WorldWideScience

Sample records for understanding respiratory carcinogenesis

  1. Carcinogenesis

    International Nuclear Information System (INIS)

    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

  2. Advances in Understanding of Penile Carcinogenesis: The Search for Actionable Targets.

    Science.gov (United States)

    Chipollini, Juan; Chaing, Sharon; Azizi, Mounsif; Kidd, Laura C; Kim, Patricia; Spiess, Philippe E

    2017-08-16

    Penile cancer (PeCa) is a rare malignancy with potentially devastating effects. Squamous cell carcinoma is the most common variant with distinct precancerous lesions before development into invasive disease. Involvement of the inguinal lymph nodes is the most important prognostic factor in PeCa, and once disease is present outside the groin, prognosis is poor. Metastatic PeCa is challenging to treat and often requires multidisciplinary approaches in management. Due to its rarity, molecular understanding of the disease continues to be limited with most studies based on small, single center series. Thus far, it appears PeCa has diverse mechanisms of carcinogenesis affecting similar molecular pathways. In this review, we evaluate the current landscape of the molecular carcinogenesis of PeCa and explore ongoing research on potential actionable targets of therapy. The emergence of anti-epidermal growth factor receptor (EGFR) and other immunotherapeutic strategies may improve outcomes for PeCa patients.

  3. Didactic tools for understanding respiratory physiology

    Energy Technology Data Exchange (ETDEWEB)

    Kehoe, P Donnelly; Bratovich, C; Perrone, Ms; Castells, L Mendez [Catedra de FisiologIa y BiofIsica - Facultad de Ingenieria - Universidad Nacional de Entre Rios - Ruta Provincial N011 Km. 10, 5 - Oro Verde C.P. 3101 - Entre Rios (Argentina)

    2007-11-15

    The challenges in Bioengineering are not only the application of engineering knowledge to the measurement of physiological variables, but also the simulation of biological systems. Experience has shown that the physiology of the respiratory system involves a set of concepts that cannot be effectively taught without the help of a group of didactic tools that contribute to the measurement of characteristic specific variables and to the simulation of the system itself. This article describes a series of tools designed to optimize the teaching of the respiratory system, including the use of spirometers and software developed entirely by undergraduate Bioengineering students from Universidad Nacional de Entre Rios (UNER). The impact these resources have caused on the understanding of the topic and how each of them has facilitated the interpretation of the concepts by the students is also discussed.

  4. Understanding Alterations in Cell Nano-architecture during Early Carcinogenesis using Optical Microscopy

    Science.gov (United States)

    Damania, Dhwanil

    Carcinogenesis is a complex multi-step process which eventually results in a malignant phenotype that often progresses into a fatal metastatic stage. There are several molecular changes (e.g. DNA methylation, activation of proto-oncogenes, loss of tumor-suppressor genes, histone acetylation) that occur in cells prior to the microscopically detectable morphological alterations. Hence, it is intuitive that these molecular changes should impact various biochemical, biophysical and transport processes within the cell and therefore its nanoscale morphology. Furthermore, recent studies have established that apparently `normal' cells (i.e., away from the actual tumor location) undergo similar genetic/epigenetic changes as the actual cancer cells, giving rise to the phenomenon of field carcinogenesis. Unfortunately, traditional microscopy or histopathology cannot resolve structures below 300 nm due to diffraction-limited resolution. Hence, we developed a novel optical imaging technique, partial wave spectroscopic (PWS) microscopy or optical nanocytology which quantifies the nanoscale refractive-index fluctuations (i.e. mass-density variations such as chromatin compaction) in an optically measured biomarker, disorder strength (Ld). This dissertation proves the nanoscale sensitivity of PWS nanocytology and shows that increase in Ld parallels neoplastic potential of a cell by using standardized cell-lines and animal-models. Based on concept of field carcinogenesis, we employ PWS nanocytology in a multi-center clinical study on approximately 450 patients in four different cancer-types (colon, ovarian, thyroid and lung) and we illustrate that nanoscale disorder increase is a ubiquitous phenomenon across different organs. We further demonstrate the potential of PWS nanocytology in predicting risk for developing future neoplasia. Biologically, we prove that cytoskeletal organization in both nucleus and cytoplasm plays a crucial role in governing L d-differences. Moreover, we

  5. Using salmonid microarrays to understand the dietary modulation of carcinogenesis in rainbow trout.

    Science.gov (United States)

    Gallagher, Evan P

    2006-03-01

    The highlighted article in this issue by Tilton et al. (2005a) is an innovative approach to evaluate the modulation of estrogen receptor (ER) and aryl hydrocarbon (Ah)-receptor pathways as mechanisms underlying indole-3-carbinol (I3C) tumor promotion in rainbow trout (Onchorhynchus mykiss). I3C and its major in vivo component 3,3'-diindolylmethane (DIM) are potent tumor promoters that appear to target both of the aforementioned receptor pathways. However, the relative importance of I3C modulation of ER and AhR-dependent pathways in the promotion of rainbow trout hepatocarcinogenesis has not been established. Previously, researchers within this group reported that I3C promotes aflatoxin B1 (AFB1)-induced trout hepatocarcinogenesis post-initiation at low concentrations in the diet that induce the expression of vitellogenin, a downstream marker for the activation of ER-dependent pathways in fish. Furthermore, the promotional effects of I3C on AFB1 hepatocarcinogenesis in rainbow trout occur at concentrations that differentially induce vitellogenin, but not CYP1A expression. Interestingly, higher I3C concentrations induce the expression of both CYP1A and vitellogenin. Thus, the relative induction of vitellogenin and CYP1A expression, which are respective markers for activation of fish ER and AhR-mediated gene expression, suggest that these pathways may be important for tumor promotion by dietary I3C in trout. Understanding the complexities of I3C-mediated tumor promotion is essential from several perspectives. For example, there is the obvious need to increase our basic understanding of dietary modulation of carcinogenesis. In addition, I3C also exhibits significant antioxidant and cancer chemoprotective effects under certain experimental conditions and in certain models which have led to its recent marketing as a dietary supplement, as well as its development as a possible chemopreventive agent in humans.

  6. The respiratory practical persons: new understanding and approaches.

    Directory of Open Access Journals (Sweden)

    Ruslanov D.V.

    2011-02-01

    Full Text Available It is analysed modern information about existent respiratory practices. The methodological, physiological and psychological aspects of respiratory practices are examined. 2 groups of students of higher humanitarian institute are participated in experiment: healthy (students of basic group, n1=180 and with different chronic pathology in the stage of remission (students of group of medical physical education, n2=50. Duration of experiment made about two months. Frequency of the controlled respiratory practice - 1-2 times per a week. The algorithm of respiratory practice is presented. Exercises and recommendations are resulted on their application.

  7. Neonatal respiratory distress: recent progress in understanding pathogenesis and treatment outcomes

    OpenAIRE

    So Young Kim

    2010-01-01

    Transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), and persistent pulmonary hypertension (PPHN) are the three most common disorders that cause respiratory distress after birth. An understanding of the pathophysiology of these disorders and the development of effective therapeutic strategies is required to control these conditions. Here, we review recent papers on the pathogenesis and treatment of neonatal respiratory disease.

  8. Neonatal respiratory distress: recent progress in understanding pathogenesis and treatment outcomes

    Directory of Open Access Journals (Sweden)

    So Young Kim

    2010-01-01

    Full Text Available Transient tachypnea of the newborn (TTN, respiratory distress syndrome (RDS, and persistent pulmonary hypertension (PPHN are the three most common disorders that cause respiratory distress after birth. An understanding of the pathophysiology of these disorders and the development of effective therapeutic strategies is required to control these conditions. Here, we review recent papers on the pathogenesis and treatment of neonatal respiratory disease.

  9. 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

  10. Chemical carcinogenesis

    Directory of Open Access Journals (Sweden)

    Paula A. Oliveira

    2007-12-01

    Full Text Available The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the needs of millions of people, a condition that has led to an increase in levels of life expectancy. Yet, at times, these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds used. Exposure to these compounds can have varying effects, ranging from instant death to a gradual process of chemical carcinogenesis. There are three stages involved in chemical carcinogenesis. These are defined as initiation, promotion and progression. Each of these stages is characterised by morphological and biochemical modifications and result from genetic and/or epigenetic alterations. These genetic modifications include: mutations in genes that control cell proliferation, cell death and DNA repair - i.e. mutations in proto-oncogenes and tumour suppressing genes. The epigenetic factors, also considered as being non-genetic in character, can also contribute to carcinogenesis via epigenetic mechanisms which silence gene expression. The control of responses to carcinogenesis through the application of several chemical, biochemical and biological techniques facilitates the identification of those basic mechanisms involved in neoplasic development. Experimental assays with laboratory animals, epidemiological studies and quick tests enable the identification of carcinogenic compounds, the dissection of many aspects of carcinogenesis, and the establishment of effective strategies to prevent the cancer which results from exposure to chemicals.A sociedade obtém numerosos benefícios da utilização de compostos químicos. A aplicação dos pesticidas, por exemplo, permitiu obter alimento em quantidade suficiente para satisfazer as necessidades alimentares de milhões de pessoas, condição relacionada com o aumento da esperança de vida. Os benefícios estão, por

  11. Respiratory

    Science.gov (United States)

    The words "respiratory" and "respiration" refer to the lungs and breathing. ... Boron WF. Organization of the respiratory system. In: Boron WF, Boulpaep EL, eds. Medical Physiology . 3rd ed. Philadelphia, PA: Elsevier; 2017:chap 26.

  12. Numerical simulation of two consecutive nasal respiratory cycles: toward a better understanding of nasal physiology.

    Science.gov (United States)

    de Gabory, Ludovic; Reville, Nicolas; Baux, Yannick; Boisson, Nicolas; Bordenave, Laurence

    2018-01-16

    Computational fluid dynamic (CFD) simulations have greatly improved the understanding of nasal physiology. We postulate that simulating the entire and repeated respiratory nasal cycles, within the whole sinonasal cavities, is mandatory to gather more accurate observations and better understand airflow patterns. A 3-dimensional (3D) sinonasal model was constructed from a healthy adult computed tomography (CT) scan which discretized in 6.6 million cells (mean volume, 0.008 mm 3 ). CFD simulations were performed with ANSYS©FluentTMv16.0.0 software with transient and turbulent airflow (k-ω model). Two respiratory cycles (8 seconds) were simulated to assess pressure, velocity, wall shear stress, and particle residence time. The pressure gradients within the sinus cavities varied according to their place of connection to the main passage. Alternations in pressure gradients induced a slight pumping phenomenon close to the ostia but no movement of air was observed within the sinus cavities. Strong movements were observed within the inferior meatus during expiration contrary to the inspiration, as in the olfactory cleft at the same time. Particle residence time was longer during expiration than inspiration due to nasal valve resistance, as if the expiratory phase was preparing the next inspiratory phase. Throughout expiration, some particles remained in contact with the lower turbinates. The posterior part of the olfactory cleft was gradually filled with particles that did not leave the nose at the next respiratory cycle. This pattern increased as the respiratory cycle was repeated. CFD is more efficient and reliable when the entire respiratory cycle is simulated and repeated to avoid losing information. © 2018 ARS-AAOA, LLC.

  13. Global Consensus Theorem and Self-Organized Criticality: Unifying Principles for Understanding Self-Organization, Swarm Intelligence and Mechanisms of Carcinogenesis

    Science.gov (United States)

    Rosenfeld, Simon

    2013-01-01

    Complex biological systems manifest a large variety of emergent phenomena among which prominent roles belong to self-organization and swarm intelligence. Generally, each level in a biological hierarchy possesses its own systemic properties and requires its own way of observation, conceptualization, and modeling. In this work, an attempt is made to outline general guiding principles in exploration of a wide range of seemingly dissimilar phenomena observed in large communities of individuals devoid of any personal intelligence and interacting with each other through simple stimulus-response rules. Mathematically, these guiding principles are well captured by the Global Consensus Theorem (GCT) equally applicable to neural networks and to Lotka-Volterra population dynamics. Universality of the mechanistic principles outlined by GCT allows for a unified approach to such diverse systems as biological networks, communities of social insects, robotic communities, microbial communities, communities of somatic cells, social networks and many other systems. Another cluster of universal laws governing the self-organization in large communities of locally interacting individuals is built around the principle of self-organized criticality (SOC). The GCT and SOC, separately or in combination, provide a conceptual basis for understanding the phenomena of self-organization occurring in large communities without involvement of a supervisory authority, without system-wide informational infrastructure, and without mapping of general plan of action onto cognitive/behavioral faculties of its individual members. Cancer onset and proliferation serves as an important example of application of these conceptual approaches. In this paper, the point of view is put forward that apparently irreconcilable contradictions between two opposing theories of carcinogenesis, that is, the Somatic Mutation Theory and the Tissue Organization Field Theory, may be resolved using the systemic approaches

  14. Global consensus theorem and self-organized criticality: unifying principles for understanding self-organization, swarm intelligence and mechanisms of carcinogenesis.

    Science.gov (United States)

    Rosenfeld, Simon

    2013-01-01

    Complex biological systems manifest a large variety of emergent phenomena among which prominent roles belong to self-organization and swarm intelligence. Generally, each level in a biological hierarchy possesses its own systemic properties and requires its own way of observation, conceptualization, and modeling. In this work, an attempt is made to outline general guiding principles in exploration of a wide range of seemingly dissimilar phenomena observed in large communities of individuals devoid of any personal intelligence and interacting with each other through simple stimulus-response rules. Mathematically, these guiding principles are well captured by the Global Consensus Theorem (GCT) equally applicable to neural networks and to Lotka-Volterra population dynamics. Universality of the mechanistic principles outlined by GCT allows for a unified approach to such diverse systems as biological networks, communities of social insects, robotic communities, microbial communities, communities of somatic cells, social networks and many other systems. Another cluster of universal laws governing the self-organization in large communities of locally interacting individuals is built around the principle of self-organized criticality (SOC). The GCT and SOC, separately or in combination, provide a conceptual basis for understanding the phenomena of self-organization occurring in large communities without involvement of a supervisory authority, without system-wide informational infrastructure, and without mapping of general plan of action onto cognitive/behavioral faculties of its individual members. Cancer onset and proliferation serves as an important example of application of these conceptual approaches. In this paper, the point of view is put forward that apparently irreconcilable contradictions between two opposing theories of carcinogenesis, that is, the Somatic Mutation Theory and the Tissue Organization Field Theory, may be resolved using the systemic approaches

  15. Optimization Aspects of Carcinogenesis

    OpenAIRE

    Brutovsky, B.; Horvath, D.

    2009-01-01

    Any process in which competing solutions replicate with errors and numbers of their copies depend on their respective fitnesses is the evolutionary optimization process. As during carcinogenesis mutated genomes replicate according to their respective qualities, carcinogenesis obviously qualifies as the evolutionary optimization process and conforms to common mathematical basis. The optimization view accents statistical nature of carcinogenesis proposing that during it the crucial role is actu...

  16. Recent advances in understanding acute respiratory distress syndrome [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Peter Wohlrab

    2018-03-01

    Full Text Available Acute respiratory distress syndrome (ARDS is characterized by acute diffuse lung injury, which results in increased pulmonary vascular permeability and loss of aerated lung tissue. This causes bilateral opacity consistent with pulmonary edema, hypoxemia, increased venous admixture, and decreased lung compliance such that patients with ARDS need supportive care in the intensive care unit to maintain oxygenation and prevent adverse outcomes. Recently, advances in understanding the underlying pathophysiology of ARDS led to new approaches in managing these patients. In this review, we want to focus on recent scientific evidence in the field of ARDS research and discuss promising new developments in the treatment of this disease.

  17. Estimating energetics in cetaceans from respiratory frequency: why we need to understand physiology

    Directory of Open Access Journals (Sweden)

    A. Fahlman

    2016-04-01

    Full Text Available The accurate estimation of field metabolic rates (FMR in wild animals is a key component of bioenergetic models, and is important for understanding the routine limitations for survival as well as individual responses to disturbances or environmental changes. Several methods have been used to estimate FMR, including accelerometer-derived activity budgets, isotope dilution techniques, and proxies from heart rate. Counting the number of breaths is another method used to assess FMR in cetaceans, which is attractive in its simplicity and the ability to measure respiration frequency from visual cues or data loggers. This method hinges on the assumption that over time a constant tidal volume (VT and O2 exchange fraction (ΔO2 can be used to predict FMR. To test whether this method of estimating FMR is valid, we measured breath-by-breath tidal volumes and expired O2 levels of bottlenose dolphins, and computed the O2 consumption rate (V̇O2 before and after a pre-determined duration of exercise. The measured V̇O2 was compared with three methods to estimate FMR. Each method to estimate V̇O2 included variable VT and/or ΔO2. Two assumption-based methods overestimated V̇O2 by 216-501%. Once the temporal changes in cardio-respiratory physiology, such as variation in VT and ΔO2, were taken into account, pre-exercise resting V̇O2 was predicted to within 2%, and post-exercise V̇O2 was overestimated by 12%. Our data show that a better understanding of cardiorespiratory physiology significantly improves the ability to estimate metabolic rate from respiratory frequency, and further emphasizes the importance of eco-physiology for conservation management efforts.

  18. A Functional Approach towards Understanding the Role of the Mitochondrial Respiratory Chain in an Endomycorrhizal Symbiosis

    Science.gov (United States)

    Mercy, Louis; Lucic-Mercy, Eva; Nogales, Amaia; Poghosyan, Areg; Schneider, Carolin; Arnholdt-Schmitt, Birgit

    2017-01-01

    Arbuscular mycorrhizal fungi (AMF) are crucial components of fertile soils, able to provide several ecosystem services for crop production. Current economic, social and legislative contexts should drive the so-called “second green revolution” by better exploiting these beneficial microorganisms. Many challenges still need to be overcome to better understand the mycorrhizal symbiosis, among which (i) the biotrophic nature of AMF, constraining their production, while (ii) phosphate acts as a limiting factor for the optimal mycorrhizal inoculum application and effectiveness. Organism fitness and adaptation to the changing environment can be driven by the modulation of mitochondrial respiratory chain, strongly connected to the phosphorus processing. Nevertheless, the role of the respiratory function in mycorrhiza remains largely unexplored. We hypothesized that the two mitochondrial respiratory chain components, alternative oxidase (AOX) and cytochrome oxidase (COX), are involved in specific mycorrhizal behavior. For this, a complex approach was developed. At the pre-symbiotic phase (axenic conditions), we studied phenotypic responses of Rhizoglomus irregulare spores with two AOX and COX inhibitors [respectively, salicylhydroxamic acid (SHAM) and potassium cyanide (KCN)] and two growth regulators (abscisic acid – ABA and gibberellic acid – Ga3). At the symbiotic phase, we analyzed phenotypic and transcriptomic (genes involved in respiration, transport, and fermentation) responses in Solanum tuberosum/Rhizoglomus irregulare biosystem (glasshouse conditions): we monitored the effects driven by ABA, and explored the modulations induced by SHAM and KCN under five phosphorus concentrations. KCN and SHAM inhibited in vitro spore germination while ABA and Ga3 induced differential spore germination and hyphal patterns. ABA promoted mycorrhizal colonization, strong arbuscule intensity and positive mycorrhizal growth dependency (MGD). In ABA treated plants, R. irregulare

  19. Towards Better Understanding of the Pathogenesis of Neuronal Respiratory Network in Sudden Perinatal Death

    Directory of Open Access Journals (Sweden)

    Riffat Mehboob

    2017-07-01

    Full Text Available Sudden perinatal death that includes the victims of sudden infant death syndrome, sudden intrauterine death syndrome, and stillbirth are heartbreaking events in the life of parents. Most of the studies about sudden perinatal death were reported from Italy, highlighting two main etiological factors: prone sleeping position and smoking. Other probable contributory factors are prematurity, male gender, lack of breastfeeding, respiratory tract infections, use of pacifiers, infant botulism, extensive use of pesticides and insecticides, etc. However, extensive studies across the world are required to establish the role of these factors in a different subset of populations. Previous studies confirmed the widely accepted hypothesis that neuropathology of the brainstem is one of the main cause of sudden perinatal death. This study is an effort to summarize the neuropathological evaluation of the brainstems and their association to sudden perinatal death. Brainstem nuclei in vulnerable infants undergo certain changes that may alter the sleep arousal cycle, cardiorespiratory control, and ultimately culminate in death. This review focuses on the roles of different brainstem nuclei, their pathologies, and the established facts in this regard in terms of it’s link to such deaths. This study will also help to understand the role of brainstem nuclei in controlling the cardiorespiratory cycles in sudden perinatal death and may provide a better understanding to resolve the mystery of these deaths in future. It is also found that a global initiative to deal with perinatal death is required to facilitate the diagnosis and prevention in developed and as well as developing countries.

  20. Understanding Heroin Overdose: A Study of the Acute Respiratory Depressant Effects of Injected Pharmaceutical Heroin.

    Science.gov (United States)

    Jolley, Caroline J; Bell, James; Rafferty, Gerrard F; Moxham, John; Strang, John

    2015-01-01

    Opioids are respiratory depressants and heroin/opioid overdose is a major contributor to the excess mortality of heroin addicts. The individual and situational variability of respiratory depression caused by intravenous heroin is poorly understood. This study used advanced respiratory monitoring to follow the time course and severity of acute opioid-induced respiratory depression. 10 patients (9/10 with chronic airflow obstruction) undergoing supervised injectable opioid treatment for heroin addiction received their usual prescribed dose of injectable opioid (diamorphine or methadone) (IOT), and their usual prescribed dose of oral opioid (methadone or sustained release oral morphine) after 30 minutes. The main outcome measures were pulse oximetry (SpO2%), end-tidal CO2% (ETCO2%) and neural respiratory drive (NRD) (quantified using parasternal intercostal muscle electromyography). Significant respiratory depression was defined as absence of inspiratory airflow >10s, SpO2% 10s and ETCO2% per breath >6.5%. Increases in ETCO2% indicated significant respiratory depression following IOT in 8/10 patients at 30 minutes. In contrast, SpO2% indicated significant respiratory depression in only 4/10 patients, with small absolute changes in SpO2% at 30 minutes. A decline in NRD from baseline to 30 minutes post IOT was also observed, but was not statistically significant. Baseline NRD and opioid-induced drop in SpO2% were inversely related. We conclude that significant acute respiratory depression is commonly induced by opioid drugs prescribed to treat opioid addiction. Hypoventilation is reliably detected by capnography, but not by SpO2% alone. Chronic suppression of NRD in the presence of underlying lung disease may be a risk factor for acute opioid-induced respiratory depression.

  1. Understanding Heroin Overdose: A Study of the Acute Respiratory Depressant Effects of Injected Pharmaceutical Heroin.

    Directory of Open Access Journals (Sweden)

    Caroline J Jolley

    Full Text Available Opioids are respiratory depressants and heroin/opioid overdose is a major contributor to the excess mortality of heroin addicts. The individual and situational variability of respiratory depression caused by intravenous heroin is poorly understood. This study used advanced respiratory monitoring to follow the time course and severity of acute opioid-induced respiratory depression. 10 patients (9/10 with chronic airflow obstruction undergoing supervised injectable opioid treatment for heroin addiction received their usual prescribed dose of injectable opioid (diamorphine or methadone (IOT, and their usual prescribed dose of oral opioid (methadone or sustained release oral morphine after 30 minutes. The main outcome measures were pulse oximetry (SpO2%, end-tidal CO2% (ETCO2% and neural respiratory drive (NRD (quantified using parasternal intercostal muscle electromyography. Significant respiratory depression was defined as absence of inspiratory airflow >10s, SpO2% 10s and ETCO2% per breath >6.5%. Increases in ETCO2% indicated significant respiratory depression following IOT in 8/10 patients at 30 minutes. In contrast, SpO2% indicated significant respiratory depression in only 4/10 patients, with small absolute changes in SpO2% at 30 minutes. A decline in NRD from baseline to 30 minutes post IOT was also observed, but was not statistically significant. Baseline NRD and opioid-induced drop in SpO2% were inversely related. We conclude that significant acute respiratory depression is commonly induced by opioid drugs prescribed to treat opioid addiction. Hypoventilation is reliably detected by capnography, but not by SpO2% alone. Chronic suppression of NRD in the presence of underlying lung disease may be a risk factor for acute opioid-induced respiratory depression.

  2. Optimization aspects of carcinogenesis.

    Science.gov (United States)

    Brutovsky, B; Horvath, D

    2010-05-01

    Any process in which competing solutions replicate with errors and numbers of their copies depend on their respective fitnesses is the evolutionary optimization process. As during carcinogenesis mutated genomes replicate according to their respective qualities, carcinogenesis obviously qualifies as the evolutionary optimization process and conforms to common mathematical basis. The optimization view accents statistical nature of carcinogenesis proposing that during it the crucial role is actually played by the allocation of trials. Optimal allocation of trials requires reliable schemas' fitnesses estimations which necessitate appropriate, fitness landscape dependent, statistics of population. In the spirit of the applied conceptual framework, features which are known to decrease efficiency of any evolutionary optimization procedure (or inhibit it completely) are anticipated as "therapies" and reviewed. Strict adherence to the evolutionary optimization framework leads us to some counterintuitive implications which are, however, in agreement with recent experimental findings, such as sometimes observed more aggressive and malignant growth of therapy surviving cancer cells.

  3. 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.

  4. Experimental radiation carcinogenesis

    International Nuclear Information System (INIS)

    Walburg, H.E. Jr.

    1974-01-01

    Literature on radioinduced carcinogenesis in experimental animals is reviewed with emphasis on the basic principles which could lead to a better predictability of radiation effects in man. It was concluded that the animal systems studied thus far are quantitatively inadequate for determining radiation risk estimates in man. (350 references.) (U.S.)

  5. Asthma exacerbations: Understanding role of viral respiratory tract infections and possible treatment strategies

    Directory of Open Access Journals (Sweden)

    Kavita Sekhri

    2015-01-01

    Full Text Available Asthma is common, affecting around 500 billion people worldwide. It is a complex disease influenced by both genetic and environmental factors. Upper respiratory tract infections with viruses commonly precipitate severe and sustained asthma exacerbations (AEs. Exacerbations are responsible for the enormous amount of emotional and economic stress apart from imposing risk of hospitalization and even death. Hence, agents targeting these infections can contribute toward decreasing asthma morbidity and associated financial burden. Over the past years novel, pharmacological therapies are evolved for the treatment of asthma, but their exact role in exacerbations is still unclear. This article reviews the role of respiratory viral infections in AEs and discusses role of new therapeutic approaches to overcome it. Medline, Medscape, EMBASE, Cochrane database, Scopus and clinicaltrials.gov were searched using terms such as "asthma," "AE" and "viral respiratory infections." Journal articles published from 2000 to 2013 describing AEs were screened.

  6. Understanding the internet-based distance learning preferences of European respiratory specialists.

    Science.gov (United States)

    Roberts, C M; Milon, S; Kurosinski, P

    2006-08-01

    We studied the learning preferences of 160 respiratory specialists from four European countries who participated in ten internet-based learning modules and answered linked survey questions. Specialists were enthusiastic for internet learning amongst all national groups and particularly wanted to access material for teaching others. The value of social interactive learning was acknowledged but British and German subjects appeared more reluctant to participate. Internet delivered distance learning is well perceived amongst respiratory specialists. There is potential for both individual and group learning that could be realized by developing Europe-wide continuing professional development communities.

  7. Carcinogenesis of cutaneous malignancies.

    Science.gov (United States)

    Buzzell, R A

    1996-03-01

    Over the past several years significant progress has been made in identifying the cellular and biochemical mechanisms underlying carcinogenesis. This review summarizes recent advances that have helped clarify the process of malignant transformation in cutaneous tumors. Ultraviolet radiation-induced mutations in the p53 tumor suppressor gene and human papilloma virus inhibition of the p53 and retinoblastoma tumor suppressor gene products appear to play significant roles in the development of many cutaneous squamous cell carcinomas. Studies of patients with the nevoid basal cell carcinoma syndrome suggest the existence of an additional regulatory gene that may be involved in the development of basal cell carcinomas. Carcinogenesis is multistep process involving genetic and epigenetic alterations to specific proto-oncogene and tumor suppressor gene products that progressively release the cell from normal controlled growth and replication.

  8. 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.)

  9. The significance of Candida in the human respiratory tract: our evolving understanding.

    Science.gov (United States)

    Pendleton, Kathryn M; Huffnagle, Gary B; Dickson, Robert P

    2017-04-01

    Candida is an opportunistic pathogen and the most commonly isolated fungal genus in humans. Though Candida is often detected in respiratory specimens from humans with and without lung disease, its significance remains undetermined. While historically considered a commensal organism with low virulence potential, the status of Candida as an innocent bystander has recently been called into question by both clinical observations and animal experimentation. We here review what is currently known and yet to be determined about the clinical, microbiological and pathophysiological significance of the detection of Candida spp. in the human respiratory tract. Published by Oxford University Press on behalf of FEMS 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. Variability of breath condensate pH may contribute to the better understanding of non-allergic seasonal respiratory diseases

    Science.gov (United States)

    Kullmann, Tamás; Szipőcs, Annamária

    2017-09-01

    The seasonal variability of certain non-allergic respiratory diseases is not clearly understood. Analysis of the breath condensate, the liquid that can be collected by breathing into a cold tube, has been proposed to bring closer to the understanding of airway pathologies. It has been assumed, that (1) airway lining fluid was a stable body liquid and (2) the breath condensate samples were representative of the airway lining fluid. Research was focussed on the identification of biomarkers indicative of respiratory pathologies. Despite 30 years of extended investigations breath condensate analysis has not gained any clinical implementation so far. The pH of the condensate is the characteristic that can be determined with the highest reproducibility. The present paper shows, that contrary to the initial assumptions, breath condensate is not a representative of the airway lining fluid, and the airway lining fluid is not a stable body liquid. Condensate pH shows baseline variability and it is influenced by drinking and by the ambient temperature. The changes in condensate pH are linked to changes in airway lining fluid pH. The variability of airway lining fluid pH may explain seasonal incidence of certain non-allergic respiratory diseases such as the catching of a common cold and the increased incidence of COPD exacerbations and exercise-induced bronchoconstriction in cold periods.

  11. Bone histological correlates for air sacs and their implications for understanding the origin of the dinosaurian respiratory system.

    Science.gov (United States)

    Lambertz, Markus; Bertozzo, Filippo; Sander, P Martin

    2018-01-01

    Air sacs are an important component of the avian respiratory system, and corresponding structures also were crucial for the evolution of sauropod dinosaur gigantism. Inferring the presence of air sacs in fossils so far is restricted to bones preserving internal pneumatic cavities and foramina as osteological correlates. We here present bone histological correlates for air sacs as a new potential identification tool for these elements of the respiratory system. The analysis of several avian and non-avian dinosaur samples revealed delicate fibres in secondary trabecular and secondary endosteal bone that in the former case (birds) is known or in the latter (non-avian dinosaurs) assumed to have been in contact with air sacs, respectively. The bone histology of this 'pneumosteal tissue' is markedly different from those regions where muscles attached presenting classical Sharpey's fibres. The pneumatized bones of several non-dinosaurian taxa do not exhibit the characteristics of this 'pneumosteum'. Our new histology-based approach thus can be instrumental in reconstructing the origin of air sacs among dinosaurs and hence for our understanding of this remarkable evolutionary novelty of the respiratory system. © 2018 The Author(s).

  12. 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.)

  13. 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

  14. Experimental, statistical and biological models of radon carcinogenesis

    International Nuclear Information System (INIS)

    Cross, F.T.

    1992-01-01

    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 with 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 programme 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 co-pollutant 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. (author)

  15. Cell proliferation in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, S.M.; Ellwein, L.B. (Univ. of Nebraska Medical Center, Omaha (USA))

    1990-08-31

    Chemicals that induce cancer at high doses in animal bioassays often fail to fit the traditional characterization of genotoxins. Many of these nongenotoxic compounds (such as sodium saccharin) have in common the property that they increase cell proliferation in the target organ. A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds. The carcinogenic dose-response relationship for genotoxic chemicals (such as 2-acetylaminofluorene) was also due in part to increased cell proliferation. Mechanistic information is required for determination of the existence of a threshold for the proliferative (and carcinogenic) response of nongenotoxic chemicals and the estimation of risk for human exposure.

  16. Recent advances in metal carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W. Jr.

    Recent advances in metal carcinogenesis are comprehensively reviewed, including (a) epidemiological and clinical aspects, (b) carcinogenesis bioassays, (c) bacterial mutagenesis, (d) mammalian cell mutagenesis, (e) chromosomal damage, (f) mammalian cell transformation, (g) microsomal metabolism, (h) DNA strandbreaks and crosslinks, (i) DNA polymerase infidelity, (j) RNA strand initiation, and (k) helical transition of B-DNA to Z-DNA. Based upon these observations, several hypotheses are proposed for the molecular pathogenesis of carcinogenesis by metal compounds. These hypotheses are amenable to experimental test by existing techniques of molecular biology.

  17. Gene amplification in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Lucimari Bizari

    2006-01-01

    Full Text Available Gene amplification increases the number of genes in a genome and can give rise to karyotype abnormalities called double minutes (DM and homogeneously staining regions (HSR, both of which have been widely observed in human tumors but are also known to play a major role during embryonic development due to the fact that they are responsible for the programmed increase of gene expression. The etiology of gene amplification during carcinogenesis is not yet completely understood but can be considered a result of genetic instability. Gene amplification leads to an increase in protein expression and provides a selective advantage during cell growth. Oncogenes such as CCND1, c-MET, c-MYC, ERBB2, EGFR and MDM2 are amplified in human tumors and can be associated with increased expression of their respective proteins or not. In general, gene amplification is associated with more aggressive tumors, metastases, resistance to chemotherapy and a decrease in the period during which the patient stays free of the disease. This review discusses the major role of gene amplification in the progression of carcinomas, formation of genetic markers and as possible therapeutic targets for the development of drugs for the treatment of some types of tumors.

  18. contribution to carcinogenesis

    Directory of Open Access Journals (Sweden)

    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.

  19. The Role of the Stroma in Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Nurija Bilalović

    2006-02-01

    Full Text Available This systematic review considers the most recent attitudes and news regarding the influence of the stroma on tumor initiation and progression. It is now widely accepted that tumor stroma plays an active role in carcinogenesis. Many different signaling molecules, ligands and signaling pathways recently have been discovered. This review considers the complexity of interactions between malignant cells and its stroma (cross-talk. The recent advances and better understanding of the tumor-stroma interactions will have important impact on the new and combined therapeutic approaches and modalities.

  20. 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)

  1. Respiratory mechanics

    CERN Document Server

    Wilson, Theodore A

    2016-01-01

    This book thoroughly covers each subfield of respiratory mechanics: pulmonary mechanics, the respiratory pump, and flow. It presents the current understanding of the field and serves as a guide to the scientific literature from the golden age of respiratory mechanics, 1960 - 2010. Specific topics covered include the contributions of surface tension and tissue forces to lung recoil, the gravitational deformation of the lung, and the interdependence forces that act on pulmonary airways and blood vessels. The geometry and kinematics of the ribs is also covered in detail, as well as the respiratory action of the external and internal intercostal muscles, the mechanics of the diaphragm, and the quantitative compartmental models of the chest wall is also described. Additionally, flow in the airways is covered thoroughly, including the wave-speed and viscous expiratory flow-limiting mechanisms; convection, diffusion and the stationary front; and the distribution of ventilation. This is an ideal book for respiratory ...

  2. 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)

  3. 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

  4. 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.

  5. 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

  6. Carcinogenesis mechanisms of Fusobacterium nucleatum.

    Science.gov (United States)

    Gholizadeh, Pourya; Eslami, Hosein; Kafil, Hossein Samadi

    2017-05-01

    Transformed cells of cancers may be related to stromal cells, immune cells, and some bacteria such as Fusobacterium nucleatum. This review aimed to evaluate carcinogenesis mechanisms of Fusobacterium spp. in the oral cavity, pancreatic and colorectal cancers. These cancers are the three of the ten most prevalence cancer in the worldwide. Recent findings demonstrated that F. nucleatum could be considered as the risk factor for these cancers. The most important carcinogenesis mechanisms of F. nucleatum are chronic infection, interaction of cell surface molecules of these bacteria with immune system and stromal cells, immune evasion and immune suppression. However, there are some uncertainty carcinogenesis mechanisms about these bacteria, but this review evaluates almost all the known mechanisms. Well-characterized virulence factors of F. nucleatum such as FadA, Fap2, LPS and cell wall extracts may act as effector molecules in the shift of normal epithelial cells to tumor cells. These molecules may provide new targets, drugs, and strategies for therapeutic intervention. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. MECHANISM OF CARCINOGENESIS OF THE POLYCYCLIC AROMATICHYDROCARBONS

    Energy Technology Data Exchange (ETDEWEB)

    Cavalieri, E.; Calvin, M.

    1970-08-01

    The carcinogenic activity of the benzo[a]pyrene 1, the 7,12-dimethylbenz[a]anthracene 2 and the 3-methylcholanthrene 3 is suggested to be determine by the electrophilic attack of the active oxygen, induced by the hydroxylating enzyme systems, on the most reactive substituting carbon atom(s). The cationic intermediate(s) with the charge mainly localized on a complementary, interrelated position(s) of the hydroxyl substituted position(s) reacts further with the cellular nucleophiles. The electrophilic nature of the ultimate chemical carcinogens constitutes the common distinctive feature that correlates their different structures and allows us to understand their carcinogenicity. The formation of a covalent bond with the nucleophiles of the biological macromolecules, nucleic acids and proteins, appears to be the essential requirement in the primary process of carcinogenesis.

  8. Maternal obesity mediated predisposition to respiratory complications at birth and in later life: understanding the implications of the obesogenic intrauterine environment.

    Science.gov (United States)

    McGillick, Erin V; Lock, Mitchell C; Orgeig, Sandra; Morrison, Janna L

    2017-01-01

    More women than not are entering pregnancy either overweight or obese. This presents a significant health care burden with respect to maternal morbidities and offspring complications at birth and in later life. In recent years it has also become clear that maternal obesity is an even greater global health problem than anticipated, because the effects are not limited to the mother but are also programmed in the fetus, known as the 'intergenerational cycle of obestiy'. Despite a large body of epidemiological evidence reporting outcomes of obese pregnancies, including offspring respiratory complications, much less is known about the molecular effects of maternal obesity on fetal lung development. This review focuses on the influence of altered substrate supply associated with the obesogenic intrauterine environment on fetal lung development. Understanding the molecular mechanisms contributing to altered fetal lung development will lead to improved respiratory outcomes for offspring at birth and in later life. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Carcinogenesis

    International Nuclear Information System (INIS)

    Reilly, C.A. Jr.

    1979-01-01

    This section contains summaries of research in the following areas: use of liver for mechanistic studies of multistage hepatocarcinogenesis and for screening of environmental contaminants for tumor initiating and promoting activity; molecular properties of rat liver ornithine aminotransferase; regulation of gene expression in rat liver; methods of tumor detection; mechanisms of radiation and viral oncogenesis; biphenyl metabolism by rat liver microsomes; and studies on aryl hydrocarbon hydroxylase activity

  10. Carcinogenesis

    International Nuclear Information System (INIS)

    Buess, E.M.; Cerny, E.A.; Chan, E.W.

    1977-01-01

    The first section deals with the assessment of carcinogens and cocarcinogens and the underlying mechanisms of their actions. The second concerns cancer induction by bone-seeking radionuclides and seeks to provide a firm foundation for estimating cancer risks to human populations in the event of accidental incorporation of radionuclides. The third is aimed at defining the role of oncornavirus activation in tumor induction by radiation and other environmental pollutants. The other two sections describe the new studies, one dealing with the development of an in vitro cell system (murine teratocarcinoma cells) to screen chemicals rapidly for carcinogenic and mutagenic capacity, and the other investigating the potential use of plasma isozymes as indicators of mutagenesis in mammals. Accomplishments and projections for each of these studies follow

  11. Respiratory tract carcinogenesis induced by radionuclides in the Syrian hamister

    International Nuclear Information System (INIS)

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

    1979-01-01

    Syrian hamsters were exposed to lung irradiation by various modalities that differed in degree of localization and the fraction of lung exposed. The animals were given alpha emitters under several exposure conditions: intratracheal (IT) instillation of 210 Po and 239 PuO 2 -ZrO 2 microspheres; inhalation (INH) of 238 239 PuO 2 -ZrO 2 particles; and/or intravenous (IV) injection of 238 239 PuO 2 -ZrO 2 microspheres. Beta-emitting 147 Pm was also administered; the radionuclide was incorporated into 10 μm diameter ZrO 2 microspheres and deposited in the lungs via the jugular vein. These microspheres lodge quantitatively in the pulmonary capillary bed for the duration of the animal's life span. Total IV Pu microsphere lung burdens have ranged from 0.14 nCi to 484 nCi and the number of spheres from 1500 to 880 000. Pu burdens from inhalation have ranged from 8 nCi to 101 nCi, IT Po burdens from 25 to 122 nCi, and Pm-laden microsphere burdens from 427 to 15 750 nCi. Intratracheal instillation of 210 Po solution gave nearly uniform alpha irradiation of the entire lung, intravenous injection of large numbers of ZrO 2 microspheres laden with 147 Pm gave whole lung exposures to low LET radiation, and IV injection of Pu-microspheres provided a gradation of focal alpha exposures. The Po and Pm exposures were highly tumorigenic, whereas the Pu microspheres produced tumors only when a large fraction of the lung was exposed to large radiation doses. However, Pu-ZrO 2 administered via inhalation was very carcinogenic and resulted in tumor incidences of 50% in some experiments. The IT instillation of Fe 2 O 3 following IV or IT Pu-ZrO 2 microsphere administration dramatically enhanced lung tumor induction

  12. 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.)

  13. Respiratory acidosis

    Science.gov (United States)

    Ventilatory failure; Respiratory failure; Acidosis - respiratory ... Causes of respiratory acidosis include: Diseases of the airways (such as asthma and COPD ) Diseases of the lung tissue (such as ...

  14. Biological aspects of radiation carcinogenesis

    International Nuclear Information System (INIS)

    Upton, A.C.

    1984-01-01

    Ionizing radiation has been observed to increase the incidence of virtually every type of neoplasm, and carcinogenic effects have been noted in all species investigated. Susceptibility varies markedly, however, with species, strain, organ, cell type, sex, age at irradiation, physiological condition, exposure to other physical or chemical agents, and additional variables. Because of the multicausal, multistage nature of the cancer process, and the diversity of mechanisms through which carcinogenesis may be influenced by irradiation, the variety of observed dose-incidence relationships is not unexpected. The data are consistent with the concept that cancer arises from a single transformed cell, through a stepwise succession of undefined changes, and that the process of transformation may be initiated by radiation-induced damage to the DNA of the affected cell. There is also evidence that intercellular interactions may play an important role in the evolution of the neoplastic process, the nature and radiobiology of which remain to be determined

  15. Genetic factors for breast carcinogenesis

    Directory of Open Access Journals (Sweden)

    Pedro Enrique Miguel-Soca

    2016-12-01

    Full Text Available Breast cancer is a multifactorial genenetic disease in which oncogenes derived from normal cellular genes intervene, which constitute positive signals of cellular proliferation and tumour suppressor genes and represent negative signals of cells multiplication and differentiation. Although these alterations which affect germinal cells produce inherited cancers, in most of the cases somatic cell genes are affected. To the susceptibility of cancer due to genes as BRCA1 and BCRA2, the effect of factors associated to environment, life style and toxic habits are added, these determine a complex interrelation genes-environment which imply an activation of oncogenes and inactivation of tumour suppressors. The objective of this review in to offer an updated view about the main genes implied in breast carcinogenesis. The topic is controversial y currently deeply investigated.

  16. 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

  17. 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)

  18. Regulatory miRNAs in Colorectal Carcinogenesis and Metastasis.

    Science.gov (United States)

    Guo, Yongchen; Bao, Yonghua; Yang, Wancai

    2017-04-22

    Colorectal cancer is one of the most common malignancies and is the second-leading cause of cancer-related death world-wide, which is linked to genetic mutations, epigenetic alterations, and oncogenic signaling activation. MicroRNAs, one of the categories of epigenetics, have been demonstrated significant roles in carcinogenesis and progression through regulating of oncogenic signaling pathways, stem cells, epithelial-mesenchymal transition, and metastasis. This review summarizes the roles of microRNAs in the regulating of Wnt, Ras, TGF-β, and inflammatory signaling pathways, stemness, and epithelial-mesenchymal transition, for carcinogenesis and metastasis in colorectal cancer. Improving our understanding of the mechanisms of regulatory interactions of microRNAs with signaling pathways in colorectal cancer formation and progression will aid in determining the genes responsible for colorectal cancer initiation, progression, metastasis, and recurrence and, finally, in developing personalized approaches for cancer prevention and therapy.

  19. 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

  20. 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.

  1. Somatic Host Cell Alterations in HPV Carcinogenesis.

    Science.gov (United States)

    Litwin, Tamara R; Clarke, Megan A; Dean, Michael; Wentzensen, Nicolas

    2017-08-03

    High-risk human papilloma virus (HPV) infections cause cancers in different organ sites, most commonly cervical and head and neck cancers. While carcinogenesis is initiated by two viral oncoproteins, E6 and E7, increasing evidence shows the importance of specific somatic events in host cells for malignant transformation. HPV-driven cancers share characteristic somatic changes, including apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC)-driven mutations and genomic instability leading to copy number variations and large chromosomal rearrangements. HPV-associated cancers have recurrent somatic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA ) and phosphatase and tensin homolog ( PTEN ), human leukocyte antigen A and B ( HLA-A and HLA-B ) -A/B , and the transforming growth factor beta (TGFβ) pathway, and rarely have mutations in the tumor protein p53 ( TP53 ) and RB transcriptional corepressor 1 ( RB1 ) tumor suppressor genes. There are some variations by tumor site, such as NOTCH1 mutations which are primarily found in head and neck cancers. Understanding the somatic events following HPV infection and persistence can aid the development of early detection biomarkers, particularly when mutations in precancers are characterized. Somatic mutations may also influence prognosis and treatment decisions.

  2. Somatic Host Cell Alterations in HPV Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tamara R. Litwin

    2017-08-01

    Full Text Available High-risk human papilloma virus (HPV infections cause cancers in different organ sites, most commonly cervical and head and neck cancers. While carcinogenesis is initiated by two viral oncoproteins, E6 and E7, increasing evidence shows the importance of specific somatic events in host cells for malignant transformation. HPV-driven cancers share characteristic somatic changes, including apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC-driven mutations and genomic instability leading to copy number variations and large chromosomal rearrangements. HPV-associated cancers have recurrent somatic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA and phosphatase and tensin homolog (PTEN, human leukocyte antigen A and B (HLA-A and HLA-B-A/B, and the transforming growth factor beta (TGFβ pathway, and rarely have mutations in the tumor protein p53 (TP53 and RB transcriptional corepressor 1 (RB1 tumor suppressor genes. There are some variations by tumor site, such as NOTCH1 mutations which are primarily found in head and neck cancers. Understanding the somatic events following HPV infection and persistence can aid the development of early detection biomarkers, particularly when mutations in precancers are characterized. Somatic mutations may also influence prognosis and treatment decisions.

  3. Human papillomaviruses and carcinogenesis: well-established and novel models.

    Science.gov (United States)

    Viarisio, Daniele; Gissmann, Lutz; Tommasino, Massimo

    2017-10-01

    Human papillomaviruses (HPVs) infect the cutaneous or mucosal epithelia and are classified phylogenetically as genera and species. Persistent infections by the mucosal high-risk (HR) HPV types from genus alpha are associated with cancer development of the genital and upper respiratory tracts. The products of two early genes, E6 and E7, are the major HR HPV oncoproteins, being essential in all steps of the carcinogenic process. Cutaneous beta HPV types are proposed, together with ultraviolet (UV) radiation, to promote non-melanoma skin cancer development. However, in contrast to the HR HPV types, beta HPV types appear to be required only at an early stage of carcinogenesis, facilitating the accumulation of UV-induced DNA mutations. Although findings in experimental models also suggest that beta HPV types and other carcinogens may synergize in the induction of malignancies, these possibilities need to be confirmed in human studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. 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.

  5. Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Gudjonsson, Thorkell; Nielsen, Ole Haagen

    2011-01-01

    -driven mechanisms of DNA damage, including the generation and effects of reactive oxygen species, microsatellite instability, telomere shortening and chromosomal instability, are reviewed, as are the molecular responses to genomic stress. We also discuss how these mechanisms can be translated into usable biomarkers....... Although progress has been made in the understanding of inflammation-driven carcinogenesis, markers based on these findings possess insufficient sensitivity or specificity to be usable as reliable biomarkers for risk of colorectal cancer development in patients with ulcerative colitis. However, screening...

  6. Modeling Multiple Causes of Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T D

    1999-01-24

    multiple causes of carcinogenesis and shifts the risk-assessment logic to considerations of "what dose does?" in contrast to the current process of the substance-specific question of "what dose is?" Whether reactive oxygen is the proximate or contributing cause of disease or simply a better estimate of biologically effective dose, it has enormous advantages for improved risk- and policy-based decisions. Various estimates of immune system modulation will be given based on radiobiology.

  7. Bacterionomics and vironomics in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Pratiwi Sudarmono

    2017-02-01

    Full Text Available Virus and bacteria are microbes which are very common cause human infection. Most of the bacterial infection can be eradicated by antibiotics and infection symptoms disappear. But for virus infection, once infected, the virus will persistently stay in the host, even undergo not only a lytic cycle but also integrated into host genome. Nowadays, at least 6 virus type are consistently related to human cancer, such as EBV,HPV,HTLV,HBV,HCV,HKSV, and the new one Merkel Virus (MCV. Although not every infected people will get cancer, but around 20% of the whole cancer in human are caused by viral oncogene. Class one oncogenic bacterial is Helicobacter pylori. Infection with this bacteria can cause persistent gastro duodenal inflammation which cause some alteration in gastric cell growth into transformation. Expression of Cag gene and Vac gene and some expression of OMP protein usually link to gastric cancer. Molecular mechanisms of carcinogenesis for every virus which cause infection  is a very complex , which include several processes caused by cell transformation. Besides, other host and environmental factors are also play a significant role in cancer development. Some scientist put a Hallmark analysis as a model to quickly summarize what pathobiology process will happen and what gene or protein caused the process. The Hallmark analysis comprise of several process which may happen simultaneously because some of the Hallmark is caused by the same protein. The Hallmark consists of various virus strategies in oncogenesis such as promoting angiogenesis, avoiding immune destruction, genome instability and mutation, deregulating cellular energetic, resisting cell death, sustaining proliferative signaling, evading growth suppressors, enabling cellular immortality, promoting inflammation and activation metastasis. For example, infection by HPV, will cause low grade dysplasia which can continue to invasive cervical cancer. After host cell transformation, in

  8. 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

  9. Attachment Orientations, Respiratory Sinus Arrhythmia, and Stress Are Important for Understanding the Link Between Childhood Socioeconomic Status and Adult Self-Reported Health.

    Science.gov (United States)

    Murdock, Kyle W; Fagundes, Christopher P

    2017-04-01

    Low childhood socioeconomic status (SES) is reliably associated with poor adult health. Social environments early in life and physiological stress responses are theorized to underlie this link; however, the role of attachment orientations is relatively unknown. In this study, we examined whether attachment orientations (i.e., attachment anxiety and attachment avoidance) and self-reported stress were mediators of the association between childhood SES and self-reported health in adulthood. Furthermore, we examined whether parasympathetic nervous system functioning was a moderator of associations between attachment orientations and self-reported stress. Participants (N = 213) provided self-reports of childhood SES, attachment orientations, general stress, and self-rated health. Respiratory sinus arrhythmia (RSA) was measured at rest, as well as during an acute social stressor. Low childhood SES was associated with poor self-reported health via the serial pathway from attachment anxiety to general stress. Moreover, attachment avoidance was associated with self-reported health via general stress, but only among those with high stress-induced RSA. Findings were independent of participant age, sex, race, body mass index, baseline RSA, and adult SES. Attachment theory is useful for understanding why those from low SES backgrounds are at greater risk of negative health outcomes in adulthood. Findings extend our knowledge of how interpersonal relationships in childhood can shape emotional and physical health outcomes in adulthood.

  10. 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

  11. 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.)

  12. 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

  13. Oral mucosal carcinogenesis in SENCAR mice.

    Science.gov (United States)

    Kim, Tae-Won; Chen, Qianming; Shen, Xiaodong; Regezi, Joseph A; Ramos, Daniel M; Tanaka, Hironori; Jordan, Richard C K; Kramer, Randall H

    2002-01-01

    Animal models of oral carcinogenesis have been developed but most use the hamster buccal pouch or rat oral mucosa. With completion of human and murine genome sequencing, the development of a mouse model of oral carcinogenesis may prove useful for future genomic studies of oral carcinogenesis. To achieve this objective, 30 SENCAR mice were initiated by brush application of palatal, buccal and tongue mucosa with 200 nmol 7,12-dimethylbenz[a]anthracene (DMBA) using 3 treatment regimens, and promoted by brush application with 5 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) for a total of 28 weeks. Alternatively, 5 mice were treated with 0.5% 4-nitroquinoline-1-oxide (4NQO) alone by brush application for 28 weeks. There were another 6 control mice treated with vehicle alone. The tumor samples were analyzed for the presence of H-ras codon 61 gene mutations using a mutant-allele-specific amplification-polymerase chain reaction (MASA-PCR) technique. The results showed that among the group of 24 mice initiated with DMBA for 2 or 6 weeks, a range of papilliferous lesions were seen on the buccal mucosa comprising papillomas, papillomas with dysplasia and 7 squamous cell carcinomas (SCC). In those 6 mice initiated with 1 week of DMBA, only papillomas developed. In the 5 mice treated with 4NQO, one developed papillomas with dysplasia and two had SCCs in the tongue mucosa but not the buccal mucosa. Both carcinogens induced codon 61 mutation of the H-ras gene at a high frequency. The results indicated that DMBA/TPA and 4NQO in SENCAR mice reliably produced preneoplastic and malignant oral cavity lesions, which resemble the multistages for human oral carcinogenesis, and targeted to site-specific zones of the oral mucosa, namely the buccal mucosa and tongue, respectively. These results show that SENCAR mice can be used as a unique model of oral carcinogenesis with the potential for detailed molecular studies of neoplastic progression to SCC.

  14. The human respiratory gate

    Science.gov (United States)

    Eckberg, Dwain L.

    2003-01-01

    Respiratory activity phasically alters membrane potentials of preganglionic vagal and sympathetic motoneurones and continuously modulates their responsiveness to stimulatory inputs. The most obvious manifestation of this 'respiratory gating' is respiratory sinus arrhythmia, the rhythmic fluctuations of electrocardiographic R-R intervals observed in healthy resting humans. Phasic autonomic motoneurone firing, reflecting the throughput of the system, depends importantly on the intensity of stimulatory inputs, such that when levels of stimulation are low (as with high arterial pressure and sympathetic activity, or low arterial pressure and vagal activity), respiratory fluctuations of sympathetic or vagal firing are also low. The respiratory gate has a finite capacity, and high levels of stimulation override the ability of respiration to gate autonomic responsiveness. Autonomic throughput also depends importantly on other factors, including especially, the frequency of breathing, the rate at which the gate opens and closes. Respiratory sinus arrhythmia is small at rapid, and large at slow breathing rates. The strong correlation between systolic pressure and R-R intervals at respiratory frequencies reflects the influence of respiration on these two measures, rather than arterial baroreflex physiology. A wide range of evidence suggests that respiratory activity gates the timing of autonomic motoneurone firing, but does not influence its tonic level. I propose that the most enduring significance of respiratory gating is its use as a precisely controlled experimental tool to tease out and better understand otherwise inaccessible human autonomic neurophysiological mechanisms.

  15. Respiratory Failure

    Science.gov (United States)

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, such as ... need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can't ...

  16. Respiratory system

    Science.gov (United States)

    Bartlett, R. G., Jr.

    1973-01-01

    The general anatomy and function of the human respiratory system is summarized. Breathing movements, control of breathing, lung volumes and capacities, mechanical relations, and factors relevant to respiratory support and equipment design are discussed.

  17. Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Gudjonsson, Thorkell; Nielsen, Ole Haagen

    2011-01-01

    One of the most serious complications of ulcerative colitis is the development of colorectal cancer. Screening patients with ulcerative colitis by standard histological examination of random intestinal biopsy samples might be inefficient as a method of cancer surveillance. This Review focuses...... on the current understanding of the pathogenesis of ulcerative colitis-associated colorectal cancer and how this knowledge can be transferred into patient management to assist clinicians and pathologists in identifying patients with ulcerative colitis who have an increased risk of colorectal cancer. Inflammation....... Although progress has been made in the understanding of inflammation-driven carcinogenesis, markers based on these findings possess insufficient sensitivity or specificity to be usable as reliable biomarkers for risk of colorectal cancer development in patients with ulcerative colitis. However, screening...

  18. Mismatch repair pathway: molecules, functions, and role in colorectal carcinogenesis.

    Science.gov (United States)

    Sameer, Aga Syed; Nissar, Saniya; Fatima, Kaneez

    2014-07-01

    The microsatellite instability (MSI) pathway is one of the important mutational pathways that play a critical role in colorectal carcinogenesis. About 15% of colorectal cancers (CRCs) are characterized by MSI. MSI tumors usually arise because of a genetic defect in mismatch repair (MMR) genes, one of the main DNA-repairing systems. MMR is a highly conserved biological pathway that plays a key role in maintaining genomic stability by correcting the base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Mutations in at least five pivotal genes of MMR, namely, in those encoding mutS homolog 2 (MSH2), mutL homolog 1 (MLH1), mutS homolog 6 (MSH6), postmeiotic segregation increased 1 (PMS1), and postmeiotic segregation, increased 2 (PMS2) have been found in CRC, highlighting the importance of understanding the basic structure and functions of the essential molecules that make up the MMR system. In this review, we have attempted to focus on this aspect, that is, the role that MMR molecules play in CRC carcinogenesis.

  19. 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

  20. Somatic Host Cell Alterations in HPV Carcinogenesis

    OpenAIRE

    Tamara R. Litwin; Megan A. Clarke; Michael Dean; Nicolas Wentzensen

    2017-01-01

    High-risk human papilloma virus (HPV) infections cause cancers in different organ sites, most commonly cervical and head and neck cancers. While carcinogenesis is initiated by two viral oncoproteins, E6 and E7, increasing evidence shows the importance of specific somatic events in host cells for malignant transformation. HPV-driven cancers share characteristic somatic changes, including apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC)-driven mutations and genomic instability ...

  1. 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

  2. Inhibition of carcinogenesis by retinoids. [Review

    Energy Technology Data Exchange (ETDEWEB)

    Nettesheim, P.

    1979-01-01

    Progress made in recent years in the search for retinoids with anticarcinogenic activity is reviewed. There are many studies to be found in the literature which show no substantial effect of retinoids on carcinogenesis or tumor growth. Some of these negative findings may be related to the carcinogen dose used, the type of retinoid used, the dose, dose schedule or mode of administration of the retinoid. Others may indicate that the particular type of tumor or tumor system is, indeed, refractory to retinoids in general or to those retinoids that were tested. A great gap still exists in our knowledge concerning the pharmake-kinetics of most retinoids their availability to various normal and cancerous tissues, and the role and existence of transport and binding proteins. There are studies which indicate that under certain conditions, particularly conditions of topical application, some retinoids may even enhance carcinogenesis. It seems, however, indisputable by now that some retinoids are effective inhibitors of carcinogenesis in some organ systems and can even inhibit the growth of some established tumors. While the mechanisms of these inhibitory effects are presently not understood, it does seem clear that they are not mediated via the cytotoxic mechanisms typical of chemotherapeutic agents. The hope that retinoids might become an effective tool to halt the progression of some neoplastic diseases, seems to be justified.

  3. 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.)

  4. Oxidative stress in prostate hypertrophy and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Waldemar M. Przybyszewski

    2009-07-01

    Full Text Available Aging, significant impairment of the oxidation/reduction balance, infection, and inflammation are recognized risk factors of benign hyperplasia and prostate cancer. Chronic symptomatic and asymptomatic prostate inflammatory processes generate significantly elevated levels of reactive oxygen and nitrogen species, and halogenated compounds. Prostate cancer patients showed significantly higher lipid peroxidation and lower antioxidant levels in peripheral blood than healthy controls, whereas patients with prostate hyperplasia did not show such symptoms. Oxidative/nitrosative/halogenative stress causes DNA modifications leading to genome instability that may initiate carcinogenesis; however, it was shown that oxidative damage alone is not sufficient to initiate this process. Peroxidation products induced by reactive oxygen and nitrogen species seem to take part in epigenetic mechanisms regulating genome activity. One of the most common changes occurring in more than 90�0of all analyzed prostate cancers is the silencing of GSTP1 gene activity. The gene encodes glutathione transferase, an enzyme participating in detoxification processes. Prostate hyperplasia is often accompanied by chronic inflammation and such a relationship was not observed in prostate cancer. The participation of infection and inflammation in the development of hyperplasia is unquestionable and these factors probably also take part in initiating the early stages of prostate carcinogenesis. Thus it seems that therapeutic strategies that prevent genome oxidative damage in situations involving oxidative/nitrosative/halogenative stress, i.e. use of antioxidants, plant steroids, antibiotics, and non-steroidal anti-inflammatory drugs, could help prevent carcinogenesis.

  5. 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.

  6. [The role of sonic hedgehog pathway in skin carcinogenesis].

    Science.gov (United States)

    Lesiak, Aleksandra; Sysa-Jedrzejowska, Anna; Narbutt, Joanna

    2010-08-01

    Non melanoma skin cancers (NMSC) involving basal (BCC)--and squamosus cell carcinomas (SCC) and are the most frequent skin cancers in Caucasians. Ultraviolet radiation is the main environmental risk factor for NMSC development. The aim of this paper is to review the latest opinions concerning the role of sonic hedgehog pathway in non-melanoma skin cancers development. Experimental data indicate that sonic hedgehog pathway might be involved in skin carcinogenesis. Under physiological conditions sonic hedgehog pathway is responsible for normal embryogenesis, regeneration of damaged tissues and for regulation of cell proliferation. It was revealed that UVR caused inactivated mutation in PATCHED gene encoding Ptch1 protein. These events lead to deregulation of sonic hedgehog pathway trough activation of Smo protein and Gli transcriptional factors what stimulates cell proliferation and in consequence NMSC development. Literature data indicate that understanding of molecular background of skin cancers might be a reason for introduction of new therapeutic approaches including sonic hedgehog pathway inhibitors.

  7. 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.

  8. Physiology of respiratory disturbances in muscular dystrophies

    Directory of Open Access Journals (Sweden)

    Antonella Lo Mauro

    2016-12-01

    To understand the mechanisms leading to respiratory disturbances in patients with muscular dystrophy. To understand the impact of respiratory disturbances in patients with muscular dystrophy. To provide a brief description of the main forms of muscular dystrophy with their respiratory implications.

  9. 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.

  10. NADPH Oxidases and Their Roles in Skin Homeostasis and Carcinogenesis.

    Science.gov (United States)

    Rudolf, Jana; Raad, Houssam; Taieb, Alain; Rezvani, Hamid Reza

    2017-11-17

    Skin protects the body from dehydration, pathogens, and external mutagens. NADPH oxidases are central components for regulating the cellular redox balance. There is increasing evidence indicating that reactive oxygen species (ROS) generated by members of this enzyme family play important roles in the physiology and pathophysiology of the skin. Recent Advances: NADPH oxidases are active producers of ROS such as superoxide and hydrogen peroxide. Different isoforms are found in virtually all tissues. They play pivotal roles in normal cell homeostasis and in the cellular responses to various stressors. In particular, these enzymes are integral parts of redox-sensitive prosurvival and proapoptotic signaling pathways, in which they act both as effectors and as modulators. However, continuous (re)activation of NADPH oxidases can disturb the redox balance of cells, in the worst-case scenario in a permanent manner. Abnormal NADPH oxidase activity has been associated with a wide spectrum of diseases, as well as with aging and carcinogenesis. Sunlight with its beneficial and deleterious effects induces the activation of NADPH oxidases in the skin. Evidence for the important roles of this enzyme family in skin cancer and skin aging, as well as in many chronic skin diseases, is now emerging. Understanding the precise roles of NADPH oxidases in normal skin homeostasis, in the cellular responses to solar radiation, and during carcinogenesis will pave the way for their validation as therapeutic targets not only for the prevention and treatment of skin cancers but also for many other skin-related disorders. Antioxid. Redox Signal. 00, 000-000.

  11. Paradoxes in carcinogenesis: New opportunities for research directions

    Directory of Open Access Journals (Sweden)

    Kramer Barnett S

    2007-08-01

    Full Text Available Abstract Background The prevailing paradigm in cancer research is the somatic mutation theory that posits that cancer begins with a single mutation in a somatic cell followed by successive mutations. Much cancer research involves refining the somatic mutation theory with an ever increasing catalog of genetic changes. The problem is that such research may miss paradoxical aspects of carcinogenesis for which there is no likely explanation under the somatic mutation theory. These paradoxical aspects offer opportunities for new research directions that should not be ignored. Discussion Various paradoxes related to the somatic mutation theory of carcinogenesis are discussed: (1 the presence of large numbers of spatially distinct precancerous lesions at the onset of promotion, (2 the large number of genetic instabilities found in hyperplastic polyps not considered cancer, (3 spontaneous regression, (4 higher incidence of cancer in patients with xeroderma pigmentosa but not in patients with other comparable defects in DNA repair, (5 lower incidence of many cancers except leukemia and testicular cancer in patients with Down's syndrome, (6 cancer developing after normal tissue is transplanted to other parts of the body or next to stroma previously exposed to carcinogens, (7 the lack of tumors when epithelial cells exposed to a carcinogen were transplanted next to normal stroma, (8 the development of cancers when Millipore filters of various pore sizes were was inserted under the skin of rats, but only if the holes were sufficiently small. For the latter paradox, a microarray experiment is proposed to try to better understand the phenomena. Summary The famous physicist Niels Bohr said "How wonderful that we have met with a paradox. Now we have some hope of making progress." The same viewpoint should apply to cancer research. It is easy to ignore this piece of wisdom about the means to advance knowledge, but we do so at our peril.

  12. Curcumin: the spicy modulator of breast carcinogenesis.

    Science.gov (United States)

    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.

  13. Oncogenomic disruptions in arsenic-induced carcinogenesis.

    Science.gov (United States)

    Sage, Adam P; Minatel, Brenda C; Ng, Kevin W; Stewart, Greg L; Dummer, Trevor J B; Lam, Wan L; Martinez, Victor D

    2017-04-11

    Chronic exposure to arsenic affects more than 200 million people worldwide, and has been associated with many adverse health effects, including cancer in several organs. There is accumulating evidence that arsenic biotransformation, a step in the elimination of arsenic from the human body, can induce changes at a genetic and epigenetic level, leading to carcinogenesis. At the genetic level, arsenic interferes with key cellular processes such as DNA damage-repair and chromosomal structure, leading to genomic instability. At the epigenetic level, arsenic places a high demand on the cellular methyl pool, leading to global hypomethylation and hypermethylation of specific gene promoters. These arsenic-associated DNA alterations result in the deregulation of both oncogenic and tumour-suppressive genes. Furthermore, recent reports have implicated aberrant expression of non-coding RNAs and the consequential disruption of signaling pathways in the context of arsenic-induced carcinogenesis. This article provides an overview of the oncogenomic anomalies associated with arsenic exposure and conveys the importance of non-coding RNAs in the arsenic-induced carcinogenic process.

  14. Modifying factors in urinary bladder carcinogenesis

    Science.gov (United States)

    Ito, Nobuyuki; Fukushima, Shoji; Shirai, Tomoyuki; Nakanishi, Keisuke; Hasegawa, Ryohei; Imaida, Katsumi

    1983-01-01

    N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is a potent carcinogen in the urinary bladder of animals. The BBN model of bladder cancer is an excellent model of human urinary bladder cancer and has already led to a greater knowledge of its pathogenesis. In our studies, histogenesis and morphological characteristics of BBN urinary bladder cancer were analyzed in different animal species such as rats, mice, hamsters and guinea pigs and also in different rat strains. Papillary or nodular hyperplasia (PN hyperplasia) is found to be a preneoplastic lesion of the rat urinary bladder. Therefore, the promoting and inhibitory effects of various chemicals in two-stage urinary bladder carcinogenesis were judged by measuring PN hyperplasia in rats. Dose-dependent and organ-specific effects of the urinary bladder promoter, saccharin, in the induction of PN hyperplasia were shown in rats after initiation by BBN. The promoting effect of saccharin was seen more clearly in the urinary bladder of rats after potent initiation. A strain difference in susceptibility of the urinary bladder to the promoter was also shown. These results suggest that the above various factors may also have modifying activities on urinary bladder carcinogenesis in man. PMID:6832095

  15. 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

  16. Transgenerational teratogenesis and carcinogenesis by radiation

    International Nuclear Information System (INIS)

    Nomura, Taisei

    2000-01-01

    This paper thoroughly reviews studies on transgenerational teratogenesis and carcinogenesis induced by radiation and summarizes currently available data from animal studies. The discussions focus on the incidence of tumors, malformations, and mutations in the offspring after parental exposure to radiation, as well as estimated relative risks of congenital malformations and stillbirths in the offspring after parental X-ray exposure. The data suggest that different types of tumors are induced in offspring, because of strain differences in the experimental animals. The results of epidemiological studies in human populations, such as the children of atomic bomb survivors, conflict with the findings in animal studies. The author points to the following reasons for the differences between the results in animals and humans: differences in radiation doses, timing of exposure, and genetic predisposition, etc. While pointing out issues that need to be investigated further, the author indicates that clear strain differences exist in types of tumors induced and in tumor incidences in the offspring of animals that were irradiated before the offspring were conceived, and that genetic predisposition is therefore important in transgenerational carcinogenesis. (K.H.)

  17. Transgenerational teratogenesis and carcinogenesis by radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Taisei [Osaka Univ., Suita (Japan). Graduate School of Medicine

    2000-07-01

    This paper thoroughly reviews studies on transgenerational teratogenesis and carcinogenesis induced by radiation and summarizes currently available data from animal studies. The discussions focus on the incidence of tumors, malformations, and mutations in the offspring after parental exposure to radiation, as well as estimated relative risks of congenital malformations and stillbirths in the offspring after parental X-ray exposure. The data suggest that different types of tumors are induced in offspring, because of strain differences in the experimental animals. The results of epidemiological studies in human populations, such as the children of atomic bomb survivors, conflict with the findings in animal studies. The author points to the following reasons for the differences between the results in animals and humans: differences in radiation doses, timing of exposure, and genetic predisposition, etc. While pointing out issues that need to be investigated further, the author indicates that clear strain differences exist in types of tumors induced and in tumor incidences in the offspring of animals that were irradiated before the offspring were conceived, and that genetic predisposition is therefore important in transgenerational carcinogenesis. (K.H.)

  18. In Vivo Testing of Chemopreventive Agents Using the Dog Model of Spontaneous Prostate Carcinogenesis

    Science.gov (United States)

    2001-03-01

    that there would be tional health survey of 211 Irish setter dogs (L.T. Glick- no advantage for members of a highly domesticated man, unpublished results...understand the mechanisms of prostate cancer development. This research will benefit the health and welfare of both dogs and humans. ACKNOWLEDGMENT This...AD Award Number: DAMD17-98-1-8550 TITLE: In Vivo Testing of Chemopreventive Agents Using the Dog Model of Spontaneous Prostate Carcinogenesis

  19. Pulmonary carcinogenesis from plutonium-containing particles

    International Nuclear Information System (INIS)

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

    1980-01-01

    Plutonium administered as an alpha radiation source to the respiratory tracts of Syrian hamsters has resulted in various incidences of neoplasia. Adenomas are the primary lung tumor observed, but adenocarcinomas are also prevalent

  20. Respiratory alkalosis

    Science.gov (United States)

    ... a condition marked by a low level of carbon dioxide in the blood due to breathing excessively. ... aimed at the condition that causes respiratory alkalosis. Breathing ... dioxide -- sometimes helps reduce symptoms when anxiety is the ...

  1. Angiogenesis, Thrombospondin-1 and Cervical Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Ming-Ping Wu

    2005-06-01

    Full Text Available Angiogenesis, the growth of new vessels from existing vasculature, plays an essential role in tumor development. The process involves interaction among cancer cells, endothelial cells, and components of the extracellular matrix, and is regulated by the balance of angiogenesis activators and angiogenesis inhibitors. This review profiles some fundamental concepts of angiogenesis, the importance of angiogenesis in cervical neoplasm, and the role of thrombospondin-1 as an angiogenesis inhibitor in cervical carcinogenesis. The usefulness and limitations of microvessel density in evaluation of angiogenic status are also discussed. Recent research and evolving concepts have led to a paradigm shift in anticancer therapy, from conventional cancer-centered chemotherapy to angiogenic or “metronomic” chemotherapy and/or combined angiogenesis inhibitors. The epigenetic strategy, which views the tumor system as a whole, transcends the cancer gene-centered approach.

  2. (Radiation carcinogenesis in the whole body system)

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Parasite Infection, Carcinogenesis and Human Malignancy

    Directory of Open Access Journals (Sweden)

    Hoang van Tong

    2017-02-01

    Full Text Available Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity.

  4. 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.

  5. Defining the role of polyamines in colon carcinogenesis using mouse models

    Directory of Open Access Journals (Sweden)

    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.

  6. Dynamic changes in the gene expression profile during rat oral carcinogenesis induced by 4-nitroquinoline 1-oxide.

    Science.gov (United States)

    Ge, Shuyun; Zhang, Ji; Du, Yanzhi; Hu, Bin; Zhou, Zengtong; Lou, Jianing

    2016-03-01

    The typical progression of oral cancer is from hyperplastic epithelial lesions through dysplasia to invasive carcinoma. It is important to investigate malignant oral cancer progression and development in order to determine useful approaches of prevention of dysplastic lesions. The present study aimed to gain insights into the underlying molecular mechanism of oral carcinogenesis by establishing a rat model of oral carcinogenesis using 4‑nitroquinoline 1‑oxide. Subsequently, transcription profile analysis using an integrating microarray was performed. The dynamic gene expression changes of the six stages of rat oral carcinogenesis (normal, mild epithelial dysplasia, moderate dysplasia, severe dysplasia, carcinoma in situ and oral squamous cell carcinomas) were analyzed using component plane presentations (CPP)‑self‑organizing map (SOM). Six genes were verified by quantitative polymerase chain reaction, immunohistochemistry and succinate dehydrogenase (SDH) activity assay kit. Numerous differentially expressed genes (DEGs) were identified during rat oral carcinogenesis. CPP‑SOM determined that these DEGs were primarily enriched during cell cycle, apoptosis, inflammatory response and tricarboxylic acid cycle, indicating the coordinated regulation of molecular networks. In addition, the expression of specific DEGs, such as janus kinase 3, cyclin‑dependent kinase A‑1, B‑cell chronic lymphocytic leukaemia/lymphoma 2‑like 2, nuclear factor‑κB, tumor necrosis factor receptor superfamily member 1A, cyclin D1 and SDH were identified to have high concordance with the results from microarray data. The current study demonstrated that oral carcinogenesis is a multi‑step and multi‑gene process, with a distinct pattern alteration along a continuum of malignant transformation. In addition, this comprehensive investigation provided a theoretical basis for the understanding of the molecular alterations associated with oral carcinogenesis.

  7. Implementing change in respiratory care.

    Science.gov (United States)

    Stoller, James K

    2010-06-01

    Though people are generally averse to change, change and innovation are critically important in respiratory care to maintain scientific and clinical progress. This paper reviews the issue of change in respiratory care. I summarize several available models of organizational and personal change (ie, those of Kotter and of Silversin and Kornacki, and the Intentional Change Theory of Boyatzis), review the characteristics of change-avid respiratory therapy departments, offer an example of a change effort in respiratory care (implementation of respiratory care protocols) and then analyze this change effort as it took place at one institution, the Cleveland Clinic, using these models. Finally, I present the results of an analysis of change-avid respiratory therapy departments and offer some suggestions regarding change management for the profession and for individual respiratory care clinicians. Common features of theories of organizational change include developing a sense of urgency, overcoming resistance, developing a guiding coalition, and involving key stakeholders early. With the understanding that change efforts may seem unduly "clean" and orderly in retrospect, the models help explain the sustainable success of efforts to implement the Respiratory Therapy Consult Service at the Cleveland Clinic. By implication, these models offer value in planning change efforts prospectively. Further analysis of features of change-avid respiratory therapy departments indicates 11 highly desired features, of which four that especially characterize change-avid departments include: having an up-to-date leadership team; employee involvement in change; celebrating wins; and an overall sense of progressiveness in the department. This analysis suggests that understanding and embracing change is important. To anchor change in our profession, greater attention should be given to developing a pipeline of respiratory care clinicians who, by virtue of their advanced training, have the skills

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Exocrine pancreatic carcinogenesis and autotaxin expression.

    Directory of Open Access Journals (Sweden)

    Sandeep Kadekar

    Full Text Available Exocrine pancreatic cancer is an aggressive disease with an exceptionally high mortality rate. Genetic analysis suggests a causative role for environmental factors, but consistent epidemiological support is scarce and no biomarkers for monitoring the effects of chemical pancreatic carcinogens are available. With the objective to identify common traits for chemicals inducing pancreatic tumors we studied the National Toxicology Program (NTP bioassay database. We found that male rats were affected more often than female rats and identified eight chemicals that induced exocrine pancreatic tumors in males only. For a hypothesis generating process we used a text mining tool to analyse published literature for suggested mode of actions (MOA. The resulting MOA analysis suggested inflammatory responses as common feature. In cell studies we found that all the chemicals increased protein levels of the inflammatory protein autotaxin (ATX in Panc-1, MIA PaCa-2 or Capan-2 cells. Induction of MMP-9 and increased invasive migration were also frequent effects, consistent with ATX activation. Testosterone has previously been implicated in pancreatic carcinogenesis and we found that it increased ATX levels. Our data show that ATX is a target for chemicals inducing pancreatic tumors in rats. Several lines of evidence implicate ATX and its product lysophosphatidic acid in human pancreatic cancer. Mechanisms of action may include stimulated invasive growth and metastasis. ATX may interact with hormones or onco- or suppressor-genes often deregulated in exocrine pancreatic cancer. Our data suggest that ATX is a target for chemicals promoting pancreatic tumor development.

  14. Inflammation, oxidative DNA damage, and carcinogenesis

    International Nuclear Information System (INIS)

    Lewis, J.G.; Adams, D.O.

    1987-01-01

    Inflammation has long been associated with carcinogenesis, especially in the promotion phase. The mechanism of action of the potent inflammatory agent and skin promoter 12-tetradecanoyl phorbol-13-acetate (TPA) is unknown. It is though that TPA selectively enhances the growth of initiated cells, and during this process, initiated cells progress to the preneoplastic state and eventually to the malignant phenotype. The authors and others have proposed that TPA may work, in part, by inciting inflammation and stimulating inflammatory cells to release powerful oxidants which then induce DNA damage in epidermal cells. Macrophages cocultured with target cells and TPA induce oxidized thymine bases in the target cells. This process is inhibited by both catalase and inhibitors of lipoxygenases, suggesting the involvement of both H 2 O 2 and oxidized lipid products. In vivo studies demonstrated that SENCAR mice, which are sensitive to promotion by TPA, have a more intense inflammatory reaction in skin that C57LB/6 mice, which are resistant to promotion by TPA. In addition, macrophages from SENCAR mice release more H 2 O 2 and metabolites of AA, and induce more oxidative DNA damage in cocultured cells than macrophages from C57LB/6 mice. These data support the hypothesis that inflammation and the release of genotoxic oxidants may be one mechanism whereby initiated cells receive further genetic insults. They also further complicate risk assessment by suggesting that some environmental agents may work indirectly by subverting host systems to induce damage rather than maintaining homeostasis

  15. Hypoxia and Angiogenesis in Endometrioid Endometrial Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Nicole Horrée

    2007-01-01

    Full Text Available Background: Hypoxia-inducible factor 1α (HIF-1α plays an essential role in the adaptive response of cells to hypoxia, triggering biologic events associated with aggressive tumor behavior. Methods: Expression of HIF-1α and proteins in the HIF-1α pathway (Glut-1, CAIX, VEGF in paraffin-embedded specimens of normal (n = 17, premalignant (n = 17 and endometrioid endometrial carcinoma (n = 39 was explored by immunohistochemistry, in relation to microvessel density (MVD. Results: HIF-1α overexpression was absent in inactive endometrium but present in hyperplasia (61% and carcinoma (87%, with increasing expression in a perinecrotic fashion pointing to underlying hypoxia. No membranous expression of Glut-1 and CAIX was noticed in inactive endometrium, in contrast with expression in hyperplasia (Glut-1 0%, CAIX 61%, only focal and diffuse and carcinoma (Glut-1 94.6%, CAIX 92%, both mostly perinecrotically. Diffuse HIF-1α was accompanied by activation of downstream targets. VEGF was significantly higher expressed in hyperplasias and carcinomas compared to inactive endometrium. MVD was higher in hyperplasias and carcinomas than in normal endometrium (p < 0.001. Conclusion: HIF-1α and its downstream genes are increasingly expressed from normal through premalignant to endometrioid adenocarcinoma of the endometrium, paralleled by activation of its downstream genes and increased angiogenesis. This underlines the potential importance of hypoxia and its key regulator HIF-1α in endometrial carcinogenesis.

  16. Carcinogenesis induced by low-dose radiation

    Directory of Open Access Journals (Sweden)

    Piotrowski Igor

    2017-11-01

    Full Text Available Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.

  17. Multistage chemical carcinogenesis in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Slaga, T.J.; Fischer, S.M.; Weeks, C.E.; Klein-Szanto, A.J.P.

    1979-01-01

    Skin tumors in mice can be induced by the sequential application of a subthreshold dose of a carcinogen (initiation phase) followed by repetitive treatment with a noncarcinogenic tumor promoter. The initiation phase requires only a single application of either a direct acting carcinogen or a procarcinogen which has to be metabolized before being active and is essentially an irreversible step which probably involves a somatic cell mutation. There is a good correlation between the skin tumor initiating activites of several polycyclic aromatic hydrocarbons (PAH) and their ability to bind covalently to epidermal DNA. Laboratory results suggest that bay region diol-epoxides are the ultimate carcinogenic form of PAH carcinogens. Potent inhibitors and stimulators of PAH tumor initiation appear to affect the level of the PAH diol-epoxide reacting with specific DNA bases. Reecent data suggests that the tumor promotion stage involves at least three important steps: (1) the induction of embryonic looking cells (dark cells) in adult epidermis; (2) an increased production of epidermal prostaglandins and polyamines; (3) sustained proliferation of dark cells. Retinoic acid specifically inhibits step two whereas the anti-inflammatory steriod fluocinolone acetonide is a potent inhibitor of steps one and three. The mechanism and the importance of a specific sequence for each step in chemical carcinogenesis in mouse skin are detailed.

  18. Experimental carcinogenesis induced by incorporated plutonium

    Energy Technology Data Exchange (ETDEWEB)

    Oghiso, Yoichi [National Inst. of Radiological Sciences, Chiba (Japan)

    1999-06-01

    The carcinogenic effects of an alpha-emitter, {sup 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)

  19. Loss of HLTF function promotes intestinal carcinogenesis

    Directory of Open Access Journals (Sweden)

    Sandhu Sumit

    2012-03-01

    Full Text Available Abstract Background HLTF (Helicase-like Transcription Factor is a DNA helicase protein homologous to the SWI/SNF family involved in the maintenance of genomic stability and the regulation of gene expression. HLTF has also been found to be frequently inactivated by promoter hypermethylation in human colon cancers. Whether this epigenetic event is required for intestinal carcinogenesis is unknown. Results To address the role of loss of HLTF function in the development of intestinal cancer, we generated Hltf deficient mice. These mutant mice showed normal development, and did not develop intestinal tumors, indicating that loss of Hltf function by itself is insufficient to induce the formation of intestinal cancer. On the Apcmin/+ mutant background, Hltf- deficiency was found to significantly increase the formation of intestinal adenocarcinoma and colon cancers. Cytogenetic analysis of colon tumor cells from Hltf -/-/Apcmin/+ mice revealed a high incidence of gross chromosomal instabilities, including Robertsonian fusions, chromosomal fragments and aneuploidy. None of these genetic alterations were observed in the colon tumor cells derived from Apcmin/+ mice. Increased tumor growth and genomic instability was also demonstrated in HCT116 human colon cancer cells in which HLTF expression was significantly decreased. Conclusion Taken together, our results demonstrate that loss of HLTF function promotes the malignant transformation of intestinal or colonic adenomas to carcinomas by inducing genomic instability. Our findings highly suggest that epigenetic inactivation of HLTF, as found in most human colon cancers, could play an important role in the progression of colon tumors to malignant cancer.

  20. 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.)

  1. Biologically-based mechanistic models of radiation-related carcinogenesis applied to epidemiological data.

    Science.gov (United States)

    Rühm, Werner; Eidemüller, Markus; Kaiser, Jan Christian

    2017-10-01

    Biologically-based mechanistic models that are used in combining current understanding of human carcinogenesis with epidemiological studies were reviewed. Assessment was made of how well they fit the data, whether they account for non-linear radiobiological low-dose effects, and whether they suggest any implications for the dose response at low doses and dose rates. However, the present paper does not make an attempt to provide a complete review of the existing literature on biologically-based models and their application to epidemiological data. In most studies the two-stage clonal expansion (TSCE) model of carcinogenesis was used. The model provided robust estimates of identifiable parameters and radiation risk. While relatively simple, it is flexible, so that more stages can easily be added, and tests made of various types of radiation action. In general, the model performed similarly or better than descriptive excess absolute and excess relative risk models, in terms of quality of fit and number of parameters. Only very rarely the shape of dose-response predicted by the models was investigated. For some tumors, when more detailed biological information was known, additional pathways were included in the model. The future development of these models will benefit from growing knowledge on carcinogenesis processes, and in particular from use of biobank tissue samples and advances in omics technologies. Their use appears a promising approach to investigate the radiation risk at low doses and low dose rates. However, the uncertainties involved are still considerable, and the models provide only a simplified description of the underlying complexity of carcinogenesis. Current assumptions in radiation protection including the linear-non-threshold (LNT) model are not in contradiction to what is presently known on the process of cancer development.

  2. Respiratory Home Health Care

    Science.gov (United States)

    ... Healthy Living > Living With Lung Disease > Respiratory Home Health Care Font: Aerosol Delivery Oxygen Resources Immunizations Pollution Nutrition ... Disease Articles written by Respiratory Experts Respiratory Home Health Care Respiratory care at home can contribute to improved ...

  3. Implications of tyrosine phosphoproteomics in cervical carcinogenesis

    Directory of Open Access Journals (Sweden)

    DeFord James

    2008-01-01

    Full Text Available Abstract Background Worldwide cervical cancer remains a leading cause of mortality from gynecologic malignancies. The link between cervical cancer and persistent infection with HPV has been established. At a molecular level little is known about the transition from the precancerous state to invasive cancer. To elucidate this process, cervical biopsies from human specimens were obtained from precancerous state to stage III disease. Methods Cervical biopsies were obtained from patients with a diagnosis of cervical cancer undergoing definitive surgery or staging operation. Biopsies were obtained from patients with precancerous lesions at the time of their excisional procedure. Control samples were obtained from patients undergoing hysterectomy for benign conditions such as fibroids. Samples were subjected to proteomic profiling using two dimensional gel electrophoresis with subsequent trypsin digestion followed by MALDI-TOF protein identification. Candidate proteins were then further studied using western blotting, immunoprecipitation and immunohistochemistry. Results Annexin A1 and DNA-PKcs were found to be differentially expressed. Phosphorylated annexin A1 was up regulated in diseased states in comparison to control and its level was strongly detected in the serum of cervical cancer patients compared to controls. DNA-PKcs was noted to be hyperphosphorylated and fragmented in cancer when compared to controls. By immunohistochemistry annexin A1 was noted in the vascular environment in cancer and certain precancerous samples. Conclusion This study suggests a probable role for protein tyrosine phosphorylation in cervical carcinogenesis. Annexin A1 and DNA-PK cs may have synergistic effects with HPV infection. Precancerous lesions that may progress to cervical cancer may be differentiated from lesions that will not base on similar immunohistochemical profile to invasive squamous cell carcinoma.

  4. Mustard gas exposure and carcinogenesis of lung.

    Science.gov (United States)

    Hosseini-khalili, Alireza; Haines, David D; Modirian, Ehsan; Soroush, Mohammadreza; Khateri, Shahriar; Joshi, Rashmi; Zendehdel, Kazem; Ghanei, Mostafa; Giardina, Charles

    2009-08-01

    Sulfur mustard (SM), also known as mustard gas, is an alkylating compound used as a chemical weapon in World War I and by Iraqi forces against Iranians and indigenous Iraqi Kurds during the Iran-Iraq War of the 1980s. Although SM is a proven carcinogen there are conflicting views regarding the carcinogenicity of a single exposure. The present study characterizes lung cancers formed in mustard gas victims from the Iran-Iraq War. Demographic information and tumor specimens were collected from 20 Iranian male lung cancer patients with single high-dose SM exposures during the Iran-Iraq War. Formalin-fixed, paraffin-embedded lung cancers were analyzed by immunohistochemistry for p53 protein. In addition, DNA was extracted from the tissues, PCR amplified and sequenced to identify mutations in the p53 and KRAS genes associated with SM exposure. A relatively early age of lung cancer onset (ranging from 28 to 73 with a mean of 48) in mustard gas victims, particularly those in the non-smoking population (mean age of 40.7), may be an indication of a unique etiology for these cancers. Seven of the 20 patients developed lung cancer before the age of 40. Five of 16 cancers from which DNA sequence data was obtainable provided information on eight p53 mutations (within exons 5-8). These mutations were predominately G to A transitions; a mutation consistent with the DNA lesion caused by SM. Two of the lung cancers had multiple p53 point mutations, similar to results obtained from factory workers chronically exposed to mustard agent. No mutations were detected in the KRAS gene. The distinguishing characteristics of lung carcinogenesis in these mustard gas victims suggest that a single exposure may increase the risk of lung cancer development in some individuals.

  5. Physiology of respiratory disturbances in muscular dystrophies.

    Science.gov (United States)

    Lo Mauro, Antonella; Aliverti, Andrea

    2016-12-01

    breathing. To understand the mechanisms leading to respiratory disturbances in patients with muscular dystrophy.To understand the impact of respiratory disturbances in patients with muscular dystrophy.To provide a brief description of the main forms of muscular dystrophy with their respiratory implications.

  6. Respiratory Muscle Plasticity

    Science.gov (United States)

    Gransee, Heather M.; Mantilla, Carlos B.; Sieck, Gary C.

    2014-01-01

    Muscle plasticity is defined as the ability of a given muscle to alter its structural and functional properties in accordance with the environmental conditions imposed on it. As such, respiratory muscle is in a constant state of remodeling, and the basis of muscle’s plasticity is its ability to change protein expression and resultant protein balance in response to varying environmental conditions. Here, we will describe the changes of respiratory muscle imposed by extrinsic changes in mechanical load, activity, and innervation. Although there is a large body of literature on the structural and functional plasticity of respiratory muscles, we are only beginning to understand the molecular-scale protein changes that contribute to protein balance. We will give an overview of key mechanisms regulating protein synthesis and protein degradation, as well as the complex interactions between them. We suggest future application of a systems biology approach that would develop a mathematical model of protein balance and greatly improve treatments in a variety of clinical settings related to maintaining both muscle mass and optimal contractile function of respiratory muscles. PMID:23798306

  7. 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.

  8. Predicting cancer rates in astronauts from animal carcinogenesis studies and cellular markers

    Science.gov (United States)

    Williams, J. R.; Zhang, Y.; Zhou, H.; Osman, M.; Cha, D.; Kavet, R.; Cuccinotta, F.; Dicello, J. F.; Dillehay, L. E.

    1999-01-01

    The radiation space environment includes particles such as protons and multiple species of heavy ions, with much of the exposure to these radiations occurring at extremely low average dose-rates. Limitations in databases needed to predict cancer hazards in human beings from such radiations are significant and currently do not provide confidence that such predictions are acceptably precise or accurate. In this article, we outline the need for animal carcinogenesis data based on a more sophisticated understanding of the dose-response relationship for induction of cancer and correlative cellular endpoints by representative space radiations. We stress the need for a model that can interrelate human and animal carcinogenesis data with cellular mechanisms. Using a broad model for dose-response patterns which we term the "subalpha-alpha-omega (SAO) model", we explore examples in the literature for radiation-induced cancer and for radiation-induced cellular events to illustrate the need for data that define the dose-response patterns more precisely over specific dose ranges, with special attention to low dose, low dose-rate exposure. We present data for multiple endpoints in cells, which vary in their radiosensitivity, that also support the proposed model. We have measured induction of complex chromosome aberrations in multiple cell types by two space radiations, Fe-ions and protons, and compared these to photons delivered at high dose-rate or low dose-rate. Our data demonstrate that at least three factors modulate the relative efficacy of Fe-ions compared to photons: (i) intrinsic radiosensitivity of irradiated cells; (ii) dose-rate; and (iii) another unspecified effect perhaps related to reparability of DNA lesions. These factors can produce respectively up to at least 7-, 6- and 3-fold variability. These data demonstrate the need to understand better the role of intrinsic radiosensitivity and dose-rate effects in mammalian cell response to ionizing radiation. Such

  9. Risk, assessment and multiple stages in radiation carcinogenesis

    International Nuclear Information System (INIS)

    Burns, F.J.; Sawey, M.J.; Hosselet, S.; Garte, S.J.

    1989-01-01

    The authors discuss the multistage theory of carcinogenesis in terms of time-response and dose-response function, considering various workers' studies using irradiated rat skin. The authors' own results of experiments conducted to determine if two or more individual radiation doses add together to produce carcinogenic effects are presented (no such effect was observed due to skin cell repair), together with their data comparing the induction and repair kinetics of DNA breaks with carcinogenesis in the rat skin, which indicated that single strand breaks are not the initial lesion in the dual action theory. (UK)

  10. Health outcomes associated with lung function decline and respiratory symptoms and disease in a community cohort

    DEFF Research Database (Denmark)

    Baughman, Penelope; Marott, Jacob L; Lange, Peter

    2011-01-01

    BACKGROUND: In workplace respiratory disease prevention, a thorough understanding is needed of the relative contributions of lung function loss and respiratory symptoms in predicting adverse health outcomes. METHODS: Copenhagen City Heart Study respiratory data collected at 4 examinations (1976...

  11. Neonatal respiratory distress syndrome

    Science.gov (United States)

    Hyaline membrane disease (HMD); Infant respiratory distress syndrome; Respiratory distress syndrome in infants; RDS - infants ... after that. Some infants with severe respiratory distress syndrome will die. This most often occurs between days ...

  12. 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...

  13. 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

  14. Lack of cyclin D1 overexpression in gastric carcinogenesis

    NARCIS (Netherlands)

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

    2000-01-01

    Cyclin D1 overexpression was examined in early gastric carcinomas and precursor lesions with the following aims; (1) to assess the chronology of cyclin D1 overexpression in various stages of gastric carcinogenesis, (2) to correlate cyclin D1 overexpression with the Lauren type, the grade of

  15. 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.

  16. Molecular oncology focus - Is carcinogenesis a 'mitochondriopathy'?

    Directory of Open Access Journals (Sweden)

    Ścińska Anna

    2010-04-01

    Full Text Available Abstract Mitochondria are sub-cellular organelles that produce adenosine triphosphate (ATP through oxidative phosphorylation (OXPHOS. As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and in mitochondrial DNA (mtDNA appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, and some reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients. Nevertheless, a careful reanalysis of methodological criteria and methodology applied in those reports has shown that numerous papers can't be used as relevant sources of data for systematic review, meta-analysis, or finally for establishment of clinically applicable markers. In this review technical and conceptual errors commonly occurring in the literature are summarized. In the first place we discuss, why many of the published papers cannot be used as a valid and clinically useful sources of evidence in the biomedical and healthcare contexts. The reasons for introduction of noise in data and in consequence - bias for the interpretation of the role of mitochondrial DNA in the complex process of tumorigenesis are listed. In the second part of the text practical aspects of mtDNA research and requirements necessary to fulfill in order to use mtDNA analysis in clinics are shown. Stringent methodological criteria of a case-controlled experiment in molecular medicine are indicated. In the third part we suggest, what lessons can be learned for the future and propose guidelines for mtDNA analysis in oncology. Finally we conclude that, although several conceptual and methodological difficulties hinder the research on mitochondrial patho-physiology in cancer cells, this area of molecular medicine should be considered of high importance for future clinical practice.

  17. Determinants of respiratory pump function in patients with cystic fibrosis.

    Science.gov (United States)

    Dassios, Theodore

    2015-01-01

    Respiratory failure constitutes the major cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Respiratory failure could either be due to lung parenchyma damage or to insufficiency of the respiratory pump which consists of the respiratory muscles, the rib cage and the neuromuscular transmission pathways. Airway obstruction, hyperinflation and malnutrition have been historically recognised as the major determinants of respiratory pump dysfunction in CF. Recent research has identified chronic infection, genetic predisposition, dietary and pharmaceutical interventions as possible additional determinants of this impairment. Furthermore, new methodological approaches in assessing respiratory pump function have led to a better understanding of the pathogenesis of respiratory pump failure in CF. Finally, respiratory muscle function could be partially preserved in CF patients with structured interventions such as aerobic exercise, inspiratory muscle training and non-invasive ventilation and CF patients could consequently be relatively protected from respiratory fatigue and respiratory failure. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Alterations in keratins and associated proteins during 4- Nitroquinoline-1-oxide induced rat oral carcinogenesis

    Directory of Open Access Journals (Sweden)

    Deepak Kanojia

    2012-01-01

    Full Text Available Background: Oral squamous cell carcinoma (OSCC is the sixth largest group of malignancies globally and the single largest group of malignancies in the Indian subcontinent. Despite the advances in treatment and therapeutic modalities the five year survival rate of OSCC has not changed in the last few decades, and remains less than 40%. Several studies have focused on defining molecular markers that can either detect cancer at an early stage or can predict patient′s outcome. However, such markers are still undefined. Keratins (K are epithelia predominant intermediate filament proteins which are expressed in a differentiation dependent and site specific manner. Keratins are being used as biomarkers in different epithelial disorders including cancer. They are associated with desmoplakin and α6β4 integrin which are components of desmosomes and hemidesmosomes respectively. Materials and Methods: 4-Nitroquinoline 1-Oxide (4NQO was used as a carcinogen for the development of various stages of oral carcinogenesis in rat lingual mucosa. Two-Dimentional gel electrophoresis was performed for the separation of Keratins followed by western blotting for their specific identification. Western blotting and RT PCR was carried out for desmoplakin and α6β4 integrin respectively to understand their levels. Immunohistochemical analysis was carried out to further study the localization of desmoplakin and α6 integrin. Results: In this study we have analysed the alterations in Keratins and associated proteins during sequential stages of 4NQO induced rat oral carcinogenesis. Our results showed that the alterations primarily begin after the dysplastic changes in the lingual epithelium like the elevation of Keratins 5/6a, ectopic expression of Keratin 8, increase in suprabasal expression of α6 integrin and increase in desmoplakin levels. Most of these alterations persisted till the development of SCC except desmoplakin, the levels of which were downregulated in

  19. Middle East Respiratory Syndrome

    Centers for Disease Control (CDC) Podcasts

    2014-07-07

    This podcast discusses Middle East Respiratory Syndrome, or MERS, a viral respiratory illness caused by Middle East Respiratory Syndrome Coronavirus—MERS-CoV.  Created: 7/7/2014 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 7/7/2014.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Christopher E. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Wang, Xihai [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Robinson, Robert J. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Brooks, Antone L. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Lovaglio, Jamie A. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Patton, Kristin M. [Battelle Toxicology Northwest, Richland, WA (United States); McComish, Stacey [United States Transuranium and Uranium Registries, Washington State University, College of Pharmacy, Richland, WA (United States); Tolmachev, Sergei Y. [United States Transuranium and Uranium Registries, Washington State University, College of Pharmacy, Richland, WA (United States); Morgan, William F. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

    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.

  1. Cervical Carcinogenesis and Immune Response Gene Polymorphisms: A Review

    Directory of Open Access Journals (Sweden)

    Akash M. Mehta

    2017-01-01

    Full Text Available The local immune response is considered a key determinant in cervical carcinogenesis after persistent infection with oncogenic, high-risk human papillomavirus (HPV infections. Genetic variation in various immune response genes has been shown to influence risk of developing cervical cancer, as well as progression and survival among cervical cancer patients. We reviewed the literature on associations of immunogenetic single nucleotide polymorphism, allele, genotype, and haplotype distributions with risk and progression of cervical cancer. Studies on HLA and KIR gene polymorphisms were excluded due to the abundance on literature on that subject. We show that multiple genes and loci are associated with variation in risk of cervical cancer. Rather than one single gene being responsible for cervical carcinogenesis, we postulate that variations in the different immune response genes lead to subtle differences in the effectiveness of the antiviral and antitumour immune responses, ultimately leading to differences in risk of developing cervical cancer and progressive disease after HPV infection.

  2. Nucleophilic targets in carcinogenesis, mutagenesis and chemotherapy of cancer.

    Science.gov (United States)

    Raikov, Z D; Christova-Georgieva, N I; Raikova, E T

    1987-01-01

    A hypothesis is suggested, which emphasizes the role in carcinogenesis of the attack on low molecular nucleophilic substances (LMN) by electrophilic agents - chemical carcinogens, phisical factors, and antitumor alkylating agents. The significance of the degree of nucleophilicity (electronic charge, order of bonds, index of valence) as a locus minoris resistentiae of the LMN in the electrophilic attack on the latter is emphasized as well as the probable role of the hydrogenated pteridines in influencing carcinogenesis by means of ascorbate, tocopherol, SH-containing compounds etc. In support of this hypothesis the preference of electrophilic agents (derivatives of nitrogen mustard and nitrosoureas) for the places with highest degree of nucleophilicity as targets, in experiments in vitro with nucleic bases and pteridines is emphasized.

  3. Plastics and carcinogenesis: The example of vinyl chloride

    Directory of Open Access Journals (Sweden)

    Paul Wesley Brandt-Rauf

    2012-01-01

    Full Text Available The manufacture, use and disposal of various plastics can pose numerous health risks, including the risk of cancer. A model example of carcinogenic risk from plastics is provided by polyvinyl chloride, since it is composed of the known human carcinogen vinyl chloride (VC. In recent years, much has been learned about the molecular biological pathways of VC carcinogenesis. This has led to molecular epidemiologic studies of VC carcinogenesis in exposed human populations which have identified useful biomarkers of exposure, effect and susceptibility for VC. These studies have in turn provided the basis for new molecular approaches for the prevention and treatment of VC cancers. This model could have much wider applicability for many other carcinogenic exposures and many other human cancers.

  4. Inhibitory effects of acetylsalicylic acid on exocrine pancreatic carcinogenesis.

    Science.gov (United States)

    Yıldız, H; Oztas, H; Yıldız, D; Koc, A; Kalipci, E

    2013-05-01

    We investigated short (6 months) and long (12 months) term inhibitory effects of low (200 ppm) and high (400 ppm) dosages of acetylsalicylic acid (aspirin) on exocrine pancreatic carcinogenesis. It is known that exocrine pancreatic carcinogenesis can be detected by the presence of atypical acinar cell foci (AACF) in pancreas. We investigated possible inhibitory effects of acetylsalicylic acid in an azaserine-treated rat model. AACF were produced in rats by injection with azaserine according to previous studies. Our findings showed that the number, volume and diameter of pancreatic AACF were reduced after acetylsalicylic acid application. These observations suggest that acetylsalicylic acid may exert a protective effect against neoplastic development of pancreatic acinar cells in azaserine injected rats. Our findings corroborate reports in the literature concerning the effects of aspirin in reducing neoplastic development.

  5. Basic concepts of inflammation and its role in carcinogenesis.

    Science.gov (United States)

    Maher, Stephen G; Reynolds, John V

    2011-01-01

    While the normal inflammatory cascade is self-limiting and crucial for host protection against invading pathogens and in the repair of damaged tissue, a wealth of evidence suggests that chronic inflammation is the engine driving carcinogenesis. Over a period of almost 150 years the link between inflammation and cancer development has been well established. In this chapter we discuss the fundamental concepts and mechanisms behind normal inflammation as it pertains to wound healing. We further discuss the association of inflammation and its role in carcinogenesis, highlighting the different stages of cancer development, namely tumour initiation, promotion and progression. With both the innate and adaptive arms of the immune system being central to the inflammatory process, we examine the role of a number of immune effectors in contributing to the carcinogenic process. In addition, we highlight the influences of host genetics in altering cancer risk.

  6. Stem cells and respiratory diseases

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, Soraia Carvalho; Maron-Gutierrez, Tatiana; Garcia, Cristiane Sousa Nascimento Baez; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Biofisica Carlos Chagas Filho. Lab. de Investigacao]. E-mail: prmrocco@biof.ufrj.br

    2008-12-15

    Stem cells have a multitude of clinical implications in the lung. This article is a critical review that includes clinical and experimental studies of MedLine and SciElo database in the last 10 years, where we highlight the effects of stem cell therapy in acute respiratory distress syndrome or more chronic disorders such as lung fibrosis and emphysema. Although, many studies have shown the beneficial effects of stem cells in lung development, repair and remodeling; some important questions need to be answered to better understand the mechanisms that control cell division and differentiation, therefore enabling the use of cell therapy in human respiratory diseases. (author)

  7. Synergistic chemopreventive effects of nobiletin and atorvastatin on colon carcinogenesis.

    Science.gov (United States)

    Wu, Xian; Song, Mingyue; Qiu, Peiju; Rakariyatham, Kanyasiri; Li, Fang; Gao, Zili; Cai, Xiaokun; Wang, Minqi; Xu, Fei; Zheng, Jinkai; Xiao, Hang

    2017-04-01

    Different cancer chemopreventive agents may act synergistically and their combination may produce enhanced protective effects against carcinogenesis than each individual agent alone. Herein, we investigated the chemopreventive effects of nobiletin (NBT, a citrus polymethoxyflavone) and atorvastatin (ATST, a lipid-lowering drug) in colon cancer cells/macrophages and an azoxymethane (AOM)-induced colon carcinogenesis rat model. The results demonstrated that co-treatments of NBT/ATST produced enhanced growth inhibitory and anti-inflammatory effects on the colon cancer cells and macrophages, respectively. Isobologram analysis confirmed that these interactions between NBT and ATST were synergistic. NBT/ATST co-treatment also synergistically induced extensive cell cycle arrest and apoptosis in colon cancer cells. Oral administration of NBT (0.1%, w/w in diet) or ATST (0.04%, w/w in diet) significantly decreased colonic tumor incidence and multiplicity in AOM-treated rats. Most importantly, co-treatment of NBT/ATST at their half doses (0.05% NBT + 0.02% ATST, w/w in diet) resulted in even stronger inhibitory effects on colonic tumor incidence and multiplicity than did NBT or ATST alone at higher doses. Statistical analysis confirmed that the enhanced chemopreventive activities against colon carcinogenesis in rats by the NBT/ATST combination were highly synergistic. Our results further demonstrated that NBT/ATST co-treatment profoundly modulated key cellular signaling regulators associated with inflammation, cell proliferation, cell cycle progression, apoptosis, angiogenesis and metastasis in the colon of AOM-treated rats. In conclusion, for the first time, our results demonstrated a strong synergy in inhibiting colon carcinogenesis produced by the co-treatment of NBT and ATST, which provided a scientific basis for using NBT in combination with ATST for colon cancer chemoprevention in humans. © The Author 2017. Published by Oxford University Press. All rights reserved

  8. 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)

  9. Wnt Lipidation and Modifiers in Intestinal Carcinogenesis and Cancer

    Directory of Open Access Journals (Sweden)

    Elke Kaemmerer

    2016-07-01

    Full Text Available The wingless (Wnt signaling is suggested as a fundamental hierarchical pathway in regulation of proliferation and differentiation of cells. The Wnt ligands are small proteins of about 40 kDa essentially for regulation and initiation of the Wnt activity. They are secreted proteins requiring acylation for activity in the Wnt signaling cascade and for functional interactivity with transmembrane proteins. Dual lipidation is important for posttranslational activation of the overwhelming number of Wnt proteins and is probably involved in their spatial distribution. The intestinal mucosa, where Wnt signaling is essential in configuration and maintenance, is an established model to study Wnt proteins and their role in carcinogenesis and cancer. The intestinal crypt-villus/crypt-plateau axis, a cellular system with self-renewal, proliferation, and differentiation, is tightly coordinated by a Wnt gradient. In the review, some attention is given to Wnt3, Wnt3A, and Wnt2B as important members of the Wnt family to address the role of lipidation and modifiers of Wnt proteins in intestinal carcinogenesis. Wnt3 is an important player in establishing the Wnt gradient in intestinal crypts and is mainly produced by Paneth cells. Wnt2B is characterized as a mitochondrial protein and shuttles between mitochondria and the nucleus. Porcupine and ACSL5, a long-chain fatty acid activating enzyme, are introduced as modifiers of Wnts and as interesting strategy to targeting Wnt-driven carcinogenesis.

  10. Molecular insight of arsenic-induced carcinogenesis and its prevention.

    Science.gov (United States)

    Mandal, Paramita

    2017-05-01

    Population of India and Bangladesh and many other parts of the world are badly exposed to arsenic through drinking water. Due to non-availability of safe drinking water, they are dependent on arsenic-contaminated water. Generally, poverty level is high in those areas with lack of proper nutrition. Arsenic is considered to be an environmental contaminant and widely distributed in the environment due to its natural existence and anthropogenic applications. Contamination of arsenic in both human and animal could occur through air, soil, and other sources. Arsenic exposure mainly occurs in food materials through drinking water with high levels of arsenic in it. High levels of arsenic in groundwater have been found to be associated with various health-related problems including arsenicosis, skin lesions, cardiovascular diseases, reproductive problems, psychological, neurological, immunotoxic, and carcinogenesis. The mechanism of arsenic toxicity consists in its transformation in metaarsenite, which acylates protein sulfhydryl groups, affect on mitochondria by inhibiting succinic dehydrogenase activity and can uncouple oxidative phosphorylation with production of active oxygen species by tissues. A variety of dietary antioxidant supplements are useful to protect the carcinogenetic effects of arsenic. They play crucial role for counteracting oxidative damage and protect carcinogenesis by chelating with heavy metal moiety. Phytochemicals and chelating agents will be beneficial for combating heavy metal-induced carcinogenesis through its biopharmaceutical properties.

  11. Role of the Vanins–Myeloperoxidase Axis in Colorectal Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Francesco Mariani

    2017-04-01

    Full Text Available The presence of chronic inflammation in the colonic mucosa leads to an increased risk of cancer. Among proteins involved in the regulation of mucosal inflammation and that may contribute both to structural damage of the intestinal mucosa and to intestinal carcinogenesis, there are myeloperoxidase (MPO and vanins. The infiltration of colonic mucosa by neutrophils may promote carcinogenesis through MPO, a key enzyme contained in the lysosomes of neutrophils that regulates local inflammation and the generation of reactive oxygen species (ROS and mutagenic species. The human vanin gene family consists of three genes: vanin-1, vanin-2 and vanin-3. All vanin molecules are pantetheinases, that hydrolyze pantetheine into pantothenic acid (vitamin B5, and cysteamine, a sulfhydryl compound. Vanin-1 loss confers an increased resistance to stress and acute intestinal inflammation, while vanin-2 regulates adhesion and transmigration of activated neutrophils. The metabolic product of these enzymes has a prominent role in the inflammation processes by affecting glutathione levels, inducing ulcers through a reduction in mucosal blood flow and oxygenation, decreasing local defense mechanisms, and in carcinogenesis by damaging DNA and regulating pathways involved in cell apoptosis, metabolism and growth, as Nrf2 and HIF-1α.

  12. Heel spur radiotherapy and radiation carcinogenesis risk estimation.

    Science.gov (United States)

    Surenkok, Serdar; Dirican, Bahar; Beyzadeoglu, Murat; Oysul, Kaan

    2006-10-01

    Radiotherapy is a nonsurgical alternative therapy of painful heel spur patients. Nonetheless, cancer induction is the most important somatic effect of ionizing radiation. This study was designed to evaluate the carcinogenesis risk factor in benign painful heel spur patients treated by radiotherapy. Between 1974 and 1999, a total of 20 patients received mean 8.16 Gy total irradiation dose in two fractions. Thermoluminescent dosimeters (TLD(100)) were placed on multiple phantom sites in vivo within the irradiated volume to verify irradiation accuracy and carcinogenesis risk factor calculation. The 20 still-alive patients, who had a minimum 5-year and maximum 29-year follow-up (mean 11.9 years), have been evaluated by carcinogenic radiation risk factor on the basis of tissue weighting factors as defined by the International Commission on Radiological Protection Publication 60. Reasonable pain relief has been obtained in all 20 patients. The calculated mean carcinogenesis risk factor is 1.3% for radiation portals in the whole group, and no secondary cancer has been clinically observed. Radiotherapy is an effective treatment modality for relieving pain in calcaneal spur patients. The estimated secondary cancer risk factor for irradiation of this benign lesion is not as high as was feared.

  13. 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

  14. Anatomy and physiology of respiratory system relevant to anaesthesia

    OpenAIRE

    Patwa, Apeksh; Shah, Amit

    2015-01-01

    Clinical application of anatomical and physiological knowledge of respiratory system improves patient's safety during anaesthesia. It also optimises patient's ventilatory condition and airway patency. Such knowledge has influence on airway management, lung isolation during anaesthesia, management of cases with respiratory disorders, respiratory endoluminal procedures and optimising ventilator strategies in the perioperative period. Understanding of ventilation, perfusion and their relation wi...

  15. The impact of inflammation on respiratory plasticity.

    Science.gov (United States)

    Hocker, Austin D; Stokes, Jennifer A; Powell, Frank L; Huxtable, Adrianne G

    2017-01-01

    Breathing is a vital homeostatic behavior and must be precisely regulated throughout life. Clinical conditions commonly associated with inflammation, undermine respiratory function may involve plasticity in respiratory control circuits to compensate and maintain adequate ventilation. Alternatively, other clinical conditions may evoke maladaptive plasticity. Yet, we have only recently begun to understand the effects of inflammation on respiratory plasticity. Here, we review some of common models used to investigate the effects of inflammation and discuss the impact of inflammation on nociception, chemosensory plasticity, medullary respiratory centers, motor plasticity in motor neurons and respiratory frequency, and adaptation to high altitude. We provide new data suggesting glial cells contribute to CNS inflammatory gene expression after 24h of sustained hypoxia and inflammation induced by 8h of intermittent hypoxia inhibits long-term facilitation of respiratory frequency. We also discuss how inflammation can have opposite effects on the capacity for plasticity, whereby it is necessary for increases in the hypoxic ventilatory response with sustained hypoxia, but inhibits phrenic long term facilitation after intermittent hypoxia. This review highlights gaps in our knowledge about the effects of inflammation on respiratory control (development, age, and sex differences). In summary, data to date suggest plasticity can be either adaptive or maladaptive and understanding how inflammation alters the respiratory system is crucial for development of better therapeutic interventions to promote breathing and for utilization of plasticity as a clinical treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Oxidative Stress Resulting From Helicobacter pylori Infection Contributes to Gastric CarcinogenesisSummary

    Directory of Open Access Journals (Sweden)

    Lindsay D. Butcher

    2017-05-01

    Full Text Available Helicobacter pylori is a gram-negative, microaerophilic bacterium that infects the stomach and can lead to, among other disorders, the development of gastric cancer. The inability of the host to clear the infection results in a chronic inflammatory state with continued oxidative stress within the tissue. Reactive oxygen species and reactive nitrogen species produced by the immune and epithelial cells damage the host cells and can result in DNA damage. H pylori has evolved to evoke this damaging response while blunting the host’s efforts to kill the bacteria. This long-lasting state with inflammation and oxidative stress can result in gastric carcinogenesis. Continued efforts to better understand the bacterium and the host response will serve to prevent or provide improved early diagnosis and treatment of gastric cancer. Keywords: AP Endonuclease, DNA Damage, H pylori, Gastric Cancer, Oxidative Stress

  17. The respiratory microbiome and respiratory infections

    NARCIS (Netherlands)

    Unger, Stefan A.; Bogaert, Debby

    2017-01-01

    Despite advances over the past ten years lower respiratory tract infections still comprise around a fifth of all deaths worldwide in children under five years of age with the majority in low- and middle-income countries. Known risk factors for severe respiratory infections and poor chronic

  18. Respiratory Development and Respiratory Distress Syndrome.

    Science.gov (United States)

    Rubarth, Lori Baas; Quinn, Jenny

    2015-01-01

    Respiratory development is crucial for all newborn infants. Premature infants may be born at an early stage of development and lack sufficient surfactant production. This results in respiratory distress syndrome. This article reviews the normal fetal development of the lung as well as the disorder that develops because of an early birth.

  19. Upper respiratory tract (image)

    Science.gov (United States)

    The major passages and structures of the upper respiratory tract include the nose or nostrils, nasal cavity, mouth, throat (pharynx), and voice box (larynx). The respiratory system is lined with a mucous membrane that ...

  20. Respiratory Issues in OI

    Science.gov (United States)

    Respiratory Issues in Osteogenesis Imperfecta \\ Introduction The respiratory system’s job is to bring oxygen into the body and remove carbon dioxide, the waste product of breathing. Because oxygen is the fuel ...

  1. Avian respiratory system disorders

    Science.gov (United States)

    Olsen, Glenn H.

    1989-01-01

    Diagnosing and treating respiratory diseases in avian species requires a basic knowledge about the anatomy and physiology of this system in birds. Differences between mammalian and avian respiratory system function, diagnosis, and treatment are highlighted.

  2. Aquaporins in Respiratory System.

    Science.gov (United States)

    Song, Yuanlin; Wang, Linlin; Wang, Jian; Bai, Chunxue

    2017-01-01

    Aquaporins (AQPs ) are water channel proteins supposed to facilitating fluid transport in alveolar space, airway humidification, pleural fluid absorption, and submucosal gland secretion . In this chapter, we mainly focus on the expression of 4 AQPs in the lungs which include AQP1, AQP2 , AQP4 and AQP5 in normal and disease status, and the experience of AQPs function from various model and transgenic mice were summarized in detail to improve our understanding of the role of AQPs in fluid balance of respiratory system. It has been suggested that AQPs play important roles in various physiology and pathophysiology conditions of different lung diseases. There still remains unclear the exact role of AQPs in lung diseases, and thus continuous efforts on elucidating the roles of AQPs in lung physiological and pathophysilogical processes are warranted.

  3. Pharmacological inhibition of MAGL attenuates experimental colon carcinogenesis.

    Science.gov (United States)

    Pagano, Ester; Borrelli, Francesca; Orlando, Pierangelo; Romano, Barbara; Monti, Martina; Morbidelli, Lucia; Aviello, Gabriella; Imperatore, Roberta; Capasso, Raffaele; Piscitelli, Fabiana; Buono, Lorena; Di Marzo, Vincenzo; Izzo, Angelo A

    2017-05-01

    Colorectal cancer (CRC) is a major health problem in Western countries. The endocannabinoid 2-arachidonoyl-glycerol (2-AG) exerts antiproliferative actions in a number of tumoral cell lines, including CRC cells. Monoacylglycerol lipase (MAGL), a serine hydrolase that inactivates 2-AG, is highly expressed in aggressive human cancer cells. Here, we investigated the role of MAGL in experimental colon carcinogenesis. The role of MAGL was assessed in vivo by using the xenograft and the azoxymethane models of colon carcinogenesis; MAGL expression was evaluated by RT-PCR and immunohistochemistry; 2-AG levels were measured by liquid chromatography mass spectrometry; angiogenesis was evaluated in tumor tissues [by microvessel counting and by investigating the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) proteins] as well as in human umbilical vein endothelial cells (HUVEC); cyclin D1 was evaluated by RT-PCR. MAGL and 2-AG were strongly expressed in tumor tissues. The MAGL inhibitor URB602 reduced xenograft tumor volume, this effect being associated to down-regulation of VEGF and FGF-2, reduction in the number of vessels and down-regulation of cyclin D1. In HUVEC, URB602 exerted a direct antiangiogenic effect by inhibiting FGF-2 induced proliferation and migration, and by modulating pro/anti-angiogenic agents. In experiments aiming at investigating the role of MAGL in chemoprevention, URB602 attenuated azoxymethane-induced preneoplastic lesions, polyps and tumors. MAGL, possibly through modulation of angiogenesis, plays a pivotal role in experimental colon carcinogenesis. Pharmacological inhibition of MAGL could represent an innovative therapeutic approach to reduce colorectal tumor progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. 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....

  5. The dimethylhydrazine induced colorectal tumours in rat - experimental colorectal carcinogenesis

    International Nuclear Information System (INIS)

    Perse, M.; Cerar, A.

    2005-01-01

    Animal models of colorectal carcinogenesis represent invaluable research tool for investigating colorectal cancer (CRC). Experimentally induced tumours in laboratory animals provide opportunity for studying certain aspects of tumours that cannot be effectively studied in humans. Significant information on human CRC aetiology or factors influencing it has derived from studies using dimethylhydrazine (DMH) model that is one of the experimental models appreciated for its morphological similarity to human CRC. Today, DMH model represents useful research tool for the studies of colon carcinogens and chemopreventive agents. The review offers insight into morphogenesis and genetic alterations of DMH induced colorectal epithelial tumours in rats. (author)

  6. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Thresholds in chemical respiratory sensitisation.

    Science.gov (United States)

    Cochrane, Stella A; Arts, Josje H E; Ehnes, Colin; Hindle, Stuart; Hollnagel, Heli M; Poole, Alan; Suto, Hidenori; Kimber, Ian

    2015-07-03

    There is a continuing interest in determining whether it is possible to identify thresholds for chemical allergy. Here allergic sensitisation of the respiratory tract by chemicals is considered in this context. This is an important occupational health problem, being associated with rhinitis and asthma, and in addition provides toxicologists and risk assessors with a number of challenges. In common with all forms of allergic disease chemical respiratory allergy develops in two phases. In the first (induction) phase exposure to a chemical allergen (by an appropriate route of exposure) causes immunological priming and sensitisation of the respiratory tract. The second (elicitation) phase is triggered if a sensitised subject is exposed subsequently to the same chemical allergen via inhalation. A secondary immune response will be provoked in the respiratory tract resulting in inflammation and the signs and symptoms of a respiratory hypersensitivity reaction. In this article attention has focused on the identification of threshold values during the acquisition of sensitisation. Current mechanistic understanding of allergy is such that it can be assumed that the development of sensitisation (and also the elicitation of an allergic reaction) is a threshold phenomenon; there will be levels of exposure below which sensitisation will not be acquired. That is, all immune responses, including allergic sensitisation, have threshold requirement for the availability of antigen/allergen, below which a response will fail to develop. The issue addressed here is whether there are methods available or clinical/epidemiological data that permit the identification of such thresholds. This document reviews briefly relevant human studies of occupational asthma, and experimental models that have been developed (or are being developed) for the identification and characterisation of chemical respiratory allergens. The main conclusion drawn is that although there is evidence that the

  9. Raman spectroscopy detects biomolecular changes associated with nanoencapsulated hesperetin treatment in experimental oral carcinogenesis

    Science.gov (United States)

    Gurushankar, K.; Gohulkumar, M.; Kumar, Piyush; Krishna, C. Murali; Krishnakumar, N.

    2016-03-01

    Recently it has been shown that Raman spectroscopy possesses great potential in the investigation of biomolecular changes of tumor tissues with therapeutic drug response in a non-invasive and label-free manner. The present study is designed to investigate the antitumor effect of hespertin-loaded nanoparticles (HETNPs) relative to the efficacy of native hesperetin (HET) in modifying the biomolecular changes during 7,12-dimethyl benz(a)anthracene (DMBA)-induced oral carcinogenesis using a Raman spectroscopic technique. Significant differences in the intensity and shape of the Raman spectra between the control and the experimental tissues at 1800-500 cm-1 were observed. Tumor tissues are characterized by an increase in the relative amount of proteins, nucleic acids, tryptophan and phenylalanine and a decrease in the percentage of lipids when compared to the control tissues. Further, oral administration of HET and its nanoparticulates restored the status of the lipids and significantly decreased the levels of protein and nucleic acid content. Treatment with HETNPs showed a more potent antitumor effect than treatment with native HET, which resulted in an overall reduction in the intensity of several biochemical Raman bands in DMBA-induced oral carcinogenesis being observed. Principal component and linear discriminant analysis (PC-LDA), together with leave-one-out cross validation (LOOCV) on Raman spectra yielded diagnostic sensitivities of 100%, 80%, 91.6% and 65% and specificities of 100%, 65%, 60% and 55% for classification of control versus DMBA, DMBA versus DMBA  +  HET, DMBA versus DMBA  +  HETNPs and DMBA  +  HET versus DMBA  +  HETNPs treated tissue groups, respectively. These results further demonstrate that Raman spectroscopy associated with multivariate statistical algorithms could be a valuable tool for developing a comprehensive understanding of the process of biomolecular changes, and could reveal the signatures of the

  10. 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.

  11. Radiation carcinogenesis in context: how do irradiated tissues become tumors?

    Science.gov (United States)

    Barcellos-Hoff, Mary Helen; Nguyen, David H

    2009-11-01

    It is clear from experimental studies that genotype is an important determinant of cancer susceptibility in general, and for radiation carcinogenesis specifically. It has become increasingly clear that genotype influences not only the ability to cope with DNA damage but also influences the cooperation of other tissues, like the vasculature and immune system, necessary for the establishment of cancer. Our experimental data and that of others suggest that the carcinogenic action of ionizing radiation (IR) can also be considered a two-compartment problem: while IR can alter genomic sequence as a result of DNA damage, it can also induce signals that alter multicellular interactions and phenotypes that underpin carcinogenesis. Rather than being accessory or secondary to genetic damage, we propose that such non-targeted radiation effects create the critical context that promotes cancer development. This review focuses on experimental studies that clearly define molecular mechanisms by which cell interactions contribute to cancer in different organs, and addresses how non-targeted radiation effects may similarly act though the microenvironment. The definition of non-targeted radiation effects and their dose dependence could modify the current paradigms for radiation risk assessment since radiation non-targeted effects, unlike DNA damage, are amenable to intervention. The implications of this perspective in terms of reducing cancer risk after exposure are discussed.

  12. 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

  13. Considerations for skin carcinogenesis experiments using inducible transgenic mouse models.

    Science.gov (United States)

    Popis, Martyna C; Wagner, Rebecca E; Constantino-Casas, Fernando; Blanco, Sandra; Frye, Michaela

    2018-01-24

    This study was designed to estimate the percentage of non-malignant skin tumours (papillomas) progressing to malignant squamous cell carcinomas (SCCs) in a carcinogenesis study using established transgenic mouse models. In our skin cancer model, we conditionally induced oncogenic point mutant alleles of p53 and k-ras in undifferentiated, basal cells of the epidermis. Upon activation of the transgenes through administration of tamoxifen, the vast majority of mice (> 80%) developed skin papillomas, yet primarily around the mouth. Since these tumours hindered the mice eating, they rapidly lost weight and needed to be culled before the papillomas progressed to SCCs. The mouth papillomas formed regardless of the route of application, including intraperitoneal injections, local application to the back skin, or subcutaneous insertion of a tamoxifen pellet. Implantation of a slow releasing tamoxifen pellet into 18 mice consistently led to papilloma formation, of which only one progressed to a malignant SCC. Thus, the challenges for skin carcinogenesis studies using this particular cancer mouse model are low conversion rates of papillomas to SCCs and high frequencies of mouth papilloma formation.

  14. Mitochondrial DNA variants in colorectal carcinogenesis: Drivers or passengers?

    Science.gov (United States)

    Errichiello, Edoardo; Venesio, Tiziana

    2017-10-01

    Mitochondrial DNA alterations have widely been reported in many age-related degenerative diseases and tumors, including colorectal cancer. In the past few years, the discovery of inter-genomic crosstalk between nucleus and mitochondria has reinforced the role of mitochondrial DNA variants in perturbing this essential signaling pathway and thus indirectly targeting nuclear genes involved in tumorigenic and invasive phenotype. Mitochondrial dysfunction is currently considered a crucial hallmark of carcinogenesis as well as a promising target for anticancer therapy. Mitochondrial DNA alterations include point mutations, deletions, inversions, and copy number variations, but numerous studies investigating their pathogenic role in cancer have provided inconsistent evidence. Furthermore, the biological impact of mitochondrial DNA variants may vary tremendously, depending on the proportion of mutant DNA molecules carried by the neoplastic cells (heteroplasmy). In this review, we discuss the role of different type of mitochondrial DNA alterations in colorectal carcinogenesis and, in particular, we revisit the issue of whether they may be considered as causative driver or simply genuine passenger events. The advent of high-throughput techniques as well as the development of genetic and pharmaceutical interventions for the treatment of mitochondrial dysfunction in colorectal cancer are also explored.

  15. 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

  16. [THE ROLE OF ESTROGENS IN THE CARCINOGENESIS OF LUNG CANCER].

    Science.gov (United States)

    Uchikova, E; Uchikov, A; Dimitrakova, E; Uchikov, P

    2016-01-01

    Morbidity and mortality from lung cancer has dramatically increased in women as compared to men over the past few years. Historically, smoking has been considered the major risk factor for lung cancer regardless of gender. Several recent lines of evidence implicate gender differences in the observed differences in prevalence and histologic type which cannot be explained based on the carcinogenic action of nicotine. Several recent studies underscore the importance of reproductive and hormonal factors in the carcinogenesis of lung cancer Lung cancer morbidity and mortality in Bulgaria was 16.2/100000 women and 14.6/ 100000 women, resp. Lung cancer morbidity in Europe was 39/100000 women. Lung cancer is extremely sensitive to estrogens. The latter act directly or as effect modifiers for the relationship between smoking and lung cancer. Further research examining the relationship between serum estrogen levels and the estrogen receptor expression in normal and tumor lung tissue samples can help elucidate the importance of reproductive and hormonal (exogenous and endogenous) factors in the carcinogenesis of lung cancer.

  17. E-cadherin: Its dysregulation in carcinogenesis and clinical implications.

    Science.gov (United States)

    Wong, Sonia How Ming; Fang, Chee Mun; Chuah, Lay-Hong; Leong, Chee Onn; Ngai, Siew Ching

    2018-01-01

    E-cadherin is a transmembrane glycoprotein which connects epithelial cells together at adherens junctions. In normal cells, E-cadherin exerts its tumour suppressing role mainly by sequestering β-catenin from its binding to LEF (Lymphoid enhancer factor)/TCF (T cell factor) which serves the function of transcribing genes of the proliferative Wnt signaling pathway. Despite the ongoing debate on whether the loss of E-cadherin is the cause or effect of epithelial-mesenchymal transition (EMT), E-cadherin functional loss has frequently been associated with poor prognosis and survival in patients of various cancers. The dysregulation of E-cadherin expression that leads to carcinogenesis happens mostly at the epigenetic level but there are cases of genetic alterations as well. E-cadherin expression has been linked to the cellular functions of invasiveness reduction, growth inhibition, apoptosis, cell cycle arrest and differentiation. Studies on various cancers have shown that these different cellular functions are also interdependent. Recent studies have reported a rapid expansion of E-cadherin clinical relevance in various cancers. This review article summarises the multifaceted effect E-cadherin expression has on cellular functions in the context of carcinogenesis as well as its clinical implications in diagnosis, prognosis and therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Chemical and radiation carcinogenesis in man and experimental animals

    International Nuclear Information System (INIS)

    Miller, J.A.; Miller, E.C.

    1975-01-01

    It is now well established that some cancer in man results from exposures to certain chemicals and radiations, both ultraviolet and ionizing radiations. These chemical and physical agents are also carcinogenic in experimental animals and, where adequately tested, in mammalian cell cultures. However, only very limited data are available on the relative roles of and the interrelationships, if any, between these various environmental agents in the causation of the majority of the cancers in man. Nothing is known of the relationship between these agents and possible carcinogenic viral information in the etiology of cancer in man. Furthermore, little is known about the molecular mechanisms by which chemicals and radiations induce cancers in either man or experimental animals. The objective of this brief review is to present certain aspects of chemical and radiation carcinogenesis in man and experimental animals and some of the problems in the elucidation of their roles in carinogenesis in the human

  19. Thymus in experimental carcinogenesis of the prostate gland.

    Science.gov (United States)

    Borodin, Yu I; Lomshakov, A A; Astashov, V V; Kazakov, O V; Mayorov, A P; Larionov, P M

    2014-10-01

    We studied structural changes in the prostate gland, thymus, and lymph nodes in CBA mice after transplantation of Ehrlich ascites tumor cells into the prostate gland. On experimental day 5, the number of blood and lymph vessels decreased in the gland; the percentage of connective tissue elements and glandular tissue and the number of immunoblasts in the thymus increased. On day 18, the number of blood vessels in the tumor decreased; the width of the cortex and glandular tissue increased in the thymus, while the number of immunoblasts was reduced. On day 28, tumor infiltration and increased number of lymphatic vessels in its stroma were observed; parenchyma was reduced, and the area of the connective tissue increased in the thymus. These structural changes indicated the development of accidental involution of the thymus during carcinogenesis of the prostate.

  20. Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Li Jie

    2012-03-01

    Full Text Available Abstract Recent morphologic and molecular genetic studies have led to a paradigm shift in our conceptualization of the carcinogenesis and histogenesis of pelvic (non-uterine serous carcinomas. It appears that both low-grade and high-grade pelvic serous carcinomas that have traditionally been classified as ovarian in origin, actually originate, at least in a significant subset, from the distal fallopian tube. Clonal expansions of the tubal secretory cell probably give rise to serous carcinomas, and the degree of ciliated conversion is a function of the degree to which the genetic hits deregulate normal differentiation. In this article, the authors review the evidentiary basis for aforementioned paradigm shift, as well as its potential clinical implications.

  1. Studies on the multistage nature of radiation carcinogenesis

    International Nuclear Information System (INIS)

    Fry, R.J.M.; Ley, R.D.; Grube, D.; Staffeldt, E.

    1980-01-01

    With low dose levels of ionizing or ultraviolet radiation, the number of initiation events exceeds the number of tumors that grow to a detectable size. Ionizing radiation, which is a complete carcinogen, appears to be a more effective initiator than an enhancer or promoter. However, the initiation and promotion aspects of ionizing radiation have been studied in very few organ systems. In the case of UVR, with or without photosensitizers such as psoralens, the requirement of a relatively large number of exposures for carcinogenesis suggests that the expression of the initiated cells as frank tumors requires a number of events spread out over the time of the development of the tumor. Both ionizing and ultraviolet radiation are, perhaps, underutilized as tools for probing the mechanism of both initiation and promotion

  2. Collagen mRNA levels changes during colorectal cancer carcinogenesis

    DEFF Research Database (Denmark)

    Skovbjerg, Hanne; Anthonsen, Dorit; Lothe, Inger M B

    2009-01-01

    BACKGROUND: Invasive growth of epithelial cancers is a complex multi-step process which involves dissolution of the basement membrane. Type IV collagen is a major component in most basement membranes. Type VII collagen is related to anchoring fibrils and is found primarily in the basement membrane...... zone of stratified epithelia. Immunohistochemical studies have previously reported changes in steady-state levels of different alpha(IV) chains in several epithelial cancer types. In the present study we aimed to quantitatively determine the mRNA levels of type IV collagen (alpha1/alpha 4/alpha 6......) and type VII collagen (alpha1) during colorectal cancer carcinogenesis. METHODS: Using quantitative RT-PCR, we have determined the mRNA levels for alpha1(IV), alpha 4(IV), alpha 6(IV), and alpha1(VII) in colorectal cancer tissue (n = 33), adenomas (n = 29) and in normal tissue from the same individuals...

  3. Mechanistic modelling of genetic and epigenetic events in radiation carcinogenesis

    International Nuclear Information System (INIS)

    Andreev, S. G.; Eidelman, Y. A.; Salnikov, I. V.; Khvostunov, I. K.

    2006-01-01

    Methodological problems arise on the way of radiation carcinogenesis modelling with the incorporation of radiobiological and cancer biology mechanistic data. The results of biophysical modelling of different endpoints [DNA DSB induction, repair, chromosome aberrations (CA) and cell proliferation] are presented and applied to the analysis of RBE-LET relationships for radiation-induced neoplastic transformation (RINT) of C3H/10T1/2 cells in culture. Predicted values for some endpoints correlate well with the data. It is concluded that slowly repaired DSB clusters, as well as some kind of CA, may be initiating events for RINT. As an alternative interpretation, it is possible that DNA damage can induce RINT indirectly via epigenetic process. A hypothetical epigenetic pathway for RINT is discussed. (authors)

  4. 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...... IPL treatments at 2-week intervals. Simulated solar radiation was administered preoperatively [six standard erythema doses (SED) four times weekly for 11 weeks] as well as pre- and postoperatively (six SED four times weekly up to 26 weeks). Skin tumors were assessed weekly during a 12-month...... observation period. Side effects were evaluated clinically. No tumors appeared in untreated control mice or in just IPL-treated mice. Skin tumors developed in UV-exposed mice independently of IPL treatments. The time it took for 50% of the mice to first develop skin tumor ranged from 47 to 49 weeks...

  5. 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.

  6. Mushroom Ganoderma lucidum prevents colitis-associated carcinogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Daniel Sliva

    Full Text Available Epidemiological studies suggest that mushroom intake is inversely correlated with gastric, gastrointestinal and breast cancers. We have recently demonstrated anticancer and anti-inflammatory activity of triterpene extract isolated from mushroom Ganoderma lucidum (GLT. The aim of the present study was to evaluate whether GLT prevents colitis-associated carcinogenesis in mice.Colon carcinogenesis was induced by the food-borne carcinogen (2-Amino-1-methyl-6-phenylimidazol[4,5-b]pyridine [PhIP] and inflammation (dextran sodium sulfate [DSS] in mice. Mice were treated with 0, 100, 300 and 500 mg GLT/kg of body weight 3 times per week for 4 months. Cell proliferation, expression of cyclin D1 and COX-2 and macrophage infiltration was assessed by immunohistochemistry. The effect of GLT on XRE/AhR, PXR and rPXR was evaluated by the reporter gene assays. Expression of metabolizing enzymes CYP1A2, CYP3A1 and CYP3A4 in colon tissue was determined by immunohistochemistry. GLT treatment significantly suppressed focal hyperplasia, aberrant crypt foci (ACF formation and tumor formation in mice exposed to PhIP/DSS. The anti-proliferative effects of GLT were further confirmed by the decreased staining with Ki-67 in colon tissues. PhIP/DSS-induced colon inflammation was demonstrated by the significant shortening of the large intestine and macrophage infiltrations, whereas GLT treatment prevented the shortening of colon lengths, and reduced infiltration of macrophages in colon tissue. GLT treatment also significantly down-regulated PhIP/DSS-dependent expression of cyclin D1, COX-2, CYP1A2 and CYP3A4 in colon tissue.Our data suggest that GLT could be considered as an alternative dietary approach for the prevention of colitis-associated cancer.

  7. Mechanisms of caffeine-induced inhibition of UVB carcinogenesis

    Directory of Open Access Journals (Sweden)

    Allan H Conney

    2013-06-01

    Full Text Available Sunlight-induced nonmelanoma skin cancer is the most prevalent cancer in the United States with more than 2 million cases per year. Several studies have shown an inhibitory effect of caffeine administration on UVB-induced skin cancer in mice, and these studies are paralleled by epidemiology studies that indicate an inhibitory effect of coffee drinking on nonmelanoma skin cancer in humans. Strikingly, decaffeinated coffee consumption had no such inhibitory effect.Mechanism studies indicate that caffeine has a sunscreen effect that inhibits UVB-induced formation of thymine dimers and sunburn lesions in the epidermis of mice. In addition, caffeine administration has a biological effect that enhances UVB-induced apoptosis thereby enhancing the elimination of damaged precancerous cells, and caffeine administration also enhances apoptosis in tumors. Caffeine administration enhances UVB-induced apoptosis by p53-dependent and p53-independent mechanisms. Exploration of the p53-independent effect indicated that caffeine administration enhanced UVB-induced apoptosis by inhibiting the UVB-induced increase in ATR-mediated formation of phospho-Chk1 (Ser345 and abolishing the UVB-induced decrease in cyclin B1 which resulted in caffeine-induced premature and lethal mitosis in mouse skin. In studies with cultured primary human keratinocytes, inhibition of ATR with siRNA against ATR inhibited Chk1 phosphorylation and enhanced UVB-induced apoptosis. Transgenic mice with decreased epidermal ATR function that were irradiated chronically with UVB had 69% fewer tumors at the end of the study compared with irradiated littermate controls with normal ATR function. These results, which indicate that genetic inhibition of ATR (like pharmacologic inhibition of ATR via caffeine inhibits UVB-induced carcinogenesis and supports the concept that ATR-mediated phosphorylation of Chk1 is an important target for caffeine’s inhibitory effect on UVB-induced carcinogenesis.

  8. Mushroom Ganoderma lucidum Prevents Colitis-Associated Carcinogenesis in Mice

    Science.gov (United States)

    Sliva, Daniel; Loganathan, Jagadish; Jiang, Jiahua; Jedinak, Andrej; Lamb, John G.; Terry, Colin; Baldridge, Lee Ann; Adamec, Jiri; Sandusky, George E.; Dudhgaonkar, Shailesh

    2012-01-01

    Background Epidemiological studies suggest that mushroom intake is inversely correlated with gastric, gastrointestinal and breast cancers. We have recently demonstrated anticancer and anti-inflammatory activity of triterpene extract isolated from mushroom Ganoderma lucidum (GLT). The aim of the present study was to evaluate whether GLT prevents colitis-associated carcinogenesis in mice. Methods/Principal Findings Colon carcinogenesis was induced by the food-borne carcinogen (2-Amino-1-methyl-6-phenylimidazol[4,5-b]pyridine [PhIP]) and inflammation (dextran sodium sulfate [DSS]) in mice. Mice were treated with 0, 100, 300 and 500 mg GLT/kg of body weight 3 times per week for 4 months. Cell proliferation, expression of cyclin D1 and COX-2 and macrophage infiltration was assessed by immunohistochemistry. The effect of GLT on XRE/AhR, PXR and rPXR was evaluated by the reporter gene assays. Expression of metabolizing enzymes CYP1A2, CYP3A1 and CYP3A4 in colon tissue was determined by immunohistochemistry. GLT treatment significantly suppressed focal hyperplasia, aberrant crypt foci (ACF) formation and tumor formation in mice exposed to PhIP/DSS. The anti-proliferative effects of GLT were further confirmed by the decreased staining with Ki-67 in colon tissues. PhIP/DSS-induced colon inflammation was demonstrated by the significant shortening of the large intestine and macrophage infiltrations, whereas GLT treatment prevented the shortening of colon lengths, and reduced infiltration of macrophages in colon tissue. GLT treatment also significantly down-regulated PhIP/DSS-dependent expression of cyclin D1, COX-2, CYP1A2 and CYP3A4 in colon tissue. Conclusions Our data suggest that GLT could be considered as an alternative dietary approach for the prevention of colitis-associated cancer. PMID:23118901

  9. Relevance of CCL3/CCR5 axis in oral carcinogenesis.

    Science.gov (United States)

    da Silva, Janine Mayra; Moreira Dos Santos, Tálita Pollyanna; Sobral, Lays Martin; Queiroz-Junior, Celso Martins; Rachid, Milene Alvarenga; Proudfoot, Amanda E I; Garlet, Gustavo Pompermaier; Batista, Aline Carvalho; Teixeira, Mauro Martins; Leopoldino, Andréia Machado; Russo, Remo Castro; Silva, Tarcília Aparecida

    2017-08-01

    The chemokine CCL3 is a chemotactic cytokine crucial for inflammatory cell recruitment in homeostatic and pathological conditions. CCL3 might stimulate cancer progression by promoting leukocyte accumulation, angiogenesis and tumour growth. The expression of CCL3 and its receptors CCR1 and CCR5 was demonstrated in oral squamous cell carcinoma (OSCC), but their role was not defined. Here, the functions of CCL3 were assessed using a model of chemically induced tongue carcinogenesis with 4-nitroquinoline-1-oxide (4NQO). Lineages of OSCC were used to analyse the effects of CCL3 in vitro . The 4NQO-induced lesions exhibited increased expression of CCL3, CCR1 and CCR5. CCL3 -/- and CCR5 -/- mice presented reduced incidence of tongue tumours compared to wild-type (WT) and CCR1 -/- mice. Consistently, attenuated cytomorphological atypia and reduced cell proliferation were observed in lesions of CCL3 -/- and CCR5 -/- mice. OSCC from CCL3 -/- mice exhibited lower infiltration of eosinophils and reduced expression of Egf, Fgf1, Tgf-β1, Vegfa, Vegfb, Itga-4, Vtn, Mmp-1a, Mmp-2 and Mmp-9 than WT mice. In vitro , CCL3 induced invasion and production of CCL5, IL-6, MMP -2, -8, -9. Blockage of CCL3 in vitro using α-CCL3 or Evasin-1 (a CCL3-binding protein) impaired tumour cell invasion. In conclusion, CCL3/CCR5 axis has pro-tumourigenic effects in oral carcinogenesis. The induction of inflammatory and angiogenic pathways and eosinophils recruitment appear to be the underlying mechanism explaining these effects. These data reveal potential protective effects of CCL3 blockade in oral cancer.

  10. Skeletal dysplasia: Respiratory management during infancy.

    Science.gov (United States)

    Alapati, Deepthi; Shaffer, Thomas H

    2017-10-01

    Skeletal dysplasia encompasses a variety of developmental disorders of the bone and cartilage that manifest as disproportionate shortening of limbs and trunk in the neonate. Many types of skeletal dysplasia are complicated by respiratory failure at or soon after birth and require intensive care and prolonged hospitalization. Respiratory complications in these infants are complex and are characterized by airway anomalies, restrictive lung disease due to a narrow and abnormally compliant chest wall, pulmonary hypoplasia, and central apnea. Appropriate management of these unique patients requires a clear understanding of the pathophysiology and use of pulmonary function tests for early recognition and management of complications. This review provides an overview of the underlying respiratory pathology and a practical guide to the newborn care provider for the diagnosis and management of respiratory complications in infants with skeletal dysplasia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Phun Week: Understanding Physiology

    Science.gov (United States)

    Limson, Mel; Matyas, Marsha Lakes

    2009-01-01

    Topics such as sports, exercise, health, and nutrition can make the science of physiology relevant and engaging for students. In addition, many lessons on these topics, such as those on the cardiovascular, respiratory, and digestive systems, align with national and state life science education standards. Physiology Understanding Week (PhUn…

  12. Technology in respiratory medicine

    African Journals Online (AJOL)

    Repro

    Respiratory medicine is the subspecialty in medicine which requires the most regu- lar and precise evaluation of physiological function for complete assessment of the patient. The very nature of respiratory physiology requires the availability of a range of technological devices. Physiological measurements that may be.

  13. Tumor and the Microenvironment: A Chance to Reframe the Paradigm of Carcinogenesis?

    Directory of Open Access Journals (Sweden)

    Mariano Bizzarri

    2014-01-01

    Full Text Available The somatic mutation theory of carcinogenesis has eventually accumulated an impressive body of shortfalls and paradoxes, as admittedly claimed by its own supporters given that the cell-based approach can hardly explain the emergence of tissue-based processes, like cancer. However, experimental data and alternatives theories developed during the last decades may actually provide a new framework on which cancer research should be reframed. Such issue may be fulfilled embracing new theoretical perspectives, taking the cells-microenvironment interplay as the privileged level of observation and assuming radically different premises as well as new methodological frameworks. Within that perspective, the tumor microenvironment cannot be merely considered akin to new “factor” to be added to an already long list of “signaling factors”; microenvironment represents the physical-biochemical support of the morphogenetic field which drives epithelial cells towards differentiation and phenotype transformation, according to rules understandable only by means of a systems biology approach. That endeavour entails three fundamental aspects: general biological premises, the level of observation (i.e., the systems to which we are looking for, and the principles of biological organization that would help in integrating and understanding experimental data.

  14. Teaching Teaching & Understanding Understanding

    DEFF Research Database (Denmark)

    2006-01-01

    "Teaching Teaching & Understanding Understanding" is a 19-minute award-winning short-film about teaching at university and higher-level educational institutions. It is based on the "Constructive Alignment" theory developed by Prof. John Biggs. The film delivers a foundation for understanding what...

  15. Respiratory sensitization: toxicological point of view on the available assays.

    Science.gov (United States)

    Chary, Aline; Hennen, Jennifer; Klein, Sebastian G; Serchi, Tommaso; Gutleb, Arno C; Blömeke, Brunhilde

    2018-02-01

    Respiratory sensitization as a consequence of exposure to chemical products has increased over the last decades, leading to an increase of morbidity. The increased use of synthetic compounds resulted in an exponential growth of substances to which we are potentially exposed on a daily basis. Some of them are known to induce respiratory sensitization, meaning that they can trigger the development of allergies. In the past, animal studies provided useful results for the understanding of mechanisms involved in the development of respiratory allergies. However, the mechanistic understanding of the involved cellular effects is still limited. Currently, no in vitro or in vivo models are validated to identify chemical respiratory sensitizers. Nonetheless, chemical respiratory sensitizers elicit a positive response in validated assays for skin sensitization. In this review, we will discuss how these assays could be used for respiratory sensitization and if necessary, what can be learnt from these assays to develop a model to assess the respiratory sensitizing potential of chemicals. In the last decades, much work has been done to study the respiratory toxicity of inhaled compounds especially in developing in vitro assays grown at the air-liquid interface. We will discuss how possibly the tests currently used to investigate general particle toxicity could be transformed to investigate respiratory sensitization. In the present review, we describe the most known mechanism involved in the sensitization process and the experimental in vivo and alternative in vitro models, which are currently available and how to adapt and improve existing models to study respiratory sensitization.

  16. Respiratory cancer database: An open access database of respiratory cancer gene and miRNA

    Directory of Open Access Journals (Sweden)

    Jyotsna Choubey

    2017-01-01

    Results and Conclusions: RespCanDB is expected to contribute to the understanding of scientific community regarding respiratory cancer biology as well as developments of new way of diagnosing and treating respiratory cancer. Currently, the database consist the oncogenomic information of lung cancer, laryngeal cancer, and nasopharyngeal cancer. Data for other cancers, such as oral and tracheal cancers, will be added in the near future. The URL of RespCanDB is http://ridb.subdic-bioinformatics-nitrr.in/.

  17. The Interplay of LncRNA-H19 and Its Binding Partners in Physiological Process and Gastric Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2017-02-01

    Full Text Available Long non-coding RNA (lncRNA, a novel and effective modulator in carcinogenesis, has become a study hotspot in recent years. The imprinted oncofetal lncRNA H19 is one of the first identified imprinted lncRNAs with a high expression level in embryogenesis but is barely detectable in most tissues after birth. Aberrant alterations of H19 expression have been demonstrated in various tumors, including gastric cancer (GC, implicating a crucial role of H19 in cancer progression. As one of the top malignancies in the world, GC has already become a serious concern to public health with poor prognosis. The regulatory roles of H19 in gastric carcinogenesis have been explored by various research groups, which leads to the development of GC therapy. This review comprehensively summarizes the current knowledge of H19 in tumorigenesis, especially in GC pathogenesis, with emphasis on the underneath molecular mechanisms depicted from its functional partners. Furthermore, the accumulated knowledge of H19 will provide better understanding on targeted therapy of GC.

  18. Newborn Respiratory Distress.

    Science.gov (United States)

    Hermansen, Christian L; Mahajan, Anand

    2015-12-01

    Newborn respiratory distress presents a diagnostic and management challenge. Newborns with respiratory distress commonly exhibit tachypnea with a respiratory rate of more than 60 respirations per minute. They may present with grunting, retractions, nasal flaring, and cyanosis. Common causes include transient tachypnea of the newborn, respiratory distress syndrome, meconium aspiration syndrome, pneumonia, sepsis, pneumothorax, persistent pulmonary hypertension of the newborn, and delayed transition. Congenital heart defects, airway malformations, and inborn errors of metabolism are less common etiologies. Clinicians should be familiar with updated neonatal resuscitation guidelines. Initial evaluation includes a detailed history and physical examination. The clinician should monitor vital signs and measure oxygen saturation with pulse oximetry, and blood gas measurement may be considered. Chest radiography is helpful in the diagnosis. Blood cultures, serial complete blood counts, and C-reactive protein measurement are useful for the evaluation of sepsis. Most neonates with respiratory distress can be treated with respiratory support and noninvasive methods. Oxygen can be provided via bag/mask, nasal cannula, oxygen hood, and nasal continuous positive airway pressure. Ventilator support may be used in more severe cases. Surfactant is increasingly used for respiratory distress syndrome. Using the INSURE technique, the newborn is intubated, given surfactant, and quickly extubated to nasal continuous positive airway pressure. Newborns should be screened for critical congenital heart defects via pulse oximetry after 24 hours but before hospital discharge. Neonatology consultation is recommended if the illness exceeds the clinician's expertise and comfort level or when the diagnosis is unclear in a critically ill newborn.

  19. Respiratory medicine of reptiles.

    Science.gov (United States)

    Schumacher, Juergen

    2011-05-01

    Noninfectious and infectious causes have been implicated in the development of respiratory tract disease in reptiles. Treatment modalities in reptiles have to account for species differences in response to therapeutic agents as well as interpretation of diagnostic findings. Data on effective drugs and dosages for the treatment of respiratory diseases are often lacking in reptiles. Recently, advances have been made on the application of advanced imaging modalities, especially computed tomography for the diagnosis and treatment monitoring of reptiles. This article describes common infectious and noninfectious causes of respiratory disease in reptiles, including diagnostic and therapeutic regimen. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Effects of environmental stressors on histone modifications and their relevance to carcinogenesis: a systematic review.

    NARCIS (Netherlands)

    Dik, S.; Scheepers, P.T.J.; Godderis, L.

    2012-01-01

    Carcinogenesis is a complex process involving both genetic and epigenetic mechanisms. The cellular molecular epigenetic machinery, including histone modifications, is associated with changes in gene expression induced by exposure to environmental agents. In this paper, we systematically reviewed

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. 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

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

    International Nuclear Information System (INIS)

    Tanaka, Takuji

    2012-01-01

    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

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

    Data.gov (United States)

    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...

  5. 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...

  6. The effect of aging on respiratory synergy.

    Science.gov (United States)

    Kweon, Migyoung; Son, Sung Min; Kwon, Yong Hyun

    2015-04-01

    [Purpose] The purpose of this study was to investigate the effect of aging on respiratory synergy, through the comparison of an elderly group and a young group, to help further understanding of postural control in the elderly. [Subjects and Methods] Ten community-dwelling elderly subjects and ten young subjects performed standing under two different respiratory conditions: quiet breathing and apnea. Center of foot pressure displacement and joint angular movements of the head, trunk, pelvis, hips, knees and ankles were measured. [Results] The results of this study showed that the elderly group had a respiratory synergy different from that of the young group. The elderly group in quiet stance used significantly more hip and pelvis movements when compensating for respiratory disturbance than standing with apnea, while the young group used significantly more whole body segments. There were no differences in angular displacements in the quiet stance between the elderly and the young groups. [Conclusion] The elderly group demonstrated a respiratory synergy pattern different from that of the young group. The findings indicate that aging changes the respiratory synergy pattern and this change is not due to decreased functioning of the ankle joint alone.

  7. Chronic Inflammation in Colorectal Carcinogenesis: Role of Inflammatory Mediators, Intestinal Microbes, and Chemoprevention Potency

    OpenAIRE

    Tedja, Irwin; Abdullah, Murdani

    2013-01-01

    Colorectal carcinogenesis is a multi-factorial process which involves accumulation of genetic defect, protein modification, and cell interaction with matrix in colonic epithelial cells. Chronic inflammation is suspected to play role in carcinogenesis by inhibiting apoptosis, impairing DNA, and chronically stimulating mucosal proliferation. Alteration in intestinal microbes' population, either in one particular species or in overall composition, may also cause chronic inflammation which increa...

  8. 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....

  9. Chemoprevention of glandular stomach carcinogenesis through duodenogastric reflux in rats by a COX-2 inhibitor.

    OpenAIRE

    Oba, Masaru; Miwa, Koichi; Fujimura, Takashi; Harada, Shin-ichi; Sasaki, Shozo; Hattori, Takanori

    2008-01-01

    Duodenogastric reflux (DGR) causes glandular stomach carcinogenesis in rats without carcinogens. We aimed to investigate how this carcinogenesis might be prevented by a selective COX-2 inhibitor, meloxicam. A series of 188 Fisher 344 rats underwent a surgical DGR procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other an experimental chow containing meloxicam [0.3 mg/kg bw/day] (meloxicam group). The animals were sequentially sacrificed at ...

  10. Respiratory disease in pregnancy.

    Science.gov (United States)

    Mehta, Niharika; Chen, Kenneth; Hardy, Erica; Powrie, Raumond

    2015-07-01

    Many physiological and anatomical changes of pregnancy affect the respiratory system. These changes often affect the presentation and management of the various respiratory illnesses in pregnancy. This article focuses on several important respiratory issues in pregnancy. The management of asthma, one of the most common chronic illnesses in pregnancy, remains largely unchanged compared to the nonpregnant state. Infectious respiratory illness, including pneumonia and tuberculosis, are similarly managed in pregnancy with antibiotics, although special attention may be needed for antibiotic choices with more pregnancy safety data. When mechanical ventilation is necessary, consideration should be given to the maternal hemodynamics of pregnancy and fetal oxygenation. Maintaining maternal oxygen saturation above 95% is recommended to sustain optimal fetal oxygenation. Cigarette smoking has known risks in pregnancy, and current practice guidelines recommend offering cognitive and pharmacologic interventions to pregnant women to assist in smoking cessation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Short-term carcinogenesis evaluation of Casearia sylvestris

    Directory of Open Access Journals (Sweden)

    Cleide A.S. Tirloni

    Full Text Available Abstract Casearia sylvestris Sw., Salicaceae, is an important medicinal plant widely used in Brazil for the treatment of various cardiovascular disorders. This species was included as of interest by Brazilian Unified Health System. Although preclinical studies described cardiovascular protective effects and apparent absence of toxicity, no studies have evaluated its carcinogenic potential. In this study, we proposed a short-term carcinogenesis evaluation of C. sylvestris in Wistar rats, aiming to check the safety of this species to use it as proposed by Brazilian Unified Health System. C. sylvestris leaves were obtained and the crude extract was prepared by maceration from methanol/water. Wistar rats were orally treated for 12 weeks with 50, 250 or 500 mg kg−1 of crude extract or vehicle. Body weight, daily morbidity and mortality were monitored. Blood and bone marrow samples were collect for micronucleus test, comet assay and tumor markers evaluation. Vital organs were removed to macro and histopathological analyses. The crude extract did not induce mutagenic and genotoxic effects and no alterations were observed in important tumor markers. Finally, no detectable signs of injury through gross pathology or histopathological examinations were observed. Our results certify the absence of the crude extract toxicity, indicating its safety, even at prolonged exposure as proposed by Brazilian Unified Health System.

  12. Effects of retinoids on ultraviolet-induced carcinogenesis

    International Nuclear Information System (INIS)

    Epstein, J.H.

    1981-01-01

    The evidence for effects of the retinoids on UV-induced carcinogenesis is sparse. Clinical observations indicate that topical RA can cause significant regression of premalignant actinic keratoses. Also there is some evidence that this agent can cause dissolution of some basal cell epitheliomas. However this latter effect does not appear to be of therapeutic value. Systemic retinoids are of little value in the treatment of premalignant and malignant cutaneous lesions though 13-cis-retinoic acid might be of use in the basal cell nevus syndrome. Examination of the influence of the retinoids on photocarcinogenesis essentially has been confined to RA and animal experimentation. RA in nontoxic concentrations can both stimulate and inhibit photocarcinogenesis depending upon the circumstances of the study. The mechanisms of these responses are not clear. Influences on DNA synthesis directly and/or indirectly or on immune responses may be involved in both effects. Preliminary studies with oral 13-cis-retinoic acid have not demonstrated any effects to date on UV-induced skin cancer formation

  13. Recent Concepts of Ovarian Carcinogenesis: Type I and Type II

    Directory of Open Access Journals (Sweden)

    Masafumi Koshiyama

    2014-01-01

    Full Text Available Type I ovarian tumors, where precursor lesions in the ovary have clearly been described, include endometrioid, clear cell, mucinous, low grade serous, and transitional cell carcinomas, while type II tumors, where such lesions have not been described clearly and tumors may develop de novo from the tubal and/or ovarian surface epithelium, comprise high grade serous carcinomas, undifferentiated carcinomas, and carcinosarcomas. The carcinogenesis of endometrioid and clear cell carcinoma (CCC arising from endometriotic cysts is significantly influenced by the free iron concentration, which is associated with cancer development through the induction of persistent oxidative stress. A subset of mucinous carcinomas develop in association with ovarian teratomas; however, the majority of these tumors do not harbor any teratomatous component. Other theories of their origin include mucinous metaplasia of surface epithelial inclusions, endometriosis, and Brenner tumors. Low grade serous carcinomas are thought to evolve in a stepwise fashion from benign serous cystadenoma to a serous borderline tumor (SBT. With regard to high grade serous carcinoma, the serous tubal intraepithelial carcinomas (STICs of the junction of the fallopian tube epithelium with the mesothelium of the tubal serosa, termed the “tubal peritoneal junction” (TPJ, undergo malignant transformation due to their location, and metastasize to the nearby ovary and surrounding pelvic peritoneum. Other theories of their origin include the ovarian hilum cells.

  14. BRAFV600E: implications for carcinogenesis and molecular therapy.

    LENUS (Irish Health Repository)

    Cantwell-Dorris, Emma R

    2012-02-01

    The mitogen-activated protein kinase (MAPK)\\/extracellular signal-regulated kinase (ERK) pathway is frequently mutated in human cancer. This pathway consists of a small GTP protein of the RAS family that is activated in response to extracellular signaling to recruit a member of the RAF kinase family to the cell membrane. Active RAF signals through MAP\\/ERK kinase to activate ERK and its downstream effectors to regulate a wide range of biological activities including cell differentiation, proliferation, senescence, and survival. Mutations in the v-raf murine sarcoma viral oncogenes homolog B1 (BRAF) isoform of the RAF kinase or KRAS isoform of the RAS protein are found as activating mutations in approximately 30% of all human cancers. The BRAF pathway has become a target of interest for molecular therapy, with promising results emerging from clinical trials. Here, the role of the most common BRAF mutation BRAF(V600E) in human carcinogenesis is investigated through a review of the literature, with specific focus on its role in melanoma, colorectal, and thyroid cancers and its potential as a therapeutic target.

  15. [Gut microbiota: What impact on colorectal carcinogenesis and treatment?

    Science.gov (United States)

    Bruneau, Antoine; Baylatry, Minh-Tam; Joly, Anne Christine; Sokol, Harry

    2018-01-01

    The gut microbiota, composed of 10 14 microorganisms, is now considered as a "hidden organ", regarding to its digestive, metabolic and immune functions, which are helpful to its host. For the last 15 years, advances in molecular biology have highlighted the association of gut microbiota dysbiosis with several diseases, including colorectal cancer. An increased abundance of some bacteria (including Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli) is associated with cancer, whereas others seem to be protective (Faecalibacterium prausnitzii). Several mechanisms, which are species-specific, are involved in colorectal carcinogenesis. Most of the time, bacterial toxins are involved in pro-inflammatory processes and in activation of angiogenesis and cellular proliferation pathways. The identification of these bacteria leads to envisage the gut microbiota as potential screening tool for colorectal cancer. Recent studies showed a relation between the gut microbiota and the efficacy and toxicity of chemotherapies (oxaliplatin, irinotecan) and immunotherapies (including ipilimumab). Therapeutic approaches targeting the gut microbiota are now available (probiotics, fecal microbiota transplantation…). New therapeutic strategy combining both chemotherapy and/or immunotherapy with an adjuvant treatment targeting the gut microbiota can now be developed in order to improve treatment response and tolerance. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  16. HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis.

    Science.gov (United States)

    Mirabello, Lisa; Yeager, Meredith; Yu, Kai; Clifford, Gary M; Xiao, Yanzi; Zhu, Bin; Cullen, Michael; Boland, Joseph F; Wentzensen, Nicolas; Nelson, Chase W; Raine-Bennett, Tina; Chen, Zigui; Bass, Sara; Song, Lei; Yang, Qi; Steinberg, Mia; Burdett, Laurie; Dean, Michael; Roberson, David; Mitchell, Jason; Lorey, Thomas; Franceschi, Silvia; Castle, Philip E; Walker, Joan; Zuna, Rosemary; Kreimer, Aimée R; Beachler, Daniel C; Hildesheim, Allan; Gonzalez, Paula; Porras, Carolina; Burk, Robert D; Schiffman, Mark

    2017-09-07

    Although most cervical human papillomavirus type 16 (HPV16) infections become undetectable within 1-2 years, persistent HPV16 causes half of all cervical cancers. We used a novel HPV whole-genome sequencing technique to evaluate an exceptionally large collection of 5,570 HPV16-infected case-control samples to determine whether viral genetic variation influences risk of cervical precancer and cancer. We observed thousands of unique HPV16 genomes; very few women shared the identical HPV16 sequence, which should stimulate a careful re-evaluation of the clinical implications of HPV mutation rates, transmission, clearance, and persistence. In case-control analyses, HPV16 in the controls had significantly more amino acid changing variants throughout the genome. Strikingly, E7 was devoid of variants in precancers/cancers compared to higher levels in the controls; we confirmed this in cancers from around the world. Strict conservation of the 98 amino acids of E7, which disrupts Rb function, is critical for HPV16 carcinogenesis, presenting a highly specific target for etiologic and therapeutic research. Published by Elsevier Inc.

  17. LTA4H regulates cell cycle and skin carcinogenesis.

    Science.gov (United States)

    Oi, Naomi; Yamamoto, Hiroyuki; Langfald, Alyssa; Bai, Ruihua; Lee, Mee-Hyun; Bode, Ann M; Dong, Zigang

    2017-07-01

    Leukotriene A4 hydrolase (LTA4H), a bifunctional zinc metallo-enzyme, is reportedly overexpressed in several human cancers. Our group has focused on LTA4H as a potential target for cancer prevention and/or therapy. In the present study, we report that LTA4H is a key regulator of cell cycle at the G0/G1 phase acting by negatively regulating p27 expression in skin cancer. We found that LTA4H is overexpressed in human skin cancer tissue. Knocking out LTA4H significantly reduced skin cancer development in the 7,12-dimethylbenz(a)anthracene (DMBA)-initiated/12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted two-stage skin cancer mouse model. LTA4H depletion dramatically decreased anchorage-dependent and -independent skin cancer cell growth by inducing cell cycle arrest at the G0/G1 phase. Moreover, our findings showed that depletion of LTA4H enhanced p27 protein stability, which was associated with decreased phosphorylation of CDK2 at Thr160 and inhibition of the CDK2/cyclin E complex, resulting in down-regulated p27 ubiquitination. These findings indicate that LTA4H is critical for skin carcinogenesis and is an important mediator of cell cycle and the data begin to clarify the mechanisms of LTA4H's role in cancer development. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis

    Science.gov (United States)

    Valenzuela, Manuel A; Canales, Jimena; Corvalán, Alejandro H; Quest, Andrew FG

    2015-01-01

    The sequence of events associated with the development of gastric cancer has been described as “the gastric precancerous cascade”. This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia. According to this model, Helicobacter pylori (H. pylori) infection targets the normal gastric mucosa causing non-atrophic gastritis, an initiating lesion that can be cured by clearing H. pylori with antibiotics or that may then linger in the case of chronic infection and progress to atrophic gastritis. The presence of virulence factors in the infecting H. pylori drives the carcinogenesis process. Independent epidemiological and animal studies have confirmed the sequential progression of these precancerous lesions. Particularly long-term follow-up studies estimated a risk of 0.1% for atrophic gastritis/intestinal metaplasia and 6% in case of dysplasia for the long-term development of gastric cancer. With this in mind, a better understanding of the genetic and epigenetic changes associated with progression of the cascade is critical in determining the risk of gastric cancer associated with H. pylori infection. In this review, we will summarize some of the most relevant mechanisms and focus predominantly but not exclusively on the discussion of gene promoter methylation and miRNAs in this context. PMID:26668499

  19. Human AP Endonuclease 1: A Potential Marker for the Prediction of Environmental Carcinogenesis Risk

    Directory of Open Access Journals (Sweden)

    Jae Sung Park

    2014-01-01

    Full Text Available Human apurinic/apyrimidinic endonuclease 1 (APE1 functions mainly in DNA repair as an enzyme removing AP sites and in redox signaling as a coactivator of various transcription factors. Based on these multifunctions of APE1 within cells, numerous studies have reported that the alteration of APE1 could be a crucial factor in development of human diseases such as cancer and neurodegeneration. In fact, the study on the combination of an individual’s genetic make-up with environmental factors (gene-environment interaction is of great importance to understand the development of diseases, especially lethal diseases including cancer. Recent reports have suggested that the human carcinogenic risk following exposure to environmental toxicants is affected by APE1 alterations in terms of gene-environment interactions. In this review, we initially outline the critical APE1 functions in the various intracellular mechanisms including DNA repair and redox regulation and its roles in human diseases. Several findings demonstrate that the change in expression and activity as well as genetic variability of APE1 caused by environmental chemical (e.g., heavy metals and cigarette smoke and physical carcinogens (ultraviolet and ionizing radiation is likely associated with various cancers. These enable us to ultimately suggest APE1 as a vital marker for the prediction of environmental carcinogenesis risk.

  20. Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γ Agonists

    Directory of Open Access Journals (Sweden)

    Martin B. Oleksiewicz

    2008-01-01

    Full Text Available Despite clinical promise, dual-acting activators of PPARα and γ (here termed PPARα+γ agonists have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARα is invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγ can in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARα as well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γ agonists may be caused by receptor-mediated effects (exaggerated pharmacology. Based on previously published mode of action data for the PPARα+γ agonist ragaglitazar, and the available literature about the role of PPARα and γ in rodent carcinogenesis, we propose a mode of action hypothesis for the carcinogenic effect of PPARα+γ agonists in the rat urothelium, which combines receptor-mediated and off-target cytotoxic effects. The proposed mode of action hypothesis is being explored in our laboratories, towards understanding the human relevance of the rat cancer findings, and developing rapid in vitro or short-term in vivo screening approaches to faciliate development of new dual-acting PPAR agonist compounds.

  1. Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity)

    International Nuclear Information System (INIS)

    Alfarouk, Khalid O.; Shayoub, Mohammed E.A.; Muddathir, Abdel Khalig; Elhassan, Gamal O.; Bashir, Adil H.H.

    2011-01-01

    Carcinogenesis occurs through a series of steps from normal into benign and finally malignant phenotype. This cancer evolutionary trajectory has been accompanied by similar metabolic transformation from normal metabolism into Pasteur and/or Crabtree-Effects into Warburg-Effect and finally Cannibalism and/or Lactate-Symbiosis. Due to lactate production as an end-product of glycolysis, tumor colonies acquire new phenotypes that rely on lactate as energetic fuel. Presence of Warburg-Effect indicates that some tumor cells undergo partial (if not complete) de-endosymbiosis and so cancer cells have been become unicellular microorganism (anti-Dollo's Law) specially when they evolve to develop cannibalism as way of metabolism while oxidative types of cells that rely on lactate, as their energetic fuel, might represent extra-endosymbiosis. Thus, at the end, the cancer colony could be considered as integrated metabolic ecosystem. Proper understanding of tumor metabolism will contribute to discover potential anticancer agents besides conventional chemotherapy

  2. Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity)

    Energy Technology Data Exchange (ETDEWEB)

    Alfarouk, Khalid O., E-mail: Alfarouk@Hala-alfarouk.org [Department of Evolution of Tumor Metabolism and Pharmacology, Hala Alfarouk Cancer Center, Khartoum 11123 (Sudan); Shayoub, Mohammed E.A. [Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum 11111 (Sudan); Muddathir, Abdel Khalig [Department of Pharmacognosy, Faculty of Pharmacy, University of Khartoum, Khartoum 11111 (Sudan); Elhassan, Gamal O. [General Directorate of Pharmacy, Federal Ministry of Health, Khartoum 11111 (Sudan); Bashir, Adil H.H. [Department of Evolution of Tumor Metabolism and Pharmacology, Hala Alfarouk Cancer Center, Khartoum 11123 (Sudan); Al Jawda Medical Hospital, Khartoum 11111 (Sudan)

    2011-07-22

    Carcinogenesis occurs through a series of steps from normal into benign and finally malignant phenotype. This cancer evolutionary trajectory has been accompanied by similar metabolic transformation from normal metabolism into Pasteur and/or Crabtree-Effects into Warburg-Effect and finally Cannibalism and/or Lactate-Symbiosis. Due to lactate production as an end-product of glycolysis, tumor colonies acquire new phenotypes that rely on lactate as energetic fuel. Presence of Warburg-Effect indicates that some tumor cells undergo partial (if not complete) de-endosymbiosis and so cancer cells have been become unicellular microorganism (anti-Dollo's Law) specially when they evolve to develop cannibalism as way of metabolism while oxidative types of cells that rely on lactate, as their energetic fuel, might represent extra-endosymbiosis. Thus, at the end, the cancer colony could be considered as integrated metabolic ecosystem. Proper understanding of tumor metabolism will contribute to discover potential anticancer agents besides conventional chemotherapy.

  3. Increased expression of Nlp, a potential oncogene in ovarian cancer, and its implication in carcinogenesis.

    Science.gov (United States)

    Qu, Danni; Qu, Hongyan; Fu, Ming; Zhao, Xuelian; Liu, Rong; Sui, Lihua; Zhan, Qimin

    2008-08-01

    Nlp (Ninein-like protein), a novel centrosome protein involved in microtubule nucleation, has been studied extensively in our laboratory, and its overexpression has been found in some human tumors. To understand the role of Nlp in human ovarian cancer development, we studied the correlation of Nlp expression with clinicopathological parameters and survival in epithelial ovarian cancer, and the impact of Nlp overexpression on ovarian cancer cells. Nlp expression in normal, borderline, benign and malignant epithelial ovarian tissues was examined by immunohistochemistry. The correlation between Nlp expression and tumor grade, FIGO stage and histological type was also evaluated. Survival was calculated using Kaplan-Meier estimates. Cell proliferation and apoptosis were assayed after stable transfection of pEGFP-C3-Nlp or empty vector in human ovarian cancer cell line SKOV3. Nlp was positive in 1 of 10 (10%) normal ovarian tissues, 5 of 34 (14.7%) benign tumors, 9 of 26 (34.6%) borderline tumors and 73 of 131 (56.0%) ovarian tumors. Nlp immunoreactivity intensity significantly correlated with tumor grade, but not with FIGO stage or histological type. Kaplan-Meier curves showed that Nlp overexpression was marginally associated with decreased overall survival. Overexpression of Nlp enhanced proliferation and inhibited apoptosis induced by paclitaxel in the SKOV3 cell line. Overexpression of Nlp in ovarian tumors raises the possibility that Nlp may play a role in ovarian carcinogenesis.

  4. Respiratory Syncytial Virus (RSV)

    Centers for Disease Control (CDC) Podcasts

    2013-02-04

    Respiratory Syncytial Virus, or RSV, causes cold-like symptoms but can be serious for infants and older adults. In this podcast, CDC’s Dr. Eileen Schneider discusses this common virus and offers tips to prevent its spread.  Created: 2/4/2013 by National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases (DVD).   Date Released: 2/13/2013.

  5. Acute respiratory distress syndrome

    OpenAIRE

    Confalonieri, Marco; Salton, Francesco; Fabiano, Francesco

    2017-01-01

    Since its first description, the acute respiratory distress syndrome (ARDS) has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foste...

  6. Respiratory gating in cardiac PET

    DEFF Research Database (Denmark)

    Lassen, Martin Lyngby; Rasmussen, Thomas; Christensen, Thomas E

    2017-01-01

    BACKGROUND: Respiratory motion due to breathing during cardiac positron emission tomography (PET) results in spatial blurring and erroneous tracer quantification. Respiratory gating might represent a solution by dividing the PET coincidence dataset into smaller respiratory phase subsets. The aim...... stress (82)RB-PET. Respiratory rates and depths were measured by a respiratory gating system in addition to registering actual respiratory rates. Patients undergoing adenosine stress showed a decrease in measured respiratory rate from initial to later scan phase measurements [12.4 (±5.7) vs 5.6 (±4.......7) min(-1), P PET...

  7. Immunophenotypic Analysis in Early Müllerian Serous Carcinogenesis.

    Science.gov (United States)

    Nafisi, Houman; Ghorab, Zeina; Ismill, Nadia; Dubé, Valerie; Plotkin, Anna; Han, Guangming; Cesari, Matthew; Lu, Fang-I; Saad, Reda; Khalifa, Mahmoud; Nofech-Mozes, Sharon

    2015-09-01

    Studies on the immunophenotypes of early forms of serous carcinoma arising from female genital tract are limited. We aimed to examine p53, p16(Ink4a), estrogen receptor (ER), progesterone receptor (PR), ERBB2, WT1, and Ki-67 protein expression in endometrial intraepithelial carcinoma (n=29), serous tubal intraepithelial lesion (n=4) and carcinoma (STIC, n=10), and the putative precursor p53 signature (n=11). Among endometrial intraepithelial carcinoma, 80% demonstrated p53 overexpression and 10% were consistent with a null phenotype. p16(Ink4a) immunostaining were observed in all endometrial intraepithelial carcinoma cases. ER, PR, ERBB2, and WT1 were positive in 54%, 25%, 11%, and 18% of cases, respectively. STIC cases demonstrated p53 overexpression and null phenotype in 90% and 10%, respectively. All STIC cases were p16(Ink4a) and WT1 positive, whereas ER and PR were positive in 70% and 20%, respectively. All STICs were negative for ERBB2. Among serous tubal intraepithelial lesion cases, 75% demonstrated p53 overexpression and 25% a null phenotype. p53 was positive in all 11 p53 signature cases, whereas p16(Ink4a) was universally negative. Finally, ER and PR were positive in 100% and 73% of p53 signature cases, respectively. These results suggest that p16(Ink4a) has a role in early Müllerian serous carcinogenesis but is absent in the earliest noncommitted lesion. p16(Ink4a) immunohistochemistry can be used as an adjunct confirmatory tool in p53-null cases with limited surface area.

  8. Thymoquinone Attenuates Diethylnitrosamine Induction of Hepatic Carcinogenesis Through Antioxidant Signaling

    Directory of Open Access Journals (Sweden)

    Mohamed M. Sayed-Ahmed

    2010-01-01

    Full Text Available Hepatocellular carcinoma accounts for about 80–90% of all liver cancer and is the fourth most common cause of cancer mortality. Although there are many strategies for the treatment of liver cancer, chemoprevention seems to be the best strategy for lowering the incidence of this disease. Therefore, this study has been initiated to investigate whether thymoquinone (TQ, Nigella sativa derived-compound with strong antioxidant properties, supplementation could prevent initiation of hepatocarcinogenesis-induced by diethylnitrosamine (DENA, a potent initiator and hepatocarcinogen, in rats. Male Wistar albino rats were divided into four groups. Rats of Group 1 received a single intraperitoneal (I.P. injection of normal saline. Animals in Group 2 were given TQ (4 mg/kg/day in drinking water for 7 consecutive days. Rats of Group 3 were injected with a single dose of DENA (200 mg/kg, I.P.. Animals in Group 4 were received TQ and DENA. DENA significantly increased alanine transaminase (ALT, alkaline phosphatase (ALP, total bilirubin, thiobarbituric acid reactive substances (TBARS and total nitrate/nitrite (NOx and decreased reduced glutathione (GSH, glutathione peroxidase (GSHPx, glutathione-s-transferase (GST and catalase (CAT activity in liver tissues. Moreover, DENA decreased gene expression of GSHPx, GST and CAT and caused severe histopathological lesions in liver tissue. Interestingly, TQ supplementation completely reversed the biochemical and histopathological changes induced by DENA to the control values. In conclusion, data from this study suggest that: (1 decreased mRNA expression of GSHPx, CAT and GST during DENA-induced initiation of hepatic carcinogenesis, (2 TQ supplementation prevents the development of DENA-induced initiation of liver cancer by decreasing oxidative stress and preserving both the activity and mRNA expression of antioxidant enzymes.

  9. Addressing the public health burden of respiratory viruses: the Battle against Respiratory Viruses (BRaVe) Initiative

    NARCIS (Netherlands)

    Legand, Anais; Briand, Sylvie; Shindo, Nikki; Brooks, W. Abdullah; de Jong, Menno D.; Farrar, Jeremy; Aguilera, Ximena; Hayden, Frederick G.

    2013-01-01

    Given the enormous estimated burden of respiratory virus infections worldwide, a substantial number of research priorities exist in order to better understand their epidemiology, pathogenesis, prevention and clinical management across different populations and resource settings. New therapeutics and

  10. Respiratory tract carcinogenesis in large and small experimental animal following daily inhalation of radon daughters and uranium ore dust

    International Nuclear Information System (INIS)

    Stuart, B.O.; Palmer, R.F.; Filipy, R.E.; Dagle, G.E.; McDonald, K.E.

    1977-01-01

    Uranium ore miners of the Colorado plateau suffer more than 6 times the normal incidence of lung cancer, and their mortality rates due to pneumoconiosis and emphysema are 5 times greater than in the general population. Inhalation exposures of beagle dogs and rodents to radon daughters and uranium ore dust were undertaken to determine which of these uranium mine air contaminants, and at what levels, are responsible for the high incidences of these diseases. Results are discussed

  11. Respiratory tract carcinogenesis in large and small experimental animal following daily inhalation of radon daughters and uranium ore dust

    Energy Technology Data Exchange (ETDEWEB)

    Stuart, B.O.; Palmer, R.F.; Filipy, R.E.; Dagle, G.E.; McDonald, K.E.

    1977-01-01

    Uranium ore miners of the Colorado plateau suffer more than 6 times the normal incidence of lung cancer, and their mortality rates due to pneumoconiosis and emphysema are 5 times greater than in the general population. Inhalation exposures of beagle dogs and rodents to radon daughters and uranium ore dust were undertaken to determine which of these uranium mine air contaminants, and at what levels, are responsible for the high incidences of these diseases. Results are discussed.

  12. Respiratory muscle training increases respiratory muscle strength and reduces respiratory complications after stroke: a systematic review

    Directory of Open Access Journals (Sweden)

    Kênia KP Menezes

    2016-07-01

    Full Text Available Question: After stroke, does respiratory muscle training increase respiratory muscle strength and/or endurance? Are any benefits carried over to activity and/or participation? Does it reduce respiratory complications? Design: Systematic review of randomised or quasi-randomised trials. Participants: Adults with respiratory muscle weakness following stroke. Intervention: Respiratory muscle training aimed at increasing inspiratory and/or expiratory muscle strength. Outcome measures: Five outcomes were of interest: respiratory muscle strength, respiratory muscle endurance, activity, participation and respiratory complications. Results: Five trials involving 263 participants were included. The mean PEDro score was 6.4 (range 3 to 8, showing moderate methodological quality. Random-effects meta-analyses showed that respiratory muscle training increased maximal inspiratory pressure by 7 cmH2O (95% CI 1 to 14 and maximal expiratory pressure by 13 cmH2O (95% CI 1 to 25; it also decreased the risk of respiratory complications (RR 0.38, 95% CI 0.15 to 0.96 compared with no/sham respiratory intervention. Whether these effects carry over to activity and participation remains uncertain. Conclusion: This systematic review provided evidence that respiratory muscle training is effective after stroke. Meta-analyses based on five trials indicated that 30 minutes of respiratory muscle training, five times per week, for 5 weeks can be expected to increase respiratory muscle strength in very weak individuals after stroke. In addition, respiratory muscle training is expected to reduce the risk of respiratory complications after stroke. Further studies are warranted to investigate whether the benefits are carried over to activity and participation. Registration: PROSPERO (CRD42015020683. [Menezes KKP, Nascimento LR, Ada L, Polese JC, Avelino PR, Teixeira-Salmela LF (2016 Respiratory muscle training increases respiratory muscle strength and reduces respiratory

  13. Respiratory cancer database: An open access database of respiratory cancer gene and miRNA.

    Science.gov (United States)

    Choubey, Jyotsna; Choudhari, Jyoti Kant; Patel, Ashish; Verma, Mukesh Kumar

    2017-01-01

    Respiratory cancer database (RespCanDB) is a genomic and proteomic database of cancer of respiratory organ. It also includes the information of medicinal plants used for the treatment of various respiratory cancers with structure of its active constituents as well as pharmacological and chemical information of drug associated with various respiratory cancers. Data in RespCanDB has been manually collected from published research article and from other databases. Data has been integrated using MySQL an object-relational database management system. MySQL manages all data in the back-end and provides commands to retrieve and store the data into the database. The web interface of database has been built in ASP. RespCanDB is expected to contribute to the understanding of scientific community regarding respiratory cancer biology as well as developments of new way of diagnosing and treating respiratory cancer. Currently, the database consist the oncogenomic information of lung cancer, laryngeal cancer, and nasopharyngeal cancer. Data for other cancers, such as oral and tracheal cancers, will be added in the near future. The URL of RespCanDB is http://ridb.subdic-bioinformatics-nitrr.in/.

  14. Respiratory effects of trichloroethylene.

    Science.gov (United States)

    Dumas, Orianne; Despreaux, Thomas; Perros, Frédéric; Lau, Edmund; Andujar, Pascal; Humbert, Marc; Montani, David; Descatha, Alexis

    2018-01-01

    Trichloroethylene (TCE) is a chlorinated solvent that has been used widely around the world in the twentieth century for metal degreasing and dry cleaning. Although TCE displays general toxicity and is classified as a human carcinogen, the association between TCE exposure and respiratory disorders are conflicting. In this review we aimed to systematically evaluate the current evidence for the respiratory effects of TCE exposure and the implications for the practicing clinician. There is limited evidence of an increased risk of lung cancer associated with TCE exposure based on animal and human data. However, the effect of other chlorinated solvents and mixed solvent exposure should be further investigated. Limited data are available to support an association between TCE exposure and respiratory tract disorders such as asthma, chronic bronchitis, or rhinitis. The most consistent data is the association of TCE with autoimmune and vascular diseases such as systemic sclerosis and pulmonary veno-occlusive disease. Although recent data are reassuring regarding the absence of an increased lung cancer risk with TCE exposure, clinicians should be aware of other potential respiratory effects of TCE. In particular, occupational exposure to TCE has been linked to less common conditions such as systemic sclerosis and pulmonary veno-occlusive disease. Copyright © 2017. Published by Elsevier Ltd.

  15. Respiratory transfusion reactions

    Directory of Open Access Journals (Sweden)

    Ivica Marić

    2017-11-01

    Full Text Available Respiratory transfusion-related reactions are not very frequent, partly also because recognition and reporting transfusion reactions is still underemphasized. Tis article describes the most important respiratory transfusion reactions, their pathophysiology, clinical picture and treatment strategies. Respiratory transfusion related reactions can be primary or secondary. The most important primary transfusion-related reactions are TRALI - transfusion-related acute lung injury, TACO – transfusion-associated circulatory overload, and TAD - transfusion-associated dyspnea. TRALI is immuneassociated injury of alveolar basal membrane, which becomes highly permeable and causes noncardiogenic pulmonary edema. Treatment of TRALI is mainly supportive with oxygen, fluids (in case of hypotension and in cases of severe acute respiratory failure also mechanic ventilation. TACO is caused by volume overload in predisposed individuals, such as patients with heart failure, the elderly, infants, patients with anemia and patients with positive fluid balance. Clinical picture is that of a typical pulmonary cardiogenic edema, and the therapy is classical: oxygen and diuretics, and in severe cases also non-invasive or invasive mechanical ventilation. TAD is usually a mild reaction of unknown cause and cannot be classified as TACO or TRALI, nor can it be ascribed to patient’s preexisting diseases. Although the transfusion-related reactions are not very common, knowledge about them can prevent serious consequences. On the one hand preventive measures should be sought, and on the other early recognition is beneficial, so that proper treatment can take place.

  16. The microbiota of the respiratory tract : Gatekeeper to respiratory health

    NARCIS (Netherlands)

    Man, Wing Ho; De Steenhuijsen Piters, Wouter A.A.; Bogaert, Debby

    2017-01-01

    The respiratory tract is a complex organ system that is responsible for the exchange of oxygen and carbon dioxide. The human respiratory tract spans from the nostrils to the lung alveoli and is inhabited by niche-specific communities of bacteria. The microbiota of the respiratory tract probably acts

  17. Chemopreventive Strategies for Inflammation-Related Carcinogenesis: Current Status and Future Direction

    Science.gov (United States)

    Kanda, Yusuke; Osaki, Mitsuhiko; Okada, Futoshi

    2017-01-01

    A sustained and chronically-inflamed environment is characterized by the presence of heterogeneous inflammatory cellular components, including neutrophils, macrophages, lymphocytes and fibroblasts. These infiltrated cells produce growth stimulating mediators (inflammatory cytokines and growth factors), chemotactic factors (chemokines) and genotoxic substances (reactive oxygen species and nitrogen oxide) and induce DNA damage and methylation. Therefore, chronic inflammation serves as an intrinsic niche for carcinogenesis and tumor progression. In this article, we summarize the up-to-date findings regarding definitive/possible causes and mechanisms of inflammation-related carcinogenesis derived from experimental and clinical studies. We also propose 10 strategies, as well as candidate agents for the prevention of inflammation-related carcinogenesis. PMID:28422073

  18. Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis

    Science.gov (United States)

    Tian, Dongping; Lei, Zhijin; Chen, Donglin; Xu, Zexin; Su, Min

    2016-01-01

    Chronic inflammation is associated with increased risk of cancer development, whereas the link between chronic inflammation and esophageal carcinogenesis is still obscure heretofore. This study aimed to investigate the relationship between chronic inflammation and DNA damage, as well as the possible role of DNA damage in esophageal carcinogenic process. Endoscopic esophageal biopsies from 109 individuals from Chaoshan littoral, a high-risk region for esophageal squamous cell carcinoma (ESCC), were examined to evaluate the association between chronic inflammation and histological severity, while additional 204 esophageal non-tumor samples from patients with ESCC were collected. Immunohistochemistry was performed to detect the oxidative DNA damage and DNA double-strand breaks (DSBs). Significantly positive correlation was observed between degree of chronic inflammation and esophageal precursor lesions (rs = 0.37, P inflammation (rs = 0.21, P inflammation degree (P inflammation-associated genomic instability with esophageal carcinogenesis and suggest possibilities for early detection and intervention of esophageal carcinogenesis. PMID:27028857

  19. Middle East Respiratory Syndrome (MERS)

    Science.gov (United States)

    Middle East Respiratory Syndrome Coronavirus; MERS-CoV; Novel coronavirus; nCoV ... Centers for Disease Control and Prevention. Middle East Respiratory Syndrome (MERS): Frequently Asked Questions and Answers. Updated ...

  20. Respiratory failure in diabetic ketoacidosis

    Science.gov (United States)

    Konstantinov, Nikifor K; Rohrscheib, Mark; Agaba, Emmanuel I; Dorin, Richard I; Murata, Glen H; Tzamaloukas, Antonios H

    2015-01-01

    Respiratory failure complicating the course of diabetic ketoacidosis (DKA) is a source of increased morbidity and mortality. Detection of respiratory failure in DKA requires focused clinical monitoring, careful interpretation of arterial blood gases, and investigation for conditions that can affect adversely the respiration. Conditions that compromise respiratory function caused by DKA can be detected at presentation but are usually more prevalent during treatment. These conditions include deficits of potassium, magnesium and phosphate and hydrostatic or non-hydrostatic pulmonary edema. Conditions not caused by DKA that can worsen respiratory function under the added stress of DKA include infections of the respiratory system, pre-existing respiratory or neuromuscular disease and miscellaneous other conditions. Prompt recognition and management of the conditions that can lead to respiratory failure in DKA may prevent respiratory failure and improve mortality from DKA. PMID:26240698

  1. Severe acute respiratory syndrome (SARS)

    Science.gov (United States)

    ... their fever and other symptoms are gone. Hand hygiene is the most important part of SARS prevention. ... Coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). In: Bennett JE, Dolin ...

  2. The Combination of Three Natural Compounds Effectively Prevented Lung Carcinogenesis by Optimal Wound Healing.

    Directory of Open Access Journals (Sweden)

    Linxin Liu

    Full Text Available The tumor stroma has been described as "normal wound healing gone awry". We explored whether the restoration of a wound healing-like microenvironment may facilitate tumor healing. Firstly, we screened three natural compounds (shikonin, notoginsenoside R1 and aconitine from wound healing agents and evaluated the efficacies of wound healing microenvironment for limiting single agent-elicited carcinogenesis and two-stage carcinogenesis. The results showed that three compounds used alone could promote wound healing but had unfavorable efficacy to exert wound healing, and that the combination of three compounds made up treatment disadvantage of a single compound in wound healing and led to optimal wound healing. Although individual treatment with these agents may prevent cancer, they were not effective for the treatment of established tumors. However, combination treatment with these three compounds almost completely prevented urethane-induced lung carcinogenesis and reduced tumor burden. Different from previous studies, we found that urethane-induced lung carcinogenesis was associated with lung injury independent of pulmonary inflammation. LPS-induced pulmonary inflammation did not increase lung carcinogenesis, whereas decreased pulmonary inflammation by macrophage depletion promoted lung carcinogenesis. In addition, urethane damaged wound healing in skin excision wound model, reversed lung carcinogenic efficacy by the combination of three compounds was consistent with skin wound healing. Further, the combination of these three agents reduced the number of lung cancer stem cells (CSCs by inducing cell differentiation, restoration of gap junction intercellular communication (GJIC and blockade of the epithelial-to-mesenchymal transition (EMT. Our results suggest that restoration of a wound healing microenvironment represents an effective strategy for cancer prevention.

  3. 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

  4. MicroRNA, SND1, and alterations in translational regulation in colon carcinogenesis

    International Nuclear Information System (INIS)

    Tsuchiya, Naoto; Nakagama, Hitoshi

    2010-01-01

    Post-transcriptional regulation of gene expression by microRNA (miRNA) has recently attracted major interest in relation to its involvement in cancer development. miRNA is a member of small non-coding RNA, consists of 22-24 nucleotides and regulates expression of target mRNA species in a post-transcriptional manner by being incorporated with RNA-induced silencing complex (RISC). Staphylococcal nuclease homology domain containing 1 (SND1), a component of RISC, is frequently up-regulated in human colon cancers and also chemically induced colon cancers in animals. We here showed that SDN1 is involved in miRNA-mediated gene suppression and overexpression of SND1 in colon cancer cells causes down-regulation of APC without altering APC mRNA levels. As for the miRNA expression profile in human colon cancer, miR-34a was among the list of down-regulated miRNA. Expression of miR-34a is tightly regulated by p53, and ectopic expression of miR-34a in colon cancer cells causes remarkable reduction of cell proliferation and induces senescence-like phenotypes. MiR-34a also participates in the positive feedback loop of the p53 tumor suppressor network. This circuitry mechanism for p53 activation is of interest in understanding the tumor suppressive function of miR-34a in colon carcinogenesis. miRNA should also be considered as novel anti-cancer agents in tumor suppressive therapeutic applications.

  5. Aberrant GLI1 Activation in DNA Damage Response, Carcinogenesis and Chemoresistance

    Directory of Open Access Journals (Sweden)

    Komaraiah Palle

    2015-11-01

    Full Text Available The canonical hedgehog (HH pathway is a multicomponent signaling cascade (HH, protein patched homolog 1 (PTCH1, smoothened (SMO that plays a pivotal role during embryonic development through activation of downstream effector molecules, namely glioma-associated oncogene homolog 1 (GLI1, GLI2 and GLI3. Activation of GLIs must be tightly regulated as they modulate target genes which control tissue patterning, stem cell maintenance, and differentiation during development. However, dysregulation or mutations in HH signaling leads to genomic instability (GI and various cancers, for example, germline mutation in PTCH1 lead to Gorlin syndrome, a condition where patients develop numerous basal cell carcinomas and rarely rhabdomyosarcoma (RMS. Activating mutations in SMO have also been recognized in sporadic cases of medulloblastoma and SMO is overexpressed in many other cancers. Recently, studies in several human cancers have shown that GLI1 expression is independent from HH ligand and canonical intracellular signaling through PTCH and SMO. In fact, this aberrantly regulated GLI1 has been linked to several non-canonical oncogenic growth signals such as Kirsten rat sarcoma viral oncogene homolog (KRAS, avian myelocytomatosis virus oncogene cellular homolog (C-MYC, transforming growth factor β (TGFβ, wingless-type MMTV integration site family (WNT and β-catenin. Recent studies from our lab and other independent studies demonstrate that aberrantly expressed GLI1 influences the integrity of several DNA damage response and repair signals, and if altered, these networks can contribute to GI and impact tumor response to chemo- and radiation therapies. Furthermore, the ineffectiveness of SMO inhibitors in clinical studies argues for the development of GLI1-specific inhibitors in order to develop effective therapeutic modalities to treat these tumors. In this review, we focus on summarizing current understanding of the molecular, biochemical and cellular basis

  6. Allergic Respiratory Inflammation and Remodeling

    OpenAIRE

    Amin, Kawa

    2015-01-01

    Asthma and rhinitis are inflammatory diseases of the respiratory tract. Respiratory inflammation of the adaptive and innate immune system is the focus of this review, and chronic inflammation is not limited to the respiratory tissue. The inflammatory response, which consists of phagocytes, eosinophils, mast cells, and lymphocytes, spreads along the respiratory tract, leading to tissue damage. Mast cells and eosinophils are commonly recognized for their detrimental role in allergic reactions o...

  7. 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

  8. SIX1 Oncoprotein as a Biomarker in a Model of Hormonal Carcinogenesis and in Human Endometrial Cancer.

    Science.gov (United States)

    The oncofetal protein sine oculis-related homeobox 1 (SIX1) is a developmental transcription factor associated with carcinogenesis in animal models and humans. In a model of hormonal carcinogenesis, mice neonatally exposed to the soy phytoestrogen, genistein (GEN), or the synthet...

  9. [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.

  10. Respiratory manifestations of hypothyroidism

    DEFF Research Database (Denmark)

    Sorensen, Jesper Roed; Winther, Kristian Hillert; Bonnema, Steen Joop

    2016-01-01

    BACKGROUND: Hypothyroidism has been associated with increased pulmonary morbidity and overall mortality. We conducted a systematic review to identify the prevalence and underlying mechanisms of respiratory problems among patients with thyroid insufficiency. METHODS: PubMed and EMBASE databases were...... searched for relevant literature from January 1950 through January 2015 with study eligibility criteria: English-language publications; Adult subclinical or overt hypothyroid patients; Intervention, observational or retrospective studies; and respiratory manifestations. We followed the PRISMA statement......% of newly diagnosed patients with overt hypothyroidism, and demonstrated reversibility following treatment. The evidence for or against a direct effect on pulmonary function was ambiguous. However, each of the above mentioned areas were only dealt with in a limited number of studies. Therefore, we refrain...

  11. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure

    NARCIS (Netherlands)

    Kneyber, Martin C. J.; van Heerde, Marc; Twisk, Jos W. R.; Plotz, Frans B.; Markhors, Dick G.

    2009-01-01

    Introduction Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of

  12. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure

    NARCIS (Netherlands)

    Kneijber, M.C.J.; van Heerde, M.; Twisk, J.W.R.; Plotz, F.; Markhorst, D.G.

    2009-01-01

    Introduction: Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of

  13. Respiratory guiding system for respiratory motion management in respiratory gated radiotherapy

    International Nuclear Information System (INIS)

    Kang, Seong Hee; Kim, Dong Su; Kim, Tae Ho; Suh, Tae Suk

    2013-01-01

    Respiratory guiding systems have been shown to improve the respiratory regularity. This, in turn, improves the efficiency of synchronized moving aperture radiation therapy, and it reduces the artifacts caused by irregular breathing in imaging techniques such as four-dimensional computed tomography (4D CT), which is used for treatment planning in RGRT. We have previously developed a respiratory guiding system that incorporates an individual-specific guiding waveform, which is easy to follow for each volunteer, to improve the respiratory regularity. The present study evaluates the application of this system to improve the respiratory regularity for respiratory-gated radiation therapy (RGRT). In this study, we evaluated the effectiveness of an in-house-developed respiratory guiding system incorporating an individual specific guiding waveform to improve the respiratory regularity for RGRT. Most volunteers showed significantly less residual motion at each phase during guided breathing owing to the improvement in respiratory regularity. Therefore, the respiratory guiding system can clearly reduce the residual, or respiratory, motion in each phase. From the result, the CTV and the PTV margins during RGRT can be reduced by using the respiratory guiding system, which reduces the residual motions, thus improving the accuracy of RGRT

  14. Canine respiratory viruses

    OpenAIRE

    Buonavoglia , Canio; Martella , Vito

    2007-01-01

    International audience; Acute contagious respiratory disease (kennel cough) is commonly described in dogs worldwide. The disease appears to be multifactorial and a number of viral and bacterial pathogens have been reported as potential aetiological agents, including canine parainfluenza virus, canine adenovirus and Bordetella bronchiseptica, as well as mycoplasmas, Streptococcus equi subsp. zooepidemicus, canine herpesvirus and reovirus-1,-2 and -3. Enhancement of pathogenicity by multiple in...

  15. Adult respiratory distress syndrome

    International Nuclear Information System (INIS)

    Murphy, C.H.; Colvin, R.S.

    1987-01-01

    Due to improved emergency resuscitation procedures, and with advancing medical technology in the field of critical care, an increasing number of patients survive the acute phase of shock and catastrophic trauma. Patients who previously died of massive sepsis, hypovolemic or hypotensive shock, multiple fractures, aspiration, toxic inhalation, and massive embolism are now surviving long enough to develop previously unsuspected and unrecognized secondary effects. With increasing frequency, clinicians are recognizing the clinical and radiographic manifestations of pathologic changes in the lungs occurring secondary to various types of massive insult. This paper gives a list of diseases that have been shown to precipitate or predispose to diffuse lung damage. Various terms have been used to describe the lung damage and respiratory failure secondary to these conditions. The term adult respiratory distress syndrome (ARDS) is applied to several cases of sudden respiratory failure in patients with previously healthy lungs following various types of trauma or shock. Numerous investigations and experiments have studied the pathologic changes in ARDS, and, while there is still no clear indication of why it develops, there is now some correlation of the sequential pathologic developments with the clinical and radiographic changes

  16. Nanotechnology in respiratory medicine.

    Science.gov (United States)

    Omlor, Albert Joachim; Nguyen, Juliane; Bals, Robert; Dinh, Quoc Thai

    2015-05-29

    Like two sides of the same coin, nanotechnology can be both boon and bane for respiratory medicine. Nanomaterials open new ways in diagnostics and treatment of lung diseases. Nanoparticle based drug delivery systems can help against diseases such as lung cancer, tuberculosis, and pulmonary fibrosis. Moreover, nanoparticles can be loaded with DNA and act as vectors for gene therapy in diseases like cystic fibrosis. Even lung diagnostics with computer tomography (CT) or magnetic resonance imaging (MRI) profits from new nanoparticle based contrast agents. However, the risks of nanotechnology also have to be taken into consideration as engineered nanomaterials resemble natural fine dusts and fibers, which are known to be harmful for the respiratory system in many cases. Recent studies have shown that nanoparticles in the respiratory tract can influence the immune system, can create oxidative stress and even cause genotoxicity. Another important aspect to assess the safety of nanotechnology based products is the absorption of nanoparticles. It was demonstrated that the amount of pulmonary nanoparticle uptake not only depends on physical and chemical nanoparticle characteristics but also on the health status of the organism. The huge diversity in nanotechnology could revolutionize medicine but makes safety assessment a challenging task.

  17. Ocular tropism of respiratory viruses.

    Science.gov (United States)

    Belser, Jessica A; Rota, Paul A; Tumpey, Terrence M

    2013-03-01

    Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism.

  18. Acute respiratory infections among returning Hajj pilgrims-Jordan, 2014.

    Science.gov (United States)

    Al-Abdallat, Mohammad Mousa; Rha, Brian; Alqasrawi, Sultan; Payne, Daniel C; Iblan, Ibrahim; Binder, Alison M; Haddadin, Aktham; Nsour, Mohannad Al; Alsanouri, Tarek; Mofleh, Jawad; Whitaker, Brett; Lindstrom, Stephen L; Tong, Suxiang; Ali, Sami Sheikh; Dahl, Rebecca Moritz; Berman, LaShondra; Zhang, Jing; Erdman, Dean D; Gerber, Susan I

    2017-04-01

    The emergence of Middle East Respiratory Syndrome coronavirus (MERS-CoV) has prompted enhanced surveillance for respiratory infections among pilgrims returning from the Hajj, one of the largest annual mass gatherings in the world. To describe the epidemiology and etiologies of respiratory illnesses among pilgrims returning to Jordan after the 2014 Hajj. Surveillance for respiratory illness among pilgrims returning to Jordan after the 2014 Hajj was conducted at sentinel health care facilities using epidemiologic surveys and molecular diagnostic testing of upper respiratory specimens for multiple respiratory pathogens, including MERS-CoV. Among the 125 subjects, 58% tested positive for at least one virus; 47% tested positive for rhino/enterovirus. No cases of MERS-CoV were detected. The majority of pilgrims returning to Jordan from the 2014 Hajj with respiratory illness were determined to have a viral etiology, but none were due to MERS-CoV. A greater understanding of the epidemiology of acute respiratory infections among returning travelers to other countries after Hajj should help optimize surveillance systems and inform public health response practices. Published by Elsevier B.V.

  19. Anatomy and physiology of respiratory system relevant to anaesthesia.

    Science.gov (United States)

    Patwa, Apeksh; Shah, Amit

    2015-09-01

    Clinical application of anatomical and physiological knowledge of respiratory system improves patient's safety during anaesthesia. It also optimises patient's ventilatory condition and airway patency. Such knowledge has influence on airway management, lung isolation during anaesthesia, management of cases with respiratory disorders, respiratory endoluminal procedures and optimising ventilator strategies in the perioperative period. Understanding of ventilation, perfusion and their relation with each other is important for understanding respiratory physiology. Ventilation to perfusion ratio alters with anaesthesia, body position and with one-lung anaesthesia. Hypoxic pulmonary vasoconstriction, an important safety mechanism, is inhibited by majority of the anaesthetic drugs. Ventilation perfusion mismatch leads to reduced arterial oxygen concentration mainly because of early closure of airway, thus leading to decreased ventilation and atelectasis during anaesthesia. Various anaesthetic drugs alter neuronal control of the breathing and bronchomotor tone.

  20. Anatomy and physiology of respiratory system relevant to anaesthesia

    Directory of Open Access Journals (Sweden)

    Apeksh Patwa

    2015-01-01

    Full Text Available Clinical application of anatomical and physiological knowledge of respiratory system improves patient's safety during anaesthesia. It also optimises patient's ventilatory condition and airway patency. Such knowledge has influence on airway management, lung isolation during anaesthesia, management of cases with respiratory disorders, respiratory endoluminal procedures and optimising ventilator strategies in the perioperative period. Understanding of ventilation, perfusion and their relation with each other is important for understanding respiratory physiology. Ventilation to perfusion ratio alters with anaesthesia, body position and with one-lung anaesthesia. Hypoxic pulmonary vasoconstriction, an important safety mechanism, is inhibited by majority of the anaesthetic drugs. Ventilation perfusion mismatch leads to reduced arterial oxygen concentration mainly because of early closure of airway, thus leading to decreased ventilation and atelectasis during anaesthesia. Various anaesthetic drugs alter neuronal control of the breathing and bronchomotor tone.

  1. Acute respiratory acidosis and alkalosis – A modern quantitative interpretation

    Directory of Open Access Journals (Sweden)

    Andraž Stožer

    2014-03-01

    Full Text Available Background: Three different approaches for assessing the acid-base status of a patient exist, i.e. the Boston, Copenhagen, and Stewart´s approach, and they employ different parameters to assess a given acid-base disturbance. Students, researchers, and clinicians are getting confused by heated debates about which of these performs best and by the fact that during their curricula, they typically get acquainted with one of the approaches only, which prevents them to understand sources employing other approaches and to critically evaluate the advantages and drawbacks of each approach. In this paper, the authors introduce and define the basic parameters characterizing each of the approaches and point out differences and similarities between them. Special attention is devoted to how the different approaches assess the degree of change in the concentration of plasma bicarbonate that occurs during primary respiratory changes; proper understanding of these is necessary to correctly interpret chronic respiratory and metabolic acid-base changes.Conclusion: During acute respiratory acidosis the concentration of bicarbonate rises and during acute respiratory alkalosis it falls, depending on the buffering strength of non-bicarbonate buffers. During acute respiratory acid-base disturbances, buffer base (employed by the Copenhagen approach, apparent and effective strong ion difference, as well as strong ion gap (employed by the Stewart approach remain unchanged; the anion gap (employed by the Boston and Copenhagen approach falls during acute respiratory acidosis and rises during acute respiratory alkalosis.

  2. Diet, lifestyle, heritable factors and colorectal carcinogenesis: associations with histopathological and molecular endpoints

    NARCIS (Netherlands)

    Wark, P.A.

    2007-01-01

    Background: Diet, lifestyle and heritable factors have been related to colorectal cancer risk; to date, their relevance to the overall scope of colorectal carcinogenesis, has not been clearly established.Aim and Methods: To evaluate whether distinguishing colorectal tissue by its histopathological

  3. Effects of dietary fat on virus-induced pancreatic carcinogenesis in guinea fowl

    NARCIS (Netherlands)

    Kirev, T.; Woutersen, R.A.; Kril, A.

    2002-01-01

    The present study was performed to assess the effects of diets supplemented with low (5%) and high (20%) corn oil on a Pts 56 retrovirus-induced model of pancreatic carcinogenesis in guinea fowl. The early microscopic lesions appear after 3 mo after virus treatment and progress over time. Eight to

  4. 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

  5. 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

  6. 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%

  7. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

    International Nuclear Information System (INIS)

    Fabrikant, J.I.

    1981-05-01

    The current knowledge of the carcinogenic effect of radiation in man is considered. The discussion is restricted to dose-incidence data in humans, particularly to certain of those epidemiological studies of human populations that are used most frequently for risk estimation for low-dose radiation carcinogenesis in man. Emphasis is placed solely on those surveys concerned with nuclear explosions and medical exposures

  8. Radiation carcinogenesis. Comprehensive three-year progress report, 1 May 1972--15 March 1976

    International Nuclear Information System (INIS)

    Warren, S.; Gates, O.

    1976-03-01

    Progress is reported on studies on the pathological effects of various doses of x radiation on rats and mice, with emphasis on radioinduced carcinogenesis in parabiont rats with one of the pair exposed to 1000 R of whole body x radiation and the other shielded. Results are included from studies on alterations in metabolic parameters and life span induced by irradiation

  9. p21 Ablation in Liver Enhances DNA Damage, Cholestasis, and Carcinogenesis

    NARCIS (Netherlands)

    Ehedego, H.; Boekschoten, M.V.; Hu, W.; Doler, C.; Haybaeck, J.; Gassler, N.; Muller, M.R.; Liedtke, C.; Trautwein, C.

    2015-01-01

    Genetic mouse studies suggest that the NF-¿B pathway regulator NEMO (also known as IKK¿) controls chronic inflammation and carcinogenesis in the liver. However, the molecular mechanisms explaining the function of NEMO are not well defined. Here, we report that overexpression of the cell-cycle

  10. Mucosal inflammation at the respiratory interface: a zebrafish model

    OpenAIRE

    Progatzky, Fr?nze; Cook, H. Terence; Lamb, Jonathan R.; Bugeon, Laurence; Dallman, Margaret J.

    2015-01-01

    Inflammatory diseases of the respiratory system such as asthma and chronic obstructive pulmonary disease are increasing globally and remain poorly understood conditions. Although attention has long focused on the activation of type 1 and type 2 helper T cells of the adaptive immune system in these diseases, it is becoming increasingly apparent that there is also a need to understand the contributions and interactions between innate immune cells and the epithelial lining of the respiratory sys...

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  12. European Respiratory Society statement

    DEFF Research Database (Denmark)

    Miravitlles, Marc; Dirksen, Asger; Ferrarotti, Ilaria

    2017-01-01

    lung disease. A large proportion of individuals affected remain undiagnosed and therefore without access to appropriate care and treatment.The most recent international statement on AATD was published by the American Thoracic Society and the European Respiratory Society in 2003. Since then there has...... the efficacy and safety of augmentation therapy, the only specific treatment available for the pulmonary disease associated with AATD.As AATD is a rare disease, it is crucial to organise national and international registries and collect information prospectively about the natural history of the disease...

  13. Respiratory symptoms of megaesophagus

    Directory of Open Access Journals (Sweden)

    Fabio Di Stefano

    2013-03-01

    Full Text Available Megaesophagus as the end result of achalasia is the consequence of disordered peristalsis and the slow decompensation of the esophageal muscular layer. The main symptoms of achalasia are dysphagia, regurgitation, chest pain and weight loss, but respiratory symptoms, such as coughing, particularly when patients lie in a horizontal position, may also be common due to microaspiration. A 70-year old woman suffered from a nocturnal cough and shortness of breath with stridor. She reported difficulty in swallowing food over the past ten years, but had adapted by eating a semi-liquid diet. Chest X-ray showed right hemithorax patchy opacities projecting from the posterior mediastinum. Chest computed tomography scan showed a marked dilatation of the esophagus with abundant food residues. Endoscopy confirmed the diagnosis of megaesophagus due to esophageal achalasia, excluding other causes of obstruction, such as secondary esophagitis, polyps, leiomyoma or leiomyosarcoma. In the elderly population, swallowing difficulties due to esophageal achalasia are often underestimated and less troublesome than the respiratory symptoms that are caused by microaspiration. The diagnosis of esophageal achalasia, although uncommon, should be considered in patients with nocturnal chronic coughs and shortness of breath with stridor when concomitant swallowing difficulties are present.

  14. Acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Marco Confalonieri

    2017-04-01

    Full Text Available Since its first description, the acute respiratory distress syndrome (ARDS has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foster geographic variability and contrasting outcome data. A large international multicentre prospective cohort study including 50 countries across five continents reported that ARDS is underdiagnosed, and there is potential for improvement in its management. Furthermore, epidemiological data from low-income countries suggest that a revision of the current definition of ARDS is needed in order to improve its recognition and global clinical outcome. In addition to the well-known risk-factors for ARDS, exposure to high ozone levels and low vitamin D plasma concentrations were found to be predisposing circumstances. Drug-based preventive strategies remain a major challenge, since two recent trials on aspirin and statins failed to reduce the incidence in at-risk patients. A new disease-modifying therapy is awaited: some recent studies promised to improve the prognosis of ARDS, but mortality and disabling complications are still high in survivors in intensive care.

  15. Respiratory sounds compression.

    Science.gov (United States)

    Yadollahi, Azadeh; Moussavi, Zahra

    2008-04-01

    Recently, with the advances in digital signal processing, compression of biomedical signals has received great attention for telemedicine applications. In this paper, an adaptive transform coding-based method for compression of respiratory and swallowing sounds is proposed. Using special characteristics of respiratory sounds, the recorded signals are divided into stationary and nonstationary portions, and two different bit allocation methods (BAMs) are designed for each portion. The method was applied to the data of 12 subjects and its performance in terms of overall signal-to-noise ratio (SNR) values was calculated at different bit rates. The performance of different quantizers was also considered and the sensitivity of the quantizers to initial conditions has been alleviated. In addition, the fuzzy clustering method was examined for classifying the signal into different numbers of clusters and investigating the performance of the adaptive BAM with increasing the number of classes. Furthermore, the effects of assigning different numbers of bits for encoding stationary and nonstationary portions of the signal were studied. The adaptive BAM with variable number of bits was found to improve the SNR values of the fixed BAM by 5 dB. Last, the possibility of removing the training part for finding the parameters of adaptive BAMs for each individual was investigated. The results indicate that it is possible to use a predefined set of BAMs for all subjects and remove the training part completely. Moreover, the method is fast enough to be implemented for real-time application.

  16. Acute Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    Carmen Sílvia Valente Barbas

    2012-01-01

    Full Text Available This paper, based on relevant literature articles and the authors' clinical experience, presents a goal-oriented respiratory management for critically ill patients with acute respiratory distress syndrome (ARDS that can help improve clinicians' ability to care for these patients. Early recognition of ARDS modified risk factors and avoidance of aggravating factors during hospital stay such as nonprotective mechanical ventilation, multiple blood products transfusions, positive fluid balance, ventilator-associated pneumonia, and gastric aspiration can help decrease its incidence. An early extensive clinical, laboratory, and imaging evaluation of “at risk patients” allows a correct diagnosis of ARDS, assessment of comorbidities, and calculation of prognostic indices, so that a careful treatment can be planned. Rapid administration of antibiotics and resuscitative measures in case of sepsis and septic shock associated with protective ventilatory strategies and early short-term paralysis associated with differential ventilatory techniques (recruitment maneuvers with adequate positive end-expiratory pressure titration, prone position, and new extracorporeal membrane oxygenation techniques in severe ARDS can help improve its prognosis. Revaluation of ARDS patients on the third day of evolution (Sequential Organ Failure Assessment (SOFA, biomarkers and response to infection therapy allows changes in the initial treatment plans and can help decrease ARDS mortality.

  17. Respiratory mass spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Mostert, J.W. (Pretoria Univ. (South Africa). Dept. of Anesthesiology)

    1983-06-01

    The high degree of technical perfection of the respiratory mass spectrometer has rendered the instrument feasible for routine monitoring of anesthetized patients. It is proposed that the difference between inspired and expired oxygen tension in mm Hg be equated with whole body oxygen consumption in ml/min/M/sup 2/ body-surface area at STPD, by the expedient of multiplying tension-differences by a factor of 2. Years of experience have confirmed the value of promptly recognizing sudden drops in this l/E tension difference below 50 mm Hg indicative of metabolic injury from hypovolemia or respiratory depression. Rises in l/E tension-differences were associated with shivering as well as voluntary muscle activity. Tension differences of less than 25 mm Hg (equated with a whole-body O/sub 2/ consumption of less than 50 ml O/sub 2//min/M/sup 2/) occurred in a patient in the sitting position for posterior fossa exploration without acidosis, hypoxia or hypotension for several hours prior to irreversible cardiac arrest. The value of clinical monitoring by mass spectrometry is especially impressive in open-heart surgery.

  18. Management of Postoperative Respiratory Failure.

    Science.gov (United States)

    Mulligan, Michael S; Berfield, Kathleen S; Abbaszadeh, Ryan V

    2015-11-01

    Despite best efforts, postoperative complications such as postoperative respiratory failure may occur and prompt recognition of the process and management is required. Postoperative respiratory failure, such as postoperative pneumonia, postpneumonectomy pulmonary edema, acute respiratory distress-like syndromes, and pulmonary embolism, are associated with high morbidity and mortality. The causes of these complications are multifactorial and depend on preoperative, intraoperative, and postoperative factors, some of which are modifiable. The article identifies some of the risk factors, causes, and treatment strategies for successful management of the patient with postoperative respiratory failure. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Submersion and acute respiratory failure

    Directory of Open Access Journals (Sweden)

    Yu-Jang Su

    2014-01-01

    Conclusions: Submersion patients who are hypothermic on arrival of emergency department (ED are risky to respiratory failure and older, more hypothermic, longer hospital stay in suicidal submersion patients.

  20. Transgenic mouse models of hormonal mammary carcinogenesis: advantages and limitations.

    Science.gov (United States)

    Kirma, Nameer B; Tekmal, Rajeshwar R

    2012-09-01

    Mouse models of breast cancer, especially transgenic and knockout mice, have been established as valuable tools in shedding light on factors involved in preneoplastic changes, tumor development and malignant progression. The majority of mouse transgenic models develop estrogen receptor (ER) negative tumors. This is seen as a drawback because the majority of human breast cancers present an ER positive phenotype. On the other hand, several transgenic mouse models have been developed that produce ER positive mammary tumors. These include mice over-expressing aromatase, ERα, PELP-1 and AIB-1. In this review, we will discuss the value of these models as physiologically relevant in vivo systems to understand breast cancer as well as some of the pitfalls involving these models. In all, we argue that the use of transgenic models has improved our understanding of the molecular aspects and biology of breast cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. A review of experimental models in colorectal carcinogenesis

    OpenAIRE

    Machado, Vanessa Foresto; Feitosa, Marley Ribeiro; Rocha, Jose Joaquim Ribeiro da; Féres, Omar

    2016-01-01

    ABSTRACT Colorectal cancer is the leading cause of malignancy of the gastrointestinal tract. A better understanding of the molecular and cellular changes that lead to the disease is necessary to develop early diagnosis and optimal treatment modalities. Rodent models are rapid, reproducible and exhibit an adenoma-carcinoma sequence similar to that found in humans. The objective of this manuscript is to review the most common chemical carcinogens used to induce experimental tumors and the usual...

  2. Insights into the epigenetic mechanisms controlling pancreatic carcinogenesis.

    Science.gov (United States)

    McCleary-Wheeler, Angela L; Lomberk, Gwen A; Weiss, Frank U; Schneider, Günter; Fabbri, Muller; Poshusta, Tara L; Dusetti, Nelson J; Baumgart, Sandra; Iovanna, Juan L; Ellenrieder, Volker; Urrutia, Raul; Fernandez-Zapico, Martin E

    2013-01-28

    During the last couple decades, we have significantly advanced our understanding of mechanisms underlying the development of pancreatic ductual adenocarcinoma (PDAC). In the late 1990s into the early 2000s, a model of PDAC development and progression was developed as a multi-step process associated with the accumulation of somatic mutations. The correlation and association of these particular genetic aberrations with the establishment and progression of PDAC has revolutionized our understanding of this process. However, this model leaves out other molecular events involved in PDAC pathogenesis that contribute to its development and maintenance, specifically those being epigenetic events. Thus, a new model considering the new scientific paradigms of epigenetics will provide a more comprehensive and useful framework for understanding the pathophysiological mechanisms underlying this disease. Epigenetics is defined as the type of inheritance not based on a particular DNA sequence but rather traits that are passed to the next generation via DNA and histone modifications as well as microRNA-dependent mechanisms. Key tumor suppressors that are well established to play a role in PDAC may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. A noteworthy characteristic of epigenetic-based inheritance is its reversibility, which is in contrast to the stable nature of DNA sequence-based alterations. Given this nature of epigenetic alterations, it becomes imperative that our understanding of epigenetic-based events promoting and maintaining PDAC continues to grow. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Acute intermittent hypoxia induced neural plasticity in respiratory motor control.

    Science.gov (United States)

    Xing, Tao; Fong, Angelina Y; Bautista, Tara G; Pilowsky, Paul M

    2013-09-01

    Respiratory neural networks can adapt to rapid environmental change or be altered over the long term by various inputs. The mechanisms that underlie the plasticity necessary for adaptive changes in breathing remain unclear. Acute intermittent hypoxia (AIH)-induced respiratory long-term facilitation (LTF) is one of the most extensively studied types of respiratory plasticity. Acute intermittent hypoxia-induced LTF is present in several respiratory motor outputs, innervating both pump muscles (i.e. diaphragm) and valve muscles (i.e. tongue, pharynx and larynx). Long-term facilitation is present in various species, including humans, and the expression of LTF is influenced by gender, age and genetics. Serotonin plays a key role in initiating and modulating plasticity at the level of respiratory motor neurons. Recently, multiple intracellular pathways have been elucidated that are capable of giving rise to respiratory LTF. These mainly activate the metabolic receptors coupled to Gq ('Q' pathway) and Gs ('S' pathway) proteins. Herein, we discuss AIH-induced respiratory LTF in animals and humans, as well as recent advances in our understanding of the synaptic and intracellular pathways underlying this form of plasticity. We also discuss the potential to use intermittent hypoxia to induce functional recovery following cervical spinal injury. © 2013 Wiley Publishing Asia Pty Ltd.

  4. Influence of Ionizing Radiation on Stromal-Epithelial Communication in Esophageal Carcinogenesis

    Science.gov (United States)

    Huff, Janice; Patel, Zarana; Grugan, Katharine; Rustgi, Anil; Cucinotta, Francis A.

    Esophageal cancer is the 6th leading cause of cancer death worldwide and is associated with a variety of risk factors including tobacco use, heavy alcohol consumption, human papilloma virus infection, and certain dietary factors such as trace mineral and vitamin deficiencies. A connection with ionizing radiation exposure is revealed by the high excess relative risk for esophageal squamous cell carcinoma observed in the survivors of the atomic bomb detonations in Japan. Esophageal carcinomas are also seen as secondary malignancies in patients who received radiotherapy for breast and thoracic cancers; additionally, patients with head/neck and oral squamous cell cancers are at increased risk for metachronous esophageal squamous cell cancers. This malignancy is rapidly fatal, mainly because it remains asymptomatic until late, advanced stages when the disease is rarely responsive to treatment. In normal epithelium, the stromal microenvironment is essential for the maintenance and modulation of cell growth and differentiation. Cross talk between the epithelial and stromal compartments can influence many aspects of malignant progression, including tumor cell proliferation, migration, invasion and recruitment of new blood vessels. To test the hypothesis that radiation exposure plays a role in esophageal carcinogenesis via non-targeted mechanisms involving stromal-epithelial cell communication, we are studying radiation effects on hTERT-immortalized human esophageal epithelial cells and genetic variants grown in co-culture with human esophageal stromal fibrob-lasts (Okawa et al., Genes Dev. 2007. 21: 2788-2803). We examined how irradiation of stromal fibroblasts affected epithelial migration and invasion, behaviors associated with cancer promotion and progression. These assays were conducted in modified Boyden chambers using conditioned media from irradiated fibroblasts. Our results using low LET gamma radiation showed a dose-dependent increase in migration of epithelial

  5. Influence of Ionizing Radiation on Stromal-Epithelial Intercellular Communication in Esophageal Carcinogenesis

    Science.gov (United States)

    Patel, Zarana S.; Kalabis, Jiri; Rustgi, Anil K.; Cucinotta, Francis A.; Huff, Janice L.

    2010-01-01

    Esophageal cancer is the 6th leading cause of cancer death worldwide. Its development is associated with a variety of risk factors including tobacco use, heavy alcohol consumption, human papilloma virus infection, and certain dietary factors such as trace mineral and vitamin deficiencies. An association with ionizing radiation exposure is revealed by the high excess relative risk for squamous cell carcinoma of the esophagus observed in the survivors of the atomic bomb detonations in Japan. It is also seen as a secondary malignancy in patients who received radiotherapy for breast and thoracic cancers; additionally, patients with head/neck and oral squamous cell cancers are at increased risk for metachronous esophageal squamous cell cancers. This malignancy is rapidly fatal, mainly because it remains asymptomatic until late, advanced stages when the disease is rarely curable. The stromal microenvironment plays an essential role in the maintenance and modulation of normal epithelial cell growth and differentiation and cross talk between the epithelial and stromal compartments can influence many aspects of malignant progression, including tumor cell proliferation, migration, invasion and recruitment of new blood vessels. To test the hypothesis that radiation exposure plays a role in esophageal carcinogenesis via non-targeted mechanisms involving stromal-epithelial cell communication, we are studying radiation effects on hTERT-immortalized human esophageal epithelial cells and genetic variants grown in co-culture with human esophageal stromal fibroblasts (Okawa et al., Genes & Dev. 2007. 21: 2788-2803). We examined how radiation treatment of stromal fibroblasts affected epithelial migration and invasion, behaviors associated with cancer promotion and progression. Chemotactic and haptotactic migration of epithelial cells stimulated by conditioned media from irradiated fibroblasts was measured using assays conducted in Transwell cell culture chambers. Our results using

  6. The stem cell factor (SCF)/c-KIT system in carcinogenesis of reproductive tissues: What does the hormonal regulation tell us?

    Science.gov (United States)

    Figueira, Marília I; Cardoso, Henrique J; Correia, Sara; Maia, Cláudio J; Socorro, Sílvia

    2017-10-01

    The tyrosine kinase receptor c-KIT and its ligand, the stem cell factor (SCF) are expressed in several tissues of male and female reproductive tract, playing an important role in the regulation of basic biological processes. The activation of c-KIT by SCF controls, cell survival and death, cell differentiation and migration. Also, the SCF/c-KIT system has been implicated in carcinogenesis of reproductive tissues due to its altered expression pattern or overactivation in consequence of gain-of-functions mutations. Over the years, it has also been shown that hormones, the primary regulators of reproductive function and causative agents in the case of hormone-dependent cancers, are also able to control the SCF/c-KIT tissue levels. Therefore, it is liable to suppose that disturbed SCF/c-KIT expression driven by (de)regulated hormone actions can be a relevant step towards carcinogenesis. The present review describes the SCF and c-KIT expression in cancers of reproductive tissues, discussing the implications of the hormonal regulation of the SCF/c-KIT system in cancer development. Understanding the relationship between hormonal imbalance and the SCF/c-KIT expression and activity would be relevant in the context of novel therapeutic approaches in reproductive cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. 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)

  8. Cervical carcinogenesis: the role of co-factors and generation of reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Giuliano Anna

    2003-01-01

    Full Text Available Several HPV co-factors have been proposed, some more or less consistently associated with cervical dysplasia and cancer risk. More research, using prospective cohort designs, is needed to further describe where in carcinogenesis these factors are working and to assess the biological mechanism of these factors. In addition, further research is needed to define the role of various hormonal contraceptive formulations in promoting cervical carcinogenesis. While many interesting scientific questions remain to be answered, results from the numerous epidemiological studies conducted to date indicate that cervical dysplasia and cancer may be reduced if the oxidant antioxidant ratio is shifted to more of and antioxidant profile. In addition to cervical cancer screening, a reduction in cervical cancer incidence may be accomplished by reducing tobacco use, increasing nutritional status, and utilizing barrier contraception to prevent infection with other sexually acquired infections.

  9. Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Stav Sapoznik

    2016-02-01

    Full Text Available In recent years, the notion that ovarian carcinoma results from ovulation-induced inflammation of the fallopian tube epithelial cells (FTECs has gained evidence. However, the mechanistic pathway for this process has not been revealed yet. In the current study, we propose the mutator protein activation-induced cytidine deaminase (AID as a link between ovulation-induced inflammation in FTECs and genotoxic damage leading to ovarian carcinogenesis. We show that AID, previously shown to be functional only in B lymphocytes, is expressed in FTECs under physiological conditions, and is induced in vitro upon ovulatory-like stimulation and in vivo in carcinoma-associated FTECs. We also report that AID activity results in epigenetic, genetic and genomic damage in FTECs. Overall, our data provides new insights into the etiology of ovarian carcinogenesis and may set the ground for innovative approaches aimed at prevention and early detection.

  10. The 9th Conference on Metal Toxicity and Carcinogenesis: The conference overview.

    Science.gov (United States)

    Wise, James T F; Wang, Lei; Zhang, Zhuo; Shi, Xianglin

    2017-09-15

    Heavy metals, such as arsenic, chromium, cadmium, nickel, mercury, and uranium are known to cause many human diseases and health complications after occupational or environmental exposure. Consequently, metals are environmental health concerns. This manuscript is an overview of the 9th Conference on Metal Toxicity and Carcinogenesis held in October 2016 in Lexington, Kentucky. Since 2000, this biennial meeting brings together experts in the field to discuss current and prospective research in an effort to advance research pertaining to metal toxicity and carcinogenesis. In this review we summarize the major topics discussed and provide insight regarding current research in the field and an account of the direction in which the field is progressing. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Computational Models and Emergent Properties of Respiratory Neural Networks

    Science.gov (United States)

    Lindsey, Bruce G.; Rybak, Ilya A.; Smith, Jeffrey C.

    2012-01-01

    Computational models of the neural control system for breathing in mammals provide a theoretical and computational framework bringing together experimental data obtained from different animal preparations under various experimental conditions. Many of these models were developed in parallel and iteratively with experimental studies and provided predictions guiding new experiments. This data-driven modeling approach has advanced our understanding of respiratory network architecture and neural mechanisms underlying generation of the respiratory rhythm and pattern, including their functional reorganization under different physiological conditions. Models reviewed here vary in neurobiological details and computational complexity and span multiple spatiotemporal scales of respiratory control mechanisms. Recent models describe interacting populations of respiratory neurons spatially distributed within the Bötzinger and pre-Bötzinger complexes and rostral ventrolateral medulla that contain core circuits of the respiratory central pattern generator (CPG). Network interactions within these circuits along with intrinsic rhythmogenic properties of neurons form a hierarchy of multiple rhythm generation mechanisms. The functional expression of these mechanisms is controlled by input drives from other brainstem components, including the retrotrapezoid nucleus and pons, which regulate the dynamic behavior of the core circuitry. The emerging view is that the brainstem respiratory network has rhythmogenic capabilities at multiple levels of circuit organization. This allows flexible, state-dependent expression of different neural pattern-generation mechanisms under various physiological conditions, enabling a wide repertoire of respiratory behaviors. Some models consider control of the respiratory CPG by pulmonary feedback and network reconfiguration during defensive behaviors such as cough. Future directions in modeling of the respiratory CPG are considered. PMID:23687564

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

    Directory of Open Access Journals (Sweden)

    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.

  13. The substrate of the biopsychosocial influences in the carcinogenesis of the digestive tract

    OpenAIRE

    Georgică C. Târtea; Cristina Florescu; Daniel Pirici; Daniel Caragea; Elena A. Târtea; Cristin C. Vere

    2016-01-01

    Digestive cancer represents a severe public health problem, being one of the main causes of death. It is considered a multifactorial disease, with hereditary predisposition, environmental factors, and other factors involved in carcinogenesis. Both the evolution and the pathogenesis of digestive neoplasms remain incompletely elucidated. As a multifactorial disease, it can be approached by taking into account the biopsychosocial influences via enteric nervous system. Many peptides and non-pepti...

  14. Dynamic landscape of pancreatic carcinogenesis reveals early molecular networks of malignancy.

    Science.gov (United States)

    Kong, Bo; Bruns, Philipp; Behler, Nora A; Chang, Ligong; Schlitter, Anna Melissa; Cao, Jing; Gewies, Andreas; Ruland, Jürgen; Fritzsche, Sina; Valkovskaya, Nataliya; Jian, Ziying; Regel, Ivonne; Raulefs, Susanne; Irmler, Martin; Beckers, Johannes; Friess, Helmut; Erkan, Mert; Mueller, Nikola S; Roth, Susanne; Hackert, Thilo; Esposito, Irene; Theis, Fabian J; Kleeff, Jörg; Michalski, Christoph W

    2018-01-01

    The initial steps of pancreatic regeneration versus carcinogenesis are insufficiently understood. Although a combination of oncogenic Kras and inflammation has been shown to induce malignancy, molecular networks of early carcinogenesis remain poorly defined. We compared early events during inflammation, regeneration and carcinogenesis on histological and transcriptional levels with a high temporal resolution using a well-established mouse model of pancreatitis and of inflammation-accelerated Kras G12D -driven pancreatic ductal adenocarcinoma. Quantitative expression data were analysed and extensively modelled in silico. We defined three distinctive phases-termed inflammation, regeneration and refinement-following induction of moderate acute pancreatitis in wild-type mice. These corresponded to different waves of proliferation of mesenchymal, progenitor-like and acinar cells. Pancreas regeneration required a coordinated transition of proliferation between progenitor-like and acinar cells. In mice harbouring an oncogenic Kras mutation and challenged with pancreatitis, there was an extended inflammatory phase and a parallel, continuous proliferation of mesenchymal, progenitor-like and acinar cells. Analysis of high-resolution transcriptional data from wild-type animals revealed that organ regeneration relied on a complex interaction of a gene network that normally governs acinar cell homeostasis, exocrine specification and intercellular signalling. In mice with oncogenic Kras, a specific carcinogenic signature was found, which was preserved in full-blown mouse pancreas cancer. These data define a transcriptional signature of early pancreatic carcinogenesis and a molecular network driving formation of preneoplastic lesions, which allows for more targeted biomarker development in order to detect cancer earlier in patients with pancreatitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Allergic inflammation does not impact chemical-induced carcinogenesis in the lungs of mice

    Directory of Open Access Journals (Sweden)

    Doris Konstantinos

    2010-08-01

    Full Text Available Abstract Background Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice. Methods Balb/c mice received single-dose urethane (1 g/kg at day 0 and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12, tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96, or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter. In addition, interleukin (IL-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment. Results Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis. Conclusions Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer.

  16. Disease Heterogeneity and Immune Biomarkers in Preclinical Mouse Models of Ovarian Carcinogenesis

    Science.gov (United States)

    2014-08-01

    the cancer risk, including the cervical epithelial transformation zone with HPV [41], the esophageal-gastric junction and Barrett’s esophagus [42], and...Sweetwood JP, Cheng Y, Pace JL, et al. (2000) Development of a syngeneic mouse model for events related to ovarian cancer . Carcinogenesis 21: 585–591...endometriosis-associated ovarian cancer (EAOC, endometrial and clear cell). Of these genes, complement pathway genes were consistently present, suggesting

  17. Digestive forms of Chagas disease and carcinogenesis: a study of association

    OpenAIRE

    Gullo, Caio Eduardo; Estofolete, Cássia Fernanda; Gil, Cristiane Damas; Christiano, Adriana Borgonovi; Netinho, João Gomes

    2012-01-01

    The authors analyze the relation between gastrointestinal carcinogenesis and Chagas disease, based on detailed review of the literature. To this end, epidemiological, experimental and human material pathology description studies have been selected. The article discusses the possibility of protection being afforded by not fully known morphokinetic cellular, immune and neuroendocrine factors that would be secondary to plexus degeneration. Also aspects related to the parasite-host interaction fr...

  18. Differentiation and carcinogenesis: an integrated multilevel study of mechanisms from molecules to man. Progress report

    International Nuclear Information System (INIS)

    1985-01-01

    This study sought to identify and characterize mesenchymal progenitor cells (MPCs) in vitro, to identify the in vivo equivalent of the in vitro MPCs, and to determine the relationship between the presence or response of these cells both in vitro and eventually in vivo to altered proliferative capacity (in vitro cellular senescence, in vivo organismal aging) and altered susceptibility to carcinogenesis (frequency of in vitro neoplastic transformation and age-related frequency of in vivo cancer incidence). 16 refs

  19. Colonic protein fermentation and promotion of colon carcinogenesis by thermolyzed casein

    Science.gov (United States)

    Corpet, Denis E.; Yin, Y.; Zhang, X. M.; Rémésy, C.; Stamp, D.; Medline, A.; Thompson, L.U.; Bruce, W. R.; Archer, M. C.

    1995-01-01

    Thermolyzed casein is known to promote the growth of aberrant crypt foci (ACF) and colon cancer when it is fed to rats that have been initiated with azoxymethane. We speculated that the promotion was a consequence of increased colonic protein fermentation (i.e., that the thermolysis of the casein decreases its digestibility, increases the amount of protein reaching the colon, and increases colonic protein fermentation and that the potentially toxic products of this fermentation promote colon carcinogenesis). We found that the thermolysis of casein reduces its digestibility and increases colonic protein fermentation, as assessed by fecal ammonium and urinary phenol, cresol, and indol-3-ol. Thermolysis of two other proteins, soy and egg white protein, also increases colonic protein fermentation with increased fecal ammonia and urinary phenols, and thermolysis of all three proteins increases the levels of ammonia and butyric, valeric, and i-valeric acids in the cecal contents. We found, however, that the increased protein fermentation observed with thermolysis is not associated with promotion of colon carcinogenesis. With casein, the kinetics of protein fermentation with increasing thermolysis time are clearly different from the kinetics of promotion of ACF growth. The formation of the fermentation products was highest when the protein was thermolyzed for one hour, whereas promotion was highest for protein that had been thermolyzed for two or more hours. With soy and egg white, thermolysis increased colonic protein fermentation but did not promote colon carcinogenesis. Thus, although thermolysis of dietary casein increases colonic protein fermentation, products of this fermentation do not appear to be responsible for the promotion of colon carcinogenesis. Indeed, the results suggest that protein fermentation products do not play an important role in colon cancer promotion. PMID:7603887

  20. A selective cyclooxygenase-2 inhibitor prevents inflammation-related squamous cell carcinogenesis of the forestomach via duodenogastric reflux in rats

    OpenAIRE

    Oba, Masaru; Miwa, Koichi; Fujimura, Takeshi; Harada, Shin-ichi; Sasaki, Shozo; Oyama, Katsunobu; Ohta, Tetsuo; Hattori, Takanori

    2009-01-01

    Background: Duodenal reflux causes inflammation-related squamous cell carcinogenesis in the forestomach of rats without any carcinogens. The aim of this study was to investigate the efficacy of a selective cyclooxygenase (COX)-2 inhibitor, meloxicam, in preventing this carcinogenesis. Methods: A series of 188 rats underwent a surgical duodenogastric reflux procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other was given experimental chow c...

  1. 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

  2. Chronic Inflammation-Related HPV: A Driving Force Speeds Oropharyngeal Carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Xin Liu

    Full Text Available Oropharyngeal squamous cell carcinoma (OPSCC has been known to be a highly aggressive disease associated with human papilloma virus (HPV infection. To investigate the relationship between HPV and chronic inflammation in oropharyngeal carcinogenesis, we collected 140 oral mucous fresh specimens including 50 OPSCC patients, 50 cancer in situ, 30 precancerous lesions, and 10 normal oral mucous. Our data demonstrated that there was a significantly higher proportion of severe chronic inflammation in dysplastic epithelia in comparison with that in normal tissues (P<0.001. The positive rate of HPV 16 was parallel with the chronic inflammation degrees from mild to severe inflammation (P<0.05. The positive rate of HPV 16 was progressively improved with the malignant progression of oral mucous (P<0.05. In addition, CD11b+ LIN- HLA-DR-CD33+ MDSCs were a critical cell population that mediates inflammation response and immune suppression in HPV-positive OPSCC. These indicated that persistent chronic inflammation-related HPV infection might drive oropharyngeal carcinogenesis and MDSCs might pay an important role during this process. Thus, a combination of HPV infection and inflammation expression might become a helpful biomedical marker to predict oropharyngeal carcinogenesis.

  3. 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)

  4. 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

  5. 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.

  6. 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.

  7. DNA Damage in Inflammation-Related Carcinogenesis and Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Shiho Ohnishi

    2013-01-01

    Full Text Available Infection and chronic inflammation have been recognized as important factors for carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS and reactive nitrogen species (RNS are generated from inflammatory and epithelial cells and result in oxidative and nitrative DNA damage, such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG and 8-nitroguanine. The DNA damage can cause mutations and has been implicated in the initiation and/or promotion of inflammation-mediated carcinogenesis. It has been estimated that various infectious agents are carcinogenic to humans (IARC group 1, including parasites (Schistosoma haematobium (SH and Opisthorchis viverrini (OV, viruses (hepatitis C virus (HCV, human papillomavirus (HPV, and Epstein-Barr virus (EBV, and bacterium Helicobacter pylori (HP. SH, OV, HCV, HPV, EBV, and HP are important risk factors for bladder cancer, cholangiocarcinoma, hepatocellular carcinoma, cervical cancer, nasopharyngeal carcinoma, and gastric cancer, respectively. We demonstrated that 8-nitroguanine was strongly formed via inducible nitric oxide synthase (iNOS expression at these cancer sites of patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in SH-associated bladder cancer tissues and in Oct3/4- and CD133-positive stem cells in OV-associated cholangiocarcinoma tissues. Therefore, it is considered that oxidative and nitrative DNA damage in stem cells may play a key role in inflammation-related carcinogenesis.

  8. Learn about Respiratory Syncytial Virus (RSV)

    Science.gov (United States)

    ... Lung Health and Diseases > Lung Disease Lookup > RSV Learn About Respiratory Syncytial Virus (RSV) Respiratory syncytial virus ( ... file."); } }); } } --> Blank Section Header Lung Disease Lookup RSV Learn About Respiratory Syncytial Virus (RSV) RSV Symptoms, Causes & ...

  9. 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)

  10. Understanding Carbohydrates

    Science.gov (United States)

    ... Size: A A A Listen En Español Understanding Carbohydrates How much and what type of carbohydrate foods ... glucose levels in your target range. Explore: Understanding Carbohydrates Glycemic Index and Diabetes Learn about the glycemic ...

  11. Interaction between hepatitis B and C viruses in hepatocellular carcinogenesis.

    Science.gov (United States)

    Kew, M C

    2006-03-01

    Although hepatitis B (HBV) and C viruses (HCV) are, individually, major causes of hepatocellular carcinoma, the interaction, if any, between the carcinogenic effects of the two viruses is uncertain. Equal numbers of published studies have reported no risk interaction or a synergistic risk interaction. These conflicting results are explained by the rarity of concurrent infection with HBV and HCV in individuals without clinically evident liver disease, which severely limits the ability to accurately estimate the hepatocarcinogenic risk of dual infection compared with that of either infection alone. In an attempt to circumvent this difficulty, two meta-analyses have been performed, one based on studies published from a number of countries and the other on studies confined to Chinese patients. Both analyses concluded that a synergistic carcinogenic interaction existed between the two viruses and that the increased risk was super-additive but not multiplicative. If confirmed, this risk interaction will occur against a background of negative confounding effects on viral replication between HBV and HCV, which may be reciprocal. The mechanisms responsible for the carcinogenic interaction between the viruses are unknown. One possibility is that the increased incidence of cirrhosis with concurrent HBV and HCV infections acts as an even more potent tumour promoter than occurs with either virus alone. Synergism between the direct hepatocarcinogenic effects of the two viruses is another possible mechanism, but proof will have to await a fuller understanding of the pathogenetic mechanisms involved with the individual viruses.

  12. Respiratory effort from the photoplethysmogram.

    Science.gov (United States)

    Addison, Paul S

    2017-03-01

    The potential for a simple, non-invasive measure of respiratory effort based on the pulse oximeter signal - the photoplethysmogram or 'pleth' - was investigated in a pilot study. Several parameters were developed based on a variety of manifestations of respiratory effort in the signal, including modulation changes in amplitude, baseline, frequency and pulse transit times, as well as distinct baseline signal shifts. Thirteen candidate parameters were investigated using data from healthy volunteers. Each volunteer underwent a series of controlled respiratory effort maneuvers at various set flow resistances and respiratory rates. Six oximeter probes were tested at various body sites. In all, over three thousand pleth-based effort-airway pressure (EP) curves were generated across the various airway constrictions, respiratory efforts, respiratory rates, subjects, probe sites, and the candidate parameters considered. Regression analysis was performed to determine the existence of positive monotonic relationships between the respiratory effort parameters and resulting airway pressures. Six of the candidate parameters investigated exhibited a distinct positive relationship (poximeter probe and an ECG (P2E-Effort) and the other using two pulse oximeter probes placed at different peripheral body sites (P2-Effort); and baseline shifts in heart rate, (BL-HR-Effort). In conclusion, a clear monotonic relationship was found between several pleth-based parameters and imposed respiratory loadings at the mouth across a range of respiratory rates and flow constrictions. The results suggest that the pleth may provide a measure of changing upper airway dynamics indicative of the effort to breathe. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

  13. Activation of respiratory muscles during respiratory muscle training.

    Science.gov (United States)

    Walterspacher, Stephan; Pietsch, Fabian; Walker, David Johannes; Röcker, Kai; Kabitz, Hans-Joachim

    2018-01-01

    It is unknown which respiratory muscles are mainly activated by respiratory muscle training. This study evaluated Inspiratory Pressure Threshold Loading (IPTL), Inspiratory Flow Resistive Loading (IFRL) and Voluntary Isocapnic Hyperpnea (VIH) with regard to electromyographic (EMG) activation of the sternocleidomastoid muscle (SCM), parasternal muscles (PARA) and the diaphragm (DIA) in randomized order. Surface EMG were analyzed at the end of each training session and normalized using the peak EMG recorded during maximum inspiratory maneuvers (Sniff nasal pressure: SnPna, maximal inspiratory mouth occlusion pressure: PImax). 41 healthy participants were included. Maximal activation was achieved for SCM by SnPna; the PImax activated predominantly PARA and DIA. Activations of SCM and PARA were higher in IPTL and VIH than for IFRL (pVIH (pVIH differ in activation of inspiratory respiratory muscles. Whereas all methods mainly stimulate accessory respiratory muscles, diaphragm activation was predominant in IPTL. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. [Acute respiratory dyspnea in children].

    Science.gov (United States)

    Casimir, G; Hanssens, L; Mulier, S

    2009-09-01

    Acute respiratory dyspnea is very frequent in children and must be quickly treated to obtain the best prognosis. The diagnosis depends from the natural history of the disease and from the quality of clinical assessment. The use of an algorithm according to the presence of stridor or bronchospasm is very contributive to the diagnosis. The paper reviews the pathophysiology of dyspnea in children and the more common diseases that are causing respiratory distress. Finally, treatment of respiratory failure and management of specific diseases are defined.

  15. Assessing Respiratory System Mechanical Function.

    Science.gov (United States)

    Restrepo, Ruben D; Serrato, Diana M; Adasme, Rodrigo

    2016-12-01

    The main goals of assessing respiratory system mechanical function are to evaluate the lung function through a variety of methods and to detect early signs of abnormalities that could affect the patient's outcomes. In ventilated patients, it has become increasingly important to recognize whether respiratory function has improved or deteriorated, whether the ventilator settings match the patient's demand, and whether the selection of ventilator parameters follows a lung-protective strategy. Ventilator graphics, esophageal pressure, intra-abdominal pressure, and electric impedance tomography are some of the best-known monitoring tools to obtain measurements and adequately evaluate the respiratory system mechanical function. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Multiplex detection of respiratory pathogens

    Science.gov (United States)

    McBride, Mary [Brentwood, CA; Slezak, Thomas [Livermore, CA; Birch, James M [Albany, CA

    2012-07-31

    Described are kits and methods useful for detection of respiratory pathogens (influenza A (including subtyping capability for H1, H3, H5 and H7 subtypes) influenza B, parainfluenza (type 2), respiratory syncytial virus, and adenovirus) in a sample. Genomic sequence information from the respiratory pathogens was analyzed to identify signature sequences, e.g., polynucleotide sequences useful for confirming the presence or absence of a pathogen in a sample. Primer and probe sets were designed and optimized for use in a PCR based, multiplexed Luminex assay to successfully identify the presence or absence of pathogens in a sample.

  17. Recurrent respiratory papillomatosis.

    Science.gov (United States)

    Leventhal, B G; Whisnant, J; Kashima, H; Levy, H; Biggers, W P

    1985-10-01

    Recurrent respiratory papillomatosis is a disease caused by a virus in the Papovaviridae family. It tends to recur in the laryngotracheal tree, and treatment is surgical removal with a CO2 laser and suspension microlaryngoscopy. Some patients may require these procedures every few weeks, and a systemic agent to control disease would be ideal for them. Care must be taken in the selection of an agent, as these lesions, similar to other papova virus-induced lesions, are most susceptible to malignant degeneration in the presence of a carcinogen. Eight patients were given 10 courses of polyriboinosinic-polyribocytidylic acid [poly(I,C)-LC] in an attempt to control their disease. The three who were tested were able to produce good titers of interferon. The rate of disease progression was probably slowed in four patients, as reflected by a decrease in the requirement for surgery; however, the medication appeared to be relatively toxic in effective doses. Four of 10 courses were held for hepatotoxicity, and mild hepatotoxicity occurred in four more. One course was held for thrombocytopenia associated with bleeding at the tracheostomy site. We conclude that in its presently available form, poly(I,C)-LC is too toxic to be administered long term for control of this disease.

  18. Adult respiratory distress syndrome.

    Science.gov (United States)

    Sutlić, Z; Rudez, I; Biocina, B; Husedzinović, I

    1997-01-01

    In this article the authors present a case of successful treatment of a 54-year old male patient with non-insulin dependent diabetes mellitus (NIDDM) and triple-vessel coronary artery disease who underwent surgical myocardial revascularization and was reoperated on the same day because of excessive bleeding. The patient was given cca 5000 mL of whole blood and cca 3000 mL of blood derivatives. The first postoperative chest X-ray showed radiological signs of ARDS. The therapy was based upon authors' experience and was consisted of controlled mechanical ventilation (respiratory volume 12-15 mL/kg, 10-14 cycles/min, I/E ratio 1:2, FIO2 0.6, PEEP 2-5 cm H2O), daily bronchoscopies with bronchoaspiration, aggressive diuresis, negative fluid balance, specific antibiotic therapy, and last but not least, of prostaglandin E1 (PGE1) 0.5-20 micrograms/kg/min combined with dopamine inotropic support (2-5 micrograms/kg/h). Simple but careful clinical observation still remains a milestone for all therapeutic measures taken in ARDS patients.

  19. Respiratory Patients Breathing Life into the Canterbury Integrated Respiratory Service

    OpenAIRE

    Weatherall, Louise

    2017-01-01

    A group of past pulmonary rehabilitation participants have joined together to form the Pulmonary Rehabilitation Consumer Group. They have been actively engaged in Canterbury’s respiratory service design and innovation since 2013.Telling their Story: Members of the Consumer Group meet monthly to give their opinion on how pulmonary rehabilitation and the wider respiratory service support patients to look after their own health.They discuss their own positive and negative experiences to a wide r...

  20. Role of stem cells in large bowel carcinogenesis

    Directory of Open Access Journals (Sweden)

    N. A. Nefedova

    2015-01-01

    Full Text Available Сancer stem cells (CSC play a significant role in the development and progression of colorectal cancer. They are capable of self-senewal and multipotent differentiation. CSC can be formed from stem cells or mutant by dedifferentiation of crypt epithelial cells. Recently, much attention is paid to CSC in colon cancer, but very little has been published regarding their expression in colon polyps. In 2010 The World Health Organization attributed the so-called serrated lesions, including hyperplastic polyp, serrated sessile adenoma and traditional serrated adenoma to a group of precancerous lesions of the colon in addition to the classical tubular, villous and tubulo-villous adenomas. Despite the large number of publications devoted to the newly selected category, a full understanding of the processes involved in the formation of polyps and their progression into colon cancer, there is still no. Identification of CSC in colon polyps will assess their potential malignancy conduct adequate therapy, determine the amount of the operation and further treatment strategy. This in turn will contribute to the early detection and prevention of cancer. Identification of CSC, an assessment of their localization and distribution in tubular adenomas, serrated adenoma broad-based, traditional serrated adenoma and hyperplastic polyps allow to evaluate the potential of malignancy and prognosis for each of the polyps. In this regard, the definition of markers characteristic of colon CSC, is interesting not only from a scientific, but also from a practical point of view.

  1. Respiratory Viruses in Febrile Neutropenic Patients with Respiratory Symptoms.

    Science.gov (United States)

    Meidani, Mohsen; Mirmohammad Sadeghi, Seyed Alireza

    2018-01-01

    Respiratory infections are a frequent cause of fever in neutropenic patients, whereas respiratory viral infections are not frequently considered as a diagnosis, which causes high morbidity and mortality in these patients. This prospective study was performed on 36 patients with neutropenia who admitted to hospital were eligible for inclusion with fever (single temperature of >38.3°C or a sustained temperature of >38°C for more than 1 h), upper and lower respiratory symptoms. Sampling was performed from the throat of the patient by the sterile swab. All materials were analyzed by quantitative real-time multiplex polymerase chain reaction covering the following viruses; influenza, parainfluenza virus (PIV), rhinovirus (RV), human metapneumovirus, and respiratory syncytial virus (RSV). RV was the most frequently detected virus and then RSV was the most. PIV was not present in any of the tested samples. Furthermore, no substantial differences in the distribution of specific viral species were observed based on age, sex, neutropenia duration, hematological disorder, and respiratory tract symptoms and signs ( P > 0.05). Our prospective study supports the hypothesis that respiratory viruses play an important role in the development of neutropenic fever, and thus has the potential to individualize infection treatment and to reduce the extensive use of antibiotics in immunocompromised patients with neutropenia.

  2. Respiratory Viruses in Febrile Neutropenic Patients with Respiratory Symptoms

    Directory of Open Access Journals (Sweden)

    Mohsen Meidani

    2018-01-01

    Full Text Available Background: Respiratory infections are a frequent cause of fever in neutropenic patients, whereas respiratory viral infections are not frequently considered as a diagnosis, which causes high morbidity and mortality in these patients. Materials and Methods: This prospective study was performed on 36 patients with neutropenia who admitted to hospital were eligible for inclusion with fever (single temperature of >38.3°C or a sustained temperature of >38°C for more than 1 h, upper and lower respiratory symptoms. Sampling was performed from the throat of the patient by the sterile swab. All materials were analyzed by quantitative real-time multiplex polymerase chain reaction covering the following viruses; influenza, parainfluenza virus (PIV, rhinovirus (RV, human metapneumovirus, and respiratory syncytial virus (RSV. Results: RV was the most frequently detected virus and then RSV was the most. PIV was not present in any of the tested samples. Furthermore, no substantial differences in the distribution of specific viral species were observed based on age, sex, neutropenia duration, hematological disorder, and respiratory tract symptoms and signs (P > 0.05. Conclusion: Our prospective study supports the hypothesis that respiratory viruses play an important role in the development of neutropenic fever, and thus has the potential to individualize infection treatment and to reduce the extensive use of antibiotics in immunocompromised patients with neutropenia.

  3. Mucosal inflammation at the respiratory interface: a zebrafish model.

    Science.gov (United States)

    Progatzky, Fränze; Cook, H Terence; Lamb, Jonathan R; Bugeon, Laurence; Dallman, Margaret J

    2016-03-15

    Inflammatory diseases of the respiratory system such as asthma and chronic obstructive pulmonary disease are increasing globally and remain poorly understood conditions. Although attention has long focused on the activation of type 1 and type 2 helper T cells of the adaptive immune system in these diseases, it is becoming increasingly apparent that there is also a need to understand the contributions and interactions between innate immune cells and the epithelial lining of the respiratory system. Cigarette smoke predisposes the respiratory tissue to a higher incidence of inflammatory disease, and here we have used zebrafish gills as a model to study the effect of cigarette smoke on the respiratory epithelium. Zebrafish gills fulfill the same gas-exchange function as the mammalian airways and have a similar structure. Exposure to cigarette smoke extracts resulted in an increase in transcripts of the proinflammatory cytokines TNF-α, IL-1β, and MMP9 in the gill tissue, which was at least in part mediated via NF-κB activation. Longer term exposure of fish for 6 wk to cigarette smoke extract resulted in marked structural changes to the gills with lamellar fusion and mucus cell formation, while signs of inflammation or fibrosis were absent. This shows, for the first time, that zebrafish gills are a relevant model for studying the effect of inflammatory stimuli on a respiratory epithelium, since they mimic the immunopathology involved in respiratory inflammatory diseases of humans. Copyright © 2016 the American Physiological Society.

  4. Risk Factors of Respiratory Failure in Children with Guillain-Barré Syndrome

    Directory of Open Access Journals (Sweden)

    Mei-Hua Hu

    2012-10-01

    Conclusions: Respiratory failure in childhood GBS was related to the Hughes score at nadir, respiratory distress, and hypotension. Atypical presentations of symptoms were more predominant in patients younger than 6 years. The prognosis in our series was good and not related to previous events. Understanding the risk factors of severe GBS will provide better treatment strategies and improve the outcomes.

  5. Employee guide to respiratory protection

    International Nuclear Information System (INIS)

    Wright, E.M.

    1982-01-01

    This employee guide discusses use of respiratory protective equipment for particulates, gases, vapors, supplied air, and self-contained breathing apparatus. It also covers equipment selection medical factors, fitting criteria; care; and employee responsibilities

  6. Comorbidity of respiratory and cardiovascular diseases among the ...

    African Journals Online (AJOL)

    training in conducting the interviews using the respiratory health questionnaire before the start of the survey. The interviews were mainly in English and were translated into the local language if the respondent did not understand the questions. The questionnaire included sections on demography, medical history, type of ...

  7. Implementing hospital-based surveillance for severe acute respiratory infections caused by influenza and other respiratory pathogens in New Zealand

    Directory of Open Access Journals (Sweden)

    Q Sue Huang

    2014-05-01

    Full Text Available Background: Recent experience with pandemic influenza A(H1N1pdm09 highlighted the importance of global surveillance for severe respiratory disease to support pandemic preparedness and seasonal influenza control. Improved surveillance in the southern hemisphere is needed to provide critical data on influenza epidemiology, disease burden, circulating strains and effectiveness of influenza prevention and control measures. Hospital-based surveillance for severe acute respiratory infection (SARI cases was established in New Zealand on 30 April 2012. The aims were to measure incidence, prevalence, risk factors, clinical spectrum and outcomes for SARI and associated influenza and other respiratory pathogen cases as well as to understand influenza contribution to patients not meeting SARI case definition. Methods/Design: All inpatients with suspected respiratory infections who were admitted overnight to the study hospitals were screened daily. If a patient met the World Health Organization’s SARI case definition, a respiratory specimen was tested for influenza and other respiratory pathogens. A case report form captured demographics, history of presenting illness, co-morbidities, disease course and outcome and risk factors. These data were supplemented from electronic clinical records and other linked data sources. Discussion: Hospital-based SARI surveillance has been implemented and is fully functioning in New Zealand. Active, prospective, continuous, hospital-based SARI surveillance is useful in supporting pandemic preparedness for emerging influenza A(H7N9 virus infections and seasonal influenza prevention and control.

  8. Inactivity-induced respiratory plasticity: protecting the drive to breathe in disorders that reduce respiratory neural activity.

    Science.gov (United States)

    Strey, K A; Baertsch, N A; Baker-Herman, T L

    2013-11-01

    Multiple forms of plasticity are activated following reduced respiratory neural activity. For example, in ventilated rats, a central neural apnea elicits a rebound increase in phrenic and hypoglossal burst amplitude upon resumption of respiratory neural activity, forms of plasticity called inactivity-induced phrenic and hypoglossal motor facilitation (iPMF and iHMF), respectively. Here, we provide a conceptual framework for plasticity following reduced respiratory neural activity to guide future investigations. We review mechanisms giving rise to iPMF and iHMF, present new data suggesting that inactivity-induced plasticity is observed in inspiratory intercostals (iIMF) and point out gaps in our knowledge. We then survey conditions relevant to human health characterized by reduced respiratory neural activity and discuss evidence that inactivity-induced plasticity is elicited during these conditions. Understanding the physiological impact and circumstances in which inactivity-induced respiratory plasticity is elicited may yield novel insights into the treatment of disorders characterized by reductions in respiratory neural activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Inactivity-induced respiratory plasticity: Protecting the drive to breathe in disorders that reduce respiratory neural activity☆

    Science.gov (United States)

    Strey, K.A.; Baertsch, N.A.; Baker-Herman, T.L.

    2013-01-01

    Multiple forms of plasticity are activated following reduced respiratory neural activity. For example, in ventilated rats, a central neural apnea elicits a rebound increase in phrenic and hypoglossal burst amplitude upon resumption of respiratory neural activity, forms of plasticity called inactivity-induced phrenic and hypoglossal motor facilitation (iPMF and iHMF), respectively. Here, we provide a conceptual framework for plasticity following reduced respiratory neural activity to guide future investigations. We review mechanisms giving rise to iPMF and iHMF, present new data suggesting that inactivity-induced plasticity is observed in inspiratory intercostals (iIMF) and point out gaps in our knowledge. We then survey conditions relevant to human health characterized by reduced respiratory neural activity and discuss evidence that inactivity-induced plasticity is elicited during these conditions. Understanding the physiological impact and circumstances in which inactivity-induced respiratory plasticity is elicited may yield novel insights into the treatment of disorders characterized by reductions in respiratory neural activity. PMID:23816599

  10. Climate Change and Respiratory Infections.

    Science.gov (United States)

    Mirsaeidi, Mehdi; Motahari, Hooman; Taghizadeh Khamesi, Mojdeh; Sharifi, Arash; Campos, Michael; Schraufnagel, Dean E

    2016-08-01

    The rate of global warming has accelerated over the past 50 years. Increasing surface temperature is melting glaciers and raising the sea level. More flooding, droughts, hurricanes, and heat waves are being reported. Accelerated changes in climate are already affecting human health, in part by altering the epidemiology of climate-sensitive pathogens. In particular, climate change may alter the incidence and severity of respiratory infections by affecting vectors and host immune responses. Certain respiratory infections, such as avian influenza and coccidioidomycosis, are occurring in locations previously unaffected, apparently because of global warming. Young children and older adults appear to be particularly vulnerable to rapid fluctuations in ambient temperature. For example, an increase in the incidence in childhood pneumonia in Australia has been associated with sharp temperature drops from one day to the next. Extreme weather events, such as heat waves, floods, major storms, drought, and wildfires, are also believed to change the incidence of respiratory infections. An outbreak of aspergillosis among Japanese survivors of the 2011 tsunami is one such well-documented example. Changes in temperature, precipitation, relative humidity, and air pollution influence viral activity and transmission. For example, in early 2000, an outbreak of Hantavirus respiratory disease was linked to a local increase in the rodent population, which in turn was attributed to a two- to threefold increase in rainfall before the outbreak. Climate-sensitive respiratory pathogens present challenges to respiratory health that may be far greater in the foreseeable future.

  11. Understanding classification

    NARCIS (Netherlands)

    Subianto, M.

    2009-01-01

    In practical data analysis, the understandability of models plays an important role in their acceptance. In the data mining literature, however, understandability plays is hardly ever mentioned. If it is mentioned, it is interpreted as meaning that the models have to be simple. In this thesis we

  12. Embodied understanding.

    Science.gov (United States)

    Johnson, Mark

    2015-01-01

    Western culture has inherited a view of understanding as an intellectual cognitive operation of grasping of concepts and their relations. However, cognitive science research has shown that this received intellectualist conception is substantially out of touch with how humans actually make and experience meaning. The view emerging from the mind sciences recognizes that understanding is profoundly embodied, insofar as our conceptualization and reasoning recruit sensory, motor, and affective patterns and processes to structure our understanding of, and engagement with, our world. A psychologically realistic account of understanding must begin with the patterns of ongoing interaction between an organism and its physical and cultural environments and must include both our emotional responses to changes in our body and environment, and also the actions by which we continuously transform our experience. Consequently, embodied understanding is not merely a conceptual/propositional activity of thought, but rather constitutes our most basic way of being in, and engaging with, our surroundings in a deep visceral manner.

  13. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure.

    Science.gov (United States)

    Kneyber, Martin C J; van Heerde, Marc; Twisk, Jos W R; Plötz, Frans B; Markhors, Dick G

    2009-01-01

    Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of mechanical ventilation with heliox in these patients is unclear. The objective of this prospective cross-over study was to determine the effects of mechanical ventilation with heliox 60/40 versus conventional gas on respiratory system resistance, air-trapping and CO2 removal. Mechanically ventilated, sedated and paralyzed infants with proven RSV were enrolled within 24 hours after paediatric intensive care unit (PICU)admission. At T = 0, respiratory system mechanics including respiratory system compliance and resistance, and peak expiratory flow rate were measured with the AVEA ventilator. The measurements were repeated at each interval (after 30 minutes of ventilation with heliox, after 30 minutes of ventilation with nitrox and again after 30 minutes of ventilation with heliox). Indices of gas exchange (ventilation and oxygenation index) were calculated at each interval. Air-trapping (defined by relative change in end-expiratory lung volume) was determined by electrical impedance tomography (EIT) at each interval. Thirteen infants were enrolled. In nine, EIT measurements were performed. Mechanical ventilation with heliox significantly decreased respiratory system resistance. This was not accompanied by an improved CO2 elimination, decreased peak expiratory flow rate or decreased end-expiratory lung volume. Importantly, oxygenation remained unaltered throughout the experimental protocol. Respiratory system resistance is significantly decreased by mechanical ventilation with heliox (ISCRTN98152468).

  14. 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

  15. Kimchi protects against azoxymethane/dextran sulfate sodium-induced colorectal carcinogenesis in mice.

    Science.gov (United States)

    Kim, Hee-Young; Song, Jia-Le; Chang, Hee-Kyung; Kang, Soon-Ah; Park, Kun-Young

    2014-08-01

    The chemopreventive effects of different types and quantities of kimchi prepared with different subingredients, including commercial kimchi (CK), standardized kimchi (SK), cancer-preventive kimchi (CPK), and anticancer kimchi (ACK), on colorectal carcinogenesis in mice were evaluated. The development of colon cancer was induced in male BALB/c mice with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and subsequent treatment with 2% dextran sulfate sodium (DSS) in drinking water for 7 days for two cycles. After exposure to AOM and DSS, treatment with the methanolic extracts from different kimchis, particularly 1.89 g/kg of ACK, significantly increased colon length, decreased the ratio of colon weight/length, and resulted in the lowest number of tumors compared with the other kimchi-treated groups. Histological observation revealed that ACK was able to suppress AOM- and DSS-induced colonic mucosal damage and neoplasia. ACK also significantly decreased the mRNA levels of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) as well as the mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2). In addition, the mRNA and protein expression of p53 and p21 was elevated in colon tissues from the ACK-treated mice compared with the other kimchi-treated groups. Our results suggest that kimchi exerted a suppressive effect on AOM- and DSS-induced colorectal carcinogenesis in the BALB/c mice. The anticancer effects of ACK were particularly potent. Thus, it is possible that the health-promoting subingredients added to ACK might be used to prevent colon carcinogenesis in humans.

  16. Kimchi Protects Against Azoxymethane/Dextran Sulfate Sodium–Induced Colorectal Carcinogenesis in Mice

    Science.gov (United States)

    Kim, Hee-Young; Song, Jia-Le; Chang, Hee-Kyung; Kang, Soon-Ah

    2014-01-01

    Abstract The chemopreventive effects of different types and quantities of kimchi prepared with different subingredients, including commercial kimchi (CK), standardized kimchi (SK), cancer-preventive kimchi (CPK), and anticancer kimchi (ACK), on colorectal carcinogenesis in mice were evaluated. The development of colon cancer was induced in male BALB/c mice with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and subsequent treatment with 2% dextran sulfate sodium (DSS) in drinking water for 7 days for two cycles. After exposure to AOM and DSS, treatment with the methanolic extracts from different kimchis, particularly 1.89 g/kg of ACK, significantly increased colon length, decreased the ratio of colon weight/length, and resulted in the lowest number of tumors compared with the other kimchi-treated groups. Histological observation revealed that ACK was able to suppress AOM- and DSS-induced colonic mucosal damage and neoplasia. ACK also significantly decreased the mRNA levels of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) as well as the mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2). In addition, the mRNA and protein expression of p53 and p21 was elevated in colon tissues from the ACK-treated mice compared with the other kimchi-treated groups. Our results suggest that kimchi exerted a suppressive effect on AOM- and DSS-induced colorectal carcinogenesis in the BALB/c mice. The anticancer effects of ACK were particularly potent. Thus, it is possible that the health-promoting subingredients added to ACK might be used to prevent colon carcinogenesis in humans. PMID:25029638

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Protective Effect of Lactobacillus casei on DMH-Induced Colon Carcinogenesis in Mice.

    Science.gov (United States)

    Irecta-Nájera, Cesar Antonio; Del Rosario Huizar-López, María; Casas-Solís, Josefina; Castro-Félix, Patricia; Santerre, Anne

    2017-06-01

    The administration of probiotics is a promising approach to reduce the prevalence of colon cancer, a multifactorial disease, with hereditary factors, as well as environmental lifestyle-related risk factors. Biogenic polyamines, putrescine, spermidine, and spermine are small cationic molecules with great roles in cell proliferation and differentiation as well as regulation of gene expression. Ornithine decarboxylase is the first rate-limiting enzyme for polyamine synthesis, and upregulation of ornithine decarboxylase activity and polyamine metabolism has been associated with abnormal cell proliferation. This paper is focused on studying the protective role of Lactobacillus casei ATCC 393 in a chemically induced mouse model of colon carcinogenesis, directing our attention on aberrant crypt foci as preneoplastic markers, and on polyamine metabolism as a possible key player in carcinogenesis. BALB/c mice were administered 1,2-dimethylhydrazine dihydrochloride (DMH) to induce colon cancer (20 mg/kg body weight, subcutaneous, twice a week for 24 weeks). L. casei ATCC 393 was given orally (10 6  CFU, twice a week), 2 weeks before DMH administration. Hematoxylin and eosin staining, high-performance liquid chromatography, and Western blotting were used to evaluate aberrant crypt foci, urinary polyamines, and ornithine decarboxylase expression in the colon. The experimental data showed that the preventive administration of L. casei ATCC 393 may delay the onset of cancer as it significantly reduced the number of DMH-induced aberrant crypt foci, the levels of putrescine, and the expression of ornithine decarboxylase. Hence, this probiotic strain has a prospective role in protection against colon carcinogenesis, and its antimutagenic activity may be associated with the maintenance of polyamine metabolism.

  19. Effects of selenium on Pteridium aquilinum and urethane-induced lung carcinogenesis.

    Science.gov (United States)

    Nakahara, Sheila B R; Sanches, Daniel S; Caniceiro, Beatriz D; Wysochi, Harry L; da Silva, Graziela B; Latorre, Andreia O

    2013-10-01

    The results of our previous study demonstrated that ptaquiloside, the main toxic agent found in Pteridium aquilinum, suppresses natural killer (NK) cell-mediated cytotoxicity. However, the ability of ptaquiloside to suppress the cytotoxicity of NK cells was prevented by selenium supplementation. NK cells play an important role in the innate immune response and have the ability to kill tumor cells. Therefore, we hypothesized that selenium may prevent the higher susceptibility to urethane-induced lung carcinogenesis that has been observed in mice treated with P. aquilinum. The immunosuppressive effects of ptaquiloside have been associated with a higher number of urethane-induced lung nodules in mice. Hence, we assessed the effects of P. aquilinum-induced immunosuppression on urethane-induced lung carcinogenesis in C57BL/6 mice that had been supplemented with selenium. For these experiments, mice were treated with both an aqueous extract of P. aquilinum (20 g/kg/day) and selenium (1.3 mg/kg) by gavage once daily for 14 days followed by a once-weekly intraperitoneal injection of urethane (1 g/kg) for 10 weeks that was accompanied by gavage 5 days a week. Lung adenomas in mice that had been treated with P. aquilinum plus urethane occurred with a frequency that was 44% higher than that in mice that had been treated with only urethane. In mice that had been supplemented with selenium and treated with P. aquilinum plus urethane, the occurrence of lung adenomas was reduced to 26%. These results suggest that selenium prevents the immunosuppressive effects of P. aquilinum on urethane-induced lung carcinogenesis.

  20. 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.

  1. 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.

  2. 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.

  3. 1,8-cineole prevents UVB-induced skin carcinogenesis by targeting the aryl hydrocarbon receptor

    Science.gov (United States)

    Park, Joon; Kim, Yong Ho; Lee, Nam Hyouck; Kim, Young Eon; Kim, Yoonsook; Song, Kyung-Mo; Jung, Sung Keun

    2017-01-01

    1,8-cineole is a natural monoterpene cyclic ether present in Eucalyptus, and has been reported to exhibit anti-inflammatory and antioxidant effects. However, the preventive effect of 1,8-cineole on skin carcinogenesis and the molecular mechanism of action responsible remains unknown. In the present study, we investigated the effect of 1,8-cineole on UVB-induced skin carcinogenesis. 1,8-cineole inhibited UVB-induced cyclooxygenase-2 (COX-2) protein and mRNA expression and prostaglandin E2 (PGE2) generation in HaCaT cells. 1,8-cineole also inhibited phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, and phosphorylation of its upstream kinases, c-Src and epidermal growth factor receptor (EGFR). Quantitative real-time RT-PCR (qRT-PCR) and drug affinity responsive target stability (DARTS) assay results showed that 1,8-cineole suppressed UVB-induced expression of a target gene of the aryl hydrocarbon receptor (AhR), cyp1a1, and directly binds to AhR. Knockdown of AhR suppressed COX-2 expression as well as phosphorylation of ERK1/2 in HaCaT cells. Furthermore, topical treatment of 1,8-cineole on mouse skin delayed tumor incidence and reduced tumor numbers, while inhibiting COX-2 expression in vivo. Taken together, these results suggest that 1,8-cineole is a potent chemopreventive agent that inhibits UVB-induced COX-2 expression by targeting AhR to suppress UVB-induced skin carcinogenesis. PMID:29285309

  4. Long non-coding RNA HOTAIR promotes carcinogenesis and invasion of gastric adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Na Keum; Lee, Jung Hwa; Park, Chan Hyuk; Yu, Dayeon; Lee, Yong Chan [Division of Gastroenterology, Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cheong, Jae-Ho; Noh, Sung Hoon [Department of Surgery, Yonsei University College of Medicine (Korea, Republic of); Lee, Sang Kil, E-mail: sklee@yuhs.ac [Division of Gastroenterology, Department of Internal Medicine, Yonsei Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-08-22

    Highlights: • HOTAIR expression was tested in fifty patients with gastric cancer. • Cell proliferation was measured after HOTAIR silencing in gastric cancer cell line. • siRNA–HOTAIR suppresses cell invasiveness and capacity of migration. • Knock down of HOTAR leads to decreased expression of EMT markers. • Inhibition of HOTAIR induces apoptosis and cell cycle arrest. - Abstract: Gastric cancer is one of the major causes of cancer death worldwide; however, the mechanism of carcinogenesis is complex and poorly understood. Long non-coding RNA HOTAIR (HOX transcript antisense RNA) recently emerged as a promoter of metastasis in various cancers including gastric cancer. Here we investigated the impact of HOTAIR on apoptosis, cell proliferation and cell cycle to dissect the carcinogenesis of gastric cancer. We examined the mechanism of invasion and metastasis and analyzed the clinical significance of HOTAIR. Downregulation of HOTAIR was confirmed by two different siRNAs. The expression of HOTAIR was significantly elevated in various gastric cancer cell lines and tissues compared to normal control. si-HOTAIR significantly reduced viability in MKN 28, MKN 74, and KATO III cells but not in AGS cells. si-HOTAIR induced apoptosis in KATO III cells. Lymphovascular invasion and lymph node metastasis were more common in the high level of HOTAIR group. si-HOTAIR significantly decreased invasiveness and migration. si-HOTAIR led to differential expression of epithelial to mesenchymal transition markers. We found that HOTAIR was involved in inhibition of apoptosis and promoted invasiveness, supporting a role for HOTAIR in carcinogenesis and progression of gastric cancer.

  5. Thrombospondin-2 overexpression in the skin of transgenic mice reduces the susceptibility to chemically induced multistep skin carcinogenesis.

    Science.gov (United States)

    Kunstfeld, Rainer; Hawighorst, Thomas; Streit, Michael; Hong, Young-Kwon; Nguyen, Lynh; Brown, Lawrence F; Detmar, Michael

    2014-05-01

    We have previously reported stromal upregulation of the endogenous angiogenesis inhibitor thrombospondin-2 (TSP-2) during multistep carcinogenesis, and we found accelerated and enhanced skin angiogenesis and carcinogenesis in TSP-2 deficient mice. To investigate whether enhanced levels of TSP-2 might protect from skin cancer development. We established transgenic mice with targeted overexpression of TSP-2 in the skin and subjected hemizygous TSP-2 transgenic mice and their wild-type littermates to a chemical skin carcinogenesis regimen. TSP-2 transgenic mice showed a significantly delayed onset of tumor formation compared to wild-type mice, whereas the ratio of malignant conversion to squamous cell carcinomas was comparable in both genotypes. Computer-assisted morphometric analysis of blood vessels revealed pronounced tumor angiogenesis already in the early stages of carcinogenesis in wild type mice. TSP-2 overexpression significantly reduced tumor blood vessel density in transgenic mice but had no overt effect on LYVE-1 positive lymphatic vessels. The percentage of desmin surrounded, mature tumor-associated blood vessels and the degree of epithelial differentiation remained unaffected. The antiangiogenic effect of transgenic TSP-2 was accompanied by a significantly increased number of apoptotic tumor cells in transgenic mice. Our results demonstrate that enhanced levels of TSP-2 in the skin result in reduced susceptibility to chemically-induced skin carcinogenesis and identify TSP-2 as a new target for the prevention of skin cancer. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications.

    Science.gov (United States)

    Cao, Yi

    2015-09-01

    Environmental pollution is one of the main causes of human cancer. Exposures to environmental carcinogens result in genetic and epigenetic alterations which induce cell transformation. Epigenetic changes caused by environmental pollution play important roles in the development and progression of environmental pollution-related cancers. Studies on DNA methylation are among the earliest and most conducted epigenetic research linked to cancer. In this review, the roles of DNA methylation in carcinogenesis and their significance in clinical medicine were summarized, and the effects of environmental pollutants, particularly air pollutants, on DNA methylation were introduced. Furthermore, prospective applications of DNA methylation to environmental pollution detection and cancer prevention were discussed.

  7. Thyroid cancer. Reevaluation of an experimental model for radiogenic endocrine carcinogenesis

    International Nuclear Information System (INIS)

    Clifton, K.H.

    1984-11-01

    The status of experimental studies of radiogenic thyroid cancer is appraised, and some older data are reinterpreted in the light of more recent findings. Problems of thyroid dosimetry, particularly the dosimetry of internal radioiodides, are discussed. The steps in radiation carcinogenesis during the acute phase, the latent phase, and the phase of tumor growth are discussed in terms of thyroid epithelial cell population changes. The roles of three cell populations (undamaged or completely repaired epithelial cells, oncogenically initiated cells, and terminally damaged but functionally competent cells) in neoplasia are described. Finally, the implications for man of these experimental results and conclusions are discussed. 89 refs., 4 figs

  8. Thermodynamic considerations on the role of heat and mass transfer in biochemical causes of carcinogenesis

    Science.gov (United States)

    Lucia, Umberto; Grisolia, Giulia; Ponzetto, Antonio; Deisboeck, Thomas S.

    2018-01-01

    Cellular homoeostasis involves a continuous interaction between the cell and its microenvironment. As such, active and passive transport of ions, nutrients, molecules and water are the basis for biochemical-physical cell life. These transport phenomena change the internal and external ionic concentrations, and, as a consequence, the cell membrane's electric potential and the pH. In this paper we focus on the relationship between these ion transport-induced pH and membrane voltage changes to highlight their impact on carcinogenesis. The preliminary results suggest a critical role for Cl- in driving tumour transformation towards a more malignant phenotype.

  9. Development of Carcinogenesis Bioassay Models: Response of Small Fish Species to Various Classes of Carcinogens

    Science.gov (United States)

    1991-12-20

    453-465. I Hawkins, W.E., R.M. Overstreet, and W.W. Walker. 1988. Carcinogenicity tests with small fish species. Aquatic Toxicology 11:113-128. I...Journal of Aquatic Animal Health 3: 213-220. I Hendricks, J.D. 1982. Chemical carcinogenesis in fish. In: Aquatic Toxicology , LJ. Weber (Editor...Regulatory Toxicology and Pharmacology 9: I 5-22. Malins, D.C. and G.K. Ostrander. 1991. Perspectives in aquatic toxicology . Annual Review I of

  10. Understanding semantics

    DEFF Research Database (Denmark)

    Thrane, Torben

    1997-01-01

    Understanding natural language is a cognitive, information-driven process. Discussing some of the consequences of this fact, the paper offers a novel look at the semantic effect of lexical nouns and the identification of reference types....

  11. Understanding Alzheimer's

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Understanding Alzheimer's Past Issues / Fall 2007 Table of Contents For ... and brain scans. No treatment so far stops Alzheimer's. However, for some in the disease's early and ...

  12. Understanding homelessness

    OpenAIRE

    Somerville, Peter

    2013-01-01

    This paper reviews the literature on understanding homelessness. It criticizes approaches that ignore, distort or diminish the humanity of homeless people, or else, add little to our understanding of that humanity. In particular, it rejects what it calls “epidemiological” approaches, which deny the possibility of agency for homeless people, insofar as those approaches view the situation of those people largely as a “social fact”, to be explained in terms of causal variables or “risk factors” ...

  13. Altered Respiratory Physiology in Obesity

    Directory of Open Access Journals (Sweden)

    Krishnan Parameswaran

    2006-01-01

    Full Text Available The major respiratory complications of obesity include a heightened demand for ventilation, elevated work of breathing, respiratory muscle inefficiency and diminished respiratory compliance. The decreased functional residual capacity and expiratory reserve volume, with a high closing volume to functional residual capacity ratio of obesity, are associated with the closure of peripheral lung units, ventilation to perfusion ratio abnormalities and hypoxemia, especially in the supine position. Conventional respiratory function tests are only mildly affected by obesity except in extreme cases. The major circulatory complications are increased total and pulmonary blood volume, high cardiac output and elevated left ventricular end-diastolic pressure. Patients with obesity commonly develop hypoventilation and sleep apnea syndromes with attenuated hypoxic and hypercapnic ventilatory responsiveness. The final result is hypoxemia, pulmonary hypertension and progressively worsening disability. Obese patients have increased dyspnea and decreased exercise capacity, which are vital to quality of life. Decreased muscle, increased joint pain and skin friction are important determinants of decreased exercise capacity, in addition to the cardiopulmonary effects of obesity. The effects of obesity on mortality in heart failure and chronic obstructive pulmonary disease have not been definitively resolved. Whether obesity contributes to asthma and airway hyper-responsiveness is uncertain. Weight reduction and physical activity are effective means of reversing the respiratory complications of obesity.

  14. Radiation carcinogenesis

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1976-01-01

    The risk of iatrogenic tumors with radiation therapy is so outweighed by the benefit of cure that estimates of risk have not been considered necessary. However, with the introduction of chemotherapy, combined therapy, and particle radiation therapy, the comparative risks should be examined. In the case of radiation, total dose, fractionation, dose rate, dose distribution, and radiation quality should be considered in the estimation of risk. The biological factors that must be considered include incidence of tumors, latent period, degree of malignancy, and multiplicity of tumors. The risk of radiation induction of tumors is influenced by the genotype, sex, and age of the patient, the tissues that will be exposed, and previous therapy. With chemotherapy the number of cells at risk is usually markedly higher than with radiation therapy. Clearly the problem of the estimation of comparative risks is complex. This paper presents the current views on the comparative risks and the importance of the various factors that influence the estimation of risk

  15. Coordinated Increased Expression of Cyclooxygenase2 and Nuclear Factor B Is a Steady Feature of Urinary Bladder Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Stylianos Kontos

    2010-01-01

    Full Text Available Objectives. The inescapable relationship between chronic inflammation and carcinogenesis has long been established. Our objective was to investigate COX-2 and NF-B immunohistochemical expression in a large series of normal epithelium and bladder carcinomas. Methods. Immunohistochemical methodology was performed on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients (94 males and 46 females with bladder carcinomas. Results. COX-2 expression is increased in the cytoplasm of bladder cells, during loss of cell differentiation (s=0.61, -value<.001 and in muscle invasive carcinomas (-value<.001. A strong positive association between tumor grade and nuclear expression of NFB has been established. A positive correlation between COX-2 and nuclear NFB immunoreactivity was observed. Conclusions. The possible coordinated upregulation of NFB and COX-2, during bladder carcinogenesis, indicates that agents inhibitors of these two molecules may represent a possible new treatment strategy, by virtue of their role in bladder carcinogenesis.

  16. 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

  17. Chemical respiratory allergy: Reverse engineering an adverse outcome pathway

    International Nuclear Information System (INIS)

    Kimber, Ian; Dearman, Rebecca J.; Basketter, David A.; Boverhof, Darrell R.

    2014-01-01

    Allergic sensitisation of the respiratory tract by chemicals is associated with rhinitis and asthma and remains an important occupational health issue. Although less than 80 chemicals have been confirmed as respiratory allergens the adverse health effects can be serious, and in rare instances can be fatal, and there are, in addition, related socioeconomic issues. The challenges that chemical respiratory allergy pose for toxicologists are substantial. No validated methods are available for hazard identification and characterisation, and this is due in large part to the fact that there remains considerable uncertainty and debate about the mechanisms through which sensitisation of the respiratory tract is acquired. Despite that uncertainty, there is a need to establish some common understanding of the key events and processes that are involved in respiratory sensitisation to chemicals and that might in turn provide the foundations for novel approaches to safety assessment. In recent years the concept of adverse outcome pathways (AOP) has gained some considerable interest among the toxicology community as a basis for outlining the key steps leading to an adverse health outcome, while also providing a framework for focusing future research, and for developing alternative paradigms for hazard characterisation. Here we explore application of the same general principles to an examination of the induction by chemicals of respiratory sensitisation. In this instance, however, we have chosen to adopt a reverse engineering approach and to model a possible AOP for chemical respiratory allergy working backwards from the elicitation of adverse health effects to the cellular and molecular mechanisms that are implicated in the acquisition of sensitisation

  18. Differential Expression of MicroRNAs in Uterine Cervical Cancer and Its Implications in Carcinogenesis; An Integrative Approach.

    Science.gov (United States)

    Nair, Veena B; Manasa, V G; Sinto, M S; Jayasree, K; James, Francis V; Kannan, S

    2018-03-01

    Cervical cancer is the second most common cancer in women in developing countries, including India. Recently, microRNAs (miRNAs) are gaining importance in cancer biology because of their involvement in various cellular processes. The present study aimed to profile miRNA expression pattern in cervical cancer, identify their target genes, and understand their role in carcinogenesis. Human papillomavirus (HPV) infection statuses in samples were assessed by heminested polymerase chain reaction followed by direct DNA sequencing. Next-generation sequencing and miRNA microarray were used for miRNA profiling in cervical cancer cell lines and tissue samples, respectively. MicroRNA signature was validated by quantitative real-time PCR, and biological significance was elucidated using various in silico analyses. Cervical cancer tissues samples were mostly infected by HPV type 16 (93%). MicroRNA profiling showed that the pattern of miRNA expression differed with respect to HPV positivity in cervical cancer cell lines. However, target and pathway analyses indicated identical involvement of these significantly deregulated miRNAs in HPV-positive cervical cancer cell lines irrespective of type of HPV infected. Microarray profiling identified a set of miRNAs that are differentially deregulated in cervical cancer tissue samples which were validated using quantitative real-time PCR. In silico analyses revealed that the signature miRNAs are mainly involved in PI3K-Akt and mTOR pathways. The study identified that high-risk HPV induces similar carcinogenic mechanism irrespective of HPV type. The miRNA signature of cervical cancer and their target genes were also elucidated, thereby providing a better insight into the molecular mechanism underlying cervical cancer development.

  19. Crucial Involvement of Tumor-Associated Neutrophils in the Regulation of Chronic Colitis-Associated Carcinogenesis in Mice

    Science.gov (United States)

    Wang, Chen; Wang, Zhen; Gu, Hong-Yu; Du, Xiang; Zhou, Xiao-Yan; Zheng, Chun-Lei; Chi, Ya-Yun; Mukaida, Naofumi; Li, Ying-Yi

    2012-01-01

    Ulcerative colitis (UC) is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC). However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs) in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM), followed by repeated dextran sulfate sodium (DSS) ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP)-9 and neutrophil elastase (NE), accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2–CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer. PMID:23272179

  20. Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Kun Shang

    Full Text Available Ulcerative colitis (UC is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC. However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM, followed by repeated dextran sulfate sodium (DSS ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP-9 and neutrophil elastase (NE, accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer.

  1. Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: Relevance to human cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Labib, Sarah, E-mail: Sarah.Labib@hc-sc.gc.ca; Guo, Charles H., E-mail: Charles.Guo@hc-sc.gc.ca; Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca; Yauk, Carole L., E-mail: Carole.Yauk@hc-sc.gc.ca; White, Paul A., E-mail: Paul.White@hc-sc.gc.ca; Halappanavar, Sabina, E-mail: Sabina.Halappanavar@hc-sc.gc.ca

    2013-12-01

    Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50, and 75 mg BaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans. - Highlights: • Benzo(a)pyrene-mediated transcriptomic response in the forestomach was examined. • The immunoproteosome subunits and MHC class I

  2. Colon carcinogenesis: influence of Western diet-induced obesity and targeting stem cells using dietary bioactive compounds.

    Science.gov (United States)

    Kasdagly, Maria; Radhakrishnan, Sridhar; Reddivari, Lavanya; Veeramachaneni, D N Rao; Vanamala, Jairam

    2014-01-01

    Colon cancer strikes more than 1 million people annually and is responsible for more than 500,000 cancer deaths worldwide. Recent evidence suggests that the majority of malignancies, including colon cancer are driven by cancer stem cells (CSCs) that are resistant to current chemotherapeutic approaches leading to cancer relapse. Wnt signaling plays a critical role in colon stem cell renewal and carcinogenesis. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a Wnt target gene, and aldehyde dehydrogenase 1 B1 (ALDH1B1) are good markers for normal and malignant human colon stem cells. Diet contributes to 20% to 42% of all human cancers and 50% to 90% of colon cancer. Recent evidence shows that the Western diet has a causative link to colon cancer; however, mechanisms of action are not fully elucidated. Western diet-induced obesity elevates systemic insulin-like growth factor-1 and insulin levels, which could lead to elevated proliferation and suppressed apoptosis of CSCs through PI3K/AKT/Wnt pathway. Although conventional chemotherapy targets the PI3K/AKT pathways and can significantly reduce tumor size, it fails to eliminate CSCs and has serious side effects. Dietary bioactive compounds such as grape seed extract, curcumin, lycopene, and resveratrol have promising chemopreventive effects, without serious side effects on various types of cancers due to their direct and indirect actions on CSC self-renewal pathways such as the Wnt pathway. Understanding the role of CSCs in diet-induced colon cancer will aid in development of evidence-based dietary chemopreventive strategies and/or therapeutic agents targeting CSCs. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. [Respiratory treatments in neuromuscular disease].

    Science.gov (United States)

    Martínez Carrasco, C; Cols Roig, M; Salcedo Posadas, A; Sardon Prado, O; Asensio de la Cruz, O; Torrent Vernetta, A

    2014-10-01

    In a previous article, a review was presented of the respiratory pathophysiology of the patient with neuromuscular disease, as well as their clinical evaluation and the major complications causing pulmonary deterioration. This article presents the respiratory treatments required to preserve lung function in neuromuscular disease as long as possible, as well as in special situations (respiratory infections, spinal curvature surgery, etc.). Special emphasis is made on the use of non-invasive ventilation, which is changing the natural history of many of these diseases. The increase in survival and life expectancy of these children means that they can continue their clinical care in adult units. The transition from pediatric care must be an active, timely and progressive process. It may be slightly stressful for the patient before the adaptation to this new environment, with multidisciplinary care always being maintained. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  4. Macrophage Heterogeneity in Respiratory Diseases

    Directory of Open Access Journals (Sweden)

    Carian E. Boorsma

    2013-01-01

    Full Text Available Macrophages are among the most abundant cells in the respiratory tract, and they can have strikingly different phenotypes within this environment. Our knowledge of the different phenotypes and their functions in the lung is sketchy at best, but they appear to be linked to the protection of gas exchange against microbial threats and excessive tissue responses. Phenotypical changes of macrophages within the lung are found in many respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD, and pulmonary fibrosis. This paper will give an overview of what macrophage phenotypes have been described, what their known functions are, what is known about their presence in the different obstructive and restrictive respiratory diseases (asthma, COPD, pulmonary fibrosis, and how they are thought to contribute to the etiology and resolution of these diseases.

  5. Understanding Maple

    CERN Document Server

    Thompson, Ian

    2016-01-01

    Maple is a powerful symbolic computation system that is widely used in universities around the world. This short introduction gives readers an insight into the rules that control how the system works, and how to understand, fix, and avoid common problems. Topics covered include algebra, calculus, linear algebra, graphics, programming, and procedures. Each chapter contains numerous illustrative examples, using mathematics that does not extend beyond first-year undergraduate material. Maple worksheets containing these examples are available for download from the author's personal website. The book is suitable for new users, but where advanced topics are central to understanding Maple they are tackled head-on. Many concepts which are absent from introductory books and manuals are described in detail. With this book, students, teachers and researchers will gain a solid understanding of Maple and how to use it to solve complex mathematical problems in a simple and efficient way.

  6. Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

    International Nuclear Information System (INIS)

    Takahashi, Mami; Hori, Mika; Mutoh, Michihiro; Wakabayashi, Keiji; Nakagama, Hitoshi

    2011-01-01

    Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5′ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention

  7. STICS, SCOUTs and p53 signatures; a new language for pelvic serous carcinogenesis.

    Science.gov (United States)

    Mehra, Karishma; Mehrad, Mitra; Ning, Geng; Drapkin, Ronny; McKeon, Frank D; Xian, Wa; Crum, Christopher P

    2011-01-01

    The events leading to the most common and most lethal ovarian carcinoma - high grade serous carcinoma - have been poorly understood. However, the detailed pathologic study of asymptomatic women with germ-line BRCA 1 or BRCA2 (BCRA+) mutations has unearthed an early malignancy, serous tubal intraepithelial carcinomas (STIC), which has linked many peritoneal and ovarian serous carcinomas to the fimbria. The distinction between high-grade serous and endometrioid carcinomas continues to narrow, with shared alterations in expression of pTEN, PAX2 and p53. Moreover, the discovery of clonal alterations in p53 in benign tubal epithelium, - p53 signatures - has established a foundation for a serous cancer precursor in the fimbria. We have expanded this concept to include a generic secretory cell outgrowth (SCOUT) in the fallopian tube that is associated with altered PAX2 expression. As the repertoire of gene alterations is expanded and its link to serous carcinogenesis clarified, a cogent pathway to high-grade Mullerian carcinomas will emerge. This will challenge conventional thinking about ovarian carcinogenesis but will provide a new template for studies of ovarian cancer prevention.

  8. Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Mami, E-mail: mtakahas@ncc.go.jp; Hori, Mika; Mutoh, Michihiro [Division of Cancer Development System, Carcinogenesis Research Group, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan); Wakabayashi, Keiji [Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Yada 52-1, Suruga-ku, Shizuoka 422-8526 (Japan); Nakagama, Hitoshi [Division of Cancer Development System, Carcinogenesis Research Group, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan)

    2011-02-09

    Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5′ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.

  9. Gut Microbe-Mediated Suppression of Inflammation-Associated Colon Carcinogenesis by Luminal Histamine Production.

    Science.gov (United States)

    Gao, Chunxu; Ganesh, Bhanu Priya; Shi, Zhongcheng; Shah, Rajesh Rasik; Fultz, Robert; Major, Angela; Venable, Susan; Lugo, Monica; Hoch, Kathleen; Chen, Xiaowei; Haag, Anthony; Wang, Timothy C; Versalovic, James

    2017-10-01

    Microbiome-mediated suppression of carcinogenesis may open new avenues for identification of therapeutic targets and prevention strategies in oncology. Histidine decarboxylase (HDC) deficiency has been shown to promote inflammation-associated colorectal cancer by accumulation of CD11b + Gr-1 + immature myeloid cells, indicating a potential antitumorigenic effect of histamine. Here, we demonstrate that administration of hdc + Lactobacillus reuteri in the gut resulted in luminal hdc gene expression and histamine production in the intestines of Hdc -/- mice. This histamine-producing probiotic decreased the number and size of colon tumors and colonic uptake of [ 18 F]-fluorodeoxyglucose by positron emission tomography in Hdc -/- mice. Administration of L. reuteri suppressed keratinocyte chemoattractant (KC), Il22, Il6, Tnf, and IL1α gene expression in the colonic mucosa and reduced the amounts of proinflammatory, cancer-associated cytokines, keratinocyte chemoattractant, IL-22, and IL-6, in plasma. Histamine-generating L. reuteri also decreased the relative numbers of splenic CD11b + Gr-1 + immature myeloid cells. Furthermore, an isogenic HDC-deficient L. reuteri mutant that was unable to generate histamine did not suppress carcinogenesis, indicating a significant role of the cometabolite, histamine, in suppression of chronic intestinal inflammation and colorectal tumorigenesis. These findings link luminal conversion of amino acids to biogenic amines by gut microbes and probiotic-mediated suppression of colorectal neoplasia. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis

    Science.gov (United States)

    Ro, Seung-Hyun; Xue, Xiang; Ramakrishnan, Sadeesh K; Cho, Chun-Seok; Namkoong, Sim; Jang, Insook; Semple, Ian A; Ho, Allison; Park, Hwan-Woo; Shah, Yatrik M; Lee, Jun Hee

    2016-01-01

    The mTOR complex 1 (mTORC1) and endoplasmic reticulum (ER) stress pathways are critical regulators of intestinal inflammation and colon cancer growth. Sestrins are stress-inducible proteins, which suppress both mTORC1 and ER stress; however, the role of Sestrins in colon physiology and tumorigenesis has been elusive due to the lack of studies in human tissues or in appropriate animal models. In this study, we show that human SESN2 expression is elevated in the colon of ulcerative colitis patients but is lost upon p53 inactivation during colon carcinogenesis. In mouse colon, Sestrin2 was critical for limiting ER stress and promoting the recovery of epithelial cells after inflammatory injury. During colitis-promoted tumorigenesis, Sestrin2 was shown to be an important mediator of p53’s control over mTORC1 signaling and tumor cell growth. These results highlight Sestrin2 as a novel tumor suppressor, whose downregulation can accelerate both colitis and colon carcinogenesis. DOI: http://dx.doi.org/10.7554/eLife.12204.001 PMID:26913956

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Environment and breast cancer - the role of xenooestrogens in breast cancer carcinogenesis

    International Nuclear Information System (INIS)

    Plesnicar, A.; Kralj, B.; Druzina, B.; Kovac, V.

    2002-01-01

    Background. The survival rate of breast cancer patients has not changed much in the last few decades in developed countries. In order to improve the efficacy of breast cancer prevention and treatment, the role of xenooestrogens in the mechanisms of its development has been evaluated. These industrial chemicals bear little structural resemblance to each other and bind to the oestrogen receptors of exposed cells and/or trigger oestrogenic responses in laboratory test systems. Exposure to xenooestrogens has been regarded as a risk factor for carcinogenesis and a preventable cause of breast carcinoma. Several epidemiological and experimental studies in in vivo and in in vitro conditions of the influence of xenooestrogens on the occurrence of breast cancer have been conducted in the last decades and have shown ambiguous results. Conclusions. No increase in breast carcinoma incidence could be found in women who were exposed to relatively high concentrations of xenooestrogens for extended periods and small quantities of these compounds that are present in the environment probably cannot act as etiological agents for the occurrence of this disease. A multi step approach is suggested regarding the sequence of studies and measures that should be taken to further assess the importance of xenooestrogens on breast cancer carcinogenesis. (author)

  13. Evaluation of carcinogenic potential of diuron in a rat mammary two-stage carcinogenesis model.

    Science.gov (United States)

    Grassi, Tony Fernando; Rodrigues, Maria Aparecida Marchesan; de Camargo, João Lauro Viana; Barbisan, Luís Fernando

    2011-04-01

    This study aimed to evaluate the carcinogenic potential of the herbicide Diuron in a two-stage rat medium-term mammary carcinogenesis model initiated by 7,12-dimethylbenz(a)anthracene (DMBA). Female seven-week-old Sprague-Dawley (SD) rats were allocated to six groups: groups G1 to G4 received intragastrically (i.g.) a single 50 mg/kg dose of DMBA; groups G5 and G6 received single administration of canola oil (vehicle of DMBA). Groups G1 and G5 received a basal diet, and groups G2, G3, G4, and G6 were fed the basal diet with the addition of Diuron at 250, 1250, 2500, and 2500 ppm, respectively. After twenty-five weeks, the animals were euthanized and mammary tumors were histologically confirmed and quantified. Tumor samples were also processed for immunohistochemical evaluation of the expressions of proliferating cell nuclear antigen (PCNA), cleaved caspase-3, estrogen receptor-α (ER-α), p63, bcl-2, and bak. Diuron treatment did not increase the incidence or multiplicity of mammary tumors (groups G2 to G4 versus Group G1). Also, exposure to Diuron did not alter tumor growth (cell proliferation and apoptosis indexes) or immunoreactivity to ER-α, p63 (myoephitelial marker), or bcl-2 and bak (apoptosis regulatory proteins). These findings indicate that Diuron does not have a promoting potential on mammary carcinogenesis in female SD rats initiated with DMBA.

  14. Gene Systems Network Inferred from Expression Profiles in Hepatocellular Carcinogenesis by Graphical Gaussian Model

    Directory of Open Access Journals (Sweden)

    Saito Shigeru

    2007-01-01

    Full Text Available Hepatocellular carcinoma (HCC in a liver with advanced-stage chronic hepatitis C (CHC is induced by hepatitis C virus, which chronically infects about 170 million people worldwide. To elucidate the associations between gene groups in hepatocellular carcinogenesis, we analyzed the profiles of the genes characteristically expressed in the CHC and HCC cell stages by a statistical method for inferring the network between gene systems based on the graphical Gaussian model. A systematic evaluation of the inferred network in terms of the biological knowledge revealed that the inferred network was strongly involved in the known gene-gene interactions with high significance , and that the clusters characterized by different cancer-related responses were associated with those of the gene groups related to metabolic pathways and morphological events. Although some relationships in the network remain to be interpreted, the analyses revealed a snapshot of the orchestrated expression of cancer-related groups and some pathways related with metabolisms and morphological events in hepatocellular carcinogenesis, and thus provide possible clues on the disease mechanism and insights that address the gap between molecular and clinical assessments.

  15. [In vitro and in vivo effects of mango pulp (Mangifera indica cv. Azucar) in colon carcinogenesis].

    Science.gov (United States)

    Corrales-Bernal, Andrea; Amparo Urango, Luz; Rojano, Benjamín; Maldonado, Maria Elena

    2014-03-01

    Mango pulp contains ascorbic acid, carotenoids, polyphenols, terpenoids and fiber which are healthy and could protect against colon cancer. The aim of this study was to evaluate the antiproliferative and preventive capacity of an aqueous extract of Mangifera indica cv. Azúcar on a human colon adenocarcinoma cell line (SW480) and in a rodent model of colorectal cancer, respectively. The content of total phenolics, flavonoids and carotenoids were also analyzed in the extract. SW480 cell growth was inhibited in a dose and time dependent manner by 22.3% after a 72h exposure to the extract (200 µg/ mL). Colon carcinogenesis was initiated in Balb/c mice by two intra-peritoneal injections of azoxymethane (AOM) at the third and fourth week of giving mango in drinking water (0.3%, 0.6%, 1.25%). After 10 weeks of treatment, in the colon of mice receiving 0.3% mango, aberrant crypt foci formation was inhibited more than 60% (p=0,05) and the inhibition was dose-dependent when compared with controls receiving water. These results show that mango pulp, a natural food, non toxic, part of human being diet, contains bioactive compounds able to reduce growth of tumor cells and to prevent the appearance of precancerous lesions in colon during carcinogenesis initiation.

  16. Influence of Chronic Moderate Sleep Restriction and Exercise on Inflammation and Carcinogenesis in Mice

    Science.gov (United States)

    Zielinski, Mark R.; Davis, J. Mark; Fadel, James R.; Youngstedt, Shawn D.

    2013-01-01

    The effects of chronic moderate sleep restriction and exercise training on carcinogenesis were examined in adenomatous polyposis coli multiple intestinal neoplasma (APC Min+/-) mice, a genetic strain which is predisposed to developing adenomatous polyposis. The mice were randomized to one of four 11 week treatments in a 2×2 design involving sleep restriction (by 4 h/day) vs. normal sleep and exercise training (1 h/day) vs. sedentary control. Wild-type control mice underwent identical experimental treatments. Compared with the wild-type mice, APC Min+/- mice had disrupted hematology and enhanced pro-inflammatory cytokine production from peritoneal exudate cells. Among the APC Min+/- mice, consistent interactions of sleep loss and exercise were found for measures of polyp formation, inflammation, and hematology. Sleep loss had little effect on these variables under sedentary conditions, but sleep loss had clear detrimental effects under exercise conditions. Exercise training resulted in improvements in these measures under normal sleep conditions, but exercise tended to elicit no effect or to exacerbate the effects of sleep restriction. Significant correlations of inflammation with polyp burden were observed. Among wild-type mice, similar, but less consistent interactions of sleep restriction and exercise were found. These data suggest that the benefits of exercise on carcinogenesis and immune function were impaired by chronic moderate sleep restriction, and that harmful effects of sleep restriction were generally realized only in the presence of exercise. PMID:22433899

  17. Enhancement of broccoli indole glucosinolates by methyl jasmonate treatment and effects on prostate carcinogenesis.

    Science.gov (United States)

    Liu, Ann G; Juvik, John A; Jeffery, Elizabeth H; Berman-Booty, Lisa D; Clinton, Steven K; Erdman, John W

    2014-11-01

    Broccoli is rich in bioactive components, such as sulforaphane and indole-3-carbinol, which may impact cancer risk. The glucosinolate profile of broccoli can be manipulated through treatment with the plant stress hormone methyl jasmonate (MeJA). Our objective was to produce broccoli with enhanced levels of indole glucosinolates and determine its impact on prostate carcinogenesis. Brassica oleracea var. Green Magic was treated with a 250 μM MeJA solution 4 days prior to harvest. MeJA-treated broccoli had significantly increased levels of glucobrassicin, neoglucobrassicin, and gluconasturtiin (P broccoli powder, or 10% MeJA broccoli powder. Diets were fed throughout the study until termination at 20 weeks of age. Hepatic CYP1A was induced with MeJA broccoli powder feeding, indicating biological activity of the indole glucosinolates. Following ∼ 15 weeks on diets, neither of the broccoli treatments significantly altered genitourinary tract weight, pathologic score, or metastasis incidence, indicating that broccoli powder at 10% of the diet was ineffective at reducing prostate carcinogenesis in the TRAMP model. Whereas broccoli powder feeding had no effect in this model of prostate cancer, our work demonstrates the feasibility of employing plant stress hormones exogenously to stimulate changes in phytochemical profiles, an approach that may be useful for optimizing bioactive component patterns in foods for chronic-disease-prevention studies.

  18. Vital-dye-enhanced multimodal imaging of neoplastic progression in a mouse model of oral carcinogenesis

    Science.gov (United States)

    Hellebust, Anne; Rosbach, Kelsey; Wu, Jessica Keren; Nguyen, Jennifer; Gillenwater, Ann; Vigneswaran, Nadarajah; Richards-Kortum, Rebecca

    2013-12-01

    In this longitudinal study, a mouse model of 4-nitroquinoline 1-oxide chemically induced tongue carcinogenesis was used to assess the ability of optical imaging with exogenous and endogenous contrast to detect neoplastic lesions in a heterogeneous mucosal surface. Widefield autofluorescence and fluorescence images of intact 2-NBDG-stained and proflavine-stained tissues were acquired at multiple time points in the carcinogenesis process. Confocal fluorescence images of transverse fresh tissue slices from the same specimens were acquired to investigate how changes in tissue microarchitecture affect widefield fluorescence images of intact tissue. Widefield images were analyzed to develop and evaluate an algorithm to delineate areas of dysplasia and cancer. A classification algorithm for the presence of neoplasia based on the mean fluorescence intensity of 2-NBDG staining and the standard deviation of the fluorescence intensity of proflavine staining was found to separate moderate dysplasia, severe dysplasia, and cancer from non-neoplastic regions of interest with 91% sensitivity and specificity. Results suggest this combination of noninvasive optical imaging modalities can be used in vivo to discriminate non-neoplastic from neoplastic tissue in this model with the potential to translate this technology to the clinic.

  19. Preventive Effects of Fermented Brown Rice and Rice Bran against Prostate Carcinogenesis in TRAP Rats

    Directory of Open Access Journals (Sweden)

    Toshiya Kuno

    2016-07-01

    Full Text Available Fermented brown rice and rice bran with Aspergillus oryzae (FBRA is considered to have the potential to prevent chemically-induced carcinogenesis in multiple organs of rodents. In the present study, we evaluated the possible chemopreventive effects of FBRA against prostate tumorigenesis. Six-week-old male rats of the transgenic rat for adenocarcinoma of prostate (TRAP strain were fed diets containing 5% or 10% FBRA for 15 weeks. Animals were sacrificed at 21 weeks of age, and the ventral and lateral prostate were removed for histopathological evaluation and immunoblot analyses. FBRA decreased the incidence of adenocarcinoma in the lateral prostate and suppressed the progression of prostate carcinogenesis. Treatment with FBRA induced apoptosis and inhibited cell proliferation in histologically high-grade prostatic intraepithelial neoplasias. Phospho-AMP-activated kinase α (Thr172 was up-regulated in the prostate of rats fed the diet supplemented with FBRA. These results indicate that FBRA controls tumor growth by activating pathways responsive to energy deprivation and suggest that FBRA has translational potential for the prevention of human prostate cancer.

  20. Nutraceutical Approach for Preventing Obesity-Related Colorectal and Liver Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Hisataka Moriwaki

    2012-01-01

    Full Text Available Obesity and its related metabolic abnormalities, including insulin resistance, alterations in the insulin-like growth factor-1 (IGF-1/IGF-1 receptor (IGF-1R axis, and the state of chronic inflammation, increase the risk of colorectal cancer (CRC and hepatocellular carcinoma (HCC. However, these findings also indicate that the metabolic disorders caused by obesity might be effective targets to prevent the development of CRC and HCC in obese individuals. Green tea catechins (GTCs possess anticancer and chemopreventive properties against cancer in various organs, including the colorectum and liver. GTCs have also been known to exert anti-obesity, antidiabetic, and anti-inflammatory effects, indicating that GTCs might be useful for the prevention of obesity-associated colorectal and liver carcinogenesis. Further, branched-chain amino acids (BCAA, which improve protein malnutrition and prevent progressive hepatic failure in patients with chronic liver diseases, might be also effective for the suppression of obesity-related carcinogenesis because oral supplementation with BCAA reduces the risk of HCC in obese cirrhotic patients. BCAA shows these beneficial effects because they can improve insulin resistance. Here, we review the detailed relationship between metabolic abnormalities and the development of CRC and HCC. We also review evidence, especially that based on our basic and clinical research using GTCs and BCAA, which indicates that targeting metabolic abnormalities by either pharmaceutical or nutritional intervention may be an effective strategy to prevent the development of CRC and HCC in obese individuals.

  1. Role of Helicobacter pylori infection in gastric carcinogenesis: Current knowledge and future directions

    Science.gov (United States)

    Sokic-Milutinovic, Aleksandra; Alempijevic, Tamara; Milosavljevic, Tomica

    2015-01-01

    Helicobacter pylori (H. pylori) plays a role in the pathogenesis of gastric cancer. The outcome of the infection depends on environmental factors and bacterial and host characteristics. Gastric carcinogenesis is a multistep process that is reversible in the early phase of mucosal damage, but the exact point of no return has not been identified. Therefore, two main therapeutic strategies could reduce gastric cancer incidence: (1) eradication of the already present infection; and (2) immunization (prior to or during the course of the infection). The success of a gastric cancer prevention strategy depends on timing because the prevention strategy must be introduced before the point of no return in gastric carcinogenesis. Although the exact point of no return has not been identified, infection should be eradicated before severe atrophy of the gastric mucosa develops. Eradication therapy rates remain suboptimal due to increasing H. pylori resistance to antibiotics and patient noncompliance. Vaccination against H. pylori would reduce the cost of eradication therapies and lower gastric cancer incidence. A vaccine against H. pylori is still a research challenge. An effective vaccine should have an adequate route of delivery, appropriate bacterial antigens and effective and safe adjuvants. Future research should focus on the development of rescue eradication therapy protocols until an efficacious vaccine against the bacterium becomes available. PMID:26556993

  2. Multistage models of carcinogenesis and their implications for dose-response models and risk projections

    International Nuclear Information System (INIS)

    Hoel, D.G.

    1992-01-01

    Multistage models are used to both describe the biological steps in developing a cancer and as a mathematical description of the relationship of exposure to tumor incidence. With the rapid development of molecular biology the stages of tumor development are becoming understood. Specifically, the effect and role of proto-oncogenes and suppressor genes are exciting developments in the field of carcinogenesis. Mathematically the field has moved from the original Armitage-Doll multistage model to the more current cell kinetic models. These latter models attempt to describe both the rate of cell mutation and the birth-death process involved in clonal expansion. This then allows modeling of both initiation and promotion or cellular proliferation. The field of radiation carcinogenesis has a considerable body of data and knowledge. Unfortunately, relatively little work has been done with the cell kinetic models as to estimation of tumor incidence. This may be due to the newness of kinetic models in general. The field holds promise and it is essential if we are to develop better human risk estimates from exposure to ionizing radiation. (author)

  3. Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis.

    Science.gov (United States)

    Duthie, Susan J

    2011-02-01

    Inappropriate diet may contribute to one third of cancer deaths. Folates, a group of water-soluble B vitamins present in high concentrations in green, leafy vegetables, maintain DNA stability through their ability to donate one-carbon units for cellular metabolism. Folate deficiency has been implicated in the development of several cancers, including cancer of the colorectum, breast, ovary, pancreas, brain, lung and cervix. Generally, data from the majority of human studies suggest that people who habitually consume the highest level of folate, or with the highest blood folate concentrations, have a significantly reduced risk of developing colon polyps or cancer. However, an entirely protective role for folate against carcinogenesis has been questioned, and recent data indicate that an excessive intake of synthetic folic acid (from high-dose supplements or fortified foods) may increase human cancers by accelerating growth of precancerous lesions. Nonetheless, on balance, evidence from the majority of human studies indicates that dietary folate is genoprotective against colon cancer. Suboptimal folate status in humans is widespread. Folate maintains genomic stability by regulating DNA biosynthesis, repair and methylation. Folate deficiency induces and accelerates carcinogenesis by perturbing each of these processes. This review presents recent evidence describing how these mechanisms act, and interact, to modify colon cancer risk.

  4. Aggravation of serum Hepatocyte Growth Factor levels during hepato carcinogenesis in Rats

    International Nuclear Information System (INIS)

    Abdelgawad, M.R.; Ghareeb, N.A.

    2010-01-01

    Hepatocyte growth factor (HGF) has an essential role during liver development and it plays an important role in the regeneration and repair of injured tissues and acting as a mitogen, motogen and morphogens for a variety of epithelial cells. The role of HGF in carcinogenesis is in straggle and so, the present study aimed to through light through the level of HGF during different steps of carcinogenesis. Forty male rats were given diethylnitrosamine (DEN) in drinking water (100 mg/l) for up to 16 weeks. Eight rats were sacrificed at 8, 12 and 16 weeks. Besides, 8 hepatoma bearing rats were exposed to a single dose gamma irradiation (3 Gy) were sacrificed after 2 weeks from exposure (2 rats died, 36 hrs post irradiation) and 8 hepatoma bearing rats were sacrificed after 4 weeks from receiving a combined antioxidant (N-acetylcysteine and Lmethionine). Serum HGF was assayed by enzyme linked immunosorbent assay (ELISA). Serum HGF level in DEN treated rats and in exposed hepatoma bearing rats was significantly higher than in control rats whereas, serum HGF level after treatment with N acetylcysteine and L-methionine for 4 weeks was significantly decreased than DEN treated rats and concluded that serum HGF may play a role during promotion and progression of hepatocellular carcinoma (HCC) and during treatment

  5. Cell Cycle Phase Abnormalities Do Not Account for Disordered Proliferation in Barrett's Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Pierre Lao-Sirieix

    2004-11-01

    Full Text Available Barrett's esophagus (BE epithelium is the precursor lesion for esophageal adenocarcinoma. Cell cycle proteins have been advocated as biomarkers to predict the malignant potential in BE. However, whether disruption of the cell cycle plays a causal role in Barrett's carcinogenesis is not clear. Specimens from the Barrett's dysplasia—carcinoma sequence were immunostained for cell cycle phase markers (cyclin D1 for G1; cyclin A for S, G2, and M; cytoplasmic cyclin B1 for G2; and phosphorylated histone 3 for M phase and expressed as a proportion of proliferating cells. Flow cytometric analysis of the cell cycle phase of prospective biopsies was also performed. The proliferation status of nondysplastic BE was similar to gastric antrum and D2, but the proliferative compartment extended to the luminal surface. In dysplastic samples, the number of proliferating cells correlated with the degree of dysplasia (P < .001. The overall levels of cyclins A and B1 correlated with the degree of dysplasia (P < .001. However, the cell cycle phase distribution measured with both immunostaining and flow cytometry was conserved during all stages of BE, dysplasia, and cancer. Hence, the increased proliferation seen in Barrett's carcinogenesis is due to abnormal cell cycle entry or exit, rather than a primary abnormality within the cell cycle.

  6. A20 restricts wnt signaling in intestinal epithelial cells and suppresses colon carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Ling Shao

    Full Text Available Colon carcinogenesis consists of a multistep process during which a series of genetic and epigenetic adaptations occur that lead to malignant transformation. Here, we have studied the role of A20 (also known as TNFAIP3, a ubiquitin-editing enzyme that restricts NFκB and cell death signaling, in intestinal homeostasis and tumorigenesis. We have found that A20 expression is consistently reduced in human colonic adenomas than in normal colonic tissues. To further investigate A20's potential roles in regulating colon carcinogenesis, we have generated mice lacking A20 specifically in intestinal epithelial cells and interbred these with mice harboring a mutation in the adenomatous polyposis coli gene (APC(min. While A20(FL/FL villin-Cre mice exhibit uninflamed intestines without polyps, A20(FL/FL villin-Cre APC(min/+ mice contain far greater numbers and larger colonic polyps than control APC(min mice. We find that A20 binds to the β-catenin destruction complex and restricts canonical wnt signaling by supporting ubiquitination and degradation of β-catenin in intestinal epithelial cells. Moreover, acute deletion of A20 from intestinal epithelial cells in vivo leads to enhanced expression of the β-catenin dependent genes cyclinD1 and c-myc, known promoters of colon cancer. Taken together, these findings demonstrate new roles for A20 in restricting β-catenin signaling and preventing colon tumorigenesis.

  7. Chemopreventive effects of nobiletin and its colonic metabolites on colon carcinogenesis.

    Science.gov (United States)

    Wu, Xian; Song, Mingyue; Wang, Minqi; Zheng, Jinkai; Gao, Zili; Xu, Fei; Zhang, Guodong; Xiao, Hang

    2015-12-01

    Nobiletin (NBT) is a major citrus flavonoid with various health benefits. Herein, we investigated the colon cancer chemopreventive effects of NBT and its colonic metabolites in a colitis-associated colon carcinogenesis mouse model as well as in human colon cancer cell models. In azoxymethane/dextran sulfate sodium treated mice, oral administration of NBT effectively decreased both incidence and multiplicity of colonic tumors. NBT showed significant antiproliferative, proapoptotic, and anti-inflammatory effects in the mouse colon. HPLC analysis revealed that oral administration of NBT resulted in high levels of metabolites, i.e. 3'-demethylnobiletin (M1), 4'-demethylnobiletin (M2), and 3',4'-didemethylnobiletin (M3) in the colonic mucosa. In contrast, the colonic level of NBT was about 20-fold lower than the total colonic level of three metabolites. Cell culture studies demonstrated that the colonic metabolites of NBT significantly inhibited the growth of human colon cancer cells, caused cell-cycle arrest, induced apoptosis, and profoundly modulated signaling proteins related with cell proliferation and cell death. All of these effects were much stronger than those produced by NBT alone. Our results demonstrated that oral administration of NBT significantly inhibited colitis-associated colon carcinogenesis in mice, and this chemopreventive effect was strongly associated with its colonic metabolites. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

    Directory of Open Access Journals (Sweden)

    Hitoshi Nakagama

    2011-02-01

    Full Text Available Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropylamine (BOP into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5’ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.

  9. Experimental animal models of pancreatic carcinogenesis for prevention studies and their relevance to human disease.

    Science.gov (United States)

    Takahashi, Mami; Hori, Mika; Mutoh, Michihiro; Wakabayashi, Keiji; Nakagama, Hitoshi

    2011-02-09

    Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5' CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.

  10. Respiratory distress in the newborn.

    Science.gov (United States)

    Reuter, Suzanne; Moser, Chuanpit; Baack, Michelle

    2014-10-01

    Respiratory distress presents as tachypnea, nasal flaring, retractions, and grunting and may progress to respiratory failure if not readily recognized and managed. Causes of respiratory distress vary and may not lie within the lung. A thorough history, physical examination, and radiographic and laboratory findings will aid in the differential diagnosis. Common causes include transient tachypnea of the newborn, neonatal pneumonia, respiratory distress syndrome (RDS), and meconium aspiration syndrome (MAS). Strong evidence reveals an inverse relationship between gestational age and respiratory morbidity. (1)(2)(9)(25)(26) Expert opinion recommends careful consideration about elective delivery without labor at less than 39 weeks’ gestation. Extensive evidence, including randomized control trials, cohort studies, and expert opinion, supports maternal group B streptococcus screening, intrapartum antibiotic prophylaxis, and appropriate followup of high-risk newborns according to guidelines established by the Centers for Disease Control and Prevention. (4)(29)(31)(32)(34) Following these best-practice strategies is effective in preventing neonatal pneumonia and its complications. (31)(32)(34). On the basis of strong evidence, including randomized control trials and Cochrane Reviews, administration of antenatal corticosteroids (5) and postnatal surfactant (6) decrease respiratory morbidity associated with RDS. Trends in perinatal management strategies to prevent MAS have changed. There is strong evidence that amnioinfusion, (49) oropharyngeal and nasopharyngeal suctioning at the perineum, (45) or intubation and endotracheal suctioning of vigorous infants (46)(47) do not decrease MAS or its complications. Some research and expert opinion supports endotracheal suctioning of nonvigorous meconium-stained infants (8) and induction of labor at 41 weeks’ gestation (7) to prevent MAS.

  11. Understanding physics

    CERN Document Server

    Mansfield, Michael

    2011-01-01

    Understanding Physics - Second edition is a comprehensive, yet compact, introductory physics textbook aimed at physics undergraduates and also at engineers and other scientists taking a general physics course. Written with today's students in mind, this text covers the core material required by an introductory course in a clear and refreshing way. A second colour is used throughout to enhance learning and understanding. Each topic is introduced from first principles so that the text is suitable for students without a prior background in physics. At the same time the book is designed to enable

  12. Modelling carcinogenesis after radiotherapy using Poisson statistics: implications for IMRT, protons and ions.

    Science.gov (United States)

    Jones, Bleddyn

    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

  13. Synthetic cannabis and respiratory depression.

    Science.gov (United States)

    Jinwala, Felecia N; Gupta, Mayank

    2012-12-01

    In recent years, synthetic cannabis use has been increasing in appeal among adolescents, and its use is now at a 30 year peak among high school seniors. The constituents of synthetic cannabis are difficult to monitor, given the drug's easy accessibility. Currently, 40 U.S. states have banned the distribution and use of some known synthetic cannabinoids, and have included these drugs in the Schedule I category. The depressive respiratory effect in humans caused by synthetic cannabis inhalation has not been thoroughly investigated in the medical literature. We are the first to report, to our knowledge, two cases of self-reported synthetic cannabis use leading to respiratory depression and necessary intubation.

  14. Protective roles of free avian respiratory macrophages in captive birds

    Directory of Open Access Journals (Sweden)

    Mbuvi P. Mutua

    Full Text Available In the mammalian lung, respiratory macrophages provide front line defense against invading pathogens and particulate matter. In birds, respiratory macrophages are known as free avian respiratory macrophages (FARM and a dearth of the cells in the avian lung has been purported to foreordain a weak first line of pulmonary defense, a condition associated with high mortality of domestic birds occasioned by respiratory inflictions. Avian pulmonary mechanisms including a three tiered aerodynamic filtration system, tight epithelial junctions and an efficient mucociliary escalator system have been known to supplement FARM protective roles. Current studies, however, report FARM to exhibit an exceptionally efficient phagocytic capacity and are effective in elimination of invading pathogens. In this review, we also report on effects of selective synthetic peroxisome proliferator activated receptor gamma (PPAR γ agonists on non phlogistic phagocytic properties in the FARM. To develop effective therapeutic interventions targeting FARM in treatment and management of respiratory disease conditions in the poultry, further studies are required to fully understand the role of FARM in innate and adaptive immune responses.

  15. Understanding Energy

    Science.gov (United States)

    Menon, Deepika; Shelby, Blake; Mattingly, Christine

    2016-01-01

    "Energy" is a term often used in everyday language. Even young children associate energy with the food they eat, feeling tired after playing soccer, or when asked to turn the lights off to save light energy. However, they may not have the scientific conceptual understanding of energy at this age. Teaching energy and matter could be…

  16. Bovine respiratory disease research (1983-2009).

    Science.gov (United States)

    Fulton, Robert W

    2009-12-01

    Bovine respiratory disease (BRD) research has provided significant understanding of the disease over the past 26 years. Modern research tools that have been used include monoclonal antibodies, genomics, polymerase chain reaction, immunohistochemistry (IHC), DNA vaccines and viral vectors coding for immunogens. Emerging/reemerging viruses and new antigenic strains of viruses and bacteria have been identified. Methods of detection and the role for cattle persistently infected bovine viral diarrhea virus (BVDV) were identified; viral subunits, cellular components and bacterial products have been characterized. Product advances have included vaccines for bovine respiratory syncytial virus, Mannheimia haemolytica and Pasteurella multocida; the addition of BVDV2 to the existing vaccines and new antibiotics. The role of Mycoplasma spp., particularly Mycoplasma bovis in BRD, has been more extensively studied. Bovine immunology research has provided more specific information on immune responses, T cell subsets and cytokines. The molecular and genetic basis for viral-bacterial synergy in BRD has been described. Attempts have been made to document how prevention of BRD by proper vaccination and management prior to exposure to infectious agents can minimize disease and serve as economic incentives for certified health programs.

  17. Neuromuscular disease and respiratory physiology in children: putting lung function into perspective.

    Science.gov (United States)

    Fauroux, Brigitte; Khirani, Sonia

    2014-08-01

    Neuromuscular diseases represent a heterogeneous group of disorders of the muscle, nerve or neuromuscular junction. The respiratory muscles are rarely spared in neuromuscular diseases even if the type of muscle involvement, severity and time course greatly varies among the different diseases. Diagnosis of respiratory muscle weakness is crucial because of the importance of respiratory morbidity and mortality. Presently, routine respiratory evaluation is based on non-invasive volitional tests, such as the measurement of lung volumes, spirometry and the maximal static pressures, which may be difficult or impossible to obtain in some young children. Other tools or parameters are thus needed to assess the respiratory muscle weakness and its consequences in young children. The measurement of oesogastric pressures can be helpful as they allow the diagnosis and quantification of paradoxical breathing, as well as the assessment of the strength of the inspiratory and expiratory muscles by means of the oesophageal pressure during a maximal sniff and of the gastric pressure during a maximal cough. Sleep assessment should also be part of the respiratory evaluation of children with neuromuscular disease with at least the recording of nocturnal gas exchange if polysomnography is not possible or unavailable. This improvement in the assessment of respiratory muscle performance may increase our understanding of the respiratory pathophysiology of the different neuromuscular diseases, improve patient care, and guide research and innovative therapies by identifying and validating respiratory parameters. © 2014 Asian Pacific Society of Respirology.

  18. Climate change and respiratory health.

    Science.gov (United States)

    Gerardi, Daniel A; Kellerman, Roy A

    2014-10-01

    To discuss the nature of climate change and both its immediate and long-term effects on human respiratory health. This review is based on information from a presentation of the American College of Chest Physicians course on Occupational and Environmental Lung Disease held in Toronto, Canada, June 2013. It is supplemented by a PubMed search for climate change, global warming, respiratory tract diseases, and respiratory health. It is also supplemented by a search of Web sites including the Environmental Protection Agency, National Oceanic and Atmospheric Administration, World Meteorological Association, National Snow and Ice Data Center, Carbon Dioxide Information Analysis Center, Inter-Governmental Panel on Climate Change, and the World Health Organization. Health effects of climate change include an increase in the prevalence of certain respiratory diseases, exacerbations of chronic lung disease, premature mortality, allergic responses, and declines in lung function. Climate change, mediated by greenhouse gases, causes adverse health effects to the most vulnerable patient populations-the elderly, children, and those in distressed socioeconomic strata.

  19. Guide to industrial respiratory protection

    International Nuclear Information System (INIS)

    Pritchard, J.A.

    1977-03-01

    The Occupational Safety and Health Act of 1970 has increased the emphasis on proper selection and use of respirators in situations where engineering controls are not feasible or are being implemented. Although a great deal of information on respiratory protection has been published, most of it is more technical than necessary for the average user faced with day-to-day problems of respiratory protection in industrial environments. This Guide is to provide the industrial user a single reference source containing enough information for establishing and maintaining a respirator program that meets the OSHA requirements outlined in 29 CFR Part 1910.134. It includes chapters on respirator selection, use, maintenance, and inspection, a complete description of all types of respirators and their advantages and limitations, and chapters on respirator fitting and wearer training, respiratory physiology, respiratory hazards, and physiological and psychological limitations. Also included are samples of the decision logic used in respirator selection, guidance on setting up an adequate respirator program through formulation of written standard operating procedures, and discussion of the meaning of the approved respirator

  20. Respiratory arrest in subarachnoid hemorrhage

    NARCIS (Netherlands)

    Hijdra, A.; Vermeulen, M.; van Gijn, J.; van Crevel, H.

    1984-01-01

    Sudden loss of consciousness and cardiorespiratory disorders occurred in 43 of 254 patients with subarachnoid hemorrhage. Two patients had ventricular fibrillation, 37 had one or more episodes with a disturbance of respiratory rhythm that required assisted ventilation, and 4 died suddenly without

  1. Severe Acute Respiratory Syndrome- SARS

    Indian Academy of Sciences (India)

    Table of contents. Severe Acute Respiratory Syndrome- SARS · PowerPoint Presentation · Slide 3 · Global pattern of SARS epidemic · Slide 5 · SARS – clinical features · Radiological features of lungs-showing progression of disease · cT Scan of SARS lungs · Imaging type,cost,therapy · SARS – Lung Pathology.

  2. Respiratory effects of borax dust.

    Science.gov (United States)

    Garabrant, D H; Bernstein, L; Peters, J M; Smith, T J; Wright, W E

    1985-12-01

    The relation of respiratory symptoms, pulmonary function, and abnormalities of chest radiographs to estimated exposures of borax dust has been investigated in a cross sectional study of 629 actively employed borax workers. Ninety three per cent of the eligible workers participated in the study and exposures ranged from 1.1 mg/m3 to 14.6 mg/m3. Symptoms of acute respiratory irritation such as dryness of the mouth, nose, or throat, dry cough, nose bleeds, sore throat, productive cough, shortness of breath, and chest tightness were related to exposures of 4.0 mg/m3 or more, and were infrequent at exposures of 1.1 mg/m3. Symptoms of persistent respiratory irritation meeting the definition of chronic simple bronchitis were related to exposure among non-smokers. Decrements in the FEV1 as a percentage of predicted were seen among smokers who had heavy cumulative borax exposures (greater than or equal to 80 mg/m3 years) but were not seen among less exposed smokers or among non-smokers. Radiographic abnormalities were uncommon and were not related to dust exposure. Borax dust appears to act as a simple respiratory irritant and perhaps causes small changes in the FEV1 among smokers who are heavily exposed.

  3. Understanding translation

    DEFF Research Database (Denmark)

    Schjoldager, Anne Gram; Gottlieb, Henrik; Klitgård, Ida

    Understanding Translation is designed as a textbook for courses on the theory and practice of translation in general and of particular types of translation - such as interpreting, screen translation and literary translation. The aim of the book is to help you gain an in-depth understanding...... of the phenomenon of translation and to provide you with a conceptual framework for the analysis of various aspects of professional translation. Intended readers are students of translation and languages, but the book will also be relevant for others who are interested in the theory and practice of translation...... - translators, language teachers, translation users and literary, TV and film critics, for instance. Discussions focus on translation between Danish and English....

  4. Understanding Resilience

    Directory of Open Access Journals (Sweden)

    Gang eWu

    2013-02-01

    Full Text Available Resilience is the ability to adapt successfully in the face of stress and adversity. Stressful life events, trauma and chronic adversity can have a substantial impact on brain function and structure, and can result in the development of PTSD, depression and other psychiatric disorders. However, most individuals do not develop such illnesses after experiencing stressful life events, and are thus thought to be resilient. Resilience as successful adaptation relies on effective responses to environmental challenges and ultimate resistance to the deleterious effects of stress, therefore a greater understanding of the factors that promote such effects is of great relevance. This review focuses on recent findings regarding genetic, epigenetic, developmental, psychosocial and neurochemical factors that are considered essential contributors to the development of resilience. Neural circuits and pathways involved in mediating resilience are also discussed. The growing understanding of resilience factors will hopefully lead to the development of new pharmacological and psychological interventions for enhancing resilience and mitigating the untoward consequences.

  5. Understand electronics

    CERN Document Server

    Bishop, Owen

    2013-01-01

    Understand Electronics provides a readable introduction to the exciting world of electronics for the student or enthusiast with little previous knowledge. The subject is treated with the minimum of mathematics and the book is extensively illustrated.This is an essential guide for the newcomer to electronics, and replaces the author's best-selling Beginner's Guide to Electronics.The step-by-step approach makes this book ideal for introductory courses such as the Intermediate GNVQ.

  6. Understanding users

    DEFF Research Database (Denmark)

    Johannsen, Carl Gustav Viggo

    2014-01-01

    Segmentation of users can help libraries in the process of understanding user similarities and differences. Segmentation can also form the basis for selecting segments of target users and for developing tailored services for specific target segments. Several approaches and techniques have been...... segmentation project using computer-generated clusters. Compared to traditional marketing texts, this article also tries to identify user segments or images or metaphors by the library profession itself....

  7. Understanding unemployment

    OpenAIRE

    Guillaume Rocheteau

    2006-01-01

    Modern economists have built models of the labor market, which isolate the market’s key drivers and describe the way these interact to produce particular levels of unemployment. One of the most popular models used by macroeconomists today is the search-matching model of equilibrium unemployment. We explain this model, and show how it can be applied to understand the way various policies, such as unemployment benefits, taxes, or technological changes, can affect the unemployment rate.

  8. Climate Change Effects on Respiratory Health: Implications for Nursing.

    Science.gov (United States)

    George, Maureen; Bruzzese, Jean-Marie; Matura, Lea Ann

    2017-11-01

    Greenhouse gases are driving climate change. This article explores the adverse health effects of climate change on a particularly vulnerable population: children and adults with respiratory conditions. This review provides a general overview of the effects of increasing temperatures, extreme weather, desertification, and flooding on asthma, chronic obstructive lung disease, and respiratory infections. We offer suggestions for future research to better understand climate change hazards, policies to support prevention and mitigation efforts targeting climate change, and clinical actions to reduce individual risk. Climate change produces a number of changes to the natural and built environments that may potentially increase respiratory disease prevalence, morbidity, and mortality. Nurses might consider focusing their research efforts on reducing the effects of greenhouse gases and in directing policy to mitigate the harmful effects of climate change. Nurses can also continue to direct educational and clinical actions to reduce risks for all populations, but most importantly, for our most vulnerable groups. While advancements have been made in understanding the impact of climate change on respiratory health, nurses can play an important role in reducing the deleterious effects of climate change. This will require a multipronged approach of research, policy, and clinical action. © 2017 Sigma Theta Tau International.

  9. Understanding Technology?

    Directory of Open Access Journals (Sweden)

    Erik Bendtsen

    2016-11-01

    Full Text Available We are facing radical changes in our ways of living in the nearest future. Not necessarily of our own choice, but because tchnological development is moving so fast, that it will have still greater impact on many aspects of our lives. We have seen the beginnings of that change within the latest 35 years or so, but according to newest research that change will speed up immensely in the nearest years to come. The impact of that change or these changes will affect our working life immensely as a consequence of automation. How these changes are brought about and which are their consequences in a broad sense is being attempted to be understood and guessed by researchers. No one knows for sure, but specific patterns are visible. This paper will not try to guess, what will come, but will rather try to understand the deepest ”nature” of technology in order to understand the driving factors in this development: the genesis of technology in a broad sense in order to contibute to the understanding of the basis for the expected development.

  10. Hypoxia-inducible factor 1 alpha expression increases during colorectal carcinogenesis and tumor progression

    International Nuclear Information System (INIS)

    Simiantonaki, Nektaria; Taxeidis, Marios; Jayasinghe, Caren; Kurzik-Dumke, Ursula; Kirkpatrick, Charles James

    2008-01-01

    Hypoxia-inducible factor 1 alpha (HIF-1α) is involved in processes promoting carcinogenesis of many tumors. However, its role in the development of colorectal cancer is unknown. To investigate the significance of HIF-1α during colorectal carcinogenesis and progression we examined its expression in precursor lesions constituting the conventional and serrated pathways, as well as in non-metastatic and metastatic adenocarcinomas. Immunohistochemistry and Western blot is used to analyse HIF-1α expression in normal colonic mucosa, hyperplastic polyps (HPP), sessile serrated adenomas (SSA), low-grade (TA-LGD) and high-grade (TA-HGD) traditional adenomas as well as in non-metastatic and metastatic colorectal adenocarcinomas. Eight colorectal carcinoma cell lines are tested for their HIF-1α inducibility after lipopolysaccharide (LPS) stimulation using western blot and immunocytochemistry. In normal mucosa, HPP and TA-LGD HIF-1α was not expressed. In contast, perinuclear protein accumulation and nuclear expression of HIF-1α were shown in half of the examined SSA and TA-HGD. In all investigated colorectal carcinomas a significant nuclear HIF-1α overexpression compared to the premalignant lesions was observed but a significant correlation with the metastatic status was not found. Nuclear HIF-1α expression was strongly accumulated in perinecrotic regions. In these cases HIF-1α activation was seen in viable cohesive tumor epithelia surrounding necrosis and in dissociated tumor cells, which subsequently die. Enhanced distribution of HIF-1α was also seen in periiflammatory regions. In additional in vitro studies, treatment of diverse colorectal carcinoma cell lines with the potent pro-inflammatory factor lipopolysaccharide (LPS) led to HIF-1α expression and nuclear translocation. We conclude that HIF-1α expression occurs in early stages of colorectal carcinogenesis and achieves a maximum in the invasive stage independent of the metastatic status. Perinecrotic

  11. Inactivation of JNK2 as carcinogenic factor in colitis-associated and sporadic colorectal carcinogenesis.

    Science.gov (United States)

    Lessel, Wiebke; Silver, Andrew; Jechorek, Doerthe; Guenther, Thomas; Roehl, Friedrich-Wilhelm; Kalinski, Thomas; Roessner, Albert; Poehlmann-Nitsche, Angela

    2017-05-01

    We recently reported that dysregulated c-Jun N-terminal kinases (JNK) activity causes defective cell cycle checkpoint control, inducing neoplastic transformation in a cellular ulcerative colitis (UC) model. In the quiescent chronic phase of UC, p-p54 JNK was down-regulated and p-p46 JNK was up-regulated. Both were up-regulated in the acute phase. Consequently, increased p21WAF1 and γ-H2AX, two JNK-regulated proteins, induced cell cycle arrest. Their down-regulation led to checkpoint override, causing increased proliferation and undetected DNA damage in quiescent chronic phase, all characteristics of tumorigenesis. We investigated expression of p-JNK2, p-JNK1-3, p21WAF1, γ-H2AX and Ki67 by immunohistochemistry in cases of quiescent UC (QUC), active UC (AUC), UC-dysplasia and UC-related colorectal carcinoma (UC-CRC). Comparison was made to normal healthy colorectal mucosa, sporadic adenoma and colorectal carcinoma (CRC), diverticulitis and Crohns disease (CD). We found p-JNK2 up-regulation in AUC and its early down-regulation in UC-CRC and CRC carcinogenesis. With down-regulated p-JNK2, p21WAF1 was also decreased. Ki67 was inversely expressed, showing increased proliferation early in UC-CRC and CRC carcinogenesis. p-JNK1-3 was increased in AUC and QUC. Less increased γ-H2AX in UC-CRC compared to CRC gave evidence that colitis-triggered inflammation masks DNA damage, thus contributing to neoplastic transformation. We hypothesize that JNK-dependent cell cycle arrest is important in AUC, while chronic inflammation causes dysregulated JNK activity in quiescent phase that may contribute to checkpoint override, promoting UC carcinogenesis. We suggest restoring p-JNK2 expression as a novel therapeutic strategy to early prevent the development of UC-related cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Post-anaesthetic Respiratory Complaints Following Endotracheal ...

    African Journals Online (AJOL)

    Background: Postanaesthetic respiratory complications represent a significant negative aspect of surgical care. Objective: To assess the incidence and possible associated risk factors for postanaesthestic respiratory complaints following endotracheal anaesthesia in lower abdominal surgery in obstetric and gynecology ...

  13. Cystic Fibrosis (CF) Respiratory Screen: Sputum

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Cystic Fibrosis (CF) Respiratory Screen: Sputum KidsHealth / For Parents / Cystic Fibrosis (CF) Respiratory Screen: Sputum What's in this article? ...

  14. [Respiratory diseases in metallurgy production workers].

    Science.gov (United States)

    Shliapnikov, D M; Vlasova, E M; Ponomareva, T A

    2012-01-01

    The authors identified features of respiratory diseases in workers of various metallurgy workshops. Cause-effect relationships are defined between occupational risk factors and respiratory diseases, with determining the affection level.

  15. Coal Mining-Related Respiratory Diseases

    Science.gov (United States)

    ... Topics Publications and Products Programs Contact NIOSH NIOSH COAL WORKERS' HEALTH SURVEILLANCE PROGRAM Recommend on Facebook Tweet Share Compartir Coal Mining-Related Respiratory Diseases Coal mining-related respiratory ...

  16. Acute respiratory infections in young Ethiopian children

    Directory of Open Access Journals (Sweden)

    Harris RA

    2015-07-01

    Full Text Available Rebecca Arden HarrisDepartment of Family and Social Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USAThe identification of risk factors for acute respiratory infections (ARI is crucial for designing interventions to both minimize transmission and augment the immune response, particularly in Sub-Saharan Africa where poverty-related ARI is still a major cause of preventable death in young children.1 I therefore read with interest Geberetsadik et al’s recent study of the factors associated with ARI in Ethiopian children.2 Their study uses nationally representative data on households and individuals to build a model of the social, demographic, and anthropometric determinants of ARI. A precise understanding of their model, however, requires clarification of several items in their paper.View original paper by Geberetsadik et al.

  17. Physiology of respiratory disturbances in muscular dystrophies

    OpenAIRE

    Lo Mauro, Antonella; Aliverti, Andrea

    2016-01-01

    Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e. when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles an...

  18. Vitamin D3Produced by Skin Exposure to UVR Inhibits Murine Basal Cell Carcinoma Carcinogenesis.

    Science.gov (United States)

    Makarova, Anastasia; Wang, Grace; Dolorito, John A; Kc, Subheksha; Libove, Eileen; Epstein, Ervin H

    2017-12-01

    The effect of UVR on human basal cell carcinoma (BCC) epidemiology is complex-the incidence rises until approximately 30,000 hours of lifetime sunlight exposure and then plateaus. We hypothesize that UVR has opposing effects on BCC carcinogenesis-stimulatory via mutagenesis and inhibitory via production of hedgehog-inhibiting vitamin D 3 (D 3 ). We find that UVR exposure of ionizing radiation-treated Ptch1 +/- mice accelerates BCC carcinogenesis in male mice, in which UVR does not produce D 3 . By contrast, in female mice, in which UVR does produce D 3 , UVR fails to accelerate BCC carcinogenesis, thus mirroring the plateauing in humans. However, if D 3 production is attenuated in female mice by deletion of keratinocyte lathosterol 5-desaturase, then UVR accelerates ionizing radiation-induced BCC carcinogenesis. Congruently, chronic topical application of D 3 inhibits ionizing radiation-induced BCC tumorigenesis. These findings confirm that UVR-induced production of D 3 in keratinocytes significantly restrains murine BCC tumorigenesis and demonstrate the counterintuitive conclusion that UVR has anti-BCC carcinogenic effects that can explain, at least in part, the complex relationship between exposure to UVR and BCC incidence. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Cytochrome P450 2E1 inhibition prevents hepatic carcinogenesis induced by diethylnitrosamine in alcohol-fed rats

    Science.gov (United States)

    Chronic alcohol ingestion increases hepatic cytochrome P450 2E1 (CYP2E1), which is associated with hepatocarcinogenesis. We investigated whether treatment with chlormethiazole (CMZ), a CYP2E1 inhibitor, protects against alcohol-associated hepatic carcinogenesis in rats. Rats were fed either an ethan...

  20. Effects of long term feeding of raw soya bean flour on virus- induced pancreatic carcinogenesis in guinea fowl

    NARCIS (Netherlands)

    Kirev, T.; Woutersen, R.A.; Kiril, A.

    1999-01-01

    The effects of a diet enriched with 25% raw soya bean flour (RSF) on the pancreas and on the avian retrovirus Pts 56-induced pancreatic carcinogenesis in guinea fowl were studied. It has been shown that prolonged RSF feeding of new-hatched virus-infected and uninfected guinea fowl-poults induced

  1. No evidence for functional inactivation of wild-type p53 protein by MDM2 overexpression in gastric carcinogenesis

    NARCIS (Netherlands)

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

    1998-01-01

    Inactivation of wild-type p53 during gastric carcinogenesis is usually caused by mutations within exons 5-8 of the p53 gene leading to mutated, usually immunohistochemically detectable p53 proteins. However, functional inactivation of wild-type p53, mimicking mutational inactivation, may also result

  2. p21(Waf1/Cip1) expression and the p53/MDM2 feedback loop in gastric carcinogenesis

    NARCIS (Netherlands)

    Craanen, M. E.; Blok, P.; Offerhaus, G. J.; Meijer, G. A.; Dekker, W.; Kuipers, E. J.; Meuwissen, S. G.

    1999-01-01

    Data are non-existent regarding coincidental alterations in the expression of p53 and its downstream target genes MDM2 and p21(Waf1/Cip1) in gastric carcinogenesis. An immunohistochemical study was therefore performed to examine the interrelationships of p53, MDM2, and p21(Waf1/Cip1) expression in a

  3. Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. I. Common molecular mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Borg, D.C.

    1984-01-01

    Some aspects of molecular mechanisms common to radiation and chemical carcinogenesis are discussed, particularly the DNA damage done by these agents. Emphasis is placed on epidemiological considerations and on dose-response models used in risk assessment to extrapolate from experimental data obtained at high doses to the effects from long-term, low-level exposures. 3 references, 6 figures. (ACR)

  4. Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. I. Common molecular mechanisms

    International Nuclear Information System (INIS)

    Borg, D.C.

    1984-01-01

    Some aspects of molecular mechanisms common to radiation and chemical carcinogenesis are discussed, particularly the DNA damage done by these agents. Emphasis is placed on epidemiological considerations and on dose-response models used in risk assessment to extrapolate from experimental data obtained at high doses to the effects from long-term, low-level exposures. 3 references, 6 figures

  5. Understanding uncertainty

    CERN Document Server

    Lindley, Dennis V

    2013-01-01

    Praise for the First Edition ""...a reference for everyone who is interested in knowing and handling uncertainty.""-Journal of Applied Statistics The critically acclaimed First Edition of Understanding Uncertainty provided a study of uncertainty addressed to scholars in all fields, showing that uncertainty could be measured by probability, and that probability obeyed three basic rules that enabled uncertainty to be handled sensibly in everyday life. These ideas were extended to embrace the scientific method and to show how decisions, containing an uncertain element, could be rationally made.

  6. Effects of Aging on the Respiratory System.

    Science.gov (United States)

    Levitzky, Michael G.

    1984-01-01

    Relates alterations in respiratory system functions occurring with aging to changes in respiratory system structure during the course of life. Main alterations noted include loss of alveolar elastic recoil, alteration in chest wall structure and decreased respiratory muscle strength, and loss of surface area and changes in pulmonary circulation.…

  7. BIOLOGY OF HUMAN RESPIRATORY SYNCYTIAL VIRUS: A ...

    African Journals Online (AJOL)

    DR. AMINU

    information about its biology which may be useful to the present and future researchers. Key words: Respiratory virus, Human Respiratory syncytial virus, biology, genome, epidemiology, immunity. INTRODUCTION. Acute lower ..... of respiratory infections in bone marrow transplant. Pneumonia develops in about one-half of ...

  8. Tobacco Smoke: Involvement of Reactive Oxygen Species and Stable Free Radicals in Mechanisms of Oxidative Damage, Carcinogenesis and Synergistic Effects with Other Respirable Particles

    Directory of Open Access Journals (Sweden)

    Konstantinos Fiotakis

    2009-02-01

    Full Text Available Tobacco smoke contains many toxic, carcinogenic and mutagenic chemicals, as well as stable and unstable free radicals and reactive oxygen species (ROS in the particulate and the gas phase with the potential for biological oxidative damage. Epidemiological evidence established that smoking is one of the most important extrinsic factor of premature morbidity and mortality. The objective of this study was to investigate oxidative and carcinogenic mechanisms of tobacco and synergistic action with other respirable particles in the respiratory system of smokers. Electron Paramagnetic Resonance (EPR and spin- trapping techniques were used to study stable free radicals in the cigarette tar, and unstable superoxide anion (O2·- and hydroxyl (HO· radicals in the smoke Results showed that the semiquinone radical system has the potential for redox recycling and oxidative action. Further, results proved that aqueous cigarette tar (ACT solutions can generate adducts with DNA nucleobases, particularly the mutagenic 8-hydroxy-2’-deoxyguanosine (a biomarker for carcinogenesis.Also, we observed synergistic effects in the generation of HO·, through the Fenton reaction, with environmental respirable particles (asbestos fibres, coal dust, etc. and ambient particulate matter (PM, such as PM10, PM2.5 and diesel exhaust particles (DEP. The highest synergistic effects was observed with the asbestos fibres (freshly grounded, PM2.5 and DEP. Finally, we discuss results from our previous study of conventional cellulose acetate filters and “bio-filters” with hemoglobin impregnated activated carbon, which showed that these filters do not substantially alter the free radical content of smoke in the particulate and in the gaseous phase.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Synergistic effect of radiation on colon carcinogenesis induced by methylazoxymethanol acetate in ACI/N rats

    International Nuclear Information System (INIS)

    Tanaka, Takuji; Morishita, Yukio; Kawamori, Toshihiko; Suzui, Masumi; Kojima, Toshihiro; Sugie, Shigeyuki; Mori, Hideki

    1993-01-01

    The effect on colon and liver carcinogenicity in rats of a single X-irradiation exposure given either before or after methylazoxymethanol (MAM) acetate was studied in ACI/N rats of both sexes. A single dose of X-irradiation (3 Gy) was administered either 3 months before or after three weekly s.c. injection of MAM acetate (25 mg/kg body weight). At 365 days after the start, the incidence and multiplicity of MAM acetate-induced intestinal tumors were enhanced by X-irradiation either prior to or after the MAM acetate treatment. In addition, X-irradiation before MAM acetate increased the incidence of hepatocellular foci in either sex. In females, X-irradiation either before or after MAM acetate exposure decreased intestinal tumorigenesis. These findings suggest an apparent synergism of these agents in intestinal carcinogenesis of male rats. (author)

  11. The potential role of infectious agents and pelvic inflammatory disease in ovarian carcinogenesis

    DEFF Research Database (Denmark)

    Ingerslev, Kasper; Hogdall, Estrid; Schnack, Tine Henrichsen

    2017-01-01

    BACKGROUND: The etiological cause of ovarian cancer is poorly understood. It has been theorized that bacterial or viral infection as well as pelvic inflammatory disease could play a role in ovarian carcinogenesis. AIM: To review the literature on studies examining the association between ovarian...... cancer and bacterial or viral infection or pelvic inflammatory disease. METHODS: Database search through MEDLINE, applying the medical subject headings: "Ovarian neoplasms", AND "Chlamydia infections", "Neisseria gonorrhoeae", "Mycoplasma genitalium", "Papillomaviridae", or "pelvic inflammatory disease...... than in studies from Western countries. Cytomegalovirus was the only other virus to be detected and was found in 50% of cases in a case-control study. The association between ovarian cancer and pelvic inflammatory disease was examined in seven epidemiological studies, two of which, reported...

  12. Radiation signatures in childhood thyroid cancers after the Chernobyl accident: possible roles of radiation in carcinogenesis.

    Science.gov (United States)

    Suzuki, Keiji; Mitsutake, Norisato; Saenko, Vladimir; Yamashita, Shunichi

    2015-02-01

    After the Tokyo Electric Power Company Fukushima Daiichi nuclear power plant accident, cancer risk from low-dose radiation exposure has been deeply concerning. The linear no-threshold model is applied for the purpose of radiation protection, but it is a model based on the concept that ionizing radiation induces stochastic oncogenic alterations in the target cells. As the elucidation of the mechanism of radiation-induced carcinogenesis is indispensable to justify the concept, studies aimed at the determination of molecular changes associated with thyroid cancers among children who suffered effects from the Chernobyl nuclear accident will be overviewed. We intend to discuss whether any radiation signatures are associated with radiation-induced childhood thyroid cancers. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  13. Extension of a generalized state-vector model of radiation carcinogenesis to consideration of dose rate

    International Nuclear Information System (INIS)

    Crawford-Brown, D.J.; Hofmann, W.

    1993-01-01

    Mathematical models for radiation carcinogenesis typically employ transition rates that either are a function of the dose to specific cells or are purely empirical constructs unrelated to biophysical theory. These functions either ignore or do not explicitly model interactions between the fates of cells in a community. This paper extends a model of mitosis, cell transformation, promotion, and progression to cases in which interacting cellular communities are irradiated at specified dose rates. The model predicts that lower dose rates are less effective at producing cancer when irradiation is by X- or gamma rays but are generally more effective in instances of irradiation by alpha particles up to a dose rate in excess of 0.01 Gy/day. The resulting predictions are compared with existing experimental data. 39 refs., 9 figs., 1 tab

  14. Human RecQL4 helicase plays critical roles in prostate carcinogenesis

    DEFF Research Database (Denmark)

    Su, Yanrong; Meador, Jarah A; Calaf, Gloria M

    2010-01-01

    ) synthesis and RecQL4-suppressed prostate cancer cells underwent an extensive apoptotic death in a PARP-1-dependent manner. Most notably, RecQL4 knockdown in metastatic prostate cancer cells drastically reduced their cell invasiveness in vitro and tumorigenicity in vivo, showing that RecQL4 is essential...... suppression of RecQL4 by small interfering RNA and short hairpin RNA vectors drastically reduced the growth and survival of metastatic prostate cancer cells, indicating that RecQL4 is a prosurvival factor for prostate cancer cells. RecQL4 suppression led to increased poly(ADP-ribose) polymerase (PARP...... for prostate cancer promotion. Observation of a direct interaction of retinoblastoma (Rb) and E2F1 proteins with RecQL4 promoter suggests that Rb-E2F1 pathway may regulate RecQL4 expression. Collectively, our study shows that RecQL4 is an essential factor for prostate carcinogenesis....

  15. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID during Inflammation-Associated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tsutomu Chiba

    2011-06-01

    Full Text Available Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID, a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  16. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Takai, Atsushi; Marusawa, Hiroyuki, E-mail: maru@kuhp.kyoto-u.ac.jp; Chiba, Tsutomu [Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)

    2011-06-22

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  17. Cancers related to viral agents that have a direct role in carcinogenesis: pathological and diagnostic techniques.

    Science.gov (United States)

    Carbone, Antonino; De Paoli, Paolo

    2012-08-01

    The International Agency for Research on Cancer has recently reassessed the carcinogenicity of the biological agents classified as 'carcinogenic to humans'. Among the biological agents having a direct role in carcinogenesis, Epstein-Barr virus, Kaposi's sarcoma-associated herpes virus and human papillomavirus contribute to a variety of malignancies worldwide in humans including nasopharyngeal carcinoma, several types of lymphomas, genital tract carcinomas and Kaposi's sarcoma. The authors review the current knowledge on cancers that have been attributed to Epstein-Barr virus, Kaposi's sarcoma-associated herpes virus and human papillomavirus looking at the pathological classification of these cancers and description of the implicated viruses, highlighting a wide range of pathological and virological diagnostic techniques. This review also focuses on the new oncological scenario ahead, once strategies against carcinogenic infectious agents are found to be effective.

  18. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    International Nuclear Information System (INIS)

    Takai, Atsushi; Marusawa, Hiroyuki; Chiba, Tsutomu

    2011-01-01

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis

  19. The effects of whole green tea infusion on mouse urinary bladder chemical carcinogenesis.

    Science.gov (United States)

    Henriques, Andreia; Arantes-Rodrigues, Regina; I Faustino-Rocha, Ana; I Teixeira-Guedes, Catarina; Pinho-Oliveira, Jacinta; Talhada, Daniela; H Teixeira, José; Andrade, Andreia; Colaço, Bruno; N Paiva-Cardoso, Maria; J Pires, Maria; Mvd Ferreira, Ana; M Nunes, Fernando; A Oliveira, Paula

    2014-02-01

    Green tea (GT) is one of the most popular beverages worldwide whose beneficial effects on health have been demonstrated. Recent studies suggest that GT may contribute to reduction of cancer risk and progression. The aim of this study was to evaluate the effects of whole GT on urinary bladder chemical carcinogenesis in male and female ICR mice. The GT characterization was performed using spectrophotometric methods. Urinary bladder lesions were induced using N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) by gavage during 10 weeks and whole GT (0.5%) was provided ad libitum during 20 weeks. Animals from groups BBN+GT and BBN only developed preneoplastic lesions. We did not observe any effects by GT infusion administration on urinary bladder cancer development.

  20. [Biological effects of arsenic and diseases: The mechanisms involved in arsenic-induced carcinogenesis].

    Science.gov (United States)

    Suzuki, Takehiro; Takumi, Shota; Okamura, Kazuyuki; Nohara, Keiko

    2016-07-01

    Chronic arsenic exposure is associated with many diseases, including cancers. Our study using in vivo assay in gpt-delta transgenic mice showed that arsenic particularly induces G : C to T : A transversions, a mutation type induced through oxidative-stress-induced 8-OHdG formation. Gestational arsenic exposure of C3H mice was reported to increase hepatic tumor incidence. We showed that gestational arsenic exposure increased hepatic tumors having activated oncogene Ha-ras by C to A mutation. We also showed that DNA methylation status of Fosb region is implicated in tumor augmentation by gestational arsenic exposure. We further showed that long-term arsenic exposure induces premature senescence. Recent studies reported that senescence is involved in not only tumor suppression, but also tumorgenesis. All these effects of arsenic might be involved in arsenic-induced carcinogenesis.

  1. Influences of age and anatomical site on ultraviolet carcinogenesis in BALB/c mice

    International Nuclear Information System (INIS)

    Ebbesen, P.; Kripke, M.L.

    1982-01-01

    Young adult BALB/c mice were mor susceptible to the induction of skin tumors from FS40 sunlamps than were 18-month-old animals. The relative contributions of tissue and host factors to this difference in susceptibility to carcinogenesis were analyzed by reciprocal grafting of skin between young and old animals, followed by repeated exposure of the grafts to UV radiation. More tumors developed in ear skin grafted to the middorsum of young recipients than in that of old recipients, regardless of the age of the skin donor. These ear skin grafts were more susceptible to tumor induction than were comparable grafts of back skin. When large areas of dorsal skin (16 cm2) were grafted to young adult mice, very old skin (greater than 2 yr) was more susceptible to tumor induction than skin that was 1 year old at the start of irradiation

  2. Radiation signatures in childhood thyroid cancers after the Chernobyl accident: Possible roles of radiation in carcinogenesis

    Science.gov (United States)

    Suzuki, Keiji; Mitsutake, Norisato; Saenko, Vladimir; Yamashita, Shunichi

    2015-01-01

    After the Tokyo Electric Power Company Fukushima Daiichi nuclear power plant accident, cancer risk from low-dose radiation exposure has been deeply concerning. The linear no-threshold model is applied for the purpose of radiation protection, but it is a model based on the concept that ionizing radiation induces stochastic oncogenic alterations in the target cells. As the elucidation of the mechanism of radiation-induced carcinogenesis is indispensable to justify the concept, studies aimed at the determination of molecular changes associated with thyroid cancers among children who suffered effects from the Chernobyl nuclear accident will be overviewed. We intend to discuss whether any radiation signatures are associated with radiation-induced childhood thyroid cancers. PMID:25483826

  3. Effect of luteolin on the levels of glycoproteins during azoxymethane-induced colon carcinogenesis in mice.

    Science.gov (United States)

    Pandurangan, Ashok Kumar; Dharmalingam, Prakash; Ananda Sadagopan, Suresh Kumar; Ganapasam, Sudhandiran

    2012-01-01

    Luteolin (LUT), a bioflavonoid has been used as a chemopreventive agent world-wide against chemically induced cancer. Hence we designed an experiment to assess chemopreventive action of LUT on lipid peroxidation (LPO) and glycoconjugates in azoxymethane (AOM)-induced colon carcinogenesis. Colon cancer was induced by 15 mg/body kg. body weight of AOM and administration of LUT (at the dose of 1.2 mg/kg. body weight) was till end of the study. Analysis of lipid peroxidative end products such as protein carbonyl (PC), malonadehyde (MDA) and conjucated dienes (CD) demonstrated significant increase in in AOM-induced animals with reduction by LUT (pLUT l(pLUT decreased the incidence of MDF. These results suggest that LUT alters the expression of glycoconjugates and suppress colon cancer. Hence, we speculate that LUT can be used as a chemopreventive agent to treat colon cancer.

  4. Cell survival following alpha particle irradiation: critical sites and implications for carcinogenesis

    International Nuclear Information System (INIS)

    Lloyd, E.L.; Gemmell, M.A.; Henning, C.B.; Gemmell, D.S.; Zabransky, B.J.

    1976-01-01

    In experiments in which mammalian cells were irradiated with 5.6 MeV alpha particles from a Tandem Van de Graaff machine we have confirmed the finding of others that the mean lethal dose (D 0 ) is about 100 rad, but by measurements of the area of the cell nuclei as irradiated we found that this mean lethal dose corresponds not to 1, as expected, but to about 27 alpha particles per cell nucleus. (The exact number appears to change slightly with cell passage number.) This allows for the possibility that the direct action of alpha particles on the nucleus may be the important event in carcinogenesis, a theory which was previously difficult to accept if a single particle hitting the nucleus anywhere was considered to be lethal. Evidence is presented to implicate the nucleolus as a possible critical site for the inhibition of reproductive integrity of the cell

  5. Ionizing radiation, human carcinogenesis and radioresistance; Rayonnements, cancerisation humaine et radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Vuillaume, M.; Queinnec, E. [Ecole Normale Superieure, Paris (France)

    1992-07-01

    H{sub 2}O{sub 2} and free radicals are correlated with inflammatory diseases, cellular transformation and carcinogenesis. Experiments studying their direct or indirect influence in vivo, and/or, in cell cultures were still positive. In the contrary, reactions or products, which decrease level(s) of free radicals/H{sub 2}O{sub 2} (i) directly, (ii) indirectly by an increase of SOD, catalase and peroxydase activities zeroed the above described phenomena. It is the case of the domain number 2 (that contains copper) of the Scorpion's blood pigment (hemocyanin), (i) which possesses SOD-, catalase-and peroxyde-like properties, resistant, at least, at 4000Gy, furthermore explaining the especially high radioresistance of scorpions. (author)

  6. 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

  7. Resistance of germfree athymic nude mice to two-stage skin carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Holland, J.M.; Perkins, E.H.

    1979-01-01

    Germfree athymic and normal littermate mice were compared with respect to their relative sensitivity to single skin application of dimethylbenzanthacine followed either by croton oil or TPA applied as a co-carcinogen. In separate experiments the acute response of both phenotypes to TPA was assessed by histologic examination of skin as well as the incorporttion of tritiated thymidine into acid insoluble material obtained from the isolated epidermis. Nude mice were observed to be less, equal, or more sensitive than normal littermate to topical skin carcinogenesis depending upon experimental variables. The tendency of solvent to spread rapidly on the skin of nude mice appeared to have the greatest influence on susceptibility to papilloma induction. Other factors of potential, although unproven importance, include differences in skin structure, possibly associated with accelerated activity of hair follicles as well as resistance to both the inflammatory and hyperplasiogenic effects of TPA.

  8. Respiratory diseases call for special attention from clinical and translational science.

    Science.gov (United States)

    Bai, Chunxue

    2013-12-01

    Respiratory diseases will become one of the top 3 leading causes of estimated mortality in 2020 and become about one third of total causes of estimated mortality. The journal of Translational Respiratory Medicine is a truly international, peer-reviewed journal devoted to the publication of articles on outstanding work with translational potentials between basic research and clinical application to understanding respiratory disease. Translational respiratory medicine will more focus on biomarker identification and validation in pulmonary diseases in combination with clinical informatics, targeted proteomics, bioinformatics, systems medicine, or mathematical science; on different translational strategies of cell-based therapy to clinical application to treat lung diseases; on targeted therapies in combination with personalized medicine; and on distant electronic medicine to monitor a large population of people's health. Translational Respiratory Medicine is an additional but unique opportunity for scientists and clinicians who work on pulmonary diseases to publish their outstanding findings, initiative results, and critical and perceptive opinions in the journal.

  9. Understanding analysis

    CERN Document Server

    Abbott, Stephen

    2015-01-01

    This lively introductory text exposes the student to the rewards of a rigorous study of functions of a real variable. In each chapter, informal discussions of questions that give analysis its inherent fascination are followed by precise, but not overly formal, developments of the techniques needed to make sense of them. By focusing on the unifying themes of approximation and the resolution of paradoxes that arise in the transition from the finite to the infinite, the text turns what could be a daunting cascade of definitions and theorems into a coherent and engaging progression of ideas. Acutely aware of the need for rigor, the student is much better prepared to understand what constitutes a proper mathematical proof and how to write one. Fifteen years of classroom experience with the first edition of Understanding Analysis have solidified and refined the central narrative of the second edition. Roughly 150 new exercises join a selection of the best exercises from the first edition, and three more project-sty...

  10. Understanding ayurveda.

    Science.gov (United States)

    Gadgil, Vaidya Dilip

    2010-01-01

    Ayurveda needs to achieve its full potential both in India and globally. This requires imparting to its students full appreciation of Ayurveda's power and strength, particularly proper understanding of the advantages of applying it to treat chronic and acute diseases. To this end, we explain the necessity of learning Sanskrit as a medium of study, and the advantages of learning the Texts in the traditional way, rather than relying on translations with all the loss of meaning and precision, which that entails. We emphasize the use of Triskandhakosha as a means to fully understand Ayurveda fundamental concepts and technical terms, so that all their shades of meaning are fully understood, and all their usages given in different places in the texts. Only by such methods can full appreciation of Ayurvedic wisdom be achieved, and the full depth and power of its knowledge be applied. Only then will its true status among systems of medicine come to be appreciated, either in India or more widely in the world as a whole.

  11. Understanding Ayurveda

    Directory of Open Access Journals (Sweden)

    Vaidya Dilip Gadgil

    2010-01-01

    Full Text Available Ayurveda needs to achieve its full potential both in India and globally. This requires imparting to its students full appreciation of Ayurveda′s power and strength, particularly proper understanding of the advantages of applying it to treat chronic and acute diseases. To this end, we explain the necessity of learning Sanskrit as a medium of study, and the advantages of learning the Texts in the traditional way, rather than relying on translations with all the loss of meaning and precision, which that entails. We emphasize the use of Triskandhakosha as a means to fully understand Ayurveda fundamental concepts and technical terms, so that all their shades of meaning are fully understood, and all their usages given in different places in the texts. Only by such methods can full appreciation of Ayurvedic wisdom be achieved, and the full depth and power of its knowledge be applied. Only then will its true status among systems of medicine come to be appreciated, either in India or more widely in the world as a whole.

  12. Histopathological and in vivo evidence of regucalcin as a protective molecule in mammary gland carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Ricardo; Vaz, Cátia V.; Maia, Cláudio J. [CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Gomes, Madalena [IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Porto (Portugal); Gama, Adelina [Department of Veterinary Sciences, Animal and Veterinary Science Research Center (CECAV), University of Trás-os-Montes and Alto Douro (UTAD) (Portugal); Alves, Gilberto; Santos, Cecília R. [CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Schmitt, Fernando [IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Porto (Portugal); Medical Faculty, University of Porto, Porto (Portugal); Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto (Canada); Department of Pathology, University Health Network, Toronto (Canada); Socorro, Sílvia, E-mail: ssocorro@fcsaude.ubi.pt [CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal)

    2015-01-15

    Regucalcin (RGN) is a calcium-binding protein, which has been shown to be underexpressed in cancer cases. This study aimed to determine the association of RGN expression with clinicopathological parameters of human breast cancer. In addition, the role of RGN in malignancy of mammary gland using transgenic rats overexpressing the protein (Tg-RGN) was investigated. Wild-type (Wt) and Tg-RGN rats were treated with 7,12-dimethylbenz[α]anthracene (DMBA). Carcinogen-induced tumors were histologically classified and the Ki67 proliferation index was estimated. Immunohistochemistry analysis showed that RGN immunoreactivity was negatively correlated with the histological grade of breast infiltrating ductal carcinoma suggesting that progression of breast cancer is associated with loss of RGN. Tg-RGN rats displayed lower incidence of carcinogen-induced mammary gland tumors, as well as lower incidence of invasive forms. Moreover, higher proliferation was observed in non-invasive tumors of Wt animals comparatively with Tg-RGN. Overexpression of RGN was associated with diminished expression of cell-cycle inhibitors and increased expression of apoptosis inducers. Augmented activity of apoptosis effector caspase-3 was found in the mammary gland of Tg-RGN. RGN overexpression protected from carcinogen-induced mammary gland tumor development and was linked with reduced proliferation and increased apoptosis. These findings indicated the protective role of RGN in the carcinogenesis of mammary gland. - Highlights: • RGN immunoreactivity was negatively correlated with breast cancer differentiation. • Transgenic overexpression of RGN diminished incidence of carcinogen-induced tumors. • Transgenic overexpression of RGN restricted proliferation and fostered apoptosis. • RGN has a protective role in the carcinogenesis of mammary gland.

  13. DPEP1, expressed in the early stages of colon carcinogenesis, affects cancer cell invasiveness.

    Science.gov (United States)

    Toiyama, Yuji; Inoue, Yasuhiro; Yasuda, Hiromi; Saigusa, Susumu; Yokoe, Takeshi; Okugawa, Yoshinaga; Tanaka, Koji; Miki, Chikao; Kusunoki, Masato

    2011-02-01

    We investigated changes in the gene expression profile in colon cancer in order to identify gene markers that may be useful in the management of this disease. The Cancer Genome Anatomy Project was used to detect differences in gene expression between normal and cancer tissue. The overexpression of dipeptidase-1 (DPEP1) in cancer tissue was confirmed in a sample of 76 patients by real-time PCR. To identify the function of DPEP1, RNA interference (RNAi) was used to inactivate this gene in the colon cancer cell line. Immunohistochemical analysis was performed to characterize the pattern of DPEP1 expression in colon cancer. DPEP1 expression in cancer was significantly higher than that in normal tissue. However, DPEP1 expression decreased with pathological differentiation, lymph-node and distant metastasis. Patients with tumors with decreased DPEP1 expression showed a poorer prognosis, and this was also true of patients with tumors who are treated with curative intent. RNAi-mediated DPEP1 reduction in the colon cancer cell line did not result in cell proliferation or apoptosis, but was associated with an increased invasive ability. DPEP1 protein was observed on the apical side of the cancer cells, and is expressed in the early stages of carcinogenesis, even in adenomas of both sporadic colorectal cancer and familial adenomatous polyposis patients. DPEP1 expression in normal colonic mucosa is very low, but it is highly expressed in colorectal adenoma and cancer specimens and is negatively correlated with parameters of pathological aggressiveness and poor prognosis. DPEP1 is expressed in the early stages of colon carcinogenesis and affects cancer cell invasiveness.

  14. A central role for heme iron in colon carcinogenesis associated with red meat intake.

    Science.gov (United States)

    Bastide, Nadia M; Chenni, Fatima; Audebert, Marc; Santarelli, Raphaelle L; Taché, Sylviane; Naud, Nathalie; Baradat, Maryse; Jouanin, Isabelle; Surya, Reggie; Hobbs, Ditte A; Kuhnle, Gunter G; Raymond-Letron, Isabelle; Gueraud, Françoise; Corpet, Denis E; Pierre, Fabrice H F

    2015-03-01

    Epidemiology shows that red and processed meat intake is associated with an increased risk of colorectal cancer. Heme iron, heterocyclic amines, and endogenous N-nitroso compounds (NOC) are proposed to explain this effect, but their relative contribution is unknown. Our study aimed at determining, at nutritional doses, which is the main factor involved and proposing a mechanism of cancer promotion by red meat. The relative part of heme iron (1% in diet), heterocyclic amines (PhIP + MeIQx, 50 + 25 μg/kg in diet), and NOC (induced by NaNO₂+ NaNO₂; 0.17 + 0.23 g/L of drinking water) was determined by a factorial design and preneoplastic endpoints in chemically induced rats and validated on tumors in Min mice. The molecular mechanisms (genotoxicity, cytotoxicity) were analyzed in vitro in normal and Apc-deficient cell lines and confirmed on colon mucosa. Heme iron increased the number of preneoplastic lesions, but dietary heterocyclic amines and NOC had no effect on carcinogenesis in rats. Dietary hemoglobin increased tumor load in Min mice (control diet: 67 ± 39 mm²; 2.5% hemoglobin diet: 114 ± 47 mm², P = 0.004). In vitro, fecal water from rats given hemoglobin was rich in aldehydes and was cytotoxic to normal cells, but not to premalignant cells. The aldehydes 4-hydroxynonenal and 4-hydroxyhexenal were more toxic to normal versus mutated cells and were only genotoxic to normal cells. Genotoxicity was also observed in colon mucosa of mice given hemoglobin. These results highlight the role of heme iron in the promotion of colon cancer by red meat and suggest that heme iron could initiate carcinogenesis through lipid peroxidation. . ©2015 American Association for Cancer Research.

  15. Modifying effects of Terminalia catappa on azoxymethane-induced colon carcinogenesis in male F344 rats.

    Science.gov (United States)

    Morioka, T; Suzui, M; Nabandith, V; Inamine, M; Aniya, Y; Nakayama, T; Ichiba, T; Yoshimi, N

    2005-04-01

    The modifying effects of dietary administration of an herb, Terminalia catappa (TC), were investigated on rat colon carcinogenesis induced by a carcinogen azoxymethane (AOM). The number of aberrant crypt foci (ACF) and beta-catenin accumulated crypts (BCACs) in the colon, and proliferating cell nuclear antigen (PCNA) labelling index in the colonic epithelium were examined in a total of 36 male F344 rats. All animals were randomly divided into five experimental groups (4-10 rats in each group). At 6 weeks of age, rats in groups 1, 2 and 3 were given s.c. injections of AOM once a week for 2 weeks at a concentration of 20 mg/kg body weight. One week before the first injection of AOM, rats in groups 2 and 3 were fed a diet containing 0.02 and 0.1% TC, respectively, throughout the experiment. Rats in group 4 were fed a diet containing 0.1% TC. Rats in group 5 were served as untreated controls. All animals were sacrificed at the experimental week 5 after the start of the experiment. Oral administration of TC at both doses significantly decreased the numbers of both ACF/colon/rat (P<0.05 for 0.02% TC, P<0.005 for 0.1% TC) and BCAC/cm/rat (P<0.05 for both 0.02 and 0.1% TC), when compared with the control group (group 1). Colonic PCNA labelling index in groups 2 and 3 was also significantly lower than that in group 1 (P<0.001 for 0.02% TC, P<0.005 for 0.1% TC). These results suggest that TC has a potent short-term chemopreventive effect on biomarkers of colon carcinogenesis and this effect may be associated with the inhibition of the development of ACF and BCACs.

  16. Beclin 1 Expression is Closely Linked to Colorectal Carcinogenesis and Distant Metastasis of Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Mei-Ying Zhang

    2014-08-01

    Full Text Available Beclin 1 participates in development, autophagy, differentiation, anti- apoptosis, neurodegeneration, tumorigenesis and cancer progression. The roles of Beclin 1 in colorectal carcinogenesis and its subsequent progression are still unclear. Here, the mRNA and protein expression of Beclin 1 were determined in colorectal carcinoma and matched mucosa by Reverse transcriptase-polymerase chain reaction and Western blot. Immunohistochemistry and in situ hybridization (ISH were performed on tissue microarryer with colorectal carcinoma, adenoma and mucosa. The expression of Beclin 1 mRNA and protein was found to be higher in colorectal carcinoma than matched mucosa by real-time PCR and Western blot (p < 0.05. According to the ISH data, Beclin 1 expression was lower in colorectal non-neoplastic mucosa (NNM than adenoma and carcinoma (p < 0.05. Immunohistochemically, primary carcinoma showed stronger Beclin 1 expression than NNM and metastatic carcinoma in the liver (p < 0.05. Beclin 1 protein expression was negatively related to liver and distant metastasis (p < 0.05, but not correlated with age, sex, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumor-node-metastasis (TNM staging, differentiation or serum carcinoembryonic antigen (CEA concentration (p > 0.05. Survival analysis indicated that Beclin 1 expression was not linked to favorable prognosis of the patients with colorectal carcinoma (p > 0.05. Cox’s model indicated that depth of invasion and distant metastasis were independent prognostic factors for colorectal carcinomas (p < 0.05. It was suggested that Beclin 1 expression is closely linked to colorectal carcinogenesis and distant metastasis of colorectal carcinoma.

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

    Science.gov (United States)

    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.

  18. Deferasirox induces mesenchymal-epithelial transition in crocidolite-induced mesothelial carcinogenesis in rats.

    Science.gov (United States)

    Nagai, Hirotaka; Okazaki, Yasumasa; Chew, Shan Hwu; Misawa, Nobuaki; Yasui, Hiroyuki; Toyokuni, Shinya

    2013-11-01

    Asbestos was used worldwide in huge quantities in the past century. However, because of the unexpected carcinogenicity to mesothelial cells with an extremely long incubation period, many countries face this long-lasting social problem. Mesothelioma is often diagnosed in an advanced stage, for which no effective therapeutic protocols are yet established. We previously reported on the basis of animal experiments that the major pathology in asbestos-induced mesothelial carcinogenesis is local iron overload. Here, we undertook to find an effective strategy to prevent, delay, or lower the malignant potential of mesothelioma during asbestos-induced carcinogenesis. We used intraperitoneal injections of crocidolite to rats. We carried out a 16-week study to seek the maximal-tolerated intervention for iron reduction via oral deferasirox administration or intensive phlebotomy. Splenic iron deposition was significantly decreased with either method, and we found that Perls' iron staining in spleen is a good indicator for iron reduction. We injected a total of 10 mg crocidolite at the age of six weeks, and the preventive measures were via repeated oral administration of 25 to 50 mg/kg/d deferasirox or weekly to bimonthly phlebotomy of 4 to 10 mL/kg/d. The animals were observed until 110 weeks. Deferasirox administration significantly increased the fraction of less malignant epithelioid subtype. Although we found a slightly prolonged survival in deferasirox-treated female rats, larger sample size and refinement of the current protocol are necessary to deduce the cancer-preventive effects of deferasirox. Still, our results suggest deferasirox serves as a potential preventive strategy in people already exposed to asbestos via iron reduction. ©2013 AACR.

  19. Progressive increase of glucose transporter-3 (GLUT-3) expression in estrogen-induced breast carcinogenesis.

    Science.gov (United States)

    Kocdor, M A; Kocdor, H; Pereira, J S; Vanegas, J E; Russo, I H; Russo, J

    2013-01-01

    Increased glucose uptake and glycolysis are main metabolic characteristics of malignant cells. A family of glucose transporters (GLUTs) facilitates glucose movement across the plasma membranes in a tumor-specific manner. Glucose transporter-1 (GLUT-1), GLUT-3 and recently GLUT-12, have been previously shown in breast cancer cells and are found to be associated with poor prognosis. In addition, it has been shown that estrogen plays critical roles in GLUT regulation, however, the stage-specific GLUT regulation of mammary carcinogenesis is unclear. GLUT expression patterns were investigated in an in vitro-in vivo progressive, estrogen-induced, mammary carcinogenesis model which consisted of four cell lines, with same genetic background. In this model, different stages of tumor initiation and progression are represented, MCF-10F being the normal stage, E2 cells the transformed stage by estrogen, C5 cells, the invasive stage, and T4 cells the tumorigenic stage. In addition, loss of ductulogenesis and solid mass formation in collagen matrix and invasiveness of the cells were counted. Real time PCR showed that GLUT1 expression was downregulated in MCF10F after treatment with 17β-estradiol (E2), and in the invasive cell type (C5), but not in the tumor cells (T4), which had no changes compared to MCF10F. C5 and T4 cells showed the highest rate of GLUT-3 expression. These cells were also found to be associated with loss of ductulogenesis, solid mass formation and higher invasive capacity, whereas, GLUT-12 was downregulated in C5 and T4 cells. Estrogen-induced malignant transformation is associated with remarkable and progressive GLUT-3 expression, GLUT-1 re-expression at further stages, as well as GLUT-12 downregulation.

  20. Local Acetaldehyde—An Essential Role in Alcohol-Related Upper Gastrointestinal Tract Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Mikko T. Nieminen

    2018-01-01

    Full Text Available The resident microbiome plays a key role in exposure of the upper gastrointestinal (GI tract mucosa to acetaldehyde (ACH, a carcinogenic metabolite of ethanol. Poor oral health is a significant risk factor for oral and esophageal carcinogenesis and is characterized by a dysbiotic microbiome. Dysbiosis leads to increased growth of opportunistic pathogens (such as Candida yeasts and may cause an up to 100% increase in the local ACH production, which is further modified by organ-specific expression and gene polymorphisms of ethanol-metabolizing and ACH-metabolizing enzymes. A point mutation in the aldehyde dehydrogenase 2 gene has randomized millions of alcohol consumers to markedly increased local ACH exposure via saliva and gastric juice, which is associated with a manifold risk for upper GI tract cancers. This human cancer model proves conclusively the causal relationship between ACH and upper GI tract carcinogenesis and provides novel possibilities for the quantitative assessment of ACH carcinogenicity in the human oropharynx. ACH formed from ethanol present in “non-alcoholic” beverages, fermented food, or added during food preparation forms a significant epidemiologic bias in cancer epidemiology. The same also concerns “free” ACH present in mutagenic concentrations in multiple beverages and foodstuffs. Local exposure to ACH is cumulative and can be reduced markedly both at the population and individual level. At best, a person would never consume tobacco, alcohol, or both. However, even smoking cessation and moderation of alcohol consumption are associated with a marked decrease in local ACH exposure and cancer risk, especially among established risk groups.

  1. Promoting effect of saccharin and DL-tryptophan in urinary bladder carcinogenesis.

    Science.gov (United States)

    Cohen, S M; Arai, M; Jacobs, J B; Friedell, G H

    1979-04-01

    The existence of at least two stages in bladder carcinogenesis was evaluated in male Fischer rats using N-[14-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) fed for six weeks at a level of 0.2% of the diet as the initiator. Sodium saccharin and DL-tryptophan were fed at levels of 5 and 2% of the diet, respectively, as possible promoting chemicals, and they were fed either immediately after FANFT administration or after six weeks of FANFT plus six weeks of control diet. All surviving rats were killed at the end of two years. Both chemicals significantly increased the incidence of bladder tumors following FANFT feeding compared to six weeks of FANFT feeding followed by control diet, and the results were similar whether saccharin or tryptophan feeding was started immediately after FANFT feeding was concluded or after a six-week delay. Saccharin was considerably more potent as a promoting agent than was tryptophan, inducing higher incidences of bladder tumors and having a shorter latent period. Long-term administration of FANFT induced a 100% incidence of bladder cancer. Sequential epithelial changes were observed by scanning and transmission electron microscopy as well as by light microscopy. Pleomorphic microvilli were present on the superficial cells of all tumors examined and on the surface cells of hyperplastic bladder epithelium after six weeks of FANFT plus six weeks of saccharin, but not after six weeks of FANFT and six weeks of control diet. Rats fed only saccharin tryptophan, or control diet did not have bladder tumors or pleomorphic microvilli on bladder epithelium. These data suggest that saccharin and tryptophan might act as tumor-promoting agents during bladder carcinogenesis.

  2. Promoter hypermethylation of KLF4 inactivates its tumor suppressor function in cervical carcinogenesis.

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    Wen-Ting Yang

    Full Text Available OBJECTIVE: The KLF4 gene has been shown to be inactivated in cervical carcinogenesis as a tumor suppressor. However, the mechanism of KLF4 silencing in cervical carcinomas has not yet been identified. DNA methylation plays a key role in stable suppression of gene expression. METHODS: The methylation status of the KLF4 promoter CpG islands was analyzed by bisulfite sequencing (BSQ in tissues of normal cervix and cervical cancer. KLF4 gene expression was detected by RT-PCR, immunohistochemistry and western blot. KLF4 promoter methylation in cervical cancer cell line was determined by BSQ and methylation-specific polymerase chain reaction (MS-PCR. Cell proliferation ability was detected by cell growth curve and MTT assay. RESULTS: The methylated allele was found in 41.90% of 24 cervical cancer tissues but only in 11.11% of 11 normal cervix tissues (P<0.005. KLF4 mRNA levels were significantly reduced in cervical cancer tissues compared with normal cervix tissues (P<0.01 and KLF4 mRNA expression showed a significant negative correlation with the promoter hypermethylation (r = -0.486, P = 0.003. Cervical cancer cell lines also showed a significant negative correlation between KLF4 expression and hypermethylation. After treatment with the demethylating agent 5-Azacytidine (5-Aza, the expression of KLF4 in the cervical cancer cell lines at both mRNA and protein levels was drastically increased, the cell proliferation ability was inhibited and the chemosensitivity for cisplatin was significantly increased. CONCLUSION: KLF4 gene is inactivated by methylation-induced silencing mechanisms in a large subset of cervical carcinomas and KLF4 promoter hypermethylation inactivates the gene's function as a tumor suppressor in cervical carcinogenesis.

  3. Genome-Wide Transcriptional Reorganization Associated with Senescence-to-Immortality Switch during Human Hepatocellular Carcinogenesis

    Science.gov (United States)

    Konu, Ozlen; Yuzugullu, Haluk; Gursoy-Yuzugullu, Ozge; Ozturk, Nuri; Ozen, Cigdem; Ozdag, Hilal; Erdal, Esra; Karademir, Sedat; Sagol, Ozgul; Mizrak, Dilsa; Bozkaya, Hakan; Ilk, Hakki Gokhan; Ilk, Ozlem; Bilen, Biter; Cetin-Atalay, Rengul; Akar, Nejat; Ozturk, Mehmet

    2013-01-01

    Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become “immortal”) by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC) development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15-gene

  4. 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

  5. Aberrant promoter methylation and expression of UTF1 during cervical carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Samuel Guenin

    Full Text Available Promoter methylation profiles are proposed as potential prognosis and/or diagnosis biomarkers in cervical cancer. Up to now, little is known about the promoter methylation profile and expression pattern of stem cell (SC markers during tumor development. In this study, we were interested to identify SC genes methylation profiles during cervical carcinogenesis. A genome-wide promoter methylation screening revealed a strong hypermethylation of Undifferentiated cell Transcription Factor 1 (UTF1 promoter in cervical cancer in comparison with normal ectocervix. By direct bisulfite pyrosequencing of DNA isolated from liquid-based cytological samples, we showed that UTF1 promoter methylation increases with lesion severity, the highest level of methylation being found in carcinoma. This hypermethylation was associated with increased UTF1 mRNA and protein expression. By using quantitative RT-PCR and Western Blot, we showed that both UTF1 mRNA and protein are present in epithelial cancer cell lines, even in the absence of its two main described regulators Oct4A and Sox2. Moreover, by immunofluorescence, we confirmed the nuclear localisation of UTF1 in cell lines. Surprisingly, direct bisulfite pyrosequencing revealed that the inhibition of DNA methyltransferase by 5-aza-2'-deoxycytidine was associated with decreased UTF1 gene methylation and expression in two cervical cancer cell lines of the four tested. These findings strongly suggest that UTF1 promoter methylation profile might be a useful biomarker for cervical cancer diagnosis and raise the questions of its role during epithelial carcinogenesis and of the mechanisms regulating its expression.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Connexin subtype expression during oral carcinogenesis: A pilot study in patients with oral squamous cell carcinoma.

    Science.gov (United States)

    Brockmeyer, Phillipp; Hemmerlein, Bernhard; Jung, Klaus; Fialka, Florian; Brodmann, Tobias; Gruber, Rudolf Matthias; Schliephake, Henning; Kramer, Franz-Josef

    2016-02-01

    Gap junctional intercellular communication (GJIC) and connexin (Cx) expression were reported in association with carcinogenesis in various types of tumours. In an earlier histomorphometric study, the protein levels of Cx subtypes 26, 43 and 45 were differentially expressed in oral squamous cell carcinoma (OSCC), corresponding lymph node metastases and dysplasia-free oral mucosa. Moreover, membrane Cx43 acted as an independent prognostic marker in OSCC tissues. This study aimed to confirm the expression of described Cx subtypes at the mRNA level. Hence, a reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis of Cx26, Cx43 and Cx45 gene expressions was performed in paired carcinoma and mucosa samples of 15 OSCC patients. Additionally, we assessed the interaction between Cx subtype expression and clinicopathological routine parameters. The RT-qPCR analysis revealed that Cx26 was downregulated in OSCC (P=0.01), while Cx43 was marginally upregulated in cancer tissue (P=0.04). Cx45 was significantly overexpressed in OSCC tissue compared with the intraoral mucosa controls (P<0.01), and remained unchanged at different tumour stages. No significant interactions between differential Cx subtype expression and clinicopathological routine parameters were observed. In conclusion, Cx regulation at the transcriptional level appears to be an early event during the initiation and development of OSCC, and is maintained during further progression. However, the mRNA-protein correlation is variable. This may be indicative of post-transcriptional, translational and degradation regulations being associated with the determination of Cx protein concentration during oral carcinogenesis.

  8. Expression of interleukin-22/STAT3 signaling pathway in ulcerative colitis and related carcinogenesis

    Science.gov (United States)

    Yu, Lian-Zhen; Wang, Hai-Yang; Yang, Shu-Ping; Yuan, Zhi-Ping; Xu, Fang-Yuan; Sun, Chao; Shi, Rui-Hua

    2013-01-01

    AIM: To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS: Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p-STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS: Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated. CONCLUSION: IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC. PMID:23674871

  9. Correlation analysis of respiratory signals by using parallel coordinate plots.

    Science.gov (United States)

    Saatci, Esra

    2018-01-01

    The understanding of the bonds and the relationships between the respiratory signals, i.e. the airflow, the mouth pressure, the relative temperature and the relative humidity during breathing may provide the improvement on the measurement methods of respiratory mechanics and sensor designs or the exploration of the several possible applications in the analysis of respiratory disorders. Therefore, the main objective of this study was to propose a new combination of methods in order to determine the relationship between respiratory signals as a multidimensional data. In order to reveal the coupling between the processes two very different methods were used: the well-known statistical correlation analysis (i.e. Pearson's correlation and cross-correlation coefficient) and parallel coordinate plots (PCPs). Curve bundling with the number intersections for the correlation analysis, Least Mean Square Time Delay Estimator (LMS-TDE) for the point delay detection and visual metrics for the recognition of the visual structures were proposed and utilized in PCP. The number of intersections was increased when the correlation coefficient changed from high positive to high negative correlation between the respiratory signals, especially if whole breath was processed. LMS-TDE coefficients plotted in PCP indicated well-matched point delay results to the findings in the correlation analysis. Visual inspection of PCB by visual metrics showed range, dispersions, entropy comparisons and linear and sinusoidal-like relationships between the respiratory signals. It is demonstrated that the basic correlation analysis together with the parallel coordinate plots perceptually motivates the visual metrics in the display and thus can be considered as an aid to the user analysis by providing meaningful views of the data. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Respiratory Management of Extremely Preterm Infants: An International Survey.

    Science.gov (United States)

    Beltempo, Marc; Isayama, Tetsuya; Vento, Máximo; Lui, Kei; Kusuda, Satoshi; Lehtonen, Liisa; Sjörs, Gunnar; Håkansson, Stellan; Adams, Mark; Noguchi, Akihiko; Reichman, Brian; Darlow, Brian A; Morisaki, Naho; Bassler, Dirk; Pratesi, Simone; Lee, Shoo K; Lodha, Abhay; Modi, Neena; Helenius, Kjell; Shah, Prakesh S

    2018-04-13

    There are significant international variations in chronic lung disease rates among very preterm infants yet there is little data on international variations in respiratory strategies. To evaluate practice variations in the respiratory management of extremely preterm infants born at < 29 weeks' gestational age (GA) among 10 neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of Neonates collaboration. A web-based survey was sent to the representatives of 390 neonatal intensive care units from Australia/New Zealand, Canada, Finland, Illinois (USA), Israel, Japan, Spain, Sweden, Switzerland, and Tuscany (Italy). Responses were based on practices in 2015. Overall, 321 of the 390 units responded (82%). The majority of units within networks (40-92%) mechanically ventilate infants born at 23-24 weeks' GA on continuous positive airway pressure (CPAP) with 30-39% oxygen in respiratory distress within 48 h after birth, but the proportion of units that offer mechanical ventilation for infants born at 25-26 weeks' GA at similar settings varied significantly (20-85% of units within networks). The most common respiratory strategy for infants born at 27-28 weeks' GA on CPAP with 30-39% oxygen with respiratory distress within 48 h after birth used by units also varied significantly among networks: mechanical ventilation (0-60%), CPAP (3-82%), intubation and surfactant administration with immediate extubation (0-75%), and less invasive surfactant administration (0-68%). There are marked variations but also similarities in respiratory management of extremely preterm infants between networks. Further collaboration and exploration is needed to better understand the association of these variations in practice with pulmonary outcomes. © 2018 S. Karger AG, Basel.

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

    Science.gov (United States)

    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.

  12. Partnering for optimal respiratory home care: physicians working with respiratory therapists to optimally meet respiratory home care needs.

    Science.gov (United States)

    Spratt, G; Petty, T L

    2001-05-01

    The need for respiratory care services continues to increase, reimbursement for those services has decreased, and cost-containment measures have increased the frequency of home health care. Respiratory therapists are well qualified to provide home respiratory care, reduce misallocation of respiratory services, assess patient respiratory status, identify problems and needs, evaluate the effect of the home setting, educate the patient on proper equipment use, monitor patient response to and complications of therapy, monitor equipment functioning, monitor for appropriate infection control procedures, make recommendations for changes to therapy regimen, and adjust therapy under the direction of the physician. Teamwork benefits all parties and offers cost and time savings, improved data collection and communication, higher job satisfaction, and better patient monitoring, education, and quality of life. Respiratory therapists are positioned to optimize treatment efficacy, maximize patient compliance, and minimize hospitalizations among patients receiving respiratory home care.

  13. Basal Cell Carcinoma: From the Molecular Understanding of the Pathogenesis to Targeted Therapy of Progressive Disease

    Directory of Open Access Journals (Sweden)

    Daniela Göppner

    2011-01-01

    Full Text Available Due to intensified research over the past decade, the Hedgehog (HH pathway has been identified as a pivotal defect implicated in roughly 25% of all cancers. As one of the most frequent cancer worldwide, the development of Basal cell carcinoma (BCC due to activation of the HH pathway has been convincingly demonstrated. Thus the discovery of this central tumor-promoting signalling pathway has not only revolutionized the understanding of BCC carcinogenesis but has also enabled the development of a completely novel therapeutic approach. Targeting just a few of several potential mutations, HH inhibitors such as GDC-0449 achieved already the first promising results in metastatic or locally advanced BCC. This paper summarizes the current understanding of BCC carcinogenesis and describes the current “mechanism-based” therapeutic strategies.

  14. Understanding physics

    CERN Document Server

    Cassidy, David; Rutherford, James

    2002-01-01

    Understanding Physics provides a thorough grounding in contemporary physics while placing physics into its social and historical context Based in large part on the highly respected Project Physics Course developed by two of the authors, it also integrates the results of recent pedagogical research The text thus - teaches about the basic phenomena in the physical world and the concepts developed to explain them - shows that science is a rational human endeavor with a long and continuing tradition, involving many different cultures and people - develops facility in critical thinking, reasoned argumentation, evaluation of evidence, mathematical modeling, and ethical values The treatment emphasizes not only what we know but also how we know it, why we believe it, and what effects that knowledge has - Why do we believe the Earth and planets revolve around the Sun? - Why do we believe that matter is made of atoms? - How do relativity theory and quantum mechanics alter our conception of Nature and in what ways do th...

  15. Respiratory challenge MRI: Practical aspects

    Directory of Open Access Journals (Sweden)

    Fiona C. Moreton

    2016-01-01

    Full Text Available Respiratory challenge MRI is the modification of arterial oxygen (PaO2 and/or carbon dioxide (PaCO2 concentration to induce a change in cerebral function or metabolism which is then measured by MRI. Alterations in arterial gas concentrations can lead to profound changes in cerebral haemodynamics which can be studied using a variety of MRI sequences. Whilst such experiments may provide a wealth of information, conducting them can be complex and challenging. In this paper we review the rationale for respiratory challenge MRI including the effects of oxygen and carbon dioxide on the cerebral circulation. We also discuss the planning, equipment, monitoring and techniques that have been used to undertake these experiments. We finally propose some recommendations in this evolving area for conducting these experiments to enhance data quality and comparison between techniques.

  16. Hypnosis in paediatric respiratory medicine.

    Science.gov (United States)

    McBride, Joshua J; Vlieger, Arine M; Anbar, Ran D

    2014-03-01

    Hypnotherapy is an often misunderstood yet effective therapy. It has been reported to be useful within the field of paediatric respiratory medicine as both a primary and an adjunctive therapy. This article gives a brief overview of how hypnotherapy is performed followed by a review of its applications in paediatric patients with asthma, cystic fibrosis, dyspnea, habit cough, vocal cord dysfunction, and those requiring non-invasive positive pressure ventilation. As the available literature is comprised mostly of case series, retrospective studies, and only a single small randomized study, the field would be strengthened by additional randomized, controlled trials in order to better establish the effectiveness of hypnosis as a treatment, and to identify the processes leading to hypnosis-induced physiologic changes. As examples of the utility of hypnosis and how it can be taught to children with respiratory disease, the article includes videos that demonstrate its use for patients with cystic fibrosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Vitamin D and respiratory disorder

    Directory of Open Access Journals (Sweden)

    Mahnaz Hushmand

    2015-09-01

    Full Text Available The active form of vitamin D is synthesized in some body organs following sun exposure and dietary intake. Vitamin D exhibits its major and critical effects not only through regulation of calcium and phosphate metabolism but also by influencing on respiratory and immune system. Serum concentrations of 25-hydroxyvitamin D below the optimum limit lead to vitamin D insufficiency or maybe deficiency. These inappropriate concentrations of vitamin D lead to different types of pulmonary diseases such as viral and bacterial respiratory infection, asthma, chronic obstructive pulmonary disease, and cancer. In this review we described the association between vitamin D deficiency and severe therapy resistant asthma. We also reviewed the underlying molecular mechanism of vitamin D deficiency in children with severe- therapy resistant asthma. Based on current information, future clinical trial are needed to study the role of vitamin D supplementation on different groups of patients with severe asthma including infants, children of school age, and ethnic minorities.

  18. [Community-acquired respiratory infections].

    Science.gov (United States)

    Romero Vivas, J; Rubio Alonso, M; Corral, O; Pacheco, S; Agudo, E; Picazo, J J

    1997-01-01

    Respiratory infections are the most frequent reason for primary health care consultation. Although generally not severe, they are responsible for a large number of days of laboral and scholar absenteeism and an excessive use of antibiotics. The clinical and epidemiologic data of extrahospitalary infections in primary health care centers throughout Spain were collected according to the one day cut off system repeated trimestrally over one year. Data of 3,732 days of consultation were collected in which a total of 144,608 patients were attended. Of these, 20,614 had respiratory infections and 11,684 extrarespiratory infections. The most frequent processes were pharyngitis (33.7%), common cold (31.7%) followed by bronchitis (18.7%), otitis (11%), influenza (4.6%), laryngitis (4%), sinusitis (3.6%) and pneumonia (1.8%). Antibiotic treatment was prescribed in 13,488 patients (65%). The type of antibiotic was analyzed in the 11,977 patients treated for only one infection. Penicillins were the antibiotics most used followed by cephalosporins. The antibiotic prescribed was considered adequate in 70% of the 8,484 patients treated for potentially bacterial infection. A total of 3,493 patients had infection considered to be of viral etiology. Twenty-two percent of the patients attending a primary health care center presented infection and of these two out of three cases had respiratory infection. Pharyngitis and common cold were the most frequent processes observed. Two thirds of the patients consulting for respiratory infection received antibiotic treatment, with 29.2% being diagnosed with infections considered to be of viral etiology. The empiric treatment chosen for the two thirds of the potentially bacterial infections was considered as adequate.

  19. Zonography in acute respiratory diseases

    International Nuclear Information System (INIS)

    Druzhinina, V.S.; Fetisova, V.M.; Kozorez, A.G.

    1984-01-01

    Radiography was performed in 94 patients whose initial condition was assessed as acute respiratory disease. Radioscopy with x-ray image amplifier, roentgenography and zonography were used. Pulmonary changes were found in 61 persons. In 45 of them acute pneumonia was revealed, in 16 changes in the pulmonary pattern assessed as residual manifestations of pneumonia. Changes in 30 patients with pneumonia and 16 patients with residual manifestations were detected by zonography only

  20. Acute respiratory distress after transfusion

    Directory of Open Access Journals (Sweden)

    Michael Jožef Gradišek

    2012-12-01

    Conclusions: Transfusion-related acute lung injury (TRALI and transfusion-associated circulatory overload (TACO are clinical syndromes with predominant pulmonary injury and respiratory distress. Anaphylactic reaction, hemolytic transfusion reaction and transfusion of contaminated blood products also impair lung function but are less frequent. Transfusion in critically ill and injured patient is an independent risk factor for acute lung injury. It remains to be determined whether transfusion is the cause of increased mortality or only an indicator of disease severity

  1. Recurrent Respiratory Infections in Children

    Directory of Open Access Journals (Sweden)

    F. Yurochko

    2012-02-01

    Full Text Available The paper covers a problem of recurrent respiratory infections (RRI in children. Their description, risk factors, diagnostic algorithm have been dwelt. A special attention is paid to the treatment. An optimal antibiotic in RRI of bacterial genesis is a high-dose amoxicillin/clavulanate (registered as Augmentin™ ES in Ukraine, the efficacy of which is 94.6–96.3 % according to different data.

  2. Respiratory function among Malaysian aboriginals

    Science.gov (United States)

    Dugdale, A. E.; Bolton, J. M.; Ganendran, A.

    1971-01-01

    Respiratory function tests have been performed on 43 Malaysian aboriginals. The forced vital capacity and forced expiratory volume in one second (FEV1) were considerably below, and the peak expiratory flow rate (PEFR) slightly below, the predicted values. The FEV1 and PEFR decreased more rapidly with advancing age than predicted from western standards. These findings may be due to physiological differences or may be the result of chronic purulent bronchitis which is common among the aboriginals. Images PMID:5144653

  3. Baby swimming and respiratory health.

    Science.gov (United States)

    Nystad, Wenche; Håberg, Siri E; London, Stephanie J; Nafstad, Per; Magnus, Per

    2008-05-01

    To estimate the effect of baby swimming in the first 6 months of life on respiratory diseases from 6 to 18 months. We used data from The Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health in children born between 1999 and 2005 followed from birth to the age of 18 months (n = 30,870). Health outcomes: lower respiratory tract infections (LRTI), wheeze and otitis media between 6 and 18 months of age. baby swimming at the age of 6 months. The effect of baby swimming was estimated by logistic regression analysis adjusting for potential confounders. About 25% of the children participated in baby swimming. The prevalence of LRTI was 13.3%, wheeze 40.0% and otitis media 30.4%. Children who were baby swimming were not more likely to have LRTI, to wheeze or to have otitis media. However, children with atopic mothers who attended baby swimming had an increased risk of wheeze, adjusted odds ratios (aOR) 1.24 (95% CI 1.11, 1.39), but not LRTI or otitis media. This was also the case for children without respiratory diseases before 6 months aOR 1.08 (95%CI 1.02-1.15). Baby swimming may be related to later wheeze. However, these findings warrant further investigation.

  4. Incidence of respiratory distress syndrome

    International Nuclear Information System (INIS)

    Ghafoor, T.; Mahmud, S.; Ali, S.; Dogar, S.A.

    2003-01-01

    Objective: To determine the incidence of respiratory distress syndrome (RDS) in hospital born babies. Subjects and Methods: All live born infants delivered at the hospital and who fulfilled the diagnostic criteria of respiratory distress syndrome (RDS) were included in the study. Results: Ninety-four neonates developed RDS. Out of these, 88 (93.61%) were preterm and 06 (6.38%) were term infants. There was a male preponderance (65.95%). RDS was documented in 1.72% of total live births. 37.28% of preterm and 0.11% of term neonates born at the hospital. The incidence of RDS was 100% at 26 or less weeks of gestation, 57.14% at 32 weeks, and 3.70% at 36 weeks. The mortality with RDS was 41 (43.61%). Conclusion: RDS is the commonest cause of respiratory distress in the newborn, particularly, in preterm infants. It carries a high mortality rate and the incidence is more than that documented in the Western world. (author)

  5. Respiratory analysis system and method

    Science.gov (United States)

    Liu, F. F. (Inventor)

    1973-01-01

    A system is described for monitoring the respiratory process in which the gas flow rate and the frequency of respiration and expiration cycles can be determined on a real time basis. A face mask is provided with one-way inlet and outlet valves where the gas flow is through independent flowmeters and through a mass spectrometer. The opening and closing of a valve operates an electrical switch, and the combination of the two switches produces a low frequency electrical signal of the respiratory inhalation and exhalation cycles. During the time a switch is operated, the corresponsing flowmeter produces electric pulses representative of the flow rate; the electrical pulses being at a higher frequency than that of the breathing cycle and combined with the low frequency signal. The high frequency pulses are supplied to conventional analyzer computer which also receives temperature and pressure inputs and computes mass flow rate and totalized mass flow of gas. From the mass spectrometer, components of the gas are separately computed as to flow rate. The electrical switches cause operation of up-down inputs of a reversible counter. The respective up and down cycles can be individually monitored and combined for various respiratory measurements.

  6. House Dust Mite Respiratory Allergy

    DEFF Research Database (Denmark)

    Calderón, Moisés A; Kleine-Tebbe, Jörg; Linneberg, Allan

    2015-01-01

    Although house dust mite (HDM) allergy is a major cause of respiratory allergic disease, specific diagnosis and effective treatment both present unresolved challenges. Guidelines for the treatment of allergic rhinitis and asthma are well supported in the literature, but specific evidence on the e......Although house dust mite (HDM) allergy is a major cause of respiratory allergic disease, specific diagnosis and effective treatment both present unresolved challenges. Guidelines for the treatment of allergic rhinitis and asthma are well supported in the literature, but specific evidence...... of specific IgE testing, but availability is limited. Treatment options for HDM allergy are limited and include HDM avoidance, which is widely recommended as a strategy, although evidence for its efficacy is variable. Clinical efficacy of pharmacotherapy is well documented; however, symptom relief does...... not extend beyond the end of treatment. Finally, allergen immunotherapy has a poor but improving evidence base (notably on sublingual tablets) and its benefits last after treatment ends. This review identifies needs for deeper physician knowledge on the extent and impact of HDM allergy in respiratory disease...

  7. Smoking and respiratory irregularity in panic disorder.

    Science.gov (United States)

    Caldirola, Daniela; Bellodi, Laura; Cammino, Stefania; Perna, Giampaolo

    2004-09-15

    The biological mechanisms underlying the link between smoking and panic attacks are unknown. Smoking might increase the risk of panic by impairing respiratory system function. We evaluated the effect of smoking on respiratory irregularity in patients with panic disorder (PD) and healthy comparison subjects and the role of the respiratory disorders in this effect. We applied the Approximate Entropy index (ApEn), a nonlinear measure of irregularity, to study breath-by-breath baseline respiratory patterns in our sample. Both smoker and nonsmoker patients had more irregular respiratory patterns than healthy subjects. Smoker patients showed higher ApEn indices of baseline respiratory rate and tidal volume than nonsmoker patients (R = 5.4, df = 2,55, p smoking in healthy subjects did not influence the regularity of respiratory patterns. Respiratory disorders did not account for the influence of smoking on respiratory irregularity. Smokers had more severe panic attacks than nonsmokers. Smoking may impair vulnerable respiratory function and act as disruptive factor on intrinsic baseline respiratory instability in patients with PD, possibly influencing the onset or maintenance of the disorder.

  8. The respiratory physiotherapy causes pain in newborns? A systematic review

    OpenAIRE

    Zanelat, Camila Ferreira; Rocha, Flávia Rodrigues; Lopes, Gabriela Menezes; Ferreira, Juliana Rodrigues; Gabriel, Letícia Silva; Oliveira, Trícia Guerra e

    2017-01-01

    Abstract Introduction: Neonatal respiratory physicaltherapy plays an important role in prevention and treatment of respiratory pathologies. In preterm neonates, immaturity of respiratory system can let development of various respiratory diseases. Meanwhile, it is discussed if respiratory physiotherapy can cause pain. Objective: Investigate presence of pain in neonates undergone to respiratory physiotherapy by a systematic review. Methods: Scientific search in electronic databases: Medli...

  9. Respiratory Changes in Patients with Stroke

    Directory of Open Access Journals (Sweden)

    Rita Ocko

    2014-05-01

    Full Text Available This study aimed to review published literature concerning the major changes that occur in the respiratory system after stroke, and also the impact of respiratory muscle training in these patients. The literature search was conducted through electronic databases (PubMed, SciELO and Pedro in Portuguese and English languages on themes related to changes in the respiratory system and methods of assessment and rehabilitation of respiratory muscle strength in individuals affected by stroke. There is scientific evidence that individuals affected by stroke may show decreased inspiratory and expiratory muscle strength. Studies suggest that respiratory muscle training through threshold load can bring benefits by improving respiratory function and respiratory muscle strength. However, more studies should be conducted to deepen the knowledge about the benefits and long-term effects of pulmonary rehabilitation in patients with stroke.

  10. A Review on Human Respiratory Modeling.

    Science.gov (United States)

    Ghafarian, Pardis; Jamaati, Hamidreza; Hashemian, Seyed Mohammadreza

    2016-01-01

    Input impedance of the respiratory system is measured by forced oscillation technique (FOT). Multiple prior studies have attempted to match the electromechanical models of the respiratory system to impedance data. Since the mechanical behavior of airways and the respiratory system as a whole are similar to an electrical circuit in a combination of series and parallel formats some theories were introduced according to this issue. It should be noted that, the number of elements used in these models might be less than those required due to the complexity of the pulmonary-chest wall anatomy. Various respiratory models have been proposed based on this idea in order to demonstrate and assess the different parts of respiratory system related to children and adults data. With regard to our knowledge, some of famous respiratory models in related to obstructive, restrictive diseases and also Acute Respiratory Distress Syndrome (ARDS) are reviewed in this article.

  11. Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction

    DEFF Research Database (Denmark)

    Walsted, Emil Schwarz; Faisal, Azmy; Jolley, Caroline J

    2017-01-01

    and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video, gastric-, esophageal- and transdiaphragmatic pressures, diaphragm electromyography and respiratory airflow. Results: The EILO and control groups had similar peak work rates and minute ventilation...... of respiratory mechanics and diaphragm electromyography with endoscopic video we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure...

  12. Respiratory failure in elderly patients.

    Science.gov (United States)

    Sevransky, Jonathan E; Haponik, Edward F

    2003-02-01

    Elderly individuals comprise an increasing proportion of the population and represent a progressively expanding number of patients admitted to the ICU. Because of underlying pulmonary disease, loss of muscle mass, and other comorbid conditions, older persons are at increased risk of developing respiratory failure. Recognition of this vulnerability and the adoption of proactive measures to prevent decompensation requiring intrusive support are major priorities together with clear delineation of patients' wishes regarding the extent of support desired should clinical deterioration occur. Further, the development of coordinated approaches to identify patients at risk for respiratory failure and strategies to prevent the need for intubation, such as the use of NIV in appropriate patients, are crucial. As soon as endotracheal intubation and mechanical ventilation are implemented strategies that facilitate the liberation of elderly patients from the ventilator are especially important. The emphasis on a team approach, which characterizes geriatric medicine, is essential in coordinating the skills of multiple health care professionals in this setting. Respiratory failure can neither be effectively diagnosed nor managed in isolation. Integration with all other aspects of care is essential. Patient vulnerability to nosocomial complications and the "cascade effect" of these problems such as the effects of medications and invasive supportive procedures all impact on respiratory care of elderly patients. For example, prolonged mechanical ventilation may be required long after resolution of the underlying cause of respiratory failure because of unrecognized and untreated delirium or residual effects of small doses of sedative and/or analgesic agents or other medications in elderly patients with altered drug metabolism. The deleterious impact of the foreign and sometimes threatening ICU environment and/or sleep deprivation on the patient's course are too often overlooked because

  13. Hypoxia-induced modulation of the respiratory CPG.

    Science.gov (United States)

    Bell, Harold J; Syed, Naweed I

    2009-01-01

    Despite recent advances in our understanding of the neural control of breathing, the precise cellular, synaptic, and molecular mechanisms underlying the generation and modulation of respiratory rhythm remain largely unknown. This lack of fundamental knowledge in the field of neural control of respiration is likely due to the complexity of the mammalian brain where synaptic connectivity between central respiratory neurons, motor neurons and their peripheral counterparts cannot be mapped reliably. We have therefore developed an invertebrate model system wherein the essential elements of the central pattern generator (CPG), the motor neurons and the peripheral chemosensory cells involved in respiratory control have been worked out both in vivo and in vitro. We discuss our recent identification of peripheral, hypoxia sensitive chemoreceptor elements in a sensory organ of the pulmonate freshwater pond snail Lymnaea stagnalis, which provide an excitatory drive to the respiratory CPG neuron RPeD1 via direct chemical synaptic connections. Further studies using this unique invertebrate model system may reveal highly conserved principles of CPG neuromodulation that will remain relevant to more complex mammalian systems.

  14. Antiviral therapy for respiratory viral infections in immunocompromised patients.

    Science.gov (United States)

    Shahani, Lokesh; Ariza-Heredia, Ella J; Chemaly, Roy F

    2017-04-01

    Respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, coronavirus, human metapneumovirus, and rhinovirus) represent the most common causes of respiratory viral infections in immunocompromised patients. Also, these infections may be more severe in immunocompromised patients than in the general population. Early diagnosis and treatment of viral infections continue to be of paramount importance in immunocompromised patients; because once viral replication and invasive infections are evident, prognosis can be grave. Areas covered: The purpose of this review is to provide an overview of the main antiviral agents used for the treatment of respiratory viral infections in immunocompromised patients and review of the new agents in the pipeline. Expert commentary: Over the past decade, important diagnostic advances, specifically, the use of rapid molecular testing has helped close the gap between clinical scenarios and pathogen identification and enhanced early diagnosis of viral infections and understanding of the role of prolonged shedding and viral loads. Advancements in novel antiviral therapeutics with high resistance thresholds and effective immunization for preventable infections in immunocompromised patients are needed.

  15. Innate Immunity to Respiratory Infection in Early Life.

    Science.gov (United States)

    Lambert, Laura; Culley, Fiona J

    2017-01-01

    Early life is a period of particular susceptibility to respiratory infections and symptoms are frequently more severe in infants than in adults. The neonatal immune system is generally held to be deficient in most compartments; responses to innate stimuli are weak, antigen-presenting cells have poor immunostimulatory activity and adaptive lymphocyte responses are limited, leading to poor immune memory and ineffective vaccine responses. For mucosal surfaces such as the lung, which is continuously exposed to airborne antigen and to potential pathogenic invasion, the ability to discriminate between harmless and potentially dangerous antigens is essential, to prevent inflammation that could lead to loss of gaseous exchange and damage to the developing lung tissue. We have only recently begun to define the differences in respiratory immunity in early life and its environmental and developmental influences. The innate immune system may be of relatively greater importance than the adaptive immune system in the neonatal and infant period than later in life, as it does not require specific antigenic experience. A better understanding of what constitutes protective innate immunity in the respiratory tract in this age group and the factors that influence its development should allow us to predict why certain infants are vulnerable to severe respiratory infections, design treatments to accelerate the development of protective immunity, and design age specific adjuvants to better boost immunity to infection in the lung.

  16. Understanding PISA

    Directory of Open Access Journals (Sweden)

    Stephen DOWNES

    2005-04-01

    Full Text Available Understanding PISA Stephen DOWNESMoncton, CANADA ABSTRACT The headline was dramatic enough to cause a ripple in the reading public. "Students who use computers a lot at school have worse maths and reading performance," noted the BBC news article, citing a 2004 study by Ludger Woessmann and Thomas Fuchs (Fuchs and Woessman, 2004. It was not long before the blogosphere took notice. Taking the theme and running with it, Alice and Bill ask, "Computers Make School Kids Dumber?" They theorize, "If you track the admitted decline of education, you'll probably notice that it follows along with the increase of technology in the classroom." In a similar vein, James Bartholomew asks, "Do you think that the government will turn down the volume of its boasting about how it has spent billions introducing computers in schools (while keeping down the pay of teachers so much that there are shortages? Do you think it will stop sending governors of state schools glossy pamphlets about insisting that computers are used in their schools as much as possible?" In this study, therefore, PISA looks well beyond educational attainment, and also includes school demographics, such as whether it is a public or private school, has large or small classes, or has access or not to technological resources. Finally, it does measure student information-their family background, access to books and computers and parental support as well. The PISA survey departs from previous surveys in disregarding the stated curricula of the schools being measured. Therefore, the conclusion is not surprising, nor even wrong for him to consider independently of any parental or teacher support, considered without reference to the software running on it, considered without reference to student attitudes and interests, does not positively impact an education. Finally, he focus on missing the reporting of results

  17. Sustained Protein Kinase D Activation Mediates Respiratory Syncytial Virus-Induced Airway Barrier Disruption

    OpenAIRE

    Rezaee, Fariba; DeSando, Samantha A.; Ivanov, Andrei I.; Chapman, Timothy J.; Knowlden, Sara A.; Beck, Lisa A.; Georas, Steve N.

    2013-01-01

    Understanding the regulation of airway epithelial barrier function is a new frontier in asthma and respiratory viral infections. Despite recent progress, little is known about how respiratory syncytial virus (RSV) acts at mucosal sites, and very little is known about its ability to influence airway epithelial barrier function. Here, we studied the effect of RSV infection on the airway epithelial barrier using model epithelia. 16HBE14o- bronchial epithelial cells were grown on Transwell insert...

  18. Respiratory muscle activity and respiratory obstruction after abdominal surgery.

    Science.gov (United States)

    Wu, A; Drummond, G B

    2006-04-01

    Respiratory movements in patients after abdominal surgery are frequently abnormal, with associated disturbances in the pattern of inspiratory pressure generation. The reasons for these abnormalities are not clear and have been attributed to impaired action of the diaphragm. However, an alternative is that partial airway obstruction could trigger reflex activation of the inspiratory ribcage muscles, which would cause a similar pattern of inspiratory pressure change. Direct measurement of electrical activity can indicate if reflex activation of inspiratory muscles occurs when partial airway obstruction is present. In an open study, we implanted electrodes to measure the EMG of scalene, intercostal and external oblique abdominal muscles in patients after lower abdominal surgery. Analgesia was with morphine i.v. by patient control. We used nasal cannulae to measure nasal airflow and compared EMG activity when airway obstruction was present with activity when breathing was not obstructed. The pattern of activity of the different muscles was distinct. Intercostal activity reached a maximum during inspiration, before the scalene muscles, whereas scalene activity increased in phase with increasing lung volume. Abdominal muscle activity commenced when expiratory flow had ceased and continued until the next inspiration. In all three muscle groups, partial airway obstruction did not alter muscle activity. Partial airway obstruction does not activate inspiratory ribcage muscles, in patients receiving morphine for postoperative analgesia after lower abdominal surgery. Changes in respiratory pressures and abnormalities of chest wall movement described in previous studies cannot be attributed to reflex responses and probably result from increased airway resistance and abdominal muscle action.

  19. Low ABCB1 gene expression is an early event in colorectal carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Vibeke Andersen

    Full Text Available The ABCB1/MDR1 gene product ABCB1/P-glycoprotein is implicated in the development of colorectal cancer (CRC. NFKB1 encodes transcription factors regulating expression of a number of genes including ABCB1. We have previously found association between the ABCB1 C-rs3789243-T polymorphism and CRC risk and interactions between the ABCB1 C-rs3789243-T and C3435T polymorphisms and meat intake in relation to CRC risk (Andersen, BMC Cancer, 2009, 9, 407. ABCB1 and NFKB1 mRNA levels were assessed in intestinal tissue from 122 CRC cases, 101 adenoma cases (12 with severe dysplasia, 89 with mild-moderate dysplasia and from 18 healthy individuals, together with gene polymorphisms in ABCB1 and NFKB1. ABCB1 mRNA levels were highest in the healthy individuals and significantly lower in mild/moderate and severe dysplasia tissue (P<0.05 for both, morphologically normal tissues close to the tumour (P<0.05, morphologically normal tissue at a distance from the tumour (P<0.05 and CRC tissue (P<0.001. Furthermore, ABCB1 mRNA levels were lower in adenomas and carcinomas compared to morphologically normal tissue from the same individuals (P<0.01. The ABCB1 C-rs3789243-T and NFKB1 -94ins/del homozygous variant genotypes were associated with low ABCB1 mRNA levels in morphologically normal sigmoid tissue from adenoma cases (P<0.05 for both. NFKB1 mRNA levels were lower in both tumour and normal tissue from cancer patients (P<0.001 as compared to healthy individuals but we were unable to show association between NFKB1 -94ins/del genotype and NFKB1 mRNA levels. This study suggests that low ABCB1 mRNA levels are an early event in CRC development and that the two polymorphisms affect ABCB1 mRNA levels whereas low NFKB1 mRNA levels occur later in carcinogenesis. Low ABCB1 protein levels may promote colorectal carcinogenesis through increasing intracellular exposure to carcinogenic ABCB1 substrates.

  20. Bladder carcinogenesis in rats subjected to ureterosigmoidostomy and treated with L-lysine.

    Science.gov (United States)

    Dornelas, Conceição Aparecida; Santos, Alessandra Marques Dos; Correia, Antonio Lucas Oliveira; Juanes, Camila de Carvalho; Coelho, João Paulo Ferreira; Cunha, Bianca Lopes; Maciel, André Vinicius Vieira; Jamacaru, Francisco Vagnaldo Fechine

    2016-01-01

    to evaluate the effect of L-lysine in the bladder and intestinal epithelia in rats submitted to vesicosigmoidostomy. we divided forty Wistar rats into four groups: group I - control group (Sham); group II - submitted to vesicosigmoidostomy and treated with L-lysine 150mg/kg; group III - submitted only to vesicosigmoidostomy; and group IV - received L-lysine 150mg/kg. After eight weeks the animals were sacrificed. in the bladders of all operated animals we observed simple, papillary and nodular hyperplasia of transitional cells, transitional cell papillomas and squamous metaplasia. As for the occurrence of aberrant crypt foci in the colons of operated animals, we did not observe statistically significant differences in any of the distal, proximal and medium fragments, or in all fragments together (p=1.0000). Although statistically there was no promotion of carcinogenesis in the epithelia of rats treated with L-lysine in the observed time, it was clear the histogenesis of bladder carcinogenesis in its initial phase in all operated rats, this being probably associated with chronic infection and tiny bladder stones. o objetivo deste trabalho é avaliar o efeito da L-lisina nos epitélios vesical e intestinal de ratas submetidas à vesicossigmoidostomia. quarenta ratas Wistar, foram divididas em quatro grupos: grupo I- grupo controle (Sham); grupo II- submetido à vesicossigmoidostomia e tratado com L-lisina 150mg/kg; grupo III- submetido apenas à vesicossigmoidostomia; e grupo IV- recebeu L-lisina 150mg/kg. Após oito semanas os animais foram sacrificados. na bexiga de todos os animais operados observou-se hiperplasia simples, papilar e nodular de células transicionais, papiloma de células transicionais e metaplasia escamosa. Quanto à ocorrência de focos de criptas aberrantes nos colos dos animais operados, não foi evidenciado diferença estatística significante em nenhum dos fragmentos distal, proximal e médio, e todos juntos (P=1,0000). apesar de