initiation, promotion and progression. This model includes the mutation of oncogenes and the loss of hetrezygosity by tumor-suppressor genes. The threshold concept of radiation cancerogenesis is proposed, under which ionizing radiation can induce in somatic cell genetic effects a s result of DNA damage and epigenetic changes as well. The epigenetic changes (through DNA or cytoplasma) can be stabilized as mutations observed in many cancer cells and play a dominant role in radiation cancerogenesis induction. The ration of epigenetic and genetic effects largely depends on radiation doses

The PTEN/NRF2 Axis Promotes Human Carcinogenesis

DEFF Research Database (Denmark)

Rojo, Ana I; Rada, Patricia; Mendiola, Marta

2014-01-01

and tumorigenic advantage. Tissue microarrays from endometrioid carcinomas showed that 80% of PTEN-negative tumors expressed high levels of NRF2 or its target heme oxygenase-1 (HO-1). INNOVATION: These results uncover a new mechanism of oncogenic activation of NRF2 by loss of its negative regulation by PTEN/GSK-3....../β-TrCP that may be relevant to a large number of tumors, including endometrioid carcinomas. CONCLUSION: Increased activity of NRF2 due to loss of PTEN is instrumental in human carcinogenesis and represents a novel therapeutic target. Antioxid. Redox Signal. 21, 2498-2514....

The pleiotropic roles of transforming growth factor beta inhomeostasis and carcinogenesis of endocrine organs.

Energy Technology Data Exchange (ETDEWEB)

Fleisch, Markus C.; Maxwell, Christopher A.; Barcellos-Hoff,Mary-Helen

2006-01-13

Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary gland. This review will address the role of TGF-beta in regulating hormone dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition (EMT), will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, and the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.

Use of medaka as a tool in studies of radiation effects and chemical carcinogenesis

International Nuclear Information System (INIS)

Hyodo-Taguchi, Y.; Aoki, K.; Matsudaira, H.

1982-01-01

The medaka, Oryzias latipes, a small freshwater oviparous fish, is common in Japan and found in some parts of Asia. Adult fish are 3.0-3.5 cm long and weigh 0.5-0.7 g. The small fish have been used extensively in this laboratory for analysis of radiation effects and for study of chemical carcinogenesis. These fish are relatively easy to rear and their reproductive biology is well known. Recently, inbred strains of the fish have been established by full sister-brother mating. In this report, we will review experimental results using medaka in studies of : 1) radiation effects on spermatogenesis, and 2) induction of hepatic tumors by MAM acetate, we will also review use of medaka in related studies of radiation effects and chemical carcinogenesis. (author)

Expression of NR1I3 in mouse lung tumors induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone

International Nuclear Information System (INIS)

Fukumasu, H.; Cordeiro, Y.G.; Rochetti, A.L.; Barra, C.N.; Sámora, T.S.; Strefezzi, R.F.; Dagli, M.L.Z.

2015-01-01

Nuclear receptor subfamily 1, group I, member 3 (NR1I3) is reported to be a possible novel therapeutic target for some cancers, including lung, brain and hematopoietic tumors. Here, we characterized expression of NR1I3 in a mouse model of lung carcinogenesis induced by 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone (NNK), the most potent tobacco carcinogen. Lung tumors were collected from mice treated with NNK (400 mg/kg) and euthanized after 52 weeks. Benign and malignant lesions were formalin-fixed and paraffin-embedded for histology and immunohistochemistry, with samples snap-frozen for mRNA analysis. Immunohistochemically, we found that most macrophages and type I and II pneumocytes expressed NR1I3, whereas fibroblasts and endothelial cells were NR1I3 − . Compared with benign lesions, malignant lesions had less NR1I3 + tumor cells. Gene expression analysis also showed an inverse correlation between NR1I3 mRNA expression and tumor size (P=0.0061), suggesting that bigger tumors expressed less NR1I3 transcripts, in accordance with our immunohistochemical NR1I3 tests. Our results indicate that NR1I3 expression decreased during progression of malignant lung tumors induced by NNK in mice

Expression of NR1I3 in mouse lung tumors induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone

Energy Technology Data Exchange (ETDEWEB)

Fukumasu, H.; Cordeiro, Y.G.; Rochetti, A.L.; Barra, C.N.; Sámora, T.S.; Strefezzi, R.F. [Laboratório de Oncologia Comparada e Translacional, Departmento de Medicina Veterinária, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, Pirassununga, SP (Brazil); Dagli, M.L.Z. [Laboratório de Oncologia Experimental e Comparada, Departmento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil)

2015-02-13

Nuclear receptor subfamily 1, group I, member 3 (NR1I3) is reported to be a possible novel therapeutic target for some cancers, including lung, brain and hematopoietic tumors. Here, we characterized expression of NR1I3 in a mouse model of lung carcinogenesis induced by 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone (NNK), the most potent tobacco carcinogen. Lung tumors were collected from mice treated with NNK (400 mg/kg) and euthanized after 52 weeks. Benign and malignant lesions were formalin-fixed and paraffin-embedded for histology and immunohistochemistry, with samples snap-frozen for mRNA analysis. Immunohistochemically, we found that most macrophages and type I and II pneumocytes expressed NR1I3, whereas fibroblasts and endothelial cells were NR1I3{sup −}. Compared with benign lesions, malignant lesions had less NR1I3{sup +} tumor cells. Gene expression analysis also showed an inverse correlation between NR1I3 mRNA expression and tumor size (P=0.0061), suggesting that bigger tumors expressed less NR1I3 transcripts, in accordance with our immunohistochemical NR1I3 tests. Our results indicate that NR1I3 expression decreased during progression of malignant lung tumors induced by NNK in mice.

Percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma under C-arm cone beam CT guidance.

Science.gov (United States)

Amouyal, G; Pernot, S; Déan, C; Cholley, B; Scotté, F; Sapoval, M; Pellerin, O

2017-11-01

The aim of this study was to assess the feasibility, safety and efficacy of percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma using C-arm cone beam computed tomography (CBCT) guidance. This single-center prospective observational study was performed from August 2013 to August 2016, and included consecutive patients referred for radiofrequency ablation of lung metastases from colorectal cancer. Radiofrequency ablation procedures were performed under C-arm CBCT guidance. Feasibility was assessed by probe accuracy placement, time to accurate placement and number of C-arm CBCT acquisitions to reach the target lesion. Safety was assessed by the report of adverse event graded using the common terminology criteria for adverse events (CTCAE-V4.0). Efficacy was assessed by metastases response rate using RECIST 1.1 and 18 FDG-PET-CT tumor uptake at 6months. Fifty-four consecutive patients (32 men, 22 women) with a mean age of 63±8 (SD) years (range: 51-81years) with a total of 56 lung metastasis from colorectal metastases were treated in a single session. The mean tumor diameter was 25.6±4.5 (SD)mm (range: 17-31mm). Median time to insert the needle into the target lesion was 10min (range: 5-25min). Median number of needles repositioning and C-arm CBCT acquisition per patient was 1 (range: 0-3) and 4 (range: 3-6) respectively. The accuracy for radiofrequency ablation probe placement was 2±0.2 (SD)mm (range: 0-9mm). Pneumothorax requiring chest tube placement occurred in one patient (CTCAE-V4.0 grade 3). At 6months, all patients were alive with tumor response rate of -27% and had no significant activity on the 18 FDG-PET CT follow-up. Percutaneous radiofrequency ablation of lung metastases from colorectal cancer under C-arm CBCT guidance is feasible and safe, with immediate and short-term results similar to those obtained using conventional CT guidance. Copyright © 2017 Éditions françaises de radiologie. Published by Elsevier Masson SAS

Interaction between APC and Fen1 during breast carcinogenesis.

Science.gov (United States)

Narayan, Satya; Jaiswal, Aruna S; Law, Brian K; Kamal, Mohammad A; Sharma, Arun K; Hromas, Robert A

2016-05-01

Aberrant DNA base excision repair (BER) contributes to malignant transformation. However, inter-individual variations in DNA repair capacity plays a key role in modifying breast cancer risk. We review here emerging evidence that two proteins involved in BER - adenomatous polyposis coli (APC) and flap endonuclease 1 (Fen1) - promote the development of breast cancer through novel mechanisms. APC and Fen1 expression and interaction is increased in breast tumors versus normal cells, APC interacts with and blocks Fen1 activity in Pol-β-directed LP-BER, and abrogation of LP-BER is linked with cigarette smoke condensate-induced transformation of normal breast epithelial cells. Carcinogens increase expression of APC and Fen1 in spontaneously immortalized human breast epithelial cells, human colon cancer cells, and mouse embryonic fibroblasts. Since APC and Fen1 are tumor suppressors, an increase in their levels could protect against carcinogenesis; however, this does not seem to be the case. Elevated Fen1 levels in breast and lung cancer cells may reflect the enhanced proliferation of cancer cells or increased DNA damage in cancer cells compared to normal cells. Inactivation of the tumor suppressor functions of APC and Fen1 is due to their interaction, which may act as a susceptibility factor for breast cancer. The increased interaction of APC and Fen1 may occur due to polypmorphic and/or mutational variation in these genes. Screening of APC and Fen1 polymorphic and/or mutational variations and APC/Fen1 interaction may permit assessment of individual DNA repair capability and the risk for breast cancer development. Such individuals might lower their breast cancer risk by reducing exposure to carcinogens. Stratifying individuals according to susceptibility would greatly assist epidemiologic studies of the impact of suspected environmental carcinogens. Additionally, a mechanistic understanding of the interaction of APC and Fen1 may provide the basis for developing new and

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

Science.gov (United States)

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

2008-01-01

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

Mesothelioma and lung cancer mortality: a historical cohort study among asbestosis workers in Hong Kong.

Science.gov (United States)

Chen, Minghui; Tse, Lap Ah; Au, Ronald K F; Yu, Ignatius T S; Wang, Xiao-rong; Lao, Xiang-qian; Au, Joseph Siu-kei

2012-05-01

To investigate the mortality pattern among a cohort of workers with asbestosis in Hong Kong, with special emphases on mesothelioma and lung cancer. All 124 male workers with confirmed asbestosis in Hong Kong during 1981-2008 were followed up to December 31, 2008 to ascertain the vital status and causes of death. Standardized mortality ratio (SMR) for each underlying cause of death was calculated by using person-year method. Axelson's indirect method was applied to adjust for the potential confounding effect of cigarette smoking. A total of 86 deaths were observed after 432.8 person-years of observations. The SMR for overall mortality (6.06, 95% CI: 4.90-7.51) increased significantly. The elevated risk of deaths from all cancers (7.53, 95% CI: 5.38-10.25) was mainly resulted from a significantly excess risk from lung cancer (SMR=7.91, 95% CI: 4.32-13.29, 14 deaths) and mesothelioma (SMR=6013.63, 95% CI: 3505.95-9621.81, 17 deaths). The SMR for lung cancer retained statistically significant after adjustment of smoking. An increased smoking adjusted SMR was also suggested for all heart diseases (2.32, 95% CI: 0.93-4.79, 7 deaths) and acute myocardial infarction (3.10, 95% CI: 0.84-7.94, 4 deaths), though the statistical significance was borderline. We found a positive association with net years of exposure to asbestos for mesothelioma and lung cancer. Our study provided further evidence on the carcinogenesis of asbestos/asbestosis with the risk of deaths from lung cancer and mesothelioma. This study also provided a preliminary support for a possible link between asbestosis and heart disease, but power is limited. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Role of atypical chemokine receptor ACKR2 in experimental oral squamous cell carcinogenesis.

Science.gov (United States)

da Silva, Janine Mayra; Dos Santos, Tálita Pollyanna Moreira; Saraiva, Adriana Machado; Fernandes de Oliveira, Ana Laura; Garlet, Gustavo Pompermaier; Batista, Aline Carvalho; de Mesquita, Ricardo Alves; Russo, Remo Castro; da Silva, Tarcília Aparecida

2018-03-14

Chemokines and chemokine receptors are critical in oral tumourigenesis. The atypical chemokine receptor ACKR2 is a scavenger of CC chemokines controlling the availability of these molecules at tumour sites, but the role of ACKR2 in the context of oral carcinogenesis is unexplored. In this study, wild-type (WT) and ACKR2 deficient mice (ACKR2 -/- ) were treated with chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) for induction of oral carcinogenesis. Tongues were collected for macro and microscopic analysis and to evaluate the expression of ACKRs, CC chemokines and its receptors, inflammatory cytokines, angiogenic factors, adhesion molecules and extracellular matrix components. An increased expression of ACKR2 in squamous cell carcinoma (SCC) lesions of 4NQO-treated WT mice was observed. No significant differences were seen in the ACKR1, ACKR3 and ACKR4 mRNA expression comparing SCC lesions from WT and ACKR2 -/- treated mice. Significantly higher expression of CCL2, IL-6 and IL-17 was detected in ACKR2 -/- treated mice. In contrast, the expression of other CC-chemokines, and receptors, angiogenic factors, adhesion molecules and extracellular matrix components were similarly increased in SCC lesions of both groups. Clinical and histopathological analysis revealed no differences in inflammatory cell recruitment and in the SCC incidence comparing WT and ACKR2 -/- treated mice. The results suggest that ACKR2 expression regulates inflammation in tumour-microenvironment but the absence of ACKR2 does not impact chemically-induced oral carcinogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Intersections of lung progenitor cells, lung disease and lung cancer.

Science.gov (United States)

Kim, Carla F

2017-06-30

The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

Intersections of lung progenitor cells, lung disease and lung cancer

Directory of Open Access Journals (Sweden)

Carla F. Kim

2017-06-01

Full Text Available The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

Bacterial infection increases risk of carcinogenesis by targeting mitochondria

DEFF Research Database (Denmark)

Strickertsson, Jesper A.B.; Desler, Claus; Rasmussen, Lene Juel

2017-01-01

pathways, and compares the impact of the bacterial alteration of mitochondrial function to that of cancer. Bacterial virulence factors have been demonstrated to induce mutations of mitochondrial DNA (mtDNA) and to modulate DNA repair pathways of the mitochondria. Furthermore, virulence factors can induce...... or impair the intrinsic apoptotic pathway. The effect of bacterial targeting of mitochondria is analogous to behavior of mitochondria in a wide array of tumours, and this strongly suggests that mitochondrial targeting of bacteria is a risk factor for carcinogenesis....

The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia.

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Chao Agnes Hsiung

2010-08-01

Full Text Available Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10(-7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30 x 10(-11. This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38 x 10(-11. A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60 x 10(-20, allelic risk = 1.54, 95% Confidence Interval (CI 1.41-1.68. Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40-1.87, and 2.35 (95% CI: 1.95-2.83, respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.

Prediction of postoperative respiratory function of lung cancer patients using quantitative lung scans

International Nuclear Information System (INIS)

Konishi, Hiroshi

1982-01-01

Quantitative sup(99m)Tc-MISA inhalation scan and sup(99m)Tc-MAA perfusion scan were performed in 35 patients with lung cancer who underwent lobectomies. Quantitative 133 Xe ventilation-perfusion scans were also performed in 34 patients with lung cancer who underwent lobectomies. To predict functional loss after lobectomy, the proportion of the No. of segments in the lobe to be resected to the No. of entire segments of that lung was provided for the study. Postoperative FVC, FEVsub(1.0) and MVV were predicted in the study, and which were compared to the respiratory function at one month after operation and more than four months after operation. The predicted postoperative respiratory function was highly correlated with the actually observed postoperative respiratory function (0.7413 lt r lt 0.9278, p lt 0.001). In this study, the postoperative respiratory function was proven to be quite accurately predicted preoperatively with combination of quantitative lung scans and spirometric respiratory function. Therefore this method is useful not only for judgement of operative indication but also for choice of operative method and for counterplan of postoperative respiratory insufficiency. (J.P.N.)

Plutonium deposits in lung tissues of Filipinos

International Nuclear Information System (INIS)

Natera, E.S.; Palad, L.J.H.; Ignacio, L.M.

1989-01-01

This initial report on the plutonium concentration in lungs of Filipino adults is based on four samples. The data obtained suggest that the average of concentration in lungs of Filipinos is similar to that observed in other countries. This could be attributed to fallout resulting from nuclear test explosions conducted by neighboring countries. The result of this study will be useful in initiating the establishment of plutonium burden of Filipinos. (ELC). 2 tabs

Expression profile of microRNA-146a along HPV-induced multistep carcinogenesis: a study in HPV16 transgenic mice.

Science.gov (United States)

Araújo, Rita; Santos, Joana M O; Fernandes, Mara; Dias, Francisca; Sousa, Hugo; Ribeiro, Joana; Bastos, Margarida M S M; Oliveira, Paula A; Carmo, Diogo; Casaca, Fátima; Silva, Sandra; Medeiros, Rui; Gil da Costa, Rui M

2018-02-01

Persistent human papillomavirus (HPV) infection is associated with the development of certain types of cancer and the dysregulation of microRNAs has been implicated in HPV-associated carcinogenesis. This is the case of microRNA-146a (miR-146a), which is thought to regulate tumor-associated inflammation. We sought to investigate the expression levels of miR-146a during HPV16-mediated carcinogenesis using skin samples from K14-HPV16 transgenic mice which develop the consecutive phases of the carcinogenesis process. Female transgenic (HPV +/- ) and wild-type (HPV -/- ) mice were sacrificed at 24-26 weeks-old or 28-30 weeks-old. Chest and ear skin samples from HPV +/- and HPV -/- mice were histologically classified and used for microRNA extraction and quantification by qPCR. Chest skin samples from 24 to 26 weeks-old HPV +/- mice presented diffuse epidermal hyperplasia and only 22.5% showed multifocal dysplasia, while at 28-30 weeks-old all (100.0%) HPV +/- animals showed epidermal dysplasia. All HPV +/- ear skin samples showed carcinoma in situ (CIS). MiR-146a expression levels were higher in HPV +/- compared to HPV -/- mice (p = 0.006). There was also an increase in miR-146a expression in dysplastic skin lesions compared with hyperplasic lesions (p = 0.011). Samples showing CIS had a significant decrease in miR-146a expression when compared to samples showing epidermal hyperplasia (p = 0.018) and epidermal dysplasia (p = 0.009). These results suggest that HPV16 induces the overexpression of miR-146a in the initial stages of carcinogenesis (hyperplasia and dysplasia), whereas decreases its expression at later stages (CIS). Taken together, these data implicate and suggest different roles of miR-146a in HPV-mediated carcinogenesis.

A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer

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Yang, Qiaoyuan [Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182 (China); Xu, Enwu [Department of Thoracic Surgery, General Hospital of Guangzhou Military Command of Chinese People' s Liberation Army, Guangzhou 510010 (China); Dai, Jiabin; Liu, Binbin; Han, Zhiyuan; Wu, Jianjun; Zhang, Shaozhu; Peng, Baoying [Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182 (China); Zhang, Yajie [Department of Pathology, Guangzhou Medical University, Guangzhou 510182 (China); Jiang, Yiguo, E-mail: jiangyiguo@vip.163.com [Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182 (China)

2015-06-01

Lung cancer is the most common form of cancer throughout the world. The specific targeting of long noncoding RNAs (lncRNAs) by resveratrol opened a new avenue for cancer chemoprevention. In this study, we found that 21 lncRNAs were upregulated and 19 lncRNAs were downregulated in lung cancer A549 cells with 25 μmol/L resveratrol treatment determined by microarray analysis. AK001796, the lncRNA with the most clearly altered expression, was overexpressed in lung cancer tissues and cell lines, but its expression was downregulated in resveratrol-treated lung cancer cells. By monitoring cell proliferation and growth in vitro and tumor growth in vivo, we observed a significant reduction in cell viability in lung cancer cells and a slow growth in the tumorigenesis following AK001796 knockdown. We also found that AK001796 knockdown caused a cell-cycle arrest, with significant increases in the percentage of cells in G{sub 0}/G{sub 1} in lung cancer cells. By using cell cycle pathway-specific PCR arrays, we detected changes in a number of cell cycle-related genes related to lncRNA AK001796 knockdown. We further investigated whether AK001796 participated in the anticancer effect of resveratrol and the results showed that reduced lncRNA AK001796 level potentially impaired the inhibitory effect of resveratrol on cell proliferation. To our knowledge, this is the first study to report the changes in an lncRNA expression profile induced by resveratrol in lung cancer. - Highlights: • LncRNA AK001796 played an oncogenic role in lung carcinogenesis. • LncRNA AK001796 was downregulated in resveratrol-treated lung cancer cells. • LncRNA AK001796 was involved in the inhibition of cell growth by resveratrol.

A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer

International Nuclear Information System (INIS)

Yang, Qiaoyuan; Xu, Enwu; Dai, Jiabin; Liu, Binbin; Han, Zhiyuan; Wu, Jianjun; Zhang, Shaozhu; Peng, Baoying; Zhang, Yajie; Jiang, Yiguo

2015-01-01

Lung cancer is the most common form of cancer throughout the world. The specific targeting of long noncoding RNAs (lncRNAs) by resveratrol opened a new avenue for cancer chemoprevention. In this study, we found that 21 lncRNAs were upregulated and 19 lncRNAs were downregulated in lung cancer A549 cells with 25 μmol/L resveratrol treatment determined by microarray analysis. AK001796, the lncRNA with the most clearly altered expression, was overexpressed in lung cancer tissues and cell lines, but its expression was downregulated in resveratrol-treated lung cancer cells. By monitoring cell proliferation and growth in vitro and tumor growth in vivo, we observed a significant reduction in cell viability in lung cancer cells and a slow growth in the tumorigenesis following AK001796 knockdown. We also found that AK001796 knockdown caused a cell-cycle arrest, with significant increases in the percentage of cells in G 0 /G 1 in lung cancer cells. By using cell cycle pathway-specific PCR arrays, we detected changes in a number of cell cycle-related genes related to lncRNA AK001796 knockdown. We further investigated whether AK001796 participated in the anticancer effect of resveratrol and the results showed that reduced lncRNA AK001796 level potentially impaired the inhibitory effect of resveratrol on cell proliferation. To our knowledge, this is the first study to report the changes in an lncRNA expression profile induced by resveratrol in lung cancer. - Highlights: • LncRNA AK001796 played an oncogenic role in lung carcinogenesis. • LncRNA AK001796 was downregulated in resveratrol-treated lung cancer cells. • LncRNA AK001796 was involved in the inhibition of cell growth by resveratrol

Fifty-four Years of Adventures in Infrared Astronomy

Science.gov (United States)

Becklin, Eric Eric

2018-01-01

My adventures in infrared astronomy started when I was a grad student in 1965 with the discovery of an infrared-bright object (now known as the Becklin-Neugebauer Object) in the Orion Nebula. In 1966, I made the first measurements of the infrared radiation from the center of the Milky Way Galaxy. I was fortunate enough to be able to take advantage of the 2.2 micron sky survey carried out by Neugebauer and Leighton (1969), which produced many remarkable discoveries, the most spectacular being the heavily dust-embedded carbon star IRC+10216, thebrightest object in the sky at 5 microns outside the solar system. In the 1970’s there was a growth in Infrared astronomy with the availability of many new facilities such as the Kuiper Airborne Observatory, (KAO) which I used extensively with Mike Werner and Ian Gatley for many unique observations. In 1977, I moved to Hawaii to work on the NASA IRTF 3- meter telescope. Many discoveries were made, including the first direct measurements of the rings of Jupiter at 2.2 microns (with Gareth Wynn-Williams) and the discovery of the first L dwarf star around a white dwarf (with Ben Zuckerman). In the 1980’s the introduction of large format arrays changed the way we did infrared astronomy. With Ian McLean, I moved to UCLA in 1990 to start the IR lab and get involved in Keck development and science. In 1995, Andrea, Ghez, Mark Morris and I started looking for evidence of a possible massive Black Hole in the Galactic Center. Spectacular observations using the Keck10 meter telescopes with large format near-infrared arrays and adaptive optics led to the confirmation of the presence of such a black hole and an estimate of its mass (4xE6 M (Sun)). In 1996, I began working on the Stratospheric Observatory For Infrared Astronomy (SOFIA) and I will finish my talk by discussing SOFIA observations of the ring of dust and gas orbiting the massive black hole in the center

Cyclooxygenase-2 inhibition in colon experimental carcinogenesis Inhibición de la ciclooxigenasa-2 en la carcinogénesis cólica experimental

Directory of Open Access Journals (Sweden)

J. F. Noguera Aguilar

2005-09-01

Full Text Available Background: an overexpression of cyclooxygenase-2 (COX-2 has been seen in colon tumors; therefore, COX-2 specific inhibitors may be used as preventive agents. The aim of this study was to investigate the effect of both selective and non-selective COX-2 inhibitors on the incidence of colonic tumors in a model of chemical carcinogenesis in the rat. Design: experimental study with 65 male Sprague-Dawley rats randomly assigned to one of four groups: (a control (n = 20, with chemical carcinogenesis using 1-2 dimethylhydrazine (1-2 DMH; (b acetylsalicylic acid (ASA (n = 15, with chemical carcinogenesis and the addition of ASA at 30 mg/kg; (c low-dose rofecoxib (n = 15, with chemical carcinogenesis and the addition of rofecoxib at a dose of 1.2 mg/kg; (d high-dose rofecoxib (n = 15, with carcinogenesis and the addition of rofecoxib at 3 mg/kg. Carcinogenic induction was performed with 1-2 DMH at a weekly dose of 25 mg/kg for 18 weeks. The main parameter evaluated was percentage of neoplastic colonic tissue, which relates tumor surface area to colon surface area. Results: rofecoxib at a dose of 3 mg/kg significantly reduced chemical colon carcinogenesis in rats (p Introducción: se ha comprobado a nivel clínico y experimental la existencia de sobreexpresión de la ciclooxigenasa-2 (COX-2 en los tumores de colon, por lo que los inhibidores de dicha enzima podrían tener un efecto preventivo. El objetivo del estudio es investigar el efecto de la inhibición de la ciclooxigenasa en un modelo de carcinogénesis cólica farmacológica en la rata. Material y métodos: estudio experimental en 65 ratas Sprague-Dawley macho, asignadas a uno de los grupos: control (n = 20, con carcinogénesis farmacológica con 1-2 dimetilhidrazina; grupo ácido acetilsalicílico (n = 15, con carcinogénesis y adición de AAS, grupo Inhibidores COX-2 a bajas dosis (n = 15, con carcinogénesis y adición de rofecoxib a dosis de 1,2 mg/kg, y grupo Inhibidores COX-2 a altas dosis

Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression.

Science.gov (United States)

Bonkhoff, Helmut

2018-01-01

The androgen receptor (AR) is the classical target for prostate cancer prevention and treatment, but more recently estrogens and their receptors have also been implicated in prostate cancer development and tumor progression. Recent experimental and clinical data were reviewed to elucidate pathogenetic mechanisms how estrogens and their receptors may affect prostate carcinogenesis and tumor progression. The estrogen receptor beta (ERβ) is the most prevalent ER in the human prostate, while the estrogen receptor alpha (ERα) is restricted to basal cells of the prostatic epithelium and stromal cells. In high grade prostatic intraepithelial neoplasia (HGPIN), the ERα is up-regulated and most likely mediates carcinogenic effects of estradiol as demonstrated in animal models. The partial loss of the ERβ in HGPIN indicates that the ERβ acts as a tumor suppressor. The tumor promoting function of the TMPRSS2-ERG fusion, a major driver of prostate carcinogenesis, is triggered by the ERα and repressed by the ERβ. The ERβ is generally retained in hormone naïve and metastatic prostate cancer, but is partially lost in castration resistant disease. The progressive emergence of the ERα and ERα-regulated genes (eg, progesterone receptor (PR), PS2, TMPRSS2-ERG fusion, and NEAT1) during prostate cancer progression and hormone refractory disease suggests that these tumors can bypass the AR by using estrogens and progestins for their growth. In addition, nongenomic estrogen signaling pathways mediated by orphan receptors (eg, GPR30 and ERRα) has also been implicated in prostate cancer progression. Increasing evidences demonstrate that local estrogen signaling mechanisms are required for prostate carcinogenesis and tumor progression. Despite the recent progress in this research topic, the translation of the current information into potential therapeutic applications remains highly challenging and clearly warrants further investigation. © 2017 Wiley Periodicals, Inc.

Carcinogenesis--a synopsis of human experience with external exposure in medicine

International Nuclear Information System (INIS)

Boice, J.D. Jr.

1988-01-01

Studies in the 1980s of medically irradiated populations have increased our knowledge of radiation carcinogenesis. (1) Investigations of prenatal x-ray exposures, especially in twins, provide evidence that very low doses of ionizing radiation may cause cancer in humans. (2) Fractionated doses appear as effective as single exposures of the same total dose in causing breast cancer, but seem less effective for lung cancer. (3) Excess breast cancers can occur among women exposed under age 10, indicating that the immature breast is susceptible to the carcinogenic action of radiation. (4) Moderate doses on the order of 1 Gy to the brains of children can cause tumors later in life; moderately high doses to the skin can cause cancer when followed by frequent exposure to ultraviolet light. (5) Radiotherapy for cervical cancer can increase the rate of subsequent leukemia with the best fitting dose-response functions including a negative exponential term to account for cell-killing. (6) Low-dose exposures of about 10 cGy may increase the risk of thyroid cancer. (7) Second cancers following radiotherapy for a variety of cancers occur primarily among long-term survivors. (8) Radiotherapy may not significantly increase the risk of leukemia following childhood cancer, whereas chemotherapy with alkylating agents is a major risk factor. (9) Bone cancer occurs after high-dose radiotherapy for childhood cancer, but children with retinoblastoma are not more susceptible to radiation-induced disease than children with other malignancies. (10) High-dose external beam therapy can cause thyroid cancer. (11) Studies of cervical cancer patients indicate that the risk of radiation-induced second malignancies follows a time-response model consistent with a constant multiplication of the underlying background incidence. 83 references

Studies on the repair of double strand break of DNA and cellular carcinogenesis, and consideration on the concept of extinction of nuclear power

International Nuclear Information System (INIS)

Teraoka, Hirobumi

2013-01-01

This paper describes the relationship between the repair of double strand break (DSB) of DNA and cellular carcinogenesis mainly on author's investigations, and his recent thought aiming at the extinction of nuclear power. The molecular repairing system is explained about DNA DSB induced by radiation and chemicals. When DSB occurs, nucleosome consisting from 4 core-histones participates to link the broken ends and then repair mechanisms of homologous recombination (HRR) and non-homologous end joining (NHEJ) begin to work. The latter is dominant in mammalians. Thus the genetic defect in these systems of DSB response and repair is a course of disorders such as ataxia telangiectasia (AT) (DSB sensor defect), genetic breast cancer (HRR defect), and radiosensitive-severe combined immunodeficiency (RS-SCID) (NHEJ defect), all of which result in cancer formation. NHEJ repair is known to be error-prone. Against multi-step carcinogenesis where accumulated gene mutations lead to the cancer formation, the author thinks chromosomal instability is one of important carcinogenic causes: the instability can be a trigger of producing cancer stem cells because the cells can be yielded from mouse embryonic stem cells where DSB is shown to participate in the process. Low dose radiation produces a small amount of DSB, to which the repair response is less sensitive at G2/M checkpoint, ultimately leading to genomic instability. Considering effects of the low dose radiation exposure above, and of the internal exposure to 3 H-thymidine beta ray in cells, of indoor Rn participating 16% of lung cancer incidence (Canadian epidemiological data) and so on, together with moral and social responsibility of scientist and technologist, the author says to have attained to the concept of the ''Extinction of Nuclear Power''. (T.T)

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

Science.gov (United States)

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

2018-02-10

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

The radioprotective effects of methylprednisolone and Sho-Saikoto on mouse lung

Energy Technology Data Exchange (ETDEWEB)

Kure, Fumio [Kyoto Prefectural Univ. of Medicine (Japan)

1992-01-01

The radioprotective effects of methylprednisolone and Sho-Saikoto (a herbal medicine) on radiation damage to lung tissue were evaluated in four main groups of female Slc-ICR mice, one control group and three groups irradiated with single doses (6 Gy, 12 Gy, 18 Gy) of {sup 60}Co gamma rays. Subgroups were established with administration of methylprednisolone and Sho-Saikoto, alone and together. Direct quantitative measurements of collagen accumulation in lung (lung fibrosis) were made by analysis of digitally processed microscopic images of Azan-Mallory stained sections 24 weeks after irradiation. Administration of methylprednisolone supressed the expected development of fibrotic lung tissue in each of the irradiated groups. In a further study, peplomycin, a lung fibrosis enhancing agent, was administered to all four groups in addition to methylprednisolone and Sho-Saikoto, alone and together. Methylprednisolone was demonstrated to be effective only in 12 Gy group. Overall, Sho-Saikoto showed a lesser degree of effect in the prevention of the fibrosis than methylprednisolone, but the administration of both was demonstrated to be more effective than either alone. (author).

Protein expression analysis of inflammation-related colon carcinogenesis

Directory of Open Access Journals (Sweden)

Yasui Yumiko

2009-01-01

Full Text Available Background: Chronic inflammation is a risk factor for colorectal cancer (CRC development. The aim of this study was to determine the differences in protein expression between CRC and the surrounding nontumorous colonic tissues in the mice that received azoxymethane (AOM and dextran sodium sulfate (DSS using a proteomic analysis. Materials and Methods: Male ICR mice were given a single intraperitoneal injection of AOM (10 mg/kg body weight, followed by 2% (w/v DSS in their drinking water for seven days, starting one week after the AOM injection. Colonic adenocarcinoma developed after 20 weeks and a proteomics analysis based on two-dimensional gel electrophoresis and ultraflex TOF/TOF mass spectrometry was conducted in the cancerous and nontumorous tissue specimens. Results: The proteomic analysis revealed 21 differentially expressed proteins in the cancerous tissues in comparison to the nontumorous tissues. There were five markedly increased proteins (beta-tropomyosin, tropomyosin 1 alpha isoform b, S100 calcium binding protein A9, and an unknown protein and 16 markedly decreased proteins (Car1 proteins, selenium-binding protein 1, HMG-CoA synthase, thioredoxin 1, 1 Cys peroxiredoxin protein 2, Fcgbp protein, Cytochrome c oxidase, subunit Va, ETHE1 protein, and 7 unknown proteins. Conclusions: There were 21 differentially expressed proteins in the cancerous tissues of the mice that received AOM and DSS. Their functions include metabolism, the antioxidant system, oxidative stress, mucin production, and inflammation. These findings may provide new insights into the mechanisms of inflammation-related colon carcinogenesis and the establishment of novel therapies and preventative strategies to treat carcinogenesis in the inflamed colon.

Chemotherapy related toxicity in locally advanced non-small cell lung cancer

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Bahl Amit

2006-01-01

Full Text Available Background: For inoperable non-small cell lung cancer combined chemotherapy and radiotherapy plays an important role as a therapeutic modality. The aim of the present study was to analyze neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and IIIB in Indian patients using Cisplatin and Etoposide combination chemotherapy. Material and methods: Forty patients of locally advanced Non small cell lung cancer received three cycles neoadjuvant chemotherapy using Injection Cisplatin and Etoposide. The patients were taken for Radical radiotherapy to a dose of 60 Gray over 30 fractions in conventional fractionation after completing chemotherapy. Chemotherapy associated toxicity was assessed using common toxicity criteria (CTC v2.0 Results: Forty patients were available for final evaluation. Median age of presentation of patients was fifty-six years. Thirteen patients had Non small cell lung cancer stage IIIA while twenty-seven patients had Stage IIIB disease. Anemia was the most common hematological toxicity observed (seen in 81% of patients. Nausea and vomiting were the most common non -hematological toxicity seen. Sensory neuropathy was seen in 38%of patients. 88% patients developed alopecia. Seven patients developed febrile neutropenias. Conclusion: Neo-adjuvant chemotherapy using Cisplatin and Etoposide continues to be a basic regimen in the Indian set up despite availability of higher molecules, since it is cost effective, well tolerated and therapeutically effective. Blood transfusions, growth factors and supportive care can be used effectively to over come toxicity associated with this regimen.

Effect of Dendrobium officinale Extraction on Gastric Carcinogenesis in Rats

OpenAIRE

Zhao, Yi; Liu, Yan; Lan, Xi-Ming; Xu, Guo-Liang; Sun, You-Zhi; Li, Fei; Liu, Hong-Ning

2016-01-01

Dendrobium officinale (Tie Pi Shi Hu in Chinese) has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg) were orally adminis...

Combination Therapy of PPAR Ligands and Inhibitors of Arachidonic Acid in Lung Cancer

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Jordi Tauler

2008-01-01

Full Text Available Lung cancer is the leading cause of cancer death in the United States and five-year survival remains low. Numerous studies have shown that chronic inflammation may lead to progression of carcinogenesis. As a result of inflammatory stimulation, arachidonic acid (AA metabolism produces proliferation mediators through complex and dynamic interactions of the products of the LOX/COX enzymes. One important mediator in the activation of the AA pathways is the nuclear protein PPAR. Targeting LOX/COX enzymes and inducing activation of PPAR have resulted in significant reduction of cell growth in lung cancer cell lines. However, specific COX-inhibitors have been correlated with an increased cardiovascular risk. Clinical applications are still being explored with a novel generation of dual LOX/COX inhibitors. PPAR activation through synthetic ligands (TZDs has revealed a great mechanistic complexity since effects are produced through PPAR-dependent and -independent mechanisms. Furthermore, PPAR could also be involved in regulation of COX-2. Overexpression of PPAR has reported to play a role in control of invasion and differentiation. Exploring the function of PPAR, in this new context, may provide a better mechanistic model of its role in cancer and give an opportunity to design a more efficient therapeutic approach in combination with LOX/COX inhibitors.

Modelling carcinogenesis after radiotherapy using Poisson statistics: implications for IMRT, protons and ions

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Jones, Bleddyn [Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus, Headington, Oxford OX3 7DQ (United Kingdom)], E-mail: Bleddyn.Jones@rob.ox.ac.uk

2009-06-01

Current technical radiotherapy advances aim to (a) better conform the dose contours to cancers and (b) reduce the integral dose exposure and thereby minimise unnecessary dose exposure to normal tissues unaffected by the cancer. Various types of conformal and intensity modulated radiotherapy (IMRT) using x-rays can achieve (a) while charged particle therapy (CPT)-using proton and ion beams-can achieve both (a) and (b), but at greater financial cost. Not only is the long term risk of radiation related normal tissue complications important, but so is the risk of carcinogenesis. Physical dose distribution plans can be generated to show the differences between the above techniques. IMRT is associated with a dose bath of low to medium dose due to fluence transfer: dose is effectively transferred from designated organs at risk to other areas; thus dose and risk are transferred. Many clinicians are concerned that there may be additional carcinogenesis many years after IMRT. CPT reduces the total energy deposition in the body and offers many potential advantages in terms of the prospects for better quality of life along with cancer cure. With C ions there is a tail of dose beyond the Bragg peaks, due to nuclear fragmentation; this is not found with protons. CPT generally uses higher linear energy transfer (which varies with particle and energy), which carries a higher relative risk of malignant induction, but also of cell death quantified by the relative biological effect concept, so at higher dose levels the frank development of malignancy should be reduced. Standard linear radioprotection models have been used to show a reduction in carcinogenesis risk of between two- and 15-fold depending on the CPT location. But the standard risk models make no allowance for fractionation and some have a dose limit at 4 Gy. Alternatively, tentative application of the linear quadratic model and Poissonian statistics to chromosome breakage and cell kill simultaneously allows estimation of

Modification of N-Methyl-N-Nitrosourea initiated bladder carcinogenesis in Wistar rats by terephthalic acid

International Nuclear Information System (INIS)

Cui Lunbiao; Shi Yuan; Dai Guidong; Pan Hongxin; Chen Jianfeng; Song Ling; Wang Shouling; Chang, Hebron C.; Sheng Hongbing; Wang Xinru

2006-01-01

The effect of terephthalic acid (TPA) on urinary bladder carcinogenesis was examined. Male Wistar rats were initiated by injection of N-Methyl-N-Nitrosourea (MNU) (20 mg/kg b.w. ip) twice a week for 4 weeks, then given basal diet containing 5% TPA, 5% TPA plus 4% Sodium bicarbonate (NaHCO 3 ) or 1% TPA for the next 22 weeks, and then euthanized. 5% TPA treatment induced a high incidence of urinary bladder calculi and a large amount of precipitate. Though 5% TPA plus 4% Sodium bicarbonate (NaHCO 3 ) and 1% TPA treatment did not induce urinary bladder calculi formation, they resulted in a moderate increase in urinary precipitate. Histological examination of urinary bladder revealed that MNU-5% TPA treatment resulted in a higher incidence of simple hyperplasia, papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer than MNU control. MNU-5% TPA plus 4% Sodium bicarbonate (NaHCO 3 ) and 1% TPA treatment increased slightly the incidence of simple hyperplasia and PN hyperplasia (not statistically significant). The major elements of the precipitate are phosphorus, potassium, sulfur, chloride, calcium and TPA. The present study indicated that the calculi induced by TPA had a strong promoting activity on urinary bladder carcinogenesis and the precipitate containing calcium terephthalate (CaTPA) may also have weak promoting activity on urinary bladder carcinogenesis

How patient positioning affects radiographic signs of canine lung disease

International Nuclear Information System (INIS)

Steyn, P.F.; Green, R.W.

1990-01-01

A single radiographic projection risks missing signs of lung disease. Four case reports of dogs are given to emphasize inadequate visualization with just one or two radiographs. It is advisable to take both right and left lateral views along with a dorsoventral view in a patient, that might have lung disease

Influence of early neurological complications on clinical outcome following lung transplant.

Science.gov (United States)

Gamez, Josep; Salvado, Maria; Martinez-de La Ossa, Alejandro; Deu, Maria; Romero, Laura; Roman, Antonio; Sacanell, Judith; Laborda, Cesar; Rochera, Isabel; Nadal, Miriam; Carmona, Francesc; Santamarina, Estevo; Raguer, Nuria; Canela, Merce; Solé, Joan

2017-01-01

Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients' survival. The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors.

[Lung transplantation in pulmonary fibrosis and other interstitial lung diseases].

Science.gov (United States)

Berastegui, Cristina; Monforte, Victor; Bravo, Carlos; Sole, Joan; Gavalda, Joan; Tenório, Luis; Villar, Ana; Rochera, M Isabel; Canela, Mercè; Morell, Ferran; Roman, Antonio

2014-09-15

Interstitial lung disease (ILD) is the second indication for lung transplantation (LT) after emphysema. The aim of this study is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona, Spain). We retrospectively studied 150 patients, 87 (58%) men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral-lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%) unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the functional results, complications and survival. The actuarial survival was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes of death included early graft dysfunction and development of chronic rejection in the form of bronchiolitis obliterans (BOS). The mean postoperative increase in forced vital capacity and forced expiratory volume in the first second (FEV1) was similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months. Sixteen percent of patients returned to work. At some point during the evolution, proven acute rejection was diagnosed histologically in 53 (35%) patients. The prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5 years. LT is the best treatment option currently available for ILD, in which medical treatment has failed. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Sensitivity of Tumor Motion Simulation Accuracy to Lung Biomechanical Modeling Approaches and Parameters

OpenAIRE

Tehrani, Joubin Nasehi; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu; Wang, Jing

2015-01-01

Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional com...

Non-invasive determination of absolute lung resistivity in adults using electrical impedance tomography

International Nuclear Information System (INIS)

Zhang, Jie; Patterson, Robert

2010-01-01

Lung resistivity is a physiological parameter that describes the electrical characteristics of the lungs. Lung composition changes due to changes in the lung tissues, fluid and air volume. Various diseases that can cause a change in lung composition may be monitored by measuring lung resistivity. Currently, there is no accepted non-invasive method to measure lung resistivity. In this study, we presented a method and framework to non-invasively determine lung resistivity using electrical impedance tomography (EIT). By comparing actual measurements from subjects with data from a 3D human thorax model, an EIT image can be reconstructed to show a resistivity difference between the model and the subject. By adjusting the lung resistivity in the model, the resistivity difference in the lung regions can be reduced to near zero. This resistivity value then is the estimation of the lung resistivity of the subject. Using the proposed method, the lung resistivities of four normal adult males (43 ± 13 years, 78 ± 10 kg) in the supine position at air volumes starting at functional residual capacity (FRC—end expiration) and increasing in 0.5 l steps to 1.5 l were studied. The averaged lung resistivity changes 12.59%, from 1406 Ω cm to 1583 Ω cm, following the inspiration of 1.5 l air from FRC. The coefficients of variation (CV) of precision for the four subjects are less than 10%. The experiment was repeated five times at each air volume on a subject to test the reproducibility. The CVs are less than 3%. The results show that it is feasible to determine absolute lung resistivity using an EIT-based method

Non-invasive determination of absolute lung resistivity in adults using electrical impedance tomography.

Science.gov (United States)

Zhang, Jie; Patterson, Robert

2010-08-01

Lung resistivity is a physiological parameter that describes the electrical characteristics of the lungs. Lung composition changes due to changes in the lung tissues, fluid and air volume. Various diseases that can cause a change in lung composition may be monitored by measuring lung resistivity. Currently, there is no accepted non-invasive method to measure lung resistivity. In this study, we presented a method and framework to non-invasively determine lung resistivity using electrical impedance tomography (EIT). By comparing actual measurements from subjects with data from a 3D human thorax model, an EIT image can be reconstructed to show a resistivity difference between the model and the subject. By adjusting the lung resistivity in the model, the resistivity difference in the lung regions can be reduced to near zero. This resistivity value then is the estimation of the lung resistivity of the subject. Using the proposed method, the lung resistivities of four normal adult males (43 +/- 13 years, 78 +/- 10 kg) in the supine position at air volumes starting at functional residual capacity (FRC--end expiration) and increasing in 0.5 l steps to 1.5 l were studied. The averaged lung resistivity changes 12.59%, from 1406 Omega cm to 1583 Omega cm, following the inspiration of 1.5 l air from FRC. The coefficients of variation (CV) of precision for the four subjects are less than 10%. The experiment was repeated five times at each air volume on a subject to test the reproducibility. The CVs are less than 3%. The results show that it is feasible to determine absolute lung resistivity using an EIT-based method.

Effects of FTY720 on Lung Injury Induced by Hindlimb Ischemia Reperfusion in Rats

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Liangrong Wang

2017-01-01

Full Text Available Background. Sphingosine-1-phosphate (S1P is a biologically active lysophospholipid mediator involved in modulating inflammatory process. We investigated the effects of FTY720, a structural analogue of S1P after phosphorylation, on lung injury induced by hindlimb ischemia reperfusion (IR in rats. Methods. Fifty Sprague-Dawley rats were divided into groups SM, IR, F3, F5, and F10. Group SM received sham operation, and bilateral hindlimb IR was established in group IR. The rats in groups F3, F5, and F10 were pretreated with 3, 5, and 10 mg/kg/d FTY720 for 7 days before IR. S1P lyase (S1PL, sphingosine kinase (SphK 1, and SphK2 mRNA expressions, wet/dry weight (W/D, and polymorphonuclear/alveolus (P/A in lung tissues were detected, and the lung injury score was evaluated. Results. W/D, P/A, and mRNA expressions of S1PL, SphK1, and SphK2 were higher in group IR than in group SM, while these were decreased in both groups F5 and F10 as compared to IR (p<0.05. The lung tissue presented severe lesions in group IR, which were attenuated in groups F5 and F10 with lower lung injury scores than in group IR (p<0.05. Conclusions. FTY720 pretreatment could attenuate lung injury induced by hindlimb IR by modulating S1P metabolism and decreasing pulmonary neutrophil infiltration.

First Fifty Years of Chemoresistive Gas Sensors

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Giovanni Neri

2015-01-01

Full Text Available The first fifty years of chemoresistive sensors for gas detection are here reviewed, focusing on the main scientific and technological innovations that have occurred in the field over the course of these years. A look at advances made in fundamental and applied research and leading to the development of actual high performance chemoresistive devices is presented. The approaches devoted to the synthesis of novel semiconducting materials with unprecedented nanostructure and gas-sensing properties have been also presented. Perspectives on new technologies and future applications of chemoresistive gas sensors have also been highlighted.

CT of chronic infiltrative lung disease: Prevalence of mediastinal lymphadenopathy

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Niimi, Hiroshi; Kang, Eun-Young; Kwong, S. [Univ. of British Columbia and Vancouver Hospital and Health Sciences Centre (Canada)] [and others

1996-03-01

Our goal was to determine the prevalence of mediastinal lymph node enlargement at CT in patients with diffuse infiltrative lung disease. The study was retrospective and included 175 consecutive patients with diffuse infiltrative lung diseases. Diagnoses included idiopathic pulmonary fibrosis (IPF) (n = 61), usual interstitial pneumonia associated with collagen vascular disease (CVD) (n = 20), idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) (n = 22), extrinsic allergic alveolitis (EAA) (n = 17), and sarcoidosis (n = 55). Fifty-eight age-matched patients with CT of the chest performed for unrelated conditions served as controls. The presence, number, and sites of enlarged nodes (short axis {ge}10 mm in diameter) were recorded. Enlarged mediastinal nodes were present in 118 of 175 patients (67%) with infiltrative lung disease and 3 of 58 controls (5%) (p < 0.001). The prevalence of enlarged nodes was 84% (46 of 55) in sarcoidosis, 67% (41 of 61) in IPF, 70% (14 of 20) in CVD, 53% (9 of 17) in EAA, and 36% (8 of 22) in BOOP. The mean number of enlarged nodes was higher in sarcoidosis (mean 3.2) than in the other infiltrative diseases (mean 1.2) (p < 0.001). Enlarged nodes were most commonly present in station 10R, followed by 7, 4R, and 5. Patients with infiltrative lung disease frequently have enlarged mediastinal lymph nodes. However, in diseases other than sarcoid, usually only one or two nodes are enlarged and their maximal short axis diameter is <15 mm. 11 refs., 2 figs., 1 tab.